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:
while over 90% of vulvar malignancies are squamous cell carcinomas , other histologic types include melanomas , basal cell carcinomas , sarcomas , extramammary paget 's disease , and bartholin gland adenocarcinomas .
 ectopic breast tissue  in the vulva was first described by hartung in 1872 , and since that time , several cases of both benign and malignant lesions arising in vulvar mammary tissue have been reported ( van der putte , 1994 ) .
the histology of the mammary - like tissue has multiple forms , ranging from simple , wide , slightly coiled tubular glands with a smooth outline , to more complicated forms in which the coiled structure has numerous branches and acini forming lobules .
similar to normal breast tissue , both epithelial and myoepithelial cells are present and the glands are subject to both the dysplastic and malignant changes that are seen in normal breast tissue ( van der putte , 1994 ) . we report a case of a mammary - like invasive carcinoma presenting as an asymptomatic vulvar nodule .
a 65  year old , multiparous , postmenopausal female status - post total hysterectomy with bilateral salpingo - oophorectomy 39  years prior for symptomatic myomatous uterus , presented for her annual well woman exam .
she was without complaints and review of systems was negative ; specifically , she denied any recent history of unintended weight loss or gain , fever , chills , nausea , melena or hematochezia , vaginal bleeding or discharge , abdominal pain or fullness .
her last mammogram was 12  years prior , after which she was diagnosed with right breast ductal papilloma which was excised .
in addition to her prior hysterectomy , gynecologic history was significant for estrogen replacement therapy for 20  years , which she stopped after developing what she reported as
two years prior to presentation , she had such a lesion removed from her right labia that had been present for one year and pathology was benign , per patient . on further discussion , she reported that the lesion had returned , was not painful , and was not associated with any further growth for the last six months .
clinical breast examination did not demonstrate evidence of palpable masses , retraction , skin changes , or axillary adenopathy .
genital examination revealed a mobile , soft , non - tender , 2.5    0.75  cm nodule at 11 o'clock on her right labia majora .
excisional biopsy was performed in clinic , which revealed ductal carcinoma in situ with positive margins .
the patient then underwent a wide local excision of the area , which pathologically revealed invasive carcinoma with negative margins . the specimen from the wide local excision revealed a surface which was predominantly dark brown and wrinkled with a smooth , white
, flat lesion measuring 0.8    0.3  cm ; the lesion was 1.2  cm from the 12 o'clock margin and 0.4  cm from the nearest ( 3 o'clock ) margin . on serial sectioning , the lesion was firm and white , and extended to a depth of 0.3  cm .
microscopic examination revealed invasive carcinoma , at least 1.6  mm in greatest dimension ( fig .  1 ) , arising from within a background of mammary - like glands of the vulva demonstrating residual focal dcis .
the invasive lesion was noted to come within 1.3  mm of the margin , but all margins were negative for invasive disease .
immunohistochemical ( ihc ) stains including smooth - muscle heavy chain ( smm - hc ) , cd 10 , and p63 were performed and while there appeared to be some myoepithelial cells present along the smooth contoured edge by smm - hc only , there were other areas without any definitive basal cell / myoepithelial cell staining ( fig .  2 ) .
the area of concern demonstrated an irregular growth pattern ( no longer lobulocentric ) and was not associated with the prior biopsy site changes .
the tissue was then tested for hormone receptor status , and was found to be estrogen receptor ( er ) positive , but progesterone receptor ( pr ) and her2/cep17 negative .
secondary to narrow margins , re - excision was performed as well as an ipsilateral groin sentinel lymph node dissection , both of which were negative for dcis or malignancy .
after referral to a medical oncologist , she was also administered letrozole , an aromatase inhibitor , as adjuvant therapy for the er positive cancer .
a relative paucity of reports has documented complications of ectopic breast tissue in the vulva , beginning with hartung in 1872 .
mammary ridges were theorized to have developed in a line from the axilla to the groin , and while the large majority of these ridges would normally regress , it was possible for rudimentary tissue to persist and develop into supernumerary mammary tissue ( van der putte , 1994 ) .
these mammary - like glands have an unknown function , but were distinguished from eccrine and apocrine glands .
the glands are simple tubular structures and are sparsely concentrated ; however , in some women they are more numerous and assume more complicated forms that resemble mammary tissue ( van der putte , 1994 ) .
the more complicated forms contain the basic coiled structure , but are obscured by numerous branches and acini which form lobules .
they are distinctly different from eccrine and apocrine glands by multiple factors including : 1 ) the type of epithelium , 2 ) the formation of diverticula , branches , and lobuli , 3 ) the shedding of clusters of epithelium , and 4 ) the expression of receptors for estrogen and progesterone .
additionally , mammary - like glands are also noted to be different than normal mammary tissue derived from the mammary ridges for multiple reasons as well : 1 ) their simpler configuration , 2 ) the higher number of glands than would be expected in rudimentary elements from mammary ridges , and 3 ) the direct relationship to eccrine glands .
furthermore , based on human embryologic studies , the mammary ridges could not involve the anogenital area , as at the height of the formation of the mammary ridges in 9  mm and 10  mm embryos , the labia majora are still far from their first appearance ( van der putte , 1994 ) .
however , ectopic breast tissue has been described in the vulva , as well as in any other area of the body .
both ectopic breast tissue and mammary - like glands are susceptible to the physiologic , dysplastic , and malignant changes seen in normal breast parenchyma ( castro and deavers , 2001 ) , as there have been reported cases of invasive ductal carcinoma , ductal carcinoma in situ ( dcis ) , lobular carcinoma , mucinous adenocarcinoma , phyllodes tumors , and fibroadenomas in accessory breast tissue in the vulva ( lopes et al . , 2006 ) .
although ectopic mammary tissue in the vulva is believed to be present in two to six percent of women , few cases of invasive ductal carcinoma have been reported in the literature ( kazakov et al . , 2011 ) .
the most common clinical presentation is a painless , solitary nodule , arising most often in the labia majora .
patient age at presentation has been between 45 and 84  years , with most being 60 or older ( kazakov et al . ,
most carcinoma cases are histologically consistent with invasive ductal carcinoma , which is also the most common histology in orthotopic breast tissue ( kazakov et al . , 2011 ) .
this still leaves a differential diagnosis of primary mammary carcinoma , carcinoma of a skin appendage , or metastatic mammary carcinoma .
recognition of an in situ component is the best clue to establishing the primary origin in the skin , as was seen in our case , rather than a metastatic process ( kazakov et al . , 2011 ) .
secondary to the rarity of these lesions , there is no widely accepted recommended management strategy .
a recent review only identified approximately 25 cases reported in the literature ( benito et al . , 2013 ) .
management strategies have ranged from wide local excision for dcis to radical vulvectomy with bilateral inguinofemoral nodal dissection for invasive carcinomas ( irvin et al . , 1999 ) .
adjuvant therapies have included radiation , anthracycline - based chemotherapy , and hormonal therapy , in an attempt to decrease recurrence and improve survival .
patients that did not receive adjuvant therapy had a median survival of 4  months ( lopes et al . , 2006 )
. only 1 patient out of 8 who received adjuvant therapy had died at the time of the previous publications , and the median survival was greater than 22  month ( lopes et al . , 2006 , irvin et al . , 1999 ) .
not surprisingly , there have been no clinical trials to evaluate the effectiveness of chemotherapy and radiation in such a small number of patients , so information on treatment has been , and should continue to be , extrapolated from treatment of cancers in the breast  i.e. excisional procedure with or without lymph node dissection , followed by other adjuvant therapies as needed .
there is little to no data reporting on the utility of sentinel lymph node biopsy in this clinical scenario .
breast carcinoma is almost exclusively managed using sentinel lymph node mapping ( krag et al . , 2010 ) , while promising data support the use of this technique for vulvar cancer ( levenback et al . , 2012 ) .
vulvar cancer is ideally suited for sentinel lymph node mapping secondary to the predictable lymphatic drainage of the vulva , the low false negative rate , and the substantially reduced morbidity ( e.g. lymphedema ) compared to a full groin lymph node dissection ( levenback et al . , 2012 ) .
we demonstrate this to be a potentially feasible technique for primary breast adenocarcinomas arising within the vulva in mammary - like glands , and in the context of such a rare histology , may be included in the management options of this disease .

Answer: highlightsprimary invasive breast carcinoma can be found arising from within mammary - like glands in the vulva.there is no standard management strategy for this rare disease ; treatment recommendations should be similar to that for primary breast carcinoma.the use of sentinel lymph node biopsy may offer another management option for this 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:
approximately 1 - 5% of peripheral blood t cells express the  t - cell receptor instead of the conventional  t - cell receptor .
the  versus  t - cell lineage commitment during intrathymic t - cell development seems to be controlled by the signal strength provided to the  t - cell receptor . in healthy donors ,
most blood  t cells carry a specific t - cell receptor composed of v9 and v2 elements .
in addition to effector functions shared with  t cells , the v9v2 t cells can acquire professional antigen - presenting capacity characteristic of dendritic cells .
in contrast to  t cells , v9v2 t cells do not see processed antigenic peptides presented by major histocompatibility complex molecules , but rather recognize small phosphorylated non - peptide molecules (  phosphoantigens ) produced by many microorganisms but also by transformed eukaryotic cells . while microbial phosphoantigens are active at pico- to nanomolar concentrations , micromolar concentrations of the eukaryotic phosphoantigen isopentenyl pyrophosphate ( ipp ) are required for  t - cell activation .
such high concentrations are not achieved in the mevalonate pathway of isoprenoid synthesis used in non - transformed cells .
interestingly , human v9v2 t cells can kill a broad variety of epithelial tumor and leukemia / lymphoma cells .
the sensitivity of tumor cells to  t - cell - mediated killing is increased upon treatment of tumor cells with aminobisphosphonates ( n - bps ) , drugs that are used in clinical practice for the treatment of osteoporosis and bone metastasis in cancer patients .
n - bps inhibit the ipp - processing enzyme farnesyl diphosphate synthase ( fpps ) , thereby leading to an accumulation of ipp , which is then sensed by the  t cells .
 t cells are poor producers of interleukin-2 ( il-2 ) , which is required for expansion of  t cells .
therefore , attempts to activate tumor - reactive  t cells endogenously by treating patients with n - bps must take into consideration an appropriate supply of il-2 .
alternative strategies consider the adoptive transfer of in vitro expanded tumor - reactive  t cells [ 10 - 14 ] .
the critical role of fpps in the control of intracellular ipp levels , and thus of the sensitivity of tumor cells toward  t - cell killing , has been recently demonstrated using short hairpin rna - mediated knock - down of fpps .
knock - down of fpps caused tumor cells , which otherwise were not recognized by  t cells , to be susceptible to  t - cell killing .
therefore , v9v2 t cells recognize and kill tumor cells on the basis of the unbalanced isoprenoid metabolic pathway in transformed cells , a pathway that is stable in non - malignant cells .
the discovery that n - bps activate  t cells by inhibiting fpps , thereby leading to accumulation of ipp , has paved the way for proof - of - principle studies to activate  t cells in patients with advanced cancer . in a phase i clinical trial , dieli and
colleagues   treated patients with hormone - refractory prostate cancer with a standard application of the n - bp zoledronate ( 4 mg intravenous infusion every 21 days ) either with or without additional low - dose ( 6  10 iu ) subcutaneous application of il-2 .
various parameters , including subset analysis of  t cells , and serum levels of prostate - specific antigen and cytokines , were monitored over time . although the two cohorts comprised only a few patients , statistically significant effects of zoledronate plus il-2 on the mobilization and effector cell maturation of  t cells were recorded . very importantly , the two cohorts showed distinct clinical outcomes , with clinical responses seen in six of nine patients treated with zoledronate plus il-2 but only in one of nine patients treated with zoledronate alone .
interestingly , a correlation between favorable outcome at 12 months and  t - cell numbers or functional status ( or both ) was observed .
similarly , wilhelm and colleagues had previously shown that the combined application of n - bp plus low - dose il-2 can induce objective tumor responses in patients with lymphoid malignancies .
together , these studies support the view that application of n - bps plus il-2 is safe , induces in vivo activation / maturation of  t cells , and may have beneficial effects in advanced cancer ( figure 1a ) .
( a ) n - bps inhibit farnesyl diphosphate synthase ( fpps ) , thus preventing processing of isopentenyl pyrophosphate ( ipp ) to farnesyl diphosphate ( fpp ) .
the combined application of n - bp plus il-2 leads to in vivo activation of  t cells .
( b ) alternatively ,  t cells can be activated in vitro with n - bp or synthetic phosphoantigens in the presence of antigen - presenting cells ( apc ) and can be subsequently expanded to large cell numbers by an exogenous supply of il-2 for subsequent adoptive transfer into cancer patients .
the cell preparation can be performed under gmp ( good manufacturing practice ) conditions . in a case study reported by laggner et al . , regression of lung and bone metastases was observed in a patient with advanced stage melanoma upon systemic treatment with zoledronate and localized radiotherapy .
although  t - cell subsets were analyzed , it is difficult to ascertain a substantial role of  t - cell activation in the resolution of metastases in this single case , particularly since il-2 was omitted in the treatment of this patient .
in addition to their  t - cell activating properties , n - bps also exhibit direct anti - tumor activities by both inhibiting proliferation and inducing apoptosis in tumor cells . while zoledronate seems to be the most potent  t - cell - activating substance among the n - bps licensed for clinical application , derivatives of zoledronate with
further improved  t - cell - stimulating capacity and enhanced direct anti - tumor activity are under development .
such modified n - bps might also exert improved in vivo activation of  t cells when given to patients together with il-2 .
t - cell - based immunotherapeutic strategy is the adoptive transfer of in vitro expanded v9v2 t cells from tumor patients ( figure 1b ) .
recently , efficient protocols for the large - scale in vitro expansion of v9v2 t cells based on stimulation with synthetic phosphoantigens   or zoledronate   have been established .
first results indicate that the repetitive adoptive transfer of in vitro expanded  t cells is well tolerated and may induce anti - tumor responses in patients with solid tumors , including renal cell carcinoma   and myeloma .
the protocol developed by dieli et al .   for the in vivo activation of  t cells based on zoledronate plus
low - dose il-2 application is ready to be explored in larger clinical trials and in other tumor entities with poor prognosis , for example , pancreatic ductal adenocarcinoma where it might be combined with standard regimens such as gemcitabine .
it is conceivable that this protocol can be further improved , for instance , by combination with tumor - targeting monoclonal antibodies . along this line
, it has been shown that b - cell lymphoma or breast tumor cell killing by fc receptor - expressing  t cells is enhanced in the presence of targeting antibodies rituximab ( cd20 ) or trastuzumab ( her2/neu ) , respectively . moreover , a  t - cell - stimulating synthetic phosphoantigen was found to enhance the depletion of cd20 b cells by rituximab in a non - human primate model in vivo , pointing to the possible use of phosphoantigen plus anti - cd20 antibodies in the treatment of cd20 leukemias and lymphomas .
furthermore , cytokines promoting homeostatic proliferation and survival of t cells , such as il-15 , or cytokines potentiating the cytolytic activity and pro - inflammatory response , such as il-21 , might be combined with il-2 or used instead of il-2 .
this could be considered both for in vivo application together with n - bps and for optimization of in vitro expansion of  t cells .
in addition , future study protocols might include the combination of in vivo activation of  t cells ( by n - bp or phosphoantigen plus il-2 ) followed by the adoptive transfer of in vitro expanded  t cells , finally , it should be stressed that  t - cell - based immunotherapy is not expected to replace established therapeutic protocols .
rather , it might offer additional benefit to the patient , for instance , in combination with conventional chemotherapy .

Answer:
t lymphocytes are a numerically small subset of t cells with potent cytotoxic activity against a variety of tumor cells .
 human  t cells expressing the v9v2 t cell antigen receptor recognize endogenous pyrophosphate molecules that are overproduced in transformed cells . moreover , the intracellular accumulation of such pyrophosphates is strongly enhanced by aminobisphosphonates used in the treatment of osteoporosis and bone metastasis in certain cancer patients .
 a new concept of cancer immunotherapy is based on the endogenous activation of  t cells with aminobisphosphonates plus low - dose interleukin-2 .


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:
five provinces in afghanistan were selected as a convenience sample ( accessibility ) that included both affected and unaffected areas .
two accessible districts in each province were randomly selected by using a random number generator .
random transects were used to select 10 households per village . to give an approximately equal male : female ratio , either the head of household , spouse ( woman ) , or the oldest person available at the time was selected .
ethical approval was provided by the institutional review board , ministry of public health , afghanistan . a standardized , structured questionnaire collected information on demographic and socioeconomic measures , avian influenza information sources and knowledge of appropriate preventive measures , poultry and animal handling , food and generic hygiene , and human influenza knowledge and treatment seeking .
the questions were ranked for importance in preventing avian influenza transmission in poultry or reducing human exposure and awarded 5 points , 3 points , or 1 point for correct answers . for each respondent ,
the sum of scores for correct answers divided by the sum of available points generated a percentage score .
data were double - entered by using microsoft access ( microsoft , redmond , wa , usa ) and analyzed by using stata 8 software ( stata corporation , college station , tx , usa ) .
percentage scores for each respondent were ranked and classified as above or below the median .
the primary analysis was conducted to compare factors ( age , sex , socioeconomic status , provincial exposure to avian influenza iec campaigns , and poultry ownership ) associated with knowledge above the median . socioeconomic quintiles ( seqs ) were defined by principle components analysis using employment , education , and household assets as indicators ( 3 ) .
factors independently associated by univariate regression at the 95% confidence level were included in a stepwise multivariate logistic regression model . to numerically evaluate kap levels , a secondary analysis assessed differences between mean percentage scores , stratified by factors identified by logistic regression analysis .
data for 304 respondents were included in the analysis . of the 5 provinces , kabul and nangahar had had influenza outbreaks in poultry in 2007 .
median age of respondents ( 38 years ) was high , but it reflected the age of heads of households and spouses .
poultry ownership was reported by 65.2% of households ( > 95% backyard ownership ) and differed significantly between seqs ( poorest 53/62 [ 85.5% ] vs. least poor 20/55 [ 36.4% ] ;   30.0 , p<0.001 ) .
provinces exposed to avian influenza and intensive information , education , and communication campaigns ( kabul , march 2007 , and nangahar , february 2007 ) .
seq was positively associated with kap score above the median ( lowest vs. highest : adjusted odds ratio [ aor ] 14.3 , 95% confidence interval [ ci ] 5.239.9 ) , as was provincial exposure to avian influenza iec campaigns ( aor 9.5 , 95% ci 4.918.6 ) .
backyard poultry ownership ( nonowners vs. owners : aor 0.3 , 95% ci 0.20.7 ) and older age group ( 1520 years vs. > 40 years : aor 0.3 , 95% ci 0.10.8 ) were both negatively associated . for secondary analysis ,
mean kap score differed between seq ( p<0.001 , by analysis of variance ) and was higher in provinces previously exposed to iec campaigns ( 50.2% vs. 40.1% ; p<0.001 , by t test ) .
reporting of sick or dead poultry to authorities was less frequent among lowest seq ( 8/47 [ 13% ] ) than highest seq ( 20/49 [ 37% ] ;  6.6 , p = 0.02 ) where selling poultry in the event of a local outbreak was more commonly reported ( 21/66 [ 66% ] vs. 10/51 [ 18% ] ;  27.2 , p<0.001 ) .
presence of coops was less frequent in lowest seq ( 9/49 [ 18.4% ] ) than in highest seq ( 21/46 [ 45.6% ] ;  8.2 , p = 0.004 ) .
human cases of avian influenza ( h5n1 ) have resulted from contact between humans and infected backyard poultry ( 4 ) .
risk to humans is also related to frequency of disease occurrence in the avian population ( 5 ) .
recently , human - to - human transmission has been reported in the neighboring northwest frontier province of pakistan ( 2 ) .
overall knowledge was low , although in provinces exposed to intensive iec campaigns , kap scores of the population were higher .
the level of concern generated by the campaign , government response , media reports , and proximity to the outbreak are all likely to contribute to this association . despite this encouraging evidence , level of knowledge was far higher among persons with higher socioeconomic status .
our results can be broadly generalized to the population , although we did not have access to unsafe districts ( most of the districts in southern and eastern afghanistan ) .
this limitation may introduce selection bias , which would underestimate the effect of socioeconomic status because those living in inaccessible areas likely have a lower status than persons in accessible areas .
preintervention and postintervention surveys would provide a more robust measure of effectiveness . in the immediacy of an outbreak ,
although there are limitations to the study design in concluding intervention effectiveness , the results provide evidence to support further intensive campaigns as a response to influenza outbreaks in poultry .
several reports have examined kaps and behavior related to avian influenza ( h5n1 ) ( 69 ) .
similar to the finding in the lao people s democratic republic ( 6 ) , our study suggests that conventional education and behavior change messages have a limited effect in populations with highest exposure .
efforts to ensure that iec messages are suitable for lower socioeconomic groups should be adopted , specifically by improving the knowledge of community leaders , designing messages in a suitable format for the poor and illiterate , and ensuring that the most accessible channels are used .
messages should carefully balance the risk for human disease against potential nutritional and economic consequences of high population concern ( e.g. , food scares ) . successfully promoting behavior change is a lengthy process and requires frequent reinforcement .
the acuteness of avian influenza ( h5n1 ) outbreaks requires a concerted effort to enhance knowledge and change behavior among those most at risk in low - income countries .

Answer:
from february through april 2007 , avian influenza ( h5n1 ) was confirmed in poultry in 4 of 34 afghan provinces . a survey conducted in 2 affected and 3 unaffected provinces found that greater knowledge about reducing exposure
 was associated with higher socioeconomic status , residence in affected provinces , and not owning backyard poultry .


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:
a 53-year - old caucasian female with complaints of dry eyes and a burning sensation in the eyes presented to our ophthalmology clinic 5 years ago .
her medical history revealed that the symptoms had persisted for 10 years , with some relief with lubricating eye drops used every 0.51 h. prior serology studies for antinuclear antibodies ( ana ) , ro and la were all negative .
she denied any symptoms of dryness of her mouth , and she had no other comorbidities .
clinical examination showed dry eyes , with slit lamp examination revealing thickening and hyperemia of the eyelids .
she was put on genteal gel alternating with artificial tears ( restasis eye drops ) four times / day . during the course of the next 5 years
, she underwent multiple surgeries for persistent eye dryness , including three procedures of silicone punctual plug placement in each eyelid , permanent thermal punctual occlusion , and later , resection of the canaliculus due to repeat reopening of the punctum despite three permanent thermal occlusions and continued patient discomfort secondary to refractory dryness of the eyes . additional evaluation to determine the etiology of dry eyes was done .
it revealed the presence of antibodies to salivary gland protein 1 ( sp1 ) and parotid secretory protein ( psp ) , leading to the diagnosis of sjogren 's syndrome ( ss ) .
a 68-year - old caucasian female with a known history of rheumatoid arthritis ( ra ) presented to our ophthalmology clinic with complaints of persistent dry eyes and irritation for the last 25 years .
she had tried artificial tears , restasis eye drops and genteal gel with some relief .
her prior workup by her rheumatologist included antibodies to ro and la , which were both negative .
on physical evaluation , she was noted to have dry eyes . slit lamp examination revealed hyperemia and thickening of the eyelids .
her laboratory evaluation in our clinic included antibodies to ro and la that were negative and antibodies to ana and rheumatoid factor , which were both positive .
evaluation of additional autoantibodies revealed the presence of antibodies to sp1 and psp , leading to the diagnosis of ss .
antibody testing for sp1 and psp in both patients was done at immco diagnostic laboratory , buffalo , n.y .
a 53-year - old caucasian female with complaints of dry eyes and a burning sensation in the eyes presented to our ophthalmology clinic 5 years ago .
her medical history revealed that the symptoms had persisted for 10 years , with some relief with lubricating eye drops used every 0.51 h. prior serology studies for antinuclear antibodies ( ana ) , ro and la were all negative .
she denied any symptoms of dryness of her mouth , and she had no other comorbidities .
clinical examination showed dry eyes , with slit lamp examination revealing thickening and hyperemia of the eyelids .
she was put on genteal gel alternating with artificial tears ( restasis eye drops ) four times / day . during the course of the next 5 years
, she underwent multiple surgeries for persistent eye dryness , including three procedures of silicone punctual plug placement in each eyelid , permanent thermal punctual occlusion , and later , resection of the canaliculus due to repeat reopening of the punctum despite three permanent thermal occlusions and continued patient discomfort secondary to refractory dryness of the eyes . additional evaluation to determine the etiology of dry eyes was done .
it revealed the presence of antibodies to salivary gland protein 1 ( sp1 ) and parotid secretory protein ( psp ) , leading to the diagnosis of sjogren 's syndrome ( ss ) .
a 68-year - old caucasian female with a known history of rheumatoid arthritis ( ra ) presented to our ophthalmology clinic with complaints of persistent dry eyes and irritation for the last 25 years .
she had tried artificial tears , restasis eye drops and genteal gel with some relief .
her prior workup by her rheumatologist included antibodies to ro and la , which were both negative .
her medications included methotrexate for her ra for the last 30 years . on physical evaluation ,
her laboratory evaluation in our clinic included antibodies to ro and la that were negative and antibodies to ana and rheumatoid factor , which were both positive .
evaluation of additional autoantibodies revealed the presence of antibodies to sp1 and psp , leading to the diagnosis of ss .
antibody testing for sp1 and psp in both patients was done at immco diagnostic laboratory , buffalo , n.y .
ss is an autoimmune disease starting in the lacrimal and salivary glands but with eventual systemic involvement of multiple other organs .
ss can also occur secondary to other autoimmune diseases such as lupus and ra , known as secondary ss .
patients with ss typically present with a dry , gritty sensation in the eyes and a dry mouth . at this stage
typically , involvement of the lachrymal and submandibular glands occurs before involvement of the parotid glands . due to this
, the presentation of dry eyes may occur much earlier in the disease process and precede the presence of a dry mouth .
about 5% of the patients with ss develop b cell lymphoma , most commonly occurring in the salivary glands and gastrointestinal tract [ 1 , 2 , 3 ] .
the diagnostic criteria for ss include clinical criteria : a schirmer test with a result of < 5 mm of wetting/5 min or a rose bengal score of > 4 ( van bijsterveld ) as well as ocular and oral symptoms .
daily persistent dry eyes for more than 3 months , use of lubricants more than 3 times / day , a recurrent feeling of sand or gravel in the eyes as well as a dry mouth for more than 3 months with a glass of water required to eat dry foods further support a diagnosis of ss . in our clinics , the limit for schirmer 's test is set at 3 mm to reduce positive results in the normal population to < 15% .
histological criteria for ss include focal sialoadenitis , and serological criteria include ana , rf and antibodies to ro and/or la .
the diagnosis of ss is excluded if there is a history of head and neck radiation treatment , hepatitis c , aids , lymphoma , sarcoidosis , graft versus host disease or anticholinergic drugs .
the 2 patients described in this case report met the clinical criteria for ss based on dry eyes and a positive schirmer test but lacked antibodies to ro or la .
the autoantibodies that are most commonly believed to be associated with ss are ro and/or la antibodies .
ro ( ss - a ) is an extractable nuclear antigen that is composed of proteins 52 kd and 60 kd combined with cytoplasmic rna species [ 1 , 6 ] .
antibodies to ro are found in patients with autoimmune mediated systemic connective disorders including ss .
antibodies to ro are detected in 4060% of the patients [ 1 , 6 , 7 ] .
la ( ss - b ) is a 48-kd protein and an extractable nuclear antigen .
antibodies to la are detected in < 20% of the patients but they are highly specific to ss [ 6 , 7 ] .
however , there are multiple other antibodies being studied , including antibodies to muscarinic receptor 3 , tissue kallikrein , alpha - fodrin , carbonic anhydrase ii and vi , psp and sp1 .
the significance of these autoantibodies has not been fully appreciated [ 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 ] .
one of the mouse models used to study ss is the interleukin 14 alpha transgenic ( il14tg ) mouse .
it reproduces all events noted to occur in ss patients in the same relative time frame [ 16 , 17 , 18 ] .
the use of this animal model led to the discovery of the novel autoantibodies in ss .
these include antibodies to sp1 , carbonic anhydrase 6 ( ca6 ) and psp . the presence of these autoantibodies in the sera of patients with ss has been confirmed . as per these studies , only 25% of the il14tg mice developed ro and/or la antibodies .
interestingly , the time course in the development of the autoantibodies showed that the sp1 and ca6 antibodies were present very late in the disease .
our first patient had symptoms of dry eyes requiring multiple procedures to help control them .
our second patient had dry eyes for many years along with the comorbidity of ra .
however , a diagnosis of ss was not made in either of our patients due to the lack of ro and/or la antibodies .
the detection of sp1 and psp antibodies in our patients led to the diagnosis of primary ss in the first and secondary ss in the second patient .
these cases stress the importance of using autoantibodies besides ro and la in the diagnosis of ss .
further studies are in progress to define whether antibodies to sp1 and psp not only define early stages of ss but also particular forms of ss .
md , and l.s . , phd , participated in the discovery of the autoantibodies to sp1 and psp .
the suny at buffalo school of medicine holds a patent on these autoantibodies that is licensed to immco and nicox .

Answer:
purposethe purpose of this report is to describe 2 patients with persistent severe dry eyes , positive schirmer tests for sjogren 's syndrome ( ss ) but lacking antibodies to either ro or la .
 these patients were diagnosed to have ss by detecting antibodies to salivary gland protein 1 ( sp1 ) and parotid secretory protein ( psp ) .
 this report emphasizes the existence of patients with ss who lack antibodies to either ro or la and may therefore be misdiagnosed .
 detection of novel autoantibodies , including antibodies to sp1 and psp , are helpful in identifying these patients .
 initial presentation may simply be dry eyes.methodstwo patients who presented to our ophthalmology clinic are described .
 one of the patients underwent multiple procedures over a period of 10 years for severe xerophthalmia .
 the other patient had rheumatoid arthritis and xerophthalmia .
 however , in both patients , chronic xerophthalmia had been considered to be idiopathic because antibodies ro and la were negative .
 further serologic testing revealed antibodies to sp1 and psp.resultstwo patients who lacked antibodies to ro and la but not to sp1 and psp were diagnosed as having ss.conclusionpatients presenting with unexplained dry eyes may not always show the serology markers in the current criteria for ss , anti - ro and anti - la . in these cases ,
 investigation for novel , early antibodies to sp1 and psp is of importance in the diagnosis of ss .


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:
a total of 226 bengali medium students ( male 99 and female 127 ) , studying in class seven and eight , were taken from two urban and two rural schools of west bengal .
jepqr - s developed by corulla is 48 item self - reported questionnaire having four dimensions extraversion , neuroticism , psychoticism , and lie scale each of which has 12 items .
the items of the questionnaire were translated into bengali by two bilingual bengali personnel . where there were inconsistencies , both
translation of the questionnaire by an expert was made and where there were any inconsistencies , the translators were consulted to get best possible solutions .
internal consistency of each items of each of the four subscales of the translated jepqr - s was completed .
inter - correlations between different subscales were also found . to find internal consistency of items under a subscale , item rest of test correlations were found .
the internal consistency of the subscales of the translated questionnaire was found by calculating chronbach 's alpha .
the statistical analysis was made with the help of statistical package for the social science ( spss ) statistics 17.0 .
a total of 226 bengali medium students ( male 99 and female 127 ) , studying in class seven and eight , were taken from two urban and two rural schools of west bengal .
jepqr - s developed by corulla is 48 item self - reported questionnaire having four dimensions extraversion , neuroticism , psychoticism , and lie scale each of which has 12 items .
jepqr - s developed by corulla is 48 item self - reported questionnaire having four dimensions extraversion , neuroticism , psychoticism , and lie scale each of which has 12 items .
the items of the questionnaire were translated into bengali by two bilingual bengali personnel . where there were inconsistencies , both
the translators were consulted . also back translation of the questionnaire by an expert was made and where there were any inconsistencies , the translators were consulted to get best possible solutions .
internal consistency of each items of each of the four subscales of the translated jepqr - s was completed .
to find internal consistency of items under a subscale , item rest of test correlations were found .
the internal consistency of the subscales of the translated questionnaire was found by calculating chronbach 's alpha .
the statistical analysis was made with the help of statistical package for the social science ( spss ) statistics 17.0 .
table 1 presents that the item rest of test correlations vary for the extraversion between 0.082 and 0.417 , for neuroticism between 0.127 and 0.552 , for psychoticism between 0.085 and 0.504 , and for the lie scale between 0.051 and 0.363 .
item rest of test correlations alpha reliability found for the four subscales were 0.620 for extraversion , 0.663 for neuroticism , 0.604 for psychoticism , and 0.620 for lie scale . the test
retest reliabilities were found 0.659 for extraversion , 0.652 for neuroticism , 0.631 for psychoticism , and 0.621 for lie scale .
the present study was aimed to examine to what extent the bengali translation of the jepqr - s is functional in bengali cultured population . the results [ table 1 ] of the first stage of data analysis indicate that most of the items within a subscale have significant correlations with rest of the items .
the alpha coefficients of all the four subscales recorded in this study do not cross 0.7 , the level recommended by kline , but they are very close to it and satisfactory .
alpha coefficients for extraversion , neuroticism and lie scale recorded in this study are less well relative to main stream studies , perhaps , due to cultural difference , as a measuring tool like personality test is always culturally loaded .
significant observation of this study is that the alpha coefficient of 0.604 for psychoticism is impressive against the historic difficulties encountered by the subscale .
retest reliabilities found in this study are satisfactory and the results are very similar to the findings of eysenck and eysenck which were for 13 years boys and girls with an interval of 6 months ; extraversion 0.67 and 0.76 , neuroticism 0.72 and 0.74 , psychoticism 0.63 and 0.66 , and lie scale 0.65 and 0.66 .
results relating to the main stream questionnaires provide that the dimensions of personality are not all orthogonal .
the inter correlations [ table 2 ] between the dimensions of the translated jepqr - s of the present study also show that they are not all orthogonal .
neuroticism and lie scale also showed negative correlation significant at the 0.05 level . on the other hand , extraversion and lie scale also neuroticism and psychoticism both showed positive correlations significant at the 0.05 level .
however , there is a significant negative correlation at the 0.01 level between psychoticism and lie scale while extraversion is independent of neuroticism .
on the basis of the present study , it may be concluded that the bengali version of the jepqr - s may be accepted as a functional tool for research work and educational purpose .
it is further recommended to administer the bengali version of jepqr - s on a larger sample for determining the psychometric properties more accurately .

Answer:
background : personality measuring instrument plays an important role in many fields of human civilization and therefore , present study was aimed to find such an instrument for bengali speaking juniors.materials and methods : bengali translation of the short - form of the revised junior eysenck personality questionnaire developed by corulla was administered on a sample of 226 bengali speaking students ( 99 boys and 127 girls ) studying in class seven and eight taken from two urban and two rural schools
 . internal consistency of each item under a subscale was calculated ; internal consistency of each of the four subscales of the translated questionnaire was calculated ; test  retest reliability was found with an interval of 3 months and inter - correlations between different subscales were found.conclusion:the findings provided satisfactory psychometric properties of the extraversion , neuroticism , psychoticism , and lie scale .


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:
leri - weill 's dyschondrosteosis ( lwd ) is anautosomal dominant condition with variable penetrance characterized by mesomelic short stature and with madelung deformity .
it is due to deletion or mutation in short stature homeobox ( shox ) gene . here
, there is deficient growth of a volar and ulnar aspect of distal radialphysis , triangulation of corpus with proximal and volar shift of the lunate .
a 13-year - old girl referred to us with a history of deformity of bilateral forearm from the age of 5 to 6 years .
there was no history of pain in the joint of hands , trauma to the wrist and no history of similar illness in the family .
patient was moderately built and significantly short for her age [ figure 1 ] . with height of 130 cm ( less than 3 percentile ) .
upper segment was 69 cm , lower segment was 61 cm , weight of 35 kg and body mass index of 20.71 kg / m .
secondary sexual characteristic tanner - whitehouse staging - b4 ( breast ) , p4 ( pubic hair ) , a3 ( axillary hair ) her elder brother had normal height for age and no any hand deformities and so were her parents .
investigation showed hemoglobin of 12.5 g / dl , liver function test and renal function test were normal ca= 9.0 mg / dl alkaline phosphates 260 iu and phosphorus = 3.5 mg / dl .
x - ray bilateral wrist showed malformed medial radial epiphysis with dorsal and ulnar shift and with increased length of phalanges suggestive of madelung deformity [ figure 2 ] .
her ultrasound abdomen showed no hepatomegaly or splenomegaly and had normal sized uterus and ovary x - ray spine and x - ray elbow were normal [ figure 3 ] .
her luteinizing hormone = 1.1 miu / ml follicle stimulating hormone = 2.4 miu / ml and karyotype was normal as was urine mucopolysaccharide screening .
x - ray bilateral wrist based on the history , clinical examination , and investigations findings , the final diagnosis of lwd as a cause of madelung deformity was made .
it is the most common cause of mesomelic deformity and is inherited as an autosomal dominant trait with variable penetrance .
it is often seen in girls and becomes apparent in late childhood or early adolescence .
madelung deformity , beside is also found in turner 's syndrome , pseudohypoparathyroidism , mucopolysaccharidosis and achondroplasia of distal radial epiphysis .
madelung deformity was first described by malgaigne in 1885 and later by madelung in 1878 as a spontaneous forward subluxation of the hand .
madelung deformity is an ulnar and dorsal curvature of the distal radius due to deficient growth of the volar and ulnar aspect of distal radialphysis , increased inclination of the distal radial joint surface , triangulation of the corpus with proximal and volar migration of and a prominent dorsal subluxation of ulnar head .
recently , two subtypes of madelung deformity have been described , one with short stature and mesomelia consistent with lwd and the other with severe involvement of the entire radius with limited range of motion of extremity , markedly bowed appearance of the forearm and conspicuous radiographic deformity of the forearm and distal radius .
the pathogenesis of lwd is linked to deletion or mutation in shox gene , present in the pseudoautosomal region of the sex chromosomes - xp23 and yp11 .
in early human embryos it is expressed in the developing limbs ( particular elbow , knee , distal radius / ulnar and wrist ) as well as first and second pharyngeal arches and plays an important role in bone growth as well as development .
shox gene is also associated with short stature in turner 's syndrome and also some causes of growth retardation like lws and langers mesomelic dysplasia .
management is usually conservative . persistent pain and or severe deformity call for orthopedic surgery involving radial osteotomy .
in addition , ulnar shortening in skeletally immature patient or excision of distal ulnar head in skeletally mature patients are done .
surgical prophylaxis by distal resection of the abnormal part of distal radial epiphysis and its replacement by autologous fat ( also known as physeolysis ) has recently been shown to restore growth and minimized deformity .
growth hormone supplementation is found to increase final height in turner 's syndrome , lws but not in langers mesomelic dysplasia .
hand deformity is corrected by orthopedic surgery and for shox gene related short stature food and drug administration has recently approved growth hormone therapy .

Answer:
madelung deformity is a rare inherited disorder associated with endocrine disorders like turner 's syndrome , pseudohypoparathyroidism , but can be seen with short stature homeobox deficiency conditions such as leri - weill dyschondrosteosis ( lwd ) and langers mesomelic dysplasia .
 it has also been reported following trauma to the distal radius epiphysis neoplasia mucopolysaccharidosis ( mps ) and achondroplasia .
 madelung deformity is an abnormality of distal radial epiphysis where in progressive ulnar and volar tilt of the articular surface occurring in association with distal subluxation of ulna .
 a 13-year - old girl was referred to us for evaluation of bilateral deformity of wrist and short stature .
 there was ulnar deviation and dorsal tilt of bilateral hands without history of pain to the joint trauma and family history of similar illness .
 on x - ray , wrist showed malformed distal radial epiphysis with dorsal and ulnar shift and with increased length of phalanges suggestive of madelung deformity .
 x - ray spine was normal .
 ultrasound abdomen showed normal uterus and ovary and her follicle stimulating hormone .
 luteinizing hormone was normal and so was urine mps screening . based on the above points the diagnosis of lwd was made .


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:
they are congenital benign tumor accounting for 15 - 20 % of intraventricular mass but only about 1% of intracranial ones ( 1 - 3 ) .
they can be diagnosed at any age but usually become symptomatic in the third to sixth decades and more common in men than women .
they usually found incidentally and are asymptomatic ; but in some instances may associate with rapid neurologic deterioration , herniation , and sudden death .
so , recognition of this rare but important diagnosis may result in decreasing mortality ( 4 ) . in this report
, we presented a 13-year - old boy with complaint of two times drop attack and final diagnosis of colloid cyst in the third brain ventricle .
a 13-year - old boy was brought to the emergency department ( ed ) with complaint of two times drop attack .
the patient mentioned that he felt sudden weakness in both lower limbs , which led to drop .
these attacks were happened about 4 hours before admission and he did not have any same experience previously .
he did not have complaint of nausea , vomiting , headache , vertigo , blurred vision , or palpitation .
the subject did not have any known structural or congenital heart disease , but suffered from asthma and used salbutamol spray irregularly .
the patient did not have trauma history and there was no positive history of any known medical illness in his parents or closed relatives . on arrival , he had 36.9c axillary temperature , 16/minute respiratory rate , 90/minute pulse rate , 120/80 mmhg blood pressure , and 96% oxygen saturation at room air .   on physical examination , he did not have focal neurologic findings or even paresthesia or paraplegia .
general examination of head and neck , chest , abdomen , and limbs did not reveal any positive findings .
following the evaluation process , a brain computed tomography ( ct ) was performed ( figure-1 ) .
a hyperdense round lesion was seen in the third ventricle consequently caused that the corresponding physician requested a neurologic consultation in the ed . finally , the brain magnetic resonance imaging ( mri ) confirmed the diagnosis of third ventricle colloid cyst and the patient was underwent surgery and discharged without any problem ( figure 2 ) .
the colloid cysts commonly settle near the foramen of monro in the anterior third ventricle and so may encounter with drainage of the cerebrospinal fluid ( csf ) ( 3 ) .
since even a small lesion can block the mentioned foramen , these cysts may result in hydrocephalus and increase the intra cranial pressure ( 5 ) .
increased intracranial pressure can be manifested with headache described as severe and intermittent , with short duration , usually located frontally .
in contrast with usual headaches , secondary to intracranial tumors , the colloid cyst induced headache can be relieved by lying down ( 4 ) .
other symptoms include drop attacks , gait abnormalities , progressive dementia , and transient loss of consciousness . in children ,
the most common symptoms are nausea , vomiting , headache , diplopia , and papilledema ( 6 ) .
the classic clinical description of intermittent headaches and drop attacks occurs in only one - third of patients .
sudden obstruction of the ventricular system and following rapid rising of intracranial pressure can lead to herniation and rarely sudden death ( 7 , 8) .
colloid cysts size varies from 3 - 40 millimeters in diameter , but the size do not related to their symptoms or outcome , as even small ones may lead to sudden death ( 9 ) .
colloid cyst is usually diagnosed by non - contrast computed tomography ( ct ) as an oval or rounded hyperdense mass on the anterior aspect of the third ventricle .
they may occasionally be hypodense or isodense to the brain , or found in other areas of the brain .
colloid cysts have different manifestation on mri . despite their variable signal characteristics , their location and shape help to the correct preoperative diagnosis in most patients ( 6 ) .
half of the cases are hyperintense on t1-weighted mri images and hypointense on t2-weighted mri images respected to brain .
isointense cysts are not easily identified on mri , and in such instances ct scan is more useful ( 9 , 10 ) .
small asymptomatic colloid cyst can be considered for close follow up by serial examinations and neuroimaging ( 11 ) .
there is also the rare report of spontaneous resolving of the third ventricle colloid cyst ( 12 , 13 ) .
all authors passed four criteria for authorship contribution based on recommendations of the international committee of medical journal editors .

Answer:
colloid cysts are mucous - filled masses with an outer fibrous layer .
 these cysts are rare developmental malformation and not a true neoplasm .
 they usually found incidentally and are asymptomatic ; but in some cases may associate with rapid neurologic deterioration , herniation , and sudden death .
 recognition of this rare but important diagnosis may result in decreasing mortality . in this report
 , we presented a 13-year - old boy with complaint of two times drop attack and final diagnosis of colloid cyst in the third brain ventricle .


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 prevalence of kidney stones in the united states has risen steadily in recent years and correlates with population dietary changes .
relative dietary intake of fluid , sodium , calcium , oxalate , citrate , and animal - based proteins has a marked influence on stone risk .
accordingly , an efficient assessment of a patient 's nutritional intake is important for the urologist and may enable an informed assessment and guided recommendations .
the traditional office based interview may not adequately assess the patient 's nutritional intake , due to time constraints and the detailed nature of a nutritional history .
furthermore , biases may exist both in how a patient wishes to represent themselves , and in how the practitioner presents a question .
we sought to determine if a physician 's impression of a patient 's dietary intake was dependent on the medium through which they obtained the nutritional data .
a typical office interview was compared to information obtained via a computerized clinical decision support system ( cdss ) , which presented a food frequency questionnaire ( ffq ) .
furthermore , the urologists made recommendations for dietary intervention based on the information ascertained via each method .
each patient completed : ( 1 ) an office - based interview with one of two fellowship - trained endourologists , and ( 2 ) a ffq administered via a cdss , presented on an ipad .
each urologist made two separate assessments via a likert - scale - based survey of the significance of a patient 's nutritional ( nutritional impact score ) and hydration factors ( hydration impact score ) as they pertained to stone disease ( fig .
each assessment was followed by specific recommendations , such as reducing sodium intake , reducing animal protein intake , and increasing fluid intake .
the first assessment ( pre - ffq ) was made after the office - based interview with the patient but without reviewing the results of the ffq .
the second assessment ( post - ffq ) was made after reviewing the patient 's ffq results .
if the urologist modified the nutritional impact score , hydration impact score , or treatment recommendations from the first assessment to the second , we assumed that the ffq results caused the urologist to believe that nutrition had a greater or lesser impact on the patient 's stone disease than previously assessed by the office - based interview .
the ffq used in this study is an 88-question nutritional survey that is similar to prior ffqs that have been validated by previous analyses for accurate assessment of a patient 's dietary habits . using the ffq , our patients recorded nutritional intake of those foods providing substantial quantities of the following : oxalate , animal - based protein , sodium , and calcium .
intake of fruits and vegetables , fluids , and nutritional supplements was also assessed ( fig .
questionnaire results were entered in the ffq 's algorithm , which generated numerical scores corresponding to patient 's relative intake in each of the following domains : oxalate , calcium , sodium , purine , and fluids . for each patient , we compared pre - ffq nutritional impact score , hydration impact score , and treatment recommendations to respective post - ffq data points .
our results were coded into the following binary variables , detailing the presence or absence of : increase in diet score , increase in hydration impact score , any change in treatment recommendations , addition of at least one treatment recommendation , and subtraction of at least one treatment recommendation .
a multivariate logistic regression model was fit to determine the impact of the numerical results of each domain in the ffq ( oxalate , calcium , sodium , purine , and fluids ) and the aforementioned binary variables .
each patient completed : ( 1 ) an office - based interview with one of two fellowship - trained endourologists , and ( 2 ) a ffq administered via a cdss , presented on an ipad .
each urologist made two separate assessments via a likert - scale - based survey of the significance of a patient 's nutritional ( nutritional impact score ) and hydration factors ( hydration impact score ) as they pertained to stone disease ( fig .
each assessment was followed by specific recommendations , such as reducing sodium intake , reducing animal protein intake , and increasing fluid intake .
the first assessment ( pre - ffq ) was made after the office - based interview with the patient but without reviewing the results of the ffq .
the second assessment ( post - ffq ) was made after reviewing the patient 's ffq results .
if the urologist modified the nutritional impact score , hydration impact score , or treatment recommendations from the first assessment to the second , we assumed that the ffq results caused the urologist to believe that nutrition had a greater or lesser impact on the patient 's stone disease than previously assessed by the office - based interview .
the ffq used in this study is an 88-question nutritional survey that is similar to prior ffqs that have been validated by previous analyses for accurate assessment of a patient 's dietary habits . using the ffq , our patients recorded nutritional intake of those foods providing substantial quantities of the following : oxalate , animal - based protein , sodium , and calcium .
intake of fruits and vegetables , fluids , and nutritional supplements was also assessed ( fig .
questionnaire results were entered in the ffq 's algorithm , which generated numerical scores corresponding to patient 's relative intake in each of the following domains : oxalate , calcium , sodium , purine , and fluids .
for each patient , we compared pre - ffq nutritional impact score , hydration impact score , and treatment recommendations to respective post - ffq data points .
our results were coded into the following binary variables , detailing the presence or absence of : increase in diet score , increase in hydration impact score , any change in treatment recommendations , addition of at least one treatment recommendation , and subtraction of at least one treatment recommendation .
a multivariate logistic regression model was fit to determine the impact of the numerical results of each domain in the ffq ( oxalate , calcium , sodium , purine , and fluids ) and the aforementioned binary variables .
between the 2 urologists in the study , there was no significant difference in the average nutritional impact scores or average the hydration impact scores assigned . from pre - ffq
to post - ffq , the urologist was more likely to increase the nutritional impact score if the patient had higher ffq scores for sodium ( odds ratio [ or ] , 1.02 ; p=0.02 ) or fluids ( or , 1.03 , p=0.04 ) . in other words
, the physician interpreted a greater contribution of diet to the patient 's stone disease when the ffq indicated higher sodium or fluid intake ( table 2 ) .
there was no difference in hydration score rendered by the physician for patients who consumed increased oxalate , calcium , sodium , purine , or fluids ( table 3 ) .
a higher ffq score for oxalate was positively associated with the addition of at least one treatment recommendation ( or , 1.07 ; p=0.02 ) ( table 4 ) .
stone disease is among the most common and costly urological conditions , with a lifetime prevalence of approximately 9% , and 5-year recurrence rates approaching 50% . in the united states alone ,
the economic burden of stone disease has been estimated to be over $ 2 billion annually .
previous studies have underscored the impact of diet on stone formation and the role of dietary interventions in prevention of stone disease .
our study revealed that using a ffq to obtain the diet history impacted how urologists perceived the effects of diet and hydration on stone disease , as well as how urologists treated the stone disease .
therefore , it is important for the urologist to effectively and expeditiously obtain a thorough diet history .
certainly , the modern urologist experiences logistical and time constraints in his or her busy clinical practice . additionally , some patients may alter their responses to dietary questions in an attempt to represent their habits more favorably .
furthermore , even skilled endourologists and stone experts may not use the most effective questions to obtain the information necessary .
finally , a comprehensive stone clinic , complete with a dietician is favorable , but not feasible in every practice setting .
previous authors have found the ffq to be an effective tool for obtaining an accurate and objective diet history . as for the method of delivering the ffq
, we believe that the computerized cdss provides physicians with a relatively bias - free mode of data collection as well as standardized evaluations of the data delivered in a timely fashion .
in other medical applications , the cdss has been shown to improve practitioner performance and patient care , for instance , by reducing medication errors . in the present study
, we found that the use of the ffq as a cdss can significantly alter the how the endourologist assesses the significance of dietary factors on a patient 's stone disease .
moreover , the recommended dietary interventions can change based on the results of the ffq . in our urolithiasis clinic ,
nearly all of the patients ( 75 of 76 ) were willing to use the ffq .
these findings suggest that the addition of the ffq to the 24-hour urine collection and other components of the comprehensive stone evaluation may alter the assessment and plan for these patients .
the major limitation of our study is that we did not determine if use of the ffq leads to improved patient outcomes , such as decreased recurrence rates or increased patient satisfaction .
future studies may be developed to link the use of the ffq to improved outcomes or patient encounters .
while our study may not yet translate into improved patient outcomes , certainly others have shown that the use of cdss can improve efficiency .
it is reasonable to hypothesize that improving efficiency may be a key component in improving patient outcomes .
other studies have also shown that ffqs can play an integral role in assessing urolithiasis patients , especially in a multidisciplinary setting , where a patient 's diet may be a key focus in stone prevention .
while our ffq was reasonably detailed , others have been able to streamline a more lengthy diet questionnaire into a more compact rapid food screener . in regards to assessing renal acid load in stone formers ,
his goal was to make this rapid assessment equivalent to a more lengthy diet questionnaire . in a follow - up study , patients were asked to complete both of these questionnaires , and their lake score assessment appeared as good as a lengthier questionnaire in determining renal acid load . while this particular study looked at a different aspect of stone disease , it appears that endourologists are attempting to gain detailed dietary information from their patients while continuing to improve efficiency and streamline their stone clinics .
certainly these approaches may prove worthwhile as we continue to develop this tool in our urolithiasis clinic .
we hope that our efforts may ultimately improve the efficiency and quality of care of our endourology patients .
given the wide body of evidence supporting the use of dietary interventions in preventing stone recurrence , it is reasonable to hypothesize that recommendations made with potentially more complete and accurate data , obtained using the ffq , would confer improved outcomes .
randomized - controlled trials are necessary to evaluate the impact of utilizing the ffq as a cdss on stone patients to patient outcomes , such as recurrence rates , quality of life , and satisfaction with the clinical experience .
a self - reported , electronic version of the ffq may be helpful in the efficient assessment and counseling of patients with stone disease . with prior comprehensive knowledge of a patient 's nutritional intake ,
the urologist may be afforded more time with which to counsel patients regarding intervention and nutritional intake .

Answer:
purposeto evaluate a physician 's impression of a urinary stone patient 's dietary intake and whether it was dependent on the medium through which the nutritional data were obtained .
 furthermore , we sought to determine if using an electronic food frequency questionnaire ( ffq ) impacted dietary recommendations for these patients.materials and methodsseventy - six patients attended the stone clinic over a period of 6 weeks .
 seventy - five gave consent for enrollment in our study .
 patients completed an office - based interview with a fellowship - trained endourologist , and a ffq administered on an ipad .
 the ffq assessed intake of various dietary components related to stone development , such as oxalate and calcium .
 the urologists were blinded to the identity of patients ' ffq results .
 based on the office - based interview and the ffq results , the urologists provided separate assessments of the impact of nutrition and hydration on the patient 's stone disease ( nutrition impact score and hydration impact score , respectively ) and treatment recommendations .
 multivariate logistic regressions were used to compare pre - ffq data to post - ffq data.resultshigher ffq scores for sodium ( odds ratio [ or ] , 1.02 ; p=0.02 ) and fluids ( or , 1.03 , p=0.04 ) were associated with a higher nutritional impact score . none of the ffq parameters impacted hydration impact score . a higher ffq score for oxalate ( or , 1.07 ; p=0.02 ) was associated with the addition of at least one treatment recommendation.conclusionsinformation derived from a ffq can yield a significant impact on a physician 's assessment of stone risks and decision for management of stone 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:
gck - mody ( gck diabetes , glucokinase diabetes , or mody2 ) is a monogenic condition caused by heterozygous mutations in the gene encoding glucokinase ( gck ) .
it is characterized by chronic , lifelong , and mild hyperglycemia present from birth , and less than 50% of patients fulfil the criteria for overt diabetes .
the increased risk of atherosclerotic vascular disease  as compared with healthy individuals without diabetes  is known in subjects with impaired glucose tolerance , patients with type 2 diabetes , and patients with metabolic syndrome [ 3 , 4 ] .
noninvasive imaging techniques , such as carotid intima - media thickness ( cimt ) measurements , may help to stratify this risk of atherosclerosis , as well as the risk of myocardial ischemia : the cimt has been shown to independently predict coronary events in type 2 diabetes and cardiovascular diseases .
however , the situation in gck - mody is likely to be different from that in type 2 diabetes : patients with gck - mody have increased fasting blood glucose and relatively low 2-hour post - ogtt blood glucose without other components of metabolic syndrome or insulin resistance .
such a blood glucose profile has been shown to be associated with lower rates of cardiovascular mortality among patients with type 2 diabetes .
importantly , niskanen et al .   demonstrated that components of insulin resistance syndrome , including hyperinsulinemia after an oral glucose load , serum lipid abnormalities , and elevated blood pressure , are major determinants of cimt in patients with diabetes .
the risk of macrovascular complications in gck - mody is considered low , but the data are scarce .
we aimed to evaluate the carotid intima - media thickness ( cimt ) as an indicator of this risk in gck - mody patients aging 35 years or older and their unaffected relatives , who share a similar environment and lifestyle .
we studied 27 patients from 20 czech families with genetically confirmed gck - mody ( age 3575 years ; median 46 years ) and 24 unaffected family members ( siblings , parents , and partners ) representing the control group ( age 3579 years ; median 50 years ) .
each of the 20 participating families contributed 1 to 3 patients with gck - mody and 1 to 3 control individuals matched by age and gender .
control individuals with fasting blood glucose more than 5.6  mmol / l ( 100  mg / dl ) and/or with a known history of diabetes were excluded from the study .
the identification of families with gck - mody has been reported previously [ 9 , 10 ] .
the study protocol was approved by the ethics committee of the 3rd faculty of medicine , charles university in prague , czech republic .
the structured assessment included a questionnaire , anthropometric examination and blood sampling for biochemical analysis .
high - resolution b - mode carotid ultrasonography ( using phillips iu22 ultrasound ) was performed to measure the cimt of the distant wall for 1  cm lengths of the carotid bifurcation and the internal carotid and right and left common carotid arteries .
the mean cimt values of 10 sites were combined in an unweighted average to produce an overall cimt .
the upper normal limit of cimt was set to 0.7  mm [ 12 , 13 ] .
the patient history of coronary heart disease and ischemic stroke was obtained from medical records .
the clinical and demographic characteristics of gck mutation carriers and control individuals were compared using welch 's two - sample t - tests ( continuous variables ) and fisher 's exact tests ( categorical variables ) .
mixed linear regression models with cimt , blood pressure , and serum creatinine as outcomes were used to estimate and test the adjusted effects of gck mutation status . age , gender , and mutation status
no significant differences in baseline characteristics were found between patients and control individuals , with the exception of fasting blood glucose ( gck - mody 7.6  mmol / l , sd  1.2 ( 136.4  mg / dl ) ; controls 5.3  mmol / l , sd  0.3 ( 95.4  mg / dl ) ; p < 0.0001 ) and glycated hemoglobin hba1c ( gck - mody 6.9% ( sd  1.0 ) , 52  mmol / mol ( sd  10 ) ; controls 5.7% ( sd  0.4 ) , 39  mmol / mol ( sd  3 ) ; p < 0.0001 ) ( table 1 ) .
the prevalence of smokers and hypertensive patients was similar in both samples ( p = 1 ) .
the measured cimt values for participants with and without gck mutations are shown in figure 1 .
the mean cimt was 0.707  mm ( range : 0.41.1 ) in gck - mody patients and was 0.692  mm ( range : 0.41.1 ) in healthy control individuals . according to the published recommendations [ 12 , 13 ]
after adjusting for age , gender , and family status , the estimated mean difference in cimt between patients and healthy individuals increased slightly to 0.049  mm ( 95% ci from 0.026 to 0.123 ; p = 0.19 ) . as expected , the estimated trends of mean cimt indicated a moderate increase in cimt with age and mutation status ( see regression lines plotted in figure 1 ) .
carotid plaques ( local intima - media thickening exceeding 1  mm and protruding into the lumen ) were identified in 7 ( 25.9% ) patients and 3 ( 12.5% ) control individuals ( p = 0.1 ) , but all of these plaques were hemodynamically insignificant .
myocardial changes typical of ischemic heart disease described on echocardiography and/or ecg were detected in three of 27 patients with gck - mody and two of the 24 healthy control individuals ( p = 0.866 ) .
three study participants had suffered from myocardial infarction ( two with gck - mody and one control individual ) ( p = 0.895 ) in the past , and two had suffered from ischemic stroke ( one with gck - mody and one control individual ) .
a similar proportion of participants ( 35% ) from both groups were treated for hypertension with one or more antihypertensive drugs .
four of the 27 patients with gck - mody ( 14.8% ) were treated with oral hypoglycemic agents , and one was treated with insulin .
to the best of our knowledge , the present study is the first case - control study including the cimt measurements of gck - mody patients older than 35 years .
the results are consistent with the mild natural course of gck - mody and confirm that gck mutation is not associated with an increased risk of developing macroangiopathic complications .
the 95% confidence interval of the cimt difference , adjusted for age , family , and gender , is 0.026 to + 0.123  mm , indicating that the possible increase in cimt associated with gck mutation is low and most likely clinically insignificant .
the absence of serious chronic microvascular complications in gck - mody was observed by page et al .   and
velho et al . [ 16 , 17 ] , who described proliferative retinopathy in less than 4% , proteinuria in 6% , and peripheral neuropathy in 5% of patients with hyperglycemia at more than 5 years after diagnosis .
a major problem with assessing diabetic complications in those patients is the differentiation between patients who only have gck - mody and those who develop type 2 diabetes in addition to gck - mody .
it is generally assumed that patients with gck - mody do not necessarily develop insulin resistance or dyslipidemia in the natural disease course , and their glucose tolerance remains stable over many years . nevertheless , carrying
a gck mutation does not protect against the development of type 2 diabetes , which occurs at a similar prevalence in gck - mody patients and in the general population .
it has been reported that metabolic syndrome and insulin resistance are the major components of atherosclerosis risk in patients with diabetes and also in individuals without diabetes with insulin resistance [ 3 , 20 , 21 ] , whereas the role of hyperglycemia in cardiovascular disease associated with type 2 diabetes is less clear .
in contrast with patients with type 2 diabetes , patients with gck - mody have mild hyperglycemia without other components of metabolic syndrome or insulin resistance . therefore , our study adds to the accumulating evidence that chronic mild hyperglycemia without additional components of metabolic syndrome has a milder effect on the development of macrovascular complications compared with the same glycemic levels associated with metabolic syndrome components .
admittedly , more subtle effects on cimt would remain undetected , as the present study is moderately sized .
the numbers of available patients in other studies are , however , comparable  a detailed analysis of the effects of p.gly299arg mutation in the gck gene was limited to a single large pedigree , whereas another study reporting selected metabolic parameters and history data included 35 families , but these subjects were not examined at a single centre , and the data did not include cimt [ 16 , 17 ] .
thus , the number of participants may reflect a compromise between the depth of the acquired data and the subjects ' willingness to undergo a complicated set of investigations .
patients with gck - mody exhibit only a small increase in glucose levels after oral glucose loading .
by contrast , patients with type 2 diabetes have relatively high 2-hour glucose levels ( as a proxy for postprandial glucose levels ) , indicating that postprandial glucose levels could be the most pathogenic glycemic factor for developing micro- and macrovascular complications .
the cimt has been shown to correlate more strongly with postprandial glycemia than with fasting hyperglycemia .
additionally , the serum hs - crp levels are lower in gck - mody patients than in patients with type 2 diabetes .
however , a common variant in the pancreatic gck promoter has been shown to influence the risk of diabetes complications .
showed   that the a allele at c.30g > a of gck was associated with an increased risk of coronary artery disease in not only patients with type 2 diabetes but also individuals who did not have diabetes , albeit with a much weaker association ( or = 1.27 ; 95% ci 1.021.59 ) . additionally , the snp rs4607517 , which is in linkage disequilibrium with c.30g > a , has been associated with fasting glucose in genome - wide association studies .
the association between components of the fasting glucose genetic risk score ( represented by five snps , including rs4607517 ) and cimt has been described with an increment of 0.0048  mm in carriers .   in conclusion ,
our data indicate that the natural course of mild lifelong hyperglycemia is associated with a low risk of developing diabetic macrovascular complications .
however , patients with gck - mody should take steps to reduce the risk of developing  classical  type 2 diabetes in addition to gck - mody that is , avoid obesity and maintain a high level of physical activity .
our data support a conservative therapeutic approach for hyperglycemia in nonpregnant patients with gck - mody .
other risk factors for micro- and macrovascular complications should be treated according to present guidelines .

Answer:
aim .
 gck - mody is an autosomal dominant form of diabetes caused by heterozygous mutations in the glucokinase gene leading to a lifelong mild hyperglycemia .
 the risk of macrovascular complications is considered low , but studies are limited .
 we , therefore , investigated the carotid intima - media thickness ( cimt ) as an indicator of macrovascular complications in a group of patients with gck - mody .
 methods . twenty - seven gck mutation carriers and 24 controls recruited among their first - degree relatives
 were compared , all aging over 35 years .
 the cimt was tested using a high - resolution b - mode carotid ultrasonography .
 medical history , anthropometry , and biochemical blood workup were obtained .
 results .
 the mean cimt was 0.707  0.215  mm ( mean  sd ) in gck mutation carriers and 0.690  0.180  mm in control individuals .
 when adjusted for age , gender , and family status , the estimated mean difference in cimt between the two groups increased to 0.049  mm ( p = 0.19 ) .
 no difference was detected for other characteristics , with the exception of fasting blood glucose ( gck - mody 7.6  mmol / l  1.2 ( 136.4  mg / dl ) ; controls 5.3  mmol / l  0.3 ( 95.4  mg / dl ) ; p < 0.0001 ) and glycated hemoglobin hba1c ( gck - mody 6.9%  1.0% , 52  mmol / mol  10 ; controls 5.7%  0.4% , 39  mmol / mol  3 ; p
 < 0.0001 ) .
 the frequency of myocardial infarction and ischemic stroke did not differ between groups .
 conclusion .
 our data indicate that the persistent hyperglycemia in gck - mody is associated with a low risk of developing diabetic macrovascular complications .


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:
multiple sclerosis ( ms ) , received its name in 1955 , is an inflammatory disorder of brain and spinal cord where in body 's immune system incorrectly attacks its own central nervous system ( cns ) , causing variable and unpredictable symptoms ( some examples including slurred speech , blurred vision , loss of balance , poor coordination , tremors , numbness , extreme fatigue , problems with memory and concentration , paralysis , and blindness ) .
even though a lot of advances have been made in past few decades , exact causes of this disorder remains unknown(environmental factor combined with genetic predisposition ) .
there is a high cost associated with this disorder and it reduces life expectancy as well as quality of life .
unfortunately , there is no cure for ms , and most of the current drugs available in the market help treat the symptoms .
ms is not the same in any two people who have it , since the underlying cause is demyelination ( along with axon degeneration ) , which can target any brain area , resulting in a broad range of clinical symptoms ( compston and coles , 2002 ; alastair compston et al .
in addition , brain lesions can sometimes outnumber the clinical symptoms by as much as 10:1 , and lesions in noncritical areas may not result in obvious functional deficits , even if brain function is in fact altered .
there are four subtypes of the disease - relapsing - remitting ms , primary progressive ms , secondary progressive ms and progressive relapsing ms , which differ in relapse rate , clinical symptoms , trajectory , underlying causes and approaches to disease management .
combined all these aspects of the disease ( various locations for demyelination , clinically silent timeline , and a highly variable disease course ) make the approach to care and treatment complex ( compston and coles , 2008 ; trapp and nave , 2008 ) .
current behavioral and imaging methods used to assess disease severity are insufficient by themselves to allow confident prediction of disease progression .
the addition of functional modeling ( modeling that correlates the functional loss to disease progression ) and objective functional measurements ( imaging as well as other assessments combined with disease status ) may greatly improve such prediction .
currently , magnetic resonance imaging ( mri ) along with clinical manifestation of the disease are used as clinical tools for diagnosing ms ( filippi and grossman , 2002 ) . the 2010 revision to the mcdonald diagnostic criteria ( polman et al . ,
2011 ) uses a combination of lesion and clinical attacks for the most confident diagnosis of ms .
lesions must be disseminated in time or space or have positive identification from cerebral spinal fluid ( csf ) measure ( lublin et al . , 2014 ) .
unfortunately , discrepancy still exists between clinical symptoms and structural measurements , because of the poor correlation between the presence of lesions and symptoms .
the two common measures used for diagnosis and monitoring with mri are hyperintense lesions on dual - echo mr , which is a nonspecific measure of macroscopic tissue injury , and enhanced abnormalities on t1 lesion weighted images , which is a measure of lesions .
however , neither of these measures do provide extent and severity of inflammation , cellular component , or resultant tissue damage information ( filippi and grossman , 2002 ) .
thus , there is a need for supplemental information from alternative techniques to have a more holistic approach .
there are emerging techniques that hold promise to quantify the brain imaging data , and relate that with clinical outcomes .
some promising examples include magnetization transfer mri ( quantitative and continuous measure of loss of myelin and reduction in axonal density ) , diffusion weighted mri ( quantitative measure of size , shape , geometry , and orientation of tissues ) , proton magnetic resonance spectroscopy ( mrs , provides measure of two major pathologic aspects of ms - the active inflammatory / demyelinating process and axonal injury ) , functional mri ( provides functional information about brain activation during motor , sensitive , and cognitive tasks ) , high field strength imaging ( ex 7 t mri , leads to improved signal - to - noise ratio , speed , and resolution in both mri and mrs ) and transcranial magnetic stimulation ( tms , highly sensitive technique to evaluate cortico - spinal conduction abnormalities in ms ) .
since t1 scan is transient , it should be only used in patients that have frequent mri , and should not be used for comparison between subjects . instead ,
given the availability of multiple brain imaging modalities , the need still exists for creating a combined assessment tool .
quite a few studies have attempted to combine various measures ( petzold et al . , 2006 ; daumer et al . , 2007 , 2009 ; castro - borrero et al . , 2012 ; sormani , 2013 ; giffroy et al . ,
multiple sclerosis severity scale ( msss ) was developed to relate expanded disability status scale ( edss ) to the disease duration .
it has been shown that msss correlates with axonal biomarkers but not with glial biomarkers ( petzold et al . , 2006 ) .
this scale was tested on 195 ms patients to predict accrual of disability over time to see if current therapies have impact on disease severity over time .
pachner and steiner ( 2009 ) concluded that the current disease modifying drug therapies lack emphasis on disease severity .
an online analytical processing tool was developed that can be used for prognosis of near term future course of an individual patient ( daumer et al . , 2007 ) .
this tool is based on matching algorithm ( using statistical analysis ) and contains data of 1,059 patients .
outcome was to show the probable progression over time which can be useful for subjects , physicians , researchers and other professionals who counsel the patients . in an attempt to test the developing treatment methods , sormani ( 2013 ) explored the use of various biomarkers that can be used to predict the clinical response to interferon beta ( ifn- ) treatment .
he concluded with the need for precise , meaningful measures of disease progression , integrated with clinical measures to help with personalized treatment for ms .
a computational classifier was modeled that can be used for predicting short term course of ms ( bejarano et al . , 2011 ) .
it combined clinical data , with mri and motor evoked potential ( mep ) , and it was found that the model did good job on predicting short time scale disability .
a description of the use of various potential biomarkers with their pros and cons was created .
it ranges from markers for immunological activation , as well as markers for demyelination , axonal damage , oxidative stress , remyelination , glycoses , and details of specimen such as blood , urine , tears and csf ( bielecki et al . , 2010 ) .
( 2010 ) concluded with a need for unification and standardization of results of various measurements and techniques .
there have been many advances in modeling and designing tools and predictive capabilities for ms .
( 2015 ) studied 1,959 patients from 19952013 with clinically isolated syndrome and found that demographic and topographic characteristics had a low effect on prognostic factors for ms , while the presence of oligoclonal band ( oligoclonal bands are proteins called immunoglobulins and their presence indicates inflammation of the central nervous system ) had medium effect , and the number of lesions had the highest impact . in an another study ,
2014 ) recruited 652 patients and studied them for prediction factors that can be classified as disseminated in time ( dit ) , disseminated in space ( dis ) , or both , and concluded that there is a need of more predictive factor combinations to help risk for ms .
an analysis of 598 ms patients was performed in norway to determine factors responsible for life expectancy , and the conclusion was that high age at the onset was correlated with unfavorable prognosis ( riise et al . , 1988 ) . in another study on early prognostic features on the late course for ms in world war veterans
, it was found that pyramidal and cerebellar scores are the best predictors ( kurtzke et al . , 1972 ) .
wang et al . ( 2015 ) performed a study to combine in vivo biomarker using electrical vestibular stimulation and eye movement recording to measure evoked vestibular - ocular reflexed ( evor ) in 18 subjects with ms ( wang et al . , 2015 ) .
the goal was to measure the axonal conduction velocity to understand the myelin process and provide a way for assessing efficacy of novel reparative therapies in ms .
there still exists a need to for quantification , combination of various results from studies , and longer longitudinal studies .
lastly , a computational approach will be necessary for various biological , clinical , imaging findings to form an integrative modeling system that encompasses grey matter pathology , myelin sheath aqueous layers , energy metabolism , and perhaps most importantly , multi - scale or integrated modeling .
my recent paper ( chaubey and goodwin , 2016 ) is a computational modeling study which makes it possible to make quantitative predictions about the degree to which electrical signals will move more slowly through axonal pathways as a function of how much of their myelin sheath they have lost as a result of ms ( using data from diffusion tensor imaging ( dti ) , and other modalities ) .
the paper identifies a new biomarker for network failure in ms that should improve our ability to predict and track loss of sensory , motor and cognitive function in the disease and a better way to measure the efficacy of new treatments .
the potential also exists to relate this  slow down  to disease progression , and eventually , to disease prediction , in which we could use the existing model to predict the disease symptoms in subsequent years . a study in my research center ( brain sciences center , va medical center ) used magnetoencephalography ( meg ) resting state recordings as a functional biomarker to classify ms and various other patient populations to their respective groups , by assessing synchronous neural interactions at high temporal resolution as a measurement of the dynamic synchronous neural interactions , an essential aspect of brain function ( georgopoulos et al . , 2007 ) .
another study used similar analysis in 50 ms patients ( 31 rrms , 15 spms , 4 ppms ) and 214 healthy controls ( carpenter et al . , 2011 ) .
ancova was performed at each of the 30,628 sensor pairs ( pccs ) using group ( ms , control ) as a fixed factor and age , gender and handedness as covariates .
similar analyses were done using each ms phenotype ( rrms , spms , etc . ) as a factor and 300 ( out of 30,628 ) sensor pairs were found to have a significant group differences after correction for multiple comparisons .
there is a need to combine such objective measures of brain function with modeling techniques to improve assessment and prediction of the disease over what is possible using established methods . to list few direct advantages of these predictions : 1 )
these predictions can identify high - risk patients who require early and more aggressive therapies , 2 ) they can help patients with clinically isolated syndrome ( cis , one of the ms disease courses , refers to a first episode of neurologic symptoms , but it is not alone enough to have diagnosis of ms , as there needs to be two episodes disseminated in time or space ) to predict how likely and at what time frame the ms diagnosis is likely , 3 ) they can provide an individual plan for various subjects depending on their current status and symptoms ( bergamaschi and montomoli , 2016 ) .
there is a need for modeling to help direct research using testable predictions and fixing the current gap in knowledge .
there is enormous amount of data available , a lot of which is open access , and it is important to make sense of it all .
computational modeling can be an essential tool to help make use and sense of all this data and lead to better understanding , diagnosis , prediction of various diseases , especially ms . as there is no cure for ms , most treatments typically focus on slowing the progression of the disease and managing symptoms .
since tissue destruction and disease onset begins much earlier than the actual clinical symptoms appear , it will be important to test future therapeutics to detect early axonal loss , axonal dysfunction and efficiency of these treatment methods .
advances in imaging technology and use of new techniques need to be established and validated to determine the success of remyelination and cessation of old damage .
finally , a combination of modeling will allow for prediction and better quality of life for people with ms .
there is a huge need for a reliable and personalized disease prediction model of ms .
it would benefit patients with ms , as they can plan and select the best individualized treatment option .
it would be helpful to the clinician working with patients , especially early stage patients , to help with selection of the best therapeutic treatment options .
integration of modeling , biology , clinical and imaging data can help provide more personalized and reliable monitoring of disease progression and in turn lead to better disease prediction .

Answer:
multiple sclerosis ( ms ) is a major cause of neurological disability in adults and has an annual cost of approximately $ 28 billion in the united states .
 ms is a very complex disorder as demyelination can happen in a variety of locations throughout the brain ; therefore , this disease is never the same in two patients making it very hard to predict disease progression . a modeling approach which combines clinical , biological and imaging measures to help treat and fight this disorder
 is needed . in this paper , i will outline ms as a very heterogeneous disorder , review some potential solutions from the literature , demonstrate the need for a biomarker and will discuss how computational modeling combined with biological , clinical and imaging data can help link disparate observations and decipher complex mechanisms whose solutions are not amenable to simple reductionism .