bluuebunny/crossref_metadata_2025 huggingface dataset:
Liver Fibrosis Regression Measured by Transient Elastography in Human Immunodeficiency Virus (HIV)-Hepatitis B Virus (HBV)-Coinfected Individuals on Long-Term HBV-Active Combination Antiretroviral Therapy
Authors: Audsley Jennifer , Robson Christopher , Aitchison Stacey , Matthews Gail V. , Iser David , Sasadeusz Joe , Lewin Sharon R.
Published: February 2016

Background.  Advanced fibrosis occurs more commonly in human immunodeficiency virus (HIV)-hepatitis B virus (HBV) coinfected individuals; therefore, fibrosis monitoring is important in this population. However, transient elastography (TE) data in HIV-HBV coinfection are lacking. We aimed to assess liver fibrosis using TE in a cross-sectional study of HIV-HBV coinfected individuals receiving combination HBV-active (lamivudine and/or tenofovir/tenofovir-emtricitabine) antiretroviral therapy, identify factors associated with advanced fibrosis, and examine change in fibrosis in those with >1 TE assessment.

Methods.  We assessed liver fibrosis in 70 HIV-HBV coinfected individuals on HBV-active combination antiretroviral therapy (cART). Change in fibrosis over time was examined in a subset with more than 1 TE result (n = 49). Clinical and laboratory variables at the time of the first TE were collected, and associations with advanced fibrosis (≥F3, Metavir scoring system) and fibrosis regression (of least 1 stage) were examined.

Results.  The majority of the cohort (64%) had mild to moderate fibrosis at the time of the first TE, and we identified alanine transaminase, platelets, and detectable HIV ribonucleic acid as associated with advanced liver fibrosis. Alanine transaminase and platelets remained independently advanced in multivariate modeling. More than 28% of those with >1 TE subsequently showed liver fibrosis regression, and higher baseline HBV deoxyribonucleic acid was associated with regression. Prevalence of advanced fibrosis (≥F3) decreased 12.3% (32.7%–20.4%) over a median of 31 months.

Conclusions.  The observed fibrosis regression in this group supports the beneficial effects of cART on liver stiffness. It would be important to study a larger group of individuals with more advanced fibrosis to more definitively assess factors associated with liver fibrosis regression.
A Critical Reappraisal of Prolonged Neutropenia as a Risk Factor for Invasive Pulmonary Aspergillosis
Authors: Abers Michael S. , Ghebremichael Musie S. , Timmons Allison K. , Warren H. Shaw , Poznansky Mark C. , Vyas Jatin M.
Published: February 2016

Prolonged neutropenia is generally thought to be the major factor for invasive pulmonary aspergillosis (IPA). In the present study, we characterize the frequency, severity, and duration of neutropenia that immediately precedes IPA. Prolonged neutropenia was identified in only one third of all IPA cases and occurred exclusively in hematologic patients.
Age-Related Changes in Binaural Interaction at Brainstem Level
Authors: Van Yper Lindsey N. , Vermeire Katrien , De Vel Eddy F. J. , Beynon Andy J. , Dhooge Ingeborg J. M.
Published: February 2016

Objectives:

Age-related hearing loss hampers the ability to understand speech in adverse listening conditions. This is attributed to a complex interaction of changes in the peripheral and central auditory system. One aspect that may deteriorate across the lifespan is binaural interaction. The present study investigates binaural interaction at the level of the auditory brainstem. It is hypothesized that brainstem binaural interaction deteriorates with advancing age.

Design:

Forty-two subjects of various age participated in the study. Auditory brainstem responses (ABRs) were recorded using clicks and 500 Hz tone-bursts. ABRs were elicited by monaural right, monaural left, and binaural stimulation. Binaural interaction was investigated in two ways. First, grand averages of the binaural interaction component were computed for each age group. Second, wave V characteristics of the binaural ABR were compared with those of the summed left and right ABRs.

Results:

Binaural interaction in the click ABR was demonstrated by shorter latencies and smaller amplitudes in the binaural compared with the summed monaural responses. For 500 Hz tone-burst ABR, no latency differences were found. However, amplitudes were significantly smaller in the binaural than summed monaural condition. An age-effect was found for 500 Hz tone-burst, but not for click ABR.

Conclusions:

Brainstem binaural interaction seems to decline with age. Interestingly, these changes seem to be stimulus-dependent.
Neuropilin-2 promotes melanoma growth and progression in vivo
Authors: Moriarty Whei F. , Kim Edward , Gerber Stephanie A. , Hammers Hans , Alani Rhoda M.
Published: February 2016

Tumor cell interactions with their microenvironment, and neighboring endothelial cells in particular, are critical for tumor cell survival and the metastatic process. Within the spectrum of tumors, melanomas are notorious for their ability to metastasize at a relatively early stage of development; however, little is known about the molecular pathways mediating this process. We recently performed a screen to assess critical mediators of melanoma metastasis by evaluating melanoma–endothelial cell communication. Neuropilin-2 (NRP2), a cell surface receptor involved in angiogenesis and axonal guidance, was found to be an important mediator of melanoma–endothelial cell cross-talk in these studies. Here we seek to further define the role of NRP2 in melanoma growth and progression. We use stable gene silencing of NRP2 in melanomas from varying stages of tumor progression to define the role of NRP2 in melanoma growth, migration, invasion, and metastasis. We found that NRP2 gene silencing in metastatic melanoma cell lines inhibited tumor cell growth in vitro; furthermore, knockdown of NRP2 expression in the metastatic melanoma cell line 1205Lu significantly inhibited in-vivo tumor growth and metastasis. We conclude that NRP2 plays an important role in mediating melanoma growth and metastasis and suggest that targeting this cell surface molecule may represent a significant therapeutic strategy for patients diagnosed with aggressive forms of melanoma.
Ultrasound of the sentinel node in melanoma patients: echo-free island is a discriminatory morphologic feature for node positivity
Authors: Voit Christiane A. , Oude Ophuis Charlotte M.C. , Ulrich Jens , van Akkooi Alexander C.J. , Eggermont Alexander M.M.
Published: February 2016

Unlike breast and thyroid cancer, the use of ultrasound (US)-guided fine needle aspiration cytology (FNAC) for preoperative staging is limited in melanoma. New US morphology criteria have shown that US-FNAC can correctly identify 50% of all involved sentinel nodes (SN) in melanoma patients before surgical excision. The aim of this study was to examine a new criterion: the echo-free island (EFI). A total of 1000 consecutively staged melanoma patients (Breslow thickness>1 or<1 mm, but ulcerated, Clark IV/V or regressed) scheduled for SN staging underwent preoperative US. US morphology items were assessed: peripheral perfusion, loss of central echoes, balloon shape, and EFI. FNAC was performed in case of suspicious and malignant US patterns. All patients proceeded to undergo an SN biopsy or direct completion lymph node dissection (CLND) (in the case of positive FNAC). In all, 57% of the patients were men. The mean/median Breslow thickness was 2.58/1.57 mm. The mean/median follow-up was 56/53 months. SN was positive in 21%. EFI information was available in 95.3%. EFI was seen in 40 patients (4%). EFI sensitivity was 10.8%, specificity was 97.6%, positive predictive value was 50%, and negative predictive value was 80.2%. EFI was significantly correlated to peripheral perfusion (67.5%). There was no correlation to balloon shape or loss of central echoes. Five-year melanoma-specific survival of patients with EFI was significantly worse: 80% versus 92% when absent. The EFI can be useful in the early detection of SN melanoma metastasis. It is an early sign of involvement and thus associated with a decreased survival.
Herpesvirus Infections and Transglutaminase Type 2 Antibody Positivity in Childhood
Authors: Jansen Michelle A.E. , van den Heuvel Diana , van der Zwet Kirsten V.M. , Jaddoe Vincent W.V. , Hofman Albert , Escher Johanna C. , Fraaij Pieter L.A. , Hooijkaas Herbert , van Zelm Menno C. , Moll Henriette A.
Published: February 2016

Objectives:

Persistent viral infections have been implicated in the etiology of autoimmune diseases in adulthood, but it is not known whether herpesviruses are associated with the development of celiac disease autoimmunity in childhood. We assessed whether herpesvirus infections are associated with transglutaminase type 2 antibody (TG2A) concentrations in children at 6 years of age.

Methods:

The present study was embedded within a population‐based prospective cohort study. Serum immunoglobulin G levels against Epstein‐Barr virus, cytomegalovirus (CMV), and herpes simplex virus type 1 were measured by enzyme‐linked immunosorbent assay , and TG2A concentrations with fluorescence enzyme immunoassay in 4420 children at 6 years of age. Children were categorized based on TG2A concentrations into negative (<7 U/mL), positive (≥7–70 U/mL), and strongly positive (≥70 U/mL), that is, 10 times upper limit normal.

Results:

Fifty‐nine children (1.3%) were TG2A positive, and of these 31 (53%) had concentrations 70 U/mL or more. Children with TG2A concentrations 70 U/mL or more were less often infected with CMV (adjusted odds ratio (aOR) 0.38, 95% CI 0.14–0.98, P = 0.04) and with any of the 3 viruses (aOR 0.38, 95% CI 0.18–0.78, P < 0.01) than children with TG2A negative concentrations. In addition, children with TG2A concentrations 70 U/mL or more were less often infected with 2 or more viruses than children with TG2A negative concentrations (aOR 0.15, 95% CI 0.03–0.65, P = 0.01).

Conclusions:

Both CMV single infection and combined CMV, Epstein‐Barr virus and/or herpes simplex virus type 1 infections are inversely associated with strongly TG2A positivity. This may indicate a protective effect of herpesvirus infections in the pathogenesis of celiac disease autoimmunity.
Quality of Reporting Nutritional Randomized Controlled Trials in Patients With Cystic Fibrosis
Authors: Daitch Vered , Babich Tanya , Singer Pierre , Leibovici Leonard
Published: February 2016

Objective:

Randomized controlled trials (RCTs) have a major role in the making of evidence‐based guidelines. The aim of the present study was to critically appraise the RCTs that addressed nutritional interventions in patients with cystic fibrosis.

Methods:

Embase, PubMed, and the Cochrane Library were systematically searched until July 2015. Methodology and reporting of nutritional RCTs were evaluated by the Consolidated Standards of Reporting Trials (CONSORT) checklist and additional dimensions relevant to patients with CF.

Results:

Fifty‐one RCTs were included. Full details on methods were provided in a minority of studies. The mean duration of intervention was <6 months. 56.9% of the RCTs did not define a primary outcome; 70.6% of studies did not provide details on sample size calculation; and only 31.4% reported on the subgroup or separated between important subgroups.

Conclusions:

The examined RCTs were characterized by a weak methodology, a small number of patients with no sample size calculations, a relatively short intervention, and many times did not examine the outcomes that are important to the patient. Improvement over the years has been minor.
Conductive Plastic Electrodes Reduce EEG Artifact During Pediatric ECMO Therapy
Authors: Matsumoto Joyce H. , McArthur David L. , Szeliga Conrad W. , Lerner Jason T. , Rao Lekha M. , Hussain Shaun A. , Wu Joyce Y. , Nuwer Marc R. , Sankar Raman
Published: February 2016

Purpose:

Extracorporeal membrane oxygenation (ECMO) is a life-saving heart and lung bypass procedure that can cause substantial EEG artifact. Continuous EEG monitoring is nonetheless a helpful neuromonitoring tool for patients receiving ECMO therapy because neurologic complications are frequent, but factors such as sedation, neuromuscular blockade, and hemodynamic instability limit clinical and radiographic evaluation. We examined whether using conductive plastic electrodes in place of conventional gold electrodes reduces artifact in clinical EEG studies of pediatric ECMO patients.

Methods:

Four masked electroencephalographers assessed artifact and its impact on overall EEG interpretation in samples from 21 consecutive EEGs recorded during ECMO therapy (14 gold and 7 plastic). A spectral power analysis then quantified 50- to 70-Hz artifact in a larger group of 14 gold and 34 plastic electrode studies during ECMO and 4 non-ECMO gold electrode studies.

Results:

The masked electroencephalographers identified less artifact (P < 0.001) and indicated greater confidence in the accuracy of EEG interpretation (P < 0.001) among studies recorded with plastic electrodes. In quantitative analyses, ECMO was associated with greater 50- to 70-Hz power among studies using gold electrodes (P < 0.001) and gold electrodes exhibited greater 50- to 70-Hz power than plastic electrodes (P < 0.001). Contrasting studies in which most of the electroencephalographers believed that interpretation was (n = 12; 7 gold and 5 plastic) or was not (n = 7; all gold) compromised by artifact, 50- to 70-Hz power was similarly higher among the compromised studies (P < 0.001).

Conclusion:

Plastic electrodes substantially reduce the burden of electrical artifact in EEG studies performed on pediatric ECMO patients and improve confidence in EEG interpretation.
Uncrossed Asymmetry in Pattern Visual Evoked Potentials: A Reappraisal
Authors: Ericson Eric J. , Lubin Jonathan , Minieka Michael M. , Nishida Takashi
Published: February 2016

Purpose:

To demonstrate the utility of an uncrossed asymmetry in full-field pattern reversal visual evoked potentials (FF-PVEPs) will accurately predict a retrochiasmal lesion confirmed by MRI.

Methods:

During an 8-year period, 754 patients had FF-PVEPs performed and analyzed without knowledge of their clinical histories and imaging studies. Interhemispheric amplitude ratios were calculated between N75-P100 and P100-N145 and deemed significant if both demonstrated greater than 50% amplitude asymmetry no matter which eye was stimulated (uncrossed symmetry).

Results:

We identified 11 patients of 754 patients evaluated for 8 years (1.5%) whose FF-PVEP fulfilled our amplitude criteria. Ten of 11 had retrochiasmal lesions confirmed with MRI for a calculated positive predictive value of 91%.

Conclusions:

These data provide initial support for the hypothesis that specified amplitude criteria in FF-PVEPs can provide evidence for a retrochiasmal lesion. An abnormal interhemispheric amplitude ratio in FF-PVEPs is underrecognized as a diagnostic criterion for retrochiasmal lesion prediction.
Rules of tissue packing involving different cell types: human muscle organization
Authors: Sánchez-Gutiérrez Daniel , Sáez Aurora , Paradas Carmen , Escudero Luis M.
Published: February 2016

Natural packed tissues are assembled as tessellations of polygonal cells that do not leave empty spaces between them. They include the epithelial sheets and the skeletal muscles. Epithelia are formed by equivalent cells that change shape and organization through development. The skeletal muscles appear as a mosaic composed by two different types of cells: the slow and fast fibres that are determined by the identities of the motor neurons that innervate them. Their relative distribution is important for the muscle function and can be altered in some neuromuscular diseases. Little is known about how the spatial organization of fast and slow fibres is established and maintained. In this work we use computerized image analysis and mathematical concepts to capture the organizational pattern in two different healthy muscles: biceps brachii and quadriceps. Here we show that each type of muscle portrays a characteristic topological pattern that allows distinguishing between them. The biceps brachii muscle presents a particular arrange based on the different size of slow and fast fibres, contrary to the quadriceps muscle where an unbiased distribution exists. Our results indicate that the relative size of each cellular type imposes an intrinsic organization into the tissue. These findings establish a new framework for the analysis of packed tissues where two or more cell types exist.
A practical guide for improving transparency and reproducibility in neuroimaging research
Authors: Gorgolewski Krzysztof J. , Poldrack Russell A.
Published: February 2016

Recent years have seen an increase in alarming signals regarding the lack of replicability in neuroscience, psychology, and other related fields. To avoid a widespread crisis in neuroimaging research and consequent loss of credibility in the public eye, we need to improve how we do science. This article aims to be a practical guide for researchers at any stage of their careers that will help them make their research more reproducible and transparent while minimizing the additional effort that this might require. The guide covers three major topics in open science (data, code, and publications) and offers practical advice as well as highlighting advantages of adopting more open research practices that go beyond improved transparency and reproducibility.
DNA from dust: comparative genomics of large DNA viruses in field surveillance samples
Authors: Pandey Utsav , Bell Andrew S. , Renner Daniel , Kennedy David A. , Shreve Jacob , Cairns Chris L. , Jones Matthew J. , Dunn Patricia A. , Read Andrew F. , Szpara Moriah L.
Published: February 2016

The intensification of the poultry industry over the last sixty years facilitated the evolution of increased virulence and vaccine breaks in Marek’s disease virus (MDV-1). Full genome sequences are essential for understanding why and how this evolution occurred, but what is known about genome-wide variation in MDV comes from laboratory culture. To rectify this, we developed methods for obtaining high quality genome sequences directly from field samples without the need for sequence-based enrichment strategies prior to sequencing. We applied this to the first characterization of MDV-1 genomes from the field, without prior culture. These viruses were collected from vaccinated hosts that acquired naturally circulating field strains of MDV-1, in the absence of a disease outbreak. This reflects the current issue afflicting the poultry industry, where virulent field strains continue to circulate despite vaccination, and can remain undetected due to the lack of overt disease symptoms. We found that viral genomes from adjacent field sites had high levels of overall DNA identity, and despite strong evidence of purifying selection, had coding variations in proteins associated with virulence and manipulation of host immunity. Our methods empower ecological field surveillance, make it possible to determine the basis of viral virulence and vaccine breaks, and can be used to obtain full genomes from clinical samples of other large DNA viruses, known and unknown.
Stochastic processes dominate community assembly in cichlid communities in Lake Tanganyika
Authors: Janzen Thijs , Alzate Adriana , Muschick Moritz , van der Plas Fons , Etienne Rampal S.
Published: February 2016

The African Great Lakes are characterized by an extraordinary diversity of endemic cichlid fish species. The cause of this diversity is still largely unknown. Most studies have tried to solve this question by focusing on macro-evolutionary processes, such as speciation. However, the ecological processes determining local cichlid diversity have so far been understudied, even though knowledge on these might be crucial for understanding larger scale biodiversity patterns.

Using trait, environmental and abundance data of cichlid fishes along 36 transects, we have studied how differences in local environmental conditions influence cichlid community assembly in the littoral of Lake Tanganyika, Zambia. We investigated changes in average trait values and in trait-based community assembly processes along three key environmental gradients.

Species diversity and local abundance decreased with increasing sand cover and diet-associated traits changed with depth. Analyses on within-community trait diversity patterns indicated that cichlid community assembly was mainly driven by stochastic processes, to a smaller extent by processes that limit the similarity among co-existing species and least by filtering processes that limit the range of species traits occurring in an environment. Despite, the low impact of habitat filtering processes, we find community dissimilarity to increase with increasing environmental difference.

Our results suggest that local environmental conditions determine cichlid abundance, while the predominance of stochastic community assembly across all environments explains why the communities with the highest abundances contain most species.
Rare Variant Phasing and Haplotypic Expression from RNA-Sequencing with phASER
Authors: Castel Stephane E. , Mohammadi Pejman , Chung Wendy K. , Shen Yufeng , Lappalainen Tuuli
Published: February 2016

Haplotype phasing of genetic variants is important for clinical interpretation of the genome, population genetic analysis, and functional genomic analysis of allelic activity. Here we present phASER, a fast and accurate approach for phasing variants that are overlapped by sequencing reads, including those from RNA-sequencing (RNA-seq), which often span multiple exons due to splicing. This provides 1) dramatically more accurate phasing of rare andde novovariants compared to population-based phasing; 2) phasing of variants in the same gene up to hundreds of kilobases away which cannot be obtained from DNA-sequencing reads; 3) high confidence measures of haplotypic expression, greatly improving power for allelic expression studies.
Model-based projections of Zika virus infections in childbearing women in the Americas
Authors: Perkins T. Alex , Siraj Amir S. , Ruktanonchai Corrine Warren , Kraemer Moritz U.G. , Tatem Andrew J.
Published: February 2016

Zika virus is a mosquito-borne pathogen that is rapidly spreading across the Americas. Due to associations between Zika virus infection and a range of fetal maladies1,2, the epidemic trajectory of this viral infection poses a significant concern for the nearly 15 million children born in the Americas each year. Ascertaining the portion of this population that is truly at risk is an important priority. One recent estimate3suggested that 5.42 million childbearing women live in areas of the Americas that are suitable for Zika occurrence. To improve on that estimate, which did not take into account the protective effects of herd immunity, we developed a new approach that combines classic results from epidemiological theory with seroprevalence data and highly spatially resolved data about drivers of transmission to make location-specific projections of epidemic attack rates. Our results suggest that 1.65 (1.45–2.06) million childbearing women and 93.4 (81.6–117.1) million people in total could become infected before the first wave of the epidemic concludes. Based on current estimates of rates of adverse fetal outcomes among infected women2,4,5, these results suggest that tens of thousands of pregnancies could be negatively impacted by the first wave of the epidemic. These projections constitute a revised upper limit of populations at risk in the current Zika epidemic, and our approach offers a new way to make rapid assessments of the threat posed by emerging infectious diseases more generally.
The Next Generation Precision Medical Record - A Framework for Integrating Genomes and Wearable Sensors with Medical Records
Authors: Waggott Daryl , Bog Anja , Singh Enakshi , Batra Prag , Wright Mark H , Ashley Euan , Fisk Dianna , Shcherbina Anna , Torresl Jessica , Wheeler Matthew , Merker Jason , Bustamante Carlos D
Published: February 2016

Current medical records are rigid with regards to emerging big biomedical data. Examples of poorly integrated big data that already exist in clinical practice include whole genome sequencing and wearable sensors for real time monitoring. Genome sequencing enables conventional diagnostic interrogation and forms the fundamental baseline for precision health throughout a patient’s lifetime. Mobile sensors enable tailored monitoring regimes for both reducing risk through precision health interventions and acute condition surveillance. In order to address the absence of these data in the Electronic Medical Record (EMR), we worked with the SAP Personalized Medicine team to re-envision a modern medical record with these components. The pilot project used 37 patient families with complex medical records, whole genome sequencing and some level of wearable monitoring. Core functionality included patient timelines with integrated text analytics, personalized genomic curation and wearable alerts. The current phase is being rolled out to over 1500 patients in clinics across the hospital system. While fundamentally research, we believe this proof of principle platform is the first of its kind and represents the future of data driven clinical medicine.
Another Take on Real Estate's Role in Mixed‐Asset Portfolio Allocations
Authors: Pagliari Joseph L.
Published: February 2016

This article examines real estate's role in institutional mixed‐asset portfolios using both private‐ and public‐real estate indices, as a means of examining varying real estate‐related risk/return opportunities. In so doing, this article also examines the effects of: (1) increasing the investment horizon, (2) placing constraints on the maximum allocation to any one asset class, and (3) varying the risk preferences of investors. The empirical results suggest—using infinite‐horizon returns and all of the caveats that accompany such a perspective—that real estate allocations of approximately 10–15% of the mixed‐asset portfolio represent an upper bound for most investors. For those investors preferring low‐risk portfolios, (unlevered) private real estate is the vehicle serving this allocation preference; for those investors preferring high‐risk portfolios, public real estate (with its embedded leverage of 40–50%) is the vehicle serving this allocation preference—with such vehicles serving as substitutes for a variety of noncore real estate strategies. In some sense, the distinction between private and public real estate is more about the use of leverage. For those investors preferring moderate‐risk portfolios, an intermediate‐leverage approach seems optimal.
Human Security and the New Global Threats: Discourse, Taxonomy and Implications
Authors: Madrueño‐Aguilar Rogelio
Published: February 2016

The metamorphosis of human security has become a topic of major importance in the context of globalisation. While its external appearance contains central tenets of the conception of security in the 20th century, human security has become increasingly sensitive to characteristics which are indissoluble from the loss of state capacity and legitimacy regarding the use of violence. These features have a direct influence on the contemporary conception of global threats. This article provides an in‐depth examination of the discursive logic behind the notion of human security from the United Nations perspective, as well as how this connects with the recent characterisation of new global threats. Likewise, it has carried out an empirical estimation by using multivariate statistical techniques in the form of a nonhierarchical cluster analysis. This enables us to establish a multidimensional taxonomy of developed and developing countries that could help us to better understand the new discursive framework of global threats and human security. Finally, some implications of these findings for the current debate on country classifications are discussed.
RNA‐seq analysis reveals new candidate genes for drip loss in a Pietrain × Duroc × Landrace × Yorkshire population
Authors: Li Bojiang , Liu Kaiqing , Weng Qiannan , Li Pinghua , Wei Wei , Li Qifa , Chen Jie , Huang Ruihua , Wu Wangjun , Liu Honglin
Published: February 2016

Drip loss, one of the most important meat quality traits, is characterized by low heritability. To date, the genetic factors affecting the drip loss trait have not been clearly elucidated. The objective of this study was to identify critical candidate genes affecting drip loss. First, we generated a Pietrain × Duroc × Landrace × Yorkshire commercial pig population and obtained phenotypic values for the drip loss trait. Furthermore, we constructed two RNA libraries from pooled samples of longissimus dorsi muscles with the highest (H group) and lowest (L group) drip loss and identified the differentially expressed genes (DEGs) between these extreme phenotypes using RNA‐seq technology. In total, 25 883 genes were detected in the H and L group libraries, and none was specifically expressed in only one library. Comparative analysis of gene expression levels found that 150 genes were differentially expressed, of which 127 were upregulated and 23 were downregulated in the H group relative to the L group. In addition, 68 drip loss quantitative trait loci (QTL) overlapping with 63 DEGs were identified, and these QTL were distributed mainly on chromosomes 1, 2, 5 and 6. Interestingly, the triadin (TRDN) gene, which is involved in muscle contraction and fat deposition, and the myostatin (MSTN) gene, which has a role in muscle growth, were localized to more than two drip loss QTL, suggesting that both are critical candidate genes responsible for drip loss.
Optimum dose of neostigmine to reverse shallow neuromuscular blockade with rocuronium and cisatracurium
Authors: Choi E. S. , Oh A. Y. , Seo K. S. , Hwang J. W. , Ryu J. H. , Koo B. W. , Kim B. G.
Published: February 2016

We examined the use of neostigmine for reversing shallow (defined as train‐of‐four ratio of 0.5), cisatracurium‐ and rocuronium‐induced neuromuscular block in 112 patients, by use of 0 μg.kg−1, 10 μg.kg−1, 20 μg.kg−1 or 40 μg.kg−1 dose of neostigmine for reversal. The times from neostigmine administration to train‐of‐four ratios of 0.7, 0.9 and 1.0 were evaluated. Analysis of variance showed that the duration of action was significantly longer after cisatracurium compared with rocuronium. The time to reach a train‐of‐four ratio of 1.0 was significantly shorter with neostigmine 40 μg.kg−1 compared with lower neostigmine doses, and at this dose the time did not differ between cisatracurium and rocuronium. The recovery time from a train‐of‐four ratio of 0.5–1.0 did not differ between cisatracurium and rocuronium, and was significantly shortened by the administration of neostigmine. We conclude that a neostigmine dose of 40 μg.kg−1 was the most effective at reducing recovery time after neuromuscular blockade.
Radiation safety for anaesthesia providers in the orthopaedic operating room
Authors: Rhea E. B. , Rogers T. H. , Riehl J. T.
Published: February 2016

In many orthopaedic operating rooms, anaesthesia providers routinely wear lead aprons for protection from radiation, but some studies have questioned whether this is needed. We conducted a systematic review to identify studies that measured the amount of radiation that anaesthetists were exposed to in the orthopaedic operating room. Multiple studies have shown that at 1.5 m from the source of radiation, anaesthetists received no radiation, or amounts so small that a person would have to be present in an unreasonable number of operations to receive cumulative doses of any significance. Radiation doses at this distance were often at the limits of the sensitivity of the measuring dosimeter. We question the need to wear lead protection for anaesthesia providers who are routinely at 1.5 m or a greater distance from standard fluoroscopy units.
Prolonged propofol infusion for mechanically ventilated children
Authors: Sasabuchi Y. , Yasunaga H. , Matsui H. , Lefor A. K. , Fushimi K.
Published: February 2016

We retrospectively analysed 30‐day mortality and duration of intubation for 8016 children ventilated for three or more days, sedated with midazolam (n = 7716) or propofol (n = 300). We matched the propensity scores of 263 pairs of children. The propensity‐matched 30‐day mortality (95% CI) was similar: 17/263 (6.5%) with midazolam vs. 24/263 (9.1%) with propofol, p = 0.26. Weaning from mechanical ventilation of children sedated with midazolam was slower than weaning of children sedated with propofol, subhazard ratio (95% CI) 1.43 (1.18–1.73), p < 0.001.
Conventional testicular sperm extraction (TESE) and non‐obstructive azoospermia: is there still a chance in the era of microdissection TESE? Results from a single non‐academic community hospital
Authors: Saccà A. , Pastore A. L. , Roscigno M. , Naspro R. , Pellucchi F. , Fuschi A. , Maruccia S. , Territo A. , Pisano F. , Zanga L. , Capitanio E. , Carbone A. , Fusi F. , Chinaglia D. , Da Pozzo L. F.
Published: February 2016

Spermatozoa can be retrieved in non‐obstructive azoospermia (NOA) patients despite the absence of ejaculated spermatozoa in their semen because of the presence of isolated foci with active spermatogenesis. Conventional testicular sperm extraction (c‐TESE) in patients with NOA has been partially replaced by micro‐TESE. It is still under debate the problem regarding the higher costs related to micro‐TESE when compared with c‐TESE. In this study, we evaluated sperm retrieval rate (SRR) of c‐TESE in naive NOA patients. Sixty‐three NOA patients were referred to our centre for a c‐TESE. For every subject, we collected demographic data, cause of infertility, time to first infertility diagnosis, serum levels of LH, FSH, total testosterone and prolactin. A statistical analysis was conducted to correlate all the clinical variables, the histology and the Johnsen score with the SRR. Sixty‐three consecutive NOA patients with a mean age of 37.3 years were included. The positive SRR was 47.6%. No statistical differences were observed between positive vs. negative SRR regarding mean FSH (17.12 vs. 19.03 mUI/mL; p = 0.72), and LH (9.72 vs. 6.92 mUI/mL; p = 0.39) values. Interestingly, we found a statistically significant difference in terms of time to first infertility diagnosis (+SRR vs. −SRR; 44.5 vs. 57 months; p = 0.02) and regarding to age (+SSR vs. −SRR; 40.1 vs. 35.3; p = 0.04). There was a statistically significant decrease in SRRs with the decline in testicular histopathology from hypospermatogenesis to maturation arrest, and SCO. The mean Johnsen score was 5.9 with a mean percentage of Johnsen score ≥8 tubules equal to 19%. The overall pregnancy rate was 26.6%. In our prospective cohort of patients successful SRR with c‐TESE was 47.6%. Lower costs and high reproducibility of this technique still support this procedure as an actual reliable option in NOA patients for sperm retrieval.
Results from the National Perinatal Patient Safety Program in Sweden: the challenge of evaluation
Authors: Millde Luthander Charlotte , Källen Karin , Nyström Monica E. , Högberg Ulf , Håkansson Stellan , Härenstam Karin P. , Grunewald Charlotta
Published: February 2016

Introduction

We studied the effects of the national Perinatal Patient Safety Program in Sweden, addressing local improvement measures, changes in the proportion of low Apgar score and the number of settled injury claims due to asphyxia.

Material and methods

Final reports on achieved improvements from all Swedish obstetric units were analyzed and categories of the improvement measures taken in perinatal risk areas were established. Data on all term newborns during 2006–12 were obtained from the Medical Birth Registry. Incidence of 5‐min Apgar score <7 was analyzed before, during and after the intervention. The odds ratio for low Apgar score in period ÍII vs. period I was calculated. Patient injury claims from The Swedish National Patient Insurance Company (LÖF) were analyzed.

Results

Numerous local improvement initiatives were reported. The incidence of 5‐min Apgar score <7 on a national level remained unchanged during the study periods. The units with the highest rate of Apgar score <7 showed a significant decrease in Apgar score of 4–6 after the intervention, whereas units with the lowest rate of Apgar score <7 showed a significant increase in Apgar score <7 after the intervention. A decline in settled claims due to substandard care was observed (7.5%, 2012–14; p for trend 0.049).

Conclusion

The national incidence of low Apgar score remained unchanged but a reduction of settled claims of severely asphyxiated neonates was observed. The study highlights the need for robust designs when evaluating large‐scale initiatives for improving patient safety at delivery, along with the difficulties in performing them.
Bayesian Inference for Latent Biologic Structure With Determinantal Point Processes (DPP)
Authors: Xu Yanxun , Müller Peter , Telesca Donatello
Published: February 2016

We discuss the use of the determinantal point process (DPP) as a prior for latent structure in biomedical applications, where inference often centers on the interpretation of latent features as biologically or clinically meaningful structure. Typical examples include mixture models, when the terms of the mixture are meant to represent clinically meaningful subpopulations (of patients, genes, etc.). Another class of examples are feature allocation models. We propose the DPP prior as a repulsive prior on latent mixture components in the first example, and as prior on feature-specific parameters in the second case. We argue that the DPP is in general an attractive prior model for latent structure when biologically relevant interpretation of such structure is desired. We illustrate the advantages of DPP prior in three case studies, including inference in mixture models for magnetic resonance images (MRI) and for protein expression, and a feature allocation model for gene expression using data from The Cancer Genome Atlas. An important part of our argument are efficient and straightforward posterior simulation methods. We implement a variation of reversible jump Markov chain Monte Carlo simulation for inference under the DPP prior, using a density with respect to the unit rate Poisson process.
Sparse Estimation of Cox Proportional Hazards Models via Approximated Information Criteria
Authors: Su Xiaogang , Wijayasinghe Chalani S. , Fan Juanjuan , Zhang Ying
Published: February 2016

We propose a new sparse estimation method for Cox (1972) proportional hazards models by optimizing an approximated information criterion. The main idea involves approximation of the norm with a continuous or smooth unit dent function. The proposed method bridges the best subset selection and regularization by borrowing strength from both. It mimics the best subset selection using a penalized likelihood approach yet with no need of a tuning parameter. We further reformulate the problem with a reparameterization step so that it reduces to one unconstrained nonconvex yet smooth programming problem, which can be solved efficiently as in computing the maximum partial likelihood estimator (MPLE). Furthermore, the reparameterization tactic yields an additional advantage in terms of circumventing postselection inference. The oracle property of the proposed method is established. Both simulated experiments and empirical examples are provided for assessment and illustration.
Flap Dynamics in Aspartic Proteases: A Computational Perspective
Authors: Mahanti Mukul , Bhakat Soumendranath , Nilsson Ulf J. , Söderhjelm Pär
Published: February 2016

Recent advances in biochemistry and drug design have placed proteases as one of the critical target groups for developing novel small‐molecule inhibitors. Among all proteases, aspartic proteases have gained significant attention due to their role in HIV/AIDS, malaria, Alzheimer's disease, etc. The binding cleft is covered by one or two β‐hairpins (flaps) which need to be opened before a ligand can bind. After binding, the flaps close to retain the ligand in the active site. Development of computational tools has improved our understanding of flap dynamics and its role in ligand recognition. In the past decade, several computational approaches, for example molecular dynamics (MD) simulations, coarse‐grained simulations, replica‐exchange molecular dynamics (REMD) and metadynamics, have been used to understand flap dynamics and conformational motions associated with flap movements. This review is intended to summarize the computational progress towards understanding the flap dynamics of proteases and to be a reference for future studies in this field.
Retinal ganglion cell neuronal damage in diabetes and diabetic retinopathy
Authors: Ng Dorothy SK , Chiang Peggy PC , Tan Gavin , Cheung CM Gemmy , Cheng Ching‐Yu , Cheung Carol Y , Wong Tien Y , Lamoureux Ecosse L , Ikram Mohammad K
Published: February 2016

Background

To examine the association of diabetes and diabetic retinopathy (DR) with retinal ganglion cell (RGC) loss.

Design

Observational case–control study.

Participants

Type 2 diabetes cases and age‐gender matched controls without diabetes.

Methods

Spectral‐domain optical coherence tomography (OCT) parameters of RGCs were calculated after automated segmentation of macular scans. DR severity was graded on fundus photographs using the modified Airlie House Classification system. Generalized estimating equation was used to compare OCT parameters between cases and controls, adjusted for covariates.

Main Outcome Measures

Average ganglion cell‐inner plexiform layer (GC‐IPL) and average retinal nerve fibre layer (RNFL) thicknesses.

Results

We analyzed 227 cases and 227 controls. The mean age (years) of cases was 58.3 and controls was 58.1 (P = 0.13). Among cases, 101 had none, 25 had mild and 101 had moderate or severe DR. Compared with controls, GC‐IPL and RNFL were thinner in all cases [mean difference (95% confidence interval [CI]): GC‐IPL −4.49 µm (−2.92; −6.06), RNFL −0.93 µm (−0.09; −1.85)], including cases with no DR [mean difference (95% CI), GC‐IPL −4.37 µm (−2.72; −6.02), RNFL −1.06 µm (−0.10; −2.02)]. Cases with any DR had thinner GC‐IPL than controls [mean difference (95% CI): GC‐IPL −4.81 µm (−2.12; −7.50)]. Among cases, subjects with moderate or severe DR had thinner GC‐IPL than subjects with no DR [mean difference (95% CI): GC‐IPL −2.07 µm (−0.08; −4.07)].

Conclusions

RGC loss is present in subjects with diabetes and no DR, and is progressive in moderate or severe DR. RGC neuronal damage in diabetes and DR can be clinically detected using OCT.
Effects of white‐nose syndrome on regional population patterns of 3 hibernating bat species
Authors: Ingersoll Thomas E. , Sewall Brent J. , Amelon Sybill K.
Published: February 2016

Hibernating bats have undergone severe recent declines across the eastern United States, but the cause of these regional‐scale declines has not been systematically evaluated. We assessed the influence of white‐nose syndrome (an emerging bat disease caused by the fungus Pseudogymnoascus destructans, formerly Geomyces destructans) on large‐scale, long‐term population patterns in the little brown myotis (Myotis lucifugus), the northern myotis (Myotis septentrionalis), and the tricolored bat (Perimyotis subflavus). We modeled population trajectories for each species on the basis of an extensive data set of winter hibernacula counts of more than 1 million individual bats from a 4‐state region over 13 years and with data on locations of hibernacula and first detections of white‐nose syndrome at each hibernaculum. We used generalized additive mixed models to determine population change relative to expectations, that is, how population trajectories differed with a colony's infection status, how trajectories differed with distance from the point of introduction of white‐nose syndrome, and whether declines were concordant with first local observation of the disease. Population trajectories in all species met at least one of the 3 expectations, but none met all 3. Our results suggest, therefore, that white‐nose syndrome has affected regional populations differently than was previously understood and has not been the sole cause of declines. Specifically, our results suggest that in some areas and species, threats other than white‐nose syndrome are also contributing to population declines, declines linked to white‐nose syndrome have spread across large geographic areas with unexpected speed, and the disease or other threats led to declines in bat populations for years prior to disease detection. Effective conservation will require further research to mitigate impacts of white‐nose syndrome, renewed attention to other threats to bats, and improved surveillance efforts to ensure early detection of white‐nose syndrome.
Genetic diversity and population structure of Raffaelea quercus‐mongolicae, a fungus associated with oak mortality in South Korea
Authors: Kim M.‐S. , Hohenlohe P. A. , Kim K.‐H. , Seo S.‐T. , Klopfenstein N. B.
Published: February 2016

Raffaelea quercus‐mongolicae is a fungus associated with oak wilt and deemed to cause extensive oak mortality in South Korea. Since the discovery of this fungus on a dead Mongolian oak (Quercus mongolica) in 2004, the mortality continued to spread southwards in South Korea. Despite continued expansion of the disease and associated significant impacts on forest ecosystems, information is lacking about the origin and genetic diversity of R. quercus‐mongolicae. Restriction‐site‐associated DNA (RAD) sequencing was used to assess genetic diversity and population structure among five populations (provinces) of R. quercus‐mongolicae in South Korea. In total, 179 single nucleotide polymorphisms (SNPs) were identified among 2,639 RAD loci across the nuclear genome of the 54 R. quercus‐mongolicae isolates (0.0012 SNPs per bp), which displayed an overall low expected heterozygosity and no apparent population structure. The low genetic diversity and no apparent population structure among South Korean populations of this ambrosia beetle‐vectored fungus support the hypothesis that this fungus was introduced to South Korea.
Season of diagnosis is associated with overall survival in patients with diffuse large B‐cell lymphoma but not with Hodgkin's lymphoma – A population‐based Swedish Lymphoma Register study
Authors: Székely Elisabeth , Lindén Ola , Peterson Stefan , Jerkeman Mats
Published: February 2016

Objective and methods

The aim of this study was to investigate the effect of season of diagnosis on the outcome of patients with diffuse large B‐cell lymphoma (DLBCL) and Hodgkin lymphoma (HL). In this study, we included curatively treated DLBCL (n = 5875) and HL (n = 1693) patients, diagnosed between 2000 and 2011, based on data from the Swedish Lymphoma Register.

Results

Overall survival was significantly better for patients diagnosed with DLBCL during the summer months, but not for patients diagnosed with HL. The difference remained in a multivariable analysis adjusted for age, stage, performance status, number of extra nodal sites and year of diagnosis (HR 1.08; 95% CI 1.02–1.14, P = 0.0069). When analyzing the DLBCL patients according to gender in the multivariable model, the effect of season was shown to be restricted to male patients (HR = 1.09, 95% CI 1.01–1.17, P = 0.0269.

Conclusions

In summary, season of diagnosis was shown to have impact on overall survival in male patients with DLBCL. Possible explanations of our results are the higher vitamin D level during the summer months, the effects of sunlight on the circadian rhythm and the immune system, or the lower risk of infectious disease during the summer. Further investigations are needed to explore these hypotheses.