bluuebunny/crossref_metadata_2025 huggingface dataset:
Bangladesh accountants and Continuing Professional Development
Authors: Halabi Abdel Karim , Chowdhury Mohammad Salahuddin
Published: November 2018

Purpose

The purpose of this paper is to examine professional accountant’s views on their satisfaction with Continuing Professional Development (CPD) offered by members of the Institute of Chartered Accountants of Bangladesh (ICAB). While there is a great deal of research on CPD and accountants in developed countries, less developing countries are absent from this literature, and there have been calls for this type of research.

Design/methodology/approach

The present study employed a survey of members of the ICAB.

Findings

Results show that accountants in Bangladesh are satisfied with the CPD provided by their profession, and when satisfaction is compared with more developed countries, Bangladesh is greater on a number of measures. ICAB members would like to also be provided with opportunities to undertake CPD in more ways than just face to face.

Practical implications

The study has important implications not only for accountants from emerging economies such as Bangladesh, but also for the International Federation of Accountants and other less developed countries (LDCs). The results advance the understanding of professional accounting bodies from an international perspective.

Originality/value

This is the first study of CPD and accounting professionals in LDCs. The information obtained can inform the development and practice of other professional accounting bodies in emerging economies.
The alternative sigma factor SigF is a key player in the control of secretion mechanisms in Synechocystis sp. PCC 6803
Authors: Flores Carlos , Santos Marina , Pereira Sara B. , Mota Rita , Rossi Federico , De Philippis Roberto , Couto Narciso , Karunakaran Esther , Wright Phillip C. , Oliveira Paulo , Tamagnini Paula
Published: November 2018

Cyanobacterial alternative sigma factors are crucial players in environmental adaptation processes, which may involve bacterial responses related to maintenance of cell envelope and control of secretion pathways. Here, we show that the Group 3 alternative sigma factor F (SigF) plays a pleiotropic role in Synechocystis sp. PCC 6803 physiology, with a major impact on growth and secretion mechanisms, such as the production of extracellular polysaccharides, vesiculation and protein secretion. Although ΔsigF growth was significantly impaired, the production of released polysaccharides (RPS) increased threefold to fourfold compared with the wild‐type. ΔsigF exhibits also impairment in formation of outer‐membrane vesicles (OMVs) and pili, as well as several other cell envelope alterations. Similarly, the exoproteome composition of ΔsigF differs from the wild‐type both in amount and type of proteins identified. Quantitative proteomics (iTRAQ) and an in silico analysis of SigF binding motifs revealed possible targets/pathways under SigF control. Besides changes in protein levels involved in secretion mechanisms, our results indicated that photosynthesis, central carbon metabolism and protein folding/degradation mechanisms are altered in ΔsigF. Overall, this work provided new evidences about the role of SigF on Synechocystis physiology and associates this regulatory element with classical and non‐classical secretion pathways.
Multilingual matrix: exploring the process of language switching by family therapists working with multilingual families
Authors: Das Sreety
Published: November 2018

This article explores the phenomenon of language switching in clinical practice in the systemic psychotherapy field. I consider multilingual therapists’ experiences of switching from use of one language to another in the therapeutic context, the therapists’ awareness of this, and the intentions or possible meanings they attribute to these experiences. The interpretative phenomenological approach was used to analyse the experiences of four female family therapists based in London and from a range of cultures and communities.

It was found that the therapists construed their multilingual position as both challenging and advantageous. Suggestions are made to explore the language switching phenomenon in supervision and training, as well as to think more widely with monolingual and multilingual colleagues and supervisors about the meaning and the use of language switching in therapeutic practice. Existing research in this area can be developed further to provide a framework that could benefit practitioners in the systemic field.

Practitioner points

Language switching was viewed as an invaluable skill by therapists, enabling them to shift between languages and understand their clients’ world in a rich way

Multilingual family therapists can address issues of power and voice with families through the practice of language switching
A Stronghold of Routine Corporatism? The Involvement of Interest Groups in Policy Making in Finland
Authors: Vesa Juho , Kantola Anu , Binderkrantz Anne Skorkjær
Published: November 2018

While the Nordic countries have a tradition of integrating privileged interest groups into policy making, a number of studies have argued that this Nordic ‘routine corporatism’ has changed over the last decades. Studies of Denmark, Norway and Sweden demonstrate that interest groups are less frequently involved in committees preparing policy, that lobbying of parliament has become more important and that the position of citizen groups has strengthened. However, systematic studies of present‐day Finland are largely missing. This article therefore adds to the literature by focusing on the Finnish case. Drawing on surveys of interest groups and civil servants, the involvement of interest groups in policy making in Finland is assessed and compared with Denmark and the United Kingdom. It is found that: (1) working groups and similar bodies are still very important sites of advocacy; (2) public administration is a more important site of advocacy than parliament or government; (3) economic groups continue to enjoy a particularly privileged position; and (4) resources predict groups’ access to policy making more strongly in Finland than in Denmark or the United Kingdom. These findings imply that routine corporatism persists in Finland to a greater extent than in Denmark. The study augments the existing evidence that corporatism may have adapted to new circumstances rather than being eliminated.
Left‐right Orientation, Homeownership and Class Position in Sweden
Authors: Davidsson Simon
Published: November 2018

Sweden is a country where left‐right orientation structures the political landscape, homeownership is increasingly important, and the importance of class for political preferences and behavior is changing or even weakening. This article explores the significance of homeownership for left‐right orientation in Sweden, and extends the relationship to include class position. By combining detailed cross‐sectional survey data with data on regional house price variations it suggests that homes function as an economic asset that affects individual political preferences. Furthermore, the relationship between homeownership and left‐right orientation is expected to be driven by particular class groups, whose labor market position imply a more leftist orientation, while their status as homeowners imply a more rightist one. The expectation is borne out, which indicates that the asset function of homes help accounting for changing class patterns of left‐right orientation in Sweden.
Mammography facilities serving vulnerable women have longer follow‐up times
Authors: Karliner Leah S. , Kaplan Celia , Livaudais‐Toman Jennifer , Kerlikowske Karla
Published: November 2018

Objective

To investigate mammography facilities’ follow‐up times, population vulnerability, system‐based processes, and association with cancer stage at diagnosis.

Data Sources

Prospectively collected from San Francisco Mammography Registry (SFMR) 2005‐2011, California Cancer Registry 2005‐2012, SFMR facility survey 2012.

Study Design

We examined time to biopsy for 17 750 abnormal mammogram results (BI‐RADS 4/5), categorizing eight facilities as short or long follow‐up based on proportion of mammograms with biopsy at 30 days. We examined facility population vulnerability (race/ethnicity, language, education), and system processes. Among women with a cancer diagnosis, we modeled odds of advanced‐stage (≥IIb) cancer diagnosis by facility follow‐up group.

Data Extraction Methods

Merged SFMR, Cancer Registry and facility survey data.

Principal Findings

Facilities (N = 4) with short follow‐up completed biopsies by 30 days for 82% of mammograms compared with 62% for facilities with long follow‐up (N = 4) (P < 0.0001). All facilities serving high proportions of vulnerable women were long follow‐up facilities. The long follow‐up facilities had fewer radiologists, longer biopsy appointment wait times, and less communication directly with women. Having the index abnormal mammogram at a long follow‐up facility was associated with higher adjusted odds of advanced‐stage cancer (OR 1.45; 95% CI 1.10‐1.91).

Conclusions

Providing mammography facilities serving vulnerable women with appropriate resources may decrease disparities in abnormal mammogram follow‐up and cancer diagnosis stage.
CRISPR/Cas‐based screening of a gene activation library in Saccharomyces cerevisiae identifies a crucial role of OLE1 in thermotolerance
Authors: Li Pengsong , Fu Xiaofen , Zhang Lei , Li Shizhong
Published: November 2018

CRISPR/Cas‐based (clustered regularly interspaced short palindromic repeats/CRISPR‐associated) screening has been proved to be an efficient method to study functional genomics from yeast to human. In this study, we report the development of a focused CRISPR/Cas‐based gene activation library in Saccharomyces cerevisiae and its application in gene identification based on functional screening towards improved thermotolerance. The gene activation library was subjected to screening at 42°C, and the same library cultured at 30°C was set as a control group. After five successive subcultures, five clones were randomly picked from the libraries cultured at 30 and 42°C, respectively. The five clones selected at 30°C contain the specificity sequences of five different single guide RNAs, whereas all the five clones selected at 42°C contain the specificity sequence of one sgRNA that targets the promoter region of OLE1. A crucial role of OLE1 in thermotolerance was identified: the overexpression of OLE1 increased fatty acid unsaturation, and thereby helped counter lipid peroxidation caused by heat stress, rendering the yeast thermotolerant. This study described the application of CRISPR/Cas‐based gene activation screening with an example of thermotolerant yeast screening, demonstrating that this method can be used to identify functional genes in yeast.
Assessing and Prioritizing Barriers to Aquatic Connectivity in the Eastern United States
Authors: Martin Erik H.
Published: November 2018

There are tens of thousands of dams and millions of road‐stream crossings in the eastern United States (U.S.) which can prevent fish and other aquatic organisms from accessing key habitats. There is growing momentum in the eastern U.S., and throughout the country, to remove dams which no longer serve their intended purpose, provide improved fish passage facilities at those dams that cannot feasibly be removed, and upgrade road‐stream crossings to benefit aquatic organism passage (AOP). However, these projects are expensive and given the extensive scope of the problem and the limited resources available to address it, it is imperative to be strategic in deciding which barriers are removed or upgraded. The Nature Conservancy, in conjunction with several partners, has conducted a suite of analyses which assess and prioritize barriers to AOP for the potential ecological gains that could be realized if they were removed or upgraded. The results of these analyses have been used both proactively and reactively by managers throughout the eastern U.S. to identify potential connectivity restoration projects, support funding requests, and help inform funding allocation decisions by providing a common evaluation system for the many thousands of potential projects. In contrast to more prescriptive barrier removal optimizations, their flexibility of use provides managers with a practical framework for planning aquatic connectivity restoration while remaining open to the element of opportunity.
Towards a systematic understanding of differences between archaeal and bacterial diversity
Authors: Spang Anja , Offre Pierre
Published: November 2018

In this crystal ball, we discuss emerging methodologies that can help reaching a synthesis on the biodiversity of Archaea and Bacteria and thereby inform a central enigma in microbiology, i.e. the fundamental split between these primary domains of life and the apparent lower diversity of the Archaea.
Drinking Risk Level Reductions Associated with Improvements in Physical Health and Quality of Life Among Individuals with Alcohol Use Disorder
Authors: Witkiewitz Katie , Kranzler Henry R. , Hallgren Kevin A. , O'Malley Stephanie S. , Falk Daniel E. , Litten Raye Z. , Hasin Deborah S. , Mann Karl F. , Anton Raymond F.
Published: November 2018

Background

Abstinence and no heavy drinking days are currently the only Food and Drug Administration–approved end points in clinical trials for alcohol use disorder (AUD). Many individuals who fail to meet these criteria may substantially reduce their drinking during treatment, and most individuals with AUD prefer drinking reduction goals. One‐ and two‐level reductions in World Health Organization (WHO) drinking risk levels have been proposed as alternative end points that reflect reduced drinking and are associated with reductions in drinking consequences, improvements in mental health, and reduced risk of developing alcohol dependence. The current study examined the association between WHO drinking risk level reductions and improvements in physical health and quality of life in a sample of individuals with alcohol dependence.

Methods

Secondary data analysis of individuals with alcohol dependence (n = 1,142) enrolled in the longitudinal, prospective COMBINE study, a multi site randomized placebo‐controlled clinical trial, examining the association between reductions in WHO drinking risk levels and change in blood pressure, liver enzyme levels, and self‐reported quality of life following treatment for alcohol dependence.

Results

One‐ and two‐level reductions in WHO drinking risk level during treatment were associated with significant reductions in systolic blood pressure (p < 0.001), improvements in liver enzyme levels (all p < 0.01), and significantly better quality of life (p < 0.001).

Conclusions

One‐ and two‐level reductions in WHO drinking risk levels predicted significant improvements in markers of physical health and quality of life, suggesting that the WHO drinking risk level reduction could be a meaningful surrogate marker of improvements in how a person “feels and functions” following treatment for alcohol dependence. The WHO drinking risk levels could be useful in medical practice for identifying drinking reduction targets that correspond with clinically significant improvements in health and quality of life.
Comparative use of active searches and artificial refuges to detect amphibians in terrestrial environments
Authors: Michael Damian R. , Blanchard Wade , Scheele Ben C. , Lindenmayer David B.
Published: November 2018

Artificial refuges (cover boards) are commonly used to survey and monitor herpetofauna in many parts of the world. Despite the extensive use of artificial refuges in mesic environments, their effectiveness for detecting amphibians in temperate zones has rarely been examined. We compared amphibian detection probabilities between two survey methods; active searches of natural habitat and artificial refuges of three different types (corrugated steel, roofing tiles and timber railway sleepers). Our study area included five bioregions encompassing a 1180‐km latitudinal gradient across a modified, temperate eucalypt woodland vegetation community in south‐eastern Australia. We deployed 14 778 artificial refuges in terrestrial environments, within patches of remnant vegetation, and collected presence and abundance data on herpetofauna between 1999 and 2017. We used Bayesian logistic regression to identify the most effective survey method for detecting frog species across all bioregions. We modelled frog detections by fitting survey method, time since refuge deployment and rainfall prior to each survey. We detected 3970 individuals from 18 frog species. Overall, we found active searches and timber substrates most effective for detecting a broad range of species, although detection rates were driven by the numerically abundant spotted marsh frog Limnodynastes tasmaniensis. Timber refuges were effective for detecting several burrowing species, whereas active searches were effective at detecting habitat generalists. Quadratic effects of rainfall prior to survey as opposed to linear effects of time since artificial refuge placement was important in explaining frog detection rates in some bioregions. Active searches, timber railway sleepers and sheets of corrugated steel provide complimentary survey methods for detecting amphibians, although detection rates are influenced by rainfall patterns. Artificial refuges provide a time‐effective and standardized method for studying amphibians in their non‐breeding terrestrial environment and should be incorporated into future surveys and biodiversity monitoring programmes.
Modern management of recurrent miscarriage
Authors: Homer Hayden Anthony
Published: November 2018

Recurrent miscarriage (RM), also known as recurrent pregnancy loss, is a distressing condition affecting around 1% of couples trying to conceive It can be very frustrating for both clinicians and patients as, despite intensive workup, no clear underlying pathology is forthcoming in at least 50% of couples. This leads to despair for patients and leaves clinicians at a loss for how to help. Desperation in both camps can promote the uptake of investigations and interventions of unproven benefit. The pathophysiology underpinning RM is incredibly diverse, involving areas such as haematology, endocrinology, immunology and genetics. During the seven to eight years since the UK Royal College of Obstetricians and Gynaecologists published guidelines on this topic in 2011, new evidence and guidance from expert authorities have emerged. Here, these important advances in this challenging field of clinical practice will be reviewed.
Efficacy of DPP‐4 inhibitors, GLP‐1 analogues, and SGLT2 inhibitors as add‐ons to metformin monotherapy in T2DM patients: a model‐based meta‐analysis
Authors: Inoue Hiroyuki , Tamaki Yoko , Kashihara Yushi , Muraki Shota , Kakara Makoto , Hirota Takeshi , Ieiri Ichiro
Published: November 2018

Aims

The aim of the present study was to quantitate the hypoglycaemic effects of dipeptidyl peptidase‐4 inhibitors (DPP‐4i), glucagon‐like peptide‐1 receptor agonists (GLP‐1r) and sodium glucose cotransporter 2 inhibitors (SGLT2i) as add‐on treatments to metformin monotherapy in patients with type 2 diabetes mellitus (T2DM) using a model‐based meta‐analysis (MBMA).

Methods

A systematic literature search of public databases was conducted to develop models that describe the time courses of the fasting plasma glucose (FPG)‐ and haemoglobin A1c (HbA1c)‐lowering effects of three antidiabetic classes using NONMEM 7.3.0.

Results

Seventy‐six publications were eligible for this study, and 873 FPG and 1086 HbA1c values were collected. We developed a physiological indirect response model that described the time courses of FPG and HbA1c and simulated reductions in these values 90 days after the initiation of add‐on treatments. FPG and HbA1c reductions with once weekly exenatide, liraglutide and dulaglutide were greater than those with other drugs. Mean changes from baseline FPG and HbA1c with these drugs were as follows: exenatide (−22.5 and −16.6%), liraglutide (−22.1 and −16.3%), and dulaglutide (−19.3 and −14.3%). The hypoglycaemic effects of DPP‐4i and SGLT2i were similar.

Conclusions

Once weekly exenatide, liraglutide and dulaglutide provided better hypoglycaemic effects among the antidiabetic drugs analysed. Long‐acting GLP‐1r appears to be more useful for T2DM patients inadequately controlled with metformin monotherapy.
Thrombotic microangiopathy associated with gemcitabine use: Presentation and outcome in a national French retrospective cohort
Authors: Daviet Florence , Rouby Franck , Poullin Pascale , Moussi‐Francès Julie , Sallée Marion , Burtey Stéphane , Mancini Julien , Duffaud Florence , Sabatier Renaud , Pourroy Bertrand , Grandvuillemin Aurélie , Grange Steven , Frémeaux‐Bacchi Véronique , Coppo Paul , Micallef Joëlle , Jourde‐Chiche Noémie
Published: November 2018

Aims

Gemcitabine has been associated with thrombotic microangiopathy (TMA). We conducted a national retrospective study of gemcitabine‐associated TMA (G‐TMA).

Methods

From 1998 to 2015, all cases of G‐TMA reported to the French Pharmacovigilance Network and the French TMA Reference Center, and cases explored for complement alternative pathway abnormalities, were analysed.

Results

G‐TMA was diagnosed in 120 patients (median age 61.5 years), after a median of 210 days of treatment, and a cumulative dose of 12 941 mg m–2. Gemcitabine indications were: pancreatic (52.9%), pulmonary (12.6%) and breast (7.6%) cancers, metastatic in 34.2% of cases. Main symptoms were oedema (56.7%) and new‐onset or exacerbated hypertension (62.2%). Most patients presented with haemolytic anaemia (95.6%) and thrombocytopenia (74.6%). Acute kidney injury was reported in 97.4% and dialysis was required in 27.8% of patients. Treatment consisted of: plasma exchange (PE; 39.8%), fresh frozen plasma (21.4%), corticosteroids (15.3%) and eculizumab (5.1%). A complete remission of TMA was obtained in 42.1% of patients and haematological remission in 23.1%, while 34.7% did not improve. The survival status was known for 52 patients, with 29 deaths (54.7%). Patients treated with PE, despite a more severe acute kidney injury, requiring dialysis more frequently, displayed comparable rates of remission, but with more adverse events. No abnormality in complement alternative pathway was documented in patients explored.

Conclusion

This large cohort confirms the severity of G‐TMA, associated with severe renal failure and death. Oedema and hypertension could be monitored in patients treated with gemcitabine to detect early TMA. The benefit of PE or eculizumab deserves further investigation.
A long winter for the Red Queen: rethinking the evolution of seasonal migration
Authors: Winger Benjamin M. , Auteri Giorgia G. , Pegan Teresa M. , Weeks Brian C.
Published: November 2018

This paper advances an hypothesis that the primary adaptive driver of seasonal migration is maintenance of site fidelity to familiar breeding locations. We argue that seasonal migration is therefore principally an adaptation for geographic persistence when confronted with seasonality – analogous to hibernation, freeze tolerance, or other organismal adaptations to cyclically fluctuating environments. These ideas stand in contrast to traditional views that bird migration evolved as an adaptive dispersal strategy for exploiting new breeding areas and avoiding competitors. Our synthesis is supported by a large body of research on avian breeding biology that demonstrates the reproductive benefits of breeding‐site fidelity. Conceptualizing migration as an adaptation for persistence places new emphasis on understanding the evolutionary trade‐offs between migratory behaviour and other adaptations to fluctuating environments both within and across species. Seasonality‐induced departures from breeding areas, coupled with the reproductive benefits of maintaining breeding‐site fidelity, also provide a mechanism for explaining the evolution of migration that is agnostic to the geographic origin of migratory lineages (i.e. temperate or tropical). Thus, our framework reconciles much of the conflict in previous research on the historical biogeography of migratory species. Although migratory behaviour and geographic range change fluidly and rapidly in many populations, we argue that the loss of plasticity for migration via canalization is an overlooked aspect of the evolutionary dynamics of migration and helps explain the idiosyncratic distributions and migratory routes of long‐distance migrants. Our synthesis, which revolves around the insight that migratory organisms travel long distances simply to stay in the same place, provides a necessary evolutionary context for understanding historical biogeographic patterns in migratory lineages as well as the ecological dynamics of migratory connectivity between breeding and non‐breeding locations.
Alveolar ridge preservation using an open membrane approach for sockets with bone deficiency: A randomized controlled clinical trial
Authors: Sun Dong‐Joo , Lim Hyun‐Chang , Lee Dong‐Woon
Published: November 2018

Background

Various approaches are used for alveolar ridge preservation (ARP); however, there is no standard method or material.

Purpose

To investigate the effect of ARP with a dense polytetrafluoroethylene (d‐PTFE) membrane and freeze‐dried irradiated allogenic bone for sockets with bone deficiency.

Materials and Methods

Thirty‐four patients (with sockets exhibiting ≥3 mm hard tissue loss in ≥1 walls) were randomized to undergo natural socket healing (control) or ARP with a d‐PTFE membrane and freeze‐dried irradiated allogenic bone (test group). After 4 months, horizontal and vertical ridge changes were measured using cone beam computed tomography.

Results

Ridge width at l mm below the ridge crest demonstrated significantly less change in the test group (median =2.3; Q1 = 0.6; Q3 = 4.3 mm) than in the control group (median =3.9; Q1 =2.6; Q3 = 7.8 mm; P = .021). There was no significant difference between the two groups in horizontal ridge changes at 3 and 5 mm below the crest or vertical changes (P > .05). Requirement for bone augmentation at implant placement was significantly reduced in the test group compared to the control group (P < .001).

Conclusion

ARP with a d‐PTFE membrane and freeze‐dried irradiated allogenic bone substitute reduced horizontal bone resorption in sockets with bone deficiency.
Wissensstand zur Anaphylaxie und Umgang mit Adrenalinautoinjektoren in Apotheken
Authors: Worm Margitta , Molaie Novin , Dölle Sabine
Published: November 2018

Hintergrund

Adrenalin intramuskulär mit Hilfe eines Autoinjektors ist das Mittel der Wahl zur Selbstbehandlung schwerer allergischer Reaktionen. Zahlen aus dem Anaphylaxie‐Register zeigen, dass Adrenalinautoinjektoren selten von Patienten eingesetzt werden. Apotheker sind eine wichtige Schnittstelle zwischen verordnendem Arzt und Patienten.

Patienten und Methodik

Ziel der vorliegenden Arbeit war es, den Wissensstand bei Apothekern zur Anaphylaxie und deren Behandlung mittels definierter Wissensfragen strukturiert zu erheben. Hierzu wurden Daten von einer standardisierten Fragebogenerhebung von 213 Apotheken analysiert.

Ergebnisse

Die Daten zeigen, dass Apotheker die Anaphylaxie als eine Erkrankung mit reduzierter Lebensqualität einschätzen. Die Benennung der häufigsten Auslöser einer Anaphylaxie durch die Apotheker entspricht den Daten aus dem Anaphylaxie‐Register (Insektengift, Nahrungsmittel und Medikamente). Die Auswertung zum Wissensstand der Apotheker zeigt, dass Fallbeschreibungen einer Anaphylaxie richtig zugeordnet werden können. Es bestehen jedoch Wissensdefizite bei Fragen zur Behandlung einer Anaphylaxie mit Adrenalin und zu den Leitlinien.

Schlussfolgerungen

Die vorliegende Untersuchung zeigt, dass der Wissensstand von Apothekern zur Anaphylaxie verbessert werden kann. Da Apotheker eine wesentliche Schnittstelle bei der Versorgung von Patienten mit allergischen Erkrankungen darstellen, sollte Ziel weiterführender Maßnahmen sein, diese Schnittstelle durch Aufklärungs‐ und Schulungsmodule zu verstärken, um somit die Patientenversorgung zu verbessern.
Therapeutisches Management bei Vitiligo
Authors: Bleuel Rachela , Eberlein Bernadette
Published: November 2018

Vitiligo ist eine erworbene Hauterkrankung, an der weltweit 0,5 % der Bevölkerung erkranken und die eine große Herausforderung in der dermatologischen Versorgung darstellt. Die Erkrankung geht für Betroffene oftmals aufgrund der fleckigen Depigmentierung mit einer kosmetischen Entstellung und großem Leidensdruck einher. Pathophysiologisch werden als Hauptursachen für den Verlust funktionierender Melanozyten eine genetische Prädisposition, autoimmune Mechanismen und oxidativer Stress angesehen. Vorgestellt werden die Therapieempfehlungen der europäischen Leitlinie in Ergänzung mit Empfehlungen aus aktuellen Übersichtsarbeiten zu Vitiligo. Bisherige therapeutische Optionen greifen auf drei Wegen: (1.) Regulation der Autoimmunantwort mit topischen und systemischen immunmodulierenden Pharmaka (Kortikosteroide und Calcineurininhibitoren), (2.) Reduktion des melanozytären, oxidativen Stress mittels topischer und systemischer Antioxidantien sowie (3.) Aktivierung der Melanozytenregeneration durch Phototherapie (v. a. UVB) und Transplantation von pigmentierten Zellen. Darüber hinaus sollten dem Patienten Techniken zur Camouflage angeboten werden. Nach erfolgreicher Repigmentierung ist eine Rezidivprophylaxe mit Calcineurininhibitoren sinnvoll. Kombinationstherapien oben genannter Therapieansätze werden generell als erfolgreicher angesehen als Monotherapien. Auch ist ein möglichst früher Therapiebeginn prognostisch günstig. Mit Hilfe der genannten Therapieansätze kann es gelingen das Fortschreiten der Erkrankung aufzuhalten, depigmentierte Herde zu stabilisieren und eine Repigmentierung zu erreichen. Nur in Ausnahmefällen kommt eine dauerhafte Depigmentierung in Frage. Weiterreichende Erkenntnisse zur Pathogenese der Erkrankung lassen auf neue Therapieansätze hoffen.
Komorbidität von lokalisierter Sklerodermie und primär biliärer Cholangitis
Authors: Bali Gábor , Szilvási Anikó , Inotai Dóra , Varga Ágnes , Sárdy Miklós , Kárpáti Sarolta , Medvecz Márta , Szegedi Anna , Hidvégi Bernadett
Published: November 2018

Hintergrund und Ziele

Morphaea ist häufig mit anderen Autoimmunerkrankungen assoziiert. Über den Zusammenhang zwischen Morphaea und primär biliärer Cholangitis (PBC) ist nur wenig bekannt. Das Ziel dieser Fallstudie war die Untersuchung eines möglichen Zusammenhangs sowie die Identifizierung der Risikofaktoren.

Patienten und Methodik

Wir testeten Morphaea‐Patienten mittels indirekter Immunfluoreszenz und/oder Immunblot auf antimitochondriale Antikörper (AMA). Bei den AMA‐positiven Patienten wurde durch Genotypisierung des Humanen Leukozytenantigens (HLA)‐ und Deep Sequencing die HLA DRB1‐Untergruppe bestätigt.

Ergebnisse

Sechs (6,6%) von 91 Patienten waren AMA‐positiv, bei 4 (4,39%) lag eine PBC vor. Das Durchschnittsalter der AMA‐positiven Patienten lag bei 69,0 Jahren. Bei zwei der 6 AMA‐positiven Patienten wurden gemeinsame prädisponierende Allele (HLA DRB1*15: 01 und HLA DRB1*08) festgestellt. Ein Patient hatte ein für PBC prädisponierendes Allel. Alle Patienten waren weiblich, in der Menopause und zeigten eine Tendenz zur Remission der Morphaea.

Schlussfolgerung

Die Koexistenz von Morphaea, AMA‐Positivität und PBC ist eine seltene, aber mögliche Assoziation. Gemeinsame prädisponierende HLA‐Allele könnten bei einer solchen Manifestation miteinander interagieren. Bei weiblichen Patienten mit generalisierter Morphaea empfehlen wir vor einer Metothrexat‐Therapie ein AMA‐Screening.
On the origin of leeches by evolution of development
Authors: Kuo Dian‐Han , Lai Yi‐Te
Published: November 2018

Leeches are a unique group of annelids arising from an ancestor that would be characterized as a freshwater oligochaete worm. Comparative biology of the oligochaetes and the leeches reveals that body plan changes in the oligochaete‐to‐leech transition probably occurred by addition or modification of the terminal steps in embryonic development and that they were likely driven by a change in the feeding behavior in the ancestor of leeches. In this review article, developmental changes that are associated with the evolution of several leech‐specific traits are discussed. These include (1) the evolution of suckers, (2) the loss of chaetae, (3) the loss of septa, and (4) a fixed number of segments. An altered developmental fate of the teloblast is further proposed to be a key factor contributing to the fixation of the segment number, and the evolutionary change in teloblast development may also account for the loss of the ability to regenerate the lost body segments in the leech.
Parallel transcriptome evolution in stream threespine sticklebacks
Authors: Kitano Jun , Ishikawa Asano , Kusakabe Makoto
Published: November 2018

Natural selection can cause similar phenotypic evolution in phylogenetically independent lineages inhabiting similar environments. Compared to morphological, behavioral, and physiological traits, little is known about the parallel evolution of transcriptome. Furthermore, the relative contribution ofcis‐ andtrans‐regulatory changes to parallel transcriptome evolution largely remains unclear. The threespine stickleback fish (Gasterosteus aculeatus) is a great model for studying parallel evolution because its ancestral marine populations independently colonized freshwater habitats in multiple geographical regions, resulting in independent pairs of marine and freshwater ecotypes in each region. Here, we investigated transcriptomic parallelism among the marine and stream ecotypes of Japanese and Canadian threespine sticklebacks by conducting common garden experiments and microarray analysis of the brain, which controls several physiological and behavioral traits differing between these ecotypes. We found parallel expression differences in 103 genes, including those encoding the enzymes involved in taurine synthesis and glycoprotein hydrolysis. The number of genes differentially expressed in parallel was significantly larger than the number of genes showing an antiparallel pattern (71 genes). To investigate the genetic architecture underlying transcriptome divergence, we re‐analyzed the previous expression quantitative trait locus (eQTL) data and found that mosteQTLs were located on the same chromosome as the transcripts, possibly incis‐regulatory regions. Furthermore, the effect sizes of theeQTLs on the same chromosomes were larger than those on different chromosomes. Thus, we found that divergence in the brain transcriptome between the ecotypes shows parallelism and is mainly caused by genetic changes occurring on the same chromosome as the target genes.
CANadian CAnagliflozin REgistry: Effectiveness and safety of canagliflozin in the treatment of type 2 diabetes mellitus in Canadian clinical practice
Authors: Woo Vincent , Bell Alan , Clement Maureen , Noronha Luis , Tsoukas Michael A. , Camacho Fernando , Traina Shana , Georgijev Natasha , Culham Matthew D. , Rose Jennifer B. , Rapattoni Wally , Bajaj Harpreet S.
Published: November 2018

Aim

There is limited information concerning the effects of canagliflozin (CANA), a sodium‐glucose co‐transporter 2 inhibitor (SGLT2i) in a real‐world clinical setting in Canada. CanCARE is a 12‐month, prospective, observational analysis to demonstrate the effectiveness and safety of CANA in usual clinical practice in Canada.

Materials and methods

SGLT2i‐naïve adult patients with type 2 diabetes mellitus (T2DM) (n = 527) on a stable antihyperglycemic agent (AHA) regimen with glycated hemoglobin (A1C) ≥ 7%, an estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73m2, were initiated on CANA as part of their usual treatment approach, and were followed for a period of 12 months. The primary effectiveness objective was the mean change in HbA1c from baseline to 6 and 12 months.

Results

Significant improvement from baseline in mean HbA1c levels were observed at 6 months (−0.90%; 95% CI, −1.02, −0.78) and at 12 months (−1.04%; 95% CI, −1.15, −0.92), regardless of duration of diabetes or background AHA treatment regimen. Similarly, significant decreases in systolic blood pressure (−4.65 mm Hg); body weight (−3.24 kg), waist circumference (−2.91 cm) and body mass index (−1.15 kg/m2) were observed at 12 months. Additionally, 40.5% of patients achieved the double endpoint (≥0.5% HbA1c reduction and ≥ 3% weight loss), while 24.3% of patients achieved the triple composite endpoint (≥0.5% HbA1c reduction, ≥3% weight loss and ≥ 4 mm Hg systolic blood pressure reduction). No unexpected adverse events were reported.

Conclusion

CANA provided sustained clinically meaningful improvements in cardiometabolic parameters in this study in a real‐world setting, confirming findings from randomized controlled trials.
Double‐blind, randomized clinical trial comparing the efficacy and safety of continuing or discontinuing the dipeptidyl peptidase‐4 inhibitor sitagliptin when initiating insulin glargine therapy in patients with type 2 diabetes: The CompoSIT‐I Study
Authors: Roussel Ronan , Duran‐García Santiago , Zhang Yilong , Shah Suneri , Darmiento Carolyn , Shankar R. Ravi , Golm Gregory T. , Lam Raymond L. H. , O'Neill Edward A. , Gantz Ira , Kaufman Keith D. , Engel Samuel S.
Published: November 2018

Aims

To compare the effects of continuing versus discontinuing sitagliptin when initiating and intensively titrating insulin glargine.

Materials and methods

Eligible patients had inadequately controlled type 2 diabetes on metformin (≥1500 mg/d) in combination with a dipeptidyl peptidase‐4 (DPP‐4) inhibitor and/or a sulphonylurea. Those on metformin + sitagliptin were directly randomized; all others were switched to metformin + sitagliptin (discontinuing other DPP‐4 inhibitors and sulphonylureas) and stabilized during a run‐in period. At randomization, patients were allocated to continuing sitagliptin or discontinuing sitagliptin, with both groups initiating insulin glargine and titrating to a target fasting glucose of 4.0 to 5.6 mmol/L.

Results

A total of 743 participants (mean glycated haemoglobin [HbA1c] 72.6 mmol/mol [8.8%], disease duration 10.8 years), were treated. After 30 weeks, the mean HbA1c and least squares (LS) mean change from baseline in HbA1c were 51.4 mmol/mol (6.85%) and −20.5 mmol/mol (−1.88%) in the sitagliptin group and 56.4 mmol/mol (7.31%) and −15.5 mmol/mol (−1.42%) in the placebo group; the difference in LS mean changes from baseline HbA1c was −5.0 mmol/mol (−0.46%; P < 0.001). The percentage of participants with HbA1c <53 mmol/mol (<7.0%) was higher (54% vs. 35%) and the mean daily insulin dose was lower (53 vs. 61 units) in the sitagliptin group. Despite lower HbA1c, event rates and incidences of hypoglycaemia were not higher in the sitagliptin group. Adverse events overall and changes from baseline in body weight were similar between the two treatment groups.

Conclusion

When initiating insulin glargine therapy, continuation of sitagliptin, compared with discontinuation, resulted in a clinically meaningful greater reduction in HbA1c without an increase in hypoglycaemia. ClinicalTrials.gov Identifier: NCT02738879.
Incomplete Preferences and Equilibrium in Contingent Markets
Authors: Chambers Robert , Melkonyan Tigran
Published: November 2018

This paper shows that betting or speculative trading between agents with incomplete preferences is likely to occur if agents have access to convex choice sets. This contrasts sharply with endowment economy models where preference incompleteness often hinders betting, speculative trading or mutually beneficial insurance arrangements. Our results imply that decision‐makers with identical tastes and identical feasible sets will potentially gain from speculative trade for generic status quo allocations. We also develop a framework for endogenizing the status quo allocations of decision‐makers that are treated exogenously in the existing literature. Finally, we provide a tractable differential representation of status quo allocations, equilibria and conditions where speculative trade may or may not emerge.
Cognitive outcomes following epilepsy in infancy: A longitudinal community‐based study
Authors: O'Reilly Helen , Eltze Christin , Bennett Kate , Verhaert Kristien , Webb Rebecca , Merrett Anna , Scott Rod C. , Whitney Andrea , Helen Cross J. , de Haan Michelle
Published: November 2018

Objective

Onset of epilepsy before 2 years of age is associated with poor cognitive outcome; however, the natural course of the range of epilepsies that occur at this age is unknown. The aim of this prospective community‐based study was to investigate the neuropsychological development of infants with newly diagnosed epilepsy longitudinally and to identify the clinical factors that predict long‐term impairment.

Methods

Sixty‐six infants <24 months of age were enrolled in the baseline phase of this study; 40 were seen again at 1‐year follow‐up and 40 at 3‐year follow‐up. Children underwent a neurological and neuropsychological assessment at each time point.

Results

More than 55% of children demonstrated impaired cognitive functioning at each assessment, with a similar percentage showing impaired memory and attention at 3‐year follow‐up. Cognitive scores obtained at each time point were correlated. More than 20 seizures/seizure clusters prior to assessment and an abnormal neurologic examination predicted poor cognitive functioning at baseline, whereas continuing seizures and baseline cognitive score predicted 3‐year intelligence quotient (IQ)/cognitive score.

Significance

These findings demonstrate the following: (1) infants who are performing poorly at baseline continue to display impaired development at follow‐up, (2) these children are delayed across a range of neuropsychological functions, and (3) a high number of seizures close to initial diagnosis and continuing seizures at follow‐up independently predict cognitive impairment. These findings help to identify those infants with new‐onset epilepsy who are most at risk for poor developmental outcome and suggest that multimodal interventions should be instituted early in the course of the disorder to improve outcomes.
Surgical and developmental outcomes of corpus callosotomy for West syndrome in patients without MRI lesions
Authors: Baba Hiroshi , Toda Keisuke , Ono Tomonori , Honda Ryoko , Baba Shiro
Published: November 2018

Objective

This retrospective study was designed to assess the impact of corpus callosotomy (CC) in patients with intractable West syndrome (WS) without lesions on magnetic resonance imaging (MRI).

Methods

This study involved 56 patients with WS who underwent CC between January 2000 and December 2014. Seizure outcomes and changes in psychomotor development were analyzed.

Results

Mean age at the onset of epilepsy and at the time of CC was 5.1 and 22.6 months, respectively. Mean duration of epilepsy before CC was 17.6 months. Video‐electroencephalography (EEG) monitoring showed bilateral ictal and interictal abnormalities before CC. Mean follow‐up duration was 36.6 months. At final follow‐up, seizure outcomes after CC were seizure‐free in 18 patients (32.1%), excellent (E: >80% reduction in seizure frequency) in 15 (26.8%), good (G: >50% reduction) in 10 (17.9%), and poor (P: <50% reduction) in 13 (23.2%). Epileptic spasms (ES) were eliminated in 24 patients (42.9%). However, tonic seizure (TS) outcomes were poor (P < 0.05). Of preoperative predictive factors related to seizure outcome, developmental delay before epilepsy onset correlated with poor outcome (P < 0.05). One year post‐CC, 6 patients (10.7%) had no epileptic abnormality on EEG, 19 (33.9%) had lateralized epileptic abnormalities, and 31 (55.4%) had bilateral asynchronous epileptic abnormalities. All patients without epileptic discharge achieved seizure freedom. Fifteen of 19 (78.9%) patients in the lateralized group and 12 of 31 (38.7%) in the bilateral asynchronous group had worthwhile outcomes (F + E). The patterns of EEG changes after CC correlated with seizure outcome (P < 0.01). Progressive declines in developmental quotient were prevented in patients with worthwhile outcomes.

Significance

CC represents an important therapeutic option for patients with WS without resectable MRI lesions. Transcallosal seizure bilateralization is critical for bilateral ES generation. Early identification of potential CC candidates and surgical intervention are important for better seizure control and cognitive capacity preservation before severe developmental delay development.
Does the Court of Justice own the Treaties? Interpretative pluralism as a solution to over‐constitutionalisation
Authors: Davies Gareth
Published: November 2018

It is often assumed that Court of Justice interpretations of EU law are definitive and binding. However, this conflicts with conventional ideas about the trias politica, as well as with the principle of conferral, and rests on no more than the Court's own assertion. It also has harmful policy consequences, forcing national courts into constitutional resistance and, in claiming to fix the meaning of the Treaties, smothering Union politics. Interpretative pluralism, by contrast, insists on the possibility of diverging interpretations. That allows for wider participation in the construction of EU law, while retaining the integrity of Union law through commitment to shared texts and a balance of power between institutions. Institutional disagreements are reframed, not as conflicts between legal orders, but as conflicts about the meaning of a shared one. This approach is more profoundly integrative than the Court's top‐down approach, and also allows for greater diversity and experiment.
Integrated Surface and Subsurface Hydrological Modeling with Snowmelt and Pore Water Freeze–Thaw
Authors: Schilling Oliver S. , Park Young‐Jin , Therrien René , Nagare Ranjeet M.
Published: November 2018

For the simulation of winter hydrological processes a gap in the availability of flow models existed: one either had the choice between (1) physically‐based and fully‐integrated, but computationally very intensive, or (2) simplified and compartamentalized, but computationally less expensive, simulators. To bridge this gap, we here present the integration of a computationally efficient representation of winter hydrological processes (snowfall, snow accumulation, snowmelt, pore water freeze–thaw) in a fully‐integrated surface water‐groundwater flow model. This allows the efficient simulation of catchment‐scale hydrological processes in locations significantly influenced by winter processes. Snow accumulation and snowmelt are based on the degree‐day method and pore water freeze–thaw is calculated with a vertical heat conduction approach. This representation of winter hydrological processes is integrated into the fully‐coupled surface water‐groundwater flow model HydroGeoSphere. A benchmark for pore water freeze–thaw as well as two illustrative examples are provided.
Azorean macroalgae (Petalonia binghamiae, Halopteris scoparia and Osmundea pinnatifida) bioprospection: a study of fatty acid profiles and bioactivity
Authors: Campos Ana M. , Matos Joana , Afonso Cláudia , Gomes Romina , Bandarra Narcisa M. , Cardoso Carlos
Published: November 2018

The Azorean macroalgae Petalonia binghamiae, Halopteris scoparia and Osmundea pinnatifida are undervalued and require further study regarding their potential use as food. These three seaweed species had low fat contents, and their fatty acid (FA) profiles were characterised by a high proportion of saturated FA (SFA) in the case of O. pinnatifida and similar weights of SFA and polyunsaturated FA (PUFA) in the other two species. Within the PUFAs, the ω3 PUFAs were the most prominent in O. pinnatifida and P. binghamiae, yielding ω3/ω6 ratios that were higher than one. Eicosapentaenoic acid (EPA, 20:5 ω3) was the most important ω3 PUFA (10–14%). Regarding the other bioactive compounds, the polyphenols were found to reach non‐negligible levels (140–220 mg/100 g dw). Significant antioxidant activity was detected. Ethanolic extracts of H. scoparia and aqueous extracts of P. binghamiae showed cyclooxygenase‐2 (COX‐2) inhibitory capacities between 40% and 79%, indicating anti‐inflammatory activity.