bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of CYP3A5 genotype on tolvaptan pharmacokinetics and their relationships with endogenous markers of CYP3A activity and serum sodium level in heart failure patients
Authors: Hoshikawa Kohei , Naito Takafumi , Akutsu Shunta , Saotome Masao , Maekawa Yuichiro , Kawakami Junichi
Published: October 2019

Tolvaptan efficacy for heart failure has a large interindividual variation. This study aimed to evaluate the influence of CYP3A5 and ABCB1 genotypes on tolvaptan pharmacokinetics and their relationships with plasma markers of CYP3A activity and laboratory test values in heart failure patients. Fifty‐eight heart failure patients receiving oral tolvaptan for volume overload were enrolled. Blood samples for determination of pre‐dose plasma concentrations of tolvaptan and its metabolites were collected. CYP3A5 and ABCB1 genotypes, plasma 4β‐hydroxycholesterol/total cholesterol ratio (4β‐OHC/TC) and 25‐hydroxyvitamin D (25‐OHD), and serum laboratory test values were evaluated. The CYP3A5*3/*3 genotype was associated with a higher plasma concentration of tolvaptan but not with its metabolic ratios. The ABCB1 3435C > T, 2677G > T/A and 1236C > T polymorphisms affected neither tolvaptan pharmacokinetics nor its metabolism. Plasma 4β‐OHC/TC and 25‐OHD concentration were not correlated with plasma tolvaptan concentration. In a stratified analysis based on CYP3A5 genotype, plasma 4β‐OHC/TC had a negative correlation with plasma tolvaptan concentration in the patients with the CYP3A5*1 allele, while the plasma concentration of 25‐OHD did not. The CYP3A5*3/*3 genotype was associated with a higher serum sodium level in the patients with volume overload. The plasma concentration of 25‐OHD had a positive correlation with the serum total bilirubin level. In conclusion, CYP3A5*3 but not ABCB1 genotypes elevated tolvaptan plasma exposure in heart failure patients. CYP3A5‐deficient patients treated with tolvaptan had a higher serum sodium level. The CYP3A5 genotype altered the relationship between plasma tolvaptan and 4β‐OHC.
Long‐lasting correction of in vivo LTP and cognitive deficits of mice modelling Down syndrome with an α5‐selective GABAA inverse agonist
Authors: Duchon Arnaud , Gruart Agnès , Albac Christelle , Delatour Benoît , Zorrilla de San Martin Javier , Delgado‐García José María , Hérault Yann , Potier Marie‐Claude
Published: October 2019

Background and Purpose

Excessive GABAergic inhibition contributes to cognitive dysfunctions in Down syndrome (DS). Selective negative allosteric modulators (NAMs) of α5‐containing GABAA receptors such as the α5 inverse agonist (α5IA) restore learning and memory deficits in Ts65Dn mice, a model of DS. In this study we have assessed the long‐lasting effects of α5IA on in vivo LTP and behaviour in Ts65Dn mice.

Experimental Approach

We made in vivo LTP recordings for six consecutive days in freely moving Ts65Dn mice and their wild‐type littermates, treated with vehicle or α5IA. In parallel, Ts65Dn mice were assessed by various learning and memory tests (Y maze, Morris water maze, or the novel object recognition) for up to 7 days, following one single injection of α5IA or vehicle.

Key Results

LTP was not evoked in vivo in Ts65Dn mice at hippocampal CA3‐CA1 synapses. However, this deficit was sustainably reversed for at least six consecutive days following a single injection of α5IA. This long‐lasting effect of α5IA was also observed when assessing working and long‐term memory deficits in Ts65Dn mice.

Conclusion and Implications

We show for the first time in vivo LTP deficits in Ts65Dn mice. These deficits were restored for at least 6 days following acute treatment with α5IA and might be the substrate for the long‐lasting pharmacological effects of α5IA on spatial working and long‐term recognition and spatial memory tasks. Our results demonstrate the relevance of negative allosteric modulators of α5‐containing GABAA receptors to the treatment of cognitive deficits associated with DS.
Food‐induced anaphylaxis in infancy compared to preschool age: A retrospective analysis
Authors: Pouessel Guillaume , Jean‐Bart Charlotte , Deschildre Antoine , Van der Brempt Xavier , Tanno Luciana Kase , Beaumont Pascale , Dumond Pascale , Sabouraud‐Leclerc Dominique , Beaudouin Etienne , Ramdane Nassima , Liabeuf Valérie , Renaudin Jean‐Marie ,   on behalf of the Allergy Vigilance Network
Published: October 2019

Objective

Little is known regarding food anaphylaxis in infancy. We aimed to describe specificities of food anaphylaxis in infants (≤12 months) as compared to preschool children (1‐6 years).

Methods

We conducted a retrospective study of all food anaphylaxis cases recorded by the Allergy Vigilance Network from 2002 to 2018, in preschool children focusing on infants.

Results

Of 1951 food anaphylaxis reactions, 61 (3%) occurred in infants and 386 (20%) in preschool children. Two infants had two anaphylaxis reactions; thus, we analyzed data among 59 infants (male: 51%; mean age: 6 months [SD: 2.9]); 31% had a history of atopic dermatitis, 11% of previous food allergy. The main food allergens were cow's milk (59%), hen's egg (20%), wheat (7%) and peanut (3%) in infants as compared with peanut (27%) and cashew (23%) in preschool children. Anaphylaxis occurred in 28/61 (46%) cases at the first cow's milk intake after breastfeeding discontinuation. Clinical manifestations were mainly mucocutaneous (79%), gastrointestinal (49%), respiratory (48%) and cardiovascular (21%); 25% of infants received adrenaline. Hives, hypotension and neurologic symptoms were more likely to be reported in infants than in preschool children (P = .02; P = .004; P = .002, respectively). Antihistamines and corticosteroids were more often prescribed in preschool children than in infants (P = .005; P = .025, respectively).

Conclusion

Our study found that in infants presenting with their first food allergy, in a setting with a high rate of infant formula use, the most predominant trigger was cow's milk. As compared to older preschool children, hives, hypotonia and hypotension were more likely to be reported in infants. We believe that this represents a distinct food anaphylaxis phenotype that can further support developing the clinical anaphylaxis criteria in infants.
Automatic three‐dimensional analysis of bone volume and quality change after maxillary sinus augmentation
Authors: Kwon Jin‐Ju , Hwang JaeJoon , Kim Yong‐Deok , Shin Sang‐Hun , Cho Bong‐Hae , Lee Jae‐Yeol
Published: October 2019

Introduction

Maxillary sinus augmentation is a widely used surgical procedure to increase the bone volume before implant placement. In order to predict the stability of the implant, analysis of the change in bone volume and quality after a sinus graft procedure is necessary. The purpose of this study was to analyze the change in volume and quality of bone graft material after maxillary sinus augmentation using cone beam computed tomography (CBCT).

Methods and Materials

Maxillary sinus lift procedures using bovine bone materials (Bio‐Oss, Geistrich, Swiss) without immediate implantation were performed at the Pusan National University Dental Hospital in 22 patients, from 2014 to 2017. CBCT images were captured before surgery (T1), a day after surgery (T2), and after 4 to 7 months at follow‐up (T3). The T2 and T3 images were registered to the T1 image using histogram matching and intensity‐based registration. A total of 30 sinuses were analyzed three‐dimensionally (3‐D), using self‐made software MATLAB 2018a (MathWorks, Natick, Massachusetts). The volume and structural indices of the bone graft material were measured and analyzed.

Results

The average volume of graft material showed a decrease, while the average gray value showed an increase during the follow‐up period, but these changes were not statistically significant. The structural indices of the graft material after histogram matching showed a significant difference in homogeneity, connectivity, thickness, and roughness at the postoperative follow‐up.

Conclusions

The volume and gray value showed no statistically significant changes after the maxillary sinus lift procedures. The results of this study show that structural analysis using histogram matching can be used as a promising tool to analyze the quality of graft materials.
Early elevated neutrophil‐to‐lymphocyte ratio associated with remote diffusion‐weighted imaging lesions in acute intracerebral hemorrhage
Authors: Li Jia‐Wen , Xu Yu‐Yu , Chen Ye‐Jun , Fan Wei‐Wei , Xu Xu‐Hua , Cai Jin‐Song , Tong Lu‐Sha , Gao Feng
Published: October 2019

Aims

To explore the relationship between the circulating neutrophil‐to‐lymphocyte ratio (NLR) and the remote diffusion‐weighted imaging lesions (R‐DWILs) after spontaneous intracerebral hemorrhage (ICH).

Methods

Consecutive patients with spontaneous ICH were prospectively collected from November 2016 to May 2018 and retrospectively analyzed. We included subjects who presented within 24 hours after symptom onset and were free of detectable infections on admission or in hospital. Blood samples were obtained at 24‐48 hours after ICH ictus, while all complete MRI scans were performed at 5‐8 days. R‐DWILs were defined as focal hyperintensities remote from the site of the ICH or the peri‐hematoma regions. NLR was calculated by dividing the absolute neutrophil counts by the absolute lymphocyte counts. Multivariate binary logistic regression models were generated to evaluate the relationship between NLR and R‐DWILs.

Results

One hundred sixty‐three subjects met eligibility criteria (age 62.3 ± 13.6 years, 60.7% males), of whom 31(19.0%) experienced R‐DWILs. Higher circulating NLR was documented in patients with R‐DWILs. With the best cutoff value of 6.01, elevated NLR was independently associated with the presence of R‐DWILs (OR = 3.170, 95% CI 1.306‐7.697, P = .011) in the bivariate logistic regression analysis with adjustment for age, sex, atrial fibrillation, previous ischemic stroke/TIA, SBP on admission, hematoma volume, and IVH.

Conclusions

This study provides significant evidence of the association between circulating NLR and R‐DWILs in spontaneous ICH patients. Patients with NLR > 6.01 at 24‐48 hours after ICH ictus should be paid more attention to when evaluating R‐DWILs.
Does board gender diversity influence voluntary disclosure of intellectual capital in initial public offering prospectuses? Evidence from China
Authors: Nadeem Muhammad
Published: October 2019

Research question/issue

Using a multitheoretic view of boards, this study examines the impact of boardroom gender diversity (BGD) on voluntary intellectual capital (IC) disclosure in initial public offering (IPO) prospectuses in China—the world's second‐biggest economy, which is moving from a planned economy to a market‐oriented one. Furthermore, this study also investigates the impact of family ownership on the relationship between BGD and IC disclosure in the Chinese environment, which is characterized by less‐developed corporate governance mechanisms.

Research findings/insights

Based on a comprehensive content analysis of Chinese IPO prospectuses between 2009 and 2017 and measuring disclosure index at 78 dimensions under six broad categories of IC, the empirical results document (a) a significant positive relation between BGD and IC disclosure—in line with resource dependence theory, (b) a significant negative impact of female independent directors on IC disclosure—opposite to agency theory predictions, and that (c) the BGD–IC disclosure relationship is generally stronger for firms with two or more women on boards—in line with critical mass theory in China. Finally, this study also reveals that family ownership has adverse impacts on the BGD–IC disclosure relationship. These results are robust to a battery of sensitivity analyses.

Practitioner/policy implications

This study provides positive capital market implications of BGD through enhanced IC disclosure in IPO prospectuses. In doing so, the study has important implications for regulators and top management teams in devising policies concerning female representation on boards and voluntary disclosure of IC to inform the market participants of the true value of the company.
Long‐term outcomes with oral therapy in liver transplant recipients with hepatitis B
Authors: Saab Sammy , Song Dana , Challita Youssef P. , Xiwen Zhou Tina , Saab Elena G. , Viramontes Matthew R. , Choi Gina , Durazo Francisco A. , Han Steven B. , El Kabany Mohammed M. , Jackson Nicholas J. , Busuttil Ronald W.
Published: October 2019

Background

The long‐term impact of oral hepatitis B antiviral therapy in liver transplant (LT) recipients is currently underexplored. The objective of this study was to evaluate how oral antiviral agents impact long‐term renal function in this population.

Methods

We studied 79 patients who received a LT for hepatitis B and were placed on all‐oral antiviral therapy after withdrawing from hepatitis B immune globulin therapy at the University of California, Los Angeles. Laboratory data were obtained through a retrospective chart review. Univariate analysis and two‐sided t tests were performed.

Results

The mean (±SD [standard deviation]) age at the time of LT was 65.4 (± 8.2) years. The overall mean (±SD) follow‐up from LT was 6.5 (±3.3) years. 22.8% (18/79) of recipients on all‐oral therapy had worsening of their chronic kidney disease stage, and 17.7% (14/79) had an increase in creatinine of at least 0.3 mg/dL. There were no significant changes in creatinine and GFR in patients while on tenofovir alafenamide. Patient survival was decreased for recipients who developed detectable HBsAg.

Conclusion

Tenofovir alafenamide appears to have less of an impact on renal function in LT recipients than other antiviral agents. HBV recurrence after transplant is associated with decreased patient survival and remains an important issue to address for LT recipients on oral antiviral therapy.
Safety, Tolerability, Pharmacokinetics, Target Occupancy, and Concentration‐QT Analysis of the Novel BTK Inhibitor Evobrutinib in Healthy Volunteers
Authors: Becker Andreas , Martin Emily C. , Mitchell David Y. , Grenningloh Roland , Bender Andrew T. , Laurent Julien , Mackenzie Harald , Johne Andreas
Published: October 2019

Bruton's tyrosine kinase (BTK) is a key regulator of B cell receptor and Fc receptor signaling, and a rational therapeutic target for autoimmune diseases. This first‐in‐human phase I, double‐blind, placebo‐controlled trial investigated the safety, tolerability, pharmacokinetics (PK), target occupancy, and effects on QT interval of evobrutinib, a highly selective, oral inhibitor of BTK, in healthy subjects. This dose escalation trial consisted of two parts. Part 1 included 48 subjects in 6 ascending dose cohorts (25, 50, 100, 200, 350, and 500 mg) randomized to a single dose of evobrutinib or placebo. Part 2 included 36 subjects in 3 ascending dose cohorts (25, 75, and 200 mg/day) randomized to evobrutinib or placebo once daily for 14 days. Safety and tolerability, as well as PK and target occupancy (total and free BTK in peripheral blood mononuclear cells), were assessed following single and multiple dosing. PK parameters were determined by noncompartmental methods. QT interval was obtained from 12‐lead electrocardiogram recordings and corrected for heart rate by Fridericia's method (QTcF). Treatment‐emergent adverse events (TEAEs) were mostly mild, occurring in 25% of subjects after single dosing, and 48.1% after multiple dosing. There was no apparent dose relationship regarding frequency or type of TEAE among evobrutinib‐treated subjects. Absorption was rapid (time to reach maximum plasma concentration (Tmax) ~ 0.5 hour), half‐life short (~ 2 hours), and PK dose‐proportional, with no accumulation or time dependency on repeat dosing. BTK occupancy was dose‐dependent, reaching maximum occupancy of > 90% within ~ 4 hours after single doses ≥ 200 mg; the effect was long‐lasting (> 50% occupancy at 96 hours with ≥ 100 mg). After multiple dosing, full BTK occupancy was achieved with 25 mg, indicating slow turnover of BTK protein in vivo. Concentration‐QTcF analyses did not show any impact of evobrutinib concentration on corrected QT (QTc). In summary, evobrutinib was well‐tolerated, showed linear and time‐independent PK, induced long‐lasting BTK inhibition, and was associated with no prolongation of QT/QTc interval in healthy subjects. Evobrutinib is, therefore, suitable for investigation in autoimmune diseases.
Body size, but not age‐at‐maturation or context, affects the expression of predator‐induced behavioural plasticity in female green swordtails (Xiphophorus hellerii)
Authors: DiSciullo Rachael A. , Basolo Alexandra L.
Published: October 2019

Behavioural plasticity is a form of reversible phenotypic plasticity in which a genotype can express different behavioural phenotypes under different environmental conditions. Though an interest in among‐individual differences in behavioural plasticity has flourished in recent decades, few studies have considered the effects of intrinsic factors, such as life‐history or morphological traits, in tandem with extrinsic factors, such as presence of conspecifics in different social contexts, on predator‐induced behavioural plasticity. Here, we present a study conducted with female green swordtail fishes, Xiphophorus hellerii, designed to assess the effects of age‐at‐maturation and body size on the expression of predator‐induced behavioural plasticity in two social contexts: (a) female‐only (two females) and (b) female‐and‐male (two females and a male). We further examined the extent to which individual expression of behavioural plasticity is consistent across these two social contexts. We found that in the presence of a predator, focal females were more timid in response to the stimulus and more tolerant of the non‐focal female, and small females expressed this change from bold/less tolerant to timid/more tolerant to a greater degree than large females, regardless of age‐at‐maturation. However, individuals were not consistent in the degree or direction of plasticity expressed in the behaviours of interest between the female‐only and the female‐and‐male context. Here, we show that within‐ and among‐individual differences in behavioural expression are common but inconsistent. How intrinsic and extrinsic factors independently or together drive expression of plasticity in antipredator and agonistic behaviours is varied and warrants further study.
A selective and low impacting traditional fishery, sustaining the economy of small coastal villages in central Mediterranean: Keep or replace the small‐scale driftnets?
Authors: Sartor Paolo , Carbonara Pierluigi , Cerasi Sandro , Lembo Giuseppe , Facchini Maria Teresa , Lucchetti Alessandro , Sabatella Rosaria Felicita , Musumeci Claudia , Zupa Walter , Spedicato Maria Teresa
Published: October 2019

Small‐scale driftnets (SSDs) have been historically used in the Mediterranean without major environmental concern. The introduction of large‐scale driftnets caused unwanted catches of protected species. Specific regulations were therefore issued in European waters, culminating in a proposed moratorium on SSDs. This study aimed to characterise the SSD fishery targeting anchovy (menaide), evaluating its environmental sustainability, economic performance and social relevance. In 2013, a survey by interviews, logbooks and observers on board assessed the order of magnitude of this fishery in terms of fishing capacity and activity, volume of landings and revenues. The menaide fleet consisted in 60 vessels <12 m overall length, moored in little harbours in southern Italy. These nets are highly selective: the target species, European anchovy, Engraulis encrasicholus (L.) and sardine, Sardina pilchardus (Walbaum), dominates the catches, while discards are negligible. The anchovies caught are of high quality and large size; the high prices support fish processing by local factories. Moreover, the results of a SWOT analysis demonstrated that replacing SSDs with a semi‐industrial fishery, like purse seining, would increase impacts on the ecosystem, and a loss of socio‐economic opportunities for several coastal villages. These findings support the option of keeping SSDs operating, in the framework of specifically oriented management measures.
Riverine transport and nutrient inputs affect phytoplankton communities in a coastal embayment
Authors: Farrow Christopher R. , Ackerman Josef D. , Smith Ralph E. H. , Snider Dave
Published: October 2019

Rivers often transport phytoplankton to coastal embayments and introduce nutrients that can enrich coastal plankton communities. We investigated the effects of the Nottawasaga River on the nearshore (i.e. within 500 μm of shore) phytoplankton composition along a 10‐km transect of Nottawasaga Bay, Lake Huron in 2015 and 2016. Imaging flow cytometry was used to identify and enumerate algal taxa, which were resolved at sizes larger than small nanoplankton (i.e. >5 μm). Multivariate analysis (perMANOVA and redundancy analysis) and a dilution model were used to examine how nutrients and the transport of algal taxa affected community composition in the bay.

Sampling stations with different percentages of river water had significantly different phytoplankton communities. Phytoplankton community composition was also strongly associated with nutrients, including total phosphorus, which also varied with the percentage of river water. The majority of the 51 phytoplankton taxa identified in 2016 had numerical abundances in the bay that could be explained simply by the dilution of incoming river water.

Phytoplankton transported from the river had a higher proportion of edible‐sized cells (<30 μm), particularly in summer when colonial cyanobacteria were numerically dominant in the bay. Six taxa were more abundant than expected from the dilution of river water and included some cyanobacteria with late summer maxima. Five of the taxa that were transported from the river were less abundant than expected in the bay.

Whereas impacts of fertilisation due to the characteristically higher nutrient concentration in the river are to be expected, the strong and highly correlated effects of transport within the narrow coastal band of this study largely concealed any distinct fertilisation effects.

Riverine inputs may strongly influence the nearshore assemblage of phytoplankton in oligotrophic embayments in large lakes, creating hotspots for productivity, species turnover, and trophic dynamics.
Clarifying effect of different fining agents on mulberry wine
Authors: Ren Mengmeng , Liu Sudian , Li Ruilong , You Yilin , Huang Weidong , Zhan Jicheng
Published: October 2019

Fining experiments have been conducted on mulberry wine, in which five fining agents (bentonite, gelatin, casein, egg albumin and PVPP) were investigated. The effect of these agents on polyphenol content, colour intensity, antioxidant activity and aromatic profile has been determined. In general, all treatments improved the limpidity of the mulberry wines to some extent. The wine was mostly negatively affected by gelatin and led to the greatest reduction of phenol content (16.61%), colour intensity (32.26%) and antioxidant activity. Concerning aroma, the addition of PVPP, casein and bentonite both significantly altered the aroma profile. It is noteworthy that egg albumin led to the lowest diminution total phenol value (5.74%) and improvement of antioxidant capacity and colour among the tested fining agents. Furthermore, the aroma profile remained mostly unaffected by egg albumin. As consequence, the optimal fining agent for mulberry wine was egg albumin.
Noncontact temperature‐dependent fluorescence depicting phase transition in Nd3+‐doped (K0.5Na0.5)NbO3 ceramics
Authors: Wang Huajing , Deng Baoyu , Lin Cong , Wu Xiao , Cheng Yao , Lin Tengfei , Zheng Xinghua , Yu Xing
Published: October 2019

A noncontact temperature measurement technique based on fluorescence variation was used to depict the temperature‐dependent evolution of phase transition of a ferroelectric material, that is, Nd3+‐doped (K0.5Na0.5)NbO3 ceramics. The slope of the fluorescence intensity curve changes dramatically in the two temperature regions of 450‐475 K and 650‐675 K, which correspond to orthorhombic‐tetragonal and tetragonal‐cubic transitions as confirmed by the temperature dependence of dielectric constant. Furthermore, the small deviations in δTO‐T and δTc indicate the good accuracy of this noncontact method. This work can guide other ergodic ferroelectrics to describe phase experience by the noncontact fluorescence method.
Management of granulomatous foreign body reaction to fillers with methotrexate
Authors: Broly M. , Marie J. , Picard C. , Demoures A. , Raimbault C. , Beylot‐Barry M. , Cogrel O.
Published: October 2019

Background

Granulomatous foreign body reactions (GFBR) have been reported after injection with almost every soft tissue fillers, more commonly with non‐biodegradable ones. Such granulomatosis is rare but can cause significant discomfort owing to their aesthetic and functional repercussions.

Objective

To determine whether immunomodulation with low doses of methotrexate is effective in the treatment of GFBR to filler material.

Methods

Clinical case series of four patients with severe, treatment‐resistant GFBR to non‐biodegradable fillers in the Department of Dermatology of Bordeaux University Hospital, Bordeaux, France, successfully treated with oral or subcutaneous methotrexate, 10–15 mg weekly during 6 months. Adverse events were monitored throughout the treatment once weekly the first month then once monthly the remaining 5 months.

Results

Four women with a mean age of 73.7 years (66–85 years) and nodularity of the face were included and treated up to 6 months. Histological findings were consistent with GFBR to liquid injectable silicone in 2 cases, polymethylmethacrylate in 1 case and hydroxyethylmethacrylate in the last case. The delay after injection of the filler material was from 17 to 30 years. In one patient, inflammatory lesions followed dental care. After 6 months of treatment with 10–15 mg once weekly, all patients were cleared. Three patients developed a mild hepatic cytolysis (grade 1 or 2). Methotrexate could be maintained in those 3 cases and was discontinuated after 6 months in all cases. Two patients developed recurrence of lesions, 28 and 9 months, respectively, after treatment stops, requiring reintroduction of treatment. The two other patients remained cleared after 6 months of follow‐up.

Conclusion

Low doses of methotrexate appear to offer a low‐risk therapeutic alternative in resistant and severe GFBR to fillers. A prospective study with long‐term follow‐up is required to confirm these preliminary observations.
Caregiving in Crisis: Fatherhood Refashioned by Sierra Leone's Ebola Epidemic
Authors: McLean Kristen E.
Published: October 2019

In much of the literature on Sierra Leone, young men have been recognized for perpetrating violence or resisting authority. This characterization extended into the Ebola crisis, as young men were depicted as “resisting” public health measures. In contrast, little scholarship has focused on men's roles as caregivers during the epidemic. This article draws on ethnographic research conducted between 2014 and 2016 in eastern Sierra Leone to demonstrate how men contributed to caregiving. Findings reveal that when men were unable to care via established means, they improvised new ways to care for their families, which included: paid labor in Ebola treatment facilities; protecting their families from risk of infection; and hands‐on nurturing. By focusing on these diverse types of male caregiving, this article challenges the ways in which “care” and “women” are often neatly linked and calls for a rethinking of stereotypes associating African men with violence
Medical school expansion to areas of need improves physician distribution
Authors: O'Sullivan Belinda G. , Chater Bruce
Published: October 2019

Commenting on Figueiredo's exploration of national expansion policy, O'Sullivan and Chater further the discussion of what medical schools can contribute to the reduction of healthcare inequalities.
Advancing professionalism, attentive to culture, to improve health systems
Authors: Manning‐Cork Nick
Published: October 2019

This commentary explores how healthcare culture informs medical professionalism and health system improvement while also examining the educational implications of those relationships.
Are Intuitions Quasi‐Perceptual “Presentations”?
Authors: Deutsch Max
Published: October 2019

John Bengson has offered a detailed theory of the nature and epistemology of intuition according to which intuitions are quasi‐perceptual conscious experiences that “present” their contents as true. The paper offered here argues that Bengson’s terminology of “presentations” is difficult to interpret. Bengson does not provide a clear meaning for “presentation” or “presentational state,” and this makes it impossible to evaluate his proposal that intuitions are presentations. This paper argues, furthermore, that intuitions are not phenomenal mental states and therefore have no perception‐like phenomenology or epistemology. It concludes that Bengson’s theory fails to metaphysically, epistemologically, or methodologically legitimize intuitions.
Epistemic Rationality
Authors: Siegel Harvey
Published: October 2019

Many epistemologists and philosophers of science, especially those with “naturalist” inclinations, argue that if there is to be any such thing as normativity or rationality in these domains, it must be instrumental—roughly, a matter of goal satisfaction—rather than something involving normative “oughts” that are independent of the satisfaction of our epistemic, cognitive, or other ends. This paper argues that while such an instrumental conception of epistemic rationality is perfectly respectable, even insofar as it concerns specifically epistemic ends, it cannot be the whole story about such normativity. Rather, it must be accompanied by a “categorical,” goal‐independent sort of normativity that cannot be reduced to instrumental rationality, both because instrumental rationality itself depends on a noninstrumental relationship between a belief/claim/theory and the evidence that renders it rational, and because the epistemic rationality of many beliefs is independent of the goals of their believers.
The EIT Food School Network: Integrating solutions to improve eating habits and reduce food wastage in secondary schoolchildren
Authors: Capper T. , Brennan S. , Woodside J. , McKinley M.
Published: October 2019

Most European children and adolescents do not meet dietary guidelines. Therefore, there is a need to develop and implement effective strategies to help young people adopt healthier dietary habits and maintain these into adulthood. The amount of time that children and adolescents spend in the school setting makes this an ideal environment in which to develop interventions that target healthy eating. Schools, however, are complex systems and a whole‐school approach that promotes consistent messages within the school environment and across the curriculum is needed to support positive food choices. Given current concerns about climate change and the environment, it is also important to ensure that any nutrition interventions implemented in the school setting are environmentally friendly and do not increase food wastage. This paper presents the results of stakeholder discussions on the topic of secondary school food in Northern Ireland, conducted as part of the recently developed European Institute for Innovation and Technology (EIT) Food School Network. The Network was established to facilitate the exchange of information within existing national schools programmes and to identify and develop strategies that positively impact on food choice and food wastage in schools across Europe. Improving schools’ adherence to the Food in Schools Policy and engaging pupils and parents to encourage a sense of ‘ownership’ of the school food system were identified as potential ways to positively impact on the dietary habits of children and adolescents.
Quantification and characterization of vegetation and functional trait diversity of the riparian zones in protected forest of Kashmir Himalaya, India
Authors: Haq Shiek Marifatul , Malik Zubair A. , Rahman Inayat Ur
Published: October 2019

Globally, riparian zones along river banks are widely recognized for their vital role in water regulation and conservation of biodiversity. Here, we specifically investigated the floristic and functional diversity of the vegetation of the riparian zones of protected forests in Kashmir Himalaya, India. A random sampling method was used for site selection while a transect method was used for data collection. Data obtained from the field was subjected to taxonomic and functional classification. Floristic analysis revealed a total of 78 species belonging to 68 genera in 40 families, suggesting an unequal distribution of species among families. Nine families contributed half of the species: Rosaceae was the dominant family with nine (12%) species followed by Asteraceae with eight species (10%), while 23 families were monotypic. In terms of functional trait diversity, herbaceous and perennial taxa dominated, and the biological spectrum showed a dominance of the therophytic life form, indicative of disturbed vegetation. The phenological spectrum revealed that the maximum flowering periods starts in March and extends into May, in which a total of 61% of the species were observed to flower. The leading leaf size spectra were mesophyll with 35%, followed by microphyll (31%). Most (64%) of the species had a simple leaf lamina type. The results of the present study serve as a means to evaluate best management practices, assess restoration and mitigation projects, prioritize riparian related resource management decisions, and establish aquatic life use standards.
Grocery store access and childhood obesity: A systematic review and meta‐analysis
Authors: Li Yamei , Luo Miyang , Wu Xinyin , Xiao Qian , Luo Jiayou , Jia Peng
Published: October 2019

Grocery store is usually considered to be a healthy food outlet as it provides access to a variety of healthy food, such as fruits and vegetables, which may potentially improve overall dietary quality and protect against obesity. However, findings of the association between grocery store and childhood obesity are controversial. This study aimed to systematically review the evidence on the association between access to grocery stores and childhood obesity. A literature search was conducted in the PubMed, Embase, and Web of Science for articles published before January 1, 2019, using the combinations of three groups of keywords separately for grocery store, children and adolescents, and weight‐related behaviours and outcomes. A total of 27 cross‐sectional and eight longitudinal studies were identified. Controversial results existed among 24 studies, which examined the association between the access to grocery stores and weight‐related outcomes. A null association was observed in almost all meta‐analyses conducted by different measures of grocery stores and weight status, except the analysis between presence of grocery stores and overweight, which reached borderline significance. For weight‐related behaviours, mixed findings were reported between grocery stores and dietary behaviours, and no significant associations were found for physical activity. This systematic review and meta‐analysis suggested that access to grocery stores may have a rather small influence on child weight.
Effectiveness of clear aligner therapy for orthodontic treatment: A systematic review
Authors: Robertson Lindsay , Kaur Harsimrat , Fagundes Nathalia Carolina Fernandes , Romanyk Dan , Major Paul , Flores Mir Carlos
Published: October 2019

Objective

To analyse through a systematic review the effectiveness of clear aligners by assessing: (a) predictability of clear aligners and (b) treatment outcome comparison of clear aligner therapy with fixed appliance therapy.

Methods

An electronic search was made from January 2014 to April 2019 using MEDLINE, Embase, Web of Science and LILACS databases without any limitations on language. Three reviewers independently assessed the articles. Quality assessment of observational studies and randomized control trial was done by using the ROBINS tool and Cochrane risk of bias tool, respectively. GRADE instrument was used to assess certainty level for each identified outcome.

Results

Seven eligible articles (one randomized controlled trial and six retrospective cohort) were included in our systematic review. Most of the studies (six out of seven) had a moderate risk of bias and one had a high risk of bias.

Conclusions

‘Low to moderate level’ of certainty in regard to specific clear aligner therapy tooth movements’ efficiency was identified. Clear aligners may produce clinically acceptable outcomes that could be comparable to fixed appliance therapy for buccolingual inclination of upper and lower incisors in mild to moderate malocclusions. However, not all potential clinical scenarios have been assessed in the included studies. Most of the tooth movements may not be predictable enough to be accomplished with only one set of trays with clear aligners despite the recent advances in technology.
Production and Capacity Utilization Strategies in Supply Chains for Complex Engineered Products
Authors: Sinha Ashesh Kumar , Krishnamurthy Ananth
Published: October 2019

We analyze production and capacity utilization strategies in a supply chain where individual components can be made either at a shared in‐house manufacturing facility or at dedicated facilities of external subcontractors. The manufacturer and the subcontractor differ in terms of costs, production capacities, rates, and service level capabilities. Using Markov decision process models, we determine the optimal policy and characterize its structure. We derive the set of conditions that partitions the state space into regions and characterize optimal policies in each region. We derive optimal policies for manufacturer and subcontractors under different settings and show that the optimal policy has a multi‐index structure in some settings.
CO2 supplementation dissociates cerebral oxygenation and middle cerebral artery blood velocity during maximal cycling
Authors: Hansen Rasmus K. , Nielsen Peter S. , Schelske Markus W. , Secher Niels H. , Volianitis Stefanos
Published: October 2019

This study evaluated whether the reduction of prefrontal cortex oxygenation (ScO2) during maximal exercise depends on the hyperventilation‐induced hypocapnic attenuation of middle cerebral artery blood velocity (MCA Vmean). Twelve endurance‐trained males (age: 25 ± 3 years, height: 183 ± 8 cm, weight: 75 ± 9 kg; mean ± SD) performed in three separate laboratory visits, a maximal oxygen uptake (VO2max) test, an isocapnic (end‐tidal CO2 tension (PetCO2) clamped at 40 ± 1 mmHg), and an ambient air controlled‐pace constant load high‐intensity ergometer cycling to exhaustion, while MCA Vmean (transcranial Doppler ultrasound) and ScO2 (near‐infrared spectroscopy) were determined. Duration of exercise (12 min 25 s ± 1 min 18 s) was matched by performing the isocapnic trial first. Pulmonary VO2 was 90 ± 6% versus 93 ± 5% of the maximal value (P = .012) and PetCO2 40 ± 1 versus 34 ± 4 mmHg (P < .05) during the isocapnic and control trials, respectively. During the isocapnic trial MCA Vmean increased by 16 ± 13% until clamping was applied and continued to increase (by 14 ± 28%; P = .017) until the end of exercise, while there was no significant change during the control trial (P = .071). In contrast, ScO2 decreased similarly in both trials (−3.2 ± 5.1% and −4.1 ± 9.6%; P < .001, isocapnic and control, respectively) at exhaustion. The reduction in prefrontal cortex oxygenation during maximal exercise does not depend solely on lowered cerebral blood flow as indicated by middle cerebral blood velocity.
Brexit and the Politics of the Rural
Authors: Brooks Sally
Published: October 2019

This article uses Woods’ (2005) term ‘politics of the rural’ as a lens to trace connections between ‘Brexit’ and countryside protests that erupted in the late 1990s following the disruption of a century old political settlement for governing rural areas. Historically, the intertwining of rurality, hierarchy and empire in national identity has shielded rural elite interests and the power structures that uphold them from progressive political developments in urban areas. The article highlights how a new political party, the UK Independence Party (UKIP), was able to occupy a space opened by Countryside Alliance and subsequently vacated by a modernising Conservative Party, to build a movement shaped by a similar type of settler populism. How these broader dynamics interacted with local contexts to structure perceptions and experiences underpinning support for Brexit calls for more contextualised, region‐specific research. ‘Politics of the rural’ provides one lens among others to bring to these analyses.
The transcriptomic responses of C4 grasses to subambient CO2 and low light are largely species specific and only refined by photosynthetic subtype
Authors: Watson‐Lazowski Alexander , Papanicolaou Alexie , Koller Fiona , Ghannoum Oula
Published: October 2019

Three subtypes of C4 photosynthesis exist (NADP‐ME, NAD‐ME and PEPCK), each known to be beneficial under specific environmental conditions. However, the influence of photosynthetic subtype on transcriptomic plasticity, as well as the genes underpinning this variability, remain largely unknown. Here, we comprehensively investigate the responses of six C4 grass species, spanning all three C4 subtypes, to two controlled environmental stresses: low light (200 µmol m−2 sec−1) and glacial CO2 (subambient; 180 ppm). We identify a susceptibility within NADP‐ME species to glacial CO2. Notably, although glacial CO2 phenotypes could be tied to C4 subtype, biochemical and transcriptomic responses to glacial CO2 were largely species specific. Nevertheless, we were able to identify subtype specific subsets of significantly differentially expressed transcripts which link resource acquisition and allocation to NADP‐ME species susceptibility to glacial CO2. Here, low light phenotypes were comparable across species with no clear subtype response, while again, transcriptomic responses to low light were largely species specific. However, numerous functional similarities were noted within the transcriptomic responses to low light, suggesting these responses are functionally relatively conserved. Additionally, PEPCK species exhibited heightened regulation of transcripts related to metabolism in response to both stresses, likely tied to their C4 metabolic pathway. These results highlight the influence that both species and subtype can have on plant responses to abiotic stress, building on our mechanistic understanding of acclimation within C4 grasses and highlighting avenues for future crop improvements.
Phagosome‐endoplasmic reticulum contacts: Kissing and not running
Authors: Levin‐Konigsberg Roni , Grinstein Sergio
Published: October 2019

The role of the endoplasmic reticulum (ER) in phagocytosis has been the subject of debate for over a decade. Proteomic determinations and dynamic microscopy of live cells led to conflicting conclusions. Recent insights into the existence of a variety of membrane contact sites (MCS) may help reconcile the seemingly disparate views. Specifically, earlier results can be rationalized considering that the ER forms specialized MCS with nascent and maturing phagosomes, without undergoing fusion. The composition and function of documented ER‐to‐phagosome contact sites is described. In addition, we speculate about the possible existence of additional phagosomal contact sites, based on available knowledge of interactions between the ER and other endocytic compartments. The interaction between phagosomes and the ER has been the subject of debate. Earlier observations that led to the suggestion that the ER fuses with the phagosomal membrane can now be explained in the light of recent evidence that intimate contacts form between the two organelles.
Multilateral stability and efficiency of trade agreements: A network formation approach
Authors: Jorzik Nathalie , Mueller‐Langer Frank
Published: October 2019

We study the endogenous network formation of bilateral and multilateral trade agreements by means of hypergraphs and introduce the equilibrium concept of multilateral stability. We consider multicountry settings with a firm in each country that produces a homogeneous good and competes as a Cournot oligopolist in each market. Under endogenous tariffs, we find that a multilateral trade agreement governing the rules and norms of tariff setting, that is the WTO/GATT regime itself, together with a bilateral preferential trade agreement (PTA) is multilaterally stable. We also find that the existence of the WTO is necessary for the stability of the trading system. We further analyse the impact of PTAs on multilateral tariffs within the WTO. We find that the formation of PTAs increases countries' incentives for multilateral tariff reduction.
Aparición de exostosis 7 años después de aumento del reborde alveolar con técnica de bolsillo
Authors: Molano Valencia Pablo Emilio , Yepes Ramírez Bibiana Inés , Londoño Espinosa Claudia
Published: October 2019

Antecedentes: Las técnicas de manejo de tejidos blandos para aumentar rebordes alveolares atrofiados incluyen el uso de injertos de tejido conectivo, con o sin collar de epitelio, y técnicas en rollo. Algunas veces generan complicaciones posoperatorias. Objetivo: Describir el caso de una paciente a la que se le realizó aumento de reborde alveolar y se produjo una exostosis. Caso clínico: A una paciente de 35 años se le realizó un aumento del reborde alveolar con la técnica de bolsillo en el área del diente incisivo central superior derecho. Se tomó un injerto de tejido conectivo sin collar epitelial del paladar que se trasplantó y cubrió con el colgajo. La paciente regresó siete años después y clínicamente presentaba una aparente exostosis en la zona vestibular del diente tratado que la afectaba estéticamente. Se realizó osteoplastia para mejorar el contorno y se tomó una biopsia del hueso cuya histopatología mostró un tejido compatible con hueso alveolar. Conclusiones: La exostosis es una complicación posoperatoria inusual en casos de reborde alveolar que puede ser tratado con éxito. Se requiere más investigación sobre dichos efectos.
Nuevo aparato ortopédico fijo para el tratamiento de maloclusiones clase II división 1. Descripción de un caso
Authors: García Ramos Rosmery Cecilia
Published: October 2019

Antecedentes: La corrección temprana de las maloclusiones clase II asociadas a retrognatismo mandibular se logra mediante avance mandibular sostenido y continuo que no requiera colaboración del paciente. Objetivo: Describir un caso de maloclusión tratado con un nuevo arco de adelantamiento mandibular fijo (AAMF). Descripción del caso: El AAMF se usó en una paciente de 11 años y 6 meses, clase II esquelética división 1, con retrognatismo mandibular y mordida profunda. Resultados: Al año de tratamiento había cambios estéticos y funcionales. El ángulo ANB disminuyó (6,6° a 5,0°). La longitud efectiva mandibular (Co-Gn) aumentó (96,1 mm a 103,4 mm). La inclinación de incisivos superiores pasó de 28,0° a 28,4°. Los incisivos inferiores se proinclinaron levemente (26,2° a 30,9°). Las cefalometrías después de la fase de ortodoncia mostraron medidas esqueléticas estables: ANB pasó de 5,0° a 5,1° y Co-Gn se mantuvo en 103,4°. Hubo cambios en la posición de los incisivos: superiores retroinclinaron de 28,4° a 22,5° e incisivos inferiores pasaron de 30,9° a 28,2°. Conclusión: El AAMF representa una alternativa de tratamiento en denticiones mixta y permanente temprana: Por ser fijo, permite lograr avance mandibular sostenido y continuo, sin requerir colaboración del paciente, y durante el tiempo necesario para generar cambios. Por la sencillez de su estructura (maxilar cementado solo en los primeros molares maxilares), avanza la mandíbula sin fijarse a ella cada vez que el paciente cierra la boca. Además es sencillo de elaborar, cementar, activar, limpiar y mantener en boca.