Question:
You will be shown the title of a chemistry paper, together with sections excerpted from the body of the paper. The paper sections may include HTML tags like `<p>` and `</p>`; please ignore these. Your task is to write an abstract for the paper. Your response should include the abstract and no other text.

Title:
Nickel-Catalyzed Cross-Electrophile Coupling of Aryl Chlorides with Primary Alkyl Chlorides

Paper sections:

Cross-electrophile coupling has rapidly become an important approach to the synthesis of Csp2-Csp3 bonds,1 but engaging less reactive C-Cl bonds, outside of activated systems2 or intramolecular reactions,3 has proven challenging. Indeed, unactivated C-Cl bonds are well-tolerated functional groups4 in cross-electrophile coupling methods (Scheme 1).5,6 The ability to cross-couple with organic chlorides is valuable for several reasons – first, organic chlorides are more abundant than organic bromides or organic iodides;7 second, the low reactivity of the C-Cl bond allows it to be introduced early in a synthesis and later diversified.8,9,10

The central challenge presented by C-Cl bonds in cross-electrophile coupling is the need for higher reactivity without sacrificing selectivity (Scheme 1). While the homodimerization of alkyl chlorides11 and aryl chlorides8c has been reported, no general cross-selective approach has yet been found.12 Recently, Zhang reported couplings of a variety of aryl chlorides, but only with an excess of ClCF2R reagents.13 Several groups have reported on the coupling of aryl chlorides with alkyl bromides14 or tertiary alkyl oxalate esters.15 However, the coupling of chlorobenzene with a simple alkyl bromide provided less than 25% yield of cross-coupled product.14a Switching to an alkyl chloride further diminishes selectivity and yield using our standard conditions (Scheme 1).16

Based upon our proposed mechanism for the coupling of aryl iodides with alkyl iodides,17–18,19, overcoming this dual reactivity-selectivity challenge requires a catalyst that selectively reacts with the Ar-Cl over the Alkyl-Cl, yet can slowly generate an alkyl radical from the Alkyl-Cl starting material. Herein we show that this can be accomplished through the use of salt additives to maintain a very low, steady-state concentration of an alkyl bromide/iodide and a uniquely selective pyridine-2,6-bis(N-cyanocarboxamidine) (PyBCamCN)20,21 ligated nickel catalyst (Scheme 1).

During reaction development, we observed a strong synergistic effect between the catalyst and the presence of substoichiometric amounts (10–30 mol%) of bromide or iodide (Table 1 and Supporting Information Figures S1, S4-S7). While no catalysts were found that provided high yields of product in the absence of bromide or iodide, high selectivity could be achieved in reactions with PyBCamCN ligand and NiBr2(dme) or NiI2•4H2O; and in reactions with PyBCam ligand and NiBr2(dme) (Table 1, bold-faced entries). Reactions with bipyridine (bpy) or pyridine 2-carboxamidine (PyCam) ligands, which are optimal for the coupling of aryl bromides with alkyl bromides,20,22 favored formation of aryl dimer products (bpy) or hydrodehalogenated arene (PyCam) without consuming the alkyl chloride. Reactions with terpyridine (tpy), which is useful for the dimerization of alkyl halides,23 converted alkyl chloride to dimeric and hydrodehalogenated products without consuming aryl chloride. In contrast to tpy, reactions with 4,4′,4″-tri-tert-butyl-2,2′:6′,2″-terpyridine (tpy‴), which is useful in Negishi cross-coupling reactions of alkyl halides,24 consumed both substrates but formed approximately 1:1:1 product/alkyl dimer/aryl dimer.25 See also Chart S1 in the Supporting Information.

Routine optimization with PyBCam and PyBCamCN demonstrated that PyBCamCN was superior, that reactions were best conducted at 60–80 °C, and that a variety of iodide and bromide additives provide similar results.25 Reactions with bromide additive provided the highest yields when the alkyl chloride was added slowly, either portionwise via syringe or dropwise through an addition funnel. Reactions with iodide additive did not benefit from slow addition. The primary side products in both cases are the alkyl dimer and aryl hydrodehalogenated product.

The optimized conditions were then applied to a variety of primary alkyl chlorides and chloroarenes (Scheme 2). Electron-rich aryl chlorides, which were unreactive under our previously published conditions, coupled in 69–72% yield (3b, 3f, 3g, 3r). However, a more sterically hindered aryl chloride, 2-chlorotoluene, coupled poorly (3e, 15% yield). While we had coupled electron-poor aryl chlorides with alkyl bromides previously,14 under these conditions electron-poor aryl chlorides could be coupled with alkyl chlorides for the first time, with yields ranging from 53–73% yield (3c, 3h, 3i, 3s, 3u, 3v). As expected with PyBCam ligands,20 a variety of heterocycles could be coupled, including both electron-poor quinoline (3s, 63%) and pyridine (3u, 66% and 3v, 73%); and electron-rich indole (3r, 71%) and thiophene (3t, 33%). A particular advantage of cross-electrophile coupling is tolerance for alkyl halides with β-leaving groups (3z-3ad). The analogous organometallic reagents would be prone to elimination. Finally, secondary alkyl chlorides do couple under these conditions, but in lower yield (3ai, 44%).

Despite the higher temperatures, functional group compatibility remained broad. The low basicity of the conditions allowed us to tolerate both aryl and alkyl pinacol boronic acid esters (3o-3q, 49–73% yield), providing opportunities for further elaboration of the products. Acidic N-H (3ag, 60%) and O-H (3ae, 57%) groups are tolerated, which would be a challenge for organomagnesium or organozinc reagents.26 As a testament to the low basicity of the conditions, a free thiol was tolerated (3g, 70% yield), avoiding competing SN2 with the alkyl electrophile and S-arylation (pKa of thiophenol in DMSO is 10.3,27 which makes it more acidic than acetic acid).28 On the other hand, despite the presence of Lewis acids (ZnII salts, Li+ salts) at 60–80 °C, Boc groups on nitrogen were still tolerated (3ag, 60%; 3ah, 71%). While esters were tolerated, we did observe scrambling when two different esters were present due to transesterification (for example, methyl and ethyl ester exchange). For this reason, we coupled chloroarenes bearing esters (3i, 3j) with 1-chlorooctane. Other functional group highlights include a benzylic diethylphosphonate ester (3n, 51%) and a trimethoxysilane (3y, 32%). Despite the low yield, the cross-coupling to form trimethoxysilane product 3y is notable because it is a different approach29,30 to forming functionalized silanes that could be useful in attaching molecules to glass or silica.31 As in our previous studies on cross-electrophile coupling reactions with less reactive substrates, this chemistry can be scaled up using standard techniques (3ac).32

The distinctive feature of this reaction, when compared to other cross-electrophile couplings of aryl halides with alkyl halides, is the ability to engage two relatively unreactive substrates in a selective manner (Scheme 1). There are three keys to the success of this method.

First, LiCl was essential for efficient reduction of the nickel catalyst by the zinc surface. We have recently noted that ZnCl2 can have an inhibitory effect on reduction of nickel catalysts and that lithium chloride is among the best agents for overcoming inhibition,33 consistent with previous reports on reduction of organic molecules.34 Here too, reactions conducted without LiCl resulted in 3% formation of the cross-coupled product and primarily returned both substrates (Supporting Information Figure S2). We also verified that neither organic chloride reacts directly with zinc to form an organozinc reagent (Supporting Information Figure S2).

Second, halide exchange plays a key role by increasing the reactivity of the alkyl chloride. We found that 10–30% of bromide or iodide, regardless of how it was introduced, was essential for reasonable reaction rates (Scheme 3 and Supporting Information Figures S4-S7). Importantly, the low concentration of bromide was essential; reactions run without any bromide (Scheme 3d) or with only alkyl bromide (Scheme 3e) provided lower yields than reactions with a catalytic amount of bromide (Scheme 3a – Scheme 3c and Table 1).

Studies on halide exchange showed that it is fast compared to the rate of reaction (reaching equilibrium in 1–2 h vs 24 h for reaction time) and unfavorable (Supporting Information Figure S8-S16). Significantly, the presence of zinc and lithium salts altered the equilibrium to more strongly favor alkyl iodide/bromide. This led to the counterintuitive outcome that increasing total chloride concentration increased alkyl iodide concentration. Under concentrations of salts chosen to mimic those present catalytic reactions, we found that the amount of alkyl iodide increased as the concentration of ZnCl2 increased, although the ratio of alkyl-Cl/alkyl-I remained large in all cases (≥98:2, Figure S10 and S16). We tentatively attribute this phenomenon to the favorable formation of LiZnCl3 over LiZnCl2Br or LiZnCl2I, resulting in sequestration of chloride as the concentration of Zn2+ increases at later reaction times.35 The halogen exchange is also somewhat faster than reported for exchanges in amide solvents with only sodium bromide, but this process could be catalyzed by zinc: catalysis of alkyl halogen exchange by titanium, zirconium, rhodium, and iron salts has been reported.36

While iodide exchange to enhance the reactivity of alkyl bromides,14 sulfonic acid esters,37 epoxides,38 and chlorides11 in cross-coupling reactions is now well established, the use of bromide is more rare.39 In cases where iodide co-catalysis isn't practical, the use of bromide co-catalysis should be considered.

Finally, studies with a variety of ligands revealed that PyBCam nickel catalysts are unique in being able to react with both substrates at similar rates, even with activation by halide exchange (Table 1 and Supporting Information Figure S1). Compared to nickel complexes of tpy‴, which could also react with both substrates but formed both biaryl and bialkyl, nickel PyBCam catalysts avoid biaryl formation entirely and form only small amounts of alkyl dimer. The origin of these differences in reactivity are not yet clear and are the subject of ongoing studies, but it is clear that PyBCam and PyBCamCN are a distinctive, new class of tridentate ligands for nickel catalysis.40

In conclusion, the first selective cross-electrophile coupling reaction of aryl chlorides with primary alkyl chlorides has been developed by the synergistic effect of three changes: a new, selective ligand (PyBCamCN), LiCl to enhance catalyst turnover, and bromide/iodide co-catalysis. The mechanism by which PyBCamCN improves yields is under investigation and will be reported in due course. We expect that the generally unreactive nature of alkyl and aryl chlorides should make this new method to functionalize them a useful addition to synthesis.

Answer: Alkyl chlorides and aryl chlorides are among the most abundant and stable carbon electrophiles. Although their coupling with carbon nucleophiles is well developed, the cross-electrophile coupling of aryl chlorides with alkyl chlorides has remained a challenge. We report here the first general approach to this transformation. The key to productive, selective cross-coupling is the use of a small amount of iodide or bromide along with a recently reported ligand, pyridine-2,6-bis(N-cyanocarboxamidine) (PyBCamCN). The scope of the reaction is demonstrated with 35 examples (63%\xc2\xb116% ave yield) and we show that the Br\xe2\x88\x92 and I\xe2\x88\x92 additives act as co-catalysts, generating a low, steady-state concentration of more-reactive alkyl bromide/iodide.


Question:
You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.

Paper text:
polycystic ovary syndrome ( pcos ) is the most common endocrine disorder among women of reproductive age , affecting nearly 7% of them .
the endocrine hallmarks are hyperandrogenemia and , to a less extent , hypersecretion of luteinizing hormone .
the characteristic clinical features of pcos are menstrual irregularity , such as amenorrhea , oligomenorrhea , or other irregular uterine bleeding , and signs of excessive androgen production , such as hirsutism , greasy skin , acne , and obesity .
pcos is considered to be not only a reproductive endocrinopathy , but also a metabolic disorder , and its morbidity may include hyperinsulinemia , insulin resistance , early onset of type 2 diabetes mellitus , and dyslipidemia .
obesity is a prominent feature of pcos , occurring in 40 - 50% of pcos patients .
also , the prevalence of pcos is increased in overweight and obese women when compared to their lean counterparts .
the prevalence rates of pcos in underweight , normal - weight , overweight , and obese women are 8.2 , 9.8 , 9.9 , and 9.0% , respectively .
prevalence rates reaches 12.4 and 11.5% in women with bmi 35 - 40 kg / m and greater than 40
obesity worsens the clinical , endocrine and metabolic features of the syndrome , mostly by increasing insulin resistance and hyperinsulinaemia . besides obesity ,
the topography of body fat is an important issue . the major endocrine symptom of pcos , hyperandrogenicity , is clearly associated with the amount of fat localized in the upper body sites .
it is suggested that there is a possible association between diet and risks of pcos .
the objective of this study was to characterize the anthropometric and dietary profile of women with pcos and to compare it with that of healthy age - matched women .
the study participants , materials , and methods were approved by the student research committee of shiraz university of medical sciences . this study was a case - control study .
the study population consisted of patients who attended the clinic for gynecology and obstetrics at motahari clinic ( shiraz medical university ) from april 2009 to august 2009 .
sixty five women aged between 17 and 48 years , who fit the diagnostic criteria for pcos served as cases .
the pcos was diagnosed byultrasound appearance of polycystic ovaries and determination of hormonal parameters based on standard rotterdam criteria 2003 .
we excluded patients with any other etiology such as liver , kidney and heart problems .
the control group consisted of 65 healthy women who attended the clinic along with their patients and were matched for age with the pcos group .
all the participants , pcos patients as well as controls , were in good health conditionandwere not on any medication which might affect hormone metabolism or body composition .
all the participants were non - smokers and none of them was on excessivephysical training .
for each participant , a questionnaire of demographic information ( job , exercise habits , education and socio- economic status , etc .
each participant was asked to provide a detailed history of menstruation and also signs and symptoms of pcos such as acne , hirsutism and greasy skin .
anthropometric information was gathered as follows : stature ( in cm ) and body weight ( in kg ) were determined for eachparticipant and bmiwas calculated . the waist and hip circumferences were measured and the waist - to - hip ratio ( whr ) was also calculated . to evaluate the dietary intake of the participants , three 24-hour dietary recall questionnaires were filled for each person ( two weekdays and a weekend ) by a trained dietition .
total energy intake ( kcal ) , levels of carbohydrate ( % ) , protein ( % ) , fat ( % ) , sfa ( gr ) , pufa ( % ) and mufa ( % ) intake in the participants were also analyzed , using food processor software nut-4 modified by incorporating the iranian food table .
statistical analysis was done using the statistical package for the social sciences , version 13.0 , for windows ( spss , inc . ,
chicago ) . the independent samplet - test and mann - whitney u test was used to compare the means of the two groups .
statistical analysis was done using the statistical package for the social sciences , version 13.0 , for windows ( spss , inc . , chicago ) .
the independent samplet - test and mann - whitney u test was used to compare the means of the two groups .
the participants of the present study were 65 women with pcos as cases and 65 healthy women as control group .
the average age of the participants in the case and control groups was 25.11  6.1 and 26.11  6.5 years , respectively .
besides the age variable , the two groups were also matched regarding the education and socio - economic status ( p = 0.499 ) .
there was no significant difference in the percentage of women who exercised regularly between the two groups ( 32.3% vs. 35.8% ; p = 0.075 ) .
a significantly higher percentage of pcos women reported pcos in their family than healthy women ( p < 0.001 ) .
there was no significant difference between the mean of body mass index of the two groups [ table 1 ] , but the mean of the waist circumference was significantly higher in the pcos group , compared to the control group ( p = 0.016 ) .
anthropometric characteristics of the participants we also compared the occurrence of three most common signs of this syndrome including acne , hirsutism and greasy skin in the normal weight and overweight subgroups of pcos women [ table 2 ] . although there were no significant differences in greasy skin and acne between the normal weight and overweight pcos patients , a significantly higher percentage of overweight patients had hirsutism compared to the normal weight ( p = 0.009 ) .
pcos signs and dietary pattern in the normal weight and overweight patients with pcos the mean intakes of calorie in the pcos and control group were 1508  581 and 1207  391 kcal , respectively [ table 3 ] .
there was a significant difference between the mean calorie intake of the pcos and control groups ( p = 0.001 ) so that the pcos women consumed more calorie than the healthy ones .
the mean fat intake ( % ) was significantly higher in the pcos group than the control group ( p = 0.019 ) .
sfa and pufa were also consumed more in the pcos group ( p = 0.043 and 0.025 , respectively ) .
as shown in table 2 , no significant difference was seen between their dietary intakes .
pcos is the most common endocrine disorder among women of reproductive age , affecting nearly 7% of them .
pcos is considered to be not only a reproductive endocrinopathy , but also a metabolic disorder , and its morbidity may include hyperinsulinemia , insulin resistance , early onset of type 2 diabetes mellitus , dyslipidemia , macrovascular disease and thrombosis , endometrial hyperplasia and carcinoma , and obstructive sleep apnea . in the present study , the dietary patterns and anthropometric characteristics of a group of women with pcos and a group of age - matched healthy women were compared .
the mean bmi of the two groups was within the normal range ( 19 - 24.9kg / m ) , and there was no significant difference between the two means .
but different patterns of fat distribution were seen between the two groups , so that the marker of abdominal obesity , mean of waist circumference was significantly higher in the pcos patients than the healthy controls .
similar results were reached in a study by kirchengast et al . , who showed that lean pcos patients have a significantly higher amount of fat tissue of the total body and the upper body region compared to the lean controls .
the gynoid type of fat distribution develops during female puberty and persistsduring the fertile phase of adult life .
peripheralfat tissue , especially in the lower body region is an importantsource of extra - ovarian estrogen synthesis , because the aromatizationfrom androgens to estrogens takes place there .
it is important to note that the major endocrine symptom of pcos , hyperandrogenicity , is clearly associated with a preponderance of fat localizedin the upper body sites .
this sex specific fat distribution , commonly called android fat distribution , is associated with obesity and a variety of metabolic characteristics , but is also mentioned as an indicator of reduced reproductivecapability of the woman .
insulin resistance is independent of the effect of obesity ; both lean and obese women with pcos have evidence of decreased insulin sensitivity , but insulin resistance is most marked where there is an interaction between obesity and the syndrome .
systemic hyperinsulinism plays a major role in the development of the hyperandrogenism characteristic of the pcos .
insulin also inhibits hepatic synthesis of sex hormone  binding globulin , the key circulating protein that binds to testosterone and thus increases the proportion of testosterone that circulates in the unbound , biologically available , or  free ,  state .
a close correlation exists between adiposity and severity of the symptoms in women with pcos , and since acne , hirsutism and greasy skin are the most common variable signs of hyperandrogenism , the prevalence of these symptoms were assessed in two bmi subgroups of our patients : the normal weight and overweight .
although there were no significant differences in greasy skin and acne between the normal weight and overweight pcos patients , a significantly higher percentage of overweight women reported hirsutism compared to the normal weight . in a study by liou et al . , the obese women with pcos did not present with a higher prevalence of hirsutism and in fact they had a lower incidence of acne than non - obese participants . in another cross - sectional study by tamimi et al .
, hirsutism , the major clinical feature of pcos , did not increase significantly from the normal weight subgroup to overweight and to obese subgroups of pcos patients .
there is a fairly general agreement that sex hormone  binding globulin ( shbg ) concentrations are much lower in obese women than the lean pcos patients .
obese women with pcos have high free androgen indices and lower shbg than non - obese women ; therefore , one would expect the obese women with pcos to show more severe functional hyperandrogenism . among hyperandrogenism symptoms ,
lifestyle modification focusing predominantly on diet and exercise behavior is considered the preferred first - line treatment for pcos management with the primary goal to normalize serum androgens and restore reproductive function .
the reported incidence of obesity and insulin resistance among the women with pcos led us to hypothesize that patients with pcos consume foods that contribute to obesity , elevated insulin concentrations , and ultimately , insulin resistance .
our major findings were that women with pcos had a diet with higher total energy and fat , saturated fat and poly - unsaturated fat compared to the healthy controls .
but we did not find any difference between the dietary intakes of normal weight and overweight pcos patients .
wild et al.21 found that women with pcos had a diet higher in saturated fat and lower in dietary fiber than age - matched control women .
, investigated the habitual diet and activity patterns of 21 uk women with pcos . in their study ,
mean percentage energy from fat was 38% ( 12% energy from saturated fat ) , with 68% of women with pcos consuming > 35% energy from fat .
epidemiological studies suggest an association between a high fat , particularly saturated fat intake and reduced insulin sensitivity . in most of the dietary studies in women with pcos
, improvements in metabolic and reproductive outcomes have been closely related to improvements in insulin sensitivity , suggesting that dietary modification designed to improve insulin resistance may produce benefits greater than those achieved by energy restriction alone . in an interventional study by thompson et al . on the effects of energy - restricted high protein diet ( 5000 - 6000 kj / d ) , weight loss via energy restriction improved reproductive function , cardiometabolic abnormalities , and hormonal parameters in overweight and obese women with pcos . as reported , in our participants ,
this high fat diet might have increased insulin resistance and caused hyperinsulinemia in patients . as we discussed previously , hyperinsulinemia can cause hyperandrogenism . we conclude that in pcos patients , android obesity in a common feature and this abdominal adiposity may be related to pcos complications .
we can also report that pcos symptoms are more severe in overweight pcos patients than the normal weight . as to the dietary pattern ,
pcos patients consume more calories and more fat in their diets and this might have been correlated to their disease .
we recommend clinical trials to be designed to assess the effects of different patterns of diet and changes in anthropometric indices on the signs and symptoms of pcos .

Answer:
objective : polycystic ovary syndrome ( pcos ) is the most common endocrine disorder among women of reproductive age .
 pcos is considered to be not only a reproductive endocrinopathy , but also a metabolic disorder .
 the objective of the present study was to characterize the anthropometric and dietary profile of women with pcos and to compare it with that of healthy age - matched women.design:in this case - control study , 65 women with pcos served as cases .
 the control group consisted of 65 age - matched healthy women .
 for each participant , demographic , anthropometric and dietary intake data were gathered and compared between the two groups.results:there was no significant difference between the mean of the body mass index of the two groups , but the mean of waist circumference was significantly higher in the pcos group , than the control group ( p = 0.016 ) . compared to the normal weight pcos patients , a significantly higher percentage of overweight patients had hirsutism ( p = 0.009 ) . in dietary analysis , women with pcos consumed more calories and more fat than healthy women ( p = 0.001 and p = 0.019 , respectively).conclusion : it is concluded that in pcos patients , android obesity is a common feature and this abdominal adiposity may be related to the syndrome 's complications .
 pcos symptoms were more severe in overweight patients than the normal weight .
 regarding the dietary pattern , it was indicated that patients with pcos consume more calories and more fat in their diets and this might have been correlated to their disease .


Question:
You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.

Paper text:
the program evaluation is generally classified into three types : planning , summative , and formative evaluation .
even though distinctions between the different types of evaluation are sometimes blurred , differentiating their intent helps us in clarifying our understanding of evaluation process ( 1 ) .
planning evaluation takes place before a program begins to give those involved in program development a precise understanding of the program , and it is sometimes referred to as " pre - formative evaluation " ( 2 ) .
summative evaluation is the typical and most common type of evaluation , which is conducted at the end of a program to provide decision - makers with judgements about the program 's overall merit or worth .
however , although necessary , it often comes too late to be much help ( 3 ) . on the other hand ,
formative evaluation occurs during the process of a program to provide those who are responsible ongoing information about whether things are going as planned and whether expected progress is being made . if not , this same information can be used to guide necessary improvements , before it is too late ( 4 ) .
even though there is a great extent of literature on formative evaluation , most of them mainly focus on its conceptual framework , methodology and use .
surprisingly , the subsequent effect of using the findings of formative evaluation has not received systematic attention , and few researches demonstrate this by comparing data from the initial program with the final program to show whether there was an improvement in program implementation and impacts ( 5 ) .
this study aimed to evaluate the subsequent effect of the formative program evaluation based on a case study of a clinical training program in lao people 's democratic republic ( pdr ) .
the main health care delivery system of lao pdr is a government - controlled , public system which has a strong vertical structure with three levels : central , provincial , and district level ( 6 ) .
even though all health care professionals in the country are required by law to continuously improve their knowledge and skills , the continuing professional development ( cpd ) training system in lao pdr has not yet been functioning well ( 7 ) . in 2012 , under the support of korea international cooperation agency ( koica ) , faculties from seoul national university ( snu ) college of medicine in korea and university of health sciences ( uhs ) in lao pdr launched the " continuing professional development training project to strengthen the capacity of provincial and district hospitals in lao pdr " ( 8) . at the beginning of the project , uhs faculties conducted a needs assessment survey in luang prabang province , which was the pilot area for this project .
based on the needs assessment results , korean and lao faculties worked together to develop a cpd training program and a handbook including 80 clinical topics on 5 major clinical specialties : internal medicine , surgery , obstetrics and gynecology , pediatrics , and emergency medicine .
and then , uhs faculties provided a 1-week ' training of trainers ' program for 30 medical faculties of the luang prabang provincial hospital .
also , the training management committee composed of provincial hospital executives and department chairs was established to monitor and manage the training effectively .
finally , the trained provincial hospital faculties provided a 10-week training program in the provincial hospital for the district hospital health professionals in luang prabang province .
the training was conducted 4 times consecutively over 2 yr , and 12 medical professionals , 1 from each district hospital , were invited to each training program . among the total 48 medical professionals , 35 of them were medical assistants , and the other 13 were medical doctors .
the training was composed of 5 major clinical sections , and the trainees rotated each clinical section every 2 weeks .
lecture about clinical topics , observation of trainers ' performance , and trainee 's own medical practice with trainers ' feedback were the main training methods .
formative program evaluation was conducted during the whole process to continuously improve the training program ( fig .
1 ) . kirkpatrick model was applied for the program evaluation covering level 1 ( reaction ) and level 3 ( transfer ) ( 9 ) .
questionnaire survey and focus group interviews with the trainees were used to evaluate the reaction of the trainees .
the questionnaire was designed by the co - work of faculties from snu and uhs based on the literature review ( 1011 ) .
it was composed of 14 items , regarding the goals and objectives , relevance , organization , trainers ' knowledge , trainers ' communication , trainers ' preparedness , training methods , discussion and interaction , practical session , handbook , facilities , schedule , applicability , and helpfulness of the training program .
the trainees were asked to rate the items with a 5-point likert scale ( 1 , strongly disagree ; 2 , disagree ; 3 , neutral ; 4 , agree ; 5 , strongly agree ) ( table 1 ) .
the survey was conducted every two weeks at the end of each clinical section of the training program .
focus group interview with the trainees was facilitated by the uhs faculties at the end of each 10-week training program .
the transfer of the trainees was evaluated through the review of medical records written by the trainees .
total 354 medical records written by 44 trainees before and 3 months after the training program were collected .
global rating with a 5-point anchored scale ( 1 , novice ; 2 , advanced beginner ; 3 , intermediate ; 4 , proficient ; 5 , expert ) was used for the evaluation .
a total of 25 trainers received a half - day workshop before assessing the medical records , and they practiced with some pilot medical records and received feedback during the workshop .
the medical records were coded by the coordinator , and they were randomly distributed to the trainers without any personal and time information .
the difference of average scores between the medical records written before the training and those written after the training was calculated to evaluate the transfer of the trainees .
the evaluation data was collected under the responsibility of the training management committee and analyzed by the study team .
the results were shared with the committee and the trainers after the end of each batch of the training program .
the committee and the trainers reached a consensus on how to improve the training program through the group discussion based on the evaluation results .
after the final end of the training program , the average scores of the survey results and the achievement of global rating scores of medical records among the four batches were analyzed statistically with the anova using spss .
the institutional review board of seoul national university college of medicine and seoul national university hospital exempted review of this study since it was an analysis of de - identified data ( irb no .
the institutional review board of seoul national university college of medicine and seoul national university hospital exempted review of this study since it was an analysis of de - identified data ( irb no .
according to the results of the survey , the trainees were quite satisfied with the training program ( table 2 ) .
however , especially in the early period of the training program , the trainees were not so satisfied in such areas as the organization and schedule of the training program , and discussion , interaction , and practical sessions during the training program . from the second batch ,
there was continuous increase of the satisfaction of the trainees in all the items of the questionnaire , and most of the significant improvement happened between the first and the second batch ( supplementary fig .
the focus group interviews provided similar but more in - depth view of the trainees ' reactions ( table 3 ) .
however , especially at the first batch of the training , some trainees suggested that there should be more practice and interaction in the training program and the trainers should pay more attention and provide more explanation to the trainees . from the second batch of the training , comments about the program and
the trainers became more positive , and there was less criticism about the issues that were previously mentioned . in the second batch , some trainees suggested that the training should be more applicable to the situation of district hospitals , which also seemed to be improved from the third batch of the training program .
the average global rating scores of the medical records which were written after the training program were higher than those written before the training , except the second batch ( table 4 ) . and the achievement of the average global rating scores between the medical records before the training and those after the training increased from the first batch to the last batch , especially between the second and the third batch ( supplementary fig .
the purpose of this study was to evaluate the effect of the formative program evaluation , which was applied to continuously improve the training program . according to the evaluation results , there was continuous improvement of the reaction and the transfer of the trainees from the first batch to the last batch of the training program .
we might have a close look at the ways how the formative program evaluation contributed to the continuous improvement of the training program . at the first batch of the training program ,
the trainees were not so satisfied in some areas like organization and schedule of the training program , and discussion , interaction , and practical sessions in the training program .
some trainees thought the training activities were not enough for them , and there should be more practical sessions like bed side teaching or real practice rather than lectures .
trainees also suggested that the trainer should pay more attention to them and there should be more discussion and interaction between the trainer and the trainees .
the review of the medical records written by the first batch trainees showed a minimal achievement of global rating scores .
these results of the formative program evaluation were shared with the committee and the trainers at the end of the first batch of the training program .
the committee and the trainers reached a consensus on how to improve the training program through the group discussion based on the evaluation results .
they decided to increase the training activities , especially practical sessions like bed side teaching and real practice under supervision . and
even during the lecture time , they agreed to foster more interaction and discussion between the trainers and the trainees .
the training management committee also emphasized to the trainers that the trainees are not young students , but experienced medical professionals . at the second batch of the training program ,
the average scores of all the items in the survey were much increased , and there was no item which was rated below 4.0 . also the trainee 's comments , especially about the trainers , in the focus group interview became more positive than before .
however , the review of the medical records written by the second batch trainees did not show any achievement of global rating scores .
after a group discussion based on the results of the survey and focus interview , the training management committee and the trainers reached on a consensus that there still should be more practical sessions for the trainees , which later could be applicable to the medical practice in the district hospitals . at the third batch of the training program ,
the trainees were more satisfied with the practical sessions and more trainees appreciated the applicability of the training program . and
the achievement of global rating scores of the medical records was much increased comparing to the first and the second batch .
the program evaluation results of the fourth batch showed a minimal improvement of the reaction and transfer of the trainees .
there were several key factors which should be noted in this study on the formative program evaluation .
first of all , two levels , level 1 ( reaction ) and level 3 ( transfer ) , of the kirkpatrick model were selected for the program evaluation for the reason that the reaction of the trainees should be closely related to the implementation of the training program and the transfer of the trainees could be a reliable parameter of the outcome or impact of the training program ( 12 ) .
second , the survey for the evaluation of the trainees ' reaction was conducted every two weeks during the training program to improve the reliability of the ratings .
it was to minimize the dominating effect of the trainee 's emotional experiences of both the peak and the end of the training program ( 13 ) .
third , focus group interviews were added to seek more deeply the problems of the training program which were discovered by the survey results . by this
, the quantitative evaluation using a likert scale and qualitative evaluation using focus group interviews , both of which have their relative merits ( 14 ) , were integrated into the formative program evaluation process . finally , to evaluate the transfer of the trainees , medical records which were written 3 months after the training program were collected , analyzed , and compared with those written before the training .
it was based on the evidence from the previous studies that most meaningful changes would take place over a longer period of time than just right after the training ( 1516 ) .
we were not able to assign a control group and conduct a case - control study due to the small size of the trainees group . and
the formative program evaluation did not cover the level 2 ( learning ) and level 4 ( result ) of the kirkpatrick model because of the feasibility and the time limit of the evaluation process .
further study is needed for more delicate study design and concrete results . however , even though it was a pilot clinical training program in lao pdr , the plan for the formative program evaluation was designed from the beginning of the project , and was shared with the all the participants .
the whole evaluation process was conducted by the lao health professionals under the guidance and support of the study team . in conclusion
, the results showed that the formative program evaluation contributed to the continuous improvement of the training program .

Answer:
this study aimed to evaluate the effect of the formative program evaluation on the continuous improvement of a clinical training program for lao health professionals .
 the training program was conducted 4 times consecutively for total 48 health professionals , and the formative program evaluation was carried out during the whole process . to evaluate
 the satisfaction and the transfer of the trainees , the questionnaire survey , the focus group interview , and the trainees ' medical records were used . after the end of each batch of the program ,
 the evaluation data were analyzed , and its results were shared with the training management committee and the trainers , who , based on the results , reached a consensus on how to improve the program .
 the evaluation results and the comparison of them among the four batches of the program showed that there was a continuous increase of the satisfaction and the transfer of the trainees , especially in the early period of the program .
 the formative program evaluation which was conducted during the whole process of the clinical training program had a positive effect on the improvement of the program , especially in the early phase , by increasing the satisfaction and transfer of the trainees .


Question:
You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.

Paper text:
management of immature root with a necrotic pulp and apical periodontitis is a challenging task .
obturation of the root canal is difficult because of lack of apical barrier for containing the root filling material .
treatment of choice in such cases is the apexification procedure , i.e. , establishing an apical barrier .
it has also been shown that the use of calcium hydroxide weakens the resistance of the dentin to fracture . in recent times ,
a bonded restoration can be placed without any delay , thus reducing the possibility of root fractures .
the major disadvantage of mta is its manipulation due to which its placement in the wide apical area is difficult to achieve .
a matrix can be used in apexification procedures against which mta can be placed and condensed .
use of an apical matrix allows for the predictable placement and judicious use of this expensive material .
several materials have been recommended to create a matrix including calcium sulfate , hydroxyapatite , resorbable collagen , and platelet - rich fibrin . in this case series , we are presenting two cases of mta apexification using polyglactin - based resorbable suture material as the apical matrix .
a 16-year - old male patient reported with a chief complaint of discolored maxillary left central incisor .
history revealed that the patient had suffered trauma 8 years back and undergone treatment in a private clinic .
clinical examination revealed grayish discoloration of tooth 21 and attempted access preparation in the same tooth .
periapical radiograph showed well - defined periapical radiolucency and wide open apex in relation to tooth 21 [ figure 1a ] .
the final diagnosis was pulpal necrosis with chronic apical periodontitis in relation to tooth 21 .
after discussing different treatment options with the patient 's parents , we opted to go for mta apexification with the use of an apical matrix .
after rubber dam isolation , the tooth 21 was accessed and working length was established radiographically [ figure 1b ] .
root canal was chemo - mechanically debrided with circumferential filing using the international organization for standardization ( iso ) 80 k - file ( dentsply maillefer , switzerland ) in conjunction with copious amount of 0.5% sodium hypochlorite ( shivam industries , india ) .
a volume of 3 ml of 17% ethylenediaminetetraacetic acid ( edta ) solution ( prevest denpro , india ) was used for smear layer removal .
apexcal medicament paste ( ivoclar vivadent ag schaan , liechtenstein ) was placed in the root canal , and access cavity was restored with temp paste ( pyrex exports , india ) .
one week later , tooth was again accessed under rubber dam isolation , and copious amount of normal saline was used to remove any remnants of the calcium hydroxide medicament .
one end of the suture material was modified to form a mesh , whereas the other end is left as such so that it could be used to adjust the position of apical matrix [ figure 1c ] .
suture material was saturated with iodine - based radiographic contrast medium iopamidol ( bracco , italy ) for 10 min to render it radio - opaque [ figure 1d ] .
the matrix was gently placed on working length with the help of preselected hand pluggers [ figure 1e ] , and its position was verified using radiographs [ figure 1f ] .
any adjustment required was done using the hand pluggers or free end of the suture material .
white mta angelus ( angelus , londrina , pr , brazil ) was mixed according to manufacturer 's instructions and using hand pluggers , gently condensed against the matrix to form 4 mm of apical plug [ figure 1 g ] . after placing a moist cotton pellet ,
next day , root canal was obturated using lateral condensation of gutta - percha ( meta biomed , korea ) and ah - plus root canal sealer ( dentsply detrey gmbh , germany ) , and tooth was restored with brilliant ng bonded resin restoration ( coltene / whaledent , switzerland ) [ figure 1h ] .
the patient was recalled after 3 months for clinical and radiographic evaluation . at the follow - up visit ,
radiograph demonstrated the resorption of the apical matrix and healing periapical lesion [ figure 1i ] .
( a ) preoperative , ( b ) working length radiograph , ( c - f ) formation and placement of suture matrix , ( g ) mineral trioxide aggregate plug , ( h ) immediate postoperative , and ( i ) 3 month follow - up a 15-year - old female patient presented with the chief complaint of discomfort while chewing in front region of upper jaw .
patient gave a history of traumatic incident 9 years back for which she had visited a private clinic .
clinical examination revealed slightly grayish discolored tooth 21 and previously attempted treatment in the same tooth .
intraoral periapical radiograph showed a well - defined periapical radiolucency surrounding the wide open apex of tooth 21 [ figure 2a ] .
after rubber dam isolation , tooth was assessed and working length determined using the radiograph [ figure 2b ] .
root canal debridement was done using iso 80 k - file ( dentsply maillefer , switzerland ) and 0.5% sodium hypochlorite ( shivam industries , india ) .
a volume of 3 ml of 17% edta solution ( prevest denpro , india ) was used for smear layer removal .
root canal was medicated with apexcal paste ( ivoclar vivadent ag schaan , liechtenstein ) for 1 week .
after 1 week , 4 mm of mta plug was formed by condensing white mta angelus ( angelus , londrina , pr , brazil ) against vicryl suture ( johnson and johnson ltd . ,
next day , the tooth was obturated using laterally condensed gutta - percha ( meta biomed , korea ) and ah - plus ( dentsply detrey gmbh , germany ) [ figure 2e ] .
bonded composite resin brilliant ng ( coltene / whaledent , switzerland ) was used for definitive restoration . at the 3-month follow - up visit ,
periapical radiograph revealed resorbed apical matrix and healing periapical lesion in relation to tooth 21 [ figure 2f ] .
( a ) preoperative , ( b ) working length determination , ( c ) suture matrix in place , ( d ) mineral trioxide aggregate plug , ( e ) immediate postoperative , and ( f ) 3 month follow - up
a 16-year - old male patient reported with a chief complaint of discolored maxillary left central incisor .
history revealed that the patient had suffered trauma 8 years back and undergone treatment in a private clinic .
clinical examination revealed grayish discoloration of tooth 21 and attempted access preparation in the same tooth .
periapical radiograph showed well - defined periapical radiolucency and wide open apex in relation to tooth 21 [ figure 1a ] .
the final diagnosis was pulpal necrosis with chronic apical periodontitis in relation to tooth 21 .
after discussing different treatment options with the patient 's parents , we opted to go for mta apexification with the use of an apical matrix .
after rubber dam isolation , the tooth 21 was accessed and working length was established radiographically [ figure 1b ] .
root canal was chemo - mechanically debrided with circumferential filing using the international organization for standardization ( iso ) 80 k - file ( dentsply maillefer , switzerland ) in conjunction with copious amount of 0.5% sodium hypochlorite ( shivam industries , india ) .
a volume of 3 ml of 17% ethylenediaminetetraacetic acid ( edta ) solution ( prevest denpro , india ) was used for smear layer removal .
apexcal medicament paste ( ivoclar vivadent ag schaan , liechtenstein ) was placed in the root canal , and access cavity was restored with temp paste ( pyrex exports , india ) .
one week later , tooth was again accessed under rubber dam isolation , and copious amount of normal saline was used to remove any remnants of the calcium hydroxide medicament .
one end of the suture material was modified to form a mesh , whereas the other end is left as such so that it could be used to adjust the position of apical matrix [ figure 1c ] .
suture material was saturated with iodine - based radiographic contrast medium iopamidol ( bracco , italy ) for 10 min to render it radio - opaque [ figure 1d ] .
the matrix was gently placed on working length with the help of preselected hand pluggers [ figure 1e ] , and its position was verified using radiographs [ figure 1f ] .
any adjustment required was done using the hand pluggers or free end of the suture material .
white mta angelus ( angelus , londrina , pr , brazil ) was mixed according to manufacturer 's instructions and using hand pluggers , gently condensed against the matrix to form 4 mm of apical plug [ figure 1 g ] . after placing a moist cotton pellet ,
next day , root canal was obturated using lateral condensation of gutta - percha ( meta biomed , korea ) and ah - plus root canal sealer ( dentsply detrey gmbh , germany ) , and tooth was restored with brilliant ng bonded resin restoration ( coltene / whaledent , switzerland ) [ figure 1h ] .
the patient was recalled after 3 months for clinical and radiographic evaluation . at the follow - up visit ,
radiograph demonstrated the resorption of the apical matrix and healing periapical lesion [ figure 1i ] .
( a ) preoperative , ( b ) working length radiograph , ( c - f ) formation and placement of suture matrix , ( g ) mineral trioxide aggregate plug , ( h ) immediate postoperative , and ( i ) 3 month follow - up
a 15-year - old female patient presented with the chief complaint of discomfort while chewing in front region of upper jaw .
patient gave a history of traumatic incident 9 years back for which she had visited a private clinic .
clinical examination revealed slightly grayish discolored tooth 21 and previously attempted treatment in the same tooth .
intraoral periapical radiograph showed a well - defined periapical radiolucency surrounding the wide open apex of tooth 21 [ figure 2a ] .
after rubber dam isolation , tooth was assessed and working length determined using the radiograph [ figure 2b ] .
root canal debridement was done using iso 80 k - file ( dentsply maillefer , switzerland ) and 0.5% sodium hypochlorite ( shivam industries , india ) .
a volume of 3 ml of 17% edta solution ( prevest denpro , india ) was used for smear layer removal .
root canal was medicated with apexcal paste ( ivoclar vivadent ag schaan , liechtenstein ) for 1 week .
after 1 week , 4 mm of mta plug was formed by condensing white mta angelus ( angelus , londrina , pr , brazil ) against vicryl suture ( johnson and johnson ltd . ,
next day , the tooth was obturated using laterally condensed gutta - percha ( meta biomed , korea ) and ah - plus ( dentsply detrey gmbh , germany ) [ figure 2e ] .
bonded composite resin brilliant ng ( coltene / whaledent , switzerland ) was used for definitive restoration . at the 3-month follow - up visit ,
periapical radiograph revealed resorbed apical matrix and healing periapical lesion in relation to tooth 21 [ figure 2f ] .
( a ) preoperative , ( b ) working length determination , ( c ) suture matrix in place , ( d ) mineral trioxide aggregate plug , ( e ) immediate postoperative , and ( f ) 3 month follow - up
apexification is defined as a method to induce a calcified barrier in a root with an open apex or the continued apical development of an incomplete root in teeth with necrotic pulp .
this chemical has several disadvantages such as difficulty of the patient 's recall management and delay in the treatment .
furthermore , there is a risk of tooth fracture after dressing with calcium hydroxide for extended periods . the most promising alternative to calcium hydroxide is mta .
the advantages of this material are ( i ) reduction in treatment time , ( ii ) immediate restoration of the tooth , ( iii ) no adverse effect on the mechanical properties of root dentin . in a prospective study ,
placement of the material in a wide open area is a challenging task and also there is a risk of extruding this expensive material into periapical tissues .
lemon advocated the use of a matrix when the diameter of the perforation is larger than 1 mm to prevent the extrusion of sealing material .
similarly , a matrix can be used for the predictable placement of mta in apexification procedures .
various materials have been advocated to be used as a matrix , for example , calcium sulfate , hydroxyapatite , collagen , platelet - rich fibrin .
the common limitation shared by these materials is that once placed their position ca n't be adjusted as required .
vicryl is a synthetic absorbable suture material composed of 90% polyglycolic acid and 10% polylactic acid .
however , the suture material lacks the radio - opacity which makes it difficult to be viewed in the radiographs .
iopamidol was used in our technique to impart radio - opacity to the suture material .
it is a water soluble nonionic iodine - based contrast medium which is routinely used for angiography , arteriography , contrast - enhanced computed tomography , and urography .
however , a proper history of the patient and sensitivity test should be done before using it . in our technique ,
one end of the suture material was used for the matrix formation , whereas other end was kept outside the tooth so that the placement of the matrix can be adjusted as required .
after the matrix was placed at the desired position , the free end of the suture was cutoff and then mta was condensed against it .
the apical matrix mentioned here in our study is cost - effective , easily available , and provides for adjustment of its position .
resorbable suture with a contrast agent may be used as a matrix for mta placement but properly designed clinical trials with long - term follow - up are mandatory to support this novel technique as there is no evidence of such procedure available in the literature presently .
research concentrating on the effect of suture material and contrast media on the healing kinetics can further through some light on this technique .

Answer:
the treatment of choice for necrotic teeth with immature root is apexification , which is induction of apical closure to produce more favorable conditions for conventional root canal filling . the most commonly advocated medicament is calcium hydroxide although recently considerable interest has been expressed in the use of mineral trioxide aggregate ( mta ) .
 mta offers the option of a two - visit apexification procedure so that the fragile tooth can be restored immediately .
 however , difficulty in placing the material in the wide apical area requires the use of an apical matrix .
 materials such as collagen , calcium sulfate , and hydroxyapatite have been used for this purpose .
 this article describes the use of resorbable suture material to form the apical matrix which offers many advantages over the contemporary materials .


Question:
You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.

Paper text:
breast cancer is one of the major causes of mortality in middle - aged women , especially in developed countries . at present , there are no effective ways to prevent breast cancer since its cause remains unknown . therefore , early detection becomes the key to improving the breast cancer prognosis and reducing the mortality rates .
mammography has been widely recognized as being one of the most effective imaging modalities for early detection of breast cancer .
however , it is a hard work for radiologists to provide both accurate and uniform evaluation for the enormous number of mammograms generated in widespread screening .
a computer - aided detection or diagnosis ( cad ) system , which uses computer technologies to detect the typical signs of breast cancer , has been developed to provide a  second opinion  for radiologists and to improve the accuracy and stability of diagnosis . in general
, there are three signs of breast cancer in a mammogram : microcalcification clusters ( mcs ) , architectural distortions , and masses . in this paper
, we particularly focus on the detection of mcs since they appear in 3050% of mammographic diagnosed cases and show a high correlation with breast cancer .
according to the breast image reporting and data system ( bi - rads ) lexicon , mcs are tiny calcium deposits that appear as small bright spots in mammograms . as an example , figure 1 shows an mc in a mediolateral - oblique ( mlo ) mammogram .
it is often hard for radiologists to find individual mcs in mammograms because they are very small ( typically , 0.051  mm ) in the size and the contrast between the mcs and the surrounding breast tissue is not high enough .
over the past two decades , there has been extensive research focused on developing the cad tools for automatic detection of mcs in mammograms .
several review papers have also been published on this topic [ 2 , 48 ] .
as described in , mc detection can be classified into four categories : ( 1 ) image enhancement methods [ 913 ] ; ( 2 ) multiscale decomposition methods [ 1417 ] ; ( 3 ) stochastic modeling methods [ 18 , 19 ] ; and ( 4 ) machine learning methods [ 2028 ] . in , a performance evaluation was summarized using free - response receiver operating characteristic ( froc ) in which a support vector machine ( svm ) approach   is found to be superior to conventional methods and is capable of achieving a true positive rate of approximately 90% when the false - positive ( fp ) rate is on average of 1.1 fp clusters per image .
however , such fp is not low enough for clinical application .   in this paper
, we present a new method based on a hybrid method which combines a morphological technique   and wavelet decomposition processing for detecting the mcs in mammograms .
compared with previous methods , the proposed method can achieve not only a high sensitivity but also a lower fp . in the proposed method , we first use a multistructuring - elements ( ses- ) based top - hat transform to enhance the intensity of microcalcification .
subsequently , we employ a wavelet decomposition to refine the enhanced results for removing the false enhanced microcalcifications .
then , based on the feature of malignant mcs , threshold processing is used to segment the mcs from mammograms .
the rest of paper is organized as follows : section 2 presents a morphological processing technique to enhance the mcs in mammogram . in section 3
section 4 presents the detection of the mcs and gives the experimental results by using the proposed method .
as mentioned in section 1 , the mcs appear as small bright spots in mammograms . in this sense , mcs can be directly segmented by using a threshold process . however , since most mammograms have a low dynamical rang and the intensity contrast between mcs and surrounding tissue is quite low , selection of a threshold for the whole image is not an easy task . as a solution ,
the difference of gaussian ( dog- ) based method which approximates the individual microcalcification as a two - dimensional ( 2d ) gaussian kernel has been reported in , but this method only is suitable for detecting the microcalcifications with approximate circle shape .   in this section
, we propose a new method which is based on a morphological filtering technique   to enhance the individual microcalcifications for mc detection .
the basic idea of the method is to use a set of top - hat transforms based on multi - structuring elements ( ses ) of which sizes and shapes are fitted to the individual microcalcifications to enhance them .
the top - hat transform of a gray - scale image f is defined as f minus its opening by structuring element b :
 ( 1)t = f(f  b ) ,
 where  denotes the opening operation ; the difference operation yields an image in which only the components fitting to the se remain .
figure 2 illustrates the concept of the top - hat transform in one dimension .
in the top - hat transform , selection of an appropriate se fitting to the target objects is the key . since
individual microcalcifications in mammograms frequently vary both in size and shape , it is imposable to use a single se to remove all of them . to solve this problem
, we use a multi - ses - based method which uses eight different flat ses , denoted as bi  ( i = 1,2 ,  , 8) to remove the individual microcalcifications in the opening processing . in this paper
, the ses are a set of lines revolving around its center in a 15  15 array . for a mammogram image with resolution 0.05  mm / pixel
, the 15  15 array indicates that the objects whose size are larger than 0.75  0.75  mm will be removed in the opening operation .
figure 3 shows the flat ses used in the top - hat transform where the dots denote the centers of the ses .   for each se bi ,  i = 1,2 ,  , 8
, the opening operation yields an image , denoted by ( f  bi ) , in which the individual microcalcifications fitting to the se are removed .
then , in order to enhance these individual microcalcifications removed by the opening operation , we use a subtraction between the original image and the maximum of the opening results to obtain an image , given by
 ( 2)e = fargmax(f    bi ) .
figure 4 shows an original mammogram and an enhanced image obtained from ( 2 ) . comparing figure 4(b ) with figure 4(a )
, we can see that individual microcalcifications appearing on a complex background were enhanced successfully .
these results indicate that the microcalcifications can be easily segmented by using a threshold process .
however , the top - hat transform also enhances some undesired objects in the mammograms , such as mammary glands , vessels , and so on .
therefore , a refinement processing is required to remove these undesirable objects from the enhanced mammogram images .
as mentioned above , although the top - hat transform is capable of enhancing microcalcifications varying in size and shape , a side effect is that the undesirable objects are also enhanced .
based on an investigation , we found that these unwanted objects are mainly caused by the soft tissues , such as mammary glands and vessels .
the typical feature of them is that they have a relatively higher intensity compared with their surrounding area as well as an inner nonhomogeneous intensity .
figure 5 shows a comparison between the microcalcification and the mammary gland after the top - hat transform . comparing figures 5(c ) and 5(g ) , we find that the intensity of microcalcification in the enhanced image approximately equals that of the mammary glands .
however , since the individual microcalcification has almost homogeneous intensity , the size of the enhanced microcalcification is generally larger than that of the mammary gland . figures 5(d ) and 5(e ) show the expanded view of the dashed rectangles in figures 5(c ) and 5(g ) , respectively . we can find that the size of the microcalcification is almost twice as large as the size of the mammary gland .
therefore , the enhanced mammary glands can be treated as noise that can be removed according to their size . in this paper
, we employ a wavelet denoising method to remove the mammary glands because the wavelet decomposition can easily separate them according to their particular size .
the wavelet - based procedure for denoising the image consists of the following four steps .

a four - scale wavelet transform is used to decompose the image obtained from the top - hat transform .
symlet-2 ,  as the decomposition filters since they have the least asymmetry and highest number of vanishing moments .
figures 6(a ) and 6(b ) show the scaling function and wavelet function used in the decomposition filtering .
figure 7 shows the decomposition results in which w(4 , m , n ) ,  w(4 , m , n ) ,  and w(4 , m , n ) denote the detail coefficients at level 4 size of half the original image .

a four - scale wavelet transform is used to decompose the image obtained from the top - hat transform .
symlet-2 ,  as the decomposition filters since they have the least asymmetry and highest number of vanishing moments .
figures 6(a ) and 6(b ) show the scaling function and wavelet function used in the decomposition filtering .
figure 7 shows the decomposition results in which w(4 , m , n ) ,  w(4 , m , n ) ,  and w(4 , m , n ) denote the detail coefficients at level 4 size of half the original image .

since the size of the microcalcification is almost twice as large as the size of the mammary gland , the noise caused by the mammary gland can be decomposed in level 4 .
therefore , we set the detail coefficients at level 4 as well as the approximation coefficients at level 1 to zeros .
figure 7 shows the result of the four - scale wavelet transform in which the shaded coefficients marked are set to zero .
  thresholding the approximation and detail coefficients .
since the size of the microcalcification is almost twice as large as the size of the mammary gland , the noise caused by the mammary gland can be decomposed in level 4 .
therefore , we set the detail coefficients at level 4 as well as the approximation coefficients at level 1 to zeros .
figure 7 shows the result of the four - scale wavelet transform in which the shaded coefficients marked are set to zero .

figures 8(a ) and 8(b ) show the results of the inverse wavelet transform of the microcalcification and mammary gland in figures 5(d ) and 5(h ) .
we see that the intensity of the mammary gland is clearly reduced so that the microcalcifications and mammary glands can be easily separated using a threshold .

figures 8(a ) and 8(b ) show the results of the inverse wavelet transform of the microcalcification and mammary gland in figures 5(d ) and 5(h ) .
we see that the intensity of the mammary gland is clearly reduced so that the microcalcifications and mammary glands can be easily separated using a threshold .

, we use a thresholding processing to obtain a binary image in which each microcalcification is segmented as connected components .

we use a thresholding processing to obtain a binary image in which each microcalcification is segmented as connected components .
in this section , we introduce a procedure that segments the mcs from the mammogram image obtained from the above sections and give some experimental results by using the proposed method .
as mentioned in section 1 , the mcs are tiny calcium deposits clustering together in the mammogram images . based on an investigation on the bi - rads
, we found that a typical mc generally has the following two features:(1)an mc usually consists of four or more individual microcalcifications;(2)an mc generally appears within a limited area of size 10  10  mm in mammogram images .
an mc usually consists of four or more individual microcalcifications ; an mc generally appears within a limited area of size 10  10  mm in mammogram images .
 according to these two features , we use the following two steps to detect the mcs .
first , the binary image is subdivided into blocks that overlap their neighbors both horizontally and vertically .
the blocks are of size 200  200 pixels ; for each pair of overlapping blocks , the overlapping boundary region is of size 100  100 pixels .
second , for each block , if the total number of the connected components is larger than three , this block will be labeled as an mc .
we developed and tested the proposed method using a database collected by the tohoku university school of medicine .
these mammograms are of size 4740  3540 pixels , with a spatial resolution of 0.05  mm / pixel and 16-bit grayscale .
the performance of the proposed method is summarized by the true positive rate and false positive cluster per image .
table 1 summarizes the experimental results of the proposed method comparing with several previous methods [ 8 , 9 , 13 , 14 , 32 , 33 ] .
the proposed method is capable of detecting 92.9% of true microcalcification clusters with an average of 0.08 false microcalcification clusters detected per image . to our best knowledge
, this performance is better than most state - of - the - art methods in mc detection [ 2 , 34 ] . in the experiments
, we found that the fps are mainly caused by the linear - structure tissues interlacing with each other or benign calcifications with nonhomogenous intensity .
since the characteristics of linear - structure tissues are quite different with that of the mcs , we consider that fps can still be reduced by using a statistic classifier , such as a support vector machine ( svm ) .
in this paper , we presented a high - accuracy method for the detection of mcs in mammograms .
the proposed method combined a multi - ses top - hat transform and a wavelet - based denoising approach to enhance the individual microcalcifications in mammograms .
experimental results demonstrated that the proposed method is capable of detecting the mcs in mammograms with high accuracy .   in further work
, we will conduct more experiments on a wider database and improve its performance both in accuracy and computational cost .

Answer:
the presence of microcalcification clusters ( mcs ) in mammogram is a major indicator of breast cancer .
 detection of an mc is one of the key issues for breast cancer control . in this paper
 , we present a highly accurate method based on a morphological image processing and wavelet transform technique to detect the mcs in mammograms .
 the microcalcifications are firstly enhanced by using multistructure elements morphological processing .
 then , the candidates of microcalcifications are refined by a multilevel wavelet reconstruction approach . finally , mcs are detected based on their distributions feature .
 experiments are performed on 138 clinical mammograms .
 the proposed method is capable of detecting 92.9% of true microcalcification clusters with an average of 0.08 false microcalcification clusters detected per image .


Question:
You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.

Paper text:
conventional inguinal hernia repair in children involves ligation of the hernial sac at the internal inguinal ring .
laparoscopic surgery has been applied in children , and the repair is based on the same principle .
this study aimed to document the authors ' experience with laparoscopic inguinal hernia repair in children .
patients were admitted in the evening 1 day before surgery and discharged within 24 hours following surgery .
two lateral ports of 3-mm were made through the right and left pararectal region to maintain a triangular orientation . in cases with small defects , laparoscopic ring closure ( lrc )
was done with 4  0 absorbable purse - string suture ( figures 1 , 2 , and 3 ) .
in early cases and when difficulty was noted , saline was injected to separate the peritoneum from cord structures .
the procedure was modified in 24% of children with a dilated internal ring ( figure 4 ) .
ligature of the hernial sac at the internal ring is inadequate in such cases . here
the sac was identified and dissected from the cord structures and then divided ( figure 5 ) . in patients with a large hernial sac ,
the landmarks identified included the iliopubic tract ( ipt ) , arching of fascia transversalis , cord structures , and the peritoneal reflection ( figure 6 ) .
the ipt was identified as a shiny white band running under the cord structures at the inferior border of the internal ring .
the tranversus arch was identified as the arching of the transversalis fascia immediately above and lateral to the internal ring .
the ipt was approximated to the transversus arch by using nonabsorbable 2 0 interrupted suture to narrow the internal ring ( figure 7 ) .
all patients were evaluated after 5 days , 4 weeks , 6 months , 1 year , and then annually , when possible .
laparoscopic ring closure : continuation of the purse string on the inferior aspect of the internal ring .
laparoscopic ring closure : completion of the purse string suture and occlusion of the internal ring .
laparoscopic iliopubic tract repair : completion of the dissection and landmarks identified : ( a ) dilated internal ring , ( b ) iliopubic tract , ( c ) cord structures , ( d ) transversalis fascial arch .
ninety - three indirect inguinal hernial sacs were closed ( 28 right , 7 left , 58 bilateral ) in 64 children ( 56 boys and 8 girls ) , ranging in age from 3 years to 13 years ( median , 5.1 years ) .
the mean operating time for lrc was 25 minutes ( range , unilateral 21 to 35 ; bilateral 28 to 50 ) .
the contralateral processus vaginalis was patent in 20% of children . in 24% of children ,
of the 29 bilateral hernias , 20 underwent lrc , 7 underwent liptr , and 2 underwent lrc on one side and liptr on the other side .
the median follow - up was 30 months ( range , 2 to 84 ) .
the first recurrence was in a 3-year - old female child after 8 months , following a right lrc .
the second one was in a 4-year - old boy after 5 months , following a left lrc .
the essential step in the conventional method for inguinal hernia repair in children is simple ligation of the hernial sac without narrowing the open ring . from our point of view
first and the most obvious is the confirmation of the hernia and looking for the contralateral side .
first championed by ger , ring closure is essentially a high ligation of the indirect hernia sac , which is the preferred technique in pediatric patients .
this technique re - establishes the usual anatomic relations of the medial aspect of the internal ring and cord structures , giving them a flush union with the transversus abdominis muscle and eliminating the lead point that allows the intestine to enter the inguinal canal .
ligature of the hernial sac at the internal ring alone is inadequate in patients with dilated internal ring ( 24% of children ) , as it does not take care of the component of the dilated ring .
reports exist in the literature of methods to tighten this dilated ring . in hernias exceeding 4 mm to 5 mm in diameter , the external hemicircumference of the neck was opened to bring the conjoined tendon closer to the crural arch with a nonresorbable suture without the use of a prosthesis .
ipt repair has been described as ringplasty , wherein the deep structures of the lateral iliopubic tract were approximated to the proximal arching musculotendinous fibers of the transversus abdominis muscle gazayerli described a laparoscopic preperitoneal ipt repair by approximating the transversus abdominis to the ipt , similar to the anterior preperitoneal approach described by nyhus and associates .
we believe that in children with a dilated internal ring , a routine lrc would be inadequate .
this is also observed in our 2 recurrences with one of them occurring within 5 months of lrc .
the recurrence rate of inguinal hernias is slightly higher with laparoscopic herniorrhaphy than with the conventional technique .
following liptr , there have been no recurrences . in children with recurrences after lrc , the surgeon has an undisturbed anatomy for the groin incision ; the risk of an injury to the vas deferens , subsequent testicular atrophy , and the risk of superior displacement of the testicle seem less likely .
the problems we faced during liptr were trivial and related to the little scar tissue at the internal ring .
this could be explained by some peritoneal fluid passing in between the knots placed during ring closure .
our series shows that both techniques are safe , reproducible , and technically easy for experienced laparoscopic surgeons .
the long - term follow - up of liptr would help assess any technical modifications .
laparoscopic inguinal hernia repair in children can be offered , as it is safe , reproducible , and technically easy for experienced laparoscopic surgeons .

Answer:
background : this study aimed to document the authors ' experience with laparoscopic inguinal hernia repair in children.methods:ninety-three hernia repairs were performed in 64 children .
 the neck was closed with a purse string suture by using 4 - 0 absorbable suture.results:ninety-three indirect inguinal hernial sacs were closed in 64 children .
 nine percent of children had an ectopic testis .
 the mean operating time for laparoscopic ring closure was 25 minutes ( range , unilateral 21 to 35 ; bilateral , 28 to 50 ) .
 the contralateral processus vaginalis was patent in 20% of children . in 24% of children ,
 the final procedure was modified based on the findings of a dilated internal ring .
 a laparoscopic ilio - pubic tract repair was done in these cases .
 laparoscopic mobilization , orchiopexy followed by ilio - pubic tract repair was done in 9% of children .
 scrotal swelling occurred in one child .
 hydrocoele occurred in one patient .
 recurrence rate was 3.1%.conclusion : laparoscopic inguinal hernia repair in children can be offered , as it is safe , reproducible , and technically easy for experienced laparoscopic surgeons .
 iliopubic tract repair may be added in cases with dilated internal ring .
 recurrence following laparoscopic ring closure can be managed with laparoscopic ilio - pubic tract repair .
 the long - term follow - up of laparoscopic ilio - pubic tract repair is awaited .


Question:
You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.

Paper text:
necrotizing sialometaplasia was first described by abrams et al.1 in 1973 , and since then , other similar cases have been reported .
necrotizing sialometaplasia is an inflammatory , ulcerative lesion of the small salivary glands that usually occurs on one side of the hard palate , although it can also occur on the lower lip , posterior molar area , buccal mucosa , the parotid gland , tongue , and in the upper airway23 .
necrotizing sialometaplasia occurs more frequently in males , with the ratio of affected males to females approximately 2 to 12 .
it is histologically similar to mucoepidermoid carcinoma and squamous cell carcinoma but is a benign disease that spontaneously heals within 4 to 10 weeks .
necrotizing sialometaplasia of the hard palate re - occurred on the contralateral side after 5 months .
a 36-year - old woman was referred to the gangnam severance hospital ( seoul , korea ) by a private practice endodontist .
the patient stated that her palate felt uncomfortable and that her throat had been swollen for a week .
she had a history of smoking more than 40 cigarettes a day for 20 years and denied any other medical history .
endodontic treatment of the upper left first premolar under local anesthesia with 2% lidocaine and 1:100,000 epinephrine was completed by the endodontist before the patient 's arrival to our hospital .
a craterlike ulceration of 3 cm diameter , with necrotic tissue inside , was found on the left hard palate .
a ) the lesion was first diagnosed as either tissue necrosis caused by local injection of lidocaine containing epinephrine or necrotizing sialometaplasia , and was treated palliatively .
it was not possible to perform a biopsy at that time because the tissue was already necrotized.(fig .
c ) after 5 months , the patient returned to the hospital for recurrence of the same symptoms on the contralateral side of the hard palate without any particular dental event.(fig .
b ) microscopically , the palatal lesion showed diffuse necrosis of acini and ducts of palatal salivary glands ; however , the overall lobular structure of the involved gland was preserved .
3 ) based on histological analyses , the final pathological diagnosis for the palatal mass was necrotizing sialometaplasia . at the 3-year follow - up ,
the patient 's oral mucosa of the hard palate was normal , without any signs or symptoms.(fig .
c ) this study was approved by institutional review board of yonsei university gangnam severance hospital ( irb # 3 - 2015 - 0114 ) , and informed consent was obtained .
the cause of necrotizing sialometaplasia is unknown , but it is thought to result from infarctions of the salivary gland tissue125 .
the causes of such infarctions may be direct injury , effects of vasoconstrictors , or injuries from needles used in local anesthesia , ill - fitting dentures , drinking , smoking , cocaine use , radiation , infection of the upper airway or allergy , intubation , surgical treatment , and systemic diseases such as sickle cell disease , buerger 's disease , raynaud 's disease , and aids2345 .
shigematsu et al.6 reported that histopathological changes similar to those associated with necrotizing sialometaplasia may be observed when local anesthesia is repeatedly injected into the hard palate of mice .
necrotizing sialometaplasia with ulceration may occur when tissues in the salivary glands are infarcted and the acinar cells are subsequently necrotized .
brannon et al.2 reported that the risk of necrotizing sialometaplasia in smokers is about 10% ( 7/69 ) .
smoking could cause infarctionsin the salivary gland by continuously stimulating the palate and inducing vascular stenosis . in a previous study ,
the researchers were unable to determine the cause of necrotizing sialometaplasia in 44% of the patient sample ( 30/69 ) , and the rate of recurrence was 0% ( 0/14)2 . a number of reports have concluded that the risk of recurrence is normally 0% , and that instances of recurrence on the opposite side are rare .
however , histologically , tissues in the salivary glands show infarction , inflammation , granulation tissue , and squamous metaplasia of the salivary duct .
because such squamous metaplasia is often observed , it may be misdiagnosed as squamous cell carcinoma , and because it is similar to mucoepidermoid carcinoma in that the squamous metaplasia is surrounded by a faint outline of necrotized acinar cells , it is easily misdiagnosed as malignant 1278 . however , despite similarities of infection and necrosis , necrotizing sialometaplasia is distinguished from malignancies because its ductal structure is preserved37 . when necrotizing sialometaplasia is misdiagnosed as a malignancy , irreversible treatment such as radical resection may follow .
in contrast , some malignancies can be misdiagnosed as necrotizing sialometaplasia and subsequently go untreated .
therefore , bascones - martnez et al.5 reported that incisional biopsy is recommended for accurate diagnosis , with periodic treatment until full recovery9 .
the stages are not clearly separated and can progress from occurrence to full recovery without any treatment .
when salivary gland tissues become infarcted and are necrotized and separated , the necrotized tissues collapse , creating a crater - shaped ulcer .
the surrounding mucous membranes show secondary healing and require approximately 4 to 10 weeks for complete recovery2347 .
pain may or may not be present ; however , if there is pain in the first period of ulcer formation , the use of an analgesic is recommended . because necrotizing sialometaplasia appears as an inflammatory ulcer ,
some doctors treat it with antibiotics or steroids , but with no reported effects on clinical symptoms7 .
our patient case had a negative medical history with the exception of smoking and local anesthesia for dental treatment .
thus , in the preliminary diagnosis , we diagnosed our patient with necrotized tissue caused by the blockage of the terminal blood vessels from complications of smoking and the use of lidocaine with epinephrine .
after 3 weeks of follow - up , the necrotized tissues were no longer present and secondary healing of the soft tissues was apparent .
five months after the first occurrence of the lesion , we observed recurrence on the contralateral side of the hard palate without any particular factors other than smoking .
the second lesion was still within the initial period of necrotizing when observed , and we therefore conducted an incisional biopsy including both normal and necrotized tissues to confirm the diagnosis of necrotizing sialometaplasia . necrotizing sialometaplasia occurs unilaterally in 71% of previously - reported cases , and on both sides of the median suture line of the hard palate in 12% of cases2 .
however , in our case , there was a second occurrence on the contralateral side with a time lapse between the first and second occurrences , a presentation that is thought to be quite rare .
our patient was not definitively diagnosed upon the second occurrence , but the second lesion may have been caused by the patient 's heavy smoking habit , because she had experienced no dental events such as the use of local anesthesia .

Answer:
necrotizing sialometaplasia usually heals within 4 to 10 weeks with conservative treatment , and rarely recurs .
 when necrotizing sialometaplasia is present on the hard palate it may occur unilaterally or bilaterally . in this case , necrotizing ulceration occurred on the left hard palate of a 36-year - old woman after root canal treatment of the upper left first premolar under local anesthesia .
 after only saline irrigation the defect of the lesion completely healed and filled with soft tissue .
 after 5 months , however , a similar focal necrosis was found on the contralateral hard palate without any dental treatment having been performed on that side and progressed in similar fashion as the former lesion .
 we conducted an incisional biopsy and obtained a final pathological diagnosis for the palatal mass of necrotizing sialometaplasia . at the 3-year follow - up ,
 the patient 's oral mucosa of the hard palate was normal , without any signs and symptoms of the condition .
 we report a case of a second occurrence of necrotizing sialometaplasia on the contralateral side from the first , with a time lapse between the first and second occurrence .


Question:
You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.

Paper text:
venous malformation is defined as malformations comprised of slow - flowing , abnormal dilated veins , and venous network .
clinically venous malformations ( vm ) are present at birth and tend to grow steadily in proportion to the somatic growth of the child .
venous malformations are congenital lesions that affect boys and girls equally with a reported risk of developing other conditions within a specified period of time .
the occurrence rate is 1 - 2 per 10,000 births and 0.1 - 1% of a population are found to have this condition .
histologic and histochemical studies show that abnormalities are formed by small and large dysplastic post - capillary , thin - walled vascular channels with patchy deficiency of mural smooth muscle .
a 28-year - old male was referred to the oral and maxillofacial clinic for evaluation of multiple swellings on the left side of the face and inside his mouth .
the patient first noticed the swelling over the temple when he was 11-years - old . as the boy grew , the swelling also proportionately increased .
multiple poorly defined swellings were noted on the left side of the head and neck region around the temple , cheek , and submandibular region [ figure 1a and b ] .
similar lesion was noted in the supraclavicular and scapular region [ figure 2a and b ] .
the swelling was pulsatile and increased in size the when patient was standing ( dependent position ) .
intraorally lobulated swelling was noted on the floor of the mouth in the left sublingual region .
the lesion measured 3  4 cm , filling the entire floor of mouth , and purplish discoloration was also noted over the swelling [ figure 3a and b ] .
( a ) photograph ( front view ) shows swelling over the temple region and ( b ) photograph ( side view ) reveals well defined swelling over temple ( large arrow ) diffused swelling in the cheek , and submandibular region ( small arrow ) .
( a ) photograph shows a well - defined swelling measuring 1  1 cm in the left supraclavicular region and ( b ) photograph of the scapular region shows a diffused swelling .
( a ) intraoral photograph shows swelling in the floor of mouth filling the entire floor of mouth ( arrow ) and a small swelling in the buccal mucosa that has a purplish hue ( small arrow ) .
( b ) intraoral photograph of the labial sulcus reveals a purplish swelling ( arrow ) .
ultrasonography of the submandibular region showed a well - defined hypoechoic lesion having anechoic areas with septations , showing flow inside the lesion .
ultrasonography of the submandibular region with 7 mhz small parts transducer shows heterogeneous hypoechoic lesion with slow flow and hyperechoic foci suggestive of calcifications ( arrow ) . magnetic resonance imaging ( mri)-t2-weighted fat suppression , post - contrast axial images showed hyperintense lesions , which are well - defined with no flow voids .
all the lesions in the submandibular , cheek , and temple region had similar findings [ figure 5 ] .
direct puncture phlebogram of the left frontal scalp region revealed pooling of contrast into cavernous spaces draining into external jugular vein [ figure 6 ] .
( a ) axial section at the submandibular region shows well - defined hyperintense lesion ( arrow ) in the floor of mouth .
( b ) axial section at the level of cheek shows well - defined hyperintense lesion in the cheek region ( arrow ) .
phlebography of the lesion in the temple region shows filling of the entire lesion and draining to the regional area ( arrow ) .
histopathological examination revealed several thin - walled venous channels lined by flattened endothelium , supported by a dense uninflamed fibrous connective tissue stroma .
hematoxylin and eosin stained specimen ( 40 ) shows irregular venous channels ( large arrow ) lined by thin endothelium .
venous malformation ( vm ) is the second most common vascular anomaly of the head and neck after hemangioma .
venous malformations can occur anywhere in the body but are most frequently seen in the head and neck ( 40% ) , extremities ( 40% ) , and trunk ( 20% ) .
vms are slow - flow vascular anomalies composed of ectatic venous channels that will continue to grow throughout the patient 's lifetime .
they grow slowly in size with age , but their growth may be exacerbated following trauma , sepsis , or hormonal changes and they do not regress spontaneously . both men and women are equally affected .
vascular malformations are believed to be the result of a congenital error of vascular morphogenesis that occurs between the 4 and 10 weeks of intrauterine life .
vascular malformations have a quiescent endothelium and are considered to be localized defects of vascular morphogenesis , likely to be caused by dysfunction in pathways regulating embryogenesis and vasculogenesis .
these lesions vary in color depending on depth of involvement and range from mild detectable color change to deep purple color .
these lesions fill when the patient is standing and are compressible , which helps to distinguish them from lymphatic malformations on physical examination .
areas frequently involved in the head and neck region are masseter , temporalis , tongue musculature , as well as oral and airway mucosa .
soft tissue lesions are most frequently facial in location , with the buccal region being the most common site followed by the mandibular space , sublingual space , tongue , and orbit .
intraosseous calvarial involvement is most frequent in the frontoparietal region and the mandible is the most frequent location within the facial skeleton .
there may , however , be no visible manifestations with deeper lesions . in our case ,
the first anatomopathologic classification of vascular lesions based on the microscopic appearance was developed by virchow and wegner .
mulliken and glowacki ( 1982 ) developed a biological classification of vascular anomalies that included physical findings , clinical behavior , and cellular kinetics and classified them as hemangiomas and vms .
a more recently updated classification of vascular anomalies by international society for the study of vascular anomalies is now widely used [ table 1 ] .
classification of vascular anomalies ( issva 2007 ) plain radiographs have limited role in the investigations as they can identify only phleboliths .
ultrasound ( us ) is often the initial investigation to evaluate vascular malformations and it may characterize and define the extent of more superficial lesions . on gray - scale imaging , venous malformations can appear as hypoechoic or heterogenous lesions with anechoic structures visible in 50% of cases .
in addition , the doppler flow is generally monophasic low velocity flow , and in some cases flow is only discernible with compression and release of the lesion .
they typically appear as isointense or hypointense lesions on t1-weighted images , but could be hyperintense depending on the presence of intralesional fat .
lesions are typically lobulated , which gives them the characteristic  bunch of grapes  configuration . septations and rounded signal voids corresponding to phleboliths are additional distinguishing features . in t2-weighted or inversion recovery sequences ,
vms demonstrate high - signal intensity.this imaging modality is used to determine the full extent of the lesion and its relationship to adjacent vital structures .
gradient echo sequences reveal areas of low signal corresponding to calcification or hemosiderin or thrombosis .
t1-weighted post contrast imaging demonstrates homogenous or heterogeneous enhancement , and dynamic contrast - enhanced mri has increased the specificity of venous malformation diagnosis .
vms are best demonstrated by direct phlebography , which fills the sinusoidal spaces and any anomalous veins , allowing assessment of the size and extent of the lesion . in the present study , phleboliths were seen on plain radiography and us features were suggestive of vascular anomaly with slow flow rate . whereas , the mri features were suggestive of venous malformation , which was confirmed by direct phlebography where the lesion was seen draining the regional vein .
venous malformations usually are associated with syndromes like proteus syndrome and blue rubber bleb nevus ( bean ) syndrome .
multiple treatment options exist for venous malformations , including conservative measures such as head of bed elevation and compression , laser therapy , sclerotherapy , and surgery .
conservative management of venous malformations is usually reserved for smaller isolated asymptomatic lesions and is also important in controlling the growth and symptoms .
elevation of the head of the bed is important as it decrease hydrostatic pressure in the malformation , which can lead to expansion and can also decrease symptoms of airway obstruction , swelling , and pain that are experienced .
sclerotherapy remains a good option for the treatment of venous malformations in the head and neck .
sclerotherapy involves percutaneous injection of a substance to induce inflammation and thrombosis of the lesion , which then will lead to more long - term fibrosis and hopefully decrease or eliminate the expansion of the lesion .
sotradecol foam or ethibloc ( glue ) , or the sclerosant is mixed with fibrin glue or ethyl cellulose , bleomycin ( pingyangmycin ) and picibanil ( ok-432 ) have recently been used as sclerosants in asia with promising results .
large cervicofacial venous malformations present a much greater challenge , and one must be prepared to use multimodal therapy to keep the lesion under control .
these lesions generally can not be cured as doing so would leave devastating functional and cosmetic results .
therefore , therapy is used to control growth , maintain cosmesis , and decrease symptoms .
venous malformations are either superficial or deep veins that are abnormally formed and dilated . a thorough examination and investigation of the condition is needed to establish the exact extension of the condition and plan proper treatment .

Answer:
vascular malformations are congenital lesions that are present at birth and do not regress
 . however , they often present later in life .
 they are subdivided into two categories : ( 1 ) slow- or low - flow and ( 2 ) fast- or high - flow malformations .
 low - flow malformations contain combinations of capillary , venous , and lymphatic components .
 venous malformations can occur anywhere in the body , but are most frequently seen in the head and neck ( 40% ) .
 these lesions present in a variety of ways , from a vague blue patch to a soft blue mass , which may be single isolated or may occur in multiple areas .
 treatment depends on the type of lesion , the location , degree of involvement , and the clinical symptoms .
 here we are report the imaging and histopathologic findings in a patient with multiple venous malformations affecting the left side of the face and trunk .