bluuebunny/crossref_metadata_2025 huggingface dataset:
Accelerated Epigenetic Ageing in Major Depressive Disorder
Authors: Whalley Heather C , Gibson Jude , Marioni Riccardo , Walker Rosie M , Clarke Toni-Kim , Howard David M , Adams Mark J , Hall Lynsey , Morris Stewart , Deary Ian J , Porteous David ,   23andMe Research Team,   Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, Evans Kathryn L , McIntosh Andrew M
Published: October 2017

Background

Major depressive disorder (MDD) is a severe, heritable psychiatric disorder associated with shortened lifespan and comorbidities of advancing age. It is unknown however whether MDD is associated with accelerated biological ageing relative to chronological age. This hypothesis was tested using the epigenetic clock as a measure of biological age.

Methods

To address the main hypothesis, using peripheral blood, we derived measures of Epigenetic Age Acceleration (EAA) in 3,833 controls and 1,219 MDD cases based on Hannum and Horvath epigenetic clocks in Generation Scotland (GS:SFHS, mean age 48 years, std dev 14.5). Models controlled for relatedness, sex, cell counts, and processing batch (basic model), as well as additional covariates of smoking and drinking status, and body mass index (BMI) (full models).

Results

Accelerated epigenetic ageing was found in MDD cases versus controls using the Horvath clock (β=0.0804, p=0.012 equivalent to 0.20 years) in both the basic and full models. Significant MDD*age interactions indicated greatest effects at younger age ranges. No significant differences were observed for the Hannum clock. BMI was the only additional covariate found to attenuate the relationship between EAAHorvathand MDD. Further, genetic correlation analysis indicated significant overlap in the genetic aetiology of EAAHorvathwith BMI (rG=0.20, p=0.03), between MDD with BMI (rG=0.10, p=9.86×10−6), but not between EAAHorvathand MDD (rG=0.14, p=0.125). Mediation analysis indicated partial mediation of the relationship between EAAHorvathand depression status through BMI (β =0.0028; p=0.0248, ~13%).

Conclusion

These data imply that accelerated biological ageing is associated with MDD and partially mediated through BMI.
runibic: a Bioconductor package for parallel row-based biclustering of gene expression data
Authors: Orzechowski Patryk , Pańszczyk Artur , Huang Xiuzhen , Moore Jason H.
Published: October 2017

Motivation

Biclustering (called also co-clustering) is an unsupervised technique of simultaneous analysis of rows and columns of input matrix. From the first application to gene expression data, multiple algorithms have been proposed. Only a handful of them were able to provide accurate results and were fast enough to be suitable for large-scale genomic datasets.

Results

In this paper we introduce a Bioconductor package with parallel version of UniBic biclustering algorithm: one of the most accurate biclustering methods that have been developed so far. For the convenience of usage, we have wrapped the algorithm in an R package calledrunibic. The package includes: (1) a couple of times faster parallel version of the original sequential algorithm,(2) muchmore efficient memory management, (3) modularity which allows to build new methods on top of the provided one, (4) integration with the modern Bioconductor packages such asSummarizedExperiment,ExpressionSetandbiclust.

Availability

The package is implemented in R (3.4) and will be available in the new release of Bioconductor (3.6). Currently it could be downloaded from the following URL:http://github.com/athril/runibic/

Contact

patryk.orzechowski@gmail.com,jhmoore@upenn.edu

Supplementary information

Supplementary informations are available in vignette of the package.
An empirical test of the temperature dependence of carrying capacity
Authors: Bernhardt Joey R. , Sunday Jennifer M. , O’Connor Mary I.
Published: October 2017

Predicting population persistence and dynamics in the context of global change is a major challenge for ecology. A widely held prediction is that population abundance at carrying capacity decreases with warming, assuming no change in resource supply, due to increased individual resource demands associated with higher metabolic rates. However, this prediction, which is based on metabolic scaling theory (MST), has not been tested empirically. Here we experimentally tested whether effects of temperature on short-term metabolic performance (rates of photosynthesis and respiration) translate directly to effects of temperature on population rates in a phytoplankton species. We found that effects of temperature on organismal metabolic rates matched theoretical predictions, and that the temperature dependence of individual metabolic performance translated to population abundance. Population abundance at carrying capacity,K, decreased with temperature less than expected based on the temperature dependence of photosynthesis. Concurrent with declines in abundance, we observed a linear decline in cell size of approximately 2.3% °C−1, which is consistent with broadly observed patterns in unicellular organisms, known as the temperature-size rule. When theoretical predictions include higher densities allowed by shifts toward smaller individual size, observed declines inKwere quantitatively consistent with theoretical predictions. Our results indicate that outcomes of population dynamics across a range of temperatures reflect organismal responses to temperature via metabolic scaling, providing a general basis for forecasting population responses to global change.
Sharing genetic admixture and diversity of public biomedical datasets
Authors: Harismendy Olivier , Kim Jihoon , Xu Xiaojun , Ohno-Machado Lucila
Published: October 2017

Genetic ancestry and admixture are critical co-factors to study phenotype-genotype associations using cohorts of human subjects. Most publically available molecular datasets – genomes, exomes or transcriptomes - are however missing this information or only share self-reported ancestry. This represents a limitation to identify and re-purpose datasets to investigate the contribution of race and ethnicity to diseases and traits. we propose an analytical framework to enrich the meta-data from publically available cohorts with admixture information and a resulting diversity score at continental resolution, calculated directly from the data. We illustrate the utility and versatility of the framework using The Cancer Genome Atlas datasets indexed and searched through the DataMed Data Discovery Index. Data repositories or data contributors can use this framework to provide, as metadata, admixture for controlled access datasets, minimizing the work involved in requesting a dataset that may ultimately prove inadequate for a researcher’s purpose. With the increasingly global scale of human genetics research, research on disease risk and susceptibility would benefit greatly from the adequate estimation and sharing of admixture data following a framework such as the one presented.
Ustekinumab treatment of pityriasis rubra pilaris: A report of five cases
Authors: Napolitano Monica , Lembo Luigi , Fania Luca , Abeni Damiano , Didona Dario , Didona Biagio
Published: October 2017

Pityriasis rubra pilaris (PRP) is a rare, chronic, inflammatory skin disease of unknown etiology. Patients refractory to conventional therapies have been treated successfully with biologic drugs such as anti‐tumor necrosis factor agents. Recently, a role of the interleukin‐23/T‐helper 17 axis in PRP has been described. Our objective was to assess the effectiveness of ustekinumab in five patients with adult‐onset PRP refractory to conventional therapies. In the present study, four patients had type I and one patient type II adult‐onset PRP. They were treated with three s.c. doses of ustekinumab at weeks 0, 4 and 16. Clinical response was evaluated monthly during treatment up to a 15‐month follow‐up period. All patients promptly showed a decrease in erythema, follicular hyperkeratosis and scaling. After three injections, complete remission of skin lesions was achieved in four out of five cases and a significant clinical improvement was shown in one case. To the best of our knowledge, this is the largest case series reported on ustekinumab treatment in PRP. Our results, in addition to previous studies from other groups, suggest that ustekinumab may be a possible first‐line treatment for PRP patients refractory to conventional therapies.
PARENTHOOD AS A TURNING POINT IN THE LIFE COURSE FOR MALE AND FEMALE GANG MEMBERS: A STUDY OF WITHIN‐INDIVIDUAL CHANGES IN GANG MEMBERSHIP AND CRIMINAL BEHAVIOR
Authors: PYROOZ DAVID C. , MCGLOIN JEAN MARIE , DECKER SCOTT H.
Published: October 2017

The impact of parenthood on leaving a street gang is not well understood. This is likely because researchers in prior studies have not accounted for multiple dimensions of gang exit, possible gender differences, and potential selection bias. In this study, we use a sample of 466 male and 163 female gang members from the National Longitudinal Study of Youth 1997 to consider the within‐individual relationship between changes in parenthood and changes in claiming gang membership and offending. These data offer the opportunity to consider gender differences and birth parity (i.e., first or second child). The results from a series of fixed‐effects models reveal that motherhood is associated with enduring reductions in both the odds of claiming gang membership and the rate of offending, whereas fatherhood has a temporary beneficial impact on gang membership and offending only for those fathers who reside with their children. In most cases, the beneficial effect of having a child rests in becoming a parent for the first time. On the whole, our study findings demonstrate that parenthood serves as a turning point for a particular group of noteworthy offenders—gang members.
Congested bile can predict the outcomes of endoscopic stenting for hilar biliary malignancies
Authors: Xia Ming Xing , Sun Bo , Xing Ling , Gao Dao Jian , Ye Xin , Wu Jun , Wang Tian Tian , Hu Bing
Published: October 2017

OBJECTIVE

Endoscopic management of malignant hilar biliary obstruction (MHBO) remains challenging, with relatively poor jaundice control and high infectious risk. The factors that affect the outcome of endoscopic therapy are still unclear. This retrospective cohort study aimed to investigate predictive factors for the outcomes of biliary stenting in patients with MHBO.

METHODS

Between June 2015 and June 2016, consecutive patients with MHBO who received primary endoscopic stenting and completed follow‐up at our institution were identified and evaluated. All patients received full aspiration of congested bile followed by plastic or metal stent(s) placement. Clinical success was achieved in patients whose total serum bilirubin decreased by over two‐thirds in a month.

RESULTS

A total of 64 patients were included. Among them, 28 received a single stent placement and 36 received multiple stent placements. Altogether 53 (82.8%) patients attained clinical success and 48 (75.0%) underwent re‐interventions within 6 months. Multivariate analyses showed that only a total bile volume of ≥30 mL aspirated from the intrahepatic ducts predicted clinical success (OR 6.83, 95% CI 1.2–38.4, P = 0.029), absence of early post‐endoscopic retrograde cholangiopancreatography cholangitis (OR 0.03, 95% CI 0.004–0.36, P = 0.001), and lack of re‐intervention within 6 months (HR 0.10, 95% CI 0.05–0.22, P < 0.001) after initial endoscopic stenting.

CONCLUSION

The volume of congested bile may effectively predict treatment outcomes of endoscopic stenting for MHBO and guide the therapeutic strategy.
Contemporary salvage post prostatectomy radiotherapy: Early implementation improves biochemical control
Authors: Kneebone Andrew , Hruby George , Harris Georgia , Rasiah Kris , Vass Justin , Whalley Deborah , McCloud Philip , Louw Sandra , Guo Linxin , Eade Thomas
Published: October 2017

Introduction

The optimal time to commence salvage radiotherapy (SRT) for a rising PSA post radical prostatectomy is not known. We wished to assess the impact of index PSA (iPSA) level prior to SRT on rates of biochemical failure (BCF) post treatment.

Methods

Patients referred to our institution for SRT for a rising PSA post surgery were accrued onto a prospective database. Baseline demographic data, tumour and treatment factors were collected including pathologic T and N stage, margin status, Gleason score (GS), lymphovascular space invasion (LVSI), use of androgen deprivation therapy (ADT) and time from surgery to salvage radiotherapy. Our endpoint was time to BCF.

Results

Between January 2008 and December 2013, 189 patients received SRT to a mean dose of 69.8 Gy in 34 fractions using Intensity Modulated Radiotherapy (IMRT). Median follow‐up was 50 months. For patients with an iPSA of <0.2 ng/mL (n = 92), iPSA ≥ 0.2 to <1.0 ng/mL (n = 75) and ≥ 1.0 ng/mL (n = 22), rates of BCF at 5 years were 28.3%, 44.3% and 73.7% respectively. Compared to the iPSA <0.2 ng/mL group, the hazard ratios for time to BCF for an iPSA ≥ 0.2 to <1.0 ng/mL was 1.73 (P = 0.05) and >1.0 ng/mL was 3.1 (P = 0.002). Factors predicting time to BCF on univariate analysis included iPSA, GS, T stage, PSA nadir post surgery and LVSI. On multivariate analysis, GS, iPSA, use of ADT, T stage, PSA post surgery nadir and margin status remained significant.

Conclusion

Rising iPSA levels are associated with an increasing risk of biochemical failure after adjusting for known prognostic factors and early salvage post prostatectomy radiotherapy is recommended.
The APEX trial: Effects of allopurinol on exercise capacity, coronary and peripheral endothelial function, and natriuretic peptides in patients with cardiac syndrome X
Authors: Lim Tiong Keng , Noman Awson , Choy Anna Maria J , Khan Faisel , Struthers Allan D , Lang Chim C
Published: October 2017

The role of endothelial dysfunction and oxidative stress in the pathogenesis of cardiac syndrome X has recently been recognized. Allopurinol has previously been shown to improve endothelial dysfunction, reduce oxidative stress burden, and improve myocardial efficiency. In this “proof of concept” study, we investigated the effect of allopurinol on exercise capacity, coronary and peripheral endothelial function, and serum B‐type natriuretic peptide (BNP: a marker of cardiac function and myocardial ischemia) in patients with cardiac syndrome X.

Methods and Results

This study was a randomized, double‐blind, placebo‐control crossover trial. Nineteen patients (mean age 59 ± 10 years, 11 women and 8 men) with cardiac syndrome X were randomized to a 6‐week treatment with either allopurinol (600 mg/day) or placebo. After 4 weeks of washout period, they were crossed over to the other arm. Outcomes measured at baseline and after treatment were maximum exercise time (ET) derived from Bruce protocol exercise treadmill test, serum BNP measurement, coronary flow reserve (CFR) as assessed by measuring the response of flow velocity in the left anterior descending artery to adenosine, and flow‐mediated vasodilatation of the brachial artery (FMD). Allopurinol significantly reduced serum uric acid levels when compared with placebo (−48 ± 24% vs 1.9 ± 11%, P < .001). There was no significant difference in maximum ET, CFR, and FMD between allopurinol and placebo. However, there was a trend that allopurinol reduced serum BNP when compared to placebo (−8% [interquartile range −22% to 65%] vs 44% [interquartile range −18% to 140%]; P = .07).

Conclusion

In patients with cardiac syndrome X, high‐dose allopurinol did not improve exercise capacity, and coronary or peripheral endothelial function.
A new resource for examining and responding to the contexts of alcohol‐related harm
Authors: Giesbrecht Norman
Published: October 2017

Commentary to: All drinking is not equal: how a social practice theory lens could enhance public health research on alcohol and other health behaviours
Impacts of voluntary and involuntary workforce transitions at mature ages: Longitudinal evidence from HILDA
Authors: Gong Cathy Honge , Kendig Hal
Published: October 2017

Objective

To assess the changes in health, well‐being and welfare dependency associated with yearly workforce transitions from working to not working among people aged 45–64 years.

Methods

Transition analysis of the nationally representative longitudinal data from the Household Incomes and Labour Dynamics in Australia survey 2002–2011.

Results

People who voluntarily left paid work had reasonable control over their situations, and their satisfaction remained relatively stable even with deteriorating health and increasing welfare dependency. Those who involuntarily left paid work had less control and preparedness, and they experienced significant decreases in their satisfaction with life overall, finances and health; they were also more likely to be psychologically distressed, welfare dependent and had a higher probability to return to paid work.

Conclusion

Voluntary and involuntary workforce transitions have different impacts on health and well‐being. Enabling mature aged workers to work longer can yield benefits for both individual well‐being and government budgets.
Risk of bowel obstruction during in vitro fertilization treatment of patients with deep infiltrating endometriosis
Authors: Seyer‐Hansen Mikkel , Egekvist Anne , Forman Axel , Riiskjær Mads
Published: October 2017

Introduction

Women with endometriosis often experience pain and infertility. Medical treatment interferes with the possibility of attaining pregnancy. For infertile women with endometriosis, surgery is a possible treatment, but with advanced disease there is an increased risk of serious complications. With only limited pain, women will often be referred for in vitro fertilization treatment instead. The disease is estrogen‐dependent and during in vitro fertilization treatment the women could theoretically experience worsening of their symptoms.

Material and methods

The study is a retrospective cohort study of 76 women with bowel endometriosis who were treated conservatively and underwent in vitro fertilization treatment.

Results

Nine (11.8%) of the women experienced severe worsening of their bowel‐related symptoms, including two patients presenting with colon ileus. One additional woman had no previous diagnosis of endometriosis before she presented with subocclusion of the bowel during in vitro fertilization. In all cases the in vitro fertilization treatment was stopped.

Conclusions

Our study revealed that bowel endometriosis increases the risk of complications during in vitro fertilization treatment. This is in contrast to several publications. However, our study population is different due to the fact that none of these women had previous operations for bowel endometriosis. In all, 88% of the women completed fertility treatment without need for surgery.
Dangerous life at the edge: Implications of seed predation for roadside revegetation
Authors: Suárez‐Esteban Alberto , Delibes Miguel , Fedriani José M.
Published: October 2017

Question

Anthropogenic edges caused by transport infrastructure such as dirt roads and trails (also known as Soft Linear Developments; SLD) are pervasive in almost every terrestrial ecosystem. Revegetating these edges may reduce some of their negative effects, such as their permeability to biological invasions and detrimental effects on wildlife, potentially becoming suitable habitat for a broad range of species. Selecting species with low post‐dispersal seed predation rates may improve the effectiveness of revegetation programmes.

Location

Mediterranean scrublands in SW Spain.

Methods

We made offerings of a total of 16,000 seeds of eight species of fleshy‐fruit shrubs both along SLD edges and scrubland interiors in two independent blocks in each of three distant locations. Using four types of selective enclosure, we assessed the relative contribution of three seed predator guilds (ants, rodents and birds) to seed predation rates both along SLD edges and scrubland interiors.

Results

The effects of anthropogenic edges on seed predation rates were species‐specific. The large and hard‐seeded species Chamaerops humilis was not predated at all. Juniperus phoenicea and Corema album seeds had higher predation rates in scrubland interiors than in edges. The small‐seeded Rubus ulmifolius experienced relatively low seed predation rates compared to the other species. Predation rates for this species were higher along SLD edges than in scrubland interiors. Ants were the main seed predators in the area, and showed marked preferences for J. macrocarpa and C. album seeds at both SLD edges and scrubland interiors.

Conclusions

Our results show the strong context‐dependency of seed predation rates in both SLD edges and scrubland interiors, and thus the importance of well spatially and temporally replicated studies. Species with large and hard seeds may be good candidates for roadside revegetation programmes. However, the relative suitability of plant species would depend on the seed predator community. Our findings confirm that studies on seed predation may help planning cost‐effective species selection for edge revegetation efforts worldwide.
3D‐QSAR, molecular docking, and ONIOM studies on the structure–activity relationships and action mechanism of nitrogen‐containing bisphosphonates
Authors: Liu Qing‐Zhu , Wang Shan‐Shan , Li Xi , Zhao Xue‐Yu , Li Ke , Lv Gao‐Chao , Qiu Ling , Lin Jian‐Guo
Published: October 2017

Nitrogen‐containing bisphosphonates (N‐BPs) have been used widely to treat various bone diseases by inhibiting the key enzyme farnesyl pyrophosphate synthase (FPPS) in the mevalonate pathway. Understanding the structure–activity relationships and the action mechanisms of these bisphosphonates is instructive for the design and the development of novel potent inhibitors. Here, a series of N‐BPs inhibitors of human FPPS (hFPPS) were investigated using a combination of three‐dimensional quantitative structure–activity relationship (3D‐QSAR), molecular docking, and three‐layer ONIOM studies. The constructed 3D‐QSAR model yielded a good correlation between the predicted and experimental activities. Based on the analysis of comparative molecular field analysis (CoMFA) contour maps, a series of novel N‐BPs inhibitors were designed and ten novel potent N‐BPs inhibitor candidates were screened out. Molecular docking and ONIOM (B3LYP/6‐31 + G*:PM6:Amber) calculations revealed that the inhibitors bound to the active site of hFPPS via hydrogen‐bonding interactions, hydrophobic interactions, and cation‐π interactions. Six novel N‐BPs inhibitors with better biological activities and higher lipophilicity were further screened out from ten candidates based on the calculated interaction energy. This study will facilitate the discovery of novel N‐BPs inhibitors with higher activity and selectivity.
Insights on Social Behavior From Studying Williams Syndrome
Authors: Sampaio Adriana , Belsky Jay , Soares Isabel , Mesquita Ana , Osório Ana , Gonçalves Óscar F.
Published: October 2017

Central to the developmental psychopathology perspective is the claim that studying normal and atypical development are related. In this article, we argue that studying a naturally occurring genetic condition—Williams syndrome—provides insight into social behavior in typically developing children. Toward this end, we describe the social phenotype of Williams syndrome, then offer three insights regarding biological and environmental factors that account for variability in social behavior in individuals who are developing typically and individuals with the syndrome. In so doing, we illuminate genetic, neural, and environmental processes that likely influence typical social development as informed by Williams syndrome.
A Life at the Intersection of Science and Social Issues
Authors: Huston Aletha C.
Published: October 2017

In this article, I summarize a lifetime of research investigating the socializing effects of contexts outside the family, specifically television, gender‐role expectations, child care, poverty, and public policy. The themes running throughout this work are (a) understanding processes underlying associations of behavior with social and environmental conditions, (b) understanding positive development as well as problem behavior, (c) questioning social values and implicit assumptions in research and policy, and (d) taking a truly interdisciplinary approach. My goals include generating knowledge and applying these themes to policy and practice. I conclude that researchers need to be prepared with good evidence when the policy windows open.
Guillain–Barré syndrome initially manifesting as motor weakness, urinary dysfunction and hyperreflexia: Case report and literature review
Authors: Oji Satoru , Narukawa Shinya , Ishizuka Keita , Sugimoto Kohei , Yoshida Norihito , Takeshita Hideki , Kaida Ken‐ichi , Nomura Kyoichi
Published: October 2017

Background

Guillain–Barré syndrome (GBS) is an acute inflammatory neuropathy characterized by areflexic quadriparesis. Urinary dysfunction has been known to occur in approximately 25% of GBS patients during the clinical course and usually emerges during peak motor weakness. According to the diagnostic criteria for GBS, bladder dysfunction at onset makes the diagnosis of GBS rather doubtful. We report here a rare case of GBS that initially manifested as motor weakness with urinary dysfunction and hyperreflexia.

Case presentation

A 66‐year‐old Japanese man experienced mild weakness in his hands that extended to the entire upper extremities the following day. At the same time, he started experiencing difficulty voiding. On the fourth day after the onset of weakness, he was admitted to Saitama Medical Center, Kawagoe, Japan, because of an inability to stand up without support. Neurological examination revealed moderate generalized weakness, hyperreflexia, and poor urinary volume and flow. Early in hospitalization, his deep tendon reflexes gradually decreased and ultimately he became areflexic. A nerve conduction study indicated the axonal form of GBS. He was treated with immunoadsorption plasmapheresis, followed by two sessions of intravenous immunoglobulin G treatment. The motor weakness and urinary dysfunction gradually ameliorated, and he was discharged and transferred for rehabilitation on hospital day 47.

Conclusions

The present case suggests that urinary dysfunction in GBS might not necessarily occur during peak motor weakness, but could start at onset. Physicians should consider GBS in differential diagnosis of patients presenting with initial symptoms of motor weakness and urinary dysfunction.
Ciprofloxacin vs levofloxacin for prophylaxis during hematopoietic stem‐cell transplantation
Authors: Copeland Vanessa , McLaughlin Milena , Trifilio Steven
Published: October 2017

The objective of the current retrospective study was to compare differences in rate of breakthrough infections for ciprofloxacin vs levofloxacin prophylaxis in autologous hematopoietic stem‐cell transplant (HSCT) patients treated for multiple myeloma. This was a retrospective, cohort study comparing autologous HSCT recipients treated for multiple myeloma who received ciprofloxacin prophylaxis vs levofloxacin prophylaxis. A total of 297 patients, 143 levofloxacin‐ and 154 ciprofloxacin‐treated were included. There was a significantly higher incidence of bloodstream infections in the ciprofloxacin group (24/154) compared to the levofloxacin group (10/143), P = .03, primarily caused by a statistically higher incidence of gram‐positive bloodstream infections (ciprofloxacin [21/154] vs levofloxacin [8/143]; P < .01). Clinically relevant differences exist between fluoroquinolone agents used for prophylaxis. Levofloxacin prophylaxis was more effective than ciprofloxacin prophylaxis to reduce the incidence of bloodstream infections in this study.
Usefulness of semiquantitative PCR‐Invader assay for selecting candidates for daclatasvir plus asunaprevir combination therapy among patients with hepatitis C virus genotype 1b
Authors: Honda Koichi , Seike Masataka , Oribe Junya , Endo Mizuki , Arakawa Mie , Tokoro Masanori , Iwao Masao , Mori Tetsu , Nishimura Junko , Takahashi Yukou , Omori Kaoru , Yamashita Tsutomu , Muro Toyokichi , Murakami Kazunari
Published: October 2017

Aims

PCR‐Invader is a highly sensitive assay for detecting non‐structural protein 5A (NS5A) resistance‐associated variants (RAVs) of hepatitis C virus (HCV). Here, we validated the accuracy of the semiquantitative PCR‐Invader (SQ‐PI) assay compared to direct sequencing (DS) for identifying NS5A RAVs, and we evaluated the treatment efficacy of daclatasvir plus asunaprevir (DCV + ASV) for patients judged to be non‐positive for NS5A RAVs by SQ‐PI.

Methods

Detection rates of NS5A RAVs by SQ‐PI and DS were compared for 204 patients with HCV genotype 1b. Patients with non‐positive results for NS5A RAVs by SQ‐PI were treated by DCV + ASV, and the efficacy of this treatment was examined.

Results

All samples judged as negative for NS5A RAVs by SQ‐PI were similarly judged by DS. However, 29.7% of samples judged as negative for Y93H by DS were judged as weakly positive or positive by SQ‐PI. Among 108 patients who were judged as negative by SQ‐PI and treated by DCV + ASV, rates of sustained virologic response at 24 weeks (SVR24) were 96.3% in intention‐to‐treat analysis and 99.0% in patients who completed treatment. Among patients who were weakly positive for Y93H on SQ‐PI, the SVR24 rate was 95.0% (19/20). This rate was 100% (78/78) in patients who were negative for Y93H on SQ‐PI and completed treatment.

Conclusion

Treatment efficacy of DCV + ASV was extremely high among patients who were non‐positive for NS5A RAVs on SQ‐PI, especially for patients with negative results.
Three Citrus flavonoids retard the digestion of starch and its working mechanisms
Authors: Luo Fang , Liu Xia , She Yin , Gao Wanru
Published: October 2017

In this work, the effects of three Citrus flavonoids (naringin, neohesperidin and hesperidin) on α‐amylase catalysed starch digestion were investigated. An inhibitory kinetics experiment demonstrated that they noncompetitively inhibit the activity of α‐amylase with Ki values of, respectively, 25.21 μm, 40.26 μm, 40.69 μm. Surface plasmon resonance assay showed three Citrus flavonoids can bind with starch with KD values of, respectively, 3.98 ± 0.20 mm, 4.92 ± 0.15 mm and 5.07 ± 0.17 mm. Scanning electron microscopy indicated they can delay the retrogradation of starch. The results of 1, 1‐diphenyl‐2‐picryl hydrazyl radical assay indicate that the antioxidant activities of three Citrus flavonoids are significantly decreased by interacting with starch. These results illustrated three Citrus flavonoids that retard the digestion of starch not only through interaction with α‐amylase, but also through interaction with starch.
Effect of pulsed ultrasound treatment compared to continuous mode on microbiological and quality of Mirabelle plum during postharvest storage
Authors: Hashemi Seyed Mohammad Bagher
Published: October 2017

The effects of pulsed and continuous ultrasound treatment on microbiological and physiological quality of Mirabelle plum fruit were investigated. Freshly harvested Mirabelle plum was treated with 30‐kHz pulsed and continuous ultrasound at 20 °C for 0, 15, 30, 45 and 60 min and subsequently stored at 4 °C for 10 days. The total count of bacteria, total fungi, decay index, titratable acidity (TA), total soluble solids (TSS), colour, texture, ascorbic acid content and total phenolics was measured. The results showed that pulsed and continuous ultrasonic treatment significantly (P < 0.05) reduced the number of microorganisms and improved the quality of Mirabelle plums during storage. Increasing pretreatment time enhanced the positive effects of pulsed and continuous ultrasound. Also, in terms of the total count of bacteria, total fungi, titratable acidity and total phenolics, the pulsed and continuous ultrasound did not show a significant difference (P < 0.05). However, pulsed ultrasound was better compared to continuous mode in preservation of TSS, colour, texture and ascorbic acid content of the fruit during storage. Our results demonstrated that pulsed ultrasound is an appropriate method for improving safety and maintaining the quality of Mirabelle plum fruit.
Effects of calcium and zinc ions injection on caspase‐3 activation and tenderness in post‐mortem beef skeletal muscles
Authors: Huang Feng , Ding Zhenjiang , Zhang Chunjiang , Hu Honghai , Zhang Liang , Zhang Hong
Published: October 2017

This study was designed to investigate the effects of Ca2+ and Zn2+ ions injection on post‐mortem tenderness and caspase activation by examining the expression of caspase‐3 and cytochrome c in post‐mortem beef skeletal muscles treated with Ca2+ and Zn2+. Results showed that Ca2+ ions injection accelerated post‐mortem tenderisation of beef skeletal muscles, whereas Zn2+ retarded the process. In the Ca2+‐injected samples, the level of caspase‐3 precursor decreased markedly without the production of activated caspase‐3, whereas the level of cytochrome c was increased markedly. So, Ca2+ possibly promoted caspases activation upstream of cytochrome c release, but inactivated caspase activity by calpain and/or fast depletion of ATP; whereas Zn2+ blocked the activation of procaspase‐3 with no visible change in the level of cytochrome c, and the block possibly resulted from its direct inhibition on caspase‐3 enzyme.
EVOLVE: The Australian Rheumatology Association’s ‘top five’ list of investigations and interventions doctors and patients should question
Authors: Morrisroe Kathleen , Nakayama Ayano , Soon Jason , Arnold Mark , Barnsley Les , Barrett Claire , Brooks Peter M. , Hall Stephen , Hanrahan Patrick , Hissaria Pravin , Jones Graeme , Katikireddi Veera S. , Keen Helen , Laurent Rodger , Nikpour Mandana , Poulsen Katherine , Robinson Philip , Soden Muriel , Wood Nigel , Cook Nicola , Hill Catherine , Buchbinder Rachelle
Published: October 2017

Background

The EVOLVE (evaluating evidence, enhancing efficiencies) initiative aims to drive safer, higher‐quality patient care through identifying and reducing low‐value practices.

Aims

To determine the Australian Rheumatology Association’s (ARA) ‘top five’ list of low‐value practices.

Methods

A working group comprising 19 rheumatologists and three trainees compiled a preliminary list. Items were retained if there was strong evidence of low value and there was high or increasing clinical use and/or increasing cost. All ARA members (356 rheumatologists and 72 trainees) were invited to indicate their ‘top five’ list from a list of 12‐items through SurveyMonkey in December 2015 (reminder February 2016).

Results

A total of 179 rheumatologists (50.3%) and 19 trainees (26.4%) responded. The top five list (percentage of rheumatologists, including item in their top five list) was: Do not perform arthroscopy with lavage and/or debridement for symptomatic osteoarthritis of the knee nor partial meniscectomy for a degenerate meniscal tear (73.2%); Do not order anti‐nuclear antibody (ANA) testing without symptoms and/or signs suggestive of a systemic rheumatic disease (56.4%); Do not undertake imaging for low back pain for patients without indications of an underlying serious condition (50.8%); Do not use ultrasound guidance to perform injections into the subacromial space as it provides no additional benefit in comparison to landmark‐guided injection (50.3%) and Do not order anti‐double‐stranded DNA antibodies in ANA negative patients unless the clinical suspicion of systemic lupus erythematosus remains high (45.3%).

Conclusions

This list is intended to increase awareness among rheumatologists, other clinicians and patients about commonly used low‐value practices that should be questioned.
Deep‐red photoluminescence and long persistent luminescence in double perovstkite‐type La2MgGeO6:Mn4+
Authors: Zhang Xiaowen , Nie Jianmin , Liu Shanshan , Li Yang , Qiu Jianrong
Published: October 2017

A novel non‐rare‐earth doped phosphor La2MgGeO6:Mn4+ (LMG:Mn4+) with near‐infrared (NIR) long persistent luminescence (LPL) was successfully synthesized by solid‐state reaction. The phosphors can be effectively excited using ultraviolet light, followed by a sharp deep‐red emission peaking at 708 nm, which is originated from 2Eg → 4A2g transition of Mn4+ ions. The luminescent performance was analyzed by photoluminescence (PL) and photoluminescence excitation (PLE) spectra. The crystal field parameters were calculated to describe the environment of Mn4+ in LMG host. The LPL behaviors as well as the mechanisms were systematically discussed. This study suggests that the phosphors will broaden new horizons in designing and fabricating novel NIR long phosphorescent materials.
Synthesis and microwave dielectric properties of new high quality Mg2NdNbO6 ceramics
Authors: Zhang Shaobo , Shi Liwei , Zhang Lanyang , Zhu Haiyan , Xia Wangsuo
Published: October 2017

New high‐quality microwave dielectric ceramics Mg2NdNbO6 were prepared by conventional solid‐state sintering method. The phases, micro‐structures and microwave dielectric properties of Mg2NdNbO6 ceramics were investigated at sintering temperature in the range of 1275°C‐1400°C. The X‐ray diffraction patterns showed that the peaks of the compounds were attributed to two phases, including the main crystalline phase of NdNbO4 that was indexed as the monoclinic phase and MgO as the second phase. Well‐developed microstructures of Mg2NdNbO6 ceramics can be achieved, and the grain size reached the maximum value (1.63 μm) at 1375°C. As the sintering temperature increased, the dielectric constant, temperature coefficient of resonant frequency and apparent density remained almost unchanged, however, the significant change in the quality factor was observed. At 1375°C, Mg2NdNbO6 ceramics possessed excellent microwave dielectric properties: εr = 16.22, Q × f = 116 000 GHz and τf = −30.96 ppm/°C.
The Keys to Success in Spinoffs
Authors: Emrick Craig , Khorana Ajay , Shivdasani Anil , Ventouras Peter
Published: October 2017

Corporate restructurings accomplished through spinoffs have long been a key tool for management to unlock shareholder value. In 2016, global spinoff volume reached $117 billion, and spinoff activity continues to unfold at a similar pace in 2017, with Hilton, Xerox, Alcoa, Johnson Controls, and Danaher all recently completing major transactions.

Spinoffs are often designed to increase strategic focus and discipline in the allocation of capital, enabling companies to respond more effectively to opportunities that create shareholder value, including transformational M&A. And intensifying shareholder activist pressure, along with favorable debt market conditions, has provided significant momentum to spinoff activity. In fact, almost 20% of the companies that announced spinoffs in the past five years were subject to some form of prior activist engagement. Moreover, part of the impetus for such activism can be traced to the record M&A volume of the past few years, which has added to investor demand for many acquisitive companies to consider shedding businesses that are no longer a strategic fit.

But even with all this M&A activity, opportunities for unlocking value through spinoffs have not been as abundant or readily identified as in the past owing to the general reduction in corporate business diversification that has taken place during the last decade or so. And perhaps reflecting this development, the average longer‐run shareholder returns from spinoffs have actually turned negative during the past five years, while the dispersion of spinoff returns has increased, representing greater downside risk for restructurings undertaken without an effective strategy and rationale for increasing efficiency and value.

Nonetheless, more than half of all spinoffs over the past five years have generated share price outperformance despite the overall decline in spinoff performance. The authors devote the second half of the article to identifying several key characteristics of the post‐separation entities that indicate the potential for such a restructuring to deliver share price outperformance. The main attributes of value‐increasing spinoffs are size and organic growth, and increases in business focus and capital efficiency; but such transactions have also produced companies that maintain the financial flexibility to pursue M&A along with a dividend policy that is both attractive and sustainable.
Statement of the Financial Economists Roundtable: Corporate Tax Reform
Authors: Boot Arnoud , Logue Dennis , Spatt Chester
Published: October 2017

Corporate tax reform has been a controversial issue in the U.S. for several years, particularly as U.S. companies have accumulated cash in lower‐tax overseas subsidiaries, while some have used “inversions” to establish overseas corporate domiciles. Two features of U.S. corporate taxation stand out:

1. U.S. corporate income tax rates are the highest in the industrialized world. The federal rate is 35%; and, when combined with state taxes, it averages 39%, as compared to an OECD average of 24%.

2. U.S. corporations pay U.S. tax on their worldwide income, but can choose to avoid indefinitely corporate tax on foreign profits by not repatriating them. Neither feature is present in most other Western countries, where the norm is a “territorial” system that taxes companies only on their domestic profits.

The Trump administration has proposed to cut U.S. corporate tax rates to 20%, thereby bringing them down to the OECD average, and to adopt a territorial tax regime like those found in most other Western nations.

In this statement signed by 31 senior financial economists, the authors recommend cutting U.S. corporate tax rates, but retaining the current system of taxing the worldwide profits of U.S. companies (while giving them credit for taxes paid in overseas jurisdictions). Once U.S. rates drop to the international average, the economists point out, U.S. companies would have much less incentive under the worldwide system to use transfer pricing schemes to shift their profits to low‐tax jurisdictions than under the proposed territorial alternative. Indeed, under the current system, if the lower rates under consideration are enacted, the location of a company's business activity (including the firm's underlying intellectual property) would not affect its taxation.

Along with lower corporate tax rates, the economists also recommend that Congress limit or remove the corporate option to defer the taxation of offshore profits and provide a schedule for repatriating off‐shore funds, using the inducement of the now lower rates as well as the possibility of a “tax holiday.”
Valuation of a Pharmaceutical Licensing Contract
Authors: Lynch John , Shockley Richard
Published: October 2017

It is quite common for boutique pharma companies, biotech firms, and university labs to license their intellectual property (a new compound) to large pharmaceutical companies. In such cases, the big pharma companies finance and manage the R&D process and, if successful, market the drugs. In exchange for use of their intellectual property, the outlicensing organizations receive licensing contracts that promise some combination of fixed payments, event‐specific milestone payments, and revenue‐ or profit‐based royalties.

The authors show how to estimate the expected present value of the future cash flows promised by such licensing deals. The complicating factor in such valuations is that the licensing contracts are essentially derivative contracts written on drugs in development, which as the authors showed in a paper published in this journal a year ago, are themselves compound options on marketed drugs. The authors use the valuation example from the earlier paper, along with a proposed licensing deal, and walk the reader through the process of valuing the licensing deal's cash flows.
Plasticity and cross‐tolerance to heterogeneous environments: divergent stress responses co‐evolved in an African fruit fly
Authors: Gotcha N. , Terblanche J. S. , Nyamukondiwa C.
Published: October 2017

Plastic adjustments of physiological tolerance to a particular stressor can result in fitness benefits for resistance that might manifest not only in that same environment but also be advantageous when faced with alternative environmental stressors, a phenomenon termed ‘cross‐tolerance’. The nature and magnitude of cross‐tolerance responses can provide important insights into the underlying genetic architecture, potential constraints on or versatility of an organism's stress responses. In this study, we tested for cross‐tolerance to a suite of abiotic factors that likely contribute to setting insect population dynamics and geographic range limits: heat, cold, desiccation and starvation resistance in adult Ceratitis rosa following acclimation to all these isolated individual conditions prior to stress assays. Traits of stress resistance scored included critical thermal (activity) limits, chill coma recovery time (CCRT), heat knockdown time (HKDT), desiccation and starvation resistance. In agreement with other studies, we found that acclimation to one stress typically increased resistance for that same stress experienced later in life. A more novel outcome, however, is that here we also found substantial evidence for cross‐tolerance. For example, we found an improvement in heat tolerance (critical thermal maxima, CTmax) following starvation or desiccation hardening and improved desiccation resistance following cold acclimation, indicating pronounced cross‐tolerance to these environmental stressors for the traits examined. We also found that two different traits of the same stress resistance differed in their responsiveness to the same stress conditions (e.g. HKDT was less cross‐resistant than CTmax). The results of this study have two major implications that are of broader importance: (i) that these traits likely co‐evolved to cope with diverse or simultaneous stressors, and (ii) that a set of common underlying physiological mechanisms might exist between apparently divergent stress responses in this species. This species may prove to be a valuable model for future work on the evolutionary and mechanistic basis of cross‐tolerance.
Comment on Tai Chi for Risk of Falls. A meta‐analysis
Authors: Schoene Daniel , Kiesswetter Eva , Lord Stephen R
Published: October 2017

See the Reply by Lomas‐Vega et al.
Reply to: Comment on Tai Chi for Risk of Falls. A Meta‐analysis
Authors: Lomas‐Vega Rafael , Obrero‐Gaitán Esteban , Molina‐Ortega Francisco Javier , del‐Pino‐Casado Rafael
Published: October 2017

This letter comments on the letter by Schoene et al.
Adolescent Externalizing Problems: Contributions of Community Crime Exposure and Neural Function During Emotion Introspection in Mexican‐Origin Youth
Authors: Weissman David G. , Gelardi Kristina L. , Conger Rand D. , Robins Richard W. , Hastings Paul D. , Guyer Amanda E.
Published: October 2017

Models of the etiology of adolescent antisocial behavior suggest that externalizing problems may reflect a susceptibility to crime exposure and a diminished capacity for emotion introspection. In this study, adolescents of Mexican origin completed a neuroimaging task that involved rating their subjective feelings of sadness in response to emotional facial expressions or a nonemotional aspect of each face. At lower levels of neural activity during sadness introspection in posterior cingulate and left temporoparietal junction, and in left amygdala, brain regions involved in mentalizing and emotion, respectively, a stronger positive association between community crime exposure and externalizing problems was found. The specification of emotion introspection as a psychological process showing neural variation may help inform targeted interventions to positively affect adolescent behavior.