bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diverticular Abscess Managed With Long-term Definitive Nonoperative Intent Is Safe
Authors: Garfinkle Richard , Kugler Aaron , Pelsser Vincent , Vasilevsky Carol-Ann , Morin Nancy , Gordon Philip , Feldman Liane , Boutros Marylise 
Published: June 2016

BACKGROUND:
Initial nonoperative management of diverticular abscess has become the standard of care; however, the need for elective resection after this index episode is unclear.

OBJECTIVE:
The purpose of this study was to assess the long-term outcomes of expectant management after initial nonoperative treatment of diverticular abscess.

DESIGN:
This was a retrospective chart review with prospective telephone follow-up of patients.

SETTINGS:
The study was conducted at a large tertiary academic colorectal surgery practice in Canada.

PATIENTS:
Adult patients with CT-documented acute sigmoid diverticulitis complicated by abscess managed nonoperatively from 2000 to 2013 were included.

INTERVENTIONS:
Long-term definitive nonoperative management of diverticular abscess.

MAIN OUTCOME MEASURES:
The primary outcome was emergency sigmoidectomy or death from recurrent diverticulitis. Secondary outcomes were recurrent diverticulitis and elective sigmoidectomy for diverticulitis.

RESULTS:
Of 135 patients with acute diverticulitis complicated by abscess, a total of 73 patients were managed with nonoperative intent and long-term expectant management. The median follow-up was 62 (Q1 to Q3: 28–98) months. After resolution of the index episode, 22 patients [30.1% (95% CI, 19.6%–40.6%)] experienced a recurrent episode of diverticulitis at a median of 23 (range, 9–40) months. Two patients [2.7% (95% CI, –1.0% to 6.4%)] had a recurrent episode with peritonitis that required sigmoidectomy with stoma at 6 and 64 months. Both patients underwent reversal after 4 and 8 months. Seven [9.6% (95% CI, 2.8%–16.4%)] patients experienced a complicated recurrence and underwent an elective sigmoidectomy [median time to colectomy, 33 (range, 16–56) months]. Thirteen patients [17.8% (95% CI, 9.0%–26.6%)] experienced an uncomplicated recurrence, all of whom were managed with continued nonoperative intent [median follow-up, 81 (range, 34–115) months]. No mortality occurred. On multivariate logistic regression, female gender (p = 0.048) and a previous episode of uncomplicated diverticulitis before the index diverticular abscess (p = 0.020) were associated with a recurrent episode.

LIMITATIONS:
This study was limited by its retrospective design and modest sample size.

CONCLUSIONS:
After initial successful nonoperative management of diverticulitis with abscess, expectant management with nonoperative intent is a safe long-term option with low rates of surgery, especially in the emergency setting. See Video, Supplemental Digital Content 1, on the nonoperative management of diverticular abscess at http://links.lww.com/DCR/A234.
The prevalence and co-occurrence of hematological complications at the time of diagnosis of chronic hepatitis C in Poland: a cross-sectional study
Authors: Pierucka Magdalena , Stalke Piotr , Zagożdżon Paweł , Smiatacz Tomasz , Zaucha Jan M. 
Published: June 2016

Objectives
To evaluate the frequency, co-occurrence, and risk factors for hematological complications at the time of diagnosis of chronic hepatitis C (CHC).

Methods
This study included 1237 patients with CHC aged 18–88 years diagnosed in the years 1998–2010 in the Pomeranian region of Poland. Clinical data, cell blood count, liver biopsy, and biochemistry results were obtained retrospectively.

Results
Hematological complications were found in 31% of patients. The most frequent complication was thrombocytopenia (23.8%). The multivariate analysis showed a 5.1-fold increased risk (P<0.05) of at least one additional hematological complication in patients with thrombocytopenia. The greatest increase in risk (7.3) was related to leukopenia and cryoglobulinemia (2.3). The risk of leukopenia was correlated with the severity of thrombocytopenia. The risk of leukopenia and thrombocytopenia increased significantly from, respectively, stages 3 and 2 of liver fibrosis compared with patients without fibrosis.

Conclusion
In patients with CHC, decreases in cell blood count occur quite frequently. The most often is mild and solitary thrombocytopenia, but if severe, it may be accompanied by leukopenia, especially in women. The presence of thrombocytopenia and leukopenia in patients with CHC may indicate advanced liver fibrosis or its final stage: cirrhosis.
Advancement in management of epidermolysis bullosa
Authors: Cohn Heather I. , Teng Joyce M.C. 
Published: June 2016

Purpose of review
Epidermolysis bullosa is a hereditary skin disorder characterized by skin fragility. However, the disease can manifest in many different organ systems, therefore children born with epidermolysis bullosa may have life long, complex medical needs. In this review, we will use a system-based approach to highlight important aspects of disease management and recent advancements in each of the areas. In addition, we will overview some of the cutting edge therapeutic developments in epidermolysis bullosa.

Recent findings
Recent advancements in supportive care of epidermolysis bullosa with focus on wound, pain, pruritus and nutrition status were discussed. Clinical surveillance and complication prevention are critical to improve clinical outcomes. Generalized epidermolysis bullosa is a systemic disease with increased morbidity and mortality; therefore, complex care using a multidisciplinary approach will provide the greatest benefits for patients. Current targeted treatments for epidermolysis bullosa aim at restoring the skin integrity using protein, cell, and gene therapies.

Summary
Improvement in care of epidermolysis bullosa in recent years results from keen clinical observation, novel molecular targeting, and the embracement of translational research.
Feeding Disorders in Children With Autism Spectrum Disorders Are Associated With Eosinophilic Esophagitis
Authors: Heifert Theresa A. , Susi Apryl , Hisle‐Gorman Elizabeth , Erdie‐Lalena Christine R. , Gorman Gregory , Min Steve B. , Nylund Cade M. 
Published: June 2016

ABSTRACTObjectives:Eosinophilic esophagitis (EoE) can present as food selectivity or feeding disorders in children. Children with autism spectrum disorders (ASDs) commonly demonstrate behavioral food selectivity in type and texture, which often leads to the diagnosis of feeding disorder. We sought to evaluate the association of ASD with EoE.Methods:A retrospective matched case‐cohort study was performed using the Military Health System database from October 2008 to September 2013. We performed a 1:5 case‐control match by age, sex, and enrollment timeframe. Feeding disorders, EoE, and atopic disorders were defined using diagnostic and procedure codes.Results:There were 45,286 children with ASD and 226,430 matched controls. EoE was more common in children with ASD (0.4%) compared with controls (0.1%). Feeding disorders were associated with EoE in both children with ASD and controls. Feeding disorders also had a higher odds ratio for EoE compared with other atopic conditions, among both children with ASD (7.17, 95% confidence interval [CI] 4.87–10.5) and controls (11.5, 95% CI 7.57–17.5). Compared with controls with a feeding disorder, children with ASD and a feeding disorder had no difference in the rate of diagnosed EoE (0.85, 0.95% CI 0.39–1.88).Conclusions:Children with ASD are more likely to be diagnosed with EoE compared with controls; however, among children with feeding disorders, there is no difference in the odds of EoE. A diagnosis of feeding disorder was strongly associated with EoE. Feeding disorders in children with ASD should not be assumed to be solely behavioral and an esophagogastroduodenoscopy should be performed to evaluate for EoE.
Geo-climatic gradient shapes functional trait variations inSalix eriocephalaMichx
Authors: Shunmugam Arun S.K. , Soolanayakanahally Raju Y. , Guy Robert D. 
Published: June 2016

AbstractIntraspecific variations in seasonal phenology and growth physiology reflect adaptation to local climate. To explore the patterns of local adaptation along latitudinal and longitudinal clines, we used thirty-four populations ofSalix eriocephalasourced from its natural ranges across Canada. The genotypes were examined for 6 phenology and 19 ecophysiology traits over two growing seasons under common garden condition. Photosynthetic assimilation rate (A) increased with increasein latitude when measured during free growth. In spite, the negative correlation between stomatal density and stomatal conductance (gs), higherAis facilitatedvialarger pore length among genotypes from short growing seasons. In addition, higherA, was positively associated with total leafnitrogen and leaf mass per unit area. No population level differences wereobserved for water use-efficiency (Δ13C), however nitrogen isotope discrimination (δ15N) displayed latitudinalclines. Growing season phenological traits considered in this study accounted highheritability (H2=0.65-0.94).Melampsorarust infestation also displayed a strong latitudinal cline with high-latitude genotypes being more susceptible. Overall, the results support the hypothesis that functional trait variations are largely explained by climate of origin and facilitate selection of parents with superior adaptive traits in the Canadian willow improvement program forbioenergy and environmental applications.
Characterizing the Non-Normal Distribution of Flow Cytometry Measurements from Transiently Expressed Constructs in Mammalian Cells
Authors: McLean Peter F. , Smolke Christina D. , Salit Marc 
Published: June 2016

AbstractIn mammalian cells, transient gene expression (TGE) is a rapid, minimal-investment alternative to single-copy integrations for testing of transgenic constructs. However, transient gene expression, as measured by flow cytometry with a fluorescent reporter, typically displays a broad, asymmetric distribution with a left-tail that is convolved with background signal. Common approaches for deriving a summary statistic for transiently expressed gene products impose a normal distribution on gated or ungated data. Summary statistics derived from these models are heavily biased by experimental conditions and instrument settings that are difficult to replicate and insufficient to accurately describe the underlying data. Here, we present a convolved gamma distribution as a superior model for TGE datasets. The 4-6 parameters of this model are sufficient to accurately describe the entire, ungated distribution of transiently transfected HEK cells expressing monomeric fluorescent proteins, that operates consistently across a range of transfection conditions and instrument settings. Based on these observations, a convolved gamma model of TGE distributions has the potential to significantly improve the accuracy and reproducibility of genetic device characterization in mammalian cells.
Binding of synGAP to PDZ Domains of PSD-95 is Regulated by Phosphorylation and Shapes the Composition of the Postsynaptic Density
Authors: Walkup Ward G. , Mastro Tara , Schenker Leslie T. , Vielmetter Jost , Hu Rebecca , Iancu Ariella , Reghunathan Meera , Bannon B. Dylan , Mary B. Kennedy 
Published: June 2016

AbstractSynGAP is a Ras/Rap GTPase-activating protein (GAP) present in high concentration in postsynaptic densities (PSDs) from mammalian forebrain where it binds to all three PDZ (PSD-95,Discs-large,ZO-1) domains of PSD-95. We show that phosphorylation of synGAP by Ca2+/calmodulin-dependent protein kinase II (CaMKII) decreases its affinity for the PDZ domains as much as 10-fold, measured by surface plasmon resonance. SynGAP is abundant enough in postsynaptic densities (PSDs) to occupy about one third of the PDZ domains of PSD-95. Therefore, we hypothesize that phosphorylation by CaMKII reduces synGAP’s ability to restrict binding of other proteins to the PDZ domains of PSD-95. We support this hypothesis by showing that three critical postsynaptic signaling proteins that bind to the PDZ domains of PSD-95 are present at a higher ratio to PSD-95 in PSDs isolated from synGAP heterozygous mice.
Human germline mutation and the erratic evolutionary clock
Authors: Moorjani Priya , Gao Ziyue , Przeworski Molly 
Published: June 2016

AbstractOur understanding of the chronology of human evolution relies on the “molecular clock” provided by the steady accumulation of substitutions on an evolutionary lineage. Recent analyses of human pedigrees have called this understanding into question, by revealing unexpectedly low germline mutation rates, which imply that substitutions accrue more slowly than previously believed. Translating mutation rates estimated from pedigrees into substitution rates is not as straightforward as it may seem, however. We dissect the steps involved, emphasizing that dating evolutionary events requires not “a mutation rate,” but a precise characterization of how mutations accumulate in development, in males and females—knowledge that remains elusive.
Improving construction sector resilience
Authors: Wilkinson Suzanne , Chang-Richards Alice Yan , Sapeciay Zulkfli , Costello Seosamh B. 
Published: June 2016

Purpose
Improving the resilience of the construction sector helps countries recover quicker from crises and can assist with improving community resilience and recovery. This study aims to explore ways in which the construction sector might improve its resilience.

Design/methodology/approach
This paper examined past disasters and the role construction plays to understand what and how better construction resilience can be built, and the impact this will have on recovery and reconstruction.

Findings
The findings showed that after a crisis, the construction sector is called upon to manage building and infrastructure recovery and reconstruction. Construction organisations are needed by the community, as they provide physical resources, people, materials, logistics, management and technical expertise and rebuilding. To ensure that recovery and reconstruction programs are successfully implemented, it is necessary for the construction sector to be resilient. To achieve improved resilience in the construction industry, disaster resilience management needs to become mainstreamed into construction processes.

Research limitations/implications
Although larger organisations have some preparation to respond to crises, including having emergency or disaster plans, smaller companies struggle to achieve a reasonable level of resilience. It appears that senior management and key people in construction organisations are familiar with the procedures but that the majority of staff in organisations lack knowledge and skills.

Practical implications
Understanding the role the construction sector plays in disasters and providing directions for improving construction sector resilience will ultimately improve recovery and reconstruction outcomes.

Social Implications
This paper discusses how communities rely on services provided by construction organisations to enable them to recover from emergencies and crises. Pre-disaster construction company resilience impacts on the ability of construction companies to function post-disaster.

Originality/value
This paper focuses on a number of cases and shows where and how the construction sector has worked in disasters and provides a new analysis of the role the industry plays, and the various disaster stages where the industry has maximum impact.
Fitness costs of animal medication: antiparasitic plant chemicals reduce fitness of monarch butterfly hosts
Authors: Tao Leiling , Hoang Kevin M. , Hunter Mark D. , de Roode Jacobus C. 
Published: June 2016

Summary

The emerging field of ecological immunology demonstrates that allocation by hosts to immune defence against parasites is constrained by the costs of those defences. However, the costs of non‐immunological defences, which are important alternatives to canonical immune systems, are less well characterized. Estimating such costs is essential for our understanding of the ecology and evolution of alternative host defence strategies.

Many animals have evolved medication behaviours, whereby they use antiparasitic compounds from their environment to protect themselves or their kin from parasitism. Documenting the costs of medication behaviours is complicated by natural variation in the medicinal components of diets and their covariance with other dietary components, such as macronutrients.

In the current study, we explore the costs of the usage of antiparasitic compounds in monarch butterflies (Danaus plexippus), using natural variation in concentrations of antiparasitic compounds among plants. Upon infection by their specialist protozoan parasite Ophryocystis elektroscirrha, monarch butterflies can selectively oviposit on milkweed with high foliar concentrations of cardenolides, secondary chemicals that reduce parasite growth. Here, we show that these antiparasitic cardenolides can also impose significant costs on both uninfected and infected butterflies.

Among eight milkweed species that vary substantially in their foliar cardenolide concentration and composition, we observed the opposing effects of cardenolides on monarch fitness traits. While high foliar cardenolide concentrations increased the tolerance of monarch butterflies to infection, they reduced the survival rate of caterpillars to adulthood. Additionally, although non‐polar cardenolide compounds decreased the spore load of infected butterflies, they also reduced the life span of uninfected butterflies, resulting in a hump‐shaped curve between cardenolide non‐polarity and the life span of infected butterflies.

Overall, our results suggest that the use of antiparasitic compounds carries substantial costs, which could constrain host investment in medication behaviours.
Comparison of the pharmacokinetics, safety, and immunogenicity of MSB11022, a biosimilar of adalimumab, with Humira® in healthy subjects
Authors: Hyland Elizabeth , Mant Tim , Vlachos Pantelis , Attkins Neil , Ullmann Martin , Roy Sanjeev , Wagner Volker 
Published: June 2016

AimsThe aim of the study was to compare the pharmacokinetics (PK), safety and tolerability of the proposed adalimumab biosimilar MSB11022 (Merck) with Humira® (AbbVie), sourced from both the US (US reference product [US‐RP]) and Europe (European reference medicinal product [EU‐RMP]).MethodsIn this phase 1 double‐blind, parallel group trial (EMR200588‐001), 213 healthy volunteers were randomized 1 : 1 : 1 to receive a single dose (40 mg) of MSB11022, US‐RP or EU‐RMP in order to achieve 80% power assuming a 5% difference among groups and a 10% dropout rate. Following a preplanned blinded sample size re‐assessment after more than 50% of the originally planned subjects had been observed, the sample size was increased to 237 (79 per arm) to ensure 213 completers. Primary PK endpoints analyzed by non‐compartmental methods, were area under the curve (AUC) from time 0 extrapolated to infinity (AUC(0,∞)), maximum observed concentration (Cmax), and AUC from time 0 to the last quantifiable concentration (AUC(0,tlast)). PK equivalence was declared if the 90% CI for the test : reference ratio lay within the 80–125% equivalence margin. Bioequivalence was demonstrated if all three PK parameters met the PK equivalence criteria. Safety and tolerability were also evaluated.ResultsMean serum concentration–time profiles for the three treatments were similar. MSB11022 demonstrated PK equivalence to US‐RP and EU‐RMP for all primary endpoints. The geometric means of AUC(0,∞), Cmax and AUC(0,tlast) following a single dose of MSB11022 were 2276.05 μg ml–1 h, 3.44 μg ml–1 and 1983.90 μg ml–1 h, respectively. Adverse events (AEs) were similar across all groups, with treatment‐emergent AEs (TEAEs) reported by 62.8%, 56.3% and 62.0% of subjects within the MSB11022, US‐RP and EU‐RMP groups, respectively. Most of the TEAEs were considered mild and unrelated to study drug. No deaths or severe AEs related to the study drug were reported.ConclusionsBioequivalence between MSB11022, US‐RP and EU‐RMP was demonstrated. Safety, tolerability and immunogenicity profiles were similar between subjects receiving MSB11022 and US‐RP or EU‐RMP. These data support the further clinical evaluation of MSB11022 as a proposed biosimilar of adalimumab.
Multifactorial Influences, Including Comorbidities, Contributing to Sleep Disturbance in Children with a Neurodevelopmental Disorder
Authors: Stores Gregory 
Published: June 2016

SummaryThe term neurodevelopmental disorder (NDD) implies an impairment of the growth and development of the CNS caused by genetic, metabolic, toxic, or traumatic factors. Childhood neuropsychiatric disorder is a subset of NDD. Sleep disturbance is reported in many children with NDD although the details of this association, including extent and types of sleep disturbance, etiology, and assessment and treatment issues, need to be clarified by further research. This review considers the nature of sleep disturbance in NDD. Emphasis is placed on sleep disorders (i.e., the specific conditions that cause sleep problems) of which many are now recognized in the International Classification of Sleep Disorders (ICSD‐3), and also intrinsic pathophysiological factors, physical and psychiatric comorbidities, and pharmacological and parental influences, which might contribute to the sleep disorders in children with NDD. The implications of this complexity for assessment and treatment in such children are then discussed. Appropriate treatment based on precise diagnosis of the causes of sleep disturbance is required to mitigate the harmful developmental effects of disordered sleep on children with NDD and their families.
Impact of age and sex on normal left heart structure and function
Authors: Hagström Linn , Henein Michael Y. , Karp Kjell , Waldenström Anders , Lindqvist Per 
Published: June 2016

SummaryBackgroundAccurate age‐ and sex‐related normal reference values of ventricular structure and function are important to determine the level of dysfunction in patients. The aim of this study therefore was to document normal age range sex‐related measurements of LV structural and functional measurements to serve such purpose.MethodsWe evaluated left ventricular structure and function in 293 healthy subjects between 20 and 90 years with equally distributed gender. Doppler echocardiography was used including measure of both systolic and diastolic functions.ResultsDue to systolic LV function, only long axis function correlated with age (r = 0·55, P<0·01) and the correlation was stronger in females. Concerning diastolic function, there was a strong age correlation in all parameters used (r = 0·40–0·74, P<0·001). Due to LV structural changes over age, females showed a larger reduction in end‐diastolic volumes, but no or trivial difference in wall thickness after the age of 60 years.ConclusionAge is associated with significant normal changes in left ventricular structure and function, which should be considered when deciding on normality. These changes are related to systemic arterial changes as well as body stature, thus reflecting overall body ageing process. Furthermore, normal cardiac ageing in females might partly explain the higher prevalence of heart failure with preserved ejection in females.