bluuebunny/crossref_metadata_2025 huggingface dataset:
Institutions, governmental performance and the rise of political newcomers
Authors: CARRERAS MIGUEL
Published: November 2016

This article analyses the institutional and contextual factors that facilitate the election of political newcomers as heads of government in democratic regimes. Using data from 870 democratic elections between 1945 and 2015, it is found that political newcomers are more likely to be successful in presidential systems, in new democracies and when party systems are weakly institutionalised. The election of politically inexperienced candidates is also related to governmental performance. Political newcomers are more successful when the economic performance of the government is bad and when the government engages in high‐level corruption.
Exploring subjectivity in competency‐based assessment judgements of assessors
Authors: Bacon Rachel , Holmes Kay , Palermo Claire
Published: November 2016

Aim

The aim of this research was to measure variations in assessors’ judgements of a student dietitian's performance and to explore the influence of group discussion on their judgements.

Methods

The assessments of a student's performance, as observed from a video recording of an authentic nutrition consultation, were measured pre‐ and post‐group discussion by 26 experienced assessors using a mixed‐methods questionnaire. The instrument included a validated 7‐point visual analogue scale (VAS) rating (1 = novice; 7 = competent), a qualitative global description of performance and an assessor's confidence rating (1 = not at all confident; 10 = extremely confident). Scales were analysed descriptively and qualitative responses coded for key themes.

Results

No agreement was found in assessors’ rating in either the pretest (median = 4, range = 5) or post‐test (median = 4, range = 4); however, the discussion led 78% of participants (20/26) to change their VAS ratings (9/26) and/or confidence levels (16/26). Three themes emerged from the thematic analysis of the participants’ global descriptions of performance: (i) discourse supports assessors to justify their judgements, identify assumptions and learn from the observations of others; (ii) discourse leads assessors to more holistic judgements; and (iii) multiple sources of evidence and student reflections are necessary for credible judgement.

Conclusions

This research questions the notion that ‘actual’ performance can be objectively measured and, rather, considers assessments as ‘interpretations’. This research calls for an integrated interpretivist student‐centred approach to competency‐based assessment.
Preparation of Zein Fibers Using Solution Blow Spinning Method
Authors: Liu Fei , Avena‐Bustillos Roberto J. , Woods Rachelle , Chiou Bor‐Sen , Williams Tina G. , Wood Delilah F. , Bilbao‐Sainz Cristina , Yokoyama Wallace , Glenn Gregory M. , McHugh Tara H. , Zhong Fang
Published: November 2016

Zein fibers were successfully fabricated via solution blow spinning (SBS) using acetic acid as solvent. Surface tension, viscosity and modulus of zein solutions were respectively determined by force tensiometer and rheometer. Increases of these properties were observed with an increase of concentration from 20% to 35% (w/w). The fabrication conditions of zein fibers were initially investigated as a function of zein concentration (25% to 35% w/w), feed rate (0.04 to 0.1 mL/min) and air pressure (0.28 to 0.62 MPa). The average fiber diameter (AFD) ranged from 174 to 9595 nm based on scanning electron microscopy (SEM). A Box–Behnken experimental design (BBD) was further performed to identify and quantify the significance of above parameters. The statistical analysis showed that the linear coefficient of concentration, the quadratic term of concentration as well as the interaction between concentration and air pressure were demonstrated statistically significant. Optimal conditions, with an AFD of 138 nm, could be obtained in the SBS of zein fibers by combining a concentration of 23% (w/w), a feed rate of 0.04 mL/min and an air pressure of 0.38 MPa. The moisture sorption capacity of fibers increased slightly as AFD decreased from ∼550 to ∼200 nm, with an increase of BET surface area from 116.5 to 140.0 m2/g.
Survey of image‐guided radiotherapy use in Australia
Authors: Batumalai Vikneswary , Holloway Lois Charlotte , Kumar Shivani , Dundas Kylie , Jameson Michael Geoffrey , Vinod Shalini Kavita , Delaney Geoff P
Published: November 2016

Introduction

This study aimed to evaluate the current use of imaging technologies for planning and delivery of radiotherapy (RT) in Australia.

Methods

An online survey was emailed to all Australian RT centres in August 2015. The survey inquired about imaging practices during planning and treatment delivery processes. Participants were asked about the types of image‐guided RT (IGRT) technologies and the disease sites they were used for, reasons for implementation, frequency of imaging and future plans for IGRT use in their department.

Results

The survey was completed by 71% of Australian RT centres. All respondents had access to computed tomography (CT) simulators and regularly co‐registered the following scans to the RT: diagnostic CT (50%), diagnostic magnetic resonance imaging (MRI) (95%), planning MRI (34%), planning positron emission tomography (PET) (26%) and diagnostic PET (97%) to aid in tumour delineation. The main reason for in‐room IGRT implementation was the use of highly conformal techniques, while the most common reason for under‐utilisation was lack of equipment capability. The most commonly used IGRT modalities were kilovoltage (kV) cone‐beam CT (CBCT) (97%), kV electronic portal image (EPI) (89%) and megavoltage (MV) EPI (75%). Overall, participants planned to increase IGRT use in planning (33%) and treatment delivery (36%).

Conclusions

IGRT is widely used among Australian RT centres. On the basis of future plans of respondents, the installation of new imaging modalities is expected to increase for both planning and treatment.
Informed Preferences? The Impact of Unions on Workers' Policy Views
Authors: Kim Sung Eun , Margalit Yotam
Published: November 2016

Despite declining memberships, labor unions still represent large shares of electorates worldwide. Yet their political clout remains contested. To what extent, and in what way, do unions shape workers' political preferences? We address these questions by combining unique survey data of American workers and a set of inferential strategies that exploit two sources of variation: the legal choice that workers face in joining or opting out of unions and the over‐time reversal of a union's policy position. Focusing on the issue of trade, we offer evidence that unions influence their members' policy preferences in a significant and theoretically predictable manner. In contrast, we find that self‐selection into membership accounts at most for a quarter of the observed “union effect.” The study illuminates the impact of unions in cohering workers' voice and provides insight on the role of information provision in shaping how citizens form policy preferences.
The use of a battery of pain models to detect analgesic properties of compounds: a two‐part four‐way crossover study
Authors: Okkerse Pieter , van Amerongen Guido , de Kam Marieke L. , Stevens Jasper , Butt Richard P. , Gurrell Rachel , Dahan Albert , van Gerven Joop M. , Hay Justin L. , Groeneveld Geert Jan
Published: November 2016

Aim

The aim was to investigate the ability of a battery of pain models to detect analgesic properties of commonly used analgesics in healthy subjects.

Methods

The battery consisted of tests eliciting electrical, mechanical and thermal (contact heat and cold pressor)‐pain and included a UVB model, the thermal grill illusion and a paradigm of conditioned pain modulation. Subjects were administered fentanyl 3 μg kg–1, phenytoin 300 mg, (S)‐ketamine 10 mg and placebo (part I), or imipramine 100 mg, pregabalin 300 mg, ibuprofen 600 mg and placebo (part II). Pain measurements were performed at baseline and up to 10 h post‐dose. Endpoints were analysed using a mixed model analysis of variance.

Results

Sixteen subjects (8 female) completed each part. The pain tolerance threshold (PTT) for electrical stimulation was increased (all P < 0.05) compared to placebo for (S)‐ketamine (+10.1%), phenytoin (+8.5%) and pregabalin (+10.8%). The PTT for mechanical pain was increased by pregabalin (+14.1%). The cold pressor PTT was increased by fentanyl (+17.1%) and pregabalin (+46.4%). Normal skin heat pain detection threshold was increased by (S)‐ketamine (+3.3%), fentanyl (+2.8%) and pregabalin (+4.1%). UVB treated skin pain detection threshold was increased by fentanyl (+2.6%) and ibuprofen (+4.0%). No differences in conditioned pain modulation were observed.

Conclusion

This study shows that these pain models are able to detect changes in pain thresholds after administration of different classes of analgesics in healthy subjects. The analgesic compounds all showed a unique profile in their effects on the pain tasks administered.
What Paves the Way to Conventional Language? The Predictive Value of Babble, Pointing, and Socioeconomic Status
Authors: McGillion Michelle , Herbert Jane S. , Pine Julian , Vihman Marilyn , dePaolis Rory , Keren‐Portnoy Tamar , Matthews Danielle
Published: November 2016

A child's first words mark the emergence of a uniquely human ability. Theories of the developmental steps that pave the way for word production have proposed that either vocal or gestural precursors are key. These accounts were tested by assessing the developmental synchrony in the onset of babbling, pointing, and word production for 46 infants observed monthly between the ages of 9 and 18 months. Babbling and pointing did not develop in tight synchrony and babble onset alone predicted first words. Pointing and maternal education emerged as predictors of lexical knowledge only in relation to a measure taken at 18 months. This suggests a far more important role for early phonological development in the creation of the lexicon than previously thought.
Diverse types of dermatologic toxicities from immune checkpoint blockade therapy
Authors: Curry Jonathan L. , Tetzlaff Michael T. , Nagarajan Priyadharsini , Drucker Carol , Diab Adi , Hymes Sharon R. , Duvic Madeleine , Hwu Wen‐Jen , Wargo Jennifer A. , Torres‐Cabala Carlos A. , Rapini Ronald P. , Prieto Victor G.
Published: November 2016

Immunomodulatory drugs that leverages host immune mechanisms to destroy tumor cells have been met with great promise in the treatment of cancer. Immunotherapy, targeting cytotoxic T‐lymphocyte‐associated antigen 4 (CTLA‐4) and the programmed cell death 1 (PD‐1) receptor and its ligand (PD‐L1) have shown tremendous improvements in the survival of patients with advanced solid tumors. However, the development of dermatologic toxicity (DT) is a consequence to immunotherapy. Review of published reports of the DT to immunotherapy revealed patients receiving anti‐CTCLA‐4 antibody or anti‐PD‐1/PD‐L1 antibody often develop a DT of any type and grade. In this article, of the 3825 patients who were treated with anti‐PD‐1 and of 556 patients receiving anti‐PD‐L1, DT of any type and grade were reported in 1474 (∼39%) and 95 (∼17%) of patients, respectively. The emergence of specific types of DT to immunotherapy is beginning to be recognized can be categorized into four groups: (a) inflammatory, (b) immunobullous, (c) alteration of keratinocytes and (d) alteration of melanocytes. Lichenoid dermatitis and bullous pemphigoid appear to be DT more associated with anti‐PD‐1/PD‐L1 antibody. The DT profile in patients receiving immunotherapy is diverse, and early recognition of specific types of DT that clinicians may encounter is critical for optimal patient care
European human‐dominated landscapes provide ample space for the recolonization of large carnivore populations under future land change scenarios
Authors: Milanesi Pietro , Breiner Frank Thomas , Puopolo Felice , Holderegger Rolf
Published: November 2016

Europe is currently being re‐colonized by large carnivore species such as brown bear Ursus arctos, Eurasian lynx Lynx lynx and grey wolf Canis lupus. Approximately one‐third of Europe currently hosts at least one of these large carnivore species: they show permanent occurrence in some regions and sporadic occurrence without reproduction in others. We investigated potential future range expansions of these three large carnivores using three different analyses. First, we compared niche overlap between the historical, current permanent and current sporadic occurrences using n‐dimensional hypervolumes. Second, we identified the environmental variables that best explain differences between current sporadic and permanent occurrences through multi‐model inference. Third, we projected permanent occurrences into the future across a range of land‐use change scenarios. We also determined future refuges (i.e. sub‐optimal habitat in the environmental model, good habitat in the human disturbance model) and ecological traps (i.e. good habitat in the environmental model, sub‐optimal habitat in the human disturbance model). In the three large carnivore species, ecological niche overlap was higher between historical and current permanent occurrences than between historical and current sporadic occurrences, and we also found low ecological niche overlap between current permanent and sporadic occurrences. Between 20 and 24% (corresponding to 86 800 to 173 200 km2) of the current sporadic occurrences could result in permanent settlement of large carnivores in the year 2040, while 17–24% (corresponding to 122 200 to 104 100 km2) and 2.7–4.6% (corresponding to 11 800 to 28 400 km2) of the current sporadic occurrences are likely to become refuges and ecological traps, respectively. Factors affecting range expansion are human activities, which were negatively related to permanent occurrences of all three species. In light of our results, human‐dominated European landscapes provide ample space for the future recolonization of large carnivores.
Abundance–occupancy relationships in deep sea wood fall communities
Authors: Webb Thomas J. , Barry James P. , McClain Craig R.
Published: November 2016

The generally positive relationship between the number of sites a species occupies and its average abundance within those sites provides an important link between population processes occurring at different spatial scales. Although such abundance–occupancy relationships (AORs) have been documented across a very wide range of taxa and in many different environments, little is known of such patterns in Earth's largest ecosystem, the deep sea. Wood falls – derived from natural or anthropogenic inputs of wood into the oceans – constitute an important deep‐sea habitat, habouring their own unique communities ultimately entirely dependent on the wood for chemical energy. In this study we take advantage of the unique features of an experimental wood fall deployment to examine AORs for the first time in deep‐sea invertebrates. The study design combines advantages of both experimental (tractability, control of key environmental parameters) and observational (natural colonisation by taxonomically diverse communities) studies. We show that the interspecific AOR is strongly positive across the 48 species occurring over 32 wood fall communities. The precise form of the AOR is mediated by both species‐level life history (body size) and by the colonisation stage at which communities were harvested, but not by environmental energy (wood fall size). Temporal dynamics within species are also generally consistent with positive intraspecific AORs. This support for positive AORs in the deep sea is an important extension of a macroecological generality into a new environment offering considerable potential for further testing and developing mechanistic macroecological theories.
Early psychosis intervention outpatient service of the 1st Psychiatric University Clinic in Athens: 3 Years of experience
Authors: Kollias Constantinos , Xenaki Lida‐Alkisti , Dimitrakopoulos Stefanos , Kosteletos Ioannis , Kontaxakis Vassilis , Stefanis Nikos , Papageorgiou Charalampos
Published: November 2016

To present the 3‐year experience of the early intervention in psychosis (EIP) service implementation of the 1st Psychiatric University Clinic in Athens. An overview of: (1) the purpose of our service, (2) the referral network, (3) the selection criteria, (4) the diagnostic procedures, (5) the therapeutic interventions and (6) the research activities. The service was established in 2012 and developed gradually aiming to provide information, early detection, treatment and support to people aged 15 to 40 years with psychotic manifestations, who are either at increased risk of developing psychosis (at‐risk mental state [ARMS]) or with first episode psychosis (FEP). In order to assess individuals with ARMS, we used the comprehensive assessment of at‐risk mental states interview and the Social and Occupational Functioning Assessment Scale The duration of untreated psychosis was estimated by using the Nottingham Onset Schedule. So far we have had 65 referrals, of which 26 were ARMS and 17 FEP. Based on the individual needs, they were offered psychotherapeutic and/or pharmacological treatment. After 3 years, the rate of transition to psychosis was 19.2% and the rate of psychosis relapse was 11.7%. The implementation of our service has had positive results, enabling young people with early psychosis to receive prompt and effective care. The rates of transition to psychosis are the first to be published from a Greek EIP service. Further development of our referral network and inter‐hospital collaboration will allow us to address the needs of a wider part of the population.
Factor structure of therapist fidelity to individual resiliency training in the Recovery After an Initial Schizophrenia Episode Early Treatment Program
Authors: Browne Julia , Edwards Alexandra N. , Penn David L. , Meyer‐Kalos Piper S. , Gottlieb Jennifer D. , Julian Paul , Ludwig Kelsey , Mueser Kim T. , Kane John M.
Published: November 2016

Background

Evidence‐based approaches and early intervention have improved the long‐term prognosis of individuals with schizophrenia. However, little is known about the therapeutic processes involved in individual therapy in first‐episode psychosis. A comprehensive psychosocial/psychiatric programme for this population, NAVIGATE, includes an individual therapy component, individual resiliency training (IRT). Fidelity of clinicians’ adherence to the IRT protocol has been collected to ensure proper implementation of this manual‐based intervention. These data can provide insight into the elements of the therapeutic process in this intervention.

Materials and Methods

To achieve this goal, we first examined the factor structure of the IRT fidelity scale with exploratory factor analysis. Second, we explored the relationships among the IRT fidelity ratings with clinician years of experience and years of education, as well as client's baseline symptom severity and duration of untreated psychosis.

Results and Conclusions

Results supported a 2‐factor structure of the IRT fidelity scale. Correlations between clinician years of education and fidelity ratings were statistically significant.
Predictors of inferior clinical outcome in patients with standard‐risk multiple myeloma
Authors: Badar Talha , Srour Samer , Bashir Qaiser , Shah Nina , Al‐Atrash Gheath , Hosing Chitra , Popat Uday , Nieto Yago , Orlowski Robert Z. , Champlin Richard , Qazilbash Muzaffar H.
Published: November 2016

Introduction

Outcome of patients with standard‐risk (SR) multiple myeloma (MM) has improved; however, subsets of patients do worse than expected. We sought to identify the factors associated with inferior outcome.

Methods

We evaluated 51 patients with SR MM that received upfront autologous hematopoietic stem cell transplantation (auto‐HCT) after induction and had a progression‐free survival (PFS) of ≤18 months.

Results

The median age of patients was 61 yr. Forty‐one (80%) patients received induction with immunomodulatory drugs, proteosome inhibitors, or combination of both. The overall response rate (ORR) after auto‐HCT was 96% (stringent complete response 23%, complete response 10%, very good partial response 22%, and partial response 39%). The median PFS was 7.8, and median overall survival (OS) was 56.3 months. On univariate analysis, concurrent light‐chain amyloidosis (AL) was associated with inferior PFS [hematological response (HR); 2.51, 95% CI; 0.64–10.58, P = 0.03] and occurrence of soft tissue plasmacytoma was associated with a significantly shorter OS (HR: 3.05, 95% CI: 0.57–16.29, P = 0.02).

Conclusion

Our analysis suggests that concurrent AL and soft tissue plasmacytoma were associated with shorter PFS and OS, respectively. Heterogeneity in clinical outcome of SR MM merits better tools for prognostication, such as gene expression profiling and minimal residual disease assessment to identify high‐risk patients.
Prognostic significance of proteinuria in stroke patients treated with intravenous thrombolysis
Authors: Gensicke H. , Frih A. A. , Strbian D. , Zini A. , Pezzini A. , Padjen V. , Haueter M. , Seiffge D. J. , Mäkitie L. , Traenka C. , Poli L. , Martinez‐Majander N. , Putaala J. , Bonati L. H. , Sibolt G. , Giovannini G. , Curtze S. , Beslac‐Bumbasirevic L. , Vandelli L. , Lyrer P. A. , Nederkoorn P. J. , Tatlisumak T. , Engelter S. T. ,   the Thrombolysis in Stroke Patients (TRISP) Collaborators
Published: November 2016

Background and purpose

Proteinuria and estimated glomerular filtration rate (eGFR) are indicators of renal function. Whether proteinuria better predicts outcome than eGFR in stroke patients treated with intravenous thrombolysis (IVT) remains to be determined.

Methods

In this explorative multicenter IVT register based study, the presence of urine dipstick proteinuria (yes/no), reduced eGFR (<60 ml/min/1.73 m2) and the coexistence of both with regard to (i) poor 3‐month outcome (modified Rankin Scale score 3–6), (ii) death within 3 months and (iii) symptomatic intracranial hemorrhage (ECASS‐II criteria) were compared. Unadjusted and adjusted odds ratios (ORs) with 95% confidence intervals were calculated.

Results

Amongst 3398 patients, 881 (26.1%) had proteinuria and 623 (18.3%) reduced eGFR. Proteinuria [ORadjusted 1.65 (1.37–2.00) and ORadjusted 1.52 (1.24–1.88)] and reduced eGFR [ORadjusted 1.26 (1.01–1.57) and ORadjusted 1.34 (1.06–1.69)] were independently associated with poor functional outcome and death, respectively. After adding both renal markers to the models, proteinuria [ORadjusted+eGFR 1.59 (1.31–1.93)] still predicted poor outcome whilst reduced eGFR [ORadjusted+proteinuria 1.20 (0.96–1.50)] did not. Proteinuria was associated with symptomatic intracranial hemorrhage [ORadjusted 1.54 (1.09–2.17)] but not reduced eGFR [ORadjusted 0.96 (0.63–1.62)]. In 234 (6.9%) patients, proteinuria and reduced eGFR were coexistent. Such patients were at the highest risk of poor outcome [ORadjusted 2.16 (1.54–3.03)] and death [ORadjusted 2.55 (1.69–3.84)].

Conclusion

Proteinuria and reduced eGFR were each independently associated with poor outcome and death but the statistically strongest association appeared for proteinuria. Patients with coexistent proteinuria and reduced eGFR were at the highest risk of poor outcome and death.
Frequency and outcome of total anterior circulation strokes without intracranial large‐vessel occlusion
Authors: Giralt‐Steinhauer E. , Ois A. , Abilleira S. , Urra X. , Cardona‐Portela P. , Gomis M. , Castellanos M. , Molina C. , Martí‐Fàbregas J. , Pellisé A. , Cànovas D. , Gómez‐Choco M. , Kuprinski J. , Cocho D. , Roquer J. ,   the Cat‐SCR Consortium
Published: November 2016

Background and purpose

The percentage of patients with clinical total anterior circulation infarct (TACI) syndrome treated with reperfusion therapies in the absence of intracranial large‐vessel occlusion (ILVO) was determined and their characteristics and outcome are described.

Methods

Data from a population‐based, prospective, externally audited registry of all stroke patients treated with intravenous thrombolysis (IVT) and endovascular therapies in Catalonia from January 2011 to December 2013 were used. Patients with a baseline TACI and initial stroke severity measured by the National Institute of Health Stroke Scale (NIHSS) ≥ 8, evaluated less than 4.5 h post‐onset, for whom a vascular study prior to treatment was available (n = 1070) were selected. Clinical characteristics, outcome and radiological data for patients treated with IVT alone (n = 605) were compared between those with detected ILVO (n = 474) and non‐ILVO patients (n = 131).

Results

A total of 1070 patients met study criteria; non‐ILVO was found in 131 (12.2%). Analysing the 605 patients treated only with IVT, no significant differences were found between non‐ILVO and ILVO patients in age, sex, risk factors, time‐to‐treatment and type of radiological studies performed. Although non‐ILVO patients had lower initial stroke severity (P < 0.001) and a better prognosis (P = 0.001), 51.3% had a poor outcome and 16% were deceased at 90 days. In 66.4% of patients without ILVO, a recent anterior territorial infarct was detected.

Conclusions

Intracranial artery patency was observed in 12.2% of TACI patients evaluated within 4.5 h. Although absence of ILVO was associated with slightly better prognosis, more than half had a poor outcome at 3 months.
Infantile spasms and encephalopathy without preceding neonatal seizures caused by KCNQ2 R198Q, a gain‐of‐function variant
Authors: Millichap John J. , Miceli Francesco , De Maria Michela , Keator Cynthia , Joshi Nishtha , Tran Baouyen , Soldovieri Maria Virginia , Ambrosino Paolo , Shashi Vandana , Mikati Mohamad A. , Cooper Edward C. , Taglialatela Maurizio
Published: November 2016

Variants in KCNQ2 encoding for Kv7.2 neuronal K+ channel subunits lead to a spectrum of neonatal‐onset epilepsies, ranging from self‐limiting forms to severe epileptic encephalopathy. Most KCNQ2 pathogenic variants cause loss‐of‐function, whereas few increase channel activity (gain‐of‐function). We herein provide evidence for a new phenotypic and functional profile in KCNQ2‐related epilepsy: infantile spasms without prior neonatal seizures associated with a gain‐of‐function gene variant. With use of an international registry, we identified four unrelated patients with the same de novo heterozygous KCNQ2 c.593G>A, p.Arg198Gln (R198Q) variant. All were born at term and discharged home without seizures or concern of encephalopathy, but developed infantile spasms with hypsarrhythmia (or modified hypsarrhythmia) between the ages of 4 and 6 months. At last follow‐up (ages 3–11 years), all patients were seizure‐free and had severe developmental delay. In vitro experiments showed that Kv7.2 R198Q subunits shifted current activation gating to hyperpolarized potentials, indicative of gain‐of‐function; in neurons, Kv7.2 and Kv7.2 R198Q subunits similarly populated the axon initial segment, suggesting that gating changes rather than altered subcellular distribution contribute to disease molecular pathogenesis. We conclude that KCNQ2 R198Q is a model for a new subclass of KCNQ2 variants causing infantile spasms and encephalopathy, without preceding neonatal seizures.

A PowerPoint slide summarizing this article is available for download in the Supporting Information section here
Kinetics of binding of fluorescent ligands to enzymes with engineered access tunnels
Authors: Kaushik Shubhangi , Prokop Zbynek , Damborsky Jiri , Chaloupkova Radka
Published: November 2016

Molecular recognition mechanisms and kinetics of binding of ligands to buried active sites via access tunnels are not well understood. Fluorescence polarization enables rapid and non‐destructive real‐time quantification of the association between small fluorescent ligands and large biomolecules. In this study, we describe analysis of binding kinetics of fluorescent ligands resembling linear halogenated alkanes to haloalkane dehalogenases. Dehalogenases possess buried active sites connected to the surrounding solvent by access tunnels. Modification of these tunnels by mutagenesis has emerged as a novel strategy to tailor the enzyme properties. We demonstrate that the fluorescence polarization method can sense differences in binding kinetics originating from even single mutations introduced to the tunnels. The results show, strikingly, that the rate constant of the dehalogenase variants varied across seven orders of magnitude, and the type of ligand used strongly affected the binding kinetics of the enzyme. Furthermore, fluorescence polarization could be applied to cell‐free extracts instead of purified proteins, extending the method's application to medium‐throughput screening of enzyme variant libraries generated in directed evolution experiments. The method can also provide in‐depth kinetic information about the rate‐determining step in binding kinetics and reveals the bottlenecks of enzyme accessibility. Assuming availability of appropriate fluorescent ligand, the method could be applied for analysis of accessibility of tunnels and buried active sites of enzymes forming a covalent alkyl–enzyme intermediate during their catalytic cycle, such as α/β‐hydrolases containing > 100 000 protein sequences based on the Pfam database.
Physiological effects of ice‐angling capture and handling on northern pike, Esox lucius
Authors: Louison M. J. , Hasler C. T. , Fenske M. M. , Suski C. D. , Stein J. A.
Published: November 2016

Understanding how released fish recover following capture is vital information for researchers examining the effects of angling on exploited populations. This information is virtually non‐existent for fish angled through the ice in winter, despite the popularity of ice‐angling in many northern areas. To address this gap, 60 northern pike, Esox lucius L., were angled through the ice from an impoundment in eastern Wisconsin, USA, and subjected to one of ten combinations of handling and recovery duration. Plasma samples were collected and analysed for cortisol, lactate and glucose. The results showed a delayed response in the elevation of plasma variables, and a significant interaction between air exposure and recovery time for plasma lactate. No fish suffered mortality during the period of holding. Collectively, these data suggest that northern pike are physiologically resilient to ice‐angling capture stress as long as air exposure times are kept at 4 min or less.
Hot spots of wheat yield decline with rising temperatures
Authors: Asseng Senthold , Cammarano Davide , Basso Bruno , Chung Uran , Alderman Phillip D. , Sonder Kai , Reynolds Matthew , Lobell David B.
Published: November 2016

Many of the irrigated spring wheat regions in the world are also regions with high poverty. The impacts of temperature increase on wheat yield in regions of high poverty are uncertain. A grain yield–temperature response function combined with a quantification of model uncertainty was constructed using a multimodel ensemble from two key irrigated spring wheat areas (India and Sudan) and applied to all irrigated spring wheat regions in the world. Southern Indian and southern Pakistani wheat‐growing regions with large yield reductions from increasing temperatures coincided with high poverty headcounts, indicating these areas as future food security ‘hot spots’. The multimodel simulations produced a linear absolute decline of yields with increasing temperature, with uncertainty varying with reference temperature at a location. As a consequence of the linear absolute yield decline, the relative yield reductions are larger in low‐yielding environments (e.g., high reference temperature areas in southern India, southern Pakistan and all Sudan wheat‐growing regions) and farmers in these regions will be hit hardest by increasing temperatures. However, as absolute yield declines are about the same in low‐ and high‐yielding regions, the contributed deficit to national production caused by increasing temperatures is higher in high‐yielding environments (e.g., northern India) because these environments contribute more to national wheat production. Although Sudan could potentially grow more wheat if irrigation is available, grain yields would be low due to high reference temperatures, with future increases in temperature further limiting production.
Women Living Together Have a Higher Frequency of Menstrual Migraine
Authors: Ferreira Karen S. , Guilherme Gisela , Faria Viviane R. , Borges Larissa M. , Uchiyama Angel A.T.
Published: November 2016

Background

Menstrual migraine is a highly prevalent disorder among adult women, resulting in disability and loss of quality of life. Some studies have reported menstrual cycle synchrony among women living together. No study has reported whether there may also be a higher prevalence of menstrual migraine among these women. Thus, they reported here the prevalence of menstrual migraine in a group of women living together compared with a control group of women living alone, and discussed the possible factors involved.

Methods

The study was conducted on female university students aged 18‐30 years with a diagnosis of migraine according to the criteria of the International Classification of Headache Disorders III, beta appendix criteria. The subjects were divided into a group of women who lived together with two or more other students and a control group of age‐matched students who lived alone, interviewed with a specific questionnaire and assessed for 3 months by means of a paper pain diary. The data evaluated included frequency of headache, presence of menstrual migraine, intensity of headache, medications used including contraceptives, and triggering factors such as diet, sleep deprivation, and stress. The menstrual data and data related to migraine were also investigated in the roommates.

Results

A higher occurrence of menstrual migraine among women living together (9, 50%) compared with women living alone (3, 16.7%) (P = .03) was detected. After binary logistic regression analysis, this finding was not related to the main influencing factors detected, that is, use of a contraceptive, test stress, or sleep deprivation (P = .03, adjusted odds ratio: 7.87; 1.23‐50.36). These women also showed menstrual cycle synchrony with their roommates (8, 44.4%) and the presence of headache crises during the menstruation of their colleagues (11, 61.1%).

Conclusion

The present study detected a higher occurrence of menstrual migraine among women who lived together. Since there was no previous description of this topic in the literature, it was believed that the present study could represent a step toward more elaborate investigations of this complex topic.
Development of hepatocellular carcinoma in Japanese patients with biopsy‐proven non‐alcoholic fatty liver disease: Association between PNPLA3 genotype and hepatocarcinogenesis/fibrosis progression
Authors: Seko Yuya , Sumida Yoshio , Tanaka Saiyu , Mori Kojiroh , Taketani Hiroyoshi , Ishiba Hiroshi , Hara Tasuku , Okajima Akira , Umemura Atsushi , Nishikawa Taichiro , Yamaguchi Kanji , Moriguchi Michihisa , Kanemasa Kazuyuki , Yasui Kohichiroh , Imai Shunsuke , Shimada Keiji , Itoh Yoshito
Published: November 2016

Aim

Some patients with non‐alcoholic fatty liver disease (NAFLD) develop hepatocellular carcinoma (HCC). Patatin‐like phospholipase domain containing 3 (PNPLA3) rs738409 (encoding the I148M variant) has been associated with advanced fibrosis and HCC. We determined the risk factors for HCC, including the PNPLA3 rs738409 polymorphism, in Japanese patients with biopsy‐proven NAFLD.

Methods

In this retrospective cohort study, we analyzed hepatocarcinogenesis in 238 patients. PNPLA3 rs738409 genotype was determined by allelic discrimination in 130 patients. Among them, 86 patients who were followed up for >5 years and without liver cirrhosis were analyzed to clarify the relationship between PNPLA3 genotype and long‐term changes in biomarkers.

Results

Of 238 patients, PNPLA3 genotype frequencies were: CC, 0.14; CG, 0.46; and GG, 0.40. During a follow‐up period of 6.1 years, 10 patients (4.2%) with non‐alcoholic steatohepatitis developed HCC. The cumulative rate of HCC was 1.9% at the end of the 5th year and 8.3% at the end of the 10th year. Multivariate analysis identified PNPLA3 genotype GG (hazard ratio, 6.36; P = 0.019) and fibrosis stage (fibrosis stage 3/4; hazard ratio, 24.4; P = 0.011) as predictors of HCC development. In the long follow‐up cohort, a larger reduction in platelet count was found in the GG group (P = 0.032) despite a larger reduction in alanine aminotransferase (P = 0.023) compared to that in the CC/CG group.

Conclusions

In Japanese patients with NAFLD, severe fibrosis and PNPLA3 GG genotype were predictors of HCC development, independent of other known risk factors. Patients with the PNPLA3 GG genotype have the potential for a decreased platelet count, even when alanine aminotransferase levels are well controlled.
Janus‐Faced Youth Justice Work and the Transformation of Accountability
Authors: ARMITAGE VICI , KELLY LAURA , PHOENIX JO
Published: November 2016

This article revisits claims about the relationship between ‘standardisation’, ‘discretion’ and ‘accountability’ in youth justice made in the wake of the Crime and Disorder Act 1998. We argue that less centralisation and less standardisation have transformed accountability, but this is experienced differently according to the place held in the organisational hierarchy. This recognition demands a more nuanced understanding of ‘practitioner discretion’, which can account for differences between managerial and frontline experiences of what we describe as ‘janus‐faced youth justice work’, and a broad definition of the youth justice field and associated actors.
Skuas (Stercorarius spp.) moult body feathers during both the breeding and inter‐breeding periods: implications for stable isotope investigations in seabirds
Authors: Graña Grilli Maricel , Cherel Yves
Published: November 2016

Seabirds are mostly thought to moult during the inter‐breeding period and the isotopic values of their feathers are often therefore assumed to relate to their assimilated diet during such periods. We observed Brown Skuas Stercorarius antarcticus lonnbergi and South Polar Skuas Stercorarius maccormicki moulting on a breeding site at King George Island, Antarctica. This raises concerns about the reliability of using stable isotopes in feathers to infer feeding localities of birds during the inter‐breeding period. We analysed the δ13C and δ15N values of growing and fully grown body feathers collected from the same individuals. For both species, δ13C values of growing feathers indicated feeding areas in the Antarctic zone (breeding grounds), whereas most fully grown feathers (100% for South Polar Skuas and 93.3% for Brown Skuas) could be assigned to northern latitudes (non‐breeding grounds). However, a few fully grown body feathers of Brown Skuas (6.7% of the feathers, belonging to two birds) showed isotopic values that indicated moult in the Antarctic zone. As the growth period of those feathers was unknown, they could not be used with confidence to depict the foraging behaviour of the birds during the non‐breeding period. Although precautions must be taken when inferring dietary information from feathers in seabirds where the moulting pattern is unknown, this study shows that if the development stage of a feather (growing/fully grown) is identified, then dietary information from both breeding and non‐breeding seasons can be obtained on the same individual birds.
Reactive Molecular Dynamics Simulations of Sodium Silicate Glasses — Toward an Improved Understanding of the Structure
Authors: Yu Yingtian , Wang Bu , Wang Mengyi , Sant Gaurav , Bauchy Mathieu
Published: November 2016

Reactive potentials are becoming increasingly popular as they are expected to bridge the gap between ab initio and classical molecular dynamics. However, their applicability and potential benefits to model multicomponent glass networks are yet to be assessed. Here, an archetypal modified silicate glass, sodium silicate glass, is simulated using the ReaxFF potential. The predicted structure is critically evaluated and compared to that obtained by a classical potential and experimental data. Our results indicate that ReaxFF offers an improved description of the atomic structure, both at the short‐ and medium‐ range. Particularly, owing to its bond order form that dynamically adjusts potential energies according to the local atomic environment, ReaxFF reproduces the effect of modifiers on the Si–O network, a demonstration of its good transferability to various compositions. Overall, ReaxFF provides a promising alternative to classical and ab initio methods for simulating complex structures and processes for multi‐component silicate glasses.
CHA2DS2VASc score predicts unsuccessful electrical cardioversion in patients with persistent atrial fibrillation
Authors: Mlodawska Elzbieta , Tomaszuk‐Kazberuk Anna , Lopatowska Paulina , Kaminski Marcin , Musial Wlodzimierz J.
Published: November 2016

Background

Atrial fibrillation (AF) is the most common arrhythmia occurring in 2% of the population. It is known that AF increases morbidity and limits quality of life. The CHA2DS2VASc score (congestive heart failure/left ventricular dysfunction, hypertension, age ≥75 (doubled), diabetes, stroke (doubled), vascular disease, age 65–74 and sex category (female)) is widely used to assess thrombotic complications. The CHA2DS2VASc score was not used until now in predicting the effectiveness of electrical cardioversion.

Aim

To assess the value of CHA2DS2VASc score in predicting unsuccessful electrical cardioversion.

Methods

We analysed 258 consecutive patients with persistent AF who underwent electrical cardioversion between January 2012 and April 2016 in a Cardiology University Centre in Poland.

Results

Out of 3500 hospitalised patients with AF, 258 (mean age 64 ± 11 years, 64% men) underwent electrical cardioversion. The CHA2DS2VASc score in analysed population (258 patients) was 2.5 ± 1.7 (range 0–8), and the HAS‐BLED (hypertension, abnormal liver or renal function, stroke, bleeding, labile international normalised ratio, elderly, drugs or alcohol) was 1 ± 0.9 (range 0–4). Electrical cardioversion was unsuccessful in 12%. Factors associated with unsuccessful cardioversion were age (P = 0.0005), history of ischaemic stroke (P = 0.04), male gender (P = 0.01) and CHA2DS2VASc score (P = 0.002). The CHA2DS2VASc score in patients who had unsuccessful cardioversion was higher compared to patients who had successful cardioversion – 3.5 versus 2.4 (P = 0.001). In the logistic regression model, if the CHA2DS2VASc score increases by 1, the odds of unsuccessful cardioversion increase by 39% (odds ratio (OR) 1.39; confidence interval (CI): 1.12–1.71; P = 0.002). The odds of unsuccessful cardioversion are three times higher in patients with a CHA2DS2VASc score ≥ 2 than in patients with a CHA2DS2VASc score of 0 or 1 (OR 3.06; CI: 1.03–9.09; P = 0.044).

Conclusion

The CHA2DS2VASc score routinely used in thromboembolic risk assessment may be a simple, easy and reliable scoring system that can be used to predict unsuccessful electrical cardioversion.
The Unintended Consequences of the Frequency of PCAOB Inspection
Authors: Tanyi Paul , Litt Barri
Published: November 2016

After more than 50 years of self‐regulation of the US auditing profession, the Sarbanes‐Oxley Act of 2002 (SOX) created the Public Company Accounting Oversight Board (PCAOB) as a quasi‐governmental entity with statutory authority to inspect accounting firms that audit public clients. The frequency of this inspection is annual or triennial, based upon the number of public clients the firm audits. We examine the effects of these two levels of inspection frequency on financial reporting quality and audit fees for clients of small and midsize public accounting firms. Our findings provide evidence of significantly higher audit quality and audit fees for clients of annually inspected firms relative to clients of triennially inspected firms. These findings are robust to auditor‐client alignment analyses, propensity score matching, time‐series analyses, examination of firms that have changed from triennial to annual inspection, and particular examination of firms with inspection deficiencies. Overall, our study suggests that the two‐tier frequency system of PCAOB inspection may have also resulted in two‐tier audit quality and audit fee systems for small and midsize public accounting firms, with more frequent inspection leading to more rigorous and informed auditor decisions. We discuss the implications of our results for the Board and the profession at large.
Heterogeneous nuclear ribonucleoprotein K is associated with poor prognosis and regulates proliferation and apoptosis in bladder cancer
Authors: Chen Xu , Gu Peng , Xie Ruihui , Han Jinli , Liu Hao , Wang Bo , Xie Weibin , Xie Weijie , Zhong Guangzheng , Chen Changhao , Xie Shujie , Jiang Ning , Lin Tianxin , Huang Jian
Published: November 2016

Heterogeneous nuclear ribonucleoprotein K (hnRNPK) is an essential RNA‐ and DNA‐binding protein that regulates diverse biological events, especially DNA transcription. hnRNPK overexpression is related to tumorigenesis in several cancers. However, both the expression patterns and biological mechanisms of hnRNPK in bladder cancer are unclear. We investigated hnRNPK expression by immunohistochemistry in 188 patients with bladder cancer, and found that hnRNPK expression levels were significantly increased in bladder cancer tissues and that high‐hnRNPK expression was closely correlated with poor prognosis. Loss‐ and gain‐of‐function assays demonstrated that hnRNPK promoted proliferation, anti‐apoptosis, and chemoresistance in bladder cancer cells in vitro, and hnRNPK knockdown suppressed tumorigenicity in vivo. Mechanistically, hnRNPK regulated various functions in bladder cancer by directly mediating cyclin D1, G0/G1 switch 2 (G0S2), XIAP‐associated factor 1, and ERCC excision repair 4, endonuclease catalytic subunit (ERCC4) transcription. In conclusion, we discovered that hnRNPK plays an important role in bladder cancer, suggesting that it is a potential prognostic marker and a promising target for treating bladder cancer.
Antithrombotic medications in dialysis patients: a double‐edged sword
Authors: Vlachopanos Georgios , Ghalli Farid Girgis
Published: November 2016

In the clinical context of end‐stage renal disease (ESRD), thrombosis and bleeding risks are simultaneously increased and may have devastating consequences. While anticoagulant and antiplatelet drugs are indispensable for the prevention of thromboembolic events, the significantly higher bleeding risk makes their handling extremely complicated. In ESRD, they are frequently administered for a wide array of conditions. For example, atrial fibrillation is quite common in ESRD and warrants the use of anticoagulants like warfarin. Unfractionated heparin and low molecular weight heparins are typically used for clotting prevention in the hemodialysis extracorporeal circuit. The antithrombotics use dilemma has worsened because ESRD patients have been excluded from major clinical trials that defined standard indications, contraindications and optimal management of these medications. That limits our knowledge and results in that the process of decision‐making depends on weaker data. Besides the substantial bleeding risk, warfarin may also increase cardiovascular risk because it is implicated in the pathogenesis of vascular calcifications in ESRD. The present article attempts to offer a comprehensive overview of practical considerations for the use of the most common antithrombotic medications in ESRD linking them, at the same time, to the best available evidence from randomized controlled trials and observational studies.