bluuebunny/crossref_metadata_2025 huggingface dataset:
Gender diversity in the Italian boardroom and firm financial performance
Authors: Gordini Niccolò , Rancati Elisa
Published: January 2017

Purpose

This study aims to analyse the relationship between board gender diversity and firm financial performance in Italy, where the recently enforced Law 120/2011 prescribes gender quotas for boards of directors.

Design/methodology/approach

Panel data analysis was used to examine the gender diversity–firm financial performance relationship in an unbalanced panel of 918 Italian listed companies during the years 2011-2014.

Findings

Gender diversity, as measured by the percentage of women on a board and by the Blau and the Shannon indices, has a positive and significant effect on Tobin’s Q, while the presence of one or more women on the boardper sehas an insignificant effect on firm financial performance.

Practical implications

The results suggest that board gender diversity is not a simple “numbers game”, greater gender diversity may generate economic gains, greater gender diversity does not destroy shareholder value, investors do not penalize companies that increase female representation on their boards and Italian companies should focus their efforts on the right mix of men and women rather than on simply the presence of at least one woman on a board of directors.

Originality/value

Most articles on this topic use data from countries with a legal system based on common law; this paper analyses Italy, a country with a civil law system. This is almost certainly the first study to examine the effect of board gender diversity on firm financial performance in the Italian market.
Videogames as a serious medium
Authors: Steinkuehler Constance
Published: January 2017

Purpose

The purpose of this paper is to inform designers and researchers about the current state of play in videogames in education and its broader context.

Design/methodology/approach

This synthetic piece reflects the author’s past decade of work and observation in the domain. It is not a research piece but a reflective essay.

Findings

Structural issues inflect the development of games for learning. Here, the author argues for the incubation of a new indie scene in educational domains on par with the burgeoning indie scene in commercial entertainment games.

Originality/value

This is a short essay for scholars, designers and leaders in games for learning who work inside academics yet aspire to have their work impact not only on publications but also on products.
Understanding strategic decision-making through a multi-paradigm perspective
Authors: Anagnostopoulos Christos , Byers Terri , Kolyperas Dimitrios
Published: January 2017

Purpose

The purpose of this paper is to illustrate the efficacy of using a multi-paradigm perspective to examine the relationship between corporate social responsibility (CSR) and strategic decision-making processes in the context of charitable foundations.

Design/methodology/approach

This paper integrates and synthesizes the micro-social processes of “assessable transcendence” (Anagnostopoulos et al., 2014) with Whittington’s (2001) perspectives on strategy. “Assessable transcendence” was achieved from the constant comparison of categories developed through an early iterative process in which data collection and analysis occurred during the same period. In all, 32 interviews were conducted among a sample of key managers in the charitable foundations for the first two divisions of English football.

Findings

The present study illustrates empirically that strategic decision making in charitable foundations does not “seat” neatly in any one of Whittington’s perspectives. On the contrary, this study indicates a great deal of overlap within these perspectives, and suggests that conflicting paradigms should be celebrated rather than viewed as signs of theoretical immaturity. Multi-paradigm approaches can potentially reveal insights into the “mechanics” of managerial decision making that are not easily discernible from a mono-paradigmatic perspective.

Originality/value

This is the first empirical work that examines CSR in relation to strategy within the context of the English football clubs’ charitable foundations, and does so by employing a multi-paradigm perspective on strategy formulation and implementation.
Suggesting a service research agenda in sports tourism: working experience(s) into business models
Authors: Perić Marko , Wise Nicholas , Dragičević Daniel
Published: January 2017

Purpose

Business models describe how value is delivered to customers/consumers. When considering sport tourism, the focus on delivering value shifts to the sport experiences being offered in a destination. The purpose of this paper is to fulfil a void that links concept of business models to the area of sport tourism management by integrating notions of experience.

Design/methodology/approach

To merge these areas, a review of literature identifies key approaches and missing links. This paper determines research gaps to propose a new holistic research agenda for sport services – specifically relevant to sport tourism.

Findings

This paper addresses types of sport experiences, economic dimensions of experiences and business models to determine capabilities of delivering different types of experiences. These inter-related fields of analysis represent a platform for both academic and business stakeholders to shape the future of delivering sport tourism experiences based on seeking a wider range of motivations in a specific spatial and activity context.

Originality/value

A series of research questions and proposals are identified to support the need for future research. Extending understandings of experience in relation to consumer demand has the potential to result in practical elements of sought after experiences being incorporated into business models – aimed at delivering service value.
The Stein Rokkan Lecture 2016 Mission impossible? Reconciling economic and social Europe after the euro crisis and Brexit
Authors: FERRERA MAURIZIO
Published: January 2017

During the crisis, the European Union's ‘social deficit’ has triggered an increasing politicisation of redistributive issues within supranational, transnational and national arenas. Various lines of conflict have taken shape, revolving aroundwhoquestions (who are ‘we’? – i.e., issues of identity and inclusion/exclusion);whatquestions (how much redistribution within and across the ‘we’ collectivities) andwho decidesquestions (the locus of authority that can produce and guarantee organised solidarity). The key challenge facing today's political leaders is how to ‘glue’ the Union together as a recogniseable and functioning polity. This requires a double rebalancing: between the logic of ‘opening’ and the logic of ‘closure’, on the one hand, and between the logic of ‘economic stability’ and ‘social solidarity’, on the other. Building on the work of Stein Rokkan and Max Weber, this article argues that reconciliation is possible, but only if carefully crafted through an extraordinary mobilisation of political and intellectual resources. A key ingredient should be the establishment of a European Social Union, capable of combining domestic and pan‐European solidarities. In this way, the EU could visibly and tangibly extend its policy menu from regulation to (limited, but effective) distribution, reaping the latter's benefits in terms of legitimacy. The journey on this road is difficult but,paceRokkan, not entirely impervious.
Getting away with foul play? The importance of formal and informal oversight institutions for electoral integrity
Authors: BIRCH SARAH , VAN HAM CAROLIEN
Published: January 2017

Electoral integrity is increasingly being recognised as an important component of democracy, yet scholars still have limited understanding of the circumstances under which elections are most likely to be free, fair and genuine. This article posits that effective oversight institutions play a key role in scrutinising the electoral process and holding those with an interest in the electoral outcome to account. The main insight is that deficiencies in formal electoral management can be effectively compensated for via one or more other institutional checks: an active and independent judiciary; an active and independent media; and/or an active and independent civil society. Flawed elections are most likely to take place when all four checks on electoral conduct fail in key ways. These hypotheses are tested and supported on a cross‐national time‐series dataset of 1,047 national‐level elections held in 156 electoral regimes between 1990 and 2012.
Estimating the Skull‐to‐Camera Distance from Facial Photographs for Craniofacial Superimposition
Authors: Stephan Carl N.
Published: January 2017

The overlay of a skull and a face image for identification purposes requires similar subject‐to‐camera distances (SCD) to be used at both photographic sessions so that differences in perspective do not compromise the anatomical comparisons. As the facial photograph is the reference standard, it is crucial to determine itsSCDfirst and apply this value to photography of the skull. So far, such a method for estimating theSCDhas been elusive (some say impossible), compromising the technical validity of the superimposition procedure. This paper tests the feasibility of using the palpebral fissure length and a well‐established photographic algorithm to accurately estimate theSCDfrom the facial photograph. Recordings at knownSCDacross a 1–10 m range (repeated under two test conditions) demonstrate that the newly formulated method works: a meanSCDestimation error of 7% that translates into <1% perspective distortion error between estimated and actual conditions.
A Comparative Study of Phenolic Antioxidant Activity and Flavonoid Biosynthesis‐Related Gene Expression Between Summer and Winter Strawberry Cultivars
Authors: Park Doori , Park Yeri , Lee Young Hun , Choi Ik‐Young , Park Kyong Cheul , Park Sang Un , Kim Byung Sup , Yeoung Young Rog , Park Nam Il
Published: January 2017

Strawberry (Fragaria ananassa Duch.) possesses good antioxidant properties. Phenolic compounds in strawberries, such as anthocyanins and ellagic acid, mainly act as antioxidants. This study aimed to compare the phenolic content and expression patterns of genes involved in flavonoid biosynthesis between summer and winter strawberry cultivars affected by seasonal variation, degree of ripeness, and genotype. Antioxidant activity and the total content of phenols and flavonoids decreased with fruit ripening. Most notably, summer strawberry cultivars showed higher antioxidant activity than winter cultivars. The expression patterns of flavonoid biosynthetic genes tested were cultivar‐dependent and were also affected by ripening. These results help us understand the nutritional and physiological characteristics of selected cultivars and provide a range of information for strawberry consumption.
Effects of Metmyoglobin Reducing Activity and Thermal Stability of NADH‐Dependent Reductase and Lactate Dehydrogenase on Premature Browning in Ground Beef
Authors: Djimsa Blanchefort A. , Abraham Anupam , Mafi Gretchen G. , VanOverbeke Deborah L. , Ramanathan Ranjith
Published: January 2017

Premature browning is a condition wherein ground beef exhibits a well‐done appearance before reaching the USDA recommended internal cooked meat temperature of 71.1 °C; however, the mechanism is unclear. The objectives of this study were: (1) to determine the effects of packaging and temperature on metmyoglobin reducing activity (MRA) of cooked ground beef patties and (2) to assess the effects of temperature and pH on thermal stability of NADH‐dependent reductase, lactate dehydrogenase (LDH), and oxymyoglobin (OxyMb)in‐vitro. Beef patties (lean: fat = 85:15) were packaged in high‐oxygen modified atmosphere (HiOX‐MAP) or vacuum (VP) and cooked to either 65 or 71 °C. Internal meat color and MRA of both raw and cooked patties were determined. Purified NADH‐dependent reductase and LDH were used to determine the effects of pH and temperature on enzyme activity. MRA of cooked patties was temperature and packaging dependent (P< 0.05). Vacuum packaged patties cooked to 71 °C had greater (P< 0.05) MRA than HiOX‐MAP counterparts. Thermal stability of OxyMb, NADH‐dependent reductase, and LDH were different and pH‐dependent. LDH was able to generate NADH at 84 °C; whereas NADH‐dependent reductase was least stable to heat. The results suggest that patties have MRA at cooking temperatures, which can influence cooked meat color.
Negative Association Between MR‐Spectroscopic Glutamate Markers and Gray Matter Volume After Alcohol Withdrawal in the Hippocampus: A Translational Study in Humans and Rats
Authors: Frischknecht Ulrich , Hermann Derik , Tunc‐Skarka Nuran , Wang Guo‐Ying , Sack Markus , van Eijk Julia , Demirakca Traute , Falfan‐Melgoza Claudia , Krumm Bertram , Dieter Sandra , Spanagel Rainer , Kiefer Falk , Mann Karl F. , Sommer Wolfgang H. , Ende Gabriele , Weber‐Fahr Wolfgang
Published: January 2017

Background

Both chronic alcohol consumption and alcohol withdrawal lead to neural tissue damage which partly recovers during abstinence. This study investigated withdrawal‐associated changes in glutamatergic compounds, markers of neuronal integrity, and gray matter volumes during acute alcohol withdrawal in the hippocampus, a key region in development and maintenance of alcohol dependence in humans and rats.

Methods

Alcohol‐dependent patients (N = 39) underwent magnetic resonance imaging (MRI) and MR spectroscopy (MRS) measurements within 24 hours after the last drink and after 2 weeks of abstinence. MRI and MRS data of healthy controls (N = 34) were acquired once. Our thorough quality criteria resulted in N = 15 available spectra from the first and of N = 21 from the second measurement in patients, and of N = 19 from healthy controls. In a translational approach, chronic intermittent ethanol‐exposed rats and respective controls (8/group) underwent 5 MRS measurements covering baseline, intoxication, 12 and 60 hours of withdrawal, and 3 weeks of abstinence.

Results

In both species, higher levels of markers of glutamatergic metabolism were associated with lower gray matter volumes in the hippocampus in early abstinence. Trends of reduced N‐acetylaspartate levels during intoxication persisted in patients with severe alcohol withdrawal symptoms over 2 weeks of abstinence. We observed a higher ratio of glutamate to glutamine during alcohol withdrawal in our animal model.

Conclusions

Due to limited statistical power, we regard the results as preliminary and discuss them in the framework of the hypothesis of withdrawal‐induced hyperglutamatergic neurotoxicity, alcohol‐induced neural changes, and training‐associated effects of abstinence on hippocampal tissue integrity.
Biomarkers for the Detection of Prenatal Alcohol Exposure: A Review
Authors: Bager Heidi , Christensen Lars Porskjær , Husby Steffen , Bjerregaard Lene
Published: January 2017

Alcohol exposure during pregnancy can cause adverse effects to the fetus, because it interferes with fetal development, leading to later physical and mental impairment. The most common clinical tool to determine fetal alcohol exposure is maternal self‐reporting. However, a more objective and useful method is based on the use of biomarkers in biological specimens alone or in combination with maternal self‐reporting. This review reports on clinically relevant biomarkers for detection of prenatal alcohol exposure (PAE). A systematic search was performed to ensure a proper overview in existing literature. Studies were selected to give an overview on clinically relevant neonatal and maternal biomarkers. The direct biomarkers fatty acid ethyl esters (FAEEs), ethyl glucuronide (EtG), ethyl sulfate, and phosphatidylethanol (PEth) were found to be the most appropriate biomarkers in relation to detection of PAE. To review each biomarker in a clinical context, we have compared the advantages and disadvantages of each biomarker, in relation to its window of detectability, ease of collection, and the ease and cost of analysis of each biomarker. The biomarkers PEth, FAEEs, and EtG were found to be applicable for detection of even low levels of alcohol exposure. Meconium is an accessible matrix for determination of FAEEs and EtG, and blood an accessible matrix for determination of PEth.
African‐American Midwifery, a History and a Lament
Authors: Goode Keisha , Katz Rothman Barbara
Published: January 2017

The medicalization of fertility and infertility, pregnancy, abortion, contraception, childbirth, and postpartum care has not always worked in the interests of women. It has had particularly devastating effects on African‐American women. Their fertility has been managed for hundreds of years, first as slaves forced to have children for owners, then as objects to be experimented on without anesthetics, and finally as mothers sterilized without their consent. The relatively high rates of infant and maternal mortality, along with limited access to safe and high‐quality reproductive services, are continuing signs of such devastation. This article discusses the history and consequences of the medicalization of pregnancy, contraception, and abortion in America. Attention is drawn to the ways in which the profession of medicine took control away from midwives, the traditional birth attendants and pregnancy caregivers, and the particular consequences for African‐American women. Ultimately, we posit that greater access to midwifery care could lower infant and maternal mortality rates and improve reproductive services. The reintroduction of spirituality through midwifery would also restore the important role of “wise women” in supporting women, babies, and communities.
Acute liver failure in Scotland: changes in aetiology and outcomes over time (the Scottish Look‐Back Study)
Authors: Donnelly M. C. , Davidson J. S. , Martin K. , Baird A. , Hayes P. C. , Simpson K. J.
Published: January 2017

Background

Acute liver failure is a rare and devastating clinical condition resulting from sudden loss of hepatic parenchyma and metabolic function. The Scottish Liver Transplant Unit (SLTU) offers specialist management and emergency liver transplantation to patients with acute liver failure from across Scotland.

Aim

To describe temporal changes in number of admissions, aetiology of acute liver failure, severity of disease at presentation and outcomes over a 22‐year period.

Methods

Retrospective analysis of the SLTU database, including all patients admitted with acute liver injury or acute liver failure between November 1992 and March 2014.

Results

There has been no change in the number of patients presenting with acute liver injury or failure secondary to paracetamol overdose, but a reduction in the number of admissions with acute liver injury or failure secondary to non paracetamol causes. Over time, disease severity at presentation has not changed in the paracetamol cohort; those with a non paracetamol aetiology have latterly presented with milder hepatic encephalopathy. Spontaneous survival rates improved significantly over time for those patients with acute liver failure due to paracetamol and non paracetamol aetiologies. The most marked improvement in survival is observed in the sickest patients meeting Kings College Hospital poor prognostic criteria.

Conclusions

The number of admissions to the SLTU with acute liver failure is decreasing, due to reduced numbers of non paracetamol cases. Outcomes in this condition are improving, due to improvements in intensive care management and use of liver transplantation, and the increase in survival is most marked in patients meeting Kings College Hospital poor prognostic criteria.
Emergence of mania in two middle‐aged patients with a history of unipolar treatment‐refractory depression receiving vagus nerve stimulation
Authors: Salloum Naji C , Walker Marie C , Gangwani Sunil , Conway Charles R
Published: January 2017

Objectives

We report on two patients who experienced emergence of full manic symptoms while receiving vagal nerve stimulation (VNS).

Methods

Two patients, both with a well‐documented and verified history of longstanding unipolar depression, were initiated on VNS for treatment of their severe major depressive episodes.

Results

The two patients had emergence of full manic symptoms after 8 and 9 months of VNS, respectively. Manic symptoms were adequately managed with standard treatments (mood stabilizer and electroconvulsive therapy) and VNS was continued in the two subjects for up to 5 years without any further occurrences of manic/hypomanic episodes.

Conclusions

These cases suggest that some patients with treatment‐resistant depression may have a previously unrecognized bipolar disorder, triggered only by VNS. This report also provides evidence that VNS‐induced manic switches, however serious and troubling to patients, can be managed safely, and that VNS maintenance can be continued for an extended period of time without manic relapses. Although the mechanism of action of VNS is not known, emerging evidence supports central nervous system dopaminergic and possibly cholinergic system involvement.
BayesCAT: Bayesian Co-estimation of Alignment and Tree
Authors: Shim Heejung , Larget Bret
Published: January 2017

Traditionally, phylogeny and sequence alignment are estimated separately: first estimate a multiple sequence alignment and then infer a phylogeny based on the sequence alignment estimated in the previous step. However, uncertainty in the alignment is ignored, resulting, possibly, in overstated certainty in phylogeny estimates. We develop a joint model for co-estimating phylogeny and sequence alignment which improves estimates from the traditional approach by accounting for uncertainty in the alignment in phylogenetic inferences. Our insertion and deletion (indel) model allows arbitrary-length overlapping indel events and a general distribution for indel fragment size. We employ a Bayesian approach using MCMC to estimate the joint posterior distribution of a phylogenetic tree and a multiple sequence alignment. Our approach has a tree and a complete history of indel events mapped onto the tree as the state space of the Markov Chain while alternative previous approaches have a tree and an alignment. A large state space containing a complete history of indel events makes our MCMC approach more challenging, but it enables us to infer more information about the indel process. The performances of this joint method and traditional sequential methods are compared using simulated data as well as real data. Software named BayesCAT (Bayesian Co-estimation of Alignment and Tree) is available at https://github.com/heejungshim/BayesCAT.
Conditional Estimation in Two-Stage Adaptive Designs
Authors: Broberg Per , Miller Frank
Published: January 2017

We consider conditional estimation in two-stage sample size adjustable designs and the consequent bias. More specifically, we consider a design which permits raising the sample size when interim results look rather promising, and which retains the originally planned sample size when results look very promising. The estimation procedures reported comprise the unconditional maximum likelihood, the conditionally unbiased Rao–Blackwell estimator, the conditional median unbiased estimator, and the conditional maximum likelihood with and without bias correction. We compare these estimators based on analytical results and a simulation study. We show how they can be applied in a real clinical trial setting.
Statistical Significance for Hierarchical Clustering
Authors: Kimes Patrick K. , Liu Yufeng , Hayes David Neil , Marron James Stephen
Published: January 2017

Cluster analysis has proved to be an invaluable tool for the exploratory and unsupervised analysis of high-dimensional datasets. Among methods for clustering, hierarchical approaches have enjoyed substantial popularity in genomics and other fields for their ability to simultaneously uncover multiple layers of clustering structure. A critical and challenging question in cluster analysis is whether the identified clusters represent important underlying structure or are artifacts of natural sampling variation. Few approaches have been proposed for addressing this problem in the context of hierarchical clustering, for which the problem is further complicated by the natural tree structure of the partition, and the multiplicity of tests required to parse the layers of nested clusters. In this article, we propose a Monte Carlo based approach for testing statistical significance in hierarchical clustering which addresses these issues. The approach is implemented as a sequential testing procedure guaranteeing control of the family-wise error rate. Theoretical justification is provided for our approach, and its power to detect true clustering structure is illustrated through several simulation studies and applications to two cancer gene expression datasets.
On Estimation of Time-Dependent Attributable Fraction from Population-Based Case-Control Studies
Authors: Zhao Wei , Chen Ying Qing , Hsu Li
Published: January 2017

Population attributable fraction (PAF) is widely used to quantify the disease burden associated with a modifiable exposure in a population. It has been extended to a time-varying measure that provides additional information on when and how the exposure's impact varies over time for cohort studies. However, there is no estimation procedure for PAF using data that are collected from population-based case-control studies, which, because of time and cost efficiency, are commonly used for studying genetic and environmental risk factors of disease incidences. In this article, we show that time-varying PAF is identifiable from a case-control study and develop a novel estimator of PAF. Our estimator combines odds ratio estimates from logistic regression models and density estimates of the risk factor distribution conditional on failure times in cases from a kernel smoother. The proposed estimator is shown to be consistent and asymptotically normal with asymptotic variance that can be estimated empirically from the data. Simulation studies demonstrate that the proposed estimator performs well in finite sample sizes. Finally, the method is illustrated by a population-based case-control study of colorectal cancer.
A Generalized Levene's Scale Test for Variance Heterogeneity in the Presence of Sample Correlation and Group Uncertainty
Authors: Soave David , Sun Lei
Published: January 2017

We generalize Levene's test for variance (scale) heterogeneity between k groups for more complex data, when there are sample correlation and group membership uncertainty. Following a two-stage regression framework, we show that least absolute deviation regression must be used in the stage 1 analysis to ensure a correct asymptotic distribution of the generalized scale (gS) test statistic. We then show that the proposed gS test is independent of the generalized location test, under the joint null hypothesis of no mean and no variance heterogeneity. Consequently, we generalize the recently proposed joint location-scale (gJLS) test, valuable in settings where there is an interaction effect but one interacting variable is not available. We evaluate the proposed method via an extensive simulation study and two genetic association application studies.
Frontotemporal lobar degeneration: Pathogenesis, pathology and pathways to phenotype
Authors: Mann David M.A. , Snowden Julie S.
Published: January 2017

Frontotemporal Lobar Degeneration (FTLD) is a clinically, pathologically and genetically heterogeneous group of disorders that affect principally the frontal and temporal lobes of the brain. There are three major associated clinical syndromes, behavioral variant frontotemporal dementia (bvFTD), semantic dementia (SD) and progressive non‐fluent aphasia (PNFA); three principal histologies, involving tau, TDP‐43 and FUS proteins; and mutations in three major genes, MAPT, GRN and C9orf72, along with several other less common gene mutations. All three clinical syndromes can exist separately or in combination with Amyotrophic Lateral Sclerosis (ALS). SD is exclusively a TDP‐43 proteinopathy, and PNFA may be so, with both showing tight clinical, histological and genetic inter‐relationships. bvFTD is more of a challenge with overlapping histological and genetic features, involvement of any of the three aggregating proteins, and changes in any of the three major genes. However, when ALS is present, all cases show a clear histological phenotype with TDP‐43 aggregated proteins, and familial forms are associated with expansions in C9orf72. TDP‐43 and FUS are nuclear carrier proteins involved in the regulation of RNA metabolism, whereas tau protein – the product of MAPT – is responsible for the assembly/disassembly of microtubules, which are vital for intracellular transport. Mutations in TDP‐43 and FUS genes are linked to clinical ALS rather than FTLD (with or without ALS), suggesting that clinical ALS may be a disorder of RNA metabolism. Conversely, the protein products of GRN and C9orf72, along with those of the other minor genes, appear to form part of the cellular protein degradation machinery. It is possible therefore that FTLD is a reflection of dysfunction within lysosomal/proteasomal systems resulting in failure to remove potentially neurotoxic (TDP‐43 and tau) aggregates, which ultimately overwhelm capacity to function. Spread of aggregates along distinct pathways may account for the different clinical phenotypes, and patterns of progression of disease.
Physicochemical and biological evaluation of a cinnamamide derivative R,S‐(2E)‐1‐(3‐hydroxypiperidin‐1‐yl)‐3‐phenylprop‐2‐en‐1‐one (KM‐608) for nervous system disorders
Authors: Gunia‐Krzyżak Agnieszka , Żesławska Ewa , Bareyre Florence M. , Nitek Wojciech , Waszkielewicz Anna M. , Marona Henryk
Published: January 2017

A cinnamamide scaffold has been successfully incorporated in several compounds possessing desirable pharmacological activities in central and peripheral nervous system such as anticonvulsant, antidepressant, neuroprotective, analgesic, anti‐inflammatory, muscle relaxant, and sedative/hypnotic properties. R,S‐(2E)‐1‐(3‐hydroxypiperidin‐1‐yl)‐3‐phenylprop‐2‐en‐1‐one (KM‐608), a cinnamamide derivative, was synthesized, its chemical structure was confirmed by means of spectroscopy and crystallography, and additionally, thermal analysis showed that it exists in one crystalline form. The compound was evaluated in vivo in rodents as anticonvulsant, antiepileptogenic, analgesic, and neuroprotective agent. The beneficial properties of the compound were found in animal models of seizures evoked electrically (maximal electroshock test, 6‐Hz) and chemically (subcutaneous pentylenetetrazole seizure test) as well as in three animal models of epileptogenesis: corneal‐kindled mice, hippocampal‐kindled rats, and lamotrigine‐resistant amygdala‐kindled rats. Quantitative pharmacological parameters calculated for the tested compound were comparable to those of currently used antiepileptic drugs. In vivo pharmacological profile of KM‐608 corresponds with the activity of valproic acid.
High-level intrathymic thyrotrophin receptor expression in thyroiditis-prone mice protects against the spontaneous generation of pathogenic thyrotrophin receptor autoantibodies
Authors: McLachlan S M , Aliesky H A , Banuelos B , Lesage S , Collin R , Rapoport B
Published: January 2017

The thyrotrophin receptor (TSHR) A-subunit is the autoantigen targeted by pathogenic autoantibodies that cause Graves' hyperthyroidism, a common autoimmune disease in humans. Previously, we reported that pathogenic TSHR antibodies develop spontaneously in thyroiditis-susceptible non-obese diabetic (NOD).H2h4 mice bearing a human TSHR A-subunit transgene, which is expressed at low levels in both the thyroid and thymus (Lo-expressor transgene). The present study tested recent evidence that high intrathymic TSHR expression protects against the development of pathogenic TSHR antibodies in humans. By successive back-crossing, we transferred to the NOD.H2h4 background a human TSHR A-subunit transgene expressed at high levels in the thyroid and thymus (Hi-expressor transgene). In the sixth back-cross generation (> 98% NOD.H2h4 genome), only transgenic offspring produced spontaneously immunoglobulin (Ig)G class non-pathogenic human TSHR A-subunit antibodies. In contrast, both transgenic and non-transgenic offspring developed antibodies to thyroglobulin and thyroid peroxidase. However, non-pathogenic human TSHR antibody levels in Hi-expressor offspring were lower than in Lo-expressor transgenic mice. Moreover, pathogenic TSHR antibodies, detected by inhibition of TSH binding to the TSHR, only developed in back-cross offspring bearing the Lo-expressor, but not the Hi-expressor, transgene. High versus low expression human TSHR A-subunit in the NOD.H2h4 thymus was not explained by the transgene locations, namely chromosome 2 (127–147 Mb; Hi-expressor) and chromosome 1 (22.9–39.3 Mb; low expressor). Nevertheless, using thyroiditis-prone NOD.H2h4 mice and two transgenic lines, our data support the association from human studies that low intrathymic TSHR expression is associated with susceptibility to developing pathogenic TSHR antibodies, while high intrathymic TSHR expression is protective.
Accounting for Life‐History Strategies and Timescales in Marine Restoration
Authors: Montero‐Serra Ignasi , Garrabou Joaquim , Doak Daniel F. , Figuerola Laura , Hereu Bernat , Ledoux Jean‐Baptiste , Linares Cristina
Published: January 2017

Understanding the drivers of restoration success is a central issue for marine conservation. Here, we explore the role of life‐history strategies of sessile marine species in shaping restoration outcomes and their associated timescales. A transplantation experiment for the extremely slow‐growing and threatened octocoralCorallium rubrumwas highly successful over a relatively short term due to high survival and reproductive potential of the transplanted colonies. However, demographic projections predict that from 30 to 40 years may be required for fully functionalC. rubrumpopulations to develop. More broadly, a comprehensive meta‐analysis revealed a negative correlation between survival after transplanting and growth rates among sessile species. As a result, simulated dynamics for a range of marine sessile invertebrates predict that longer recovery times are positively associated with survival rates. These results demonstrate a tradeoff between initial transplantation efforts and the speed of recovery. Transplantation of slow‐growing species will tend to require lower initial effort due to higher survival after transplanting, but the period required to fully recover habitat complexity will tend to be far longer. This study highlights the important role of life history as a driver of marine restoration outcomes and shows how demographic knowledge and modeling tools can help managers to anticipate the dynamics and timescales of restored populations.
Aberrant tyrosinase expression in an atypical fibroxanthoma: A case report
Authors: Weiss Amy , Vanchinathan Vijay , Kwon Eun J.
Published: January 2017

Atypical fibroxanthoma (AFX) is a histologic mimicker of a variety of spindle cell neoplasms, and careful microscopic and immunohistochemical evaluation is critical in establishing the correct diagnosis. Here we report the histologic and immunohistochemical work up of a 1 cm nodule involving the left dorsal hand of a 66‐year‐old patient. Light microscopy revealed fascicles of spindled and pleomorphic cells within the dermis showing increased mitotic activity occurring in the background of sun‐damaged skin. There were numerous multinucleated cells with hyperchromatic nuclei and ample finely vacuolated or foamy cytoplasms. There was strong and diffuse CD10 and patchy CD68 expression among the spindled cells and multinucleated cells. The neoplastic cells did not show immunoreactivity against S100, p75‐NGFR, HMB‐45 or a panel of keratinocytic, vascular and smooth muscle markers. Tyrosinase and Melan‐A were not expressed within the spindle cell component of this neoplasm; however, there was tyrosinase expression among numerous multinucleated giant cells. Melan‐A expression was also observed among rare multinucleated giant cells. Tyrosinase expression has not previously been reported in AFX.
Morbihan disease complicated by dermatosis neglecta: An unique presentation
Authors: Eber Ariel E. , Mlacker Stephanie , Verne Sebastian , Griffith Robert , Ledon Jennifer , Perper Marina , Nouri Keyvan , Cho‐Vega Jeong Hee
Published: January 2017

Morbihan disease, also referred to as solid facial edema, or rosacea lymphedema, is a rare disorder that involves chronic erythema and solid edema of the cheeks, eyelids, forehead and glabella and may arise as a complication of acne vulgaris or rosacea. Of note, it may be the only initial presenting symptom of these associated diseases. Few cases have been described in the literature, as its first description by Robert Degos in 1957. The condition is characterized by its chronicity, a typical clinical appearance and the lack of specific histopathologic or laboratory findings. The condition may wax and wane but typically does not resolve without treatment. Many cases of this condition tend to be recalcitrant to therapy, with topical and oral antibiotics regimens commonly used for rosacea generally being ineffective. The disease may easily go undiagnosed, as it mimics other more common skin conditions. We present a case of originally undiagnosed Morbihan disease mistaken for an atypical allergic rash, resistant to treatment, and complicated by dermatosis neglecta.
Clinical and histopathological features of cutaneous nontuberculous mycobacterial infection: a review of 13 cases
Authors: Li Jing Jing , Beresford Rohan , Fyfe Janet , Henderson Christopher
Published: January 2017

Background

The incidence of cutaneous nontuberculous mycobacterial (NTM) infection has increased in recent decades because of widespread use of immunosuppressive therapy and better detection methods. The histopathology of cutaneous NTM infection is not pathognomic and the organisms are slow and difficult to culture, making diagnosis challenging.

Methods

We reviewed the clinical and histopathological features of 13 cases of cutaneous NTM infection, and performed panmycobacterial polymerase chain reaction (PCR) on the paraffin blocks.

Results

The immunocompetent patients presented with localized lesions on the extremities, whereas the immunocompromised patients presented with disseminated cutaneous lesions. The histopathology in immunocompetent patients was characterized by pseudoepitheliomatous epidermal hyperplasia, intraepithelial abscesses, transepidermal elimination and dermal granulomatous inflammation accompanied by necrosis and suppuration. The immunocompromised patients showed suppurative inflammation with little granuloma formation and numerous acid‐fast bacilli. Paraffin block PCR was positive in 4 of 13 cases (31%), whereas culture was positive in 11 of 13 cases (85%).

Conclusion

The aforementioned histological features should help in diagnosing cutaneous NTM infection when combined with clinical and microbiological correlation. In our study, we did not find paraffin block PCR to be superior to conventional culture in detecting cutaneous NTM infection.
Are winter and breeding bird communities able to track rapid climate change? Lessons from the high North
Authors: Santangeli Andrea , Lehikoinen Aleksi
Published: January 2017

Aim

Climate change is a major threat to biodiversity and a major factor underlying observed shifts in species distribution, abundance and phenology. Research effort on climate change impacts on species has often been based on single‐species studies focused on a single season, typically the breeding season, of species life cycles. We test how well winter and breeding bird communities are able to track climate change.

Location

Finland.

Methods

We use a dataset consisting of bird counts from the winter and the breeding period spanning over four decades and a 1000 km latitudinal gradient across Finland, Northern Europe. We use the bird count data in combination with a species‐specific average temperature index to derive a functional index, the Community Temperature Index (CTI), which provides a measure of the relative temperature average of a community.

Results

We show that the CTI of the winter bird community (CTIw) in Finland has increased significantly over the past four decades, but not as fast as the average winter temperature. Across Finland, CTIw decreased towards the north and the east of the country and increased with increasing temperature. Further, we show that change in CTI through time (from 1970s–1980s to 2000–2014) was similar between the winter and the breeding communities.

Main conclusions

Overall, our results suggest that while the winter and breeding bird communities are, to a certain level, tracking increasing temperatures, the magnitude of temperature change is multiple times greater than the magnitude of community shifts. This is particularly true for the winter birds that are facing the most rapid temperature shifts. Our findings shed light on the importance of assessing and eventually addressing the effects of rapid climate warming beyond the breeding season of species life cycles.
The use of range size to assess risks to biodiversity from stochastic threats
Authors: Murray Nicholas J. , Keith David A. , Bland Lucie M. , Nicholson Emily , Regan Tracey J. , Rodríguez Jon Paul , Bedward Michael
Published: January 2017

Aim

Stochastic threats such as disease outbreak, pollution events, fire, tsunami and drought can cause rapid species extinction and ecosystem collapse. The ability of a species or ecosystem to persist after a stochastic threat is strongly related to the extent and spatial pattern of its geographical distribution. Consequently, protocols for assessing risks to biodiversity typically include geographic range size criteria for assessing risks from stochastic threats. However, owing in part to the rarity of such events in nature, the metrics for assessing risk categories have never been tested. In this study, we investigate the performance of alternative range size metrics, including the two most widely used, extent of occurrence (EOO) and area of occupancy (AOO), as predictors of ecosystem collapse in landscapes subject to stochastic threats.

Methods

We developed a spatially explicit stochastic simulation model to investigate the impacts of four threat types on a dataset of 1350 simulated geographic distributions of varying pattern and size. We empirically estimated collapse probability in response to each threat type and evaluated the ability of a set of spatial predictors to predict risk.

Results

The probability of ecosystem collapse increased rapidly as range size declined. While AOO and EOO were the most important predictors of collapse risk for the three spatially explicit threats included in our model (circle, swipe and cluster), core area, patch density and mean patch size were better predictors for edge effect threats.

Main conclusions

Our study is the first to quantitatively assess the range size metrics employed in biodiversity risk assessment protocols. We show that the current methods for measuring range size are the best spatial metrics for estimating risks from stochastic threats. Our simulation framework delivers an objective assessment of the performance of hitherto untested but widely used measures of geographic range size for risk assessment.
Clinical, behavioural and social indicators for poor glycaemic control around the time of transfer to adult care: a longitudinal study of 126 young people with diabetes
Authors: Castensøe‐Seidenfaden P. , Jensen A. K. , Smedegaard H. , Hommel E. , Husted G. R. , Pedersen‐Bjergaard U. , Teilmann G.
Published: January 2017

Aims

To describe and compare changes in glycaemic control in young people with Type 1 diabetes over time between the last 2 years in paediatric care and the first 2 years in adult care and to identify risk factors for poor glycaemic control.

Methods

Our retrospective cohort study followed participants aged 14–22 years from 2 years before to 2 years after transfer from paediatric to adult care. Changes in glycaemic control were calculated using repeated measurements. We adjusted for gender, age at diabetes onset, age at transfer, duration of diabetes at transfer, gap (amount of time) between last paediatric and first adult visit, comorbidity, learning disability and/or mental health conditions and family structure. We examined associations between acute hospital admissions, low visit attendance rate, loss to follow‐up and baseline HbA1c level.

Results

Among 126 participants, the mean HbA1c level was 80 mmol/mol (9.4%) pre‐transfer but decreased by an average of 3 mmol/mol (0.3%) each year post‐transfer (P = 0.005). Young people with a learning disability and/or a mental health condition had worse glycaemic control (P = 0.041) and the mean HbA1c of those with divorced parents was 14 mmol/mol (1.2%) higher (P = 0.014). Almost one‐third of participants were admitted to the hospital for acute diabetes care. Low visit attendance rate, high baseline HbA1c level, learning disability and/or mental health conditions and divorced parents predicted acute hospital admissions.

Conclusions

Glycaemic control improved significantly after transfer to adult care, but the mean HbA1c level remained high. Future interventions should focus on young people with divorced parents, those with a learning disability and/or mental health condition and those who do not attend clinical visits to improve HbA1c levels and thereby reduce hospitalization rates.
Frequency of CNKSR2 mutation in the X‐linked epilepsy‐aphasia spectrum
Authors: Damiano John A. , Burgess Rosemary , Kivity Sara , Lerman‐Sagie Tally , Afawi Zaid , Scheffer Ingrid E. , Berkovic Samuel F. , Hildebrand Michael S.
Published: January 2017

Synaptic proteins are critical to neuronal function in the brain, and their deficiency can lead to seizures and cognitive impairments. CNKSR2 (connector enhancer of KSR2) is a synaptic protein involved in Ras signaling‐mediated neuronal proliferation, migration and differentiation. Mutations in the X‐linked gene CNKSR2 have been described in patients with seizures and neurodevelopmental deficits, especially those affecting language. In this study, we sequenced 112 patients with phenotypes within the epilepsy‐aphasia spectrum (EAS) to determine the frequency of CNKSR2 mutation within this complex set of disorders. We detected a novel nonsense mutation (c.2314 C>T; p.Arg712*) in one Ashkenazi Jewish family, the male proband of which had a severe epileptic encephalopathy with continuous spike‐waves in sleep (ECSWS). His affected brother also had ECSWS with better outcome, whereas the sister had childhood epilepsy with centrotemporal spikes. This mutation segregated in the three affected siblings in an X‐linked manner, inherited from their mother who had febrile seizures. Although the frequency of point mutation is low, CNKSR2 sequencing should be considered in families with suspected X‐linked EAS because of the specific genetic counseling implications.