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:
benign acute childhood myositis ( bacm ) is a self - limiting process characterized by sudden onset of muscle pain , more often calf pain , manifested by walking difficulty . since many clinicians are not familiar with bacm , it is often misdiagnosed and interpreted as a more severe and complex disease .
we report the case of a patient suffering from bacm in absence of any previous documented viral infections .
we underline how medical history and clinical examination are sufficient for a correct diagnosis of bacm , as well as to avoid unnecessary tests . based on the previous reports
, we updated etiology and clinical data of bacm , and we propose differential diagnosis of muscle pain in children .
a 7-year - old boy with acute calf pain and progressive walking difficulty was referred to our pediatric center to rule out muscle degenerative diseases .
two days earlier the child had suffered from fever , cough , malaise and rhinorrhea , which promptly resolved .
the onset of calf pain was early in the morning , and it was so sharp that he had to walk on his heels mimicking a spastic gait .
the child had undergone all compulsory vaccinations , and his previous clinical history was not suggestive of any remarkable diseases .
no travels , trauma , vigorous exercise or similar episodes of limb pain were reported before onset of symptoms . on admission ,
reflexes and sensitivity of the upper and lower limbs were also normal . at rest , the patient kept his feet in slight plantar flexion .
gastrocnemius - soleus muscles on both sides were soft on palpation , and there were no inflammatory changes .
passive dorsiflexion of the ankles caused sharp pain as well as passive stretching and gentle palpation of his calves . despite normal neurological examination ,
the patient was hospitalized in order to allow medical observation and exclude severe diseases . on admission laboratory tests
showed a significant increase in blood levels of creatinine phosphokinase ( 2161 u / l , normal range < 227
u / l ) , alanine transaminase ( 69 u / l , normal range : 0 - 45 ) and aspartate transaminase ( 92 u / l , normal range : 17 - 59 ) .
mg / l ) and white blood cell count ( 7400/l ) were within normal limits .
complete blood count , electrolytes , blood urea nitrogen , creatinine , prothrombin time , partial thromboplastin time and other routine blood parameters were also within normal limits .
furthermore , serological tests ruled out recent viral infections by adenovirus , respiratory syncytial virus , cytomegalovirus , herpes virus and epstein  barr virus , as well as serological tests for mycoplasma pneumonia .
since the patient refused to eat and drink , he received intravenous hydration for 24 h. during the 2 day of hospitalization pain spontaneously resolved and a normal gait was regained . considering
that daily urine output was normal , the boy was discharged , and no long - term follow - up was required .
benign acute childhood myositis is a self - limiting process which frequently affects the gastrocnemius and soleus muscles . in a review of 2004
other agents such as enterovirus , mycoplasma pneumonia and dengue virus have been involved in the process . furthermore , five cases of bacm following h1n1 influenza a virus infection and human parainfluenza virus type 1 infection have been reported . in most cases ,
the disease is self - limiting and when the myositis develops the patient is already in the early convalescent phase of the viral illness .
nevertheless , it is reported that 10/316 children ( 3% ) developed severe rhabdomyolysis , and temporary dialysis was necessary in six cases . during winter 20072008 , influenza b virus was responsible for a large number of cases of bacm in germany , especially among male children aged from 6 to 9 years .
median time between the onset of fever and the beginning of bacm symptoms was 3 days . despite the clinical course of bacm being well described , mall et al .
furthermore , the exact current incidence , prevalence and pathogenesis of bacm are not known .
this could simply be explained by the increased tropism of viruses for immature muscle cells .
furthermore , each virus could act as a trigger in genetically predisposed children and in few patients with undiagnosed metabolic diseases .
nevertheless , the onset may be mistaken for very severe neurological illness such as guillain  barr syndrome or chronic autoimmune diseases . as a consequence unnecessary invasive tests , such as radiography , echocardiography ,
daily medical examination and urine dipstick ( with measurement of myoglobin ) are sufficient to promptly detect complications and rule out more severe illnesses and creatine kinase ( ck ) should be measured only at diagnosis in order to early exclude degenerative diseases .
viral tests for bacm - related viruses should not be routinely performed because of the time interval between infection and seroconversion . moreover ,
not always etiological agents can be found , and antiviral drugs are not usually recommended . nevertheless , influenza test may be useful since influenza viruses can affect the severity of bacm .
however , parents should be encouraged to monitor the child 's urine output and the appearance of coca - cola colored urine and swollen legs .
hospitalization should be scheduled only when the patient 's parents do not seem able to monitor the condition of their child at home .
we report signs and symptoms which can help clinicians to make a correct differential diagnosis when a child suffers from acute muscle pain in table 1 .
. a family history of neuromuscular disorders , myoglobinuria , trauma , chronic progression , rash , edema , muscle weakness or neurological diseases are not typically associated to bacm ; in these cases further investigation is required .

Answer:
acute muscle pain and walking difficulty are symptoms compatible with both benign and severe degenerative diseases . as a consequence , in some cases
 invasive tests and hospitalizations are improperly scheduled .
 we report the case of a 7-year - old child suffering from acute calf pain and abnormal gait following flu - like symptoms
 . a review of the literature will be helpful to better define differential diagnosis in cases of muscle pain in children .
 daily physical examination and urine dipstick are sufficient to confirm the diagnosis of benign acute childhood myositis ( bacm ) during the acute phase , to promptly detect severe complications and to rule out degenerative diseases
 . children with bacm do not require hospitalization , medical interventions or long - term follow - up .


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:
posttraumatic cerebral edema leading to refractory intracranial hypertension is the main prognostic factor in brain - injured patients .
morbidity and mortality occur as a result of transtentorial herniation caused by mass effect due to cerebral swelling .
the combined medical and surgical objective during the acute phase is to prevent raised intracranial pressure ( icp ) and maintain cerebral perfusion pressure in order to limit the development of secondary lesions .
early decompressive craniotomy ( dc ) is a method for decreasing raised icp and has been associated with better outcomes . in neonates ,
as the cranial sutures are open , any associated fracture may relieve the raised icp due to craniotomy flap - elevation like effect .
an 8-day - old male child was brought to the emergency room with a history of fall from a cradle of about 3 feet height followed by loss of consciousness for half an hour .
there was no history of convulsions , vomiting or ear , nose , and throat bleed . on examination ,
the neonate was vitally stable , alert , conscious , moving all four limbs with no focal neurological deficit .
the physical examination showed a large swelling in the left temporal region behind the ear ( battle 's sign ) [ figure 1 ] .
photograph on the day of admission showing a swelling in the left temporoparietal region with battle 's sign computed tomography ( ct ) of the brain showed a large left sided frontoparietal contusion with brain herniation through the fracture segment [ figure 2 ] .
plain axial computed tomography scan brain shows a large hyperdense area in the left frontoparietal region suggestive of a contusion ( black arrow ) , as well as brain herniation , with underlying sutural widening based on the clinical examination and ct findings , a decision was taken to medically manage the patient with anti - epileptic medications and monitor for any signs of raised icp .
the child showed progressive improvement in the neurological condition and was discharged after 8 days and asked to follow - up for dural repair and cranioplasty after 3 weeks .
the child was lost to follow - up and presented 2 months later with a cystic , nonpulsatile 5 cm  4 cm swelling in the left temporal region .
ct scan showed a large cystic lesion in the left temporoparietal region with underlying bone defect [ figure 3 ] .
a diagnosis of growing fracture skull ( posttraumatic leptomeningeal cyst ) was established , and surgical intervention planned .
the neonate underwent duraplasty with pericranial graft and cranioplasty with titanium mesh plate 70 days after the head injury insult [ figure 4 ] .
the infant tolerated the procedure well and was discharged after suture removal . on 6 months
follow - up , the infant was doing well with no neurological deficits or wound - related complications .
plain axial computed tomography scan showing a large 6 cm  3.2 cm  5.3 cm cystic lesion in the left temporoparietal region with underlying bone defect in the temporal bone ( black arrow ) intraoperative photograph showing titanium mesh plate with underlying pericranial dural graft
head injury is likely to occur in children and adolescents ranging from 0 to 19 years in approximately 200 per 100,000 populations with a mortality rate of 29% , according to the national center for health statistic .
different components , such as vasogenic and cytotoxic edema and possibly cerebral vasocongestion contribute to posttraumatic brain swelling .
this brain swelling is associated with an exponential rise in the icp and eventually leads to brain herniation syndromes . in infants with open sutures ,
the relative increases in the icp and their tolerance remain unknown though there is a concern with regards to susceptibility to ischemic injury .
any fracture extending across the cranial suture in an infant can cause bony separation leading to an open cranial vault .
linear skull fracture in association with open sutures can lead to a condition wherein an effect similar to dc is achieved . in adults with a thick solid skull , the linear undisplaced fracture can not expand and therefore probably will not tolerate an increase in icp as well .
the 2012 pediatric head injury guidelines state that decompressive craniectomy with duraplasty , leaving the bone flap out , may be considered for pediatric patients with traumatic brain injuries ( tbi ) who are showing early signs of neurological deterioration or herniation .
hypothesized that early craniotomy ( within 6 h of injury ) in pediatric patients with refractory raised icp would result in better outcomes than following the historic standard of care , which reserved surgery as a final intervention in these patients .
similar studies by kan et al . demonstrated good results with an early craniotomy . in our patient , we believe that the early dc achieved by linear undisplaced fracture and sutural diastasis prevented the development of raised icp leading to quick clinical improvement .
adelson et al . has recommended the following criteria for selecting favorable patients for craniotomy in children : ( 1 ) diffuse cerebral swelling on cranial ct imaging ; ( 2 ) within 48 h of injury ; ( 3 ) no episodes of sustained icp > 40 mm hg before surgery ; ( 4 ) glasgow coma scale score > 3 at some point subsequent to injury ; ( 5 ) secondary clinical deterioration ; and ( 6 ) evolving cerebral herniation syndrome . while , our patient initially presented with diffuse cerebral swelling on ct , the infant was otherwise neurologically intact and showed no signs of raised icp .
thus , an emergency surgery was not warranted , and early dural repair was planned .
. found high rates of bone resorption following autologous bone grafting in pediatric tbi patients similar to our previous experience .
due to this and the size of the cranial defect in our patient , we performed the cranioplasty using the titanium mesh plate .
linear undisplaced fracture in neonates along with open sutures may act as a dc relieving the raised icp almost immediately .
such infants in whom there are no signs of raised intracranial tension can be managed conservatively if the decompression effect achieved is adequate .
hence , a close clinical and radiological follow - up is essential . as the effect of decompression

Answer:
decompressive craniotomy ( dc ) is used to treat intracranial hypertension associated with traumatic brain injury .
 early dc is associated with better outcomes .
 we present a neonate with a history of fall with computed tomography scan showing a large frontoparietal contusion and associated parietal and temporal bone fracture .
 this acted as a spontaneous dc causing bony segment to separate due to which the edematous brain could be accommodated . despite the presence of a large contusion , the child was neurologically intact and medically managed .
 the neonate presented with a posttraumatic leptomeningeal cyst 2 months later , which had to be repaired surgically .
 we discuss how a linear undisplaced fracture acts as spontaneous dc and the role of early dc in improving outcomes .


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 presentation to hospital with vertigo or dizziness is common [ 1 , 2 ] .
the usual
 reason is disabling dizziness leading to nausea , vomiting , and often prostration
 or inability to mobilise .
patients with these symptoms are
 challenging with difficulty determining which specialty to refer to .
otolaryngologists have expertise
 in this area ; however , patients may be more appropriately referred to neurologists
 or general physicians in the first instance .
we discuss the close interplay of pathophysiology relating to vertigo ,
 nystagmus , oscillopsia , and the vestibulo - ocular reflex and its modulation by
 head titubation .
it may be induced by stimulation of the intact sensorimotor system or
 by dysfunction of any of the stabilising sensory systems .
general sensations of dizziness , in contrast , are often of
 nonvestibular aetiology . whether this be an impending
 faint ( type ii ) , dysequilibrium ( type iii ) , or vague lightheadedness ( type
 iv ) , it may be due to nonvestibular causes
. these can include cerebrovascular
 disease , multiple sclerosis , cns tumours , migraine , or epilepsy .

a sixty - four - year - old lady presented to her general practitioner
 ( gp ) with acute onset of unsteadiness and dizziness associated with movement .
she
 visited her doctor with a complaint of feeling dizzy and faint but had a blood
 pressure of 113/70 mmhg .
she had no abnormalities on general , vestibular ,
 neurological , and otological examinations ,
 including no nystagmus .
the dizziness was described as repeated attacks of a sensation
 of internal moving ; that is the patient was  whirling  , but the room was still .

her symptoms worsened over the
 following week , disturbing her daily activity and leading to nausea , vomiting ,
 and prostration .
the gp had noted that she had irregular and erratic eye
 movement and had developed a postural drop in her blood pressure , from
 113/70 mmhg to 97/63 mmhg on standing .
a week later she was permanently dizzy and nauseous and had noticed
 some difficulty in pronunciation of words .
the dizziness was now described as a
 constant sensation that she was turning and tilting over , when she knew she was
 upright , and the room was still .
there had also
 been the occasional sensation that the room was spinning around , although these
 were the only fleeting .
she had no visual disturbance , hearing problems , weakness
 or numbness , and her neurological examination was normal .
she was treated with antiemetics including
 prochlorperazine ; with a presumed diagnosis of vestibular failure , and her gp referred
 her to the otolaryngology services for further treatment and to investigate for
 an organic cause . on admission
on
 examination , she was noted to have a subtle head nodding tremor or titubation .

this was associated with a low - frequency tremor of the upper limbs , which appeared
 to increase on intention .
she had erratic eye movements and it was very difficult to elicit any
 nystagmus , even with frenzel glasses , whether spontaneous or positional .
this
 was due to the difficulty in keeping her eyes open secondary to overwhelming
 nausea .
the patient found that
 it very difficult to keep her eyes still and to focus on a stationary object
 and she was unable to smoothly pursue a moving target .
there was clearly a
 fixation instability and it appeared to be in the form of conjugate involuntary
 saccadic oscillations .
there was , however , a fleeting vertical nystagmus on upgaze , which may have
 indicated a gaze - evoked cause , but with no obvious horizontal element .
a halmagyi - curthoys head thrust test was
 attempted , but proved difficult to interpret due to the stimulation of
 vomiting .
it was noted , however , that the patient was unable to fix on a
 stationary object during head rotation indicating a probable suppression of the
 vestibulo - ocular reflex ( vor ) . due to
 the significant nausea and vomiting , a caloric canal test was not performed .
she had subtle
 cerebellar signs on subsequent examination , including dysmetria and
 dysdiadocokinesis .
dix - halpike test was symptomatically
 positive , with vomiting but with no rotatory nystagmus and no positional
 dependence .
she was given
 intravenous fluids and steroids and treated symptomatically for the nausea and
 vomiting .
it was
 postulated that there was a central cause for her symptoms , due to the
 combination of cerebellar signs , fixation instability / opsoclonus , possible
 upbeat nystagmus , and vor suppression .
therefore , a magnetic resonance scan ( mri )
 of the brain was ordered .
this revealed a large space - occupying lesion in the
 right lobe of the cerebellum , with a smaller lesion in the left lobe ( figure 1 ) .

the patient was referred directly to the neurosurgeons who performed a
 suboccipital craniectomy and excision of the cerebellar tumour .
as a presentation to otolaryngology , the history of this case is not
 unusual .
, it accounts for 13% of patients , but only 50% of those referred to
 otolaryngology services have an otological cause for their symptoms .
it can be argued , therefore , that patients presenting with these symptoms should
 be referred to general physicians in the first instance , to rule out serious
 nonotological causes .
the anamnesis of dizzy symptoms is especially important to elicit in
 detail in order to make informed decisions on referral route .
vertigo indicates a sensation of false movement ( generally
 described like a rotation ) , but rarely , the patient can describe it like a sensation
 of tilt . in our case ,
the patient described both rotational and tilting sensations , whilst stationary and on
 movement .
most importantly was the constant sensation that she was turning but
 that the room was still .
this specific symptom , and its duration ,
 indicates an increased risk of central origin . with peripheral vestibular causes of vertigo
this may be a result
 of oscillopsia , an optical illusion of oscillation sometimes as a direct result
 of nystagmus .
oscillopsia is common in bilateral
 labyrinthine abnormality , but the presence of vertical oscillopsia indicates a
 vertical nystagmus , which is indicative of a central lesion . in this case ,
spontaneous
 nystagmus , albeit fleeting , was vertical nystagmus and this is particularly
 specific to central lesions rather than peripheral vestibular lesions , and is a
 reliable indicator .
damage to the ventral
 tegmental tract , originating in the superior vestibular nucleus , leads to
 upward vestibular signals to the third nerve nucleus and so upbeat nystagmus
 ( ubn ) .
therefore ,
 a vertical nystagmus should give high index of suspicion for a central cause .
the general inability to stabilise the eye ,
 resulting in the erratic eye movement and opsoclonus seen may also indicate
 central pathology .
particular regions involved are the vermis , flocculus , and paraflocculus , which
 are responsible for coordinating smooth pursuit and adaptation of the
 vestibulo - ocular reflex ( vor ) .
these control mechanisms are essential to holding the eye steady for
 fixation , both immediately after saccades and in eccentric positions of gaze , particularly
 important when attempting to track a moving target .
the lesions in the cerebellum
 may well have impaired these important mechanisms in this patient , leading to opsoclonus
 and an inability to fixate .
it is also known that an impairment of adaptation
 of the vor , to compensate for movement , may lead to oscillopsia .
although
 the lesions seen on mri in this case are not in the vermis , surrounding oedema
 and paraneoplastic effects may be responsible for an impairment of vermis
 function .
the general difficulty in diagnosis , detailed
 neurotologic examination , and testing in this case may have been influenced by
 the use of prochlorperazine .
this is a phenothiazine antipsychotic agent which
 is very commonly used as a vestibular sedative for nausea due to vertigo .
it is
 widely known , however , although affording symptomatic relief for the patient ,
 this drug can result in a delay to vestibular compensation and influence
 diagnostic testing .
this is
 defined as nodding head tremor with a frequency of 3 to 4 hz and may be seen in
 midline cerebellar disease [ 12 , 13 ] .
titubation can occur in isolation or
 combined with a postural tremor elsewhere , especially in the arms .
this can be
 seen in patients with essential tremor or dystonic tremor , associated with
 posterior fossa disorders .
essential tremor , such as this , is closely related
 to the oculomotor deficits described above . these include deficits of pursuit
 initiation and suppression of the vor .
it has been shown that there is a strong
 correlation with the intensity of intention tremor and the oculomotor
 impairment and may indicate an impairment of the caudal cerebellar vermis .

there is the potential , however , that the tremor and head titubation may have
 been an extrapyramidal akathisia as a result of prochlorperazine use .
the closely related interplay of the mechanisms involved in this
 patient 's symptoms are
 difficult to sequence .
the cerebellar lesions are the only true evidence of a
 causal element to this case .
however , it remains to be understood how these
 lesions had brought about the specific symptom complex identified .
was the
 vertigo a direct result of the lesion or was it secondary to an oscillopsia
 generated by nystagmus , or due to failure of the vor ?
was ubn or gaze - evoked nystagmus present , or was it just
 a brief recognisable pattern in the otherwise erratic oculomotor impairment or
 opsoclonus , or secondary to loss of adaptation of the vor ? was the head
 titubation the key ?
oscillopsia occurs when there is failure of the vor to
 adapt and compensate for head movements .
cerebellar lesions may impair the
 normal cerebellar adaptive mechanism for the vor and so impair its ability to
 compensate for movement of the head .
simultaneously , a cerebellar lesion may
 also lead to an essential tremor , manifesting as head titubation and upper limb
 tremor .
many of the signs seen in this case , such as the impaired vor , the
 titubation , opsoclonus , and dysarthria , are classically caused by cerebellar
 vermal lesions .
however , the lesions seen on mri are in the deeper hemispheres .
 one may , therefore , suggest that surrounding oedema and local compression have led to
 vermal damage .
it can be seen in figure 1 that there is a degree of cerebellar midline shift .
one may conclude that the lesions themselves may have
 simultaneously caused a tremor and an inability for the vor to compensate for
 it .
oscillopsia due to an impaired vor has been shown to be more likely than oscillopsia due to a titubation .   also , the two cerebellar lesions may have had
 the two separate effects of tremor and impaired vor
.
			  the differentiation between central and peripheral causes of vertigo
 can be perplexing and often require the expertise of a specialist
 neurotologist .
many signs and tests , such as saccadic pursuit , gaze - evoked
 nystagmus , and the halmagyi - curthoys test , have recently been shown to be
 unreliable in distinguishing peripheral from central causes ; therefore , an
 expert opinion may be required . however , whether the vertigo in this case was
 a result of an oscillopsia , nystagmus , or central cause , the referral route
 should initially be via a general physician to rule out such life threatening
 causes as central tumours .

 suspicion of a
 central cause for vertigo on examination should prompt urgent imaging of the
 central nervous system.a vertical nystagmus should give high index of suspicion for a central
 cause.central vestibular lesions may present with a wide variety of symptoms and signs which
 may include impaired vor , head titubation and tremor , opsoclonus , and oscillopsia.initial referral
 of patients with disabling vertigo should be via general physicians .

suspicion of a
 central cause for vertigo on examination should prompt urgent imaging of the
 central nervous system .
central vestibular lesions may present with a wide variety of symptoms and signs which
 may include impaired vor , head titubation and tremor , opsoclonus , and oscillopsia .

Answer:
objective . discuss complex interplay of pathophysiological effects of cerebellar space occupying lesions on the vestibular pathway .
 discuss challenges of diagnosis and referral along with differential and final diagnosis of unusual presentation .
 case report .
 we describe the case of a patient with vertiginous symptoms complicated by neurological features , namely , head titubation and tremor .
 the patient also had signs of oscillopsia and possible impairment of the vestibulo - ocular reflex . the resulting symptom and sign complex made for a difficult diagnosis , as the interplay of the pathophysiology of these signs , were unusual . conclusion .
 the discussion has revealed that the cerebellar lesions themselves may have simultaneously caused head tremor and an inability for the vestibulo - ocular reflex to compensate , resulting in vertigo .
 however , whether the vertigo was a result of an oscillopsia , nystagmus , or central cause , the referral route should initially be via a general physician to rule out such a life threatening cause as a tumour .


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:
we grew the budding yeast saccharomyces cerevisiae in 200 l batch culture on bd falcon 96-well microtest plates at 30.7 c ( 0.2c , standard deviation ) using synthetic media ( yeast nitrogen bases + nitrogen , complete supplement mixture ) supplemented with 2% sucrose .
cultures were maintained in a well - mixed condition by growing on a shaker at 825 r.p.m .
serial dilutions were performed daily ( 23 hours of growth ) with variable dilution factors .
population densities were recorded each day before the serial dilution by measuring optical density at 600 nm using a thermo scientific varioskan flash multimode reader .
the calibration between optical density and cell density was based on the previous characterization of this system . in the group of connected populations , for each dilution factor there were 4 replicate arrays each consisting of 10 patches .
populations were connected by controlled dispersal between nearest neighbors ( dispersal rate d=0.5 , which is defined as the fraction of population going out of a patch ) . reflecting boundary conditions
were adopted , meaning that a population on the edge would have 75% of its cells remaining in the patch during the dispersal step . in the group of isolated populations ,
the experiment was performed in a similar spatial setting except that there was no dispersal ( d=0 ) ; for each dilution factor there were 4 arrays each consisting of 5 patches , thus a total of 20 replicate populations isolated from each other .
the dilution factors for the data presented in fig . 2 are 500 , 1000 , 1200 , 1400 and 1600 . in the experiment to measure recovery length ,
populations were connected by nearest - neighbor dispersal ( d=0.5 , reflecting boundary conditions ) .
the dilution factor for the bad region ( 1 patch ) was 2500 ; the dilution factor for the good region ( 5 patches ) was varied as the environmental driver .
the dilution factors for the data presented in fig . 4 are 500 , 750 , 1000 , 1133 , 1200 , 1266 , 1350 and 1400 .
statistical indicators for the connected populations were calculated among 10 populations in one array on each day and averaged over a span of at least 5 days , after the populations stabilized .
the mean value of 4 replicate arrays and sem ( n=4 ) are shown in figure 2 .
for the isolated populations , statistical indicators were calculated on each day among 20 populations over 5 days .
we used bootstrap to compute ses of the indicators by resampling 1000 times the ensemble of replicate populations ( for the coefficient of variation and the temporal correlation ) or arrays ( for the spatial correlation ) .
the coefficient of variation ( cv ) was calculated as the sample standard deviation ( supplementary fig .
3b ) divided by the sample mean . because the local populations in our experiment were grown in a homogeneous environment , in principle they could all be treated as replicates . assuming the system is ergodic , the cv calculated over an ensemble of replicates can be interpreted either as spatial cv of many populations at one time point or temporal cv of a single population over many time points .
the temporal correlation , defined as the lag-1 autocorrelation , was estimated by the pearson s correlation coefficient between the population densities at subsequent days . to correct for negative bias in small samples
n is a fixed number for different dilution factors , so using the modified estimators would not affect the trend of indicators .
the spatial correlation , defined as the two - point correlation between all neighboring pairs , was estimated by the moran s coefficient .
the expectation of moran s coefficient is 1n1 in the absence of spatial correlation ; we used a modified estimator with an additional term 1n1 so that the expectation is 0 . in this case , the sample size n is the number of patches in an array : n=10 for connected populations ; n=5 for isolated populations . for detailed formula of the statistical indicators , see supplementary note 4 . in the analysis we ensured environmental homogeneity by removing a linear gradient of population density observed in connected populations
the small gradient is presumably caused by some heterogeneity in experimental conditions ( temperature , dilution errors , etc . ) across the plate .
removing gradient - type spatial heterogeneity before statistical analysis is similar to the detrending procedure commonly used in time - series analysis ; it prevents spurious signals such as positive spatial correlation ( supplementary fig .
after the recovery profile stabilized , we tracked the population density profiles of at least 6 replicates over several days .
the half - point recovery length l was estimated by performing a shape - preserving interpolation ( matlab function pchip , piecewise cubic hermite interpolating polynomial ) to the recovery profile and then locating the position of half recovery at which n(x = lhalf)=12n(x=5 ) .
the population density of the bad region ( dilution factor 2500 ) in our experiment was close to 0 ( fig . 4 and supplementary fig .
7 ) . in the more general scenario with a sharp boundary between two regions of different quality ( supplementary fig . 6 and 8) ,
the position of half recovery can be defined as the midpoint between the equilibrium population density of the region of interest and the population density at the boundary .
the exponential recovery length was estimated by fitting an exponential function with three parameters c1 exp(x / l ) + c2 to the recovery profile n(x ) .
the data points used for exponential fitting are from position 1 to 5 ( except for dilution factor 500 , the data for fitting are from position 0 to 5 ) .
we note that our definition of exponential recovery length is phenomenological , because : 1 ) the deviation is expected to be exponential only close enough to the equilibrium ; 2 ) at higher dilution factors the profile can deviate from an exponential form ( supplementary fig .
4c ) may be due to the limited data points used in fitting or experimental errors . for both the half - point recovery length and the exponential recovery length , we used bootstrap to compute ses for the indicators by resampling the ensemble of steady - state profiles 100 times and fitting the average recovery profile .
we grew the budding yeast saccharomyces cerevisiae in 200 l batch culture on bd falcon 96-well microtest plates at 30.7 c ( 0.2c , standard deviation ) using synthetic media ( yeast nitrogen bases + nitrogen , complete supplement mixture ) supplemented with 2% sucrose .
cultures were maintained in a well - mixed condition by growing on a shaker at 825 r.p.m .
serial dilutions were performed daily ( 23 hours of growth ) with variable dilution factors .
population densities were recorded each day before the serial dilution by measuring optical density at 600 nm using a thermo scientific varioskan flash multimode reader .
the calibration between optical density and cell density was based on the previous characterization of this system . in the group of connected populations , for each dilution factor there were 4 replicate arrays each consisting of 10 patches .
populations were connected by controlled dispersal between nearest neighbors ( dispersal rate d=0.5 , which is defined as the fraction of population going out of a patch ) . reflecting boundary conditions
were adopted , meaning that a population on the edge would have 75% of its cells remaining in the patch during the dispersal step . in the group of isolated populations ,
the experiment was performed in a similar spatial setting except that there was no dispersal ( d=0 ) ; for each dilution factor there were 4 arrays each consisting of 5 patches , thus a total of 20 replicate populations isolated from each other .
the dilution factors for the data presented in fig . 2 are 500 , 1000 , 1200 , 1400 and 1600 . in the experiment to measure recovery length ,
populations were connected by nearest - neighbor dispersal ( d=0.5 , reflecting boundary conditions ) .
the dilution factor for the bad region ( 1 patch ) was 2500 ; the dilution factor for the good region ( 5 patches ) was varied as the environmental driver .
4 are 500 , 750 , 1000 , 1133 , 1200 , 1266 , 1350 and 1400 .
statistical indicators for the connected populations were calculated among 10 populations in one array on each day and averaged over a span of at least 5 days , after the populations stabilized .
the mean value of 4 replicate arrays and sem ( n=4 ) are shown in figure 2 .
for the isolated populations , statistical indicators were calculated on each day among 20 populations over 5 days .
we used bootstrap to compute ses of the indicators by resampling 1000 times the ensemble of replicate populations ( for the coefficient of variation and the temporal correlation ) or arrays ( for the spatial correlation ) .
the coefficient of variation ( cv ) was calculated as the sample standard deviation ( supplementary fig .
3b ) divided by the sample mean . because the local populations in our experiment were grown in a homogeneous environment , in principle they could all be treated as replicates .
assuming the system is ergodic , the cv calculated over an ensemble of replicates can be interpreted either as spatial cv of many populations at one time point or temporal cv of a single population over many time points .
the temporal correlation , defined as the lag-1 autocorrelation , was estimated by the pearson s correlation coefficient between the population densities at subsequent days . to correct for negative bias in small samples
n is a fixed number for different dilution factors , so using the modified estimators would not affect the trend of indicators .
the spatial correlation , defined as the two - point correlation between all neighboring pairs , was estimated by the moran s coefficient .
the expectation of moran s coefficient is 1n1 in the absence of spatial correlation ; we used a modified estimator with an additional term 1n1 so that the expectation is 0 . in this case , the sample size n is the number of patches in an array : n=10 for connected populations ; n=5 for isolated populations . for detailed formula of the statistical indicators , see supplementary note 4 .
in the analysis we ensured environmental homogeneity by removing a linear gradient of population density observed in connected populations .
the small gradient is presumably caused by some heterogeneity in experimental conditions ( temperature , dilution errors , etc . ) across the plate .
removing gradient - type spatial heterogeneity before statistical analysis is similar to the detrending procedure commonly used in time - series analysis ; it prevents spurious signals such as positive spatial correlation ( supplementary fig .
after the recovery profile stabilized , we tracked the population density profiles of at least 6 replicates over several days .
the half - point recovery length l was estimated by performing a shape - preserving interpolation ( matlab function pchip , piecewise cubic hermite interpolating polynomial ) to the recovery profile and then locating the position of half recovery at which n(x = lhalf)=12n(x=5 ) .
the population density of the bad region ( dilution factor 2500 ) in our experiment was close to 0 ( fig . 4 and supplementary fig .
7 ) . in the more general scenario with a sharp boundary between two regions of different quality ( supplementary fig . 6 and 8)
, the position of half recovery can be defined as the midpoint between the equilibrium population density of the region of interest and the population density at the boundary .
the exponential recovery length was estimated by fitting an exponential function with three parameters c1 exp(x / l ) + c2 to the recovery profile n(x ) .
the data points used for exponential fitting are from position 1 to 5 ( except for dilution factor 500 , the data for fitting are from position 0 to 5 ) .
we note that our definition of exponential recovery length is phenomenological , because : 1 ) the deviation is expected to be exponential only close enough to the equilibrium ; 2 ) at higher dilution factors the profile can deviate from an exponential form ( supplementary fig .
4c ) may be due to the limited data points used in fitting or experimental errors . for both the half - point recovery length and the exponential recovery length , we used bootstrap to compute ses for the indicators by resampling the ensemble of steady - state profiles 100 times and fitting the average recovery profile

Answer:
slower recovery from perturbations near a tipping point and its indirect signatures in fluctuation patterns have been suggested to foreshadow catastrophes in a wide variety of systems1,2 .
 recent studies of populations in the field and in the laboratory have used time - series data to confirm some of the theoretically predicted early warning indicators , such as an increase in recovery time or in the size and timescale of fluctuations36 .
 however , the predictive power of temporal warning signals is limited by the demand for long - term observations .
 large - scale spatial data are more accessible , but the performance of warning signals in spatially extended systems710 needs to be examined empirically3,1113 . here
 we use spatially extended yeast populations , an experimental system displaying a fold bifurcation6 , to evaluate early warning signals based on spatio - temporal fluctuations and to identify a novel warning indicator in space .
 we found that two leading indicators based on fluctuations increased before collapse of connected populations ; however , the magnitude of increase was smaller than that observed in isolated populations , possibly because local variation is reduced by dispersal .
 furthermore , we propose a generic indicator based on deterministic spatial patterns ,  recovery length  . as the spatial counterpart of recovery time14
 , recovery length is defined as the distance for connected populations to recover from perturbations in space ( e.g. a region of poor quality ) . in our experiments ,
 recovery length increased substantially before population collapse , suggesting that the spatial scale of recovery can provide a superior warning signal before tipping points in spatially extended systems .


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 online version of this article ( doi:10.1007/s40121 - 014 - 0043 - 9 ) contains supplementary material , which is available to authorized users .
a member of the togaviridae family , infection with the chikungunya virus ( chikv ) has emerged as a major public health concern , resulting in outbreaks of fever and debilitating arthralgia in the caribbean and globally .
the first autochthonous ( native ) transmission of chikv in the caribbean was confirmed in december 2013 on the french island of saint martin .
rapid spread and local transmission of chikv occurred in the caribbean and the americas within 9  months ( fig .  1 ) .
this has resulted in 651,344 suspected and 9,182 laboratory - confirmed chikungunya cases in the caribbean and the americas as reported by the centers for disease control and prevention .
the effective management of the rapid spread of chikungunya is integrally related to the geographic distribution and re - emergence of competent mosquito vectors , evolving chikv genotypes , susceptible human populations , environmental influences , and social mobilization .
understanding the contribution of these factors is important to improving the control of the global transmission of this disease.fig .
1introduction of chikungunya to the caribbean by epidemiological week first reported  december 2013 to august 2014 .
data from paho / who statistics   introduction of chikungunya to the caribbean by epidemiological week first reported  december 2013 to august 2014 .
there are three distinct chikv genotypes : west african , east central south african [ ecsa ; or indian ocean lineage ( iol ) ] , and asian [ 1 , 5 , 6 ] . these genotypes represent the evolution of the virus in keeping with the geographic distribution over the years . in africa , this virus is transmitted through enzootic ( sylvatic ) and urban ( human  mosquito cycle ) cycles among non - human and human primates by aedes mosquitoes species .
previous authors report the probable existence of the chikv in africa for hundreds of years , with the first suspected epidemic documented in 1779 .
subsequent reports included outbreaks in nigeria ( 1964 ) , the ivory coast ( 1981 ) , and senegal ( 1983 ) associated with the west african strain .
the resurgence of chikungunya in the twentieth century was first documented in 1953 , in the newala district of tangaiynika ( tanzania ) .
the chikv continued to spread through the suspected vectors aedesfurcifer / aedescordellieri , to other south african countries , inclusive of rhodesia ( zimbabwe ; 1961 , 1962 , and 1971 ) .
epidemics associated with the ecsa lineage subsequently occurred in cameroon ( 2006 ) and gabon ( 2007 ) with aedesafricanus and aedesalbopictus reported as the principal vectors , respectively . in gabon in 2007 , concurrent chikv and dengue fever epidemics were also experienced , with chikv transmission linked to the a.albopictus mosquito .
the iol strain originated in coastal kenya in 2004 and 2005 ( affecting 75% of the lamu island s population , via the vector aedesaegypti ) and then spread to the reunion island ( affecting one - third of the population ) and was subsequently introduced to other islands of the indian ocean and continental india , via the vector a.albopictus [ 1 , 57 , 12 ] .
it is believed that the 2007 outbreak in italy was initiated through the importation of the chikv by a traveler from reunion island .
other countries in which international travel facilitated the spread of chikv included france ( from travelers from reunion island ; 77% ) , comoros ( 14% ) , and mauritius ( 9% ) .
autochthonous transmission in france , however , was not detected until the year 2010 , in association with a. albopictus .
studies have reported a high efficiency of transmission of chikv in the temperate climates by the a. albopictus species .
there are several aedes species which are competent in the transmission of the chikv , with a.aegypti and emerging populations of a.albopictus identified as responsible vectors in asia .
the asian strain identified in thailand in 1958 was transmitted by the suspected vector , a. aegypti .
this asian strain was also reported in outbreaks in india ( 19621965 ) and southeast asia ( 19581960 and 19621964 ) , also in association with the a. aegypti mosquito .
epidemics of the 1980s and 1990s in southeast asian countries ( philippines , thailand , myanmar , and indonesia ) were associated with the asian endemic / epidemic chikv lineage . since then
, the asian endemic / epidemic chikv lineage has continued to circulate sporadically , transmitted primarily among humans by a.aegypti and was again documented in the 2006 outbreak in malaysia [ 1 , 7 ] .
emergence of an iol strain with resulting replacement of the endemic asian strain occurred during the southeast asia epidemics of 20062009 [ 1 , 7 ] .
it is thought that the e1 envelope glycoprotein mutation of the endemic asian genotype resulted in the decreased adaptability of the chikv to a.albopictus , with decreased transmission , and the facilitation of chikv evolution and strain replacement .
the caribbean region continues to encounter challenges with the control of mosquito populations including a.aegypti and other aedes species .
the aedes mosquito was introduced to the caribbean through the african slave trade . following its introduction ,
a significant increase in the a. aegypti population density was associated with the intercontinental exchange activities of the second world war .
public health interventions of national health ministries and the pan american health organization in the 1950s and 1960s successfully reduced a.aegypti vector indexes by 1972 .
this success , however , was short lived and the re - infestations of the latin american and caribbean regions by a.aegypti in the late 1970s was accompanied by the introduction of a.albopictus in the early 1980s to some caribbean countries . although both a.aegypti and a.albopictus may be found in the caribbean , a.aegypti remains the principal vector responsible for the transmission of chikv and dengue in this region . to date
, the chikv lineage identified in the 2014 caribbean outbreak belongs to the old asian lineage .
the presence of the asian lineage chikv , compounded by a nave caribbean population and high prevalence of a.aegypti , makes the probability of establishment of endemicity of chikungunya in the caribbean high .
this risk of establishment of endemicity extends to most tropical and subtropical regions of latin america areas and the southern usa , which is presently experiencing challenges with a.aegypti re - infestation . in the months preceding the caribbean s first case , china and the philippines accounted for 27.5% of travelers into the caribbean .
there were ten cases reported in spain from travelers from haiti and dominica republic during april to june 2014 .
the expansion of the chikv to north and south america from the caribbean is of great concern .
in their review of air travel from the caribbean , noted that the final destination of 52.1% of international travelers from the chikungunya - infected caribbean territories was the usa .
the most likely cities to be travelled to from the caribbean were new york ( 13.8% ) , paris ( 11.7% ) , miami ( 7.8% ) and san juan , puerto rico ( 3.9% ) .
it is expected that the change of climatic conditions , compounded by the increase of the warmer weather in temperate zones , will facilitate the further spread of this disease .
the months june through to november are designated as the  hurricane season  in the caribbean , or  the wet season  . the wet season has been shown to be associated with the increased breeding of the a.aegypti mosquitos .
florida reported its first two cases of autochthonous chikv transmission in july 2014 and , as of september 9 , 2014 , remains the only us state with autochthonous transmission .
florida now has eight cases of local transmission and 184 travel - associated laboratory - confirmed chikungunya cases as reported to arbornet .
the impact of the introduction of chikv into the caribbean region , a known tourist destination exchange of an estimated 20 million persons annually of which 9 million are us residents , remains to be seen .
the acquisition of chikv by travelers to the caribbean enhances the spread to neighboring caribbean countries and globally . as of epidemiological week 35 , among the caribbean countries affected , those with the highest incidence rates ( incidence/100,000 population ) include : guadeloupe ( 16,465 ) , martinique ( 15,087 ) , saint martin ( french part 13,401 ) , saint barthelemy ( 11,707 ) , dominica ( 5,068 ) , dominican republic ( 4,128 ) , and haiti ( 627 ) ( fig .  1 ) .
the emergence of chikungunya in the caribbean unfolds a story of the dynamic evolution and interaction of microbes and risk factors underlying the determinants of health .
the interaction of economic trade and its role in the transmission of vectors and infectious agents needs to be reviewed and policies reinforced and implemented .
. continued education to increase the awareness of this disease is needed to curtail the population growth of mosquitoes and to mitigate the spread of chikungunya by travelers to the usa and other regions . improved awareness of the epidemiology and clinical manifestations
preventative measures and epidemiological monitoring of the evolving chikv epidemic in the caribbean must be improved and sustained .
this article does not contain any new studies with human or animal subjects performed by any of the authors .

lizette mowatt and sandra t. jackson have no conflict of interest to declare with respect to this article .
this article does not contain any new studies with human or animal subjects performed by any of the authors .
this article is distributed under the terms of the creative commons attribution noncommercial license which permits any noncommercial use , distribution , and reproduction in any medium , provided the original author(s ) and the source are credited .

Answer:
chikungunya is a mosquito - borne virus that has shown increased prevalence in the caribbean since october 2013 .
 there have been several outbreaks throughout asian and african countries over the past few decades with global travel and tourism having a major impact on the further spread of this disease . improved policies and practices for preventative measures and epidemiological surveillance must be implemented to prevent the continued transmission of chikungunya.electronic supplementary materialthe online version of this article ( doi:10.1007/s40121 - 014 - 0043 - 9 ) contains supplementary material , which is available to authorized users .


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:
type 1 diabetes mellitus ( t1 dm ) is one of the most common chronic diseases in childhood and results from autoimmune destruction of pancreatic -cells , leading to insulin deficiency . t1 dm is thought to originate through a combination of genetic and unknown environmental factors , of which environmental factors remain poorly defined .
newfoundland and labrador ( nl ) , canada , is recognized as having one of the highest rates of t1 dm worldwide .
a study on hospitalizations of children in nl reported an increase in diabetes - related hospitalizations among children aged 019 years .
t1 dm is a significant disease in nl with its associated acute and chronic complications as well as the economic costs to both families and the health care system .
identification of potential perinatal environmental risk factors is examined in this study to try and elucidate potential reasons of why the disease is so common in this region of north america .
this study was a case control design involving the linkage of data extracted from the newfoundland and labrador diabetes database ( nldd ) with the live birth system ( lbs ) .
the nldd is maintained by the janeway pediatric research unit at the janeway child health care centre ( jchcc ) in st .
the nldd includes data for the majority of cases of t1 dm diagnosed in nl from 1987 to present .
children are included in the database as part of a prospective provincial study on the epidemiology of t1 dm in nl .
they have a confirmed diagnosis of t1 dm according to canadian diabetes association ( cda ) criteria .
the lbs is maintained by the newfoundland and labrador centre for health information ( nlchi ) .
data for this system are acquired from live birth notification forms that are completed in all provincial health care facilities .
the forms are provided to nlchi by the vital statistics division , service nl , and contain clinical and demographic data for all births ( resident and nonresident ) in the province .
cases included children born in nl from 1992 onwards which have been diagnosed with t1 dm before 15 years of age .
children with type 2 diabetes , maturity - onset diabetes of youth , transient hyperglycemia , and diabetes caused by chemotherapy or cystic fibrosis are excluded from the nldd and thus were not included in the study .
children born prior to 1992 were not included in the study because there are no electronic birth notification data available before this date .
a unique identifier , such as the provincial health insurance plan number , was not available for all children in the nldd . as a result case subjects were linked to the lbs using child 's date of birth and mother 's maiden name .
of the 301 cases in the nldd , 23 were excluded because they were born out of province . of the remaining 278 ,
linkage was possible for all but six children resulting in a total of 266 cases included in the study .
three control subjects ( n = 798 ) were selected for each case matched on year of birth , sex , and health authority of mother 's residence at time of delivery .
power analysis was performed to determine whether this sample size would be sufficient to detect statistical significant associations between t1 dm and the risk factors of interest .
the power analysis was conducted considering an overall rate of birth by c - section in nl as 30.9% , in order to achieve a power of 80% with a desired odds ratio of 1.5 . using the method described by kelsey et al .
the power analysis confirmed that a sample size of 266 cases and 798 controls is sufficient to detect statistically significant relationships between t1 dm and delivery by c - section .
cases and controls were grouped into two gestational age categories : preterm and term / postterm . birth weight in grams
was used to classify cases and controls as high birth weight ( > 4,000 grams ) or not ( 4,000 grams ) .
cases and controls were also classified as small / appropriate - for - gestational - age or large - for - gestational - age using the method described by kramer et al . .
cases and controls were grouped according to parity or birth order as either 1 and 2 or more .
mother 's marital status was categorized as married , single , separated , widowed , or divorced .
mother 's education level was classified into three categories : not graduated high school , graduated high school , and education beyond high school .
demographic and clinical factors of mothers , including age , marital status , education , place of residence , parity ( number of live born children delivered ) , and complications of pregnancy , were included .
cases and controls were analyzed by sex , place of residence , age of onset , length of gestation , type of delivery , birth weight , size for gestational age , and birth order .
chi - square tests were used to predict diabetes status on the basis of the independent variables .
conditional multiple logistic regression was used to assess the relationship between t1 dm risk and the variables of interest .
the first model contained birth weight , gestational age , parity , delivery method , mother 's marital status , mother 's education level , mother 's age , maternal hypertension , and mother 's t1 dm status .
the second model incorporated all variables in the first model with the exception of birth weight and gestational age which were replaced with size - for - gestational - age .
birth weight and gestational age were not included in the same model as size - for - gestational - age as they are components of this variable .   the statistical package for the social sciences ( spss ) 17.0
this study received approvals from the human investigation committee of memorial university , from each of the hospital boards and the secondary uses committee of the newfoundland and labrador centre for health information ( nlchi ) prior to commencement .
the percentages of male and female cases were similar ( 50.8 and 49.2 , resp . ) .
table 1 also demonstrates the age distribution of cases as well as their age of diagnosis .
there were more males than females diagnosed in the 04 age group ; however , this finding was not statistically significant .

table 2 presents maternal and perinatal characteristics of the study population . a higher percentage of cases than controls were born pre - term ( 9.8% versus 6.8% , resp . ) .
while there was no significant difference observed between birth weight of the cases and controls , there was a significant difference observed for size - for - gestational - age with a higher percentage of cases than controls born large - for - gestational - age ( 18.2% versus 12.8% , resp .
it was more common for cases to be delivered by c - section than controls ( 30.8% versus 22.1% , p = 0.009 ) .
t1 dm was more common among first or second born cases compared to those born third or higher ( p = 0.022 ) .

table 3 presents the results of the conditional logistic regression models . in the model which included birth weight and gestational age , delivery by c
children delivered by c - section were 1.41 times as likely to develop t1 dm ( hazard ratio ( hr ) 1.41 , p = 0.015 ) . in the second model , which included size - for - gestational - age
, c - section delivery was not associated with increased risk of t1 dm ( hr 1.3 , p = 0.076 ) . both parity and size - for - gestational - age
were found to be significant risk factors for t1 dm from chi - square analysis ( table 2 ) ; these factors did not remain statistically significant in the conditional logistic regression models .
findings of this study indicate that c - section delivery was a significant risk factor for t1 dm in children aged 015 years .
this finding is in line with a recent meta - analysis of 20 studies which found that the combined effect of c - section delivery was 1.23 ( 95% ci 1.151.32 ) .
theories of why this may be associated with the development of t1 dm in offspring includes the involvement of the role of gut bacteria in the development of the immune system .
studies have shown a difference between the compositions of gut microbiota in vaginally delivered children and those delivered by c - section .
children delivered by c - section may be primarily exposed to bacteria in the hospital and not maternal bacteria , hence the increased risk of t1 dm may be linked to a different composition of gut flora .
another possible explanation is related to the hygiene hypothesis which proposes that the risk of diabetes may be increased when children are not exposed to infections in early life .
children delivered by c - section have decreased exposures to infections compared to children born vaginally and , in turn , have increased risk for diabetes .
another theory suggests that the observed increased risk of diabetes after c - section may be related to perinatal stress .
nl has a high rate of birth by c - section as compared to other regions in canada .
the provincial rate of births by c - section was 30.9% in 2005 - 2006 versus the canadian rate of 26.3% .
the rates of c - section have increased in nl to 33% in 2010 . in the present study , maternal age at time of birth
was not found to be significantly associated with risk of t1 dm in offspring ; other studies have found significant relationships between mother 's age and t1 dm risk .
a recent meta - analysis of 37 studies found that the odds of t1 dm increased by 10% for children whose mothers were over 35 years of age at time of birth ( or = 1.10 95% ci 1.01 , 1.20 ; p = 0.03 ) .
conversely , a matched case - control study of 196 cases in the united kingdom   found that mothers of control children were older than mothers of cases ( or = 0.900 95% ci 0.854 , 0.948 ; p < 0.001 )
. for other maternal factors , such as education level and marital status , there were no associations found which is consistent with other similar studies [ 14 , 15 ] .
the present study also did not find any associations between maternal hypertension and risk of t1 dm in offspring .
other studies have found an increased risk of t1 dm in offspring with maternal history of t1 dm [ 13 , 16 , 17 ] ; however , these studies also included information on paternal history of t1 dm . a 2009 study by algert and colleagues   did not find an association between maternal t1 dm and risk of t1 dm in children .
similar to the present study , the study by algert et al . did not contain information on paternal t1 dm . there was no significant relationship between parity and t1 dm risk found in the current study .
this is different than a western australia population based cohort study of 835 cases of t1 dm diagnosed by the age of 15 that found a significant decrease in t1 dm with increasing birth order .
birth weight and gestational age were not found to be associated with risk of t1 dm in the present study ; however , chi - squared analysis revealed a significant difference between t1 dm and size - for - gestational - age with a higher percentage of cases than controls born large - for - gestational - age , but this was no longer significant in the conditional logistic regression models .
our findings do not support the findings of a meta - analysis of 11 studies examining birth weight which found that a birth weight greater than 4,000 grams was associated with an increased odds of t1 dm ( or = 1.17 95% ci 1.09 , 1.26 ; p < 0.05 ) .
findings related to the association between gestational age and t1 dm appear to be mixed .
a case - control study conducted in austria found that babies born at 3439 weeks had a significantly higher risk for t1 dm compared to those born before 33 or after 40 weeks .
however , a study by cardwell et al .   found that children born after 40 weeks gestation had a significantly lower risk of t1 dm than children born prior to 40 weeks .
while size - for - gestational - age has not been extensively studied , some studies have found significant associations .
a cohort study of 272 children in new south wales , australia , with t1 dm found that children who were small - for - gestational - age had a significantly decreased risk of t1 dm compared to children born appropriate - for - gestational age .
the findings of this study should be considered in the context of its strengths and weaknesses .
an important strength is that the use of a record linkage case - control study design eliminates recall bias that is apparent in cross - sectional study designs .
secondly , data contained in the lbs were collected at time of birth by healthcare professionals , and the nldd data were collected from physician charts at time of t1 dm diagnosis which contributes to the reliability of the data .
a limitation of this study is that there was very little information available pertaining to fathers as the majority of the information collected at the time of birth for the lbs is related to the mother and child .
this study identified c - section as a significant risk factor for the development of t1 dm among children aged 015 years in nl , a region with very high rates of t1 dm .
findings may have an impact on health practice , health care planning and future research related to t1 dm among children .

Answer:
objectives . newfoundland and labrador ( nl )
 has one of the highest incidences of type 1 diabetes mellitus ( t1 dm ) worldwide . rates of t1 dm are increasing and the search for environmental factors that may be contributing to this increase is continuing . methods .
 this was a population - based case control design involving the linkage of data from a diabetes database with live birth registration data .
 266 children aged 015 years with t1 dm were compared to age- and gender - matched controls .
 chi - square analysis and multivariate conditional logistic regression were carried out to assess maternal and infant factors ( including maternal age , marital status , education , t1 dm , hypertension , birth order , delivery method , gestational age , size - for - gestational - age , and birth weight ) .
 results .
 cases of t1 dm were more likely to be large - for - gestational - age ( p = 0.024 ) and delivered by c - section ( p = 0.009 ) as compared to controls .
 c - section delivery was associated with increased risk of t1 dm ( hr 1.41 , p = 0.015 ) when birth weight and gestational age were included in the model , but not when size - for - gestational - age was included ( hr 1.3 , p = 0.076 ) . conclusions .
 birth by c - section was found to be a risk factor for the development of t1 dm in a region with high rates of t1 dm and birth by c - section .
 these findings may have an impact on health practice , health care planning , and future research .


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:
in this issue of critical care , kao and colleagues   consider whether open lung biopsy ( olbx ) can assist in the management of patients with acute respiratory distress syndrome ( ards ) .
clinical outcome in ards remains poor despite substantial advances in our understanding of the biology of this syndrome .
although limiting transpulmonary pressure can clearly prevent worsening of ards , no other major therapeutic advances with proven benefit have occurred in this area .
progress has been limited potentially due to the heterogeneous phenotypes that are known to underlie the american european consensus definition of this disease .
thus , methods to improve diagnostic specificity are likely to be helpful in making progress .
olbx has been used for years as a method of defining the underlying pathology in patients with lung disease .
while its role has become established in the setting of interstitial lung disease , its utility and safety are more controversial in critically ill patients .
proponents of olbx argue that knowledge of underlying etiology can be helpful in defining the best course of treatment .
in addition , the risk of biopsy in experienced hands is fairly low if adequate precautions are taken .
opponents of olbx cite the lack of specific therapies for underlying etiologies of ards and believe that defining the underlying mechanism of injury is largely academic .
a similar discussion has taken place in the interstitial lung disease arena , where some advocate the demonstration of usual interstitial pneumonitis among patients with idiopathic pulmonary fibrosis , whereas others believe that a therapeutic trial of steroids in the majority of patients is justifiable until new therapeutic strategies emerge .
the work by kao and colleagues   supports the existing literature that open lung biopsy is fairly safe and frequently revealing in the context of ards .
first , the authors corroborate prior reports that the underlying pathology in clinical ards is often a pattern other than diffuse alveolar damage or fibro - proliferation . of note ,
this and prior studies were retrospective analyses making the generalizability of these findings difficult to define . without knowing the total number of ards cases potentially eligible for biopsy
, we have no easy way to know how common the observed abnormalities would be in an unselected ards population .
second , the authors found minimal morbidity attributable to the surgical procedures that their patients underwent .
these data support the existing literature that , in experienced hands , olbx can be safely performed in carefully chosen patients .
the risk of bronchopleural fistula was fairly low in the present study , which may reflect the use of protective mechanical ventilation .
we have recently observed that high pressures measured at the airway opening are strongly predictive of prolonged bronchopleural fistula risk following lung biopsy in ards .
thus , attention to mechanical ventilator settings may be one factor that led to the low risk of this procedure .
nearly 75% of patients had changes made in their therapeutic management due to findings from olbx . whether these changes were helpful to the patient is not entirely clear due to the lack of a control group
however , at least 14 patients ( 11 with infections , 1 with hypersensitivity pneumonitis , and 2 with pulmonary edema ) had a disorder found for which accepted therapies exist .
interestingly , the most common change in management recorded in response to olbx results was the institution of glucocorticoid therapy .
the role of glucocorticoid therapy in ards has been controversial , with some smaller studies showing benefits whereas other larger studies demonstrated no important benefit .
a number of critiques have emerged after the recently published new england journal of medicine trial examining the role of steroids in persistent ards , leading some to speculate that , despite the negative results of that trial , some ards patients may still benefit from anti - inflammatory therapy . in this recent study , more than 95% of patients
were excluded prior to enrollment , leading to results that may not be generalizable to the overall ards population .
the most common reason for exclusion was glucocorticoid therapy , yielding the possibility that the best candidates for steroid therapy ( from both an efficacy and safety perspective ) were excluded from the study .
in addition , the frequent use of paralytics ( in up to 50% of steroid treated participants ) and marked hyperglycemia ( mean values in excess of 200 mg / dl ) may have contributed to avoidable complications of steroid therapy .
thus , the frequent re - intubations and neuromyopathies that occurred in this recent study may have offset the potential benefits of steroid therapy .
regardless , the stratification of patients likely to benefit from steroid therapy , while avoiding the potential morbidity of pharmacological therapies and other intensive care unit measures ( including mechanical ventilation ) is likely to be a successful strategy .
future studies that aggressively limit the side effects of steroids and that examine treatment response stratified by olbx findings may demonstrate subgroups of patients that derive important benefit from this therapy . in the future ,
biomarkers that could be defined either in the serum or by bronchoalveolar lavage would be preferable to olbx to stratify the likelihood of benefit from steroid therapy .
such biomarkers may help define the underlying pathobiology and so become a surrogate for olbx in assessing the steroid responsiveness of the disease .
another class of biomarkers that may prove useful in the management of ards patients would be ones that provided information on the intrinsic steroid responsiveness of the patient .
the search for genetic polymorphisms that predict individual responsiveness to steroid therapies is well underway in other conditions such as asthma and ulcerative colitis .
both types of biomarkers would aid treatment decisions by better defining subgroups most likely to benefit from steroid therapy .
thus , further work is clearly needed to determine whether individualized therapy will improve outcome in various subgroups of ards patients .

Answer:
progress in the treatment of acute respiratory distress syndrome ( ards ) has been slow , perhaps in part due to the heterogeneity in the biology underlying this syndrome .
 open lung biopsy is a feasible approach to define various subcategories of underlying histology . in experienced hands , with careful selection of patients and close attention to details of critical care management , including mechanical ventilator settings , the procedure is safe even in patients with severe disease .
 however , further work is needed to define which patients , if any , experience a beneficial effect on outcome from this procedure .
 more research is needed on assessing efficacy of potential therapies within histologically defined subgroups . in the future
 , various biomarkers may be available to non - invasively classify ards patients from the standpoint of responsiveness to various therapies , such as gluco - corticoids .


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:
different factors , especially genetic , effect individual attitude to regular physical activity in iranian traditional medicine .
our aim was to conduct a comparative revision and evaluation of the effect of genetic factors on physical activity in classic medicine and iranian traditional medicine .
in this study , we reviewed persian resources in the research center of traditional medicine at shiraz university of medical sciences .
we also evaluated the texts on physical activity and genetics in pubmed and google scholar .
the results of classical medicine revision showed the effect of especial genes on obesity and sedentary behavior .
it is also derived from iranian traditional medicine resources that physical activity and sedentary behavior is affected by individual mizaj .
the results showed that those with hot and cold mizaj have different genetic potentials in sedentary behavior and physical activity .
such categorization would be helpful in identifying illnesses due to sedentary life in special groups of people .

Answer:
background : different factors , especially genetic , effect individual attitude to regular physical activity in iranian traditional medicine .
 it was believed that individual physical activity attitude is affected by mizaj too .
 our aim was to conduct a comparative revision and evaluation of the effect of genetic factors on physical activity in classic medicine and iranian traditional medicine.methods:in this study , we reviewed persian resources in the research center of traditional medicine at shiraz university of medical sciences .
 we also evaluated the texts on physical activity and genetics in pubmed and google scholar.results:the results of classical medicine revision showed the effect of especial genes on obesity and sedentary behavior .
 it is also derived from iranian traditional medicine resources that physical activity and sedentary behavior is affected by individual mizaj.conclusion:the results showed that those with hot and cold mizaj have different genetic potentials in sedentary behavior and physical activity .
 such categorization would be helpful in identifying illnesses due to sedentary life in special groups of people .
 it would also allow designing dedicated treatment for each person .


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:
institutional review board approval was obtained from the wake forest university , and informed consent forms were completed for all participants .
items for four concepts identified in the literature were  glucose control ,   well - being and side - effects ,   lifestyle burden ,  and  treatment complexity and convenience  and were evaluated in a series of five focus groups made up of five to eight patients drawn from an evaluation study of community diabetes clinics in north carolina ( 11 ) .
participants were male and female and white and nonwhite with simple and complex medication regimens and a1c levels that ranged from well controlled to uncontrolled .
the resulting 35-item prototype instrument was administered by mail to a convenience sample of 75 patients ( the exploratory sample ) , who were treated with diabetes medications at our study community - care site , to assess item reliability , mean and distribution , redundancy or uniqueness , skewness , and construct validity .
also examined were item correlations with a1c level , the multidimensional diabetes questionnaire ( 12 ) lifestyle interference scale , the medical outcomes studies ( mos ) health worries scale score ( 13 ) , and global items assessing extent that blood glucose has been unacceptably high or low . an item performance score was constructed ( 0 , weak ; 1 , moderate ; or 2 , ideal performance ) to guide item retention .
fifty - five ( 73% ) patients completed the survey , and nine items were removed based on skewness or redundancy ( r > 0.75 ) with other items . in the initial test sample
, patients of a large family - medicine practice treated for diabetes with a recent a1c value within the last 3 months ( the evaluation sample ) were invited to complete the study survey packet including the revised 26-item instrument and validation instrument described above .
medication complexity was assessed using a score of 0 or 1 ( no / yes ) for common diabetes medications and a score of 0 or 2 ( no / yes ) for insulin , a more demanding regimen .
self - reported adherence to medications was by recall of skipped or missed doses over the last 10 days .
packets were mailed to patients with instructions and a voucher for a 25 usd gift certificate .
exploratory factor analysis ( efa ) of the dmsat items was conducted using sas ( version 8 ; sas , cary , nc ) to assess whether the common factor model was appropriate ( 14 ) based on kaiser 's sampling adequacy , scree plot , and model fit .
discriminant validity of the dmsat was examined by comparing means across levels of a1c ( < 8% and 8% ) , treatment complexity ( low and high ) , self - reported adherence , and mos health worries . for the final test sample ,
another sample of patients from our community diabetes care clinics ( 11 ) and from an academic medical center was recruited to conduct and evaluate confirmatory factor analysis of the dmsat and confirm validity
in the evaluation sample , 194 ( 63% ) of 307 eligible patients returned the survey packet ; of these , 140 reported current medication use .
participants had a mean age of 63 years , and most had completed high school ( 77% ) and had been diagnosed with diabetes at least 5 years previously ( 61% ) .
one - third ( 2939% ) were taking one , two , or three medications for diabetes , with 16% taking insulin ; 14% had a recent a1c > 8.0% , and 19% rated their adherence to their medication regimen in the last 10 days as less than complete .
ten items displayed high inter - item correlations ( > 0.75 ) and were removed .
initial factor analysis of the reduced 16-item questionnaire identified a four - factor structure consistent with our domains of lifestyle , medical control , convenience , and well - being and explained 75% of the total variance .
as shown in table 1 , dmsat scales and total score discriminated ( p < 0.05 ) between high and low levels of treatment complexity , self - rated glucose control , mos health worries scale score , and clinical value for recent a1c ( < 8% vs. 8% ) in the expected direction .
correlation of the dmsat scores with continuous a1c values was 0.24 ( p = 0.0049 ) . in the final , confirmatory sample ,
as shown in table 1 , dmsat scales and total scores discriminated between validity groups as in the previous sample and were highly correlated with the dtsq ( r = 0.68 ; p < 0.001 ) . unlike the dmsat , the dtsq total score did not discriminate between levels of treatment complexity and clinical a1c value .
the dmsat is intended as a brief measure of diabetes medication treatment satisfaction and discriminates between important correlates of patient management .
it performed as well as the dtsq in detecting self - rated glucose control and health worries but showed superior properties in correspondence with treatment complexity and a1c .
note that appraisals of cost of medications or specific side effects that may be caused by diabetes or its treatment , such as diminished sexual functioning , bloating , or weight gain , are not separately assessed and may require assessment elsewhere .
, we believe that the 16-item dmsat offers a comprehensive assessment of satisfaction with diabetes therapy and may aid in individualizing patient diabetes treatment .

Answer:
objective  to develop and test a patient questionnaire on treatment satisfaction with diabetes regimens.research design and methods  survey items were developed from community clinic focus groups , pretested in patients with diabetes , and examined in two samples of treated patients.resultssixteen items performed well in assessing treatment experiences : ease and convenience , lifestyle burdens , well - being , and medical control .
 construct validity was supported by associations ( p < 0.05 ) with treatment complexity , self - rated glucose control , health worries , and a1c .
 internal consistency ranged from 0.89 to 0.95.conclusionsthe diabetes medication satisfaction tool offers a comprehensive assessment of patient acceptability , with diabetes therapy useful for individualizing therapeutic decision making .


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

Paper text:
breast - conserving surgery and radiation therapy are the standard alternatives to mastectomy for eligible women with stage 0 , i , or ii breast cancer [ 1 , 2 ] .
survival outcomes are equivalent to women who undergo initial mastectomy , and the long - term rates of ipsilateral breast tumor recurrence ( ibtr ) are on the order of 5% to 15% [ 36 ] . for those who develop a clinically isolated ibtr after breast - conserving surgery and whole - breast radiation , salvage mastectomy
three - quarters of local recurrences are clinically solitary [ 7 , 8 ] , with an average size of 1 - 2  cm [ 914 ] . therefore , many ibtr appear amenable to additional attempts at breast - conserving surgery .
breast conservation has many potential benefits on patient self - image , sexuality , and quality of life compared to mastectomy .
however , second attempts at breast conservation with surgery alone have been associated with high risks of second ibtr of 1848% [ 13 , 1619 ] .
arguments against reirradiation to improve local control include concerns for radiation resistance of the recurrent tumor , acute toxicity , poor cosmesis , or risk of serious late effects .
it is not possible from the few available retrospective studies of external beam boost radiation to conclude whether local control after salvage breast conservation surgery is improved by conventional re - irradiation [ 16 , 20 , 21 ] .
however , the rationale for postexcision radiation should be the same as in the initial adjuvant setting  to address the risk for microscopic residual disease in the region of the excision cavity that exists even when surgical margins are negative . and
these early reports have demonstrated low risks of complications in selected patients . accelerated partial breast irradiation ( apbi ) is radiation confined to the immediate area around an excision cavity rather than to the whole breast volume . in the setting of a clinical trial , apbi has been proposed as an alternative to salvage mastectomy for selected patients with favorable ibtr after breast - conserving surgery and whole - breast irradiation [ 21 , 22 ] .
apbi has the potential of improving local tumor control compared to breast - conserving surgery alone .
the use of hypofractionation and the accelerated treatment time with pbi could improve the tumor control of tumors that have recurred after prior conventional 2  gy fractionation by overcoming effects of intrinsic radioresistance , repair or rapid repopulation .
apbi may reduce risk of toxicity of conventional re - irradiation by limiting the volume of breast tissue and neighboring normal tissue treated to high cumulative doses .
proper patient selection for an ibtr of limited extent and favorable biology would be essential for treatment by apbi to have a chance of securing local control . a favorable profile of ibtr for such a trial of apbi would need to include isolated recurrences that are unifocal and limited in size so that a repeat breast - conserving surgery could obtain negative margins and maintain good cosmesis .
in addition , the area of involvement would need to be limited in size without multifocality or multicentricity for a focused treatment such as apbi to have a reasonable chance for local control .
tumors with a short interval to recurrence after radiation , less than 2 years being a typical cutoff , would more likely have an aggressive biology with a poorer prognosis due to a high incidence of systemic progression [ 6 , 19 ] .
to better identify candidates who could have been eligible for a salvage apbi protocol , we studied the clinical and pathologic characteristics of 157 ibtrs after salvage mastectomy to identify factors associated with a favorable recurrence profile .
we retrospectively reviewed a prospective database of 3310 consecutive women with early - stage breast cancer treated with breast - conserving surgery and radiation therapy from 1980 to 2005 .
patient demographics , tumor characteristics , and treatment - related information were entered prospectively and the data were maintained and updated by a single data manager .
the collection , storage , and retrieval of data were done in compliance with the hospital 's institutional review board and the health insurance privacy and portability act .
inclusion criteria for this study were primary breast cancer ; american joint committee on cancer 6th edition initial cancer stages 0 , i , or ii ; initial treatment with whole breast radiation therapy ; a clinically isolated ibtr ; and treatment for ibtr by mastectomy .
exclusion criteria included male breast cancer , t3-t4 disease , stage iv disease , mastectomy for initial treatment , and no radiation therapy as part of the patient 's initial treatment .
all patients were treated initially by breast - conserving surgery followed by whole - breast radiation ( 4650  gy ) , with or without regional nodal radiation , and a boost to the tumor bed ( 1018  gy ) .
the total dose was generally determined by the final margin status after lumpectomy : 60  gy for a negative margin , 64  gy for a close margin , and 66  gy for a positive final margin .
the study endpoint was a classification as a favorable ibtr defined as an isolated first site of recurrence ; unifocal ; invasive or in situ ; less than or equal to 2  cm in size ; no skin involvement ; and more than 2 years from initial treatment .
chi - square test , wilcoxon 's test , and generalized estimating equations were used for univariate and multivariate analyses .
the characteristics of the 157 patients in the study population are summarized in table 1 . at the time of their initial diagnosis and treatment
patients were approximately equally divided between pre- and postmenopausal status and laterality of the breast cancer .
the interval to recurrence was 2 years in 8% and > 2 years in 92% .
ibtr was confined to the same quadrant as the initial tumor in 55% of patients , a different quadrant in 33% , was diffuse or multicentric in 6% , and skin was involved in 3% .
histologically , most patients presented with invasive ductal carcinoma ( 77% of primary tumors and 57% of ibtr ) . receptor status was considered hormone sensitive ( er or pr positive ) or insensitive ( er and pr negative ) .
this was available for only 39% of the ibtr compared to 72% of the initial tumors .
the differences in characteristics between the initial tumor compared to the subsequent ibtr are shown in table 3 .
there were more palpable tumors at time of initial diagnosis ( 55% ) compared with ibtr ( 41% ) .
the method of detection was physical examination only in approximately 20% at time of initial diagnosis and ibtr .
more ibtr were detectable on mammogram alone compared to the initial tumors ( 55% versus 40% ) .
pathologic t stage at initial diagnosis and clinical t stage of ibtr were predominantly t1 , 65% and 57% , respectively . among patients with known receptors ,
the percentage of hormone sensitive tumors was 78% of initial tumors and 67% of ibtr ( table 3 ) .
for patients initially hormone sensitive , the ibtrs was hormone sensitive in 37 of 41 ( 90% ) . for patients known to be initially hormone insensitive ,
the ibtr was sensitive in 9 of 20 ( 45% ) . among the 90 patients with a clinical t1 ibtr , pathology from salvage mastectomy was available for 75 patients . in 71 of 75 patients ( 95% ) with clinical t1 ibtr
for those with pathologic data , the ibtr were clinical stage t1 or dcis in 77% and pathologic tis or t1 in 70% .
the median tumor size at time of both initial diagnosis and ibtr was 1  cm .
the characteristics of the initial tumor versus the ibtr were analyzed to determine predictors of pathologic t1 size at time of salvage mastectomy .
there was no significant correlation between the studied initial tumor characteristics and subsequent pathological size of ibtr .
clinical t stage at recurrence was the only independent predictor of having a t1 pathologic recurrence stage .
approximately 1020% of patients with stage i or ii invasive breast cancer will develop an ibtr by 10 years after breast - conserving surgery and rt [ 36 , 2428 ] .
in general , ibtr rates have been decreasing due to improvements in patient selection for initial treatment with breast - conserving surgery and whole breast radiotherapy , surgical and radiation techniques , and the use of systemic therapy [ 29 , 30 ] .
our study population of only 157 ibtr from an initial population of over 3,000 patients ( less than 5% ) after a median followup of 140 months is consistent with this reported decreasing risk of ibtr in other studies .
current recommendations for surveillance of patients following breast - conserving therapy include monthly patient self - examination , examination by a physician every 4 to 6 months for 5 years and then annually , and mammography 6 months after radiation and then annually . in the current study
, we found that 80% of ibtr were detectable on mammography , and the median size was 1  cm .
we have insufficient numbers of patients with ibtr t2 or larger to analyze for significant characteristics that could be prospectively identified .
if there were a common independent factor that predicted for a large size of ibtr with current methods of physical examination and mammography , then a more intensive surveillance could be recommended for such patients .
mastectomy is the standard treatment for patients with a clinically isolated ibtr after whole - breast irradiation .
salvage mastectomy is associated with local control rates of approximately 8595% [ 8 , 13 , 17 , 19 , 3134 ] . a change in this paradigm for salvage
therapy needs to be approached with caution so that new treatments for ibtr with lower rates of local control do not become commonplace .
however , in the setting of a clinical trial , for women who find mastectomy unacceptable or are medically poor candidates , identification of other salvage treatment modalities for ibtr may be appropriate .
however , second attempts at breast conservation with surgery alone have been associated with high risks of second ibtr of 1848% [ 13 , 1619 ] .
there is a limited published experience with giving further rt after prior whole - breast irradiation after salvage breast - conserving surgery for ibtr . in the study of kurtz et al .
, 11 of 50 patients who had recurrences away from the original tumor bed were given additional radiation after wide excision .
second local failures occurred in 36% of the patients treated with further irradiation , compared with 31% of those treated with wide local excision alone .
deutsch and colleagues reported on a series of 39 women treated for ibtr by repeat wide local excision and treatment to an electron field around the lumpectomy bed with an additional 50  gy .
there were no reported serious sequelae from the additional radiation . in the setting of a clinical trial ,
apbi has been proposed as an alternative to salvage mastectomy for selected patients with favorable ibtr after breast - conserving surgery and whole - breast irradiation [ 21 , 22 ] .
hannoun - levi et al . reported on 69 patients with ibtr who were treated by a second breast - conservation surgery and interstitial brachytherapy .
factors associated with better local control were an interval to recurrence of 36 months or greater and use of a greater number of catheters for the implant .
this suggests that improved methods of radiation technique that optimize dose coverage may lead to better rates of local control in future studies .
in addition to optimized apbi techniques , improved patient selection could result in improved rates of local control after salvage breast conservation for ibtr . a favorable profile of ibtr for apbi would need to be isolated , unifocal , and limited in size .
selection of tumors with a longer interval to recurrence would also include ibtr with less aggressive biology and patients with better chances for long - term survival .
we identified approximately 70% of patients with these favorable ibtr characteristics after initial breast - conserving surgery and whole - breast radiation .
the clinical estimation of tumor size was the most significant independent factor predictive of having pathologically confirmed favorable ibtr at salvage mastectomy .
this favorable subset of patients could be a pool of eligible candidates for a clinical trial of salvage breast conservation in this setting .
the radiation therapy oncology group is currently studying salvage breast - conserving surgery and apbi in this favorable subset of patients .
patient selection includes ibtr 3  cm or less in size , without imaging evidence of multicentricity , and an interval to recurrence of greater than 1 year .
our data suggests that over 70% of patients with ibtr will be eligible for enrollment given that our selection criteria for most favorable ibtr are more strict than the rtog trial eligibility .

Answer:
background and objectives . accelerated partial breast irradiation ( apbi ) has been proposed as an alternative to salvage mastectomy for patients with ipsilateral breast tumor recurrence ( ibtr ) after prior breast conservation .
 we studied factors that are associated with a more favorable local recurrence profile that could make certain patients eligible for apbi . methods . between 1980 and 2005 , 157 stage 0ii breast cancer patients had an ibtr treated by mastectomy .
 clinical and pathological features were analyzed to identify factors associated with favorable ibtr defined as unifocal dcis or t1  2  cm , without skin involvement , and > 2 year interval from initial treatment .
 results .
 median followup was 140 months and time to recurrence was 73 months .
 clinical stage distribution at recurrence was dcis in 32 pts ( 20% ) , t1 in 90 pts ( 57% ) , t2 in 14 pts ( 9% ) , t3 in 4 pts ( 3% ) , and t4 in 9 pts ( 6% ) .
 ibtr was classified as favorable in 71% .
 clinical stage of ibtr predicted for pathologic stage 95% of patients with clinical t1 ibtr had pathologic t1 disease at salvage mastectomy ( p < 0.0001 ) .

 conclusions .
 clinical stage at presentation strongly correlated with pathologic stage at mastectomy .
 more than 70% of recurrences were favorable and may be appropriate candidates for salvage apbi trials .