bluuebunny/crossref_metadata_2025 huggingface dataset:
At‐Risk Alcohol Use is Associated with Antiretroviral Treatment Nonadherence Among Adults Living with HIV/AIDS
Authors: Paolillo Emily W. , Gongvatana Assawin , Umlauf Anya , Letendre Scott L. , Moore David J.
Published: July 2017

Background

Alcohol use is a risk factor for nonadherence to antiretroviral therapy (ART) among people living with HIV/AIDS (PLWHA); however, differences in ART adherence across levels of alcohol use are unclear. This study examined whether “at‐risk” alcohol use, defined by National Institute of Alcohol Abuse and Alcoholism guidelines, was associated with ART nonadherence among PLWHA.

Methods

Participants were 535 HIV‐infected adults enrolled in studies at the HIV Neurobehavioral Research Program. ART nonadherence was identified by either self‐reported missed dose or plasma viral load detectability (≥50 copies/ml). Potential covariates for multivariable logistic regression included demographics, depression, and substance use disorders.

Results

Using a stepwise model selection procedure, we found that at‐risk alcohol use (OR = 0.64; p = 0.032) and low education (OR = 1.09 per 1 year increase in education; p = 0.009) significantly predict lower ART adherence.

Conclusions

A greater focus on the treatment of at‐risk alcohol use may improve ART adherence among HIV‐infected persons.
A new generation of mTORC1 inhibitor attenuates alcohol intake and reward in mice
Authors: Morisot Nadege , Novotny Christopher J. , Shokat Kevan M. , Ron Dorit
Published: July 2017

Alcohol use disorder (AUD) is a chronic condition associated with devastating socioeconomic consequences. Yet, pharmacotherapies to treat behavioral phenotypes such as uncontrolled heavy drinking are limited. Studies in rodents suggest that the mammalian target of rapamycin complex 1 (mTORC1) plays an important role in mechanisms underlying alcohol drinking behaviors as well as alcohol seeking and relapse. These preclinical evidence suggest that mTORC1 may be a therapeutic target for the treatment of AUD. Thus, the aim of the present study was to test the potential use of newly developed mTORC1 inhibitors, RapaLink‐1 and MLN0128, in preclinical mouse models of AUD. First, we used the intermittent access to 20 percent alcohol in a two‐bottle choice paradigm and tested the efficacy of the drugs to reduce alcohol intake in mice with a history of binge drinking and withdrawal. We found that both inhibitors reduce excessive alcohol intake and preference with RapaLink‐1 exhibiting higher efficacy. We further observed that RapaLink‐1 attenuates alcohol consumption during the first alcohol‐drinking session in naïve mice, and interestingly, the effect was still present 14 days after the initial treatment with the drug. We also found that RapaLink‐1 did not alter the consumption of water or saccharin, revealing a specific effect of the inhibitor on alcohol intake. Finally, we report that RapaLink‐1 blocks the retrieval but not acquisition of alcohol place preference without affecting locomotion. Together, our findings suggest that RapaLink‐1 may be developed as a new medication to treat and prevent the development of AUD.
Banking System Reform in China: The Challenges to Improving Its Efficiency in Serving the Real Economy
Authors: Okazaki Kumiko
Published: July 2017

The Chinese banking system reform since the country's accession to the World Trade Organization has yielded remarkable success. The major listed commercial banks have improved their operational performance significantly. However, there are some signs of changes in their financial results recently. The expanding debt of non‐profitable enterprises and local governments raises a question on the achievements of the previous reform. Considering that the competition among banks will become severer with financial liberalization under slower economic growth, the banks and supervisory authorities must continue to make greater efforts towards further reform in order to improve the banks' corporate governance and the risk management system.
Historical Ecology of Cultural Keystone Places of the Northwest Coast
Authors: Lepofsky Dana , Armstrong Chelsey Geralda , Greening Spencer , Jackley Julia , Carpenter Jennifer , Guernsey Brenda , Mathews Darcy , Turner Nancy J.
Published: July 2017

For many Indigenous peoples, their traditional lands are archives of their histories, from the deepest of time to recent memories and actions. These histories are written in the landscapes’ geological features, contemporary plant and animal communities, and associated archaeological and paleoecological records. Some of these landscapes, recently termed “cultural keystone places” (CKPs), are iconic for these groups and have become symbols of the connections between the past and the future, and between people and place. Using an historical‐ecological approach, we describe our novel methods and initial results for documenting the history of three cultural keystone places in coastal British Columbia, Canada: Hauyat, Laxgalts'ap (Old Town) and Dałk Gyilakyaw (Robin Town) (territories of Heiltsuk, Gitga'ata, and Gitsm'geelm, respectively). We combine data and knowledge from diverse disciplines and communities to tell the deep and recent histories of these cultural landscapes. Each of CKPs encompasses expansive landscapes of diverse habitats transformed by generations of people interacting with their surrounding environments. Documenting the “softer” footprints of past human‐environmental interactions can be elusive and requires diverse approaches and novel techniques.
Intravenous lignocaine in colorectal surgery: a systematic review
Authors: MacFater Wiremu S. , Rahiri Jamie‐Lee , Lauti Melanie , Su'a Bruce , Hill Andrew G.
Published: July 2017

Background

Colorectal surgery leads to morbidity during recovery including pain and fatigue. Intravenous (IV) lignocaine (IVL) has both analgesic and anti‐inflammatory effects that may improve post‐operative pain and recovery. The aim of this review is to compare the effectiveness of IVL to other perioperative analgesia regimens for reducing pain and opioid consumption following colorectal surgery.

Methods

Using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta‐Analyses) statement, a literature search was conducted to identify randomized clinical trials that compared IVL with IV placebo or epidural anaesthesia in open or laparoscopic colorectal surgery. The primary outcomes were opioid requirements and pain scores assessed by visual analogue score. Data were entered into pre‐designed electronic spreadsheets.

Results

The literature search identified 2707 studies. A total of nine randomized clinical trials met the inclusion criteria. Five studies investigated IVL compared with IV placebo and four studies investigated IVL compared with epidural anaesthesia. Two out of the five studies comparing IVL and placebo showed statistically significant reductions in opioid consumption with IVL. There was a variable degree of improvement in pain scores when IVL was compared with epidural. Two studies showed a significant difference, with lower opioid consumption and pain scores in the epidural group. Laparoscopic and open procedures could not be compared between the IVL and placebo group.

Conclusion

IVL has shown limited benefit towards reducing early pain and morphine consumption when compared with placebo in colorectal surgery. However, IVL did not show any significant reduction in pain or opioid consumption when compared with epidural. Further research investigating IVL combined with intraperitoneal local anaesthetic is warranted.
Letter: autoimmune hepatitis—drug‐induced liver injury must always be excluded. Authors’ reply
Authors: Grønbæk H. , Møller H. J. , Vistrup H.
Published: July 2017

Linked Content

This article is linked to Grønbæk et al, and Fan et al papers. To view these articles visit https://doi.org/10.1111/apt.13801 and https://doi.org/10.1111/apt.14137.
Isolating and evaluating lactic acid bacteria strains for effectiveness on silage quality at low temperatures on the Tibetan Plateau
Authors: Wang Siran , Yuan Xianjun , Dong Zhihao , Li Junfeng , Shao Tao
Published: July 2017

Four lactic acid bacteria (LAB) strains isolated from straw silages on the Tibetan Plateau were characterized, and their effects on the fermentation quality of Italian ryegrass (Lolium multiflorum Lam.) at different temperatures (10°C, 15°C and 25°C) were studied. These LAB isolates were evaluated using the acids production ability test, morphological observation, Gram staining, physiological, biochemical and acid tolerance tests. All the isolates (M1, LM8, LO7 and LOG9) could grow at 5‐20°C, pH 3.5‐7.0 and NaCl (3.0%, 6.5%). Strains M1, LM8, LO7 and LOG9 were identified as Lactobacillus plantarum, L. coryniformis, Pediococcus pentosaceus and P. acidilactici, respectively, by sequencing 16S ribosomal DNA. The four isolates were added to Italian ryegrass for ensiling for 30 days at various temperatures. Compared with the corresponding control, inoculating with isolates M1, LM8 and LO7 could improve the silage quality of Italian ryegrass at low temperatures, indicated by significantly (P < 0.05) higher lactic acid (LA) contents and ratios of lactic acid/acetic acid (LA/AA), and significantly (P < 0.05) lower pH and ammonia nitrogen/total nitrogen (AN/TN). Compared with other isolates, LM8 performed better at 10°C and 15°C, indicated by the higher (P < 0.05) LA content and ratio of LA/AA, and the lower (P < 0.05) pH and AN/TN.
Age‐stratified thresholds of anti‐Müllerian hormone improve prediction of polycystic ovary syndrome over a population‐based threshold
Authors: Quinn Molly M. , Kao Chia‐Ning , Ahmad Asima K. , Haisenleder Daniel J. , Santoro Nanette , Eisenberg Esther , Legro Richard S. , Cedars Marcelle I. , Huddleston Heather G. ,   the NIH/NICHD Reproductive Medicine Network
Published: July 2017

Objective

Due to its consistent elevation in polycystic ovary syndrome (PCOS) and correlation with polycystic ovarian morphology (PCOM), anti‐Mullerian hormone (AMH) has been proposed as a marker of the syndrome. However, prior studies reporting thresholds of AMH for a PCOS diagnosis have been limited by small sample size, inappropriate controls, and heterogeneous AMH assays. We sought to evaluate the suitability of a standardized AMH assay as a biomarker of PCOS.

Design

Cross‐sectional study at academic medical centres across the United States.

Patients

Women with PCOS were diagnosed by Rotterdam criteria and included 282 subjects from the multisite PPCOS II trial and 109 patients from a tertiary academic centre's multidisciplinary PCOS clinic. Controls included 245 participants in the ovarian ageing (OVA) study, a community‐based cohort of ovulatory women not seeking treatment for fertility.

Measurements

Determination of AMH by a central laboratory. Receiver‐operating characteristic (ROC) analyses were used to investigate the accuracy of AMH thresholds for prediction of PCOS diagnosis with stratification by age.

Results

The optimal threshold of AMH to distinguish PCOS from controls was 55.36 pmol/L (sensitivity: 0.82, specificity: 0.78, J: 0.60). When examining the population by age groups, the optimal AMH threshold decreased with increasing age.

Conclusions

AMH is an effective biomarker of PCOS. Age‐stratified thresholds more accurately predicted PCOS than an overall population‐based threshold.
Minimal Warping: Planning Incremental Novel‐view Synthesis
Authors: Leimkühler Thomas , Seidel Hans‐Peter , Ritschel Tobias
Published: July 2017

Observing that many visual effects (depth‐of‐field, motion blur, soft shadows, spectral effects) and several sampling modalities (time, stereo or light fields) can be expressed as a sum of many pinhole camera images, we suggest a novel efficient image synthesis framework that exploits coherency among those images. We introduce the notion of “distribution flow” that represents the 2D image deformation in response to changes in the high‐dimensional time‐, lens‐, area light‐, spectral‐, etc. coordinates. Our approach plans the optimal traversal of the distribution space of all required pinhole images, such that starting from one representative root image, which is incrementally changed (warped) in a minimal fashion, pixels move at most by one pixel, if at all. The incremental warping allows extremely simple warping code, typically requiring half a millisecond on an Nvidia Geforce GTX 980Ti GPU per pinhole image. We show, how the bounded sampling does introduce very little errors in comparison to re‐rendering or a common warping‐based solution. Our approach allows efficient previews for arbitrary combinations of distribution effects and imaging modalities with little noise and high visual fidelity.
Real‐Time Linear BRDF MIP‐Mapping
Authors: Xu Chao , Wang Rui , Zhao Shuang , Bao Hujun
Published: July 2017

We present a new technique to jointly MIP‐map BRDF and normal maps. Starting with generating an instant BRDF map, our technique builds its MIP‐mapped versions based on a highly efficient algorithm that interpolates von Mises‐Fisher (vMF) distributions. In our BRDF MIP‐maps, each pixel stores a vMF mixture approximating the average of all BRDF lobes from the finest level. Our method is capable of jointly MIP‐mapping BRDF and normal maps, even with high‐frequency variations, at real‐time while preserving high‐quality reflectance details. Further, it is very fast, easy to implement, and requires no precomputation.
An Appearance Model for Textile Fibers
Authors: Aliaga Carlos , Castillo Carlos , Gutierrez Diego , Otaduy Miguel A. , Lopez‐Moreno Jorge , Jarabo Adrian
Published: July 2017

Accurately modeling how light interacts with cloth is challenging, due to the volumetric nature of cloth appearance and its multiscale structure, where microstructures play a major role in the overall appearance at higher scales. Recently, significant effort has been put on developing better microscopic models for cloth structure, which have allowed rendering fabrics with unprecedented fidelity. However, these highly‐detailed representations still make severe simplifications on the scattering by individual fibers forming the cloth, ignoring the impact of fibers' shape, and avoiding to establish connections between the fibers' appearance and their optical and fabrication parameters. In this work we put our focus in the scattering of individual cloth fibers; we introduce a physically‐based scattering model for fibers based on their low‐level optical and geometric properties, relying on the extensive textile literature for accurate data. We demonstrate that scattering from cloth fibers exhibits much more complexity than current fiber models, showing important differences between cloth type, even in averaged conditions due to longer views. Our model can be plugged in any framework for cloth rendering, matches scattering measurements from real yarns, and is based on actual parameters used in the textile industry, allowing predictive bottom‐up definition of cloth appearance.
Stochastic Light Culling for VPLs on GGX Microsurfaces
Authors: Tokuyoshi Yusuke , Harada Takahiro
Published: July 2017

This paper introduces a real‐time rendering method for single‐bounce glossy caustics created by GGX microsurfaces. Our method is based on stochastic light culling of virtual point lights (VPLs), which is an unbiased culling method that randomly determines the range of influence of light for each VPL. While the original stochastic light culling method uses a bounding sphere defined by that light range for coarse culling (e.g., tiled culling), we have further extended the method by calculating a tighter bounding ellipsoid for glossy VPLs. Such bounding ellipsoids can be calculated analytically under the classic Phong reflection model which cannot be applied to physically plausible materials used in modern computer graphics productions. In order to use stochastic light culling for such modern materials, this paper derives a simple analytical solution to generate a tighter bounding ellipsoid for VPLs on GGX microsurfaces. This paper also presents an efficient implementation for culling bounding ellipsoids in the context of tiled culling. When stochastic light culling is combined with interleaved sampling for a scene with tens of thousands of VPLs, this tiled culling is faster than conservative rasterization‐based clustered shading which is a state‐of‐the‐art culling technique that supports bounding ellipsoids. Using these techniques, VPLs are culled efficiently for completely dynamic single‐bounce glossy caustics reflected from GGX microsurfaces.
Deep Shading: Convolutional Neural Networks for Screen Space Shading
Authors: Nalbach O. , Arabadzhiyska E. , Mehta D. , Seidel H.‐P. , Ritschel T.
Published: July 2017

In computer vision, convolutional neural networks (CNNs) achieve unprecedented performance for inverse problems where RGB pixel appearance is mapped to attributes such as positions, normals or reflectance. In computer graphics, screen space shading has boosted the quality of real‐time rendering, converting the same kind of attributes of a virtual scene back to appearance, enabling effects like ambient occlusion, indirect light, scattering and many more. In this paper we consider the diagonal problem: synthesizing appearance from given per‐pixel attributes using a CNN. The resulting Deep Shading renders screen space effects at competitive quality and speed while not being programmed by human experts but learned from example images.
Variance and Convergence Analysis of Monte Carlo Line and Segment Sampling
Authors: Singh Gurprit , Miller Bailey , Jarosz Wojciech
Published: July 2017

Recently researchers have started employing Monte Carlo‐like line sample estimators in rendering, demonstrating dramatic reductions in variance (visible noise) for effects such as soft shadows, defocus blur, and participating media. Unfortunately, there is currently no formal theoretical framework to predict and analyze Monte Carlo variance using line and segment samples which have inherently anisotropic Fourier power spectra. In this work, we propose a theoretical formulation for lines and finite‐length segment samples in the frequency domain that allows analyzing their anisotropic power spectra using previous isotropic variance and convergence tools. Our analysis shows that judiciously oriented line samples not only reduce the dimensionality but also pre‐filter C0 discontinuities, resulting in further improvement in variance and convergence rates. Our theoretical insights also explain how finite‐length segment samples impact variance and convergence rates only by pre‐filtering discontinuities. We further extend our analysis to consider (uncorrelated) multi‐directional line (segment) sampling, showing that such schemes can increase variance compared to unidirectional sampling. We validate our theoretical results with a set of experiments including direct lighting, ambient occlusion, and volumetric caustics using points, lines, and segment samples.
Challenges Faced by Young Mothers with a Care History and Views of Stakeholders About the Potential for Group Family Nurse Partnership to Support Their Needs
Authors: Datta Jessica , Macdonald Geraldine , Barlow Jane , Barnes Jacqueline , Elbourne Diana
Published: July 2017

Women with experience of being ‘looked after’ are more likely than their peers to become young mothers. There has been limited research investigating support for their needs. This study, embedded in a randomised trial of Group Family Nurse Partnership (gFNP), involved interviews with young mothers with care experience, Family Nurses delivering group gFNP, and health and social care professionals. This first qualitative study to explore the views of these varied stakeholders found consensus regarding young mothers’ social isolation and lack of trusting relationships but diversity in views about the potential of gFNP to meet their needs.
Measurement of liver volumes by portal vein flow by Doppler ultrasound in living donor liver transplantation
Authors: Choi Sang Hyun , Kwon Jae Hyun , Kim Kyoung Won , Jang Hye Young , Kim Ji Hye , Kwon Heon‐Ju , Lee Jeongjin , Song Gi‐Won , Lee Sung‐Gyu
Published: July 2017

Background

The accurate estimation of liver volume and right/left ratio in donor candidates is critical, but there is no method using portal vein (PV) flow.

Methods

Of 125 donor candidates, right/left liver volume ratio was estimated using ultrasound (US)‐PV area ratio and Doppler US‐PV flow ratio, and the results were compared with CT volumetry. We analyzed these results in 76 donors who underwent hemihepatectomy. We evaluated diagnostic values of Doppler US‐PV flow for <30% remnant liver volume high‐risk donors, and compared liver volume by Doppler US‐PV flow with actual graft weight.

Results

In 125 donor candidates, 96.8% showed <10% difference between liver volume ratio by Doppler US‐PV flow ratio and CT volumetry. Compared with CT volumetry, the mean percentage difference of liver volume ratio by Doppler US‐PV flow ratio was significantly smaller than that by US‐PV area ratio (±0.7% vs ±6.3%, P<.001). In 76 donors who underwent hemihepatctomy, results were similar, showing smaller mean percentage difference of liver volume ratio by Doppler US‐PV flow ratio than that by US‐PV area ratio (±1.0% vs ±6.0%, P<.001). Sensitivity and specificity for <30% remnant liver volume donors were 76.9% and 76.8%. Blood‐free liver volume by Doppler US‐PV flow was linearly correlated with graft weight (R2=0.770, P<.001), although significantly different, with 8.5% error ratio (669.3±173.2 vs 633.7±187.1, P=.001).

Conclusion

Doppler US‐PV flow can effectively estimate right/left liver volume ratio in initial donor investigation. However, Doppler US‐PV flow is not accurate in assessing donors with <30% remnant liver volume and in estimating actual graft weight.
S1 guidelines: Lipedema
Authors: Reich‐Schupke Stefanie , Schmeller Wilfried , Brauer Wolfgang Justus , Cornely Manuel E. , Faerber Gabriele , Ludwig Malte , Lulay Gerd , Miller Anya , Rapprich Stefan , Richter Dirk Frank , Schacht Vivien , Schrader Klaus , Stücker Markus , Ure Christian
Published: July 2017

The present, revised guidelines on lipedema were developed under the auspices of and funded by the German Society of Phlebology (DGP). The recommendations are based on a systematic literature search and the consensus of eight medical societies and working groups. The guidelines contain recommendations with respect to diagnosis and management of lipedema.

The diagnosis is established on the basis of medical history and clinical findings. Characteristically, there is a localized, symmetrical increase in subcutaneous adipose tissue in arms and legs that is in marked disproportion to the trunk. Other findings include edema, easy bruising, and increased tenderness. Further diagnostic tests are usually reserved for special cases that require additional workup. Lipedema is a chronic, progressive disorder marked by the individual variability and unpredictability of its clinical course.

Treatment consists of four therapeutic mainstays that should be combined as necessary and address current clinical symptoms: complex physical therapy (manual lymphatic drainage, compression therapy, exercise therapy, and skin care), liposuction and plastic surgery, diet, and physical activity, as well as psychotherapy if necessary. Surgical procedures are indicated if – despite thorough conservative treatment – symptoms persist, or if there is progression of clinical findings and/or symptoms. If present, morbid obesity should be therapeutically addressed prior to liposuction.
Dermatologische Manifestationen der tuberösen Sklerose (TSC)
Authors: Ebrahimi‐Fakhari Daniel , Meyer Sascha , Vogt Thomas , Pföhler Claudia , Müller Cornelia Sigrid Lissi
Published: July 2017

Die tuberöse Sklerose (tuberous scerlosis complex, TSC) ist eine genetische Multisystemerkrankung mit auffälliger Hautbeteiligung, die häufig in der frühen Kindheit eintritt. Zu den dermatologischen Manifestationen gehören faziale Angiofibrome, hypomelanotische Maculae, fibröse Stirnplaques, Shagreen‐Fleck (shagreen patches) und unguale Fibrome. Die Internationale TSC‐Konsensuskonferenz (International TSC Consensus Conference) von 2012 hat Leitlinien für die standardisierte Erstuntersuchung und die Nachsorge zur Verfügung gestellt. Sowohl für Kinder als auch für Erwachsene werden eine eingehende klinisch‐dermatologische Untersuchung zum Zeitpunkt der Diagnose sowie eine jährliche Hautuntersuchung empfohlen. Das erstmalige Auftreten der dermatologischen Manifestationen ist offensichtlich altersabhängig. Allerdings müssen Dermatologen die klinischen Manifestationen auch über ihr eigenes Fachgebiet hinaus beurteilen. Durch Fortschritte in der Genetik und die Einführung von TORC1‐Inhibitoren stehen neue, spezifische Therapieoptionen für TSC‐Patienten mit Hautmanifestationen zur Verfügung. Im Allgemeinen wird bei symptomatischen, sich schnell entwickelnden, entstellenden oder behindernden Läsionen ein frühes Eingreifen empfohlen. Die Konsensus‐Leitlinien empfehlen eine „der Läsion und dem klinischen Kontext angemessene Behandlung“ und schlagen die Anwendung chirurgischer Exzision, Lasertherapie oder topischer mTORC1‐Inhibitoren vor. Topische mTORC1‐Inhibitoren sind eine sinnvolle Option für TSC‐assoziierte Hautläsionen, insbesondere bei medizinisch komplexen Patienten. Sie können nachfolgende chirurgische Eingriffe sowie dauerhafte Narbenbildung verhindern oder ihr Risiko verringern.
A novel cluster of patients with Familial Mediterranean Fever (FMF) in southern Italy
Authors: Bonfrate Leonilde , Scaccianoce Giuseppe , Palasciano Giuseppe , Ben‐Chetrit Eldad , Portincasa Piero
Published: July 2017

Background

Familial Mediterranean Fever (FMF) is an autosomal recessive autoinflammatory disorder characterised by recurrent attacks of fever and serositis (peritonitis, pleuritic or synovitis) affecting mainly populations of Mediterranean origin.

Aim

To describe a relatively new cluster of FMF subjects from Apulia and Basilicata regions (southern Italy).

Patients and methods

Subjects were screened for FMF using the Tel‐Hashomer criteria and genetic analysis. Demographic data were taken from patients’ files and direct interviews. Patients were investigated about attack duration, intensity and site, body temperature, skin manifestations and overall quality of life before and after treatment with colchicine. Inflammatory parameters were also measured between these periods.

Results

Forty‐nine subjects had FMF (M : F = 26 : 23, age 38 years ± 2 SE) and followed‐up up to 8 years. The age at disease onset was 22·1 years ± 1·2SE and the diagnostic delay was 15·5 years ± 1·9SE. The majority of patients (82%) suffered from abdominal pain, and 35% had undergone prior abdominal surgery or laparotomy. Severity score (ISSF) was mild in 43% of patients and intermediate in 57% of patients. Serum amyloid A (SAA) was increased in 20% of patients (16·9 ± 3·7, normal range < 6·4 mg/dL). In over 95% of patients, inflammation markers, duration and intensity of febrile painful attacks, quality of life and ISSF score improved dramatically following colchicine treatment.

Conclusion

The Apulia region represents a new endemic area for FMF. Clinical presentation of FMF can be misleading and requires a complete and early workup to recognise the disease and avoid unjustified surgery. Colchicine remains the gold standard therapy to prevent FMF attacks and fatal long‐term complications.
Differential expression of homologous recombination DNA repair genes in the early and advanced stages of myelodysplastic syndrome
Authors: Valka Jan , Vesela Jitka , Votavova Hana , Dostalova‐Merkerova Michaela , Horakova Zuzana , Campr Vit , Brezinova Jana , Zemanova Zuzana , Jonasova Anna , Cermak Jaroslav , Belickova Monika
Published: July 2017

Background

The high incidence of mutations and cytogenetic abnormalities in patients with myelodysplastic syndrome (MDS) suggests that defects in DNA repair mechanisms. We monitored DNA repair pathways in MDS and their alterations during disease progression.

Methods

Expression profiling of DNA repair genes was performed on CD34+ cells, and paired samples were used for monitoring of RAD51 and XRCC2 gene expression during disease progression. Immunohistochemical staining for RAD51 was done on histology samples.

Results

RAD51 and XRCC2 showed differential expression between low‐risk and high‐risk MDS (P<.0001), whereas RPA3 was generally decreased among the entire cohort (FC=−2.65, P<.0001). We demonstrated that RAD51 and XRCC2 expression gradually decreased during the progression of MDS. Down‐regulation of XRCC2 and RAD51 expression was connected with abnormalities on chromosome 7 (P=.0858, P=.0457). Immunohistochemical staining revealed the presence of RAD51 only in the cytoplasm in low‐risk MDS, while in both the cytoplasm and nucleus in high‐risk MDS. The multivariate analysis identified RAD51 expression level (HR 0.49; P=.01) as significant prognostic factor for overall survival of patients with MDS.

Conclusions

Our study demonstrates that the expression of DNA repair factors, primarily RAD51 and XRCC2, is deregulated in patients with MDS and presents a specific pattern with respect to prognostic categories.
The atypical dopamine receptor agonist SKF 83959 enhances hippocampal and prefrontal cortical neuronal network activity in a rat model of cognitive dysfunction
Authors: Perreault Melissa L. , Fan Theresa , Banasikowski Tomek J. , Grace Anthony A. , George Susan R.
Published: July 2017

Deficits in neuronal network synchrony in hippocampus and prefrontal cortex have been widely demonstrated in disorders of cognitive dysfunction, including schizophrenia and Alzheimer's disease. The atypical dopamine agonist SKF 83959 has been shown to increase brain‐derived neurotrophic factor signalling and suppress activity of glycogen synthase kinase‐3 in PFC, two processes important to learning and memory. The purpose of this study was to therefore evaluate the impact of SKF 83959 on oscillatory deficits in methylazoxymethanol acetate (MAM) rat model of schizophrenia. To achieve this, local field potentials were recorded simultaneously from the hippocampus and prefrontal cortex of anesthetized rats at 15 and 90 min following both acute and repeated administration of SKF 83959 (0.4 mg/kg). In MAM rats, but not controls, repeated SKF 83959 treatment increased signal amplitude in hippocampus and enhanced the spectral power of low frequency delta and theta oscillations in this region. In PFC, SKF 83959 increased delta, theta and gamma spectral power. Increased HIP‐PFC theta coherence was also evident following acute and repeated SKF 83959. In apparent contradiction to these oscillatory effects, in MAM rats, SKF 83959 inhibited spatial learning and induced a significant increase in thigmotactic behaviour. These findings have uncovered a previously unknown role for SKF 83959 in the positive regulation of hippocampal–prefrontal cortical oscillatory network activity. As SKF 83959 is known to have affinity for a number of receptors, delineating the receptor mechanisms that mediate the positive drug effects on neuronal oscillations could have significant future implications in disorders associated with cognitive dysfunction.
Update on the mechanisms and roles of high‐frequency oscillations in seizures and epileptic disorders
Authors: Jiruska Premysl , Alvarado‐Rojas Catalina , Schevon Catherine A. , Staba Richard , Stacey William , Wendling Fabrice , Avoli Massimo
Published: July 2017

High‐frequency oscillations (HFOs) are a type of brain activity that is recorded from brain regions capable of generating seizures. Because of the close association of HFOs with epileptogenic tissue and ictogenesis, understanding their cellular and network mechanisms could provide valuable information about the organization of epileptogenic networks and how seizures emerge from the abnormal activity of these networks. In this review, we summarize the most recent advances in the field of HFOs and provide a critical evaluation of new observations within the context of already established knowledge. Recent improvements in recording technology and the introduction of optogenetics into epilepsy research have intensified experimental work on HFOs. Using advanced computer models, new cellular substrates of epileptic HFOs were identified and the role of specific neuronal subtypes in HFO genesis was determined. Traditionally, the pathogenesis of HFOs was explored mainly in patients with temporal lobe epilepsy and in animal models mimicking this condition. HFOs have also been reported to occur in other epileptic disorders and models such as neocortical epilepsy, genetically determined epilepsies, and infantile spasms, which further support the significance of HFOs in the pathophysiology of epilepsy. It is increasingly recognized that HFOs are generated by multiple mechanisms at both the cellular and network levels. Future studies on HFOs combining novel high‐resolution in vivo imaging techniques and precise control of neuronal behavior using optogenetics or chemogenetics will provide evidence about the causal role of HFOs in seizures and epileptogenesis. Detailed understanding of the pathophysiology of HFOs will propel better HFO classification and increase their information yield for clinical and diagnostic purposes.
Female wolf spiders exert cryptic control drastically reducing ejaculate size
Authors: Albo Maria J. , Costa Fernando G.
Published: July 2017

Sexes' roles in post‐copulatory processes have important effects on individual fitness and are promising to study in species showing complex mating behaviours. In the spider Schizocosa malitiosa, males perform two different copulatory patterns, pattern 1 includes 80% of total pedipalp insertions and pattern 2 includes 20%. Both patterns produce similar number of offspring, but pattern 1 induces higher female reluctance to remating than pattern 2. We hypothesised that the complex copulatory patterns are linked to post‐copulatory sexual selection, affecting males' sperm transfer and the resulting sperm storage by females. First, we examined amounts of sperm in males and live females from uninterrupted (pattern 1 + 2) and interrupted matings (pattern 1, pattern 2). Second, in order to disentangle male and female actions, we induced males to mate with dead females and examined amounts of sperm. Males transfer in total 71% of the sperm available in their pedipalps, being higher but not significant in pattern 1 than in pattern 2. Females drastically reduced the amount of sperm stored in their spermathecae and such control is stronger in pattern 1 compared to pattern 2 matings. We propose that cryptic female control is a main factor driving males to strengthen sperm transfer. Active female reduction in ejaculate most probably diminished her reluctance to remate.
Imiquimod‐applied Interleukin‐10 deficient mice better reflects severe and persistent psoriasis with systemic inflammatory state
Authors: Jin Seon‐Pil , Koh Seong‐joon , Yu Da‐Ae , Kim Min‐Woo , Yun Hee Tae , Lee Dong Hun , Yoon Hyun‐Sun , Cho Soyun , Park Hyun‐sun
Published: July 2017

Previous studies have shown that imiquimod‐induced psoriasis‐like skin inflammation in mice resembles phenotypic changes and cytokine profiles of human psoriasis. However, a psoriasis animal model reflecting the chronic inflammatory course and comorbidities has not yet been established. We aimed to evaluate the imiquimod‐applied interleukin (IL)‐10 deficient mouse model in comparison with previous models. IL‐10 deficient and wild‐type (WT) mice received either imiquimod or vehicle cream for 12 days and were sacrificed on day 15. For earlier time point data, either imiquimod or vehicle cream was applied for 2 days, and the mice were sacrificed on day 3. Imiquimod‐applied IL‐10 deficient mice showed more persistent psoriasis‐like inflammation and higher severity index than did WT between day 8 and 15. Histopathologically, they demonstrated significantly thicker epidermis and larger number of CD45+, myeloperoxidase+ and IL‐17+ cell counts on day 15. Quantitative reverse transcription‐polymerase chain reaction with skin tissue revealed significantly higher imiquimod‐induced IL‐23p19 expression in imiquimod‐applied IL‐10 deficient mice on day 15. IL‐10 deficient mice also showed significantly higher serum levels of imiquimod‐induced IL‐17A and tumor necrosis factor‐α by enzyme‐linked immunosorbent assay on day 15. Furthermore, IL‐10 deficient mice showed more prominent increase of spleen weight and decrease of body weight in response to imiquimod application on day 3 and 15. In conclusion, IL‐10 deficient mice model with imiquimod application may better reflect severe and persistent psoriasis with systemic inflammatory state.
Reconstructing 290 years of a data‐poor fishery through ethnographic and archival research: The East Pacific green turtle (Chelonia mydas) in Baja California, Mexico
Authors: Early‐Capistrán Michelle‐María , Sáenz‐Arroyo Andrea , Cardoso‐Mohedano José‐Gilberto , Garibay‐Melo Gerardo , Peckham S Hoyt , Koch Volker
Published: July 2017

Evaluating historical changes in the exploitation of marine organisms is a key challenge in fisheries ecology and marine conservation. In the Eastern Pacific, marine turtles were exploited for millennia before systematic monitoring began <50 years ago. Using ethnographic and historical data, we generated a detailed reconstruction of the East Pacific green sea turtle (Chelonia mydas) fishery in Mexico's Baja California peninsula from 1700 to 1990. Sea turtles from the region's important feeding areas were a staple food source from the earliest phases of human occupation, dating back at least 12,000 years. In contrast with regions such as the Caribbean, small human populations and limited market access resulted in apparently sustainable turtle harvests until the second half of the 20th century. We found that the estimated annual catches between 1960 and 1980 exceeded the estimated annual catches of the previous 250 years by an order of magnitude, leading to the collapse of the fishery and the depletion of the green turtle population. A total ban on sea turtle captures in 1990, comprehensive nesting beach protection, and significant conservation efforts resulted in increases in breeding females on nesting beaches and catch rates in scientific monitoring on main feeding grounds since the early 2000s. This provides a positive outlook for this once‐depleted population segment. Although further research is needed to evaluate current conservation status, we have identified a date, between 1950 and 1960, which can serve as a reliable temporal reference for future evaluations of historical baseline abundance in this region.
Substrate specificity and reaction mechanism of human prolidase
Authors: Wilk Piotr , Uehlein Monika , Kalms Jacqueline , Dobbek Holger , Mueller Uwe , Weiss Manfred S.
Published: July 2017

Prolidase is a ubiquitously distributed dipeptidase and the only dipeptidase in humans capable of cleaving the peptide bond preceding the amino acids proline (Pro) or hydroxyproline (Hyp). It is mainly implicated in the degradation of dietary and endogenous proteins. It is also involved in the terminal steps of collagen catabolism by hydrolyzing Pro and Hyp‐containing dipeptides. Finally, it is believed to play a role in the regulation of peptidic hormones. Diminished or absent prolidase activity is related to a rare autosomal disease, referred to as prolidase deficiency (PD). This disease manifests itself by a variety of clinical symptoms. To date, there is no definitive cure to PD. This may in part be due to an incomplete understanding of the wild‐type (wt) enzyme with respect to substrate‐binding mode and consequently the mechanism of the catalyzed reaction. In this work, we describe the high‐resolution crystal structures of the wt human prolidase in the ligand‐free form as well as in substrate‐bound states and in complex with the cleavage product Pro. This series of structures provides much relevant information for the definition of substrate‐binding and the reaction mechanism. A recent study on Escherichia coli prolidase revealed how substrates of different length are discriminated. Here, based on our own structural results, we evaluate and extend this analysis. Moreover, we describe and analyze substrate and product binding in the active site and we propose that the crucial catalytic moiety is actually a hydroxide ion. This information significantly advances our understanding of prolidase‐based pathologies.

Database

The refined structure coordinates as well as the corresponding structure factor amplitudes have been deposited in the PDB under the accession numbers 5M4G, 5M4J, 5M4L, and 5M4Q.
Qualitative insights into the experience of teaching shared decision making within adult education health literacy programmes for lower‐literacy learners
Authors: Muscat Danielle M. , Morony Suzanne , Smith Sian K. , Shepherd Heather L. , Dhillon Haryana M. , Hayen Andrew , Trevena Lyndal , Luxford Karen , Nutbeam Don , McCaffery Kirsten J.
Published: July 2017

Background

Enhancing health literacy can play a major role in improving healthcare and health across the globe. To build higher‐order (communicative/critical) health literacy skills among socially disadvantaged Australians, we developed a novel shared decision making (SDM) training programme for adults with lower literacy. The programme was delivered by trained educators within an adult basic education health literacy course.

Objective

To explore the experience of teaching SDM within a health literacy programme and investigate whether communicative/critical health literacy content meets learner needs and teaching and institutional objectives.

Design and participants

Qualitative interview study with 11 educators who delivered the SDM programme. Transcripts were analysed using the Framework approach; a matrix‐based method of thematic analysis.

Results

Teachers noted congruence in SDM content and the institutional commitment to learner empowerment in adult education. The SDM programme was seen to offer learners an alternative to their usual passive approach to healthcare decision making by raising awareness of the right to ask questions and consider alternative test/treatment options. Teachers valued a structured approach to training building on foundational skills, with language reinforcement and take‐home resources, but many noted the need for additional time to develop learner understanding and cover all aspects of SDM. Challenges for adult learners included SDM terminology, computational numerical risk tasks and understanding probability concepts.

Discussion and conclusions

SDM programmes can be designed in a way that both supports teachers to deliver novel health literacy content and empowers learners. Collaboration between adult education and healthcare sectors can build health literacy capacity of those most in need.
TdT expression in normal and neoplastic sebaceous cells
Authors: Tzorakoleftheraki Sofia‐Eleni , Iliadis Alexandros , Kostopoulos Ioannis , Koletsa Triantafyllia
Published: July 2017

Aims

Terminal deoxynucleotidyl transferase (TdT) is a DNA polymerase expressed in immature, normal and neoplastic, lymphoid or haematopoietic cells and in neuroendocrine carcinomas, such as Merkel cell carcinoma and small‐cell carcinoma. It has not yet been described in cells of epithelial origin. After observing TdT immunoreactivity in normal sebaceous glands, we analysed its spectrum of expression in cases of sebaceous cell hyperplasia (SGH) and sebaceous cell neoplasm.

Methods and results

Twelve cases of SGH and three cases of other benign lesions, namely sebaceoma, sebaceous adenoma, and sebaceous naevus, along with four archived cases of sebaceous cell carcinoma (SC) were collected and stained with TdT antibody. In addition, tissue microarrays were constructed from 11 cases of basal cell carcinoma (BCC) and 10 cases of squamous cell carcinoma (SCC), which had nine evaluable cases each, and, after carcinoma type confirmation with immunostaining for epithelial membrane antigen, TdT immunohistochemistry was performed. All cases of SGH and sebaceous cell neoplasm were positive for TdT. The staining intensity was variable, being often weak to moderate in a significant proportion of cells, apart from one case of SC and the case of sebaceous naevus, which were only focally positive. No BCCs and only one SCC showed immunoreactivity.

Conclusions

TdT protein can be found in cells of epithelial origin and specifically sebaceous cells, both benign and malignant. It can be hypothesized that this expression is due to sebaceous cell differentiation as a prelude to apoptosis and holocrine secretion. Additional studies are needed to further elucidate its biological role.
Approaches to obesity management
Authors: Sweeting Arianne N. , Caterson Ian D.
Published: July 2017

This review will provide an overview of the currently available approaches to obesity management available in Australia, including the various approaches to lifestyle intervention, in addition to evaluating the safety and efficacy of adjuvant therapies, including pharmacotherapy and bariatric surgery.
Online Principal Component Analysis in High Dimension: Which Algorithm to Choose?
Authors: Cardot Hervé , Degras David
Published: July 2017

Principal component analysis (PCA) is a method of choice for dimension reduction. In the current context of data explosion, online techniques that do not require storing all data in memory are indispensable to perform the PCA of streaming data and/or massive data. Despite the wide availability of recursive algorithms that can efficiently update the PCA when new data are observed, the literature offers little guidance on how to select a suitable algorithm for a given application. This paper reviews the main approaches to online PCA, namely, perturbation techniques, incremental methods and stochastic optimisation, and compares the most widely employed techniques in terms statistical accuracy, computation time and memory requirements using artificial and real data. Extensions of online PCA to missing data and to functional data are detailed. All studied algorithms are available in the  package onlinePCA on CRAN.
A qualitative study exploring how pharmacist and nurse independent prescribers make clinical decisions
Authors: Abuzour Aseel S. , Lewis Penny J. , Tully Mary P.
Published: July 2017

Aim

The aim of this study was to explore how secondary care pharmacist and nurse independent prescribers clinically reason when making prescribing decisions.

Background

Clinical reasoning is a central component of prescribers’ competence and professional autonomy when reaching a clinically appropriate decision. Like doctors, pharmacist and nurse independent prescribers in the UK have extensive prescribing rights, but little is known about their clinical reasoning.

Design

A qualitative approach using a think‐aloud methodology and semi‐structured interviews.

Methods

Eleven nurse and 10 pharmacist independent prescribers were asked to think‐aloud about validated clinical vignettes prior to interview, between March ‐ December 2015. Data were analysed using a constant‐comparative approach.

Results

A strong link between clinical knowledge, grounded in previous experience and clinical reasoning was found. Despite prescribers approaching the clinical vignettes holistically, their focus varied according to professional background and job role. Nurses were more likely to describe interacting with patients, compared with pharmacists who were more focused on medical notes and laboratory results. Think‐aloud protocol analysis revealed a distinct pattern in the process undertaken to reach a clinical decision. This is presented as a decision‐making model, encompassing case familiarization, generating hypotheses, case assessment, final hypotheses and decision‐making stages, which oscillated throughout the model.

Conclusion

This is the first study to explore the clinical reasoning processes of secondary care pharmacist and nurse independent prescribers. The resultant decision‐making model shows clinical reasoning as a complex and dynamic process. This model can inform the training of independent prescribers to become accurate problem solvers and continue making clinically appropriate decisions.