bluuebunny/crossref_metadata_2025 huggingface dataset:
Does integrating nonurgent, clinically significant radiology alerts within the electronic health record impact closed-loop communication and follow-up?
Authors: O’Connor Stacy D , Dalal Anuj K , Sahni V Anik , Lacson Ronilda , Khorasani Ramin
Published: September 2015

Objective To assess whether integrating critical result management software—Alert Notification of Critical Results (ANCR)—with an electronic health record (EHR)-based results management application impacts closed-loop communication and follow-up of nonurgent, clinically significant radiology results by primary care providers (PCPs).

Materials and Methods This institutional review board-approved study was conducted at a large academic medical center. Postintervention, PCPs could acknowledge nonurgent, clinically significant ANCR-generated alerts (“alerts”) within ANCR or the EHR. Primary outcome was the proportion of alerts acknowledged via EHR over a 24-month postintervention. Chart abstractions for a random sample of alerts 12 months preintervention and 24 months postintervention were reviewed, and the follow-up rate of actionable alerts (eg, performing follow-up imaging, administering antibiotics) was estimated. Pre- and postintervention rates were compared using the Fisher exact test. Postintervention follow-up rate was compared for EHR-acknowledged alerts vs ANCR.

Results Five thousand nine hundred and thirty-one alerts were acknowledged by 171 PCPs, with 100% acknowledgement (consistent with expected ANCR functionality). PCPs acknowledged 16% (688 of 4428) of postintervention alerts in the EHR, with the remaining in ANCR. Follow-up was documented for 85 of 90 (94%; 95% CI, 88%-98%) preintervention and 79 of 84 (94%; 95% CI, 87%-97%) postintervention alerts ( P > .99). Postintervention, 11 of 14 (79%; 95% CI, 52%-92%) alerts were acknowledged via EHR and 68 of 70 (97%; 95% CI, 90%-99%) in ANCR had follow-up ( P = .03).

Conclusions Integrating ANCR and EHR provides an additional workflow for acknowledging nonurgent, clinically significant results without significant change in rates of closed-loop communication or follow-up of alerts.
What do we know about developing patient portals? a systematic literature review
Authors: Otte-Trojel Terese , de Bont Antoinette , Rundall Thomas G , van de Klundert Joris
Published: September 2015

Objective Numerous articles have reported on the development of patient portals, including development problems and solutions. We review these articles to inform future patient portal development efforts and to provide a summary of the evidence base that can guide future research.

Materials and Methods We performed a systematic review of relevant literature to answer 5 questions: (1) What categories of problems related to patient portal development have been defined? (2) What causal factors have been identified by problem analysis and diagnosis? (3) What solutions have been proposed to ameliorate these causal factors? (4) Which proposed solutions have been implemented and in which organizational contexts? (5) Have implemented solutions been evaluated and what learning has been generated? Through searches on PubMed, ScienceDirect and LISTA, we included 109 articles.

Results We identified 5 main problem categories: achieving patient engagement, provider engagement, appropriate data governance, security and interoperability, and a sustainable business model. Further, we identified key factors contributing to these problems as well as solutions proposed to ameliorate them. While about half (45) of the 109 articles proposed solutions, fewer than half of these solutions (18) were implemented, and even fewer (5) were evaluated to generate learning about their effects.

Discussion Few studies systematically report on the patient portal development processes. As a result, the review does not provide an evidence base for portal development.

Conclusion Our findings support a set of recommendations for advancement of the evidence base: future research should build on existing evidence, draw on principles from design sciences conveyed in the problem-solving cycle, and seek to produce evidence within various different organizational contexts.
Medication-indication knowledge bases: a systematic review and critical appraisal
Authors: Salmasian Hojjat , Tran Tran H , Chase Herbert S , Friedman Carol
Published: September 2015

Objective Medication-indication information is a key part of the information needed for providing decision support for and promoting appropriate use of medications. However, this information is not readily available to end users, and a lot of the resources only contain this information in unstructured form (free text). A number of public knowledge bases (KBs) containing structured medication-indication information have been developed over the years, but a direct comparison of these resources has not yet been conducted.

Material and Methods We conducted a systematic review of the literature to identify all medication-indication KBs and critically appraised these resources in terms of their scope as well as their support for complex indication information.

Results We identified 7 KBs containing medication-indication data. They notably differed from each other in terms of their scope, coverage for on- or off-label indications, source of information, and choice of terminologies for representing the knowledge. The majority of KBs had issues with granularity of the indications as well as with representing duration of therapy, primary choice of treatment, and comedications or comorbidities.

Discussion and Conclusion This is the first study directly comparing public KBs of medication indications. We identified several gaps in the existing resources, which can motivate future research.
Description and phylogenetic position of Corlissina maricaensis gen. nov., sp. nov. (Karyorelictea, Geleiidae), a novel interstitial ciliate from Brazil, with redefinition of the family Geleiidae
Authors: Campello-Nunes Pedro H. , Fernandes Noemi , Schlegel Martin , Silva-Neto Inácio D.
Published: September 2015

Corlissina maricaensisgen. nov., sp. nov. was obtained from samples of sediment collected in a brackish lagoon of Maricá city, Rio de Janeiro state, Brazil. The morphological description was based on live observations, after protargol staining, and scanning electron microscopy. The novel species has a cylindrical body shape that is slightly contractile, 230–550 × 35–65 μm, a cytoplasm with many globular inclusions, one row of irregular cortical granules between each somatic kinety, approximately 40–62 somatic kineties, two globular macronuclei measuring 9–24 μm and one micronucleus of approximately 4–9 μm. A subapical oral cavity was approximately 20–80 × 9–25 μm, with an adoral zone on the left side of the buccal field, which was composed of 32–60 polykineties and a paroral at the right side that was composed of 40–57 short polykineties. The new genus is distinguished from other geleiids by a loop-shaped posterior end of the paroral ciliature, made up of two rows of short polykineties, and the oralization of the central superior kinety (K0i), forming a row of dikinetids that borders the adoral zone internally, followed by several rows of monokinetids. In the phylogenetic analyses, the novel species was recovered as the sister group ofParduczia orbiswith full support values based on 18S rRNA gene sequences. This work also indicates some problems in the definitions of the Geleiidae and proposes a new diagnosis for this karyorelictid family.
Extreme Mitogenomic Variation Without Cryptic Speciation in Chaetognaths
Authors: Marletaz Ferdinand , Le Parco Yannick , Liu Shenglin , Peijnenburg Katja
Published: September 2015

The extent of within-species genetic variation across the diversity of animal life is a fundamental but largely unexplored problem in ecology and evolution. The neutral theory of molecular evolution predicts that genetic variation scales positively with population size. However, the genetic diversity of mitochondrial DNA, a prominent marker used in DNA barcoding studies, shows very little variation across animal species. Here, we report an unprecedented case of extreme mitochondrial variation within natural populations of two species of chaetognaths (arrow worms). We determined that this diversity is composed of deep intraspecific mitochondrial lineages within single populations that could be as divergent as human and newt. This mitochondrial diversity is the highest ever reported in animals without evidence of cryptic speciation or allopatric divergence as supported by nuclear evidence. We sequenced 54 complete mitogenomes revealing gene order rearrangements between these intraspecific lineages. Such structural differences have never previously been reported within single species. We confirm that this divergence was not driven by positive selection, and conversely show that these lineages evolved under purifying selection, consistently with neutral expectations. Our findings question the generally accepted narrow range of genetic variation in animal mitochondria and argue for a reappraisal of DNA barcoding techniques. Furthermore, extreme levels of mitogenomic variation in chaetognaths challenge classical views regarding mitochondrial evolution and cyto-nuclear co-evolution.
Privacy-Preserving Microbiome Analysis Using Secure Computation
Authors: Wagner Justin , Paulson Joseph N. , Wang Xiao-Shaun , Bhattacharjee Bobby , Corrada Bravo Héctor
Published: September 2015

Motivation

Developing targeted therapeutics and identifying biomarkers relies on large amounts of patient data. Beyond human DNA, researchers now investigate the DNA of micro-organisms inhabiting the human body. An individual’s collection of microbial DNA consistently identifies that person and could be used to link a real-world identity to a sensitive attribute in a research dataset. Unfortunately, the current suite of DNA-specific privacy-preserving analysis tools does not meet the requirements for microbiome sequencing studies.

Results

We augment an existing categorization of genomic-privacy attacks to incorporate microbiome sequencing and provide an implementation of metagenomic analyses using secure computation. Our implementation allows researchers to perform analysis over combined data without revealing individual patient attributes. We implement three metagenomic analyses and perform an evaluation on real datasets for comparative analysis. We use our implementation to simulate sharing data between four policy-domains and measure the increase in significant discoveries. Additionally, we describe an application of our implementation to form patient pools of data to allow drug companies to query against and compensate patients for the analysis.

Availability

The software is freely available for download at:http://cbcb.umd.edu/∼hcorrada/projects/secureseq.html
Zelda overcomes the high intrinsic nucleosome barrier at enhancers during Drosophila zygotic genome activation
Authors: Sun Yujia , Nien Chung-Yi , Chen Kai , Liu Hsiao-Yun , Johnston Jeff , Zeitlinger Julia , Rushlow Christine
Published: September 2015

The Drosophila genome activator Vielfaltig (Vfl), also known as Zelda (Zld), is thought to prime enhancers for activation by patterning transcription factors (TFs). Such priming is accompanied by increased chromatin accessibility, but the mechanisms by which this occurs are poorly understood. Here, we analyze the effect of Zld on genome-wide nucleosome occupancy and binding of the patterning TF Dorsal (Dl). Our results show that early enhancers are characterized by an intrinsically high nucleosome barrier. Zld tackles this nucleosome barrier through local depletion of nucleosomes with the effect being dependent on the number and position of Zld motifs. Without Zld, Dl binding decreases at enhancers and redistributes to open regions devoid of enhancer activity. We propose that Zld primes enhancers by lowering the high nucleosome barrier just enough to assist TFs in accessing their binding motifs and promoting spatially controlled enhancer activation if the right patterning TFs are present. We envision that genome activators in general will utilize this mechanism to activate the zygotic genome in a robust and precise manner.
Obstetric consequences of subfertility: a retrospective cohort study
Authors: DoPierala AL , Bhatta S , Raja EA , Bhattacharya S , Bhattacharya S
Published: September 2015

Objective

To compare the risk of adverse pregnancy outcomes in women with and without subfertility and to investigate whether fertility treatment contributes to the adverse outcomes.

Design

Register‐based retrospective cohort study.

Setting

Aberdeen, Scotland

Population

The exposed group included women with subfertility attending Aberdeen Fertility Clinic between 1989 and 2008 and delivering a singleton (n = 3188) or twin (n = 350) at Aberdeen Maternity Hospital between 1992 and 2009. The unexposed cohort included the remainder of women (singleton n = 52443, twin n = 1125) delivering at Aberdeen Maternity Hospital between 1992 and 2009.

Methods

The Aberdeen Fertility Centre database and Aberdeen Maternity and Neonatal Databank were linked using Community Health Index numbers. Regression models were used to calculate risk ratios and 95% confidence intervals adjusting for potential confounders.

Main outcome measures

Maternal outcomes including pre‐eclampsia, antepartum haemorrhage, preterm birth, induction of labour; delivery outcomes including operative vaginal delivery, caesarean section; and offspring outcomes including low birthweight, stillbirth and neonatal death.

Results

Women with a history of subfertility who delivered a singleton were at a higher risk of pre‐eclampsia [adjusted risk ratios (aRR) 1.18, 95% confidence intervals (CI) 1.02–1.37], antepartum haemorrhage (aRR 1.32, 95% CI 1.18–1.47), induction of labour (aRR 1.21, 95% CI 1.11–1.31) and very preterm delivery (<32 weeks) (aRR 1.96, 95% CI 1.53–2.49). Subfertile women delivering twins were at a higher risk of being delivered by emergency caesarean section (aRR 2.14, 95% CI 1.26–3.66). There were no significant differences in adverse outcomes for singleton pregnancies between the treated and untreated subfertile couples.

Conclusion

Subfertility per se, rather than fertility treatment, was associated with increased risk of adverse outcomes in singleton pregnancies.

Tweetable abstract

Large cohort study found higher incidence of adverse outcome in subfertile women having singletons or twins
RNeXML: a package for reading and writing richly annotated phylogenetic, character and trait data in r
Authors: Boettiger Carl , Chamberlain Scott , Vos Rutger , Lapp Hilmar
Published: September 2015

NeXML is a powerful and extensible exchange standard recently proposed to better meet the expanding needs for phylogenetic data and metadata sharing. Here we present the RNeXML package, which provides users of the r programming language with easy‐to‐use tools for reading and writing NeXML documents, including rich metadata, in a way that interfaces seamlessly with the extensive library of phylogenetic tools already available in the r ecosystem.

Wherever possible, we designed RNeXML to map NeXML document contents, whose arrangement is influenced by the format's XML Schema definition, to their most intuitive or useful representation in r. To make NeXML's powerful facility for recording semantically rich machine‐readable metadata accessible to r users, we designed a functional programming interface to it that hides the semantic web standards leveraged by NeXML from r users who are unfamiliar with them.

RNeXML can read any NeXML document that validates, and it generates valid NeXML documents from phylogeny and character data in various r representations in use. The metadata programming interface at a basic level aids fulfilling data documentation best practices, and at an advanced level preserves NeXML's nearly limitless extensibility, for which we provide a fully working demonstration. Furthermore, to lower the barriers to sharing well‐documented phylogenetic data, RNeXML has started to integrate with taxonomic metadata augmentation services on the web, and with online repositories for data archiving.

RNeXML allows r's rich ecosystem to read and write data in the NeXML format through an interface that is no more involved than reading or writing data from other, less powerful data formats. It also provides an interface designed to feel familiar to r programmers and to be consistent with recommended practices for r package development, yet that retains the full power for users to add their own custom data and metadata to the phylogenies they work with, without introducing potentially incompatible changes to the exchange standard.
Alterations in energy homeostasis to favour adipose tissue gain: A longitudinal study in healthy pregnant women
Authors: Abeysekera Minoli V. , Morris Jack A. , Davis Gregory K. , O'Sullivan Anthony J.
Published: September 2015

Background

Pregnancy is associated with an increase in body fat; however, excessive gestational weight gain predisposes to significant maternal and neonatal morbidity and mortality. It remains unclear whether alterations in energy homeostasis have a major influence on fat storage.

Aims

To evaluate longitudinal changes in body composition and energy metabolism in healthy pregnant women.

Materials and Methods

Body composition, energy expenditure and energy intake were measured longitudinally in 26 women with singleton pregnancies at 12–14 weeks, 24–26 weeks and 34–36 weeks of gestation. Fat mass (FM) and lean body mass (LBM) were measured using bio‐impedance analysis, total energy expenditure (TEE) using the Sensewear Armband and energy intake through a 3‐day food recall diary.

Results

Throughout pregnancy, all women remained healthy. Body weight increased by 10.8 ± 3.9 kg, from 67.3 ± 14.1 kg to 78.1 ± 13.8 kg from the first to the third trimester (P < 0.001). Body fat percentage increased by 4.5 ± 4.2% (P < 0.001). LBM also increased throughout pregnancy, by 3.9 ± 2.4 kg (P < 0.001). TEE increased significantly from the first to the third trimesters (9514 kJ/day to 10 263 kJ/day; P < 0.05). In contrast, energy expenditure due to physical activity, energy intake and macronutrient intake did not change significantly throughout pregnancy.

Conclusion

Healthy women increase FM during pregnancy despite slight increases in TEE and no change in energy intake. This suggests that energy storage efficiency improves during pregnancy, which may be related to alterations in gut microbiota and activation of anabolic pathways during pregnancy. Clarifying factors leading to this more efficient fat and energy storing state, and the role of the pregnancy‐related changes in gut microbiota, may be important for managing gestational weight gain.
Prenatal maternal stress and atopic diseases in the child: a systematic review of observational human studies
Authors: Andersson N. W. , Hansen M. V. , Larsen A. D. , Hougaard K. S. , Kolstad H. A. , Schlünssen V.
Published: September 2015

Background

A growing number of studies suggest that maternal stress during pregnancy promotes atopic disorders in the offspring. This is the first systematic review to address prenatal maternal stress (PNMS) and the subsequent risk of atopy‐related outcomes in the child.

Methods

The review was performed in accordance to the PRISMA criteria. We searched and selected studies in PubMed, Scopus, Embase and PsychINFO until November 2014.

Results

Sixteen (with 25 analyses) of 426 identified articles met the review criteria. Five main PNMS exposures (negative life events, anxiety/depression, bereavement, distress and job strain) and five main atopic outcomes (asthma, wheeze, atopic dermatitis, allergic rhinitis and IgE) were assessed across the studies. Overall, 21 of the 25 analyses suggested a positive association between PNMS and atopic outcomes. Of the 11 exposure–response analyses reported, six found statistically significant trends.

Conclusion

This systematic review suggests a relationship between maternal stress during pregnancy and atopic disorders in the child. However, the existing studies are of diverse quality. The wide definitions of often self‐reported stress exposures imply a substantial risk for information bias and false‐positive results. Research comparing objective and subjective measures of PNMS exposure as well as objective measures for atopic outcome is needed.
The TLR4‐associated phospholipase D1 activation is crucial for Der f 2‐induced IL‐13 production
Authors: Choi H.‐J. , Park S.‐Y. , Cho J. H. , Park J.‐W. , Sohn J.‐H. , Kim Y.‐J. , Oh J.‐W. , Han J.‐S.
Published: September 2015

Background

House dust mites (HDMs) are the most important source of indoor aeroallergens that contribute to the rising incidence of allergic diseases such as allergic asthma. The major HDM, Der f 2, induces inflammatory cytokine expression. Little is known about the signaling pathway involved.

Objective

We wanted to define the Der f 2 signaling pathway from its receptor to the transcription factor responsible for IL‐13 expression and production.

Methods

Human bronchial epithelial cells were stimulated with Der f 2. The release and gene expression of IL‐13 were measured by means of ELISA and RT‐PCR, respectively. In the airway inflammation mouse model, airway responses were assessed using ELISA, histology, BAL fluid, and methacholine responsiveness.

Results

Here, we show that Der f 2 binds to TLR4 and induces IL‐13 expression and production. In the airway inflammation mouse model, Der f 2‐induced IL‐13 production significantly decreased with treatment of TAK‐242, a novel TLR4 inhibitor. Activation of TLR4 by Der f 2 requires the recruitment and activation of Syk, which leads to phosphorylation of PLCγ and membrane translocation of PKCα. p38 MAPK is then activated by PKCα and stimulates PLD1 activity by phosphorylating the Thr147 residue of PLD1. PLD1 activation enhanced binding of ROCK1 to ATF‐2 and leads to increased expression of IL‐13.

Conclusion

Our data extend the knowledge for a variety of possible roles of PLD1 in allergic disorders including asthma pathogenesis and suggest possible candidacy of PLD1 as a molecular target for novel therapeutic approaches.
Learning curve for cytoreductive surgery and perioperative intraperitoneal chemotherapy for peritoneal carcinomatosis
Authors: Huang Yeqian , Alzahrani Nayef A. , Liauw Winston , Morris David L.
Published: September 2015

Background

Combined cytoreductive surgery (CRS) and perioperative intraperitoneal chemotherapy (PIC) has been considered as a standard approach for peritoneal surface malignancy. This study aims to assess the learning curve of this combined approach.

Methods

Prospectively collected data of our first 800 consecutive patients treated by CRS and PIC between January 1996 and July 2014 were retrospectively reviewed. Eight hundred patients were divided into two groups and eight groups for comparison. A significant difference was defined as P < 0.05.

Results

A significant increase in the rate of the completeness of cytoreduction (CC) score‐0 from 74.0% to 83.0% was seen with a reduction in rates of other CC scores. Also, there was a decreasing trend in mean blood transfusion units. The rate of viscus perforation, fistula formation and small bowel obstruction was significantly lower in the recent 400 patients. However, there was a significant increase in the incidence of deep venous thrombosis and pulmonary embolism. There was an improvement in the 5‐year survival rate for patients with colorectal cancer, pseudomyxoma peritonei and mesothelioma.

Conclusion

Our findings demonstrate a learning curve associated with the combined approach of CRS and PIC. With adequate experience, CRS and PIC can be safely performed with acceptable mortality and morbidity.
Effect of maternal position and uterine activity on periodic maternal heart rate changes before elective cesarean section at term
Authors: Ibrahim Selma , Jarefors Erika , Nel Daniel G. , Vollmer Linda , Groenewald Coenraad A. , Odendaal Hein J.
Published: September 2015

Introduction

Because little is known about the effects of maternal position on periodic changes in the maternal heart rate (MHR) in late pregnancy, a prospective observational study was done at Tygerberg Academic Hospital in Cape Town. Pregnant women admitted for elective cesarean section were studied to determine the effect of changes in position on the maternal and fetal heart rates (FHR) and maternal blood pressure.

Material and methods

Continuous transabdominal non‐invasive recording of MHR, FHR patterns and uterine activity was done for 1 h in 119 women, using the AN24 device from Monica Health Care. Maternal position was changed every 15 min from lateral to supine, then to the other lateral position and finally supine again. Blood pressure was measured in the left arm and left lower leg three times during each 15‐min period.

Results

MHRs were four beats per minute slower in the left lateral position than in the right lateral position. Periodic MHR changes were seen in 13 (10.9%) women. Most of these (84.6%) were associated with uterine activity and not with maternal position. No changes in FHR patterns were observed after position changes.

Conclusions

In a subgroup of pregnant women at term, uterine activity was associated with periodic decelerations of the MHR. In low risk pregnancies there seems to be no effect on the FHR pattern. Implications for the compromised fetus have not yet been investigated.
Low Vitamin D Levels and Genetic Polymorphism in the Vitamin D Receptor are Associated with Increased Risk of Statin‐Induced Myopathy
Authors: Ovesjö Marie‐Louise , Skilving Ilona , Bergman Peter , Rane Anders , Ekström Lena , Björkhem‐Bergman Linda
Published: September 2015

The main aim of this study was to test the hypothesis whether 25‐hydroxyvitamin D (25OHD) levels <50 nmol/L at baseline could predict statin‐induced myopathy during the course of treatment. In addition, we analysed the association between a genetic polymorphism in the vitamin D receptor (VDR) and the risk of statin‐induced myopathy. We used serum samples from a prospective, observational study in statin‐treated patients in Sweden who were thoroughly followed with interviews and questionnaires regarding muscular symptoms (n = 127). In this cohort, 16 developed muscular symptoms and 111 had no muscular symptoms associated with statin treatment during the first year of follow‐up. Patients with 25OHD levels <50 nmol/L before starting on statin treatment had four times higher risk of developing muscular symptoms compared with individuals having 25OHD levels >50 nmol/L (RR 4.2; 95% CI 1.7–10.2; p < 0.01). The mean levels of 25OHD at baseline were 50 ± 4 nmol/L among patients developing myopathy and 60 ± 2 nmol/L among patients without myopathy (p < 0.01). Individuals homozygous for the C allele in the VDR polymorphism TaqI (rs731236) had a four times higher risk of developing muscular symptoms; (RR 4.37, 95% CI 1.9–10.1, p < 0.01). In conclusion, 25OHD levels <50 nmol/L might be a useful marker to predict muscular adverse events during statin treatment. In addition, the finding that the VDR polymorphism TaqI was associated with myopathy may indicate a causal relationship between vitamin D function and myopathy, but larger studies are needed before firm conclusions can be drawn.
Fewer but better: Proportionate size of the group affects evaluation of transgressive leaders
Authors: Travaglino Giovanni A. , Abrams Dominic , Randsley de Moura Georgina , Yetkili Orkun
Published: September 2015

A group may be badly affected if its leader transgresses important rules. Nonetheless, an emerging body of evidence suggests that in intergroup contexts, group members apply a double standard when judging ingroup leaders – They respond less punitively to transgressions by their leader than by non‐leaders. In this article, two experiments investigated how proportionate ingroup size affects reactions to transgressive ingroup leaders. We demonstrate that ingroup leaders from larger, but not smaller, groups benefit from the double standard. The experiments testing the effects of two different types of transgressions (nepotistic favouritism and corruption, respectively) show that transgressive leaders from larger groups are evaluated more positively than both comparable non‐leaders and leaders from smaller groups. In contrast, transgressive leaders from smaller groups are evaluated similarly to comparable transgressive non‐leaders. Experiment 2 investigated a potential explanation for this phenomenon. Faced with a transgressive leader, members of a smaller group report greater embarrassment than do members of larger groups in relation to the leaders’ actions. Implications of these findings and directions for future research are discussed.
Deregulation of SYCP2 predicts early stage human papillomavirus‐positive oropharyngeal carcinoma: A prospective whole transcriptome analysis
Authors: Masterson Liam , Sorgeloos Frederic , Winder David , Lechner Matt , Marker Alison , Malhotra Shalini , Sudhoff Holger , Jani Piyush , Goon Peter , Sterling Jane
Published: September 2015

This study was designed to identify significant differences in gene expression profiles of human papillomavirus (HPV)‐positive and HPV‐negative oropharyngeal squamous cell carcinomas (OPSCC) and to better understand the functional and biological effects of HPV infection in the premalignant pathway. Twenty‐four consecutive patients with locally advanced primary OPSCC were included in a prospective clinical trial. Fresh tissue samples (tumor vs. matched normal epithelium) were subjected to whole transcriptome analysis and the results validated on the same cohort with RT–quantitative real‐time PCR. In a separate retrospective cohort of 27 OPSCC patients, laser capture microdissection of formalin‐fixed, paraffin‐embedded tissue allowed RNA extraction from adjacent regions of normal epithelium, carcinoma in situ (premalignant) and invasive SCC tissue. The majority of patients showed evidence of high‐risk HPV16 positivity (80.4%). Predictable fold changes of RNA expression in HPV‐associated disease included multiple transcripts within the p53 oncogenic pathway (e.g. CDKN2A/CCND1). Other candidate transcripts found to have altered levels of expression in this study have not previously been established (SFRP1, CRCT1, DLG2, SYCP2, and CRNN). Of these, SYCP2 showed the most consistent fold change from baseline in premalignant tissue; aberrant expression of this protein may contribute to genetic instability during HPV‐associated cancer development. If further corroborated, this data may contribute to the development of a non‐invasive screening tool. This study is registered with the UK Clinical Research Network (ref.: 11945).
Gastrointestinal involvement in Fabry disease. So important, yet often neglected
Authors: Politei J. , Thurberg B.L. , Wallace E. , Warnock D. , Serebrinsky G. , Durand C. , Schenone A.B.
Published: September 2015

Fabry disease is an X‐linked metabolic storage disorder due to the deficiency of lysosomal alpha‐galactosidase A which causes accumulation of glycosphingolipids, primarily globotriaosylceramide, throughout the body. Gastrointestinal signs and symptoms – abdominal pain, nausea, diarrhea and diverticular disease – are some of the most frequently reported complaints in patients with Fabry disease but are often neglected. Gastrointestinal symptoms are due to intestinal dysmotility as well as impaired autonomic function, vasculopathy and myopathy. Since 2001, enzyme replacement therapy has been a mainstay in treatment of gastrointestinal symptoms of Fabry disease (FD), resulting in reduced gastrointestinal symptoms. Here, we report on four patients with Fabry disease (FD) who manifested early gastrointestinal involvement.
De novo mTOR inhibitor‐based immunosuppression in ABO‐incompatible kidney transplantation
Authors: Koch Martina , Wiech Thorsten , Marget Matthias , Peine Sven , Thude Hansjörg , Achilles Eike G. , Fischer Lutz , Lehnhardt Anja , Thaiss Friedrich , Nashan Bjoern
Published: September 2015

ABO‐incompatible (ABOi) kidney transplantation (KTx) has become an accepted therapeutic option in renal replacement therapy for patients without a blood group‐compatible living donor. Using different desensitization strategies, most centers apply B‐cell depletion with rituximab and maintenance immunosuppression (IS) with tacrolimus and mycophenolic acid. This high load of total IS leads to an increased rate of surgical complications and virus infections in ABOi patients. Our aim was to establish ABOi KTx using an immunosuppressive regimen, which is effective in preventing acute rejection without increasing the risk for viral infections. Therefore, we selected a de novo immunosuppressive protocol with low‐dose calcineurin inhibitor and the mTOR inhibitor everolimus for our ABOi program. Here, we report the first 25 patients with a complete three‐yr follow‐up treated with this regimen. Three‐yr patient survival and graft survival were 96% and 83%. The rate of acute T‐cell‐mediated rejections was low (12%). Cytomegalovirus (CMV) infection was evident in one patient only (4%). Surgical complications were common (40%), but mild in 80% of cases. We demonstrate that ABOi KTx with a de novo mTOR inhibitor‐based regimen is feasible without severe surgical or immunological complications and a low rate of viral infections.
Latin Americans in Spain and their attitude toward living kidney donation
Authors: Ríos A. , López‐Navas A. , Martínez‐Alarcón L. , Ramírez P. , Parrilla P.
Published: September 2015

Introduction

The Latin American (LA) population in Spain is ever increasing in size and is perfectly integrated into the social structure. The objectives were to analyze the attitude of citizens, born in Latin America and living in Spain, toward living kidney donation (LKD) and to determine the psychosocial variables affecting this attitude.

Material and Methods

A sample of LA residents living in Spain was obtained randomly in 2010 and stratified according to the respondent's nationality (n = 1314). Attitude was evaluated using a validated questionnaire (“Proyecto Colaborativo Internacional Donante sobre Donación de Vivo Renal” Ríos). The survey was self‐administered and completed anonymously.

Results

The questionnaire completion rate was 86% (n = 1.132). A total of 89% (n = 1003) were in favor of related living donation, and 30% if the donation were unrelated. The variables associated with attitude toward LKD were as follows: sex (p = 0.043); marital status (p = 0.013); previous experience of organ donation (p = 0.009); attitude toward deceased organ donation (p < 0.001); a respondent's belief that he or she could be a possible recipient of a future transplant (p < 0.001); knowledge of a partner's opinion (p = 0.021); family discussion about organ donation (p = 0.001); knowledge of the view of one's religion toward donation (p < 0.001); concern about “mutilation” after donation (p = 0.004); and evaluation of the risk from living donation (p = 0.036).

Conclusions

The attitude of LA citizens residing in Spain was favorable both toward related LKD and unrelated living donation.
LABOR MARKET OPENNESS, H‐1B VISA POLICY, AND THE SCALE OF INTERNATIONAL STUDENT ENROLLMENT IN THE UNITED STATES
Authors: Shih Kevin
Published: September 2015

International students have long comprised an important part of U.S. higher education. However, little is known regarding the factors that encourage students from across the world to enroll in U.S. colleges and universities each year. This paper examines the relationship between international enrollment and the openness of the United States' skilled labor market, currently regulated by the H‐1B program. Gravity regressions reveal that H‐1B visa issuances to a country are positively and significantly related to the number of international students from that country. Causal estimates of the impact of labor market openness are achieved by exploiting a dramatic fall in the H‐1B visa cap in October 2003. Triple difference estimates show that the fall in the cap lowered foreign enrollment by 10%. (JEL F22, I21, J11)
MITIGATING HYPOTHETICAL BIAS IN STATED PREFERENCE DATA: EVIDENCE FROM SPORTS TOURISM
Authors: Whitehead John C. , Weddell Melissa S. , Groothuis Peter A.
Published: September 2015

One of the major criticisms of stated preference data is hypothetical bias. Using a unique dataset of both stated and actual behavior, we test for hypothetical bias of stated preference survey responses. We consider whether respondents tend to overstate their participatory sporting event behavior ex ante when compared to their actual behavior at different registration fees. We find that stated behavior accurately predicts actual behavior at a middle level of respondent certainty, overpredicts actual behavior at a lower level of certainty, and underpredicts behavior at a higher level of certainty. This result suggests that respondent uncertainty corrections can be used to mitigate hypothetical bias and stated preference data can be used to better understand actual behavior in situations where no data exist. (JEL L83, Q51, Z2)
Mortality and lamb body mass growth in free‐ranging domestic sheep – environmental impacts including lethal and non‐lethal impacts of predators
Authors: Mabille Géraldine , Stien Audun , Tveraa Torkild , Mysterud Atle , Brøseth Henrik , Linnell John D. C.
Published: September 2015

The management and recovery of large predator populations in areas where human persecution has driven them to ecological extinction requires a solid understanding of the effects of both predation and food limitation on prey populations. We used 11 yr of data on reported losses among 17.3 million free‐ranging sheep Ovis aries in the Norwegian farming industry to elucidate the relative roles of climate, vegetation characteristics, sheep densities, lamb body mass and densities of predators and alternative prey on the number of lambs and ewes lost on summer pastures. We first examined whether predator densities predicted autumn lamb body mass through possible impacts of predators on body growth (non‐lethal effects) but found no evidence for such effects in our study system. This might be due to weak anti‐predator behavioral responses in domesticated sheep. However, autumn lamb body mass was predicted by both sheep density and winter and spring weather conditions, probably through food availability. Losses of both lambs and ewes were positively and strongly related to the density of Eurasian lynx Lynx lynx, wolverine Gulo gulo and brown bear Ursus arctos. In addition, food availability and spring weather conditions were associated to losses of lambs, while precipitation in May predicted losses of ewes. There was little evidence for interaction effects of predator species on losses, suggesting that most of the effects of the predators were additive to each other. Given the strong effect of predator densities on sheep losses, we conclude that changing livestock husbandry practices towards a system that actively protects sheep and/or active management of predator densities may be necessary to reduce sheep losses where predators are recolonizing.
Differences in spatial synchrony and interspecific concordance inform guild‐level population trends for aerial insectivorous birds
Authors: Michel Nicole L. , Smith Adam C. , Clark Robert G. , Morrissey Christy A. , Hobson Keith A.
Published: September 2015

Many animal species exhibit spatiotemporal synchrony in population fluctuations, which may provide crucial information about ecological processes driving population change. We examined spatial synchrony and concordance among population trajectories of five aerial insectivorous bird species: chimney swift Chaetura pelagica, purple martin Progne subis, barn swallow Hirundo rustica, tree swallow Tachycineta bicolor, and northern rough‐winged swallow Stelgidopteryx serripennis. Aerial insectivores have undergone severe guild‐wide declines that were considered more prevalent in northeastern North America. Here, we addressed four general questions including spatial synchrony within species, spatial concordance among species, frequency of declining trends among species, and geographic location of declining trends. We used dynamic factor analysis to identify large‐scale common trends underlying stratum‐specific annual indices for each species, representing population trajectories shared by spatially synchronous populations, from 46 yr of North American Breeding Bird Survey data. Indices were derived from Bayesian hierarchical models with continuous autoregressive spatial structures. Stratum‐level spatial concordance among species was assessed using cross‐correlation analysis. Probability of long‐term declining trends was compared among species using Bayesian generalized linear models. Chimney swifts exhibited declining trends throughout North America, with less severe declines through the industrialized Mid‐Atlantic and Great Lakes regions. Northern rough‐winged swallows exhibited declining trends throughout the west. Spatial concordance among species was limited, the proportion of declining trends varied among species, and contrary to previous reports, declining trends were not more prevalent in the northeast. Purple martins, barn swallows, and tree swallows exhibited synchrony across smaller spatial scales. The extensive within‐species synchrony and limited concordance suggest that population trajectories of these aerial insectivores are responding to large‐scale but complex and species‐ and region‐specific environmental conditions (e.g. climate, land use). A single driver of trends for aerial insectivores as a guild appears unlikely.
Fighting in fig wasps: do males avoid killing brothers or do they never meet them?
Authors: COOK JAMES M. , REUTER CAROLINE , MOORE JAMIE C. , WEST STUART A.
Published: September 2015

1. In many fig wasp species, armoured wingless males regularly engage in lethal fights for access to females inside figs, which act as discrete mating patches.

2. Kin selection generally opposes killing brothers, because their reproductive success provides indirect genetic benefits (inclusive fitness). However, siblicide may be avoided if (i) brothers do not occur in the same figs, or (ii) males avoid fighting brothers in the same fig. Alternatively, (iii) siblicide may occur because intense mate competition between brothers at the local scale overcomes kin selection effects, or (iv) males do not recognise kin.

3. A fig may also contain wasps from other closely related species and it is not known if males also fight with these individuals.

4. Nine microsatellite loci were used in the first genetic analysis of fighting in fig wasps. We assigned species and sibling identities to males and tested alternative fighting scenarios for three Sycoscapter wasp species in figs of Ficus rubiginosa.

5. Approximately 60% of figs contained males from more than one Sycoscapter species and approximately 80% of fights were between conspecifics, but a surprising 20% were between heterospecific males.

6. Within species, few figs contained brothers, suggesting that females typically lay one son per fig. Overall, most males do not compete with brothers and all fights observed were between unrelated males.
Optimal range of prey size for antlions
Authors: HUMEAU ANTOINE , ROUGÉ JUSTINE , CASAS JÉRÔME
Published: September 2015

1. Antlions are opportunistic trap building predators that cannot control prey encounter. Their trap should ideally retain a great diversity of prey. However, building a single trap that captures many prey with varying characteristics can be challenging.

2. A series of five different ant species ranging from thin to large, of sizes ranging from 2.75 to 6.5 mm, and a mean weight ranging from 0.54 to 6.00 mg were offered in a random succession to antlions. The state of satiation of the antlions was controlled, and their mass and the depth of their pit were recorded. The reaction of antlion to the prey, the probability of capture as well as the time to escape were recorded.

3. The probability of an antlion reaction is an increasing function of the pit depth and a decreasing function of antlion mass. The probability of capture is highest for intermediate prey mass and is an increasing function of pit depth. The time to escape is a declining function of prey mass and an increasing function of pit depth.

4. There is an upper limit to prey mass given that large prey escape out of the pit. There is a lower limit to prey mass given the difficulty to apprehend the smallest, thin species. Consequently, there is a range of prey mass, corresponding to a medium‐sized ant of 2 mg, for which the pit functions best. The physics of insect locomotion on sandy slopes was identified as the key to understanding the functioning of antlion pits.
Dispersal response to climate change: scaling down to intraspecific variation
Authors: Bestion Elvire , Clobert Jean , Cote Julien
Published: September 2015

Range shift, a widespread response to climate change, will depend on species abilities to withstand warmer climates. However, these abilities may vary within species and such intraspecific variation can strongly impact species responses to climate change. Facing warmer climates, individuals should disperse according to their thermal optimum with consequences for species range shifts. Here, we studied individual dispersal of a reptile in response to climate warming and preferred temperature using a semi‐natural warming experiment. Individuals with low preferred temperatures dispersed more from warmer semi‐natural habitats, whereas individuals with higher preferred temperatures dispersed more from cooler habitats. These dispersal decisions partly matched phenotype‐dependent survival rates in the different thermal habitats, suggesting adaptive dispersal decisions. This process should result into a spatial segregation of thermal phenotypes along species moving ranges which should facilitate local adaptation to warming climates. We therefore call for range shift models including intraspecific variation in thermal phenotype and dispersal decision.
Restricted distribution of mrg‐1 mRNA in C. elegans primordial germ cells through germ granule‐independent regulation
Authors: Miwa Takashi , Takasaki Teruaki , Inoue Kunio , Sakamoto Hiroshi
Published: September 2015

The chromodomain protein MRG‐1 is an essential maternal factor for proper germline development that protects germ cells from cell death in C. elegans. Unlike germ granules, which are exclusively segregated to the germline blastomeres at each cell division from the first cleavage of the embryo, MRG‐1 is abundant in all cells in early embryos and is then gradually restricted to the primordial germ cells (PGCs) by the morphogenesis stage. Here, we show that this characteristic spatiotemporal expression pattern is dictated by the mrg‐1 3'UTR and is differentially regulated at the RNA level between germline and somatic cells. Asymmetric segregation of germ granules is not necessary to localize MRG‐1 to the PGCs. We found that MES‐4, an essential chromatin regulator in germ cells, also accumulates in the PGCs in a germ granule‐independent manner. We propose that C. elegans PGCs have a novel mechanism to accumulate at least some chromatin‐associated proteins that are essential for germline immortality.