bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparative efficacy of anti‐diabetic agents on nonalcoholic fatty liver disease in patients with type 2 diabetes mellitus: a systematic review and meta‐analysis of randomized and non‐randomized studies
Authors: Tang Wenjuan , Xu Qianyue , Hong Ting , Tong Guoyu , Feng Wenhuan , Shen Shanmei , Bi Yan , Zhu Dalong
Published: September 2015

Background

Nonalcoholic fatty liver disease (NAFLD) has a high prevalence in patients with type 2 diabetes mellitus (T2DM). In this study, we sought to provide a comprehensive assessment regarding the effects of anti‐diabetic agents on NAFLD in patients with T2DM.

Methods

MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials were searched for randomized controlled trials (RCTs) with different anti‐diabetic agents in T2DM. Observational trials were also recruited to expand our population. Hepatic fat content and liver histology were evaluated as primary outcomes. Pooled estimates were calculated using a fixed effect model.

Results

One thousand one hundred ninety‐six participants in 19 RCTs and 14 non‐randomized studies were included. Evidence from RCTs and observational studies suggested that greater hepatic fat content reduction and improved liver histology were seen in thiazolidinediones for 12–72 weeks; glucagon‐like peptide‐1 receptor agonists had beneficial effects on hepatic fat content after 26–50 weeks intervention, and insulin/metformin combination with 3–7 months improved hepatic fat content. Initiating metformin or dapagliflozin showed no benefit on hepatic fat content or liver histology in 16–48 weeks. Besides, nateglinide for 18 months was reported in a small sample‐size RCT to improve hepatic fat content and liver histology. Sitagliptin therapy of 1 year also provided benefit on nonalcoholic steatohepatitis score in an observational study.

Conclusions

For T2DM with NAFLD, administrating thiazolidinediones and glucagon‐like peptide‐1 receptor agonists seems to provide more identified advances in attenuating hepatic fat content. Further RCTs are warranted to assess the efficacy of various hypoglycemic agents on clinical outcomes associated with NAFLD in T2DM. Copyright © 2015 John Wiley & Sons, Ltd.
Type 2 diabetes after gestational diabetes: greater than fourfold risk among Indigenous compared with non‐Indigenous Australian women
Authors: Chamberlain Catherine R. , Oldenburg Brian , Wilson Alyce N. , Eades Sandra J. , O'Dea Kerin , Oats Jeremy J. N. , Wolfe Rory
Published: September 2015

Background

Gestational diabetes is associated with a high risk of type 2 diabetes. However, progression rates among Indigenous women in Australia who experience high prevalence of gestational diabetes are unknown.

Methods

This retrospective cohort study includes all births to women at a regional hospital in Far North Queensland, Australia, coded as having ‘gestational diabetes’ from 1 January 2004 to 31 December 2010 (1098 births) and receiving laboratory postpartum screening from 1 January 2004 to 31 December 2011 (n = 483 births). Women who did not receive postpartum screening were excluded from the denominator. Data were linked between hospital electronic records, routinely collected birth data and laboratories, with sample validation by reviews of medical records. Analysis was conducted using Cox‐proportional regression models.

Results

Indigenous women had a greater than fourfold risk of developing type 2 diabetes within 8 years of having gestational diabetes, compared with non‐Indigenous women (hazards ratio 4.55, 95% confidence interval 2.63–7.88, p < 0.0001). Among women receiving postpartum screening tests, by 3, 5 and 7 years postpartum, 21.9% (15.8–30.0%), 25.5% (18.6–34.3%) and 42.4% (29.6–58.0%) Indigenous women were diagnosed with type 2 diabetes after gestational diabetes, respectively, compared with 4.2% (2.5–7.2%), 5.7% (3.3–9.5%) and 13.5% (7.3–24.2%) non‐Indigenous women. Multivariate analysis showed an increased risk of developing type 2 diabetes among women with an early pregnancy body mass index ≥25 kg/m2, only partially breastfeeding at hospital discharge and gestational diabetes diagnosis prior to 17 weeks gestation.

Conclusions

This study demonstrates that, compared with non‐Indigenous women, Indigenous Australian women have a greater than fourfold risk of developing type 2 diabetes after gestational diabetes. Strategies are urgently needed to reduce rates of type 2 diabetes by supporting a healthy weight and breastfeeding and to improve postpartum screening among Indigenous women with gestational diabetes. Copyright © 2015 John Wiley & Sons, Ltd.
Glycaemic control and its associated factors in Chinese adults with type 1 diabetes mellitus
Authors: Liu Li , Yang Daizhi , Zhang Yan , Lin Shuo , Zheng Xueying , Lin Shaoda , Chen Lishu , Zhang Xiuwei , Li Lu , Liang Ganxiong , Yao Bin , Yan Jinhua , Weng Jianping
Published: September 2015

Background

Glycaemic control is a great challenge in the management of type 1 diabetes mellitus (T1DM). There is limited data concerning glycaemic control among adults with T1DM. We used data from the Guangdong T1DM Translational Medicine Study to evaluate glycaemic control and its associated factors in Chinese adults with T1DM.

Methods

This cross‐sectional analysis included 827 participants who were 18 years of age or older and had been living with T1DM for at least 1 year. Participants with HbA1c levels <7% were compared against those with HbA1c levels ≥ 7%. A multivariate logistic regression model was used to examine factors associated with glycaemic control.

Results

Among the 827 participants, the mean age was 34.2 ± 12.1 years and the median (interquartile range) duration of diabetes was 6.1 (3.4, 10.4) years. The median HbA1c level was 8.5% (7.5%, 10.2%). Only one‐fifth of participants had HbA1c levels <7%. Insufficient glycaemic control (HbA1c ≥ 7%) was strongly associated with infrequent self‐monitoring of blood glucose (OR = 1.21, 95% CI 1.14 ~ 1.29, p = 0.000), high insulin dose (OR = 1.27, 95% CI 1.07 ~ 1.52, p = 0.006), smoking (OR = 3.11, 95% CI 1.44 ~ 6.72, p = 0.004), low‐frequency clinical visits (OR = 2.74, 95% CI 1.47 ~ 5.10, p = 0.001), the presence of diabetic autoantibodies (OR = 1.63, 95% CI 1.07 ~ 2.48, p = 0.022) and low fasting C‐peptide (FCP) levels (OR = 1.21, 95% CI 1.01 ~ 1.46, p = 0.049) after adjustment for age at disease onset, education level, household income and diet control.

Conclusions

Most adult patients with T1DM did not achieve the HbA1c target. Identifying determinants for glycaemic control provides us valuable information to improve glycaemic control in these patients. Copyright © 2015 John Wiley & Sons, Ltd.
Expanded test method for peptides >2 kDa employing immunoaffinity purification and LC‐HRMS/MS
Authors: Thomas Andreas , Walpurgis Katja , Tretzel Laura , Brinkkötter Paul , Fichant Eric , Delahaut Philippe , Schänzer Wilhelm , Thevis Mario
Published: September 2015

Bioactive peptides with an approximate molecular mass of 2–12 kDa are of considerable relevance in sports drug testing. Such peptides have been used to manipulate several potential performance‐enhancing processes in the athlete's body and include for example growth hormone releasing hormones (sermorelin, CJC‐1293, CJC‐1295, tesamorelin), synthetic/animal insulins (lispro, aspart, glulisine, glargine, detemir, degludec, bovine and porcine insulin), synthetic ACTH (synacthen), synthetic IGF‐I (longR3‐IGF‐I) and mechano growth factors (human MGF, modified human MGF, ‘full‐length’ MGF). A combined initial test method using one analytical procedure is a desirable tool in doping controls and related disciplines as requests for higher sample throughput with utmost comprehensiveness preferably at reduced costs are constantly issued. An approach modified from an earlier assay proved fit‐for‐purpose employing pre‐concentration of all target analytes by means of ultrafiltration, immunoaffinity purification with coated paramagnetic beads, nano‐ultra high performance liquid chromatography (UHPLC) separation, and subsequent detection by means of high resolution tandem mass spectrometry. The method was shown to be applicable to blood and urine samples, which represent the most common doping control specimens. The method was validated considering the parameters specificity, recovery (11–69%), linearity, imprecision (<25%), limit of detection (5–100 pg in urine, 0.1–2 ng in plasma), and ion suppression. The analysis of administration study samples for insulin degludec, detemir, aspart, and synacthen provided the essential data for the proof‐of‐principle of the method. Copyright © 2015 John Wiley & Sons, Ltd.
Assessment of microsatellite and SNP markers for parentage assignment in ex situ African Penguin (Spheniscus demersus) populations
Authors: Labuschagne Christiaan , Nupen Lisa , Kotzé Antoinette , Grobler Paul J. , Dalton Desiré L.
Published: September 2015

Captive management of ex situ populations of endangered species is traditionally based on pedigree information derived from studbook data. However, molecular methods could provide a powerful set of complementary tools to verify studbook records and also contribute to improving the understanding of the genetic status of captive populations. Here, we compare the utility of single nucleotide polymorphisms (SNPs) and microsatellites (MS) and two analytical methods for assigning parentage in ten families of captive African penguins held in South African facilities. We found that SNPs performed better than microsatellites under both analytical frameworks, but a combination of all markers was most informative. A subset of combined SNP (n = 14) and MS loci (n = 10) provided robust assessments of parentage. Captive or supportive breeding programs will play an important role in future African penguin conservation efforts as a source of individuals for reintroduction. Cooperation among these captive facilities is essential to facilitate this process and improve management. This study provided us with a useful set of SNP and MS markers for parentage and relatedness testing among these captive populations. Further assessment of the utility of these markers over multiple (>3) generations and the incorporation of a larger variety of relationships among individuals (e.g., half‐siblings or cousins) is strongly suggested.
Multi‐Level Environmental Governance: Exploring the economic explanations
Authors: Paavola Jouni
Published: September 2015

Multi‐level environmental governance (MLEG) has become commonplace, yet few attempts have been made to explain in economic terms why it should have emerged. This article examines four economic explanations for MLEG. The first considers it as a solution for overcoming collective action challenges when a large number of actors are involved. The second explanation is that multiple levels of environmental governance may be needed to minimize governance costs. Thirdly, path dependence could explain MLEG. Fourthly, complex and multifunctional resource systems may generate ecosystem service flows that have benefit catchments of different size, and multi‐level governance solutions may be needed to link providers and beneficiaries. While they are to a degree complementary, the analysis suggests that the multi‐functionality explanation is the most nuanced one of them and offers the best diagnostic for governance challenges that an environmental resource system poses. © 2015 The Authors. Environmental Policy and Governance published by ERP Environment and John Wiley & Sons Ltd
Modeling viscous damping in nonlinear response history analysis of buildings for earthquake excitation
Authors: Chopra Anil K. , McKenna Frank
Published: September 2015

The Rayleigh damping model, which is pervasive in nonlinear response history analysis (RHA) of buildings, is shown to develop ‘spurious’ damping forces and lead to inaccurate response results. We prove that a viscous damping matrix constructed by superposition of modal damping matrices—irrespective of the number of modes included or values assigned to modal damping ratios—completely eliminates the ‘spurious’ damping forces. This is the damping model recommended for nonlinear RHA.

Replacing the stiffness‐proportional part of Rayleigh damping by the tangent stiffness matrix is shown to improve response results. However, this model is not recommended because it lacks a physical basis and has conceptual implications that are troubling: hysteresis in damping force–velocity relationship and negative damping at large displacements. Furthermore, the model conflicts with the constant‐damping model that has been the basis for fundamental concepts and accumulated experience about the inelastic response of structures.

With a distributed plasticity model, the structural response is not sensitive to the damping model; even the Rayleigh damping model leads to acceptable results. This perspective on damping provides yet another reason to employ the superior distributed plasticity models in nonlinear RHA.

OpenSees software has been extended to include a damping matrix defined as the superposition of modal damping matrices. Although this model leads to a full populated damping matrix, the additional computational demands are demonstrated to be minimal. Copyright © 2015 John Wiley & Sons, Ltd.
Competing mechanisms for perfluoroalkyl acid accumulation in plants revealed using an Arabidopsis model system
Authors: Müller Claudia E. , LeFevre Gregory H. , Timofte Anca E. , Hussain Fatima A. , Sattely Elizabeth S. , Luthy Richard G.
Published: September 2015

Perfluoroalkyl acids (PFAAs) bioaccumulate in plants, presenting a human exposure route if present in irrigation water. Curiously, accumulation of PFAAs in plant tissues is greatest for both the short-chain and long-chain PFAAs, generating a U-shaped relationship with chain length. In the present study, the authors decouple competing mechanisms of PFAA accumulation using a hydroponic model plant system (Arabidopsis thaliana) exposed to a suite of 10 PFAAs to determine uptake, depuration, and translocation kinetics. Rapid saturation of root concentrations occurred for all PFAAs except perfluorobutanoate, the least-sorptive (shortest-chain) PFAA. Shoot concentrations increased continuously, indicating that PFAAs are efficiently transported and accumulate in shoots. Tissue concentrations of PFAAs during depuration rapidly declined in roots but remained constant in shoots, demonstrating irreversibility of the translocation process. Root and shoot concentration factors followed the U-shaped trend with perfluoroalkyl chain length; however, when normalized to dead-tissue sorption, this relationship linearized. The authors therefore introduce a novel term, the “sorption normalized concentration factor,” to describe PFAA accumulation in plants; because of their hydrophobicity, sorption is the determining factor for long-chain PFAAs, whereas the shortest-chain PFAAs are most effectively transported in the plant. The present study provides a mechanistic explanation for previously unexplained PFAA accumulation trends in plants and suggests that shorter-chained PFAAs may bioaccumulate more readily in edible portions. Environ Toxicol Chem 2016;35:1138–1147. © 2015 SETAC
Optimization of the marinating conditions of cassava fish (Pseudotolithus sp.) fillet for Lanhouin production through application of Doehlert experimental design
Authors: Kindossi Janvier Mêlégnonfan , Anihouvi Victor Bienvenu , Vieira‐Dalodé Générose , Akissoé Noël Houédougbé , Hounhouigan Djidjoho Joseph
Published: September 2015

Lanhouin is a traditional fermented salted fish made from the spontaneous and uncontrolled fermentation of whole salted cassava fish (Pseudotolithus senegalensis) mainly produced in the coastal regions of West Africa. The combined effects of NaCl, citric acid concentration, and marination time on the physicochemical and microbiological characteristics of the fish fillet used for Lanhouin production were studied using a Doehlert experimental design with the objective of preserving its quality and safety. The marination time has significant effects on total viable and lactic acid bacteria counts, and NaCl content of the marinated fish fillet while the pH was significantly affected by citric acid concentration and marination duration with high regression coefficient R2 of 0.83. The experiment showed that the best conditions for marination process of fish fillet were salt ratio 10 g/100 g, acid citric concentration 2.5 g/100 g, and marination time 6 h. These optimum marinating conditions obtained present the best quality of marinated flesh fish leading to the safety of the final fermented product. This pretreatment is necessary in Lanhouin production processes to ensure its safety quality.
Distributed category‐specific recognition‐memory signals in human perirhinal cortex
Authors: Martin Chris B. , Cowell Rosemary A. , Gribble Paul L. , Wright Jessey , Köhler Stefan
Published: September 2015

Evidence from a large body of research suggests that perirhinal cortex (PrC), which interfaces the medial temporal lobe with the ventral visual pathway for object identification, plays a critical role in item‐based recognition memory. The precise manner in which PrC codes for the prior occurrence of objects, however, remains poorly understood. In the present functional magnetic resonance imaging (fMRI) study, we used multivoxel pattern analyses to examine whether the prior occurrence of faces is coded by distributed patterns of PrC activity that consist of voxels with decreases as well as increases in signal. We also investigated whether pertinent voxels are preferentially tuned to the specific object category to which judged stimuli belong. We found that, when no a priori constraints were imposed on the direction of signal change, activity patterns that allowed for successful classification of recognition‐memory decisions included some voxels with decreases and others with increases in signal in association with perceived prior occurrence. Moreover, successful classification was obtained in the absence of a mean difference in activity across the set of voxels in these patterns. Critically, we observed a positive relationship between classifier accuracy and behavioral performance across participants. Additional analyses revealed that voxels carrying diagnostic information for classification of memory decisions showed category specificity in their tuning for faces when probed with an independent functional localizer in a nonmnemonic task context. These voxels were spatially distributed in PrC, and extended beyond the contiguous voxel clusters previously described as the anterior temporal face patch. Our findings provide support for proposals, recently raised in the neurophysiological literature, that the prior occurrence of objects is coded by distributed PrC representations. They also suggest that the stimulus category to which an item belongs shapes the organization of these distributed representations. © 2015 Wiley Periodicals, Inc.
Food restriction modifies ultrastructure of hippocampal synapses
Authors: Babits Réka , Szőke Balázs , Sótonyi Péter , Rácz Bence
Published: September 2015

Consumption of high‐energy diets may compromise health and may also impair cognition; these impairments have been linked to tasks that require hippocampal function. Conversely, food restriction has been shown to improve certain aspects of hippocampal function, including spatial memory and memory persistence. These diet‐dependent functional changes raise the possibility that the synaptic structure underlying hippocampal function is also affected. To examine how short‐term food restriction (FR) alters the synaptic structure of the hippocampus, we used quantitative electron microscopy to analyze the organization of neuropil in the CA1 stratum radiatum of the hippocampus in young rats, consequent to reduced food. While four weeks of FR did not modify the density, size, or shape of postsynaptic spines, the synapses established by these spines were altered, displaying increased mean length, and more frequent perforations of postsynaptic densities. That the number of perforated synapses (believed to be an indicator of synaptic enhancement) increased, and that the CA1 spine population had on average significantly longer PSDs suggests that synaptic efficacy of axospinous synapses also increased in the CA1. Taken together, our ultrastructural data reveal previously unrecognized structural changes at hippocampal synapses as a function of food restriction, supporting a link between metabolic balance and synaptic plasticity. © 2015 Wiley Periodicals, Inc.
Comparison of 60 and 80 mg/m2 of daunorubicin in induction therapy of acute myeloid leukaemia
Authors: Vaezi Mohammad , Bahar Babak , Mousavi Asadollah , Yaghmai Marjan , Kasaeian Amir , Souri Maryam , Jahani Mohammad , Alimoghaddam Kamran , Ghavamzadeh Ardeshir
Published: September 2015

For finding better method of acute myeloid leukaemia (AML) induction, we designed a prospective clinical trial to find a more effective regimen with least toxicity for induction therapy of AML. Hence, we examined different accepted doses of daunorubicin and their outcomes. Total of 114 patients were included in the study. Fifty‐five patients received 60 mg/m2 of daunorubicin (arm 1) 1 h IV infusion for 3 days, and the remaining 59 received 80 mg/m2 (arm 2) 1 h IV infusion for 3 days. Continuous infusion of 100 mg/m2/day of cytosine arabinozide IV for 24 h for 7 days was given in both groups. Complete remission rate was 77.78% in group 1 and 76.92% in group 2 (p = 0.92). One‐year overall survival was 55.85% [standard error (SE) = 8.05%] in arm 1 and 57.94% (SE = 7.32%) in arm 2. Median follow‐up time was 11.1 (SE = 1.43) and 10.28 (SE = 1.29) months, respectively. One‐year disease‐free survival was 64.41% (SE = 7.39%) in arm 1 and 54.86% (SE = 7.53%) in arm 2. Complete remission, overall survival and disease‐free survival were statistically the same in both groups (p = 0.92, 0.697, 0.31). Toxicity and safety profile were similar in two groups but need to transfusion was higher in arm 2. Febrile neutropenia, days of antibiotics consumption and invasive fungal infection prevalence did not show any difference. Mean transfused packed cells and platelets rate were higher in the group that received higher dose of daunorubicin. Considering these results, we found that 60 mg/m2 of daunorubicin would be more rational and as effective with lower toxicity to 80 mg/m2 in induction therapy of AML patients at least as scheduled in our trial. Copyright © 2015 John Wiley & Sons, Ltd.
Policy Characteristics for the Prevention of Workplace Bullying Anteceded by Heterosexism: A Delphi Study
Authors: McCalla Scott A.
Published: September 2015

The aim of this study's was to obtain organizational practices or policies that can help diminish the risk of heterosexism as it pertains to workplace bullying of lesbian, gay, bisexual, and transgendered (LGBT) workers. Heterosexism and workplace bullying are still prevalent concerns for LGBT workers, causing psychological and physical illness and reduced organizational effectiveness. This study contributes to social change by informing leaders, politicians, advocacy groups, and scholars on recommendations to help safeguard the health of employees, safeguard operational effectiveness of an organization, and reduce workplace bullying of LGBT and other marginalized employees. Findings of this study include that “organizational programs and policies should be developed and implemented to provide anti‐bullying policies that protect all employees, not just minority or potentially marginalized employees.” Additionally, the results support the direction that “organizational leaders should begin to mitigate the damage of workplace bullying through enforcement of current policies.”
Loss of ACSS2 expression predicts poor prognosis in patients with gastric cancer
Authors: Hur Hoon , Kim Young‐Bae , Ham In‐Hye , Lee Dakeun
Published: September 2015

Background

Recent studies have demonstrated that acetyl‐CoA synthetase 2 (ACSS2) plays a critical role in cancer cell survival; however, the role of ACSS2 in gastric carcinogenesis has not been determined.

Methods

We investigated the expression of ACSS2 in human gastric cancer (GC) tissues using immunohistochemistry, and analyzed its clinicopathological correlation and prognostic relevance.

Results

Among 350 GCs, 219 cases (62.6%) were classified as ACSS2‐low, whereas 131 cases (37.4%) were ACSS2‐high. Loss of ACSS2 expression (ACSS2‐low) was more frequently observed in undifferentiated histology (P = 0.002), in cases with MLH1‐loss (P = 0.003), and in cases with SIRT3‐low (P < 0.001). The ACSS2‐low cases showed significantly lower mean disease‐free survival (DFS, 68.5 vs. 81.8 months; P = 0.025) and overall survival (OS, 73.5 vs. 86.6 months; P = 0.029). In multivariate analysis, loss of ACSS2 expression was identified as one of the independent prognostic factors predicting worse DFS (HR: 1.547, P = 0.018) and OS (HR: 1.476, P = 0.036).

Conclusions

We revealed that the loss of ACSS2 expression is a reliable independent poor prognostic factor in GC. Our results may expand our understanding of the involvement of glucose metabolism, including the role of ACSS2, in the pathogenesis of GC. J. Surg. Oncol. 2015;112:585–591. © 2015 Wiley Periodicals, Inc.
Developing a prognostic model for patients with localized osteosarcoma treated with uniform chemotherapy protocol without high dose methotrexate: A single‐center experience of 237 patients
Authors: Nataraj Vijayamurugan , Batra Atul , Rastogi Shishir , Khan Shah Alam , Sharma Mehar Chand , Vishnubhatla Sreenivas , Bakhshi Sameer
Published: September 2015

Background

Studies of baseline prognostic factors in patients with localized osteosarcoma treated without high dose methotrexate are limited.

Methods

This is single‐institutional review of localized osteosarcoma patients treated without high dose methotrexate between June 2003–December 2012. A multivariate analysis of impact of baseline and treatment characteristics on outcome was performed and a prognostic model was developed based solely on baseline factors for predicting event‐free survival (EFS) and overall survival (OS).

Results

Of 237 patients with median age of 17 years (range 2–66 yrs), neoadjuvant chemotherapy (NACT) was administered in 220 (92.82%) patients. Post NACT, 200/237 (84.38%) patients underwent surgery. At 30 months median follow‐up, 5‐year EFS and OS were 36.60 ± 0.03%, and 50.33 ± 0.04%, respectively. In multivariate analysis, baseline factors including duration of symptom >4 months (P < 0.001) and good performance status (PS) (P < 0.001) predicted better EFS whereas good PS (P = 0.01) and normal serum alkaline phosphatase (SAP) (P = 0.03) predicted better OS. The 5‐year EFS without any risk factor (symptom duration <4 months, PS>1) was 58.7 ± 0.1%, with either one factor 31.5 ± 0.1% and with both factors 21.9 ± 0.1%. The 5‐year OS without any risk factor (PS>1, elevated SAP) was 66.9 ± 0.1%, with either one factor 57.9 ± 0.1% and with both factors 25.6 ± 0.1%

Conclusions

This prognostic model assists in categorizing risk‐groups within localized osteosarcoma. J. Surg. Oncol. 2015;112:662–668. © 2015 Wiley Periodicals, Inc.
Long term water clarity changes in North America's Great Lakes from multi‐sensor satellite observations
Authors: Binding Caren E. , Greenberg Tracie A. , Watson Sue B. , Rastin Shannah , Gould Jessica
Published: September 2015

Water clarity in North America's Laurentian Great Lakes has undergone considerable change over the last several decades as a consequence of invasive species, eutrophication, and implemented nutrient management practices. Satellite observations from the CZCS, SeaWiFS, and MODIS‐Aqua sensors have been used in tandem with long term records of Secchi disk depth (ZSD) to provide a retrospective analysis of spatial and temporal variations in water clarity over the Great Lakes. A simple empirical algorithm is presented, relating ZSD to remote‐sensing reflectance at ∼ 550 nm (Rrs∼550). Results suggest remarkable and complex changes in water clarity over the Great Lakes. Lakes Ontario, Huron, and Michigan have seen increases in average ZSD over the three sensor periods of 58%, 49%, and 62%, respectively. Lake Erie shows highly variable ZSD with no consistent long term trends, while Lake Superior has remained fairly consistent in its lake‐wide water clarity conditions. Temporal trends document the decrease in whiting events on Lake Michigan while capturing the ongoing occurrence of these seasonal bright‐water events on Lake Ontario. Results indicate a divergence in ZSD trends between nearshore and offshore environments; with larger increases in offshore than nearshore ZSD and some nearshore areas suggesting a decrease in ZSD. Offshore regions of Lakes Huron, Michigan, and Superior show diminished ZSD seasonality in contrast to increasing seasonal variance in the nearshore. Spatial and temporal variations in ZSD are in agreement with documented reductions in Great Lakes bioproductivity, degrading nearshore water quality, and changing biogeochemical processes influencing whiting events and sediment resuspension.
Star‐Shaped Polypeptides: Synthesis and Opportunities for Delivery of Therapeutics
Authors: Byrne Mark , Murphy Robert , Kapetanakis Antonios , Ramsey Joanne , Cryan Sally‐Ann , Heise Andreas
Published: September 2015

Significant advances in the synthesis of polypeptides byN‐carboxyanhydride (NCA) polymerisation over the last decade have enabled the design of advanced polypeptide architectures such as star‐shaped polypeptides. These materials combine the functionality offered by amino acids with the flexibility of creating stable nanoparticles with adjustable cargo space for therapeutic delivery. This review highlights recent advances in the synthesis of star polypeptides by NCA polymerisation followed by a critical review of the applications of this class of polymer in the delivery of therapeutic agents. This includes examples of traditional small‐molecule drugs as well as the emerging class of biologics such as genetic therapeutics (gene delivery).

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Striatal and Cortical β‐Amyloidopathy and Cognition in Parkinson's Disease
Authors: Shah Neha , Frey Kirk A. , L.T.M Müller Martijn , Petrou Myria , Kotagal Vikas , Koeppe Robert A. , Scott Peter J.H. , Albin Roger L. , Bohnen Nicolaas I.
Published: September 2015

Introduction

Although most previous cognitive studies of β‐amyloidopathy in PD focused on cortical plaque deposition, recent postmortem studies point to an important role of striatal β‐amyloid plaque deposition. The aim of this study was to investigate the relative contributions of striatal and cortical β‐amyloidopathy to cognitive impairment in PD.

Methods

Patients with PD (n = 62; age, 68.9 ± 6.4 years; H & Y stage: 2.7 ± 0.5; MoCA score: 25.2 ± 3.0) underwent [11C]Pittsburgh compound B β‐amyloid, [11C]dihydrotetrabenazine monoaminergic, and [11C]methyl‐4‐piperidinyl propionate acetylcholinesterase brain PET imaging and neuropsychological assessment. [11C]Pittsburgh compound B β‐amyloid data from young to middle‐aged healthy subjects were used to define elevated [11C]Pittsburgh compound B binding in patients.

Results

Elevated cortical and striatal β‐amyloid deposition were present in 37% and 16%, respectively, of this predominantly nondemented cohort of patients with PD. Increased striatal β‐amyloid deposition occurred in half of all subjects with increased cortical β‐amyloid deposition. In contrast, increased striatal β‐amyloid deposition did not occur in the absence of increased cortical β‐amyloid deposition. Analysis of covariance using global composite cognitive z scores as the outcome parameter showed significant regressor effects for combined striatal and cortical β‐amyloidopathy (F = 4.18; P = 0.02) after adjusting for covariate effects of cortical cholinergic activity (F = 5.67; P = 0.02), caudate nucleus monoaminergic binding, duration of disease, and age (total model: F = 3.55; P = 0.0048). Post‐hoc analysis showed significantly lower cognitive z score for combined striatal and cortical β‐amyloidopathy, compared to cortical‐only β‐amyloidopathy and non‐β‐amyloidopathy subgroups.

Conclusions

The combined presence of striatal and cortical β‐amyloidopathy is associated with greater cognitive impairment than cortical β‐amyloidopathy alone in PD. © 2015 International Parkinson and Movement Disorder Society
Cost‐effectiveness of Occupational Therapy in Older People: Systematic Review of Randomized Controlled Trials
Authors: Nagayama Hirofumi , Tomori Kounosuke , Ohno Kanta , Takahashi Kayoko , Yamauchi Keita
Published: September 2015

A systematic review of the cost‐effectiveness of occupational therapy for older people was conducted. MEDLINE, CINAHL, Web of Science, PsycINFO, Cochrane Library, OT seeker and unpublished trials registers were searched. Reference lists of all potentially eligible studies were searched with no language restrictions. We included trial‐based full economic evaluations that considered both costs and outcomes in occupational therapy for older people compared with standard care (i.e. other therapy) or no intervention. We reviewed each trial for methodological quality using the Cochrane risk of bias tool and assessed the quality of economic evaluations using a Drummond checklist. In the results of this review, we included five eligible studies (1–5) that were randomized controlled trials with high‐quality economic evaluation. Two studies were full economic evaluations of interventions for fall prevention (1 and 2); two studies were full economic evaluations of preventive occupational therapy interventions (3 and 4; one was a comparison of an occupational therapy group with a social work group); one study was a full economic evaluation of occupational therapy for individuals with dementia (5). Two of the studies (one was preventive occupational therapy [3] and the other was occupational therapy for dementia [5]) found a significant effect and confirmed the cost‐effectiveness of occupational therapy for older people compared with the control group. These studies found that occupational therapy for older people was clinically effective and cost‐effective in comparison with standard care or other therapies. With reference to their clinical implication, these intervention studies (using a client‐centred approach) suggested potentially cost‐effective means to motivate clients to maintain their own health. However, this review has limitations because of the high heterogeneity of the reviewed studies on full economic evaluations of occupational therapy for older people. Future studies on the cost‐effectiveness of occupational therapy in older people are strongly warranted. Copyright © 2015 John Wiley & Sons, Ltd.
Structural insights into the intertwined dimer of fyn SH2
Authors: Huculeci Radu , Garcia‐Pino Abel , Buts Lieven , Lenaerts Tom , van Nuland Nico
Published: September 2015

Src homology 2 domains are interaction modules dedicated to the recognition of phosphotyrosine sites incorporated in numerous proteins found in intracellular signaling pathways. Here we provide for the first time structural insight into the dimerization of Fyn SH2 both in solution and in crystalline conditions, providing novel crystal structures of both the dimer and peptide‐bound structures of Fyn SH2. Using nuclear magnetic resonance chemical shift analysis, we show how the peptide is able to eradicate the dimerization, leading to monomeric SH2 in its bound state. Furthermore, we show that Fyn SH2's dimer form differs from other SH2 dimers reported earlier. Interestingly, the Fyn dimer can be used to construct a completed dimer model of Fyn without any steric clashes. Together these results extend our understanding of SH2 dimerization, giving structural details, on one hand, and suggesting a possible physiological relevance of such behavior, on the other hand.
The Impact of FDI Inflow on Domestic Firms’ Uptake of CSR Activities: The Moderating Effects of Host Institutions
Authors: Nyuur Richard B. , Ofori Daniel F. , Debrah Yaw A.
Published: September 2015

This study examines whether foreign direct investment (FDI) inflow helps or hinders local firms’ uptake of corporate social responsibility (CSR) activities in a developing host country. The study further examines the interaction effect of host institutions on the relationship between FDI inflow and local firms’ uptake of CSR activities. Results of hierarchical regression analysis of data from a sample of 227 local firms in Ghana, reveal that local firms’ uptake of CSR improves significantly with an increasing inflow of FDI through knowledge transfer. Host institutions are also found to influence the transfer of CSR activities from foreign firms to local firms. However, when the quality of institutions is very high, the impact of FDI on local firms’ CSR activities diminishes. Research and practical implications of these findings are discussed. © 2015 Wiley Periodicals, Inc.
Magnetic and Spectroscopic Study on a New Asymmetric Mixed‐valence Mn2(II,III) Coordination Compound
Authors: Jung Martin , Rentschler Eva
Published: September 2015

A new dinuclear mixed‐valence compound [MnIIMnIII(bttpnol)(O2C–C6H4–NO2)2]ClO4 was synthesized by using the asymmetric heptadentate ligand N‐(2‐hydroxybenzyl)‐N,N′,N′‐tris(2‐pyridylmethyl)‐1,3‐diaminopropan‐2‐ol (H2btppnol). One central manganese atom assumes N3O3 and the other N2O4 coordination sphere. Both manganese ions are bridged by the alkoxy‐group of the dinucleating ligand and two bidentate carboxylate groups of the nitrobenzoate ligands. The structural data show clearly that MnIII prefers the more oxygen rich donor set. Cyclic voltammetry measurements reveal that the mixed‐valence state Mn2(II,III) could be reduced to Mn2(II,II) at E1/2(1) = –0.53 V and oxidized to Mn2(III,III) at E1/2(2) = 0.52 V (vs. ferrocene). Measurements of the magnetic susceptibility reveal a weak antiferromagnetic coupling with J = –8.5 cm–1. The mixed valence state was additionally confirmed by EPR spectroscopy showing the hyperfine signal of the S = 1/2 state of Mn2(II,III).
Local Responses to the English Reformation
Authors: Whiting Robert
Published: September 2015

This major new study re-examines one of the most controversial issues of early modern history: the impact of the English Reformation upon the English people. It represents an advance from the conventional reign-by-reign narrative to a more incisively thematic approach. Drawing on the author’s own research in church art as well as in written records such as wills and parish accounts, and evaluating the findings of other recent historians, it forcefully challenges several of the currently fashionable interpretations of this crucial era.
An epidemiological study of paediatric motocross injuries in the United Kingdom
Authors: Singh Rohit , Malhotra Akshay , Kyle Nigel , Hay Stuart
Published: September 2015

Purpose

Although off-road motorcycling is one of the most popular sports activities practised by millions of people worldwide, little has been written on motocross injuries and their prevention. In the UK alone, motocross has grown into a phenomenally ambitious and popular franchise. There are >200 motocross clubs across the country holding >900 events annually. The aim of this study is to categorise and quantify the magnitude of motocross paediatric injuries and associated morbidity.

Methods

Data were collected prospectively over 4 years (2010−2014) at our unit. All injuries caused by motocross biking that were referred to our trauma and orthopaedic department were included in this study, regardless of whether the rider was performing the sport competitively or recreationally.

Results

During the study period, 130 patients (aged 4−17 years) were identified with a total of 142 injuries, ranging from one to six injuries per patient. Most of the injuries were sustained within the early spring and summer months, representing the start of the motocross season; 76 patients required hospital admission, with 60 (42 %) requiring surgical intervention.

Conclusion

We present the first epidemiological study of motocross paediatric injuries in the UK. The results from this study highlight the frequency and severity of motocross-related injuries in the paediatric population in the UK. This may assist in providing recommendations and guidelines to governing bodies and to parents. The injuries sustained during motocross have significant resource implications, especially for smaller rural hospitals, as shown by the number of injuries doubling over the past 4 years.
CHANG’S CONJECTURE, GENERIC ELEMENTARY EMBEDDINGS AND INNER MODELS FOR HUGE CARDINALS
Authors: FOREMAN MATTHEW
Published: September 2015

We introduce a natural principleStrong Chang Reflectionstrengthening the classical Chang Conjectures. This principle is between a huge and a two huge cardinal in consistency strength. In this note we prove that it implies the existence of an inner model with a huge cardinal. The technique we explore for building inner models with huge cardinals adapts to show thatdecisiveideals imply the existence of inner models with supercompact cardinals. Proofs for all of these claims can be found in [10].1,2
THE CONSTRAINT SATISFACTION PROBLEM AND UNIVERSAL ALGEBRA
Authors: BARTO LIBOR
Published: September 2015

This paper gives a brief survey of current research on the complexity of the constraint satisfaction problem over fixed constraint languages.
A boundary layer model for ice stream margins
Authors: Haseloff M. , Schoof C. , Gagliardini O.
Published: September 2015

The majority of Antarctic ice is discharged via long and narrow fast-flowing ice streams. At ice stream margins, the rapid transition from the vertical shearing flow in the ice ridges surrounding the stream to a rapidly sliding plug flow in the stream itself leads to high stress concentrations and a velocity field whose form is non-trivial to determine. In this paper, we develop a boundary layer theory for this narrow region separating a lubrication-type ice ridge flow and a membrane-type ice stream flow. This allows us to derive jump conditions for the outer models describing ridge and stream self-consistently. Much of our focus is, however, on determining the velocity and shear heating fields in the margin itself. Ice stream margins have been observed to change position over time, with potentially significant implications for ice stream discharge. Our boundary layer model allows us to extend previous work that has determined rates of margin migration from a balance between shear heating in the margin and the cooling effect of margin migration into the colder ice of the surrounding ice ridge. Solving for the transverse velocity field in the margin allows us to include the effect of advection due to lateral inflow of ice from the ridge on margin migration, and we demonstrate that this reduces the rate of margin migration, as previously speculated.
Comparative analysis of the Cancer Council of Victoria and the online Commonwealth Scientific and Industrial Research Organisation FFQ
Authors: Gardener Samantha L. , Rainey-Smith Stephanie R. , Macaulay S. Lance , Taddei Kevin , Rembach Alan , Maruff Paul , Ellis Kathryn A. , Masters Colin L. , Rowe Christopher C. , Ames David , Keogh Jennifer B. , Martins Ralph N. ,   The AIBL Research Group
Published: September 2015

FFQ are commonly used to examine the association between diet and disease. They are the most practical method for usual dietary data collection as they are relatively inexpensive and easy to administer. In Australia, the Cancer Council of Victoria FFQ (CCVFFQ) version 2 and the online Commonwealth Scientific and Industrial Research Organisation FFQ (CSIROFFQ) are used. The aim of our study was to establish the level of agreement between nutrient intakes captured using the online CSIROFFQ and the paper-based CCVFFQ. The CCVFFQ and the online CSIROFFQ were completed by 136 healthy participants. FFQ responses were analysed to give g per d intake of a range of nutrients. Agreement between twenty-six nutrient intakes common to both FFQ was measured by a variety of methods. Nutrient intake levels that were significantly correlated between the two FFQ were carbohydrates, total fat, Na and MUFA. When assessing ranking of nutrients into quintiles, on average, 56 % of the participants (for all nutrients) were classified into the same or adjacent quintiles in both FFQ, with the highest percentage agreement for sugar. On average, 21 % of participants were grossly misclassified by three or four quintiles, with the highest percentage misclassification for fibre and Fe. Quintile agreement was similar to that reported by other studies, and we concluded that both FFQ are suitable tools for dividing participants’ nutrient intake levels into high- and low-consumption groups. Use of either FFQ was not appropriate for obtaining accurate estimates of absolute nutrient intakes.
Multi-factorial Approaches to Substance Use Disorders and Addiction
Authors: Stratyner Harris B.
Published: September 2015

One cannot get through a day (certainly not in the United States) without hearing about the devastation that substance abuse, addiction, and, in many cases, co-occurring disorders (ie, substance abuse or addiction in conjunction with a major psychiatric clinical syndrome and/or personality disorder) cast upon countless numbers of lives. For years, there has been a controversy as to whether addiction was simply a moral failing or a brain disease. Obviously, the latter is true.

As with any disease, addiction and co-occurring disorders are frequently considered to be primary, progressive, chronic, and, if untreated, fatal. With the advent of more sophisticated neurobiological and multivariate research, we can get beyond trivializing this serious disease entity by labeling it as a weakness or character defect, and get on with the significant work of focusing on those neurological pathways and their etiology that are responsible for addictive patterns of behavior.
Circulation Models Cannot Simulate Organized Tropical Convection
Authors: Cook Terri
Published: September 2015

Challenges in predicting and simulating the Madden-Julian Oscillation indicate a lack of understanding of the atmospheric circulation pattern's fundamental physics.
Hypothalamic PKA regulates leptin sensitivity and adiposity
Authors: Yang Linghai , McKnight G. Stanley
Published: September 2015

Mice lacking the RIIβ regulatory subunit of cyclic AMP-dependent protein kinase A (PKA) display reduced adiposity and resistance to diet-induced obesity. Here we show that RIIβ knockout (KO) mice have enhanced sensitivity to leptin’s effects on both feeding and energy metabolism. After administration of a low dose of leptin, the duration of hypothalamic JAK/STAT3 signalling is increased, resulting in enhanced POMC mRNA induction. Consistent with the extended JAK/STAT3 activation, we find that the negative feedback regulator of leptin receptor signalling, Socs3, is inhibited in the hypothalamus of RIIβ KO mice. During fasting, RIIβ–PKA is activated and this correlates with an increase in CREB phosphorylation. The increase in CREB phosphorylation is absent in the fasted RIIβ KO hypothalamus. Selective inhibition of PKA activity in AgRP neurons partially recapitulates the leanness and resistance to diet-induced obesity of RIIβ KO mice. Our findings suggest that RIIβ–PKA modulates the duration of leptin receptor signalling and therefore the magnitude of the catabolic response to leptin.
Erratum: A molecular propeller effect for chiral separation and analysis
Authors: Clemens Jonathon B. , Kibar Osman , Chachisvilis Mirianas
Published: September 2015

Nature Communications 6: Article number: 7868 (2015); Published: 28 July 2015; Updated: 18 September 2015 The image in Supplementary Fig. 1 that accompanies this Article was incorrectly rendered while the Supplementary Information file was being prepared for publication. Supplementary Fig. 1 as it should have been published appears below.