bluuebunny/crossref_metadata_2025 huggingface dataset:
When earwig mothers do not care to share: Parent–offspring competition and the evolution of family life
Authors: Kramer Jos , Körner Maximilian , Diehl Janina M. C. , Scheiner Christine , Yüksel‐Dadak Aytül , Christl Teresa , Kohlmeier Philip , Meunier Joël
Published: June 2017

Kin competition often reduces – and sometimes entirely negates – the benefits of cooperation among family members. Surprisingly, the impact of kin competition on the fitness effects of family life only received close scrutiny in studies on sibling rivalry, whereas the possibility of parent–offspring competition has attracted much less attention. As a consequence, it remains unclear whether and how parent–offspring competition could have affected the early evolution of parental care and family life.

Here, we examined the occurrence and consequences of parent–offspring competition over food access in the European earwigForficula auricularia, an insect with facultative family life reminiscent of an ancestral state. Specifically, we (1) raised earwig offspring under food limitation either together with or without their mother, and (2) tested whether and how the — potentially competitive — weight gains of mothers and offspring during family life affected the offsprings' survival rate and morphology, and the future reproductive investment of their mother.

In line with the occurrence of parent–offspring competition, we showed that high maternal weight gains during family life reduced the survival prospects of maternally tended offspring, while they increased the mothers' investment into the production of a second clutch (but not the body size of the surviving offspring). Conversely, high offspring weight gains generally increased the offsprings' survival, but did so to a larger extent when they were together with their mother. Intriguingly, mothers that had exhibited a low initial weight showed especially high weight gains.

Overall, our results demonstrate that maternal presence under food restriction triggered a local competition between mothers and their offspring. This competition limited offspring survival, but allowed mothers to increase their investment into future reproduction and/or to maintain their current body condition. On a general level, our findings reveal that parent–offspring competition can counteract the benefits of (facultative) parental care, and may thus impede the evolution of family life in resource‐poor environments.

Aplain language summaryis available for this article.
Liberalization Outcomes and Competitive Behaviour in an Emerging Insurance Market
Authors: Alhassan Abdul Latif , Biekpe Nicholas
Published: June 2017

The liberalization of financial services industry has generally been associated with the creation of large firms, increased foreign presence and the ability to diversify into a broad range of activities. In this paper, we examine the effect of these outcomes on competitive behaviour in the non‐life insurance market in South Africa. Using annual data on 79 non‐life insurers, we employ the Panzar–Rosse model to estimate the H‐statistics competitive index for samples of large versus small insurers, domestic‐owned versus foreign‐owned insurers and single versus multi‐line insurers. Overall, our findings reveal that non‐life insurers in South Africa conduct their pricing under conditions of monopolistic competition. The sub‐market estimates of the H‐statistics indicate that the activities of small, foreign‐owned and single‐line insurers improve competitive behaviour in the market. This suggests that while liberalization outcome in increased foreign presence improves competition, the creation of large firms from consolidation reduces competitive pressures in the non‐life market. The results are robust to both static and dynamic specification of the Panzar–Rosse Model.
Financial Inclusion and the Role of Women in Nigeria
Authors: Ogunleye Toyin Segun
Published: June 2017

The study tests the assertion that greater lending to microfinance female clients leads to an improvement in repayment rate. The study uses unbalanced panel data framework of 752 microfinance banks (MFBs) in Nigeria during the period 2011 to 2014. Findings from the regressions confirm a positive impact of female inclusion on loan repayment rate. A higher proportion of female clients is associated with a greater repayment rate and with fewer loan provisions. The study recommends that microfinance banks should target specifically women clients in Nigeria, as greater lending to them will improve outreach to the poor.
The Impact of Oil Price on South African GDP Growth: A Bayesian Markov Switching‐VAR Analysis
Authors: Balcilar Mehmet , van Eyden Reneé , Uwilingiye Josine , Gupta Rangan
Published: June 2017

One characteristic of many macroeconomic and financial time series is their asymmetric behaviour during different phases of a business cycle. Oil price shocks have been amongst those economic variables that have been identified in theoretical and empirical literature to predict phases of business cycles. However, the role of oil price shocks to determine business cycle fluctuations has received less attention in emerging and developing economies. The aim of this study is to investigate the role of oil price shocks in predicting phases of the South African business cycle associated with higher and lower growth regimes. By adopting a regime dependent analysis, we investigate the impact of oil price shocks under two phases of the business cycle, namely high and low growth regimes. As a net importer of oil, South Africa is expected to be vulnerable to oil price shocks irrespective of the phase of the business cycle. Using a Bayesian Markov switching vector autoregressive (MS‐VAR) model and data for the period 1960Q2 to 2013Q3, we found the oil price to have predictive content for real output growth under the low growth regime. The results also show the low growth state to be shorter‐lived compared to the higher growth state.
Consumer Perspectives on Access to Direct‐to‐Consumer Genetic Testing: Role of Demographic Factors and the Testing Experience
Authors: GOLLUST SARAH E. , GRAY STACY W. , CARERE DEANNA ALEXIS , KOENIG BARBARA A. , LEHMANN LISA SOLEYMANI , McGUIRE AMY L. , SHARP RICHARD R. , SPECTOR‐BAGDADY KAYTE , WANG NA , GREEN ROBERT C. , ROBERTS J. SCOTT ,   for the PGen Study Group
Published: June 2017

Policy Points:

The policy context of direct‐to‐consumer personal genomic testing (DTC‐PGT) has been evolving over the last decade, with little empirical data available about consumers’ perspectives.

A majority of consumers of DTC‐PGT supported expanded access to services and their integration into the medical context and opposed more governmental regulation.

Consumers’ attitudes about access to services and regulation did not vary based on the specific genetic risk information they received from companies, but may vary based on whether consumers perceived their DTC experience negatively.

Context

While policymakers have been considering the appropriateness of direct‐to‐consumer personal genomic testing (DTC‐PGT) for more than a decade, there is little empirical data on consumers’ views regarding the regulation of these products. No research has assessed whether consumers’ personal experience with testing is related to their views about access to and regulation of DTC tests.

Methods

Data were analyzed from the PGen Study, a longitudinal prospective cohort of DTC‐PGT customers of 23andMe (n = 564) and Pathway Genomics (n = 377; total N = 941). Consumers were sent an electronic survey before receiving genetic test results and again 6 months after receipt of results.

Findings

At the 6‐month follow‐up, more than 80% of participants believed that people have a right to access genetic information directly, that parents should be able to get DTC‐PGT testing for their children, and that genetic information should be kept private. Participants supported health insurance coverage of PGT (60%), wider availability of PGT (68%), and inclusion of genetic information in medical records (63%). Participants were less supportive of government regulation (28%) and restricting testing to clinical settings (14%). Conservative political ideology was associated with less support for government regulation (P < 0.001), as was feeling more confident in one's genetic knowledge (P < 0.05). Participants’ level of computed genetic risk for common diseases, as indicated by their actual test results received from companies, showed no relationship with attitudes. However, those who perceived that they had received elevated risk results expressed lower support for expanded availability and incorporation of PGT into health care (P < 0.01). Those who reported being upset by their genetic test results were less likely to endorse access to DTC products without a medical professional (P < 0.01).

Conclusions

PGT consumers supported expanded access to these services and opposed additional regulation. Users who had a negative personal experience with PGT testing were less supportive of expanded availability without a medical professional.
Financing Long‐Term Services and Supports: Ideas From Singapore
Authors: GRAHAM WAN CHEN KANG , BILGER MARCEL
Published: June 2017

Policy Points:

In Singapore, long‐term services and supports (LTSS) are financed through a mix of public and private sources comprising tiered means‐tested public subsidies and government grants to care providers, charitable donations, voluntary long‐term care insurance, and other private resources.

Singapore's high take‐up rate of voluntary long‐term care insurance is explained by plans offering partial coverage, medical underwriting, early automatic enrollment, direct debit of insurance premiums, and defined cash benefits.

Singapore's experience in long‐term care financing is relevant to the US debate, as it provides policy ideas that may be transferable to the American context.

We recommend maximizing the population's total contribution to voluntary long‐term care insurance by striking the right balance between coverage adequacy and take‐up rate while targeting subsidies to low‐income individuals.

Context

Financing long‐term services and supports (LTSS) for the elderly is a pressing issue in the United States with reforms of long‐term care insurance (LTCI) presently being explored. Singapore, with 65% of residents aged 40 to 83 covered by basic LTCI, including 22% with supplementary LTCI plans, has the highest voluntary LTCI rate in the world. This article contributes to the discourse by presenting the case of LTSS financing in Singapore.

Methods

We first reviewed Singapore's LTSS policies through a comprehensive search of academic papers, governmental reports, parliamentary debate transcripts, print media, and official websites of LTSS providers. We then estimated the LTSS financing mix, conducted an in‐depth analysis of the main policies, and illustrated the financial protection they procure for the elderly using realistic hypothetical scenarios.

Findings

The main principles governing Singapore's LTSS policies are shared responsibility for long‐term care financing, targeted assistance for the poor, centralized governance and administration, separation from other income and housing policies, and limited intergenerational cross‐subsidizing. We estimate the financing mix to consist of out‐of‐pocket spending (40%), government spending (42%), long‐term care insurance (9%), and charitable donations (9%). Assuming a monthly LTSS bill of US$1,545 to US$2,575, between 11% and 19% of LTSS expense is offset by LTCI for severely disabled individuals with basic coverage. Overall, 63% of care recipients are eligible for public subsidies that amount to 20% to 80% of their expenses.

Conclusions

The high take‐up of voluntary LTCI in Singapore is explained by the high prevalence of plans offering partial coverage, medical underwriting, early automatic enrollment, direct debit of insurance premiums, and defined cash benefits. We recommend setting the coverage of voluntary long‐term care insurance plans at levels that maximize the population's total contribution by striking the right balance between coverage adequacy and take‐up rate while targeting subsidies to low‐income individuals.
UNAIDS 90‐90‐90 Campaign to End the AIDS Epidemic in Historic Perspective
Authors: KAZANJIAN POWEL
Published: June 2017

Policy Points:

Examining the reasons for the failure of 20th‐century syphilis eradication programs (difficulties in finding cases, tracing contacts, procuring consistent funding, overcoming moral framing, and rectifying social problems that create vulnerable environments) provides insight into the possibility that today's UNAIDS campaign may not achieve its goal.

Disease eradication, although applicable to smallpox, may not be a realistic goal for public health officials who are designing programs to control sexually transmitted diseases (STDs) like AIDS. STDs such as AIDS have a distinctive array of socioeconomic, behavioral, biologic, and epidemiologic features that may not make these diseases amenable to eradication.

Context

Throughout its course, there has been talk of ending the AIDS epidemic. Initially aspirational in nature, this discourse has now taken the form of an explicit UNAIDS proposal to maximize the number of infected people who are tested and receive antiretroviral treatment (ART). If the milestones are met by 2020, the proposal states, an end to the AIDS pandemic could be achieved by 2030. This article uses a historical approach to explore whether this strategy to end the epidemic is feasible.

Methods

In this article, I identify historical analogues of today's UNAIDS plan for STDs. I then examine features of today's HIV campaign and compare them with elements of syphilis eradication campaigns that carried out widespread testing and treatment between the 1930s and 1960s.

Findings

Twentieth‐century syphilis campaigns failed because they did not issue specific proposals that would enable them to achieve their eradication goal. They could not change the features of the disease that impeded their test‐and‐treat strategy: the moral framing (stigma deters people from testing), biologic factors (asymptomatic periods of contagiousness), and epidemiologic issues (difficulty tracking contacts occurring in private settings). Furthermore, they could not ensure sustainable funding, rectify social problems that create vulnerable environments, or issue educational messages to curb unsafe behaviors. Today's UNAIDS campaign offers no new provisions to address those factors that led to the failure of earlier syphilis campaigns.

Conclusions

The distinctive array of socioeconomic, biologic, and epidemiologic factors that characterize STDs like syphilis also apply to AIDS and weaken the assumption that the AIDS epidemic can be ended by implementing today's UNAIDS plan. The discourse of ending the AIDS epidemic may be a carryover from the successful elimination, before the appearance of AIDS, of smallpox—a disease that is not comparable to AIDS owing to different biologic qualities, social concerns, epidemiologic behaviors, and the possession of an effective vaccine. Future AIDS control campaigns should therefore concentrate on maximizing ART distribution and not targeting the end of the epidemic.
Agenda control in EU referendum campaigns: The power of the anti‐EU side
Authors: ATIKCAN ECE ÖZLEM
Published: June 2017

European Union (EU) referendums provide unique opportunities to study voters’ attitudes toward a distant level of governance. Scholars have long tried to understand whether EU referendum results reflect domestic (dis‐)satisfaction with the incumbent governments or actual attitudes toward the Union. Finding evidence supporting both domestic and European factors, the recent focus has thus turned to referendum campaigns. Recent studies emphasise the importance of the information provided to voters during these campaigns in order to analyse how domestic or European issues become salient in the minds of voters. These studies nonetheless overlook the asymmetrical political advantage in such campaigns. The broader literature on referendums and public opinion suggest that in a referendum, the ‘No’ side typically has the advantage since it can boost the public's fears by linking the proposal to unpopular issues. This article explores whether this dynamic applies to EU treaty ratification referendums. Does the anti‐EU treaty campaign have more advantage than the pro‐EU treaty campaign in these referendums? Campaign strategies in 11 EU treaty ratification referendums are analysed, providing a clear juxtaposition between pro‐treaty (‘Yes’) and anti‐treaty (‘No’) campaigns. Based on 140 interviews with campaigners in 11 referendums, a series of indicators on political setting and campaign characteristics, as well as an in‐depth case study of the 2012 Irish Fiscal Compact referendum, it is found that the anti‐treaty side indeed holds the advantage if it engages the debate. Nonetheless, the findings also show that this advantage is not unconditional. The underlying mechanism rests on the multidimensionality of the issue. The extent to which the referendum debate includes a large variety of ‘No’ campaign arguments correlates strongly with the campaigners’ perceived advantage/disadvantage, and the referendum results. When the ‘No’ side's arguments are limited (either through a single‐issue treaty or guarantees from the EU), this provides the ‘Yes’ side with a ‘cleaner’ agenda with which to work. Importantly, the detailed data demonstrate that the availability of arguments is important for the ‘Yes’ side as well. They tend to have the most advantage when they can tap into the economic costs of an anti‐EU vote. This analysis has implications for other kinds of EU referendums such as Brexit, non‐EU referendums such as independence referendums, and the future of European integration.
Lentigo maligna of the face: A quantitative simple method to identify individual patient risk probability on dermoscopy
Authors: Carbone Anna , Ferrari Angela , Paolino Giovanni , Buccini Pierluigi , De Simone Paola , Eibenschutz Laura , Piemonte Paolo , Silipo Vitaliano , Sperduti Isabella , Catricalà Caterina , Frascione Pasquale
Published: June 2017

Background/Objectives

The clinical and dermoscopic differential diagnosis of flat pigmented facial lesions represents a great challenge for the clinicians. Our aim was to report a quantitative method based on dermoscopic features to better classify pigmented facial lesions.

Methods

This is a retrospective case‐series study that analysed the dermoscopic features of 582 pigmented facial lesions.

Results

The individual patient probability of lentigo maligna (LM) was predicted by a multivariate model, with an accuracy of 0.72. According to the odds ratio at the multivariate analysis, an individual scoring index was assigned to each criterion, and a value of 4.56 was identified as optimal cut‐off point. Up to a score of 2.5, the probability that a lesion is an LM is 0. The probability increases from 10 to 50% for a score ranging between 4.5 and 6. It is about 90% for a score of 7.

Conclusion

The optimal cut‐off point obtained and the curve that identifies the probability of a patient having a LM could improve the classification and the management strategies of equivocal pigmented facial lesions.
2016 Society for Humanistic Anthropology Fiction/Creative Nonfiction Third Prize How Grades Had Been Gotten for Penguins and Money
Authors: Cherkaev Xenia A.
Published: June 2017

This is a story about penguins and passing grades, about the practices and ethics of informal exchange in 1980s Leningrad and 2010s St. Petersburg, and about things' incommensurability spurring stories. It is, specifically, about one dead penguin: a bird that was killed, found, bought, gifted, found, stolen, and gifted again. [Gifting, storytelling, planned economy, post‐Socialism, materiality]
Computational Fluid Dynamic Analysis of the Hemodialysis Plastic Cannula
Authors: Fulker David , Sayed Zakir , Simmons Anne , Barber Tracie
Published: June 2017

The jet of fluid returning to the patient through a hemodialysis venous needle has previously been reported as a potential source of endothelial damage which can lead to intimal hyperplasia (IH) in arteriovenous fistulae (AVF). Metal needles are the current standard practice for accessing the vascular system in hemodialysis. However, plastic cannulae have been used in Japan for 30 years. This study utilized computational fluid dynamics to analyze the hemodynamics of blood exiting a plastic cannula and determined the optimal placement and blood flow rate. Transient simulations were run using a 15G Argyle Safety Fistula Cannula with Anti‐Reflux Valve inserted into an idealized cephalic vein. The cannula tip was fixed at three different locations within the vein (upper third, middle, and lower third) with blood flow rates of 200 mL/min, 300 mL/min, and 400 mL/min imposed. The high degree of jet break down immediately after exiting the cannula was attributed to the staggered side hole arrangement, position of the cannula in the vein, and the imposed blood flow rate. Elevated levels of wall shear stress which may lead to IH were identified at the site of jet impingement on the vein floor as well as regions of high residency time. The risk of IH may be minimized by enhancing the breakdown of the jet through the use of optimal blood flow rates between 300 and 400 mL/min and ensuring the cannula tip is placed away from the walls of the vein.
The Effect of Impella CP on Cardiopulmonary Physiology During Venoarterial Extracorporeal Membrane Oxygenation Support
Authors: Lim Hoong Sern
Published: June 2017

Left ventricle (LV) distension is a complication of venoarterial extracorporeal membrane oxygenation (VA‐ECMO) support. The effects of Impella on the pulmonary circulatory physiology were studied in a single‐center study of six consecutive patients on VA‐ECMO support who had LV unloading with Impella. Right ventricular stroke volume, pulmonary hemodynamics, and partial pressure of end‐tidal CO2 (PETCO2) were measured on echocardiogram, pulmonary artery catheter, and capnography, respectively. The addition of Impella CP increased total blood flow and reduced pulmonary artery wedge pressure. There was a small reduction in arterial oxygen saturation as Impella increased LV output. The increase in pulmonary artery capacitance (PCap) exceeded the reduction in pulmonary vascular resistance (PVR), thereby increasing the pulmonary artery time constant (product of PCap and PVR). The right ventricular stroke volume increased and the improvement in pulmonary hemodynamics and blood flow were associated with reduced arterial‐PETCO2 gradient. The Impella CP unloads the LV during VA‐ECMO support, increasing total flow, reducing RV afterload, and facilitating RV output and pulmonary blood flow with improvement in gas exchange.
Editorial: biologics in inflammatory bowel disease―time for direct comparisons
Authors: Ungaro R. C. , Colombel J.‐F.
Published: June 2017

Linked Content

This article is linked to Cholapranee et al paper. To view this article visit https://doi.org/10.1111/apt.14030.
Letter: sublingual dosing of tacrolimus in transplant patients―interesting concept to overcome first pass effects. Authors' reply
Authors: Benítez C. , Vargas J. I. , Solari S.
Published: June 2017

Linked Content

This article is linked to Solari et al and Srinivas papers. To view these articles visit https://doi.org/10.1111/apt.14022 and https://doi.org/10.1111/apt.14087.
Systematic review: exercise‐induced gastrointestinal syndrome—implications for health and intestinal disease
Authors: Costa R. J. S. , Snipe R. M. J. , Kitic C. M. , Gibson P. R.
Published: June 2017

Background

“Exercise‐induced gastrointestinal syndrome” refers to disturbances of gastrointestinal integrity and function that are common features of strenuous exercise.

Aim

To systematically review the literature to establish the impact of acute exercise on markers of gastrointestinal integrity and function in healthy populations and those with chronic gastrointestinal conditions.

Methods

Search literature using five databases (PubMed, EBSCO, Web of Science, SPORTSdiscus, and Ovid Medline) to review publications that focused on the impact of acute exercise on markers of gastrointestinal injury, permeability, endotoxaemia, motility and malabsorption in healthy populations and populations with gastrointestinal diseases/disorders.

Results

As exercise intensity and duration increases, there is considerable evidence for increases in indices of intestinal injury, permeability and endotoxaemia, together with impairment of gastric emptying, slowing of small intestinal transit and malabsorption. The addition of heat stress and running mode appears to exacerbate these markers of gastrointestinal disturbance. Exercise stress of ≥2 hours at 60% VO2max appears to be the threshold whereby significant gastrointestinal perturbations manifest, irrespective of fitness status. Gastrointestinal symptoms, referable to upper‐ and lower‐gastrointestinal tract, are common and a limiting factor in prolonged strenuous exercise. While there is evidence for health benefits of moderate exercise in patients with inflammatory bowel disease or functional gastrointestinal disorders, the safety of more strenuous exercise has not been established.

Conclusions

Strenuous exercise has a major reversible impact on gastrointestinal integrity and function of healthy populations. The safety and health implications of prolonged strenuous exercise in patients with chronic gastrointestinal diseases/disorders, while hypothetically worrying, has not been elucidated and requires further investigation.
Value Relevance of Comprehensive Income
Authors: Khan Shahwali , Bradbury Michael E. , Courtenay Stephen
Published: June 2017

In this paper, we investigate the value relevance of comprehensive income and its components for a sample of 92 New Zealand companies over the period 2003–2010. We find a stronger association of aggregate comprehensive income with stock price and market returns relative to net income. The change in the asset revaluation reserve and the change in fair value of available‐for‐sale securities drive this association. However, foreign currency translation and cash flow hedges are also associated with prices and returns.
Can Employees Be Used to Overcome Independent Audit Limitations?
Authors: Christopher Joe , Leung Philomena , Leong Shane
Published: June 2017

Independent financial statement auditors are appointed by shareholders to provide reasonable assurance on the reliability of financial statements published by management of reporting entities. However, in the last two decades questions have been raised concerning the credibility of external audits due to their apparent failure, especially following the spate of corporate collapses. This paper applies a critical review of literature and a multi‐theoretical governance perspective to examine the inherent limitation of independent external audits and argues that employees can contribute to reducing the limitation gap by strengthening governance through a structure that incorporates a board and employee management representation. It is argued that through this arrangement, auditors can benefit as they will be privy to additional information from employees about issues such as irregular matters that impact upon shareholders and other stakeholders, and control weaknesses across governance levels, allowing auditors to establish a broader understanding of organisational information that may otherwise be less readily available. Thus auditors can base their judgements in terms of audit risks, and develop audit plans based on more reliable information. The theoretical proposition emerging from these findings is that the traditional governance model should be refined to include employees as an additional component of governance.
Winter supplementary feeding influences forest soil seed banks and vegetation
Authors: Jaroszewicz Bogdan , Kwiecień Kamil , Czortek Patryk , Olech Wanda , Pirożnikow Ewa
Published: June 2017

Question

To what extent does winter supplementary feeding influence vegetation and soil seed banks in forest ecosystems?

Location

Białowieża Primaeval Forest, NE Poland.

Methods

Several dozen feeding stations, each composed of one to several haystacks, are used in Białowieża Forest for supplementary winter feeding of European bison (Bison bonasus). We checked the species composition and availability of seeds in hay in 15 haystacks of the eight oldest feeding stations, which could be a potential source of seeds. Vegetation and soil seed bank were sampled on the overlapping 10 m × 10 m plots distributed along 500‐m long transects running south and north of the studied feeding stations. Seed content in the soil samples was studied by the seedling emergence method in an unheated greenhouse.

Results

We revealed high dissimilarity of species composition of the hayseed, soil seed bank and standing vegetation. The dissimilarity between soil seed banks and standing vegetation increased with the distance from the haystack. The species richness of the standing vegetation was not affected by distance to the haystack, while seed bank species richness showed a significant negative correlation with distance. The mean weighted ecological indicator values of pH, light and soil fertility were negatively correlated with the distance from the haystack for the seed bank and the standing vegetation. The percentage of damaged bushes and juvenile trees was positively correlated with their density and decreased with the distance from the haystack.

Conclusions

We revealed distinct but local (25–50 m off the haystack) effect of supplementary feeding on the vegetation and soil seed banks of forest ecosystems. Taking into account the ecosystem approach to nature conservation, the winter feeding in forest ecosystems should be concentrated in few places to avoid the expansion of non‐native plant species in forest ecosystems. To prevent potential plant invasions, the origin of the hay used as supplementary winter fodder should be carefully selected, with a preference for local origin and making of hay of native plant species in the forest's meadows or in its surroundings.
A Gatekeeping Procedure to Test a Primary and a Secondary Endpoint in a Group Sequential Design with Multiple Interim Looks
Authors: Tamhane Ajit C. , Gou Jiangtao , Jennison Christopher , Mehta Cyrus R. , Curto Teresa
Published: June 2017

Glimm et al. (2010) and Tamhane et al. (2010) studied the problem of testing a primary and a secondary endpoint, subject to a gatekeeping constraint, using a group sequential design (GSD) with looks. In this article, we greatly extend the previous results to multiple () looks. If the familywise error rate (FWER) is to be controlled at a preassigned level then it is clear that the primary boundary must be of level . We show under what conditions one -level primary boundary is uniformly more powerful than another. Based on this result, we recommend the choice of the O'Brien and Fleming (1979) boundary over the Pocock (1977) boundary for the primary endpoint. For the secondary endpoint the choice of the boundary is more complicated since under certain conditions the secondary boundary can be refined to have a nominal level , while still controlling the FWER at level , thus boosting the secondary power. We carry out secondary power comparisons via simulation between different choices of primary–secondary boundary combinations. The methodology is applied to the data from the RALES study (Pitt et al., 1999; Wittes et al., 2001). An R library package gsrsb to implement the proposed methodology is made available on CRAN.
Characterization of functional μ opioid receptor turnover in rat locus coeruleus: an electrophysiological and immunocytochemical study
Authors: Medrano María Carmen , Santamarta María Teresa , Pablos Patricia , Aira Zigor , Buesa Itsaso , Azkue Jon Jatsu , Mendiguren Aitziber , Pineda Joseba
Published: June 2017

Background and Purpose

Regulation of μ receptor dynamics such as its trafficking is a possible mechanism underlying opioid tolerance that contributes to inefficient recycling of opioid responses. We aimed to characterize the functional turnover of μ receptors in the noradrenergic nucleus locus coeruleus (LC).

Experimental Approach

We measured opioid effect by single‐unit extracellular recordings of LC neurons from rat brain slices. Immunocytochemical techniques were used to evaluate μ receptor trafficking.

Key Results

After near‐complete, irreversible μ receptor inactivation with β–funaltrexamine (β‐FNA), opioid effect spontaneously recovered in a rapid and efficacious manner. In contrast, α2‐adrenoceptor‐mediated effect hardly recovered after receptor inactivation with the irreversible antagonist EEDQ. When the recovery of opioid effect was tested after various inactivating time schedules, we found that the longer the β‐FNA pre‐exposure, the less efficient and slower the functional μ receptor turnover became. Interestingly, μ receptor turnover was slower when β‐FNA challenge was repeated in the same cell, indicating constitutive μ receptor recycling by trafficking from a depletable pool. Double immunocytochemistry confirmed the constitutive nature of μ receptor trafficking from a cytoplasmic compartment. The μ receptor turnover was slowed down when LC neuron calcium‐ or firing‐dependent processes were prevented or vesicular protein trafficking was blocked by a low temperature or transport inhibitor.

Conclusions and Implications

Constitutive trafficking of μ receptors from a depletable intracellular pool (endosome) may account for its rapid and efficient functional turnover in the LC. A finely‐tuned regulation of μ receptor trafficking and endosomes could explain neuroadaptive plasticity to opioids in the LC.
1,3‐Bis(aryloxy)propan‐2‐ols as potential antileishmanial agents
Authors: Lavorato Stefânia N. , Duarte Mariana C. , Lage Daniela P. , Tavares Carlos A. P. , Coelho Eduardo A. F. , Alves Ricardo J.
Published: June 2017

We describe herein the synthesis and antileishmanial activity of 1,3‐bis(aryloxy)propan‐2‐ols. Five compounds (2, 3, 13, 17, and 18) exhibited an effective antileishmanial activity against stationary promastigote forms of Leishmania amazonensis (IC50 < 15.0 μm), and an influence of compound lipophilicity on activity was suggested. Most of the compounds were poorly selective, as they showed toxicity toward murine macrophages, except 17 and 18, which presented good selective indexes (SI ≥ 10.0). The five more active compounds (2, 3, 13, 17, and 18) were selected for the treatment of infected macrophages, and all of them were able to reduce the number of internalized parasites by more than 80%, as well as the number of infected macrophages by more than 70% in at least one of the tested concentrations. Altogether, these results demonstrate the potential of these compounds as new hits of antileishmanial agents and open future possibilities for them to be tested in in vivo studies.
Diagnostic accuracy of increased urinary cortisol/cortisone ratio to differentiate ACTH‐dependent Cushing's syndrome
Authors: Ceccato Filippo , Trementino Laura , Barbot Mattia , Antonelli Giorgia , Plebani Mario , Denaro Luca , Regazzo Daniela , Rea Federico , Frigo Anna Chiara , Concettoni Carolina , Boscaro Marco , Arnaldi Giorgio , Scaroni Carla
Published: June 2017

Background and aim

Differential diagnosis between Cushing's Disease (CD) and Ectopic ACTH Syndrome (EAS) may be a pitfall for endocrinologists. The increasing use in clinical practice of chromatography and mass spectrometry improves the measurement of urinary free cortisol (UFF) and cortisone (UFE). We have recently observed that cortisol to cortisone ratio (FEr) was higher in a small series of EAS; in this study we collected a larger number of ACTH‐dependent Cushing's Syndrome (CS) to study the role of FEr to characterize the source of corticotropin secretion.

Materials and methods

High‐pressure liquid chromatography with UV detection (HPLC‐UV, n=35) or liquid chromatography‐tandem mass spectrometry (LC‐MS/MS, n=72) were used to measure UFF, UFE and FEr in 83 patients with CD and 24 with EAS.

Results

UFF, UFE and FEr levels were higher in EAS than in CD (UFF: 6671 vs 549 nmol/24 hours; UFE: 2069 vs 464 nmol/24 hours; FEr: 4.13 vs 0.97; all P<.001). FEr >1.15 (the best ROC‐based threshold) was able to distinguish CD from EAS with 75% sensitivity (SE) and 75% specificity (SP), AUC 0.811; results were similar between HPLC‐UV (SE 73%, SP 79%, AUC 0.708) and LC‐MS/MS (SE 77%, SP 73%, AUC 0.834; P=.727). The diagnostic accuracy of FEr was similar to that of CRH test or high‐dose dexamethasone suppression test (respectively P=.171 and P=.683), also combined. Finally, FEr was able to increase the number of correct diagnosis in patients with discordant dynamic tests.

Conclusions

Urinary FEr >1.15 was able to suggest EAS, with a diagnostic accuracy similar to that of other dynamic tests proposed to study ACTH‐dependent CS.
Identification of novel BCL11A variants in patients with epileptic encephalopathy: Expanding the phenotypic spectrum
Authors: Yoshida M. , Nakashima M. , Okanishi T. , Kanai S. , Fujimoto A. , Itomi K. , Morimoto M. , Saitsu H. , Kato M. , Matsumoto N. , Chiyonobu T.
Published: June 2017

BCL11A encodes a zinc finger protein that is highly expressed in hematopoietic tissues and the brain, and that is known to function as a transcriptional repressor of fetal hemoglobin (HbF). Recently, de novo variants in BCL11A have been reported in individuals with intellectual disability syndrome without epilepsy. In this study, we performed whole‐exome sequencing of 302 patients with epileptic encephalopathies (EEs), and identified 2 novel BCL11A variants, c.577delC (p.His193Metfs*3) and c.2351A>C (p.Lys784Thr). Both the patients shared major physical features characteristic of BCL11A‐related intellectual disability syndrome, suggesting that characteristic physical features and the persistence of HbF should lead clinicians to suspect EEs caused by BCL11A pathogenic variants. Patient 1, with a frameshift variant, presented with Lennox‐Gastaut syndrome, which expands the phenotypic spectrum of BCL11A haploinsufficiency. Patient 2, with a p.Lys784Thr variant, presented with West syndrome followed by drug‐resistant focal seizures and more severe developmental disability. These 2 newly described patients contribute to delineating the associated, yet uncertain phenotypic characteristics of BCL11A disease‐causing variants.
Urban Childhoods and Subjectification: Perspectives and Practices of Children on their Way to School
Authors: Fegter Susann
Published: June 2017

The aim of the article is to reflect theoretically and empirically on the question of how growing up in a city and having an urban childhood is relevant for children's agency and identity. It argues that agency and identity are a product of social and discursive practices that children take part in (e.g. on their way to school and after school). Based on an ethnographic project on urban childhoods in a big city in Germany, the article outlines the framework of this study and describes some findings on the basis of interviews, city walks and observation protocols. The function of the empirical data and analysis is to give an impression of what comes into focus if we reconstruct the entangled (re)production of urban spaces, agency and identity.
An international survey about nail histology processing techniques
Authors: Wlodek Christina , Lecerf Pauline , Andre Josette , Ruben Beth S. , de Berker David
Published: June 2017

Background

There are limited data on nail histopathology techniques. The objective of this study was to examine nail histopathology techniques currently in use internationally.

Methods

An online survey was sent to the European Nail Society and Council for Nail Disorders during 2015–2016.

Results

There were 57 respondents, from twenty countries comprising dermatologists, podiatrists and pathologists.

Specimens were unmarked or marked using ink or a suture and fixed in 10% formalin, from 6 to 48 hours before embedding in paraffin wax (90% [17/19]), liquid nitrogen (frozen section, 1/19) and 2‐hydroxyethylmethacrylate (plastic, 1/19).

Nail softening was undertaken by 71% (17/24) of respondents for 6 to 48 hours using Mollifex Gurr (12.5%, 3/24), 10% potassium hydroxide solution (12.5%, 3/24) or 10% potassium thioglycolate cream (12.5%, 3/24).

Section thickness was 4 to 9 µm (62.5%), using a steel microtome (92%,12/13) on glass slides (91.6%, 11/12).

Hematoxylin and eosin (H&E) was routine for all biopsies and Periodic acid Schiff (PAS) for fungus. The favored stain for differentiating melanin and hemoglobin was Fontana‐Masson (60%, 6/10). For pigmented lesions, Melan‐A was always employed by all respondents (9/9).

Conclusion

Nail histopathology processing has some small variations from normal skin processing.
Dermatologische Erkrankungen bei Palliativpatienten: eine prospektive Studie an 271 Patienten
Authors: Neloska Lenche , Damevska Katerina , Kuzmanova Andjelka , Pavleska Lidija , Kostov Milenko , Zovic Biljana Petreska
Published: June 2017

Hintergrund

Zahlreiche Faktoren erhöhen das Risiko von Palliativpatienten, an Hautinfektionen, Hautentzündungen oder Druckgeschwüren zu erkranken. Darüber hinaus sind eine Verschlechterung chronischer Hauterkrankungen sowie die Entwicklung behandlungsbedingter und malignitäts‐assoziierter Dermatosen zu erwarten. Ziel der vorliegenden Studie war es, Prävalenz und Behandlung dermatologischer Erkrankungen bei Patienten in stationärer Palliativversorgung zu untersuchen.

Methoden

Zweihunderteinundsiebzig Palliativpatienten wurden eingeschlossen. Alle Beurteilungen wurden von Dermatologen durchgeführt. Hautläsionen wurden in sieben Kategorien eingeteilt: Infektionen, Hauttumoren, Dermatitis, chronische Wunden, Nagel‐ und Haarerkrankungen, Pruritus und andere nicht klassifizierte Erkrankungen. Therapien wurden als topisch oder systemisch klassifiziert.

Ergebnisse

Insgesamt wurden 1.267 dermatologische Erkrankungen dokumentiert, von denen 49 % im Krankenhaus erworben wurden. Alle Patienten hatten mindestens eine dermatologische Erkrankung, und mehr als 50 verschiedene dermatologische Störungen wurden festgestellt. Die häufigste Gruppe von Hautkrankheiten waren Dermatitiden (18,3 % aller dermatologischen Erkrankungen), gefolgt von Nagel‐ und Haarerkrankungen (17,5 %). Fast 16 % der dermatologischen Erkrankungen wurden systemisch behandelt.

Schlussfolgerungen

Dermatologische Erkrankungen sind ein häufiges und klinisch bedeutsames Problem für Palliativpatienten. Die Einbeziehung von Dermatologen in multidisziplinäre Palliativteams zur Behandlung dieser Patienten ist daher sinnvoll.
Kutane Sarkome
Authors: Kohlmeyer Judith , Steimle‐Grauer Susanne Annette , Hein Rüdiger
Published: June 2017

Kutane Sarkome umfassen eine heterogene Gruppe von mesenchymalen spindelzelligen Tumoren der Dermis und Subkutis. Zu den bekanntesten Vertretern zählt das Dermatofibrosarcoma protuberans. Weitere Sarkome, die in diesem Artikel berücksichtigt werden, sind das atypische Fibrosarkom, das dermale undifferenzierte pleomorphe Sarkom, das Leiomyosarkom, das Liposarkom und das Angiosarkom. Kutane Sarkome kommen mit Ausnahme des Dermatofibrosarcoma protuberans, das seinen Häufigkeitsgipfel bei Erwachsenen mittleren Lebensalters hat, bei älteren Patienten ab der 6. bis 7. Lebensdekade vor. Die Pathogenese der unterschiedlichen Entitäten ist nicht einheitlich und im Einzelnen nicht abschließend geklärt. Zentral für eine korrekte Diagnosestellung ist die dermatohistopathologische Beurteilung, die auch immer dem Ausschluss anderer Neoplasien der Haut wie dem malignen Melanom dienen sollte. Molekulargenetische Methoden ermöglichten in den letzten Jahren tiefere Einblicke in die Pathogenese und bahnten den Weg für neue zielgerichtete Therapien. Therapie der Wahl bei kutanen Sarkomen ist die Exzision mit Sicherheitsabstand. Adjuvante und neoadjuvante Therapiekonzepte umfassen die Radiatio, den Einsatz von zielgerichteten Therapien oder auch Chemotherapien. Lokalrezidive werden bei kutanen Sarkomen häufig beschrieben. Die Prognose quoad vitam ist im Gegensatz zu Sarkomen des tiefen Binde‐ und Weichgewebes bei adäquater Therapie mit Ausnahme des Angiosarkoms sehr gut. Dies gilt es insbesondere dem Patienten gegenüber zu betonen.
Retrospective evaluation of exposure to natural UV radiation: experiences with the online UV history tool in a field study
Authors: Weistenhöfer Wobbeke , Hiller Julia , Drexler Hans , Kiesel Johannes
Published: June 2017

Background

Cutaneous squamous cell carcinoma and multiple actinic keratoses can be recognized as occupational diseases if the site affected has been subjected to additional occupational UV exposure of at least 40 %. An online UV history tool that allows for the quantification of occupational and recreational UV doses was now tested in a field study.

Patients and methods

Ninety‐nine patients with nonmelanoma skin cancer were examined. Patient history with respect to UV exposure was obtained using the online UV history tool. Initial validation was carried out with data from ten additional patients. In the context of a pilot study, the applicability of the tool was assessed using a questionnaire.

Results

Overall, patient history revealed a UV exposure between 3,792 and 53,163 SEDs. Patients with squamous cell carcinoma, actinic keratoses, or Bowen's disease (n  =  22) had significantly higher SED values and were significantly older (73 vs. 66 years) than patients with basal cell carcinoma (n  =  77). Occupational UV exposure was reported by 19 patients, two of whom showed an additional occupational UV exposure of more than 40 %, which prompted the filing of a (suspected) occupational disease report. With respect to validation, there was evidence of good inter‐investigator reliability. The applicability of the tool was rated as good.

Conclusions

The online UV history tool enables quick retrospective quantification of occupational and recreational UV exposure in case of suspicion of the occupational disease “cutaneous squamous cell carcinoma or multiple actinic keratoses caused by natural UV radiation”.
Modified continuity equation using left ventricular outflow tract three‐dimensional imaging for aortic valve area estimation
Authors: Pinto Teixeira Pedro , Ramos Ruben , Rio Pedro , Moura Branco Luísa , Portugal Guilherme , Abreu Ana , Galrinho Ana , Marques Hugo , Figueiredo Luísa , Cruz Ferreira Rui
Published: June 2017

Purpose

Aortic valve area (AVA) is usually estimated by the continuity equation (CE) in which the left ventricular outflow tract (LVOT) area is calculated assuming a circular shape. This study aimed to compare measurements of LVOT area using standard 2D transthoracic echocardiography (2DTTE), 3D transesophageal echocardiography (3DTEE), and multidetector computed tomography (MDCT) and assess their relative impact on AVA estimated by the CE.

Methods and Results

We prospectively enrolled 60 patients with severe aortic stenosis (AS) referred for transcatheter aortic valve replacement (TAVR) who systematically underwent 2DTTE, 3DTEE, and MDCT. Mean LVOT areas obtained by 2DTTE (3.28±0.66 cm2) and 3DTEE (3.95±0.90 cm2) were significantly underestimated when compared to the mean MDCT LVOT area (4.31±0.99 cm2). LVOT was rather elliptical than round, with a mean eccentricity index of 1.47 (ratio of maximum to minimum LVOT diameters) assessed by MDCT. Mean TTE AVA estimated by the CE was 0.62±0.20 cm2. Substitution of 2DTTE LVOT area by 3DTEE LVOT area in the CE resulted in AVA of 0.74±0.24 cm2, while using MDCT LVOT area held an AVA of 0.80±0.24 cm2. MDCT‐derived AVA was similar to MDCT planimetric AVA and allowed 24% of patients to be reclassified from severe to moderate AS.

Conclusions

2DTTE and 3DTEE underestimate LVOT area when compared to MDCT with significant impact on AVA estimation. Assessment through MDCT fusion AVA may be of incremental value in patients with discrepant severity criteria for AS.