bluuebunny/crossref_metadata_2025 huggingface dataset:
Climate–fire interactions constrain potential woody plant cover and stature in North American Great Plains grasslands
Authors: Scholtz R. , Fuhlendorf S. D. , Archer S. R.
Published: August 2018

Aim

Disturbances such as fire operate against a backdrop of constraints imposed by climate and soils to influence grass–woody plant abundance. However, little is known of how these factors interact to determine the upper limits of woody cover and stature in grasslands, in which shrub/tree abundance has been increasing globally.

Location

Kansas, Oklahoma, Texas, USA.

Time period

2004–2014.

Major taxa studied

Angiosperms and gymnosperms.

Methods

Using a database of 1,466 sites and quantile regression to derive precipitation‐based upper limits to woody cover and height within grasslands of the central/southern Great Plains, USA, we assessed how soil texture and climate‐related fire probabilities [two groups; low fire probability, P(Flow), versus high fire probability, P(Fhi)] might influence realization of the climate potential.

Results

Soil texture had no substantive influence on regional‐scale woody cover, but taller plants were predicted on sandy soils. Woody plant height potential increased linearly with increasing annual precipitation, becoming asymptotic at c. 800 mm for both the P(Flow) and the P(Fhi) fire groups, after which P(Flow) areas were predicted to support taller plants. Potential woody cover also increased linearly with annual precipitation until c. 800 mm, after which predictions of maximum % cover were similar under both fire groups.

Main conclusions

Precipitation was the overriding factor constraining potential woody cover and height, particularly in drier regions, with fire playing a minor role at these regional scales. In contrast to height potential, cover potential remained similar for both P(Flow) and P(Fhi) sites. Dynamic adjustments in woody plant architecture and allocation to foliage and stems, wherein areal cover is maintained when height is suppressed has implications for remote sensing, primary production and biogeochemical processes. Our analyses indicate drier grasslands [< 800 mm mean annual precipitation (MAP)] undergoing woody plant encroachment have the potential to become shrublands (e.g. short woody plants, low cover), whereas wetter areas have the potential to become woodland or forest (taller woody plants, high cover).
Haemophilia care in Latin America: Assessment and perspectives
Authors: Boadas Apsara , Ozelo Margareth C. , Solano Maria , Berges Adolfina , Ruiz‐Saez Arlette , Linares Adriana , Lamas José Luis , Aparicio Rafael , Aversa Luis , Baques Alejandra , Estrada Armando , Herrejon Misael , Mancia Ana , Nieves‐Paulino Rosa , Pinto Ieda , Prezoti Alessandra , Soto Verónica , Ugalde Dani
Published: August 2018

Introduction

The study is the first application of the Principles of Haemophilia Care for Europe (PHCE) in other regions of the world, specifically in Latin America.

Objective

To identify strengths in the care of haemophilia, and the aspects that should be improved.

Methods

The information was obtained through a questionnaire designed according to the PHCE and answered by specialists in mid‐2016. The countries included were as follows: Argentina, Brazil, Chile, Colombia, Costa Rica, El Salvador, Mexico, Panama, Dominican Republic and Venezuela.

Results

In most countries, there is a central organization for haemophilia care supported by local groups. The existence of a national registry of people with haemophilia (PWH) was verified in eight countries. Centres of integrated care are located in large cities. In the majority of countries, there was no evidence of the participation of multiple actors in the decision‐making. The supply of factor concentrates presents constraints, although it is reported as adequate in half of the countries. In most countries, home treatment is available under special conditions. In most countries, there are restrictions on the use of prophylaxis. The coordination of specialized and emergency services depends on each centre. Unrestricted treatment of inhibitors is performed in most countries. In all countries, there are human resources training programmes; however, clinical and health services researches are not widely developed.

Conclusion

The study identifies the initial situation of principles of care, as well as the alternatives that must be implemented to achieve improvements in the quality of life of PWH in the region.
High‐Volume Anesthetic Suboccipital Nerve Blocks for Treatment Refractory Chronic Cluster Headache With Long‐Term Efficacy Data: An Observational Case Series Study
Authors: Rozen Todd D.
Published: August 2018

Objective

To determine the efficacy of high‐volume anesthetic suboccipital nerve blocks (HVSON) for chronic cluster headache (CCH) and to define consistency of response over long‐term use.

Background

There are studies showing efficacy of greater occipital and suboccipital nerve block injections for CCH and also their possible use as a preventive treatment modality. There are scant data about the long‐term efficacy of repetitive greater occipital and suboccipital nerve injections in CCH. HVSON has not been studied for CH.

Methods

This was an open label, observational, case series study. Patients with CCH seen at a dedicated headache clinic over a 7‐year time period and injected on at least 2 separate occasions were used for analysis. All were deemed medicinal treatment refractory. HVSON consisted of 9 mL 1% lidocaine and 1 mL triamcinolone 40 mg/mL injected on the side of CH.

Results

Ten CCH patients were retrospectively studied. Range of mean average response to HVSON (all patients had complete pain freedom) was 1.5–31 weeks (longest: 44 weeks in 2 patients). Only one patient did not respond; 2 patients had 1.5–2 weeks of response; the remainder had at least 4 weeks of response. The mean average duration of effect was 10.3 weeks in the responders. Five patients were injected serially for 2–4 years (30x, 17x, 15x, 10x and 3x, respectively) with a consistent response of 6 weeks, 4 weeks, 12 weeks, 4 weeks, and 31 weeks, respectively, after each injection. Response duration was very reliable per individual patient. All 5 patients felt HVSON was effective as a preventive treatment. Smoking history did not appear to alter treatment response (8/10 were chronic current smokers and 7/8 responded to HVSON). The one patient who received the most injections developed avascular necrosis of the hip; the remainder of the subjects had no adverse events.

Conclusion

HVSON from this open label study appears to be effective in the preventive treatment of medicinal refractory CCH and shows consistent response over long‐term use with high rates of pain freedom.
Probiotic supplementation with Lactobacillus plantarum and Pediococcus acidilactici for Helicobacter pylori therapy: A randomized, double‐blind, placebo‐controlled trial
Authors: McNicholl Adrian G. , Molina‐Infante Javier , Lucendo Alfredo J. , Calleja José Luis , Pérez‐Aisa Ángeles , Modolell Inés , Aldeguer Xavier , Calafat Margalida , Comino Luis , Ramas Mercedes , Callejo Ángel , Badiola Carlos , Serra Jordi , Gisbert Javier P.
Published: August 2018

Objective

To evaluate the safety, tolerability and efficacy of a probiotic supplementation for Helicobacter pylori (H. pylori) eradication therapy.

Design

Consecutive adult naive patients with a diagnosis of H. pylori infection who were prescribed eradication therapy according to clinical practice (10‐day triple or nonbismuth quadruple concomitant therapy) randomly received probiotics (1 × 109 colony‐forming units each strain, Lactobacillus plantarum and Pediococcus acidilactici) or matching placebo. Side effects at the end of the treatment, measured through a modified De Boer Scale, were the primary outcome. Secondary outcomes were compliance with therapy and eradication rates.

Results

A total of 209 patients (33% triple therapy, 66% non‐bismuth quadruple therapy) were included [placebo (n = 106) or probiotic (n = 103)]. No differences were observed regarding side effects at the end of the treatment between groups (β −0.023, P 0.738). Female gender (P < 0.001) and quadruple therapy (P 0.007) were independent predictors of side effects. No differences in compliance were observed, regardless of the study group or eradication therapy. Eradication rates were similar between groups [placebo 95% (95% confidence interval (CI), 89% to 98%) vs probiotic 97% (95% CI, 92% to 99%), P 0.721]. There were no relevant differences in cure rates (>90% in all cases) between triple and quadruple concomitant therapy.

Conclusion

Probiotic supplementation containing Lactobacillus Plantarum and Pediococcus acidilactici to H. pylori treatment neither decreased side effects nor improved compliance with therapy or eradication rates.
Therapeutic potential of lenvatinib for unresectable hepatocellular carcinoma in clinical practice: Multicenter analysis
Authors: Hiraoka Atsushi , Kumada Takashi , Kariyama Kazuya , Takaguchi Koichi , Itobayashi Ei , Shimada Noritomo , Tajiri Kazuto , Tsuji Kunihiko , Ishikawa Toru , Ochi Hironori , Hirooka Masashi , Tsutsui Akemi , Shibata Hiroshi , Tada Toshifumi , Toyoda Hidenori , Nouso Kazuhiro , Joko Kouji , Hiasa Yoichi , Michitaka Kojiro ,   Real‐life Practice Experts for HCC (RELPEC) Study Group and the HCC 48 Group (hepatocellular carcinoma experts from 48 clinics in Japan)
Published: August 2018

Aim

Lenvatinib (LEN) has recently become available as a first‐line tyrosine‐kinase inhibitor (TKI) for unresectable hepatocellular carcinoma (u‐HCC). In patients who showed intolerability or failure in other TKI treatments, alternative treatment options are needed. This retrospective study evaluated the therapeutic potential of LEN in clinical practice.

Methods

We enrolled 57 u‐HCC patients treated with LEN from March to June 2018. Lenvatinib was given orally to patients weighing <60 kg at 8 mg/day and at 12 mg/day to those ≥60 kg. Following the exclusion of patients whose initial LEN dose was reduced, 49 patients were evaluated in regard to their characteristics and early therapeutic response using modified Response Evaluation Criteria in Solid Tumors for findings of follow‐up computed tomography (CT)/magnetic resonance imaging (MRI) examinations at 4 weeks after introducing LEN.

Results

The average patient age was 72.4 ± 9.3 years and 38 (77.6%) were men. The LEN dose was 8 and 12 mg in 32 and 17 patients, respectively. Twenty‐nine (59.2%) had history of treatment with sorafenib and six of them (20.7%) with regorafenib. Of the 49 patients, 27 were evaluated using findings obtained by enhanced CT/MRI at 4 weeks after introducing LEN. Partial response was shown in 11, stable disease in 12, and progressive disease in four (overall response rate [ORR], 40.7%; disease control rate [DCR], 85.2%). The ORR and DCR of TKI‐naïve patients (n = 8) were 50.0% and 87.5%, respectively, whereas those of TKI‐experienced patients (n = 19) were 36.8% and 84.2%, respectively (P = 0.675 and P = 1.00, respectively).

Conclusion

Early therapeutic response to LEN was favorable. This new TKI could have therapeutic potential both in patients with and without past TKI treatments.
TECHNOLOGY, POLICY DISTORTIONS, AND THE RISE OF LARGE FARMS
Authors: Cai Wenbiao
Published: August 2018

Between 1900 and 2002, mean farm size in the United States tripled; productive resources were increasingly concentrated in large farms. These observations are difficult to explain as results of profit maximization by farmers in a frictionless equilibrium model, given exogenous factor endowment and technology. I show that notable shifts in the farm size distribution coincided with important changes in farm legislation and that farm programs provided larger farms more subsidy per dollar of output produced. These farm‐level distortions are crucial for the increasing dominance of large farms but have little impact on employment and productivity in agriculture.
Obstructive sleep apnea, low transferrin saturation levels, and male‐pattern baldness
Authors: Baik Inkyung , Lee SeungKu , Thomas Robert J. , Shin Chol
Published: August 2018

Background

There are limited data on the association between obstructive sleep apnea (OSA), which is characterized by intermittent hypoxia, and male‐pattern baldness (MPB). Low blood iron levels are reportedly associated with hypoxia and hair loss. This study explored a possible link amongOSA, iron status, andMPB.

Methods

Polysomnography (PSG) and hair assessments were conducted in a cross‐sectional study including 932 men aged 46–76 years.OSAwas defined as an apnea‐hypopnea index ≥5 byPSGevaluation andMPBas scales fromIVtoVIIaccording to the Norwood‐Hamilton scale classification. Serum transferrin saturation (TSA) levels were assessed.

Results

A total of 224 men (24%) were identified asMPBcases and 495 men (53%) as havingOSA. After considering potential risk factors,OSAand other sleep‐related variables were not associated withMPB. In joint analysis ofOSAand family history of hair loss, men with these two factors showed a sevenfold higher multivariate odds ratio (95% confidence interval: 3.70, 12.56) forMPBthan those without both of them (P < 0.05 for the interaction betweenOSAand family history of hair loss).TSAlevels were significantly associated withMPBandOSA.OSAcases withoutMPBas well asMPBcases showed lowerTSAlevels than those with neitherOSAnorMPB(P < 0.05).

Conclusions

These findings suggest thatOSAmay be a risk factor forMPBin men who have a family history of hair loss and that low serumTSAlevels associated with hypoxia may be involved in a pathway linkingOSAandMPB.
mTORC1 activation in B cells confers impairment of marginal zone microarchitecture by exaggerating cathepsin activity
Authors: Meena Naresh Kumar , Pattanayak Shakti Prasad , Ben‐Nun Yael , Benhamron Sandrine , Kumar Saran , Merquiol Emmanuelle , Hövelmeyer Nadine , Blum Galia , Tirosh Boaz
Published: August 2018

Mammalian target of rapamycin complex 1 (mTORC1) is a key regulator of cell metabolism and lymphocyte proliferation. It is inhibited by the tuberous sclerosis complex (TSC), a heterodimer of TSC1 and TSC2. Deletion of either gene results in robust activation of mTORC1. Mature B cells reside in the spleen at two major anatomical locations, the marginal zone (MZ) and follicles. The MZ constitutes the first line of humoral response against blood‐borne pathogens and undergoes atrophy in chronic inflammation. In previous work, we showed that mice deleted for TSC1 in their B cells (TSC1BKO) have almost no MZ B cells, whereas follicular B cells are minimally affected. To explore potential underlying mechanisms for MZ B‐cell loss, we have analysed the spleen MZ architecture of TSC1BKO mice and found it to be severely impaired. Examination of lymphotoxins (LTα and LTβ) and lymphotoxin receptor (LTβR) expression indicated that LTβR levels in spleen stroma were reduced by TSC1 deletion in the B cells. Furthermore, LTα transcripts in B cells were reduced. Because LTβR is sensitive to proteolysis, we analysed cathepsin activity in TSC1BKO. A higher cathepsin activity, particularly of cathepsin B, was observed, which was reduced by mTORC1 inhibition with rapamycin in vivo. Remarkably, in vivo administration of a pan‐cathepsin inhibitor restored LTβR expression, LTα mRNA levels and the MZ architecture. Our data identify a novel connection, although not elucidated at the molecular level, between mTORC1 and cathepsin activity in a manner relevant to MZ dynamics.
Eu‐substitution‐induced commensurate phase with enhanced ferroelectric property in Ba4(EuxLa1−x)2Fe2Nb8O30 multiferroics
Authors: Hong Jiang Sheng , Huang Yu Hui , Wu Yong Jun , Fu Mao Sen , Li Juan , Liu Xiao Qiang
Published: August 2018

Effects of Eu‐substitution on the crystal structure, dielectric, ferroelectric, and magnetic properties have been systematically studied for Ba4(EuxLa1−x)2Fe2Nb8O30 (x = 0, 0.3, 0.5, 0.7, 0.9, 0.95, 1) tungsten bronze ceramics. The tetragonal bronze structure is confirmed in all compositions. With the increase of x, Ba4(EuxLa1−x)2Fe2Nb8O30 ceramics transform from paraelectric to ferroelectric. The compositions of x = 0.9, 0.95, and 1 show first‐order ferroelectric phase transitions above room temperature (391 K for x = 0.9, 404 K for x = 0.95, and 425 K for x = 1). The ferroelectric behavior is associated with a commensurate octahedral tilting, which is caused by large A2‐A1 ionic‐radius difference. Magnetic hysteresis loops for all compositions at room temperature have been obtained, which could be ascribed to both the secondary phase and tungsten bronze structure per se. It is confirmed that the radius difference between A2 and A1 cations plays a critical role on the structure, dielectric, and ferroelectric characteristics.
Laser‐induced coloration of ceramic tiles covered with magnetron sputtered precursor layers
Authors: Rico Víctor J. , Lahoz Ruth , Rey‐García Francisco , de Francisco Isabel , Gil‐Rostra Jorge , Espinós Juan Pedro , de la Fuente Germán F. , González‐Elipe Agustín R.
Published: August 2018

This paper reports a new methodology for the coloring of glazed ceramic tiles consisting of the near infrared pulsed laser processing of copper containing oxide coatings prepared by magnetron sputtering. As a second approach, the employ for the same purpose of a novel laser furnace technique is also described. Changing the laser parameters and using the laser furnace to treat the tiles at high temperature during irradiation has resulted in a wide color palette. The optical characterization of the modified tiles by UV‐Vis spectroscopy has been complemented with their microstructural and compositional analysis by Scanning Electron Microscopy (SEM), Transmission Electron Microscopy (TEM), and Time Of Flight Secondary Ion Mass Spectrometry (TOF‐SIMS). The chemical composition of the surface was obtained by X‐ray Photoemission Spectroscopy (XPS) and its structure determined by X?ray diffraction (XRD). The chemical resistance was characterized by several tests following the norm ISO 10545‐13. Color changes have been attributed to surface microstructural and chemical transformations that have been accounted for by simple models involving different ablation, melting, diffusion, and segregation/agglomeration phenomena depending on the laser treatments employed.
Employee‐friendly practices, product market competition and firm value
Authors: Chang Saeyoung , Jo Hoje
Published: August 2018

In this paper, we examine whether employee‐friendly practices are associated with product market competition, and whether firm value is related to employee‐friendly practices and product market competition. Using a large sample of US firms, we find positive and significant associations between employee friendliness and product market competition, and between firm value and employee friendliness when product market competition is high, consistent with the value creation theory. Both positive relations hold when we account for corporate governance. In addition, using the list of Fortune's ‘100 Best Companies to Work For’ as an alternative measure of employee‐friendly policies, we find firms in more competitive industries are more likely to treat their workers favourably. Furthermore, we find that the market reaction is more positive when firms in more competitive industries are selected for the Fortune list.
Is “chronic kidney disease” a disease?
Authors: Smart Benjamin T.H. , Stevens Richard J. , Verbakel Jan Y.
Published: August 2018

Several philosophers of medicine have attempted to answer the question “what is disease?” In current clinical practice, an umbrella term “chronic kidney disease” (CKD) encompasses a wide range of kidney health states from commonly prevalent subclinical, asymptomatic disease to rare end‐stage renal disease requiring transplant or dialysis to support life. Differences in severity are currently expressed using a “stage” system, whereby stage 1 is the least severe, and stage 5 the most. Early stage CKD in older patients is normal, of little concern, and does not require treatment. However, studies have shown that many patients find being informed of their CKD distressing, even in its early stages. Using existing analyses of disease in the philosophy literature, we argue that the most prevalent diagnoses of CKD are not, in fact, diseases. We conclude that, in many diagnosed cases of CKD, diagnosing a patient with a “disease” is not only redundant, but unhelpful.
Food searching behaviour in adult Atlantic codGadus morhuaduring acoustic training: social learning and leadership within a school
Authors: Björnsson Björn , Karlsson Hjalti , Macrander Andreas
Published: August 2018

Food searching behaviour in a group of individually tagged 1–5 kg Atlantic codGadus morhuawas studied in a set of three experiments in a sea cage with two underwater platforms, where restricted amounts of food was delivered several times per day during an acoustic training period. It tookc.1 week to train 20 naïve cod to associate low frequency (250 Hz) sound with food, whereas the training time was reduced to less than 2 days when 19 naïveG. morhuawere accompanied with one trained fish. The fish formed a school that cruised between the platforms in search of food. Usually, there was one leader in the school, a fish that swam faster, arrived first at the platforms and visited the platforms more frequently than other members of the school. The leader spent more energy on swimming but also received more food and grew faster than the rest of the fish. At the start of the experiments, the leaders were not larger than the average fish but always among the leanest ones in the group. The study reveals how social learning can facilitate the acoustic training in adultG. morhua, information that may be useful in finding ways to aggregate valuable fish species for environmentally friendly fishing and ranching.
Acyclovir inhibits Cyprinid herpesvirus 3 multiplication in vitro
Authors: Troszok Agnieszka , Kolek Ludmiła , Szczygieł Joanna , Wawrzeczko Joanna , Borzym Ewa , Reichert Michał , Kamińska Teresa , Ostrowski Tomasz , Jurecka Patrycja , Adamek Mikołaj , Rakus Krzysztof , Irnazarow Ilgiz
Published: August 2018

Cyprinid herpesvirus 3 (CyHV‐3), also known as koi herpesvirus (KHV), is an aetiological agent of a virulent and lethal disease in common and koi carp. In this study, we examined in vitro the anti‐CyHV‐3 activity of acyclovir (ACV), nucleoside analogue commonly used against human herpesviruses, as well as acyclovir monophospate (ACV‐MP). The cytotoxicity of theACVand theACV‐MPfor two common carp cell lines,CCB(Common carp brain) andKF1 (Koi carp fin 1), was determined by means ofMTTand crystal violet assays. In subsequent studies, the concentration of 66.67 μM was applied. TheACVand theACV‐MP(66.67 μM) inhibited a cytopathic effect (CPE) induced by the CyHV‐3 virus in theCCB(ACVby 66%,ACV‐MPby 58%) and theKF1 (ACVby 25%,ACV‐MPby 37%). The viral load measured by the means of TaqManqPCRwas reduced in a range of 67%–93% depending on the analogue, the cell line and the time of incubation. The expression of viral genes (ORF149,ORF3,ORF134 andORF78) inCCBcells infected with the CyHV‐3 was strongly downregulated within the range of 78%–91%. In summary, both theACVand theACV‐MPcan inhibit CyHV‐3 replication in vitro.
First examination of the Lough Neagh European eel (Anguilla anguilla) population for eel virus European, eel virus European X and Anguillid Herpesvirus‐1 infection by employing novel molecular techniques
Authors: McConville James , Fringuelli Elena , Evans Derek , Savage Paul
Published: August 2018

Lough Neagh is home to the largest wild‐caught European eel (Anguilla anguilla) commercial fishery in the EU, producing 14% of the EU catch and worth £3.2 million to the local economy. Viral infections have been suggested to play a contributory role in the decline of the worldwide eel stock, but previous studies of the Lough Neagh European eel population had not observed either acute or chronic viral signs. Eel virus European (EVE), Eel virus European X (EVEX) and Anguillid herpesvirus‐1 (HVA) have been detected throughout Europe and as the Lough Neagh eel fishery is supplemented by re‐stocking of eels from France, Spain and the United Kingdom and these viral infections may be asymptomatic, it is vital that the viral pathogen prevalence in the Lough is accurately determined. This study aimed to ascertain the presence of these viruses in the Lough Neagh European eel population by employing novel molecular techniques testing specifically for the presence of EVE, EVEX and HVA. No evidence was found of HVA infection, whereas EVE and EVEX were found, albeit at a very low prevalence.
Correlates of burnout among professionals working with people with intellectual and developmental disabilities
Authors: Finkelstein A. , Bachner Y. G. , Greenberger C. , Brooks R. , Tenenbaum A.
Published: August 2018

Background

Although burnout has been recognised as an important stress‐related problem among staff working with people with intellectual and developmental disabilities (IDD), literature on the subject is limited yet emerging. The aim of this study is twofold: (1) to evaluate the level of burnout within different professions working with IDD; (2) to examine the association between socio‐demographic, professional and organisational characteristics and burnout.

Method

One hundred ninety‐nine professionals working with people with IDD were enrolled in the study (66% response rate). Participants were recruited from several facilities that provide care for people with IDD of all ages, in the Jerusalem area and in other cities in central Israel. The anonymous questionnaires included valid and reliable measures of burnout, socio‐demographic variables, professional variables and organisational variables.

Results

Participants' mean age was 38.3 years, and most were women. There were no significant differences in burnout levels among the different professionals. Role ambiguity, perceived overload, care‐recipient group and job involvement were significant predictors of burnout. The model explained a high percentage (46.8%) of the observed variance.

Conclusions

Most of these predictors are organisational measures. These findings demonstrate that organisational variables are more significantly associated with burnout of staff working with people with IDD than the socio‐demographic factors or professional characteristics. Identifying and better understanding the specific factors associated with burnout among professionals working with IDD could facilitate unique intervention programs to reduce burnout levels in staff.
The catalytic function of the gephyrin‐binding protein IQSEC3 regulates neurotransmitter‐specific matching of pre‐ and post‐synaptic structures in primary hippocampal cultures
Authors: Früh Simon , Tyagarajan Shiva K. , Campbell Benjamin , Bosshard Giovanna , Fritschy Jean‐Marc
Published: August 2018

In dissociated neuronal cultures the absence of spatial and temporal cues causes the emergence of mismatched synapses, where post‐synaptic proteins of GABAergic synapses are in part apposed to glutamatergic pre‐synaptic terminals and vice versa. This mismatch offers an opportunity to study the mechanisms that regulate correct apposition of pre‐ and post‐synaptic elements. We report here that the IQ motif and Sec7 domain‐containing protein 3 (IQSEC3; BRAG3; synArfGEF) specifically regulates the mislocalization of GABAergic post‐synaptic density (PSD) proteins. Over‐expression of IQSEC3 constructs harboring mutations that ablate Sec7 domain or IQ motif function revealed that IQSEC3 catalytic activity is involved in the control of apposition between the GABAergic PSD and glutamatergic terminals. Neurons co‐expressing eGFP‐gephyrin with IQSEC3 Sec7 mutant displayed a drastically increased fraction of mismatched eGFP‐gephyrin clusters compared to other IQSEC3 constructs. Along with eGFP‐gephyrin, endogenous GABAA receptor cluster mismatching was increased by IQSEC3 Sec7 mutant over‐expression. Conversely, GFP‐PSD‐95 clusters were unaffected by over‐expression of any IQSEC3 construct. The GABAergic PSD mismatch phenotype was recapitulated by Arf6 dominant‐negative mutant over‐expression, suggesting that Arf6 activation by IQSEC3 is an essential step in this pathway. In addition, we provide biochemical evidence to confirm gephyrin/IQSEC3 interaction near the IQSEC3 IQ motif, which in turn binds calmodulin at low Ca2+ concentrations. Taken together, our findings identify a post‐synaptic protein which specifically regulates correct apposition of the GABAergic PSD to pre‐synaptic terminals.

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Amyloid oligomerization of the Parkinson's disease related protein α‐synuclein impacts on its curvature‐membrane sensitivity
Authors: Gallea José Ignacio , Ambroggio Ernesto E. , Vilcaes Aldo Alejandro , James Nicholas G. , Jameson David M. , Celej María Soledad
Published: August 2018

The amyloid aggregation of the presynaptic protein α‐synuclein (AS) is pathognomonic of Parkinson's disease and other neurodegenerative disorders. Physiologically, AS contributes to synaptic homeostasis by participating in vesicle maintenance, trafficking, and release. Its avidity for highly curved acidic membranes has been related to the distinct chemistry of the N‐terminal amphipathic helix adopted upon binding to appropriated lipid interfaces. Pathologically, AS populate a myriad of toxic aggregates ranging from soluble oligomers to insoluble amyloid fibrils. Different gain‐of‐toxic function mechanisms are linked to prefibrillar oligomers which are considered as the most neurotoxic species. Here, we investigated if amyloid oligomerization could hamper AS function as a membrane curvature sensor. We used fluorescence correlation spectroscopy to quantitatively evaluate the interaction of oligomeric species, produced using a popular method based on lyophilization and rehydration, to lipid vesicles of different curvatures and compositions. We found that AS oligomerization has a profound impact on protein‐lipid interaction, altering binding affinity and/or curvature sensitivity depending on membrane composition. Our work provides novel insights into how the formation of prefibrillar intermediate species could contribute to neurodegeneration due to a loss‐of‐function mechanism.

Open Practices

This article has received a badge for *Open Materials* because it provided all relevant information to reproduce the study in the manuscript. The complete Open Science Disclosure form for this article can be found at the end of the article. More information about the Open Practices badges can be found at https://cos.io/our-services/open-science-badges/.

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The S100B story: from biomarker to active factor in neural injury
Authors: Michetti Fabrizio , D'Ambrosi Nadia , Toesca Amelia , Puglisi Maria Ausiliatrice , Serrano Alessia , Marchese Elisa , Corvino Valentina , Geloso Maria Concetta
Published: August 2018

S100B is a Ca2+‐binding protein mainly concentrated in astrocytes. Its levels in biological fluids (cerebrospinal fluid, peripheral and cord blood, urine, saliva, amniotic fluid) are recognized as a reliable biomarker of active neural distress. Although the wide spectrum of diseases in which the protein is involved (acute brain injury, neurodegenerative diseases, congenital/perinatal disorders, psychiatric disorders) reduces its specificity, its levels remain an important aid in monitoring the trend of the disorder. Mounting evidence now points to S100B as a Damage‐Associated Molecular Pattern molecule which, when released at high concentration, through its Receptor for Advanced Glycation Endproducts, triggers tissue reaction to damage in a series of different neural disorders. This review addresses this novel scenario, presenting data indicating that S100B levels and/or distribution in the nervous tissue of patients and/or experimental models of different neural disorders, for which the protein is used as a biomarker, are directly related to the progress of the disease: acute brain injury (ischemic/hemorrhagic stroke, traumatic injury), neurodegenerative diseases (Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, multiple sclerosis), congenital/perinatal disorders (Down syndrome, spinocerebellar ataxia‐1), psychiatric disorders (schizophrenia, mood disorders), inflammatory bowel disease. In many cases, over‐expression/administration of the protein induces worsening of the disease, whereas its deletion/inactivation produces amelioration. This review points out that the pivotal role of the protein resulting from these data, opens the perspective that S100B may be regarded as a therapeutic target for these different diseases, which appear to share some common features reasonably attributable to neuroinflammation, regardless their origin.

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Improved metabolism and body composition beyond normal levels following gastric bypass surgery: a longitudinal study
Authors: Andersson D. P. , Dahlman I. , Eriksson Hogling D. , Bäckdahl J. , Toft E. , Qvisth V. , Näslund E. , Thorell A. , Rydén M. , Arner P.
Published: August 2018

Background

The cardiometabolic risk profile improves following bariatric surgery. However, the degree of improvement in relation to weight‐stable control subjects is unknown.

Objectives

To study the differences in cardiometabolic risk profile between formerly obese patients following Roux‐en‐Y gastric bypass (RYGB) surgery and control subjects.

Methods

Subjects undergoing RYGB and reaching a BMI <30 kg m−2 2 years postsurgery were matched with control subjects regarding age, sex and BMI. The following examinations were performed: insulin sensitivity measured by hyperinsulinaemic–euglycaemic clamp, insulin clearance, homeostatic model assessment of insulin resistance (HOMA‐IR), lipid profile, inflammatory marker levels, dual‐energy X‐ray absorptiometry and subcutaneous adipose tissue cellularity (fat cell size and number).

Results

Sixty‐nine subjects undergoing RYGB were matched to a control subject. Insulin sensitivity measured by hyperinsulinaemic–euglycaemic clamp, blood pressure, inflammatory status and glucose, triglyceride and HDL cholesterol levels were comparable to values of control subjects. However, HOMA‐IR (1.0 ± 0.5 vs. 1.3 ± 0.7, P = 0.005), insulin clearance (0.38 ± 0.08 vs. 0.34 ± 0.08 μL m−2 min−1, P < 0.0001) and circulating levels of insulin (31 ± 15 vs. 37 ± 17 pmol L−1, P = 0.008), total cholesterol (4.1 ± 0.7 vs. 4.8 ± 0.9 mmol L−1, P < 0.0001) and LDL cholesterol (2.1 ± 0.6 vs. 2.9 ± 0.8 mmol L−1, P < 0.0001) were improved beyond the levels in matched control subjects. Furthermore, formerly obese subjects had higher lean and lower fat mass as well as a more benign type of adipose cellularity (hyperplasia with many small fat cells) compared to control subjects.

Conclusions

Subjects who underwent RYGB and reached a postobese state demonstrated a beneficial body composition, slightly increased insulin sensitivity as indirectly measured by HOMA‐IR and higher insulin clearance, lower atherogenic lipid/lipoprotein levels and benign adipocyte morphology compared with control subjects who had never been obese. In line with previous results, our findings may in part explain why RYGB confers long‐term protection against metabolic complications.
Genes that make you fat, but keep you healthy
Authors: Loos R. J. F. , Kilpeläinen T. O.
Published: August 2018

Obesity prevalence continues to rise worldwide, posing a substantial burden on people's health. However, up to 45% of obese individuals do not suffer from cardiometabolic complications, also called the metabolically healthy obese (MHO). Concurrently, up to 30% of normal‐weight individuals demonstrate cardiometabolic risk factors that are generally observed in obese individuals, the metabolically obese normal weight (MONW). Besides lifestyle, environmental factors and demographic factors, innate biological mechanisms are known to contribute to the aetiology of the MHO and MONW phenotypes, as well. Experimental studies in animal models have shown that adipose tissue expandability, fat distribution, adipogenesis, adipose tissue vascularization, inflammation and fibrosis, and mitochondrial function are the main mechanisms that uncouple adiposity from its cardiometabolic comorbidities. We reviewed current genetic association studies to expand insights into the biology of MHO/MONW phenotypes. At least four genetic loci were identified through genome‐wide association studies for body fat percentage (BF%) of which the BF%‐increasing allele was associated with a protective effect on glycemic and lipid outcomes. For some, this association was mediated through favourable effects on body fat distribution. Other studies that characterized the genetic susceptibility of insulin resistance found that a higher susceptibility was associated with lower overall adiposity due to less fat accumulation at hips and legs, suggesting that an impaired capacity to store fat subcutaneously or a preferential storage in the intra‐abdominal cavity may be metabolically harmful. Clearly, more work remains to be done in this field, first through gene discovery and subsequently through functional follow‐up of identified genes.
“Obesity‐associated metabolic complications, the second wave of the tsunami” 14th Key Symposium
Authors: Vidal‐Puig A. , Enerback S.
Published: August 2018

Content List – 14th Key Symposium ‐ “Metabolic Complications of Obesity”.
Clinical Practices and Barriers to Best Practice Implementation of Psychologists Working with Adults with Intellectual Disability and Comorbid Mental Ill Health
Authors: Man Joyce , Kangas Maria , Trollor Julian , Sweller Naomi
Published: August 2018

Evidence‐based practice (EBP) has not been well established in the area of intellectual disability (ID) and comorbid mental ill health. Some attempts in the form of policies and practice guidelines have been made. The aim of this study was to investigate assessment practices of Australian psychologists working with adults from this specialist population and explore barriers to best practice implementation. One hundred and two psychologists completed a self‐report online survey exploring barriers to EBP implementation. Sixty‐one psychologists completed questions relating to their practice including diagnostic practices, application of special considerations, and use of specialist resources. Psychologists reported many assessment practices that were in line with current national and international guidelines including utilization of specialist assessment resources, interdisciplinary collaboration, and application of reasonable adjustments to standard practice to suit the needs of individuals with dual disabilities. However, the sample also reported a number of barriers to implementing best practice recommendations such as diagnostic issues, limited access, and awareness of clinical resources and limited access to mental health services. Findings from this study have implications for best practice guidelines and policies in how mental health services for individuals with IDs and their families are delivered in Australia. This includes facilitating collaboration between health and disability services, adequate training, and access to specialist resources and access to mental health services equipped to support the needs of this specialist population.
Real‐world impact of direct acting antiviral therapy on health‐related quality of life in HIV/Hepatitis C co‐infected individuals
Authors: Saeed Sahar , Moodie Erica E. M. , Strumpf Erin , Gill John , Wong Alexander , Cooper Curtis , Walmsley Sharon , Hull Mark , Martel‐Laferriere Valerie , Klein Marina B. ,   For the Canadian Co‐Infection Cohort Study Investigators
Published: August 2018

Clinical trial results of direct acting antivirals (DAAs) for the treatment of hepatitis C virus (HCV) have shown improvements in health‐related quality of life (HR‐QoL). However, the extent to which these results are broadly generalizable to real‐world settings is unknown. We investigated the real‐world impact of oral DAA therapy on HR‐QoL among individuals coinfected with HIV/HCV. We used data from the Canadian HIV/HCV Co‐Infection Cohort Study that prospectively follows 1795 participants from 18 centres. Since 2007, clinical, lifestyle, and HR‐QoL data have been collected biannually through self‐administered questionnaires and chart review. HR‐QoL was measured using the EQ‐5D instrument. Participants initiating oral DAAs, having at least one visit before treatment initiation and at least one visit after DAA treatment response was ascertained, were included. Successful treatment response was defined as a sustained viral response (SVR). Segmented multivariate linear mixed models were used to evaluate the impact of SVR on HR‐QoL, controlling for pretreatment trends. 227 participants met our eligibility criteria, 93% of whom achieved SVR. Before treatment, the EQ‐5D utility index decreased 0.6 percentage‐point/y (95% CI, −0.9, −0.3) and health state was constant over time. The immediate effect of SVR resulted in an increase of 2.3‐units (−0.1, 4.7) in patients’ health state and 2.0 percentage‐point increase (−0.2, 4.0) in utility index. Health state continued to increase post‐SVR by 1.4 units/y (−0.9, 3.7), while utility trends post‐SVR plateaued over the observation period. Overall using real‐world data, we found modest improvements in HR‐QoL following SVR, compared to previously published clinical trials.
Medical costs associated with chronic kidney disease progression in an Asian population with type 2 diabetes mellitus
Authors: Low Serena , Lim Su C , Zhang Xiao , Wang Jiexun , Yeo Su J D , Yeoh Lee Y , Liu Yan L , Subramaniam Tavintharan , Sum Chee F
Published: August 2018

Aim

We aim to examine difference in incremental direct medical costs between non‐progressive and progressive chronic kidney disease (CKD) in type 2 diabetes mellitus (T2DM) in Singapore.

Methods

This was a prospective study on 676 patients with T2DM attending a diabetes centre in a regional hospital. Annual direct medical costs were extracted from the administrative database. Ordinary least squares regression was used to estimate contribution of CKD progression to annual costs, adjusting for demographics and baseline clinical covariates.

Results

Over mean follow‐up period of 2.8 ± 0.4 years, 266 (39.3%) had CKD progression. The excess total follow‐up medical costs from baseline was S$4243 higher in progressors compared to non‐progressors (P = 0.002). The mean cost differential between the two groups increased from S$2799 in Stages G1–G2 to S$11180 in Stage G4. Inpatient cost accounted for 63.4% of total cost of progression. When stratified by glomerular filtration rate stages, the respective total mean annual costs at stages glomerular filtration rate Stages G3a–G3b and G4 were S$3290 (132%; P = 0.001) and S$4416 (135%; P = 0.011) higher post‐progression.

Conclusion

Chronic kidney disease progression in T2DM is associated with high medical costs. The cost of progression is higher with higher severity of CKD stage at baseline and could be largely driven by inpatient admission.
The price of safety: food deprivation in early life influences the efficacy of chemical defence in an aposematic moth
Authors: Burdfield‐Steel Emily , Brain Morgan , Rojas Bibiana , Mappes Johanna
Published: August 2018

Aposematism is the combination of a primary signal with a secondary defence that predators must learn to associate with one another. However, variation in the level of defence, both within and between species, is very common. As secondary defences influence individual fitness, this variation in quality and quantity requires an evolutionary explanation, particularly as it may or may not correlate with variation in primary signals. The costs of defence production are expected to play a considerable role in generating this variation, yet studies of the cost of chemical defence have focused on species that sequester their defences, while studies in species that produce them de novo are scarce. Here we examine effects of resource availability on the production of chemical defences in female wood tiger moths Arctia plantaginis. This species produces defensive fluids when attacked, and advertises this protection with bright colours on its hindwings. Furthermore, the chemicals in these fluids are produced de novo. In order to establish if the production of this chemical protection is costly, and thus resource‐limited, we manipulated resource availability (i.e. food) during larval development and measured its subsequent effects on adult chemical defence. We presented defensive fluids from female moths to wild blue tits, in the absence of any visual cues, to determine their effectiveness against avian predators. Our results demonstrate that the defensive fluids produced by female moths repel birds, and that these defences require resource investment to produce. We found that moths that were resource‐limited during development had less effective chemical defences, despite producing the same volume of defensive fluids as the control moths. As a reduction in available resources negatively influences the effectiveness of the chemical defence, resource availability may explain the variation seen among individuals.
Rejecting Supererogationism
Authors: Tarsney Christian
Published: August 2018

Even if I think it very likely that some morally good act is supererogatory rather than obligatory, I may nonetheless be rationally required to perform that act. This claim follows from an apparently straightforward dominance argument, which parallels Jacob Ross's argument for ‘rejecting’ moral nihilism. These arguments face analogous pairs of objections that illustrate general challenges for dominance reasoning under normative uncertainty, but (I argue) these objections can be largely overcome. This has practical consequences for the ethics of philanthropy – in particular, it means that donors are often rationally required to maximize the positive impact of their donations.
Identification and validation of number of pod ‐ and seed ‐ related traits QTLs in soybean
Authors: Li Candong , Zou Jianan , Jiang Hongwei , Yu Jingyao , Huang Shiyu , Wang Xinyu , Liu Chunyan , Guo Tai , Zhu Rongsheng , Wu Xiaoxia , Hu Zhenbang , Wang Zhixin , Zheng Wei , Zhang Zhenyu , Zhao Haihong , Wang Nannan , Cheng Chunguang , Xin Dawei , Chen Qingshan , Qi Zhaoming
Published: August 2018

Traits related to the number of pods and seeds are important yield factors on soybean. The relationships between phenotype and quantitative trait loci (QTLs) of these traits may reveal the mechanisms underlying productivity. Our study objectives were to analyse phenotypic correlations, detect stable QTLs and identify candidate genes useful for marker‐assisted selection. Phenotypic analyses revealed that NThSP (number of three‐seeded pods) was positively correlated with NPPP (number of pods per plant) and SNPP (number of seeds per plant). Seventy‐five QTLs were identified based on the mean phenotypic data for at least 2 years. We detected two to 15 and one to three significant QTLs identified at the same location, respectively. Six consensus QTLs associated with at least two NPS‐related (number of pods and seeds related) traits were identified. Two of these were verified in another population. The QTLs for NPPP, SNPP and NThSP formed a consensus QTL cluster on GM02. Another 27 QTLs also formed clusters in five regions. Fifteen candidate genes were mined and discussed. The results will provide more information to soybean breeding.