bluuebunny/crossref_metadata_2025 huggingface dataset:
Cardiovascular safety of sulphonylureas: over 40 years of continuous controversy without an answer
Authors: Abdelmoneim A. S. , Eurich D. T. , Light P. E. , Senior P. A. , Seubert J. M. , Makowsky M. J. , Simpson S. H.
Published: February 2015

More than 40 years after publication of the University Group Diabetes Program trial, the cardiovascular safety of sulphonylureas is still contentious. Although several hypotheses linking sulphonylureas to adverse cardiovascular effects exist, none provide conclusive evidence. Adding to the controversy, current clinical trials and observational studies provide inconsistent, and sometimes conflicting, evidence for the cardiovascular effects of sulphonylureas. Overall, observational evidence suggests that an increased risk of adverse cardiovascular outcomes is associated with sulphonylureas; however, these data may be subject to residual confounding and bias. Although evidence from randomized controlled trials has suggested a neutral effect, the majority of these studies were not specifically designed to assess the effect of sulphonylureas on adverse cardiovascular event risk. Current ongoing large clinical trials may provide some clarity on the cardiovascular safety of sulphonylureas, but the results are not expected for several years. With the continued uncertainties concerning the cardiovascular safety of all antidiabetic drugs, a clear answer with regard to sulphonylureas is warranted. The objectives of the present article were to provide an overview of the controversy surrounding sulphonylurea‐related cardiovascular effects, to discuss the limitations of the current literature, and to provide recommendations for future studies aiming to elucidate the true relationship between sulphonylureas and adverse cardiovascular effects in people with type 2 diabetes.
High‐frequency stimulation of the medial prefrontal cortex decreases cellular firing in the dorsal raphe
Authors: Srejic Luka R. , Hamani Clement , Hutchison William D.
Published: February 2015

High‐frequency deep brain stimulation (HFS‐DBS) of the subcallosal cingulate (SCC) region has been investigated as a treatment for refractory forms of depression with a ~50% remission rate in open label studies. However, the therapeutic mechanisms of DBS are still largely unknown. Using anaesthetized Sprague Dawley rats, we recorded neuronal spiking activity in 102 neurons of the dorsal raphe (DR) before, during and after the induction of a 5‐min HFS train in the infralimbic region (IL) of the medial prefrontal cortex (mPFC), the rodent homologue of the human SCC. The majority of DR cells (82%) significantly decreased firing rate during HFS (P < 0.01, 55.7 ± 4.5% of baseline, 35 rats). To assess whether mPFC‐HFS mediates inhibition of DR cellular firing by stimulating local GABAergic interneurons, the GABAA antagonist bicuculline (Bic, 100 μm) was injected directly into the DR during HFS. Neurons inhibited by HFS recovered their firing rate during Bic+HFS (P < 0.01, n = 15, seven rats) to levels not different from baseline. Cells that were not affected by HFS did not change firing rate during Bic+HFS (P = 0.968, n = 7, three rats). These results indicate that blocking GABAA reverses HFS‐mediated inhibition of DR neurons. As the cells that were not inhibited by HFS were also unaffected by HFS+Bic, they are probably not innervated by local GABA. Taken together, our results suggest that mPFC‐HFS may exert a preferential effect on DR neurons with GABAA receptors.
Generation of resonance‐dependent oscillation by mGluR‐I activation switches single spiking to bursting in mesencephalic trigeminal sensory neurons
Authors: Chung Gehoon , Saito Mitsuru , Kawasaki Yasuhiro , Kawano Tsutomu , Yin Dongxu , Lee Soojung , Kogo Mikihiko , Takada Masahiko , Bae Yong Chul , Kim Joong Soo , Oh Seog Bae , Kang Youngnam
Published: February 2015

The primary sensory neurons supplying muscle spindles of jaw‐closing muscles are unique in that they have their somata in the mesencephalic trigeminal nucleus (MTN) in the brainstem, thereby receiving various synaptic inputs. MTN neurons display bursting upon activation of glutamatergic synaptic inputs while they faithfully relay respective impulses arising from peripheral sensory organs. The persistent sodium current (INaP) is reported to be responsible for both the generation of bursts and the relay of impulses. We addressed how INaP is controlled either to trigger bursts or to relay respective impulses as single spikes in MTN neurons. Protein kinase C (PKC) activation enhanced INaP only at low voltages. Spike generation was facilitated by PKC activation at membrane potentials more depolarized than the resting potential. By injection of a ramp current pulse, a burst of spikes was triggered from a depolarized membrane potential whereas its instantaneous spike frequency remained almost constant despite the ramp increases in the current intensity beyond the threshold. A puff application of glutamate preceding the ramp pulse lowered the threshold for evoking bursts by ramp pulses while chelerythrine abolished such effects of glutamate. Dihydroxyphenylglycine, an agonist of mGluR1/5, also caused similar effects, and increased both the frequency and impedance of membrane resonance. Immunohistochemistry revealed that glutamatergic synapses are made onto the stem axons, and that mGluR1/5 and Nav1.6 are co‐localized in the stem axon. Taken together, glutamatergic synaptic inputs onto the stem axon may be able to switch the relaying to the bursting mode.
After the Crash: A Perspective on Multilevel European Democracy
Authors: Scharpf Fritz W.
Published: February 2015

From a social‐market perspective, European integration has reduced the capacity of democratic politics to deal with the challenges of global capitalism, and it has contributed to rising social inequality. The article summarises the institutional asymmetries which have done most to constrain democratic political choices and to shift the balance between capital, labour and the state: the priority of negative over positive integration and of monetary integration over political and social integration. It will then explain why efforts to democratise European politics will not be able to overcome these asymmetries and why politically feasible reforms will not be able to remove them. On the speculative assumption that the aftermath of a deep crisis might indeed create the window of opportunity for a political re‐foundation of European integration, the concluding section will outline institutional ground rules that might facilitate democratic political action at both European and national levels.
Habitat corridors facilitate genetic resilience irrespective of species dispersal abilities or population sizes
Authors: Christie Mark R. , Knowles L. Lacey
Published: February 2015

Corridors are frequently proposed to connect patches of habitat that have become isolated due to human‐mediated alterations to the landscape. While it is understood that corridors can facilitate dispersal between patches, it remains unknown whether corridors can mitigate the negative genetic effects for entire communities modified by habitat fragmentation. These negative genetic effects, which include reduced genetic diversity, limit the potential for populations to respond to selective agents such as disease epidemics and global climate change. We provide clear evidence from a forward‐time, agent‐based model (ABM) that corridors can facilitate genetic resilience in fragmented habitats across a broad range of species dispersal abilities and population sizes. Our results demonstrate that even modest increases in corridor width decreased the genetic differentiation between patches and increased the genetic diversity and effective population size within patches. Furthermore, we document a trade‐off between corridor quality and corridor design whereby populations connected by high‐quality habitat (i.e., low corridor mortality) are more resilient to suboptimal corridor design (e.g., long and narrow corridors). The ABM also revealed that species interactions can play a greater role than corridor design in shaping the genetic responses of populations to corridors. These results demonstrate how corridors can provide long‐term conservation benefits that extend beyond targeted taxa and scale up to entire communities irrespective of species dispersal abilities or population sizes.
Genetic screens and functional genomics using CRISPR/Cas9 technology
Authors: Hartenian Ella , Doench John G.
Published: February 2015

Functional genomics attempts to understand the genome by perturbing the flow of information from DNA to RNA to protein, in order to learn how gene dysfunction leads to disease. CRISPR/Cas9 technology is the newest tool in the geneticist's toolbox, allowing researchers to edit DNA with unprecedented ease, speed and accuracy, and representing a novel means to perform genome‐wide genetic screens to discover gene function. In this review, we first summarize the discovery and characterization of CRISPR/Cas9, and then compare it to other genome engineering technologies. We discuss its initial use in screening applications, with a focus on optimizing on‐target activity and minimizing off‐target effects. Finally, we comment on future challenges and opportunities afforded by this technology.
Parkin structure and function
Authors: Seirafi Marjan , Kozlov Guennadi , Gehring Kalle
Published: February 2015

Mutations in the parkin or PINK1 genes are the leading cause of the autosomal recessive form of Parkinson's disease. The gene products, the E3 ubiquitin ligase parkin and the serine/threonine kinase PINK1, are neuroprotective proteins, which act together in a mitochondrial quality control pathway. Here, we review the structure of parkin and mechanisms of its autoinhibition and function as a ubiquitin ligase. We present a model for the recruitment and activation of parkin as a key regulatory step in the clearance of depolarized or damaged mitochondria by autophagy (mitophagy). We conclude with a brief overview of other functions of parkin and considerations for drug discovery in the mitochondrial quality control pathway.
Does the non‐native European catfish Silurus glanis threaten French river fish populations?
Authors: Guillerault Nicolas , Delmotte Sébastien , Boulêtreau Stéphanie , Lauzeral Christine , Poulet Nicolas , Santoul Frédéric
Published: February 2015

The European catfish, Silurus glanis, was widely introduced in western Europe, and it has now established self‐sustaining populations in numerous large rivers of western France. Using data collected from surveys conducted by the French National Agency for Water and Aquatic Environment (Onema) from 1989 to 2010 in more than 500 sites throughout the country (10636 electrofishing surveys), we investigated the potential impact of the European catfish on fish communities in French rivers.

In the first part of the analysis, we compared trends observed before and after the European catfish was established at given sites (before–after analysis). Species richness, evenness and diversity decreased significantly after the European catfish was established at 1.4%, 1.4% and 5.8% of the sites, respectively. Total fish biomass and density decreased significantly at 6.6% and 2.9% of the sites, respectively. In the second part of the analysis, we compared sites with European catfish against sites lacking European catfish during the same period (with–without analysis). Fish species richness was significantly higher in sites with European catfish. No significant differences in fish diversity, evenness, total fish biomass or density were found between sites with or without European catfish.

While our results indicate that the European catfish may in a few cases impact fish communities or populations, it does not appear to be responsible for a countrywide collapse in fish assemblages.
Twenty‐five years of change in southern African passerine diversity: nonclimatic factors of change
Authors: Péron Guillaume , Altwegg Res
Published: February 2015

We analysed more than 25 years of change in passerine bird distribution in South Africa, Swaziland and Lesotho, to show that species distributions can be influenced by processes that are at least in part independent of the local strength and direction of climate change: land use and ecological succession. We used occupancy models that separate species' detection from species' occupancy probability, fitted to citizen science data from both phases of the Southern African Bird Atlas Project (1987–1996 and 2007–2013). Temporal trends in species' occupancy probability were interpreted in terms of local extinction/colonization, and temporal trends in detection probability were interpreted in terms of change in abundance. We found for the first time at this scale that, as predicted in the context of bush encroachment, closed‐savannah specialists increased where open‐savannah specialists decreased. In addition, the trend in the abundance of species a priori thought to be favoured by agricultural conversion was negatively correlated with human population density, which is in line with hypotheses explaining the decline in farmland birds in the Northern Hemisphere. In addition to climate, vegetation cover and the intensity and time since agricultural conversion constitute important predictors of biodiversity changes in the region. Their inclusion will improve the reliability of predictive models of species distribution.
Regional‐scale directional changes in abundance of tree species along a temperature gradient in Japan
Authors: Suzuki Satoshi N. , Ishihara Masae I. , Hidaka Amane
Published: February 2015

Climate changes are assumed to shift the ranges of tree species and forest biomes. Such range shifts result from changes in abundances of tree species or functional types. Owing to global warming, the abundance of a tree species or functional type is expected to increase near the colder edge of its range and decrease near the warmer edge. This study examined directional changes in abundance and demographic parameters of forest trees along a temperature gradient, as well as a successional gradient, in Japan. Changes in the relative abundance of each of four functional types (evergreen broad‐leaved, deciduous broad‐leaved, evergreen temperate conifer, and evergreen boreal conifer) and the demography of each species (recruitment rate, mortality, and population growth rate) were analyzed in 39 permanent forest plots across the Japanese archipelago. Directional changes in the relative abundance of functional types were detected along the temperature gradient. Relative abundance of evergreen broad‐leaved trees increased near their colder range boundaries, especially in secondary forests, coinciding with the decrease in deciduous broad‐leaved trees. Similarly, relative abundance of deciduous broad‐leaved trees increased near their colder range boundaries, coinciding with the decrease in boreal conifers. These functional‐type‐level changes were mainly due to higher recruitment rates and partly to the lower mortality of individual species at colder sites. This is the first report to show that tree species abundances in temperate forests are changing directionally along a temperature gradient, which might be due to current or past climate changes as well as recovery from past disturbances.
Constraining groundwater flow in the glacial drift and saginaw aquifers in the Michigan Basin through helium concentrations and isotopic ratios
Authors: Wen T. , Castro M. C. , Hall C. M. , Pinti D. L. , Lohmann K. C.
Published: February 2015

3He and 4He concentrations in excess of those in water in solubility equilibrium with the atmosphere by up to two and three orders of magnitude are observed in the shallow Glacial Drift and Saginaw aquifers in the Michigan Basin. A simplified He transport model shows that in situ production is negligible and that most He excesses have a source external to the aquifer. Simulated results show that 3He and 4He fluxes entering the bottom of the Saginaw aquifer are 7.5 × 10−14 and 6.1 × 10−7 cm3STPcm−2 yr−1, both of which are lower than fluxes entering the underlying Marshall aquifer, 1.0 × 10−13 and 1.6 × 10−6 cm3STPcm−2 yr−1 for 3He and 4He, respectively. In contrast, He fluxes entering the Saginaw aquifer are higher than fluxes entering the overlying Glacial Drift aquifer of 5.2 × 10−14 and 1.5 × 10−7 cm3STPcm−2 yr−1 for 3He and 4He, respectively. The unusually high He fluxes and their decreasing values from the lower Marshall to the upper Glacial Drift aquifer strongly suggest the presence of an upward cross‐formational flow, with increasing He dilution toward the surface by recharge water. These fluxes are either comparable to or far greater than He fluxes in deeper aquifers around the world. Model simulations also suggest an exponential decrease in the horizontal groundwater velocity with recharge distance. Horizontal velocities vary from 13 to 2 myr−1 for the Saginaw aquifer and from 18 to 6 myr−1 for the Marshall aquifer. The highly permeable Glacial Drift aquifer displays a greater velocity range, from 250 to 5 myr−1. While Saginaw 4He ages estimated based on the simulated velocity field display an overall agreement with 14C ages, 14C and 4He ages in the Glacial Drift and Marshall aquifers deviate significantly, possibly due to simplifications introduced in the He transport model leading to calculation of first‐order approximation He ages and high uncertainties in Glacial Drift 14C ages.
Meta‐analysis of grass ley response to phosphorus fertilization in Finland
Authors: Valkama E. , Virkajärvi P. , Uusitalo R. , Ylivainio K. , Turtola E.
Published: February 2015

Studies have shown that yield responses of grass leys to phosphorus (P) fertilization vary considerably and initial soil test P (STP) does not always predict such variation. To identify the sources of variation in dry‐matter (DM) yield responses to P, we used a meta‐analysis to review quantitatively 38 Finnish field experiments on various soil types and growth conditions and to develop yield‐response models. The major sources of variation in the yield responses to annually applied P were soil type, soil acidity (for organic soils), initial STP and control yields fertilized with nitrogen (N) and potassium (K). According to Mitscherlich‐type exponential models, the maximum yield increases due to P fertilization in the low‐STP class were 18% over the control on mineral soils and 28% on organic soils. However, only about 40% of the variation in yield could be attributed to annual fertilizer P applications. Control yields explained about 25% of variation in yield responses to P fertilization, and P addition became less efficient with increasing control yields, which were associated with rising N rates. While applied P leads to infrequent or small yield responses on mineral soils, other practices to increase grass yields should be prioritized, including optimal N fertilization. On moderately acidic organic soils that show clearly lower P responses than do similar but less acidic soils, liming should be the first step to increase yields. Moreover, the models derived in this work indicate that revising P fertilizer recommendations in Finland would avoid unnecessary application at non‐responsive STP levels.
Reported consent processes and demographics: a substudy of the INSIGHT Strategic Timing of AntiRetroviral Treatment (START) trial
Authors: Denning E , Sharma S , Smolskis M , Touloumi G , Walker S , Babiker A , Clewett M , Emanuel E , Florence E , Papadopoulos A , Sánchez A , Tavel J , Grady C ,   International Network for Strategic Initiatives in Global HIV Trials (INSIGHT) START Study Group
Published: February 2015

Objectives

Efforts are needed to improve informed consent of participants in research. The Strategic Timing of AntiRetroviral Therapy (START) study provides a unique opportunity to study the effect of length and complexity of informed consent documents on understanding and satisfaction among geographically diverse participants.

Methods

Interested START sites were randomized to use either the standard consent form or the concise consent form for all of the site's participants.

Results

A total of 4473 HIV‐positive participants at 154 sites world‐wide took part in the Informed Consent Substudy, with consent given in 11 primary languages. Most sites sent written information to potential participants in advance of clinic visits, usually including the consent form. At about half the sites, staff reported spending less than an hour per participant in the consent process. The vast majority of sites assessed participant understanding using informal nonspecific questions or clinical judgment.

Conclusions

These data reflect the interest of START research staff in evaluating the consent process and improving informed consent. The START Informed Consent Substudy is by far the largest study of informed consent intervention ever conducted. Its results have the potential to impact how consent forms are written around the world.
Global HIV‐1 transmitted drug resistance in the INSIGHT Strategic Timing of AntiRetroviral Treatment (START) trial
Authors: Baxter JD , Dunn D , White E , Sharma S , Geretti AM , Kozal MJ , Johnson MA , Jacoby S , Llibre JM , Lundgren J ,   International Network for Strategic Initiatives in Global HIV Trials (INSIGHT) START Study Group
Published: February 2015

Objectives

HIV‐1 transmitted drug resistance (TDR) in treatment‐naïve individuals is a well‐described phenomenon. Baseline genotypic resistance testing is considered standard of care in most developed areas of the world. The aim of this analysis was to characterize HIV‐1 TDR and the use of resistance testing in START trial participants.

Methods

In the Strategic Timing of AntiRetroviral Treatment (START) trial, baseline genotypic resistance testing results were collected at study entry and analysed centrally to determine the prevalence of TDR in the study population. Resistance was based on a modified 2009 World Health Organization definition to reflect newer resistance mutations.

Results

Baseline resistance testing was available in 1946 study participants. Higher rates of testing occurred in Europe (86.7%), the USA (81.3%) and Australia (89.9%) as compared with Asia (22.2%), South America (1.8%) and Africa (0.1%). The overall prevalence of TDR was 10.1%, more commonly to nonnucleoside reverse transcriptase inhibitors (4.5%) and nucleoside reverse transcriptase inhibitors (4%) compared with protease inhibitors (2.8%). The most frequent TDR mutations observed were M41L, D67N/G/E, T215F/Y/I/S/C/D/E/V/N, 219Q/E/N/R, K103N/S, and G190A/S/E in reverse transcriptase, and M46I/L and L90M in protease. By country, the prevalence of TDR was highest in Australia (17.5%), France (16.7%), the USA (12.6%) and Spain (12.6%). No participant characteristics were identified as predictors of the presence of TDR.

Conclusions

START participants enrolled in resource‐rich areas of the world were more likely to have baseline resistance testing. In Europe, the USA and Australia, TDR prevalence rates varied by country.
Development of an improved method for quantitative analysis of skin blotting: increasing reliability and applicability for skin assessment
Authors: Ogai K. , Matsumoto M. , Minematsu T. , Kitamura K. , Kobayashi M. , Sugama J. , Sanada H.
Published: February 2015

Objective

A novel skin assessment tool named ‘skin blotting’ has been recently developed, which can easily predict the skin status to avoid its deterioration. The aim of this study was to propose a normalization method for skin blotting to compensate for individual differences that can hamper the quantitative comparisons and clinical applications.

Methods

To normalize individual differences, we utilized a total protein as a ‘normalizer’ with calibration curves. For evaluation, we performed a simple simulation experiment, in which the same concentration of a protein of interest [tumour necrosis factor (TNF)‐α] was applied at different volumes as a virtual individual difference. Moreover, to demonstrate the applicability of this normalization, male volunteers were recruited for skin blotting followed by the estimation of TNF‐α with normalization.

Results

We obtained good calibration curves for total protein (R2 = 0.995) and TNF‐α (R2 = 0.997), both of which were necessary for an exact quantification. In the simulation experiment, we estimated the exact concentration of TNF‐α regardless of the applied volume, demonstrating the applicability of this normalization method in skin blotting. Further, skin blotting on human subjects showed a wide range of variation in the total protein content, although the normalization was thought to reduce such individual variations.

Conclusion

This study has proposed total protein normalization for skin blotting with calibration curves. This method may strengthen the quantitative performance of skin blotting, which may expand the applicability of this method as a skin assessment tool in broader fields, such as nursing and cosmetology.
More action, less resistance: report of the 2014 summit of the Global Respiratory Infection Partnership
Authors: Altiner Attila , Bell John , Duerden Martin , Essack Sabiha , Kozlov Roman , Noonan Laura , Oxford John , Pignatari Antonio Carlos , Sessa Aurelio , van der Velden Alike
Published: February 2015

‘Antimicrobial resistance is a global health security threat that requires concerted cross-sectional action by governments and society as a whole,’ according to a report published by the WHO in April 2014[1]. On 24–25 June 2014, the Global Respiratory Infection Partnership (GRIP) met in London, UK, together with delegates from 18 different countries to discuss practical steps that can be taken at a local level to address this global problem in an aligned approach.

This was the second annual summit of GRIP. The group, formed in 2012, includes primary care and hospital physicians, microbiologists, researchers, and pharmacists from nine core countries. GRIP aims to unite healthcare professionals (HCPs) around the world to take action against inappropriate antibiotic use, focussing on one of the most prevalent therapy areas where antibiotics are inappropriately prescribed – upper respiratory tract infections (URTIs).

Chaired by GRIP member, Professor John Oxford (UK), the 2014 summit included engaging presentations by guest speakers examining the latest science regarding the impact of inappropriate antibiotic use.
Community pharmacists’ experience and perceptions of the New Medicines Service (NMS)
Authors: Lucas Beverley , Blenkinsopp Alison
Published: February 2015

Objectives

The New Medicines Service (NMS) is provided by community pharmacists in England to support patient adherence after the initiation of a new treatment. It is provided as part of the National Health Service (NHS) pharmacy contractual framework and involves a three-stage process: patient engagement, intervention and follow-up. The study aims to explore community pharmacists’ experiences and perceptions of NMS within one area of the United Kingdom.

Methods

In-depth semi-structured telephone interviews were conducted with 14 community pharmacists. Interviews were audio-recorded, independently transcribed and thematically analysed.

Key findings

Pharmacists gave a mixed response to the operationalisation, ranging from positive opportunities for improving adherence and enhancement of practice to difficulties in terms of its administration. Pharmacists generally welcomed opportunities to utilise their professional expertise to achieve better patient engagement and for pharmacy practice to develop as a patient resource. There was a perceived need for better publicity about the service. Different levels of collaborative working were reported. Some pharmacists were working closely with local general practices most were not. Collaboration with nurses in the management of long-term conditions was rarely reported but desired by pharmacists. Where relationships with general practitioners (GPs) and nurses were established, NMS was an opportunity for further collaboration; however, others reported a lack of feedback and recognition of their role.

Conclusions

Community pharmacists perceived the NMS service as beneficial to patients by providing additional advice and reassurance, but perceptions of its operationalisation were mixed. Overall, our findings indicate that NMS provides an opportunity for patient benefit and the development of contemporary pharmacy practice, but better collaboration with GPs and practice nurses could enhance the service.
Differentiation of lower urinary tract dysfunctions: The role of ambulatory urodynamic monitoring
Authors: Rademakers Kevin LJ , Drossaerts Jamie MAFL , Rahnama'i Mohammad S , van Koeveringe Gommert A
Published: February 2015

Objectives

To determine the value of ambulatory urodynamic monitoring in the assessment of patients with lower urinary tract symptoms.

Methods

This was a cross‐sectional study including patients who underwent both conventional urodynamic and ambulatory urodynamic assessment at our Center between December 2002 and February 2013. The ambulatory urodynamic studies were interpreted in a standardized way by a resident experienced with urodynamic measurements, and one staff member who specialized in incontinence and urodynamics.

Results

A total of 239 patients (71 male and 168 female) were included in the present study. The largest subgroup of patients, 79 (33%), underwent ambulatory urodynamic monitoring based on suspicion of an acontractile bladder. However, 66 of these patients (83.5%) still showed contractions on ambulatory urodynamics. Other groups that were analyzed were patients with suspected storage dysfunction (47 patients), inconclusive conventional urodynamic studies (68 patients) and incontinence of unclear origin (45 patients). Particularly in this last group, ambulatory urodynamics appeared to be useful for discrimination between different causes of incontinence.

Conclusions

Ambulatory urodynamic monitoring is a valuable discriminating diagnostic tool in patients with lower urinary tract symptoms who have already undergone conventional urodynamics, particularly in the case of patients with suspected bladder acontractility and incontinence of unclear origin during ambulatory urodynamics. Further study is required to determine the clinical implications of the findings and their relationship with treatment outcome.
Results of a pilot study using self‐collected mid‐turbinate nasal swabs for detection of influenza virus infection among pregnant women
Authors: Thompson Mark G. , Ferber Jeannette R. , Odouli Roxana , David Donna , Shifflett Pat , Meece Jennifer K. , Naleway Allison L. , Bozeman Sam , Spencer Sarah M. , Fry Alicia M. , Li De‐Kun
Published: February 2015

Background

We evaluated the feasibility of asking pregnant women to self‐collect and ship respiratory specimens.

Methods

In a preliminary laboratory study, we compared the RT‐PCR cycle threshold (CT) values of influenza A and B viruses incubated at 4 storage temperatures (from 4 to 35°C) for 6 time periods (8, 24, 48, 72, and 168 hours and 30 days), resulting in 24 conditions that were compared to an aliquot tested after standard freezing (−20°C) (baseline condition). In a subsequent pilot study, during January–February, 2014, we delivered respiratory specimen collection kits to 53 pregnant women with a medically attended acute respiratory illness using three delivery methods.

Results

CT values were stable after storage at temperatures <27°C for up to 72 hours for influenza A viruses and 48 hours for influenza B viruses. Of 53 women who received kits during the pilot, 89% collected and shipped nasal swabs as requested. However, 30% (14/47) of the women took over 2 days to collect and ship their specimen. The human control gene, ribonuclease P (RNase P), was detected in 100% of nasal swab specimens. However, the mean CT values for RNase P (26·5, 95% confidence interval [CI] = 26·0–27·1) and for the 8 influenza A virus positives in our pilot (32·2, 95% CI = 28·9–35·5) were significantly higher than the CTs observed in our 2010–2012 study using staff‐collected nasal pharyngeal swabs (P‐values < 0·01).

Discussion

Self‐collection of respiratory specimens is a promising research method, but further research is needed to quantify the sensitivity and specificity of the approach.
LEADERSHIP IN ACTION TEAMS: TEAM LEADER AND MEMBERS’ AUTHENTICITY, AUTHENTICITY STRENGTH, AND TEAM OUTCOMES
Authors: HANNAH SEAN T. , WALUMBWA FRED O. , FRY LOUIS W.
Published: February 2015

A field study was conducted with 47 Army action teams spanning 9 weeks to assess the influence of team leader authenticity on team authenticity and team outcomes. Results showed that team leader authenticity at Time 1 predicted teamwork behavior and team productivity at Time 3, with these relationships mediated by team authenticity at Time 2. We further explored the moderating role of authenticity strength in the team authenticity–teamwork behavior relationship. Team authenticity interacted with authenticity strength such that the team authenticity–teamwork behavior relationship was stronger when authenticity strength was higher rather than lower. Implications of these findings for theories of shared leadership, team leadership, and authentic leadership are discussed.
Seasonal mortality and sequential density dependence in a migratory bird
Authors: Rakhimberdiev Eldar , van den Hout Piet J. , Brugge Maarten , Spaans Bernard , Piersma Theunis
Published: February 2015

Migratory bird populations may be limited during one or more seasons, and thus at one or more places, but there is a dearth of empirical examples of this possibility. We analyse seasonal survival in a migratory shellfish‐eating shorebird (red knot Calidris canutus islandica) during a series of years of intense food limitation on the nonbreeding grounds (due to overfishing of shellfish stocks), followed by a relaxation period when destructive harvesting had stopped and food stocks for red knots recovered. For the estimation of seasonal survival from the 15 yr‐long near‐continuous capture–resight dataset, we introduce a ‘rolling window’ approach for data exploration, followed by selection of the best season definition. The average annual apparent survival over all the years was 0.81 yr−1. During the limitation period, survival probability of adult red knots was low in winter (0.78 yr−1), but this was compensated by high survival in summer (0.91 yr−1). During the relaxation period survival rate levelled out with a winter value of 0.81 yr−1 and a summer survival of 0.82 yr−1. The fact that during the cockle‐dredging period the dip in survival in winter was completely compensated by higher survival later in the annual cycle suggests sequential density dependence. We conclude that seasonal compensation in local survival (in concert with movements to areas apparently below carrying capacity) allowed the islandica population as a whole to cope, in 1998–2003, with the loss of half of the suitable feeding habitat in part of the nonbreeding range, the western Dutch Wadden Sea. As a more general point, we see no reason why inter‐seasonal density dependence should not be ubiquitous in wildlife populations, though its limits and magnitude will depend on the specific ecological contexts. We elaborate the possibility that with time, and in stable environments, seasonal mortality evolves so that differences in mortality rates between seasons would become erased.
Annual Research Review: Infant development, autism, and ADHD – early pathways to emerging disorders
Authors: Johnson Mark H. , Gliga Teodora , Jones Emily , Charman Tony
Published: February 2015

Background

Autism spectrum disorders (ASD) and attention deficit hyperactivity disorder (ADHD) are two of the most common neurodevelopmental disorders, with a high degree of co‐occurrence.

Methods

Prospective longitudinal studies of infants who later meet criteria for ASD or ADHD offer the opportunity to determine whether the two disorders share developmental pathways.

Results

Prospective studies of younger siblings of children with autism have revealed a range of infant behavioral and neural markers associated with later diagnosis of ASD. Research on infants with later ADHD is less developed, but emerging evidence reveals a number of relations between infant measures and later symptoms of inattention and hyperactivity.

Conclusions

We review this literature, highlighting points of convergence and divergence in the early pathways to ASD and ADHD.
Commentary: Insights from across diagnostic boundaries: ADHD in the RDoC era – a commentary on Scerif and Baker (2015)
Authors: Doyle Alysa E.
Published: February 2015

Unbiased genomewide association studies of tens of thousands of individuals are transforming our understanding of the origins and structure of psychopathology across the lifespan. Together with findings from epidemiology and cognitive neuroscience, these recent molecular genetic studies underscore the importance of studying phenotypes across as well as within conventional psychiatric diagnoses in order to construct a more pathophysiologically grounded taxonomy from the bottom up. Such efforts, promoted by NIMH's Research Domain Criteria (RDoC) framework, are critical to developing more accurate models of the risk mechanisms that are shared and distinct across various psychopathologic outcomes. In turn, these models could reveal new treatment targets and early intervention opportunities. In their article in the 2015 JCPP Annual Research Review, Scerif and Baker remind us that bottom‐up insights into psychiatric illness might also be gained by examining specific genetic disorders that often fall within the purview of pediatrics and neurology. These authors note high rates of symptoms of attention‐deficit hyperactivity disorder (ADHD) in syndromes with known and often monogenic genetic causes (e.g. Fragile X) and suggest that studying the ADHD‐like phenomena in these conditions may provide insight into ADHD itself. This commentary highlights themes from Scerif and Baker's review that overlap with the core tenets of RDoC and notes their significance for advancing our understanding of ADHD in the coming years. It concludes by suggesting ways in which further attention to the RDoC framework could also enhance Scerif and Baker's agenda.
High‐definition optical coherence tomography algorithm for discrimination of basal cell carcinoma from clinical BCC imitators and differentiation between common subtypes
Authors: Boone M.A.L.M. , Suppa M. , Pellacani G. , Marneffe A. , Miyamoto M. , Alarcon I. , Ruini C. , Hofmann‐Wellenhof R. , Malvehy J. , Jemec G.B.E. , Del Marmol V.
Published: February 2015

Background

Preliminary studies have described morphological features of basal cell carcinoma (BCC) imaged by high‐definition optical coherence tomography (HD‐OCT) and suggested that this technique may aid in its diagnosis and management. However, systematic studies evaluating the accuracy of HD‐OCT for the diagnosis of BCC are lacking.

Objective

The aim of this study was to identify three‐dimensional (3‐D) HD‐OCT features able i) to distinguish BCC from clinical BCC imitators and ii) to discriminate between the most common BCC subtypes. Based on these particular features, a diagnostic algorithm will be suggested.

Method

A total of 50 histopathologically confirmed BCCs (18 superficial, 19 nodular, 13 infiltrative) were imaged by HD‐OCT at the centre of the lesion prior to standard surgical excision and subsequent histopathological analysis. Fifty images of clinical BCC imitators were also retrieved as a ‘pitfalls’ group.

Results

The simultaneous presence of grey/dark subepidermal (hemi‐spherical) or intradermal lobulated structure(s) presenting a typical cockade feature in both HD‐OCT modes was a significant feature for BCC diagnosis. Features discriminating between BCC subtypes were location of the roof of BCC lobules, vascular pattern of the papillary plexus and stretching effect on the stroma. Clinical BCC imitators such as actinic keratosis, compound and intradermal naevi, amelanotic melanoma, sebaceous hyperplasia and small haemangioma could be differentiated from BCC by means of HD‐OCT.

Conclusion

This study provides a thorough description of 3‐D HD‐OCT features that can permit discrimination of BCC from clinical BCC imitators and differentiation of BCC subtypes. Based on these features, a diagnostic algorithm is proposed which requires additional validation, but enhances current understanding of the morphological correlates of HD‐OCT images in skin.
Oral isotretinoin as the most effective treatment in folliculitis decalvans: a retrospective comparison of different treatment regimens in 28 patients
Authors: Tietze J.K. , Heppt M.V. , von Preußen A. , Wolf U. , Ruzicka T. , Wolff H. , Sattler E.C.
Published: February 2015

Background

Folliculitis decalvans leads to scarring alopecia through inflammatory destruction of the hair follicle. Currently, antibiotics are most commonly used to treat this disease. However, treatment regimens with antibiotics feature a high relapse rate and encourage the development of resistant bacteria.

Objective

To evaluate the outcome of different treatment options for folliculitis decalvans.

Methods

Retrospective study to compare the efficacy of different treatment regimens in 28 patients with folliculitis decalvans.

Results

The success of treatment with clindamycin and rifampicin, clarithromycin, dapsone and isotretinoin was analysed. The evaluation of the combination of clindamycin and rifampicin showed the lowest success rate in achieving long‐term remission, since 80% of the patients relapsed shortly after end of treatment. Clarithromycin and dapsone were more successful with long‐term and stable remission rates of 33% and 43% respectively. Treatment with isotretinoin was the most successful oral treatment in our analysis with 90% of the patients experiencing stable remission during and up to two years after cessation of the treatment.

Conclusion

The common use of antibiotics as first‐line therapy in folliculitis decalvans needs to be re‐evaluated critically and oral isotretinoin should be considered as valid treatment alternative.
Characterization of Two Species of Trypanosomatidae from the Honey Bee Apis mellifera: Crithidia mellificae Langridge and McGhee, and Lotmaria passim n. gen., n. sp.
Authors: Schwarz Ryan S. , Bauchan Gary R. , Murphy Charles A. , Ravoet Jorgen , de Graaf Dirk C. , Evans Jay D.
Published: February 2015

Trypanosomatids are increasingly recognized as prevalent in European honey bees (Apis mellifera) and by default are attributed to one recognized species, Crithidia mellificae Langridge and McGhee, 1967. We provide reference genetic and ultrastructural data for type isolates of C. mellificae (ATCC 30254 and 30862) in comparison with two recent isolates from A. mellifera (BRL and SF). Phylogenetics unambiguously identify strains BRL/SF as a novel taxonomic unit distinct from C. mellificae strains 30254/30862 and assign all four strains as lineages of a novel clade within the subfamily Leishmaniinae. In vivo analyses show strains BRL/SF preferably colonize the hindgut, lining the lumen as adherent spheroids in a manner identical to previous descriptions from C. mellificae. Microscopy images show motile forms of C. mellificae are distinct from strains BRL/SF. We propose the binomial Lotmaria passim n. gen., n. sp. for this previously undescribed taxon. Analyses of new and previously accessioned genetic data show C. mellificae is still extant in bee populations, however, L. passim n. gen., n. sp. is currently the predominant trypanosomatid in A. mellifera globally. Our findings require that previous reports of C. mellificae be reconsidered and that subsequent trypanosomatid species designations from Hymenoptera provide genetic support.
Gut dysbiosis in acute‐on‐chronic liver failure and its predictive value for mortality
Authors: Chen Yanfei , Guo Jing , Qian Guirong , Fang Daiqiong , Shi Ding , Guo Lihua , Li Lanjuan
Published: February 2015

Background

Bacterial translocation from the gut plays an important role in the pathophysiology of acute‐on‐chronic liver failure (ACLF). However, gut dysbiosis in ACLF was not widely documented in previous studies.

Aim

This research characterized the fecal microbiota in patients with ACLF and analyzed the temporal stability of gut microbiota during illness.

Methods

Fecal microbiota of 79 ACLF patients (42 patients were followed in the next 4 weeks after the first visit for longitudinal study) and 50 healthy controls was analyzed by 16S ribosomal DNA pyrosequencing.

Results

There was a marked difference between the ACLF group and the control group. The overall microbial diversity and richness were significantly lower in ACLF than in controls. ACLF patients had lower abundance of Bacteroidaceae, Ruminococcaceae, and Lanchnospiraceae, but higher abundance of Pasteurellaceae, Streptococcaceae, and Enterecoccaceae. The relative abundance of Lachnospiraceae was obviously decreased in ACLF patients with hepatic encephalopathy. The gut microbiota kept relatively stable in a short term after the onset of ACLF. The use of antibiotics only showed moderate impacts on the gut microbiota. The relative abundance of Pasteurellaceae and Model of End Stage Liver Disease score were independent factors predicting mortality rate. Network analysis comparison showed robust correlations between specific bacterial families (Ruminococcaceae and Lachnospiraceae) and inflammatory cytokines (interleukin [IL]‐6, tumor necrosis factor alpha, IL‐2) in ACLF patients.

Conclusions

These data suggest gut dysbiosis in ACLF and its predictive value for mortality. The results thus open up the possibility of designing diagnostic biomarkers and targeted probiotics aimed at decreasing mortality in ACLF.
Mechanical Basis of Osmosensory Transduction in Magnocellular Neurosecretory Neurones of the Rat Supraoptic Nucleus
Authors: Prager‐Khoutorsky M. , Bourque C. W.
Published: February 2015

Rat magnocellular neurosecretory cells (MNCs) release vasopressin and oxytocin to promote antidiuresis and natriuresis at the kidney. The osmotic control of oxytocin and vasopressin release at the neurohypophysis is required for osmoregulation in these animals, and this release is mediated by a modulation of the action potential firing rate by the MNCs. Under basal (isotonic) conditions, MNCs fire action potentials at a slow rate, and this activity is inhibited by hypo‐osmotic conditions and enhanced by hypertonicity. The effects of changes in osmolality on MNCs are mediated by a number of different factors, including the involvement of synaptic inputs, the release of taurine by local glial cells and regulation of ion channels expressed within the neurosecretory neurones themselves. We review recent findings that have clarified our understanding of how osmotic stimuli modulate the activity of nonselective cation channels in MNCs. Previous studies have shown that osmotically‐evoked changes in membrane potential and action potential firing rate in acutely isolated MNCs are provoked mainly by a modulation of nonselective cation channels. Notably, the excitation of isolated MNCs during hypertonicity is mediated by the activation of a capsaicin‐insensitive cation channel that MNCs express as an N‐terminal variant of the transient receptor potential vanilloid 1 (Trpv1) channel. The activation of this channel during hypertonicity is a mechanical process associated with cell shrinking. The effectiveness of this mechanical process depends on the presence of a thin layer of actin filaments (F‐actin) beneath the plasma membrane, as well as a densely interweaved network of microtubules (MTs) occupying the bulk of the cytoplasm of MNCs. Although the mechanism by which F‐actin contributes to Trpv1 activation remains unknown, recent data have shown that MTs interact with Trpv1 channels via binding sites on the C‐terminus, and that the force mediated through this complex is required for channel gating during osmosensory transduction. Indeed, displacement of this interaction prevents channel activation during shrinking, whereas increasing the density of these interaction sites potentiates shrinking‐induced activation of Trpv1. Therefore, the gain of the osmosensory transduction process can be regulated bi‐directionally through changes in the organisation of F‐actin and MTs.