bluuebunny/crossref_metadata_2025 huggingface dataset:
Older Adolescents’ Understanding of Participant Rights in the BlackBerry Project, a Longitudinal Ambulatory Assessment Study
Authors: Meter Diana J. , Ehrenreich Samuel E. , Carker Christopher , Flynn Elinor , Underwood Marion K.
Published: October 2019

For a long‐term, longitudinal study that used BlackBerry smartphones for passive ambulatory assessment among older adolescents, this study focused on three areas of ethical concern: (1) adolescents’ competence to give assent; (2) understanding of confidentiality, the protection of information, and project goals; and (3) awareness of procedures and benefits, and comfort with the research design. One hundred and seventy‐eight participants were 17 and 18 years old (84 girls). Results suggested that participants freely gave consent and understood most, but not all of the informed consent information. Participants reported a high level of satisfaction. Participants showed less understanding of when their confidentiality would be broken and how data would be protected.
The Practicalities and Perils of Ambulatory Assessment's Promise: Introduction to a Special Section
Authors: Modecki Kathryn Lynn , Goldberg Rachel E. , Ehrenreich Samuel E. , Russell Michael , Bellmore Amy
Published: October 2019

Ambulatory assessment (AA) offers one of the most exciting approaches for opening the dynamic “black box” of adolescents’ daily lives. In this introduction, we spotlightAA's surprisingly restricted market share within adolescent scholarship. We describe thorny challenges these intense methods can pose when conducting adolescent research “in situ” and underscore that capturing qualityAAdata means placing adolescents’ developmental stage at the forefront. The novel research reported in this special section speaks to these challenges and underscores the promise ofAAfor conducting developmentally salient science. The nine articles included in the section span multiple disciplines (Sociology, Psychology, Public Health) and reflect diverse viewpoints, approaches, and theories. All provide multiple novel best‐practice strategies for conductingAAscholarship with adolescents.
Why Digital Tools Have Not Yet Revolutionized Adolescent Health Research and What We Can Do
Authors: Odgers Candice L.
Published: October 2019

The promise of digital tools and devices for spurring new discoveries in adolescent health research is enticing. This special section draws attention to many of the advantages that mobile and wearable devices offer for ambulatory assessment research, which have now been realized. Despite such progress, digital tools have not yet delivered on their predicted revolution of adolescent health research. I offer four reasons for why digital devices have fallen short of this predicted promise. For each barrier, I suggest parallel strategies for ensuring adolescent research benefits from Ambulatory Assessment advances. To avoid missing out on opportunities to support young people, adolescence scholarship must develop in time with innovations in digital devices and platforms and move past what has, to date, been an overwhelming focus on fears about their usage.
Subsidy competition and imperfect labor markets
Authors: Morita Tadashi , Sawada Yukiko , Yamamoto Kazuhiro
Published: October 2019

This study presents a two‐country model of subsidy competition for manufacturing firms under labor market imperfections. Because subsidies affect the distribution of firms, subsidies influence unemployment rates and welfare in both countries. We show that when labor market frictions are high, subsidy competition is beneficial, although subsidies under subsidy competition are inefficiently high. In the coordinated equilibrium, the supranational authority provides a subsidy to firms that equal the expected total search costs, which increases the number of firms relative to laissez‐faire and improves welfare relative to laissez‐faire and subsidy competition. Finally, we find that a rise in a country's labor market frictions raises the equilibrium subsidy rate, affects unemployment rates, and lowers welfare.
In-vitro–in-silico investigation of the negative food effect of zolpidem when administered as immediate-release tablets
Authors: Paraiso Rafael Leal Monteiro , Watanabe Ayahisa , Andreas Cord J , Turner David , Zane Patricia , Dressman Jennifer
Published: October 2019

Objectives

The main objective of the present work was to combine in-vitro and in-silico tools to better understand the in-vivo behavior of the immediate release (IR) formulation of zolpidem in the fasted and fed states.

Methods

The dissolution of zolpidem was evaluated using biorelevant media simulating the gastric and intestinal environment in the fasted and fed states. Additionally, the influence of high viscosity and high fat content on the release of zolpidem under fed state conditions was investigated. The in-vitro results were combined with a physiologically based pharmacokinetic (PBPK) model constructed with Simcyp® to simulate the zolpidem pharmacokinetic profile in both prandial states.

Key findings

In vitro biorelevant dissolution experiments representing the fasted and fed states, combinedwith PBPKmodelling, were able to simulate the plasma profiles from the clinical food effect studies well. Experiments reflecting the pH and fat content of themeal led to a good prediction of the zolpidem plasma profile in the fed state, whereas increasing the viscosity of the gastricmedia led to an under-prediction.

Conclusions

This work demonstrates that the combination of biorelevant dissolution testing and PBPK modelling is very useful for understanding the in-vivo behavior of zolpidem in the fasted and fed states. This approach could be implemented in the development of other drugs exhibiting negative food effects, saving resources and bringing new drug products to the market faster.
Intra‐Annual Variability in Responses of a Canopy Forming Kelp to Cumulative Low Tide Heat Stress: Implications for Populations at the Trailing Range Edge
Authors: Hereward Hannah F. R. , King Nathan G. , Smale Dan A.
Published: October 2019

Anthropogenic climate change is driving the redistribution of species at a global scale. For marine species, populations at trailing edges often live very close to their upper thermal limits and, as such, poleward range contractions are one of the most pervasive effects of ongoing and predicted warming. However, the mechanics of processes driving such contractions are poorly understood. Here, we examined the response of the habitat forming kelp, Laminaria digitata, to realistic terrestrial heatwave simulations akin to those experienced by intertidal populations persisting at the trailing range edge in the northeast Atlantic (SW England). We conducted experiments in both spring and autumn to determine temporal variability in the effects of heatwaves. In spring, heatwave scenarios caused minimal stress to L. digitata but in autumn all scenarios tested resulted in tissue being nonviable by the end of each assay. The effects of heatwave scenarios were only apparent after consecutive exposures, indicating erosion of resilience over time. Monthly field surveys corroborated experimental evidence as the prevalence of bleaching (an indication of physiological stress and tissue damage) in natural populations was greatest in autumn and early winter. Overall, our data showed that L. digitata populations in SW England persist close to their upper physiological limits for emersion stress in autumn. As the intensity of extreme warming events is likely to increase with anthropogenic climate change, thermal conditions experienced during periods of emersion will soon exceed physiological thresholds and will likely induce widespread mortality and consequent changes at the population level.
Long‐term observation on hepatitis B surface antigen seroclearance in therapy experienced HIV/HBV co‐infected Chinese
Authors: Yang Rongrong , Gui Xien , Ke Hengning , Xiong Yong , Gao Shicheng
Published: October 2019

The aim of this retrospective study was to observe hepatitis B surface antigen (HBsAg) seroclearance and explore predictors of HBsAg loss in HIV/HBV‐co‐infected patients receiving long‐term lamivudine or both tenofovir and lamivudine containing therapies. Quantification of HBsAg, hepatitis B e antigen and HBV DNA before and after initiation of HBV‐active antiretroviral therapy in a total of 268 HIV/HBV‐co‐infected patients started treatment between 2005 and 2017 were performed. Over a median of 65.63 months of follow‐up, 10 (3.7%) were observed HBsAg loss and the quantification of HBsAg in 7 (2.6%) patients were less than 50 IU/mL. With the prolongation of antiretroviral therapy duration time, the rates of HBsAg seroclearance tended to increase gradually, rising from 1.8% (3/163) during 2‐4 years treatment to 29.4% (10/34) after antiretroviral therapy for up to 10 years. Lower baseline qHBsAg and HBV DNA levels and strong 12‐month declines in qHBsAg were significantly associated with HBsAg seroclearance. The event of HBsAg seroclearance is uncommon among Chinese individuals with HIV/HBV co‐infection who have been treated with anti‐HBV containing antiretroviral therapy, and lifelong therapy for HBV is needed for HIV/HBV co‐infected patients. Baseline qHBsAg and HBV DNA levels and qHBsAg decline rate were predictors for HBsAg seroclearance.
Fibroblast growth factor 23 and symmetric dimethylarginine concentrations in geriatric cats
Authors: Sargent Hannah J. , Jepson Rosanne E. , Chang Yu‐mei , Biourge Vincent C. , Bijsmans Esther S. , Elliott Jonathan
Published: October 2019

Background

Fibroblast growth factor 23 (FGF23) is a phosphaturic hormone that is increased in azotemic cats with chronic kidney disease (CKD) and predictive of the onset of azotemia in older cats. The introduction of symmetric dimethylarginine (SDMA) as a biomarker of glomerular filtration rate has led to the identification of cats in which SDMA is increased, but plasma creatinine concentrations remains within reference range. There is currently little understanding of the metabolic changes present in such cats.

Objectives

To examine the relationship between plasma FGF23 and SDMA concentrations in non‐azotemic geriatric cats.

Animals

Records of a cross section of client‐owned cats (n = 143) without azotemic CKD.

Methods

Clinicopathological information was obtained from cats (≥ 9 years) from records of 2 first opinion practices. The relationship between plasma SDMA and FGF23 concentrations was examined using Spearman's correlation and variables compared using the Mann‐Whitney U test.

Results

Cats with increased SDMA concentrations had significantly higher plasma FGF23 (P < .001) and creatinine (P < .001) concentrations compared to cats with SDMA concentrations within reference range. A weak positive relationship was demonstrated between plasma FGF23 and SDMA concentrations (r = .35, P < .001) and between plasma FGF23 and creatinine (r = .23, P = .005) concentrations.

Conclusions and Clinical Importance

More cats with increased SDMA concentrations had higher FGF23 concentrations than those with SDMA concentrations within the reference range, suggesting the presence of an alteration in phosphate homeostasis. Further studies are warranted to identify influencing factors and to explore the utility of FGF23 concentration to inform management of cats with early stage CKD.
Plant diversity in deciduous temperate forests reflects interplay among ancient and recent environmental stress
Authors: Šipoš Jan , Chudomelová Markéta , Vild Ondřej , Macek Martin , Kopecký Martin , Szabó Péter , Hédl Radim
Published: October 2019

Questions

Recent studies have suggested that response patterns of species and phylogenetic diversity may differ. Here, we address the following questions: What are the most important drivers and is there a difference in the responses to environmental drivers between species and phylogenetic diversity? If so, which ecological mechanisms determine these patterns and will different habitat types host plants of different evolutionary lineages?

Location

Czech Republic.

Methods

We used a unique data set of 419 permanent plots in thermophilous temperate deciduous forests. Vegetation of the herbaceous layer was sampled along a wide range of environmental gradients. Soil characteristics were measured in the laboratory from field‐collected samples. Topographic variables were derived from a digital elevation model.

Results

Communities of shaded habitats on moist fertile soils were characterized by phylogenetically older lineages (pteridophytes and ancient lineages of lilioids and dicots) resulting in a higher phylogenetic diversity. On the other hand, dry oligotrophic habitats were distinguished by short‐lived light‐demanding species (some asterids) and showed higher species, but relatively lower phylogenetic diversity. Besides simple effects of soil, light availability and topographic properties, interactions between the factors played an important role.

Conclusions

Our results indicate that both types of biodiversity were mainly driven by environmental stress created by the interplay among factors. Patterns of phylogenetic diversity suggest that historical factors, i.e., the shifting of species’ habitats at the evolutionary scale, could also provide plausible explanations.
Forest fragmentation shapes the alpha–gamma relationship in plant diversity
Authors: Almoussawi Ali , Lenoir Jonathan , Jamoneau Aurélien , Hattab Tarek , Wasof Safaa , Gallet‐Moron Emilie , Garzon‐Lopez Carol X. , Spicher Fabien , Kobaissi Ahmad , Decocq Guillaume
Published: October 2019

Questions

Forest fragmentation affects biodiversity locally (α diversity) and beyond — at relatively larger scales (γ diversity) — by increasing dispersal and recruitment limitations. Yet, does an increase in fragmentation affect the relationship between α and γ diversity and what can we learn from it?

Location

Northern France.

Methods

We surveyed 116 forest patches across three fragmentation levels: none (continuous forest); intermediate (forest patches connected by hedgerows); and high (isolated forest patches). Plant species richness of both forest specialists and generalists was surveyed at five nested spatial resolutions across each forest patch: 1 m2; 10 m2; 100 m2; 1,000 m2; and total forest patch area. First, we ran log‐ratio models to quantify the α–γ relationship. We did that separately for all possible combinations of fragmentation level (none vs intermediate vs high) × spatial scale (e.g., α‐1 m2 vs γ‐10 m2) × species type (e.g., α‐specialists vs γ‐specialists). We then used linear mixed‐effects models to analyze the effect of fragmentation level, spatial scale, species type and all two‐way interaction terms on the slope coefficient extracted from all log‐ratio models.

Results

We found an interaction effect between fragmentation level and species type, such that forest specialists shifted from a linear (i.e., proportional sampling) to a curvilinear plateau (i.e., community saturation) relationship at low and high fragmentation, respectively, while generalists shifted from a curvilinear to a linear pattern.

Conclusions

The impact of forest fragmentation on the α–γ relationship supports generalist species persistence over forest specialists, with contrasting mechanisms for these two guilds. As fragmentation increases, forest specialists shift from proportional sampling towards community saturation, thus reducing α diversity likely due to dispersal limitation. Contrariwise, generalists shift from community saturation towards proportional sampling, thus increasing α diversity likely due to an increase in the edge:core ratio. To ensure long‐term conservation of forest specialists, one single large forest patch should be preferred over several small ones.
Is it possible to diagnose fulminant Wilson's disease with simple laboratory tests?
Authors: Güngör Şükrü , Selimoğlu Mukadder A. , Bağ Harika G.G. , Varol Fatma İ.
Published: October 2019

Background

Wilson's disease is a rare cause of acute liver failure and is highly fatal without liver transplantation. Fast and accurate diagnostic methods are needed for fulminant Wilson's disease (FWD). In this study, we aimed to develop an early, simple and accurate diagnostic method to differentiate FWD from nonwilsonian acute liver failure (NWALF) causes using routine biochemical data.

Methods

The medical records of 24 paediatric FWD and 120 paediatric NWALF cases diagnosed at the Department of Pediatric Gastroenterology, Hepatology, and Nutrition between January 2007 and February 2017 were retrospectively reviewed.

Results

Using receiver operator characteristics curve (ROC) analysis, we have determined the best cut‐off point for laboratory findings in FWD. Patients meeting these cut‐off points were assigned one point and others were assigned zero point. We then formed a new variable consisting of the combination of 14 variables and performed a new ROC analysis. We obtained a cut‐off point of ≥4.5 for FWD. The diagnostic performance of the score was characterized by a sensitivity of 0.889, a specificity of 0.879 (P < .001). A scoring system based only on aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase, AST/ALT ratio, uric acid and haemoglobin had a best cut‐off point of ≥2.5 for FWD, which had a sensitivity of 0.875, a specificity of 0.867 (P < .001).

Conclusions

Our study demonstrated that biochemical markers offer almost as reliable, fast and accurate diagnosis of FWD as offered by ceruloplasmin and 24‐hour urinary copper.
Gene signature‐MELD score and alcohol relapse determine long‐term prognosis of patients with severe alcoholic hepatitis
Authors: Deltenre Pierre , Trépo Eric , Fujiwara Naoto , Goossens Nicolas , Marot Astrid , Dubois Margaux , Spahr Laurent , Henrion Jean , Moreno Christophe , Hoshida Yujin
Published: October 2019

Background

The gene‐signature‐model for end stage liver disease (gs‐MELD) score has been shown to be a strong predictor of 6‐month survival in severe alcoholic hepatitis (AH). Currently, only a few studies have evaluated the long‐term prognosis of patients with severe AH.

Aim

To assess the prognostic value of the gs‐MELD score at 5 years in patients with severe AH.

Methods

Forty‐eight consecutive patients with AH (25 males, median age 52 years [95% IC: 48‐56]) were included.

Results

The median gs‐MELD score was 2.6 (95% CI: 2.2‐3.0). According to the gs‐MELD score, 22 patients (46%) were considered to have a poor prognosis. During a median follow‐up of 29 months (95% CI: 4‐43), 19 patients (40%) were abstinent and 24 patients (50%) died. At 5 years, rates of survival were 61% (95% CI: 41‐81) and 26% (95% CI: 11‐55) in patients with low and high gs‐MELD scores (P = .001), and 81% (95% CI: 58‐96) and 22% (95% CI: 10‐47) in abstainers and in consumers (P < .001) respectively. In multivariable competing risk regression modelling, gs‐MELD score (subdistribution hazard ratio: 5.78, 95% CI: 2.17‐15.38, P < .001) and recurrent alcohol consumption (subdistribution hazard ratio: 12.18, 95% CI: 3.16‐46.95, P < .001) were independently associated with 5‐year mortality.

Conclusions

Both gs‐MELD score and alcohol consumption drive AH long‐term prognosis. The gs‐MELD score may guide the development of molecularly targeted therapies in AH.
Cardiovascular safety of antimuscarinic add‐on therapy in patients with overactive bladder who had a suboptimal response to mirabegron monotherapy: A post hoc analysis from the Japanese MILAI II study
Authors: Katoh Takao , Igawa Yasuhiko , Yamaguchi Osamu , Kato Daisuke , Hamada Takuya , Kuroishi Kentaro
Published: October 2019

Objective

This analysis was conducted to investigate the cardiovascular (CV) safety outcomes from the MILAI II study. MILAI II was conducted to evaluate the long‐term safety and efficacy of antimuscarinic add‐on therapy to mirabegron over 52 weeks in patients with overactive bladder (OAB) symptoms.

Methods

MILAI II consisted of a 2‐week screening period (patients received mirabegron 50 mg once daily) plus a 52‐week treatment period (patients were randomized to receive a combination of mirabegron 50 mg/d plus solifenacin 5 mg/d, propiverine 20 mg/d, imidafenacin 0.2 mg/d, or tolterodine 4 mg/d). CV safety was assessed using treatment‐emergent adverse events (TEAEs), vital signs, and 12‐lead electrocardiograms (ECGs). Vital signs and ECG data were evaluated for each patient using worst post‐baseline values reported.

Results

Of 647 patients, 570 (88.1%) were female with a mean age of 65 years. CV history at baseline and CV‐related concomitant medication use throughout the study were balanced between groups. The incidences of overall and drug‐related CV TEAEs were ≤8.1% and ≤6.2%, respectively, for all groups. The most common TEAEs were ECG T wave amplitude decreased, ECG QT prolonged, and ventricular extrasystoles. Overall, 36 TEAEs of interest related to the CV system that were possibly/probably related to treatment were reported with similar incidences for each group. For the worst post‐baseline vital signs and ECGs, no relationships were noted in terms of either timing or treatment group.

Conclusion

A favorable CV safety profile was observed following long‐term combination treatment with mirabegron and an antimuscarinic in patients with OAB symptoms.
Learning to see
Authors: Millar Boyd
Published: October 2019

It is often assumed that the empirical literature on sight restoration tells us something important about the relationship between visual and haptic representations of shape. However, I maintain that, immediately after having their sight restored, at least some newly sighted individuals undergo visual experiences that instantiate basic shape phenomenology but which do not present the corresponding shape properties. Consequently, the empirical literature on sight restoration tells us something important about the role that perceptual phenomenology plays in our perceptual awareness of an object's properties—it tells us that the properties presented by perceptual experiences are not “built into” perceptual phenomenology.
Satiety testing in diabetic gastroparesis: Effects of insulin pump therapy with continuous glucose monitoring on upper gastrointestinal symptoms and gastric myoelectrical activity
Authors: Koch Kenneth L. , Hasler William L. , Van Natta Mark , Calles‐Escandon Jorge , Grover Madhusudan , Pasricha Pankaj J. , Snape William J. , Parkman Henry P. , Abell Thomas L. , McCallum Richard W. , Nguyen Linda A. , Sarosiek Irene , Farrugia Gianrico , Tonascia James , Lee Linda , Miriel Laura , Hamilton Frank ,   the NIDDK Gastroparesis Clinical Research Consortium
Published: October 2019

Background

Symptoms induced by caloric or non‐caloric satiety test meals and gastric myoelectrical activity (GMA) have not been studied in patients with diabetic gastroparesis (DGP) before and after intense glucose management.

Aims

We determined the effects of continuous subcutaneous insulin infusion (CSII) with continuous glucose monitoring (CGM) on GI symptoms, volume consumed, and GMA induced by the caloric meal satiety test (CMST) and water load satiety test (WLST) in DGP.

Methods

Forty‐five patients with DGP underwent CMST and WLST at baseline and 24 weeks after CSII with CGM. Subjects ingested the test meals until they were completely full. Visual analog scales were used to quantify pre‐ and postmeal symptoms, and GMA was recorded with cutaneous electrodes and analyzed visually and by computer.

Key Results

At baseline and 24‐week visits, nausea, bloating, abdominal discomfort, and fullness were immediately increased after CMST and WLST (Ps < 0.01). The meal volumes ingested were significantly less than normal controls at both visits in almost one‐third of the subjects. After the CMST, the percentage 3 cycle per minute GMA increased and bradygastria decreased compared with WLST (Ps < 0.05). After treatment for 24 weeks meal volumes ingested, postmeal symptoms and GMA were no different than baseline.

Conclusions and inferences

(a) Satiety test meals elicited symptoms of nausea, bloating, and abdominal discomfort; (b) CMST stimulated more symptoms and changes in GMA than WLST; and (c) CSII with CGM for 24 weeks did not improve symptoms, volumes ingested, or GMA elicited by the two satiety test meals in these patients with diabetic GP. Satiety tests in diabetic gastropresis are useful to study acute postprandial symptoms and GMA, but these measures were not improved by intensive insulin therapy.
Initial soil community drives heathland fungal community trajectory over multiple years through altered plant–soil interactions
Authors: Radujković Dajana , van Diggelen Rudy , Bobbink Roland , Weijters Maaike , Harris Jim , Pawlett Mark , Vicca Sara , Verbruggen Erik
Published: October 2019

Dispersal limitation, biotic interactions, and environmental filters interact to drive plant and fungal community assembly, but their combined effects are rarely investigated.

This study examines how different heathland plant and fungal colonization scenarios realized via three biotic treatments – addition of mature heathland‐derived sod, addition of hay, and no additions – affect soil fungal community development over 6 yr along a manipulated pH gradient in a large‐scale experiment starting from an agricultural, topsoil removed state.

Our results show that both biotic and abiotic (pH) treatments had a persistent influence on the development of fungal communities, but that sod additions diminished the effect of abiotic treatments through time. Analysis of correlation networks between soil fungi and plants suggests that the reduced effect of pH in the sod treatment, where both soil and plant propagules were added, might be due to plant–fungal interactions since the sod additions caused stronger, more specific, and more consistent connections compared with the no addition treatment.

Based on these results, we suggest that the initial availability of heathland fungal and plant taxa, which reinforce each other, can significantly steer further fungal community development to an alternative configuration, overriding the otherwise prominent effect of abiotic (pH) conditions.
Defence compounds in pollen: why do they occur and how do they affect the ecology and evolution of bees?
Authors: Rivest Sébastien , Forrest Jessica R. K.
Published: October 2019

Pollen plays two important roles in angiosperm reproduction, serving as a vehicle for the plant’s male gametes, but also, in many species, as a lure for pollen‐feeding animals. Despite being an important food source for many pollinators, pollen often contains compounds with known deterrent or toxic properties, as documented in a growing number of studies. Here we review these studies and discuss the role of pollen defensive compounds in the coevolutionary relationship between plants and bees, the preeminent consumers of pollen. Next, we evaluate three hypotheses that may explain the existence of defensive compounds in pollen. The pleiotropy hypothesis, which proposes that defensive compounds in pollen merely reflect physiological spillover from other plant tissues, is contradicted by evidence from several species. Although plants may experience selection to defend pollen against poor‐quality pollinators, we also find only partial support for the protection‐against‐pollen‐collection‐hypothesis. Finally, pollen defences might protect pollen from colonisation by antagonistic microorganisms (antimicrobial hypothesis), although data to evaluate this idea are scarce. Further research on the effects of pollen defensive compounds on pollinators, pollen thieves, and pollen‐colonising microbes will be needed to understand why many plants have chemically defended pollen, and the consequences of those defences for pollen consumers.
Brown adipocytes from induced pluripotent stem cells—how far have we come?
Authors: Brown Aaron C.
Published: October 2019

A global increase in the number of individuals who are either overweight or obese is leading to a higher incidence of type 2 diabetes (T2D). Behavioral interventions for the treatment of obesity have yet to deliver desired outcomes, thus introducing a pressing need for molecular‐ and cellular‐based therapies. Excess energy from food is stored in the form of triglycerides in white adipose tissue, which expands during weight gain and can lead to insulin resistance and T2D. By contrast, brown adipose tissue (BAT) releases energy from metabolic substrates in the form of heat and secretes factors that can reverse metabolic disease by acting systemically. Therefore, the ability to increase BAT activity is a promising approach to improve energy balance and metabolic homeostasis. Methods are now being developed to generate brown adipocytes from human induced pluripotent stem cells (hiPSCs), which would (1) provide an unlimited source of cellular material to study human brown adipogenesis, and (2) could be used to develop drug‐ and cell‐based therapies for the treatment of metabolic complications associated with obesity. This article reviews basic BAT biology and details the current progress toward developing brown adipocytes from hiPSCs.
Economic evaluation of interventions for the treatment of asthma in children: A systematic review
Authors: Halmai Luca Adél , Neilson Aileen Rae , Kilonzo Mary
Published: October 2019

Objectives

This systematic review aimed to identify and critique full economic evaluations (EEs) of childhood asthma treatments with the intention to guide researchers and commissioners of pediatric asthma services toward potentially cost‐effective strategies.

Methods

“MEDLINE,” “Embase,” “EconLit,” “NHS EED,” and “CEA” databases were searched to identify relevant EEs published between 2005 and May 2017. Quality of included studies was assessed with a published checklist.

Results

Eighteen studies were identified and comprised one cost‐benefit analysis, 11 cost‐effectiveness analyses, one cost‐minimization analysis, and six cost‐utility analyses. Treatments included pharmaceutical (n = 11) and non‐pharmaceutical (n = 7) interventions. Fourteen studies identified cost‐effective strategies. The quality of the studies varied and there were uncertainties due to the methods and relevance of data used.

Conclusion

Good‐quality economic evaluation studies of pediatric asthma treatments are lacking. EE of new technologies adapted to local settings is recommended and can result in cost savings.
Quantitative trait loci for fruit size and flowering time‐related traits under domestication and diversifying selection in cucumber (Cucumis sativus)
Authors: Sheng Yunyan , Pan Yupeng , Li Yuhong , Yang Luming , Weng Yiqun
Published: October 2019

In cucumber, the genetic basis of traits under domestication and/or diversifying selection is not well understood. Here, we reported QTL mapping for flowering time and fruit size‐related traits with segregating populations derived from a cultivated × wild cross. Phenotypic data of flowering time (FT), fruit size (FS), fruit number (FN) and fruit weight per plant (FW) were collected in multiple environments. QTL analysis identified 19 QTL for these traits. We found that the major‐effect QTL FT1.1 played an important role in regulating flowering time in cultivated cucumber, whereas the minor‐effect QTL FT6.3 contributed to photoperiod sensitive flowering time during domestication. Two novel consensus FS QTL, FS1.4 and FS2.3, seem to be the targets of selection during breeding for the US processing cucumber. All other FS QTL were co‐localized with previously detected QTL using populations derived from cultivated cucumbers, suggesting that they were under selection during both initial domestication and subsequent improvement. Results from this study also suggested that the wild cucumber is a useful resource for capturing positive transgressive segregation and novel alleles that could be explored in cucumber breeding.
Limited sampling strategy to predict the area under the curve of tacrolimus in Mexican renal transplant pediatric patients receiving Prograf® or non‐innovator formulations
Authors: Medina‐Aymerich Lorena , González‐Ramírez Rodrigo , García‐Roca Pilar , Reyes Herlinda , Hernández Ana María , Medeiros Mara , Castañeda‐Hernández Gilberto
Published: October 2019

TDM of tacrolimus is usually performed with trough levels (C0h). However, in pediatric patients, C0h may not be an adequate marker. The AUC is considered a more suitable indicator of drug exposure. As several blood samples are needed for the estimation of AUC, and LSS for predicting tacrolimus AUC and optimizing the dose adjustment have been proposed. Moreover, in emerging countries such as Mexico, non‐innovator formulations, which bioequivalence has not been demonstrated, are frequently used. Hence, the aim of this study was to develop and validate a LSS to predict the tacrolimus AUC0‐12h in Mexican pediatric kidney transplant recipients who received either Prograf® or non‐innovator tacrolimus formulations. A total of 56 pharmacokinetic profiles were randomized into two groups: model development (n = 28) and model validation (n = 28). The limited sampling equations were obtained after a stepwise multiple regression using AUC as the dependent variable and tacrolimus blood concentrations, quantified by CMIA, at different time points as the independent variables. The final equation included observed concentrations at 1 hour (C1h) and 4 hours (C4h) after dose administration. The predictive performance of the model was adequate in terms of both, bias and precision. Results strongly suggest that the clinical use of this LSS could provide an ethical, cost‐, and time‐effective method in the TDM of tacrolimus in pediatric patients with kidney transplant. The model proved to be adequate with either Prograf® or non‐innovator tacrolimus formulations of dubious bioequivalence.
The practice of meditation is not associated with improved interoceptive awareness of the heartbeat
Authors: Khalsa Sahib S. , Rudrauf David , Hassanpour Mahlega S. , Davidson Richard J. , Tranel Daniel
Published: October 2019

Meditation is commonly assumed to be associated with enhanced interoceptive accuracy. We previously found that experienced meditators did not exhibit a greater ability than nonmeditators to detect heartbeat sensations at rest, despite the meditators' reported subjective ratings of higher accuracy and lower difficulty. Here, attempting to overcome previous methodological limitations, we assessed interoceptive awareness of heartbeat and breathing sensations across physiological arousal levels using infusions of isoproterenol, a beta‐adrenergic agonist similar to adrenaline. We hypothesized that meditators would display greater interoceptive awareness than nonmeditators, as evidenced by higher interoceptive detection rates, increased interoceptive accuracy, and differences in localization of heartbeat sensations. We studied 15 meditators and 15 nonmeditators, individually matched on age, gender, and body mass index, using randomized, double‐blinded, and placebo‐controlled bolus infusions of isoproterenol. Participants reported their experience of heartbeat and breathing sensations using a dial during infusions and the location of heartbeat sensations on a two‐dimensional manikin afterward. There was no evidence of higher detection rates or increased accuracy across any dose, although meditators showed a tendency to report cardiorespiratory sensation changes sooner at higher doses. Relative to nonmeditators, meditators exhibited prominent geographical differences in heartbeat localization, disproportionally reporting sensations throughout central regions of the chest, abdomen, neck, back, and head. To further assess indications of potential differences in cardiac interoceptive accuracy between meditators and nonmeditators, we conducted a meta‐analysis including 724 participants and found little evidence for such differences. We conclude that the practice of meditation is not associated with improved cardiac interoceptive awareness.
Emotional and feature‐based modulation of the early posterior negativity
Authors: Farkas Andrew H. , Oliver Katelyn I. , Sabatinelli Dean
Published: October 2019

The early posterior negativity (EPN) has been shown to be enhanced by emotional relative to neutral scene perception. A subset of studies has also reported a bias in the EPN toward pleasant relative to unpleasant scenes. Functional MRI research has also identified a region in lateral occipital cortex that shows a sensitivity to the visual perception of body parts, which may contribute to the EPN. Here, we assess the roles of rated scene pleasantness and the depiction of body parts on modulation of the EPN in two studies, using scenes that are chosen to be of equivalent perceptual complexity. In Study 1, we presented two distinct highly pleasant and arousing scene contents (erotic couples and moments of jubilant victory) as well as neutral people, threat, and mutilation scenes. As in prior research, the EPN was enhanced by emotionally arousing scenes, with the greatest modulation evoked by erotic scenes, although victory scenes elicited stronger ratings of pleasantness and equivalent ratings of arousal. This result suggests that the EPN may be sensitive to distinct features found in erotic scenes. To determine the extent to which body part perception modulates the EPN, Study 2 compared EPN modulation evoked by erotic scenes with nonerotic nudist scenes. Ratings of pleasantness and arousal were reduced, yet nudist scenes led to stronger modulation of the EPN compared to erotic scenes. These data indicate that, in addition to the emotional intensity of scenes, modulation of the EPN may in part reflect the discrimination of unclothed body parts.
Restoration ecology: the study of applied optimism
Authors: Palmer Brianne
Published: October 2019

As a young trainee in the field of restoration ecology in the modern age, it is difficult to feel optimistic about our future. As many environmental protections are de‐regulated and the climate crisis heightens, I turned to restoration to find hope in a changing world. Restoration ecologists are the optimists of biology. We work every day to make the world a better place and our passion and forward thinking spurred the United Nation's “decade of restoration.” Learning about the successes of the hardworking members of this field gives me hope. As the earth moves toward an unimaginable future, we should continue to try to make the world a better place and encourage those around us to act and restore the environments they value, whether it be large‐scale restoration or preserving garden pollinator habitat. I am forever thankful to restoration ecology and the optimism the field provides.
Can decision transparency increase citizen trust in regulatory agencies? Evidence from a representative survey experiment
Authors: Grimmelikhuijsen Stephan , Herkes Feie , Leistikow Ian , Verkroost Jos , de Vries Femke , Zijlstra Wilte G.
Published: October 2019

Decision transparency is often proposed as a way to maintain or even increase citizen trust, yet this assumption is still untested in the context of regulatory agencies. We test the effect of transparency of a typical decision tradeoff in regulatory enforcement: granting forbearance or imposing a sanction. We employed a representative survey experiment (n = 1,546) in which we test the effect of transparency in general (providing information about a decision or not) and the effect of specific types of transparency (process or rationale transparency). We do this for agencies supervising financial markets, education, and health care. We find that overall decision transparency significantly increases citizen trust in only two of the three agencies. Rationale transparency has a more pronounced positive effect only for the Education Inspectorate. We conclude that the overall effect of decision transparency is positive but that the nature of the regulatory domain may weaken or strengthen this effect.
“I Was There for the Free Food”: Accidental Conversions in College
Authors: Gillis Alanna , Krull Laura
Published: October 2019

How and why do some college students have conversion experiences, while others do not? To answer this question, we inductively analyzed in‐depth interviews with 30 students at a residential college in the southeast who had varying conversion experiences: some never began a conversion (n = 16), some started toward conversion but ultimately did not convert (n = 4), and some completed a religious (n = 5) or nonreligious conversion (n = 5). We conceptualize conversion as socialization into new beliefs and practices, as evidenced by reorganizing daily behaviors. We extend conversion to experiences not generally understood as such. We find religious and nonreligious conversions follow the same process during college, facilitated by student organizations, demonstrating that religious conversions are not a unique transformation. Furthermore, we find that organizational context matters in conversion processes: the structural context of college allows some students, who share biographical ability, a desire to make new friends, and openness to new groups, to unintentionally join student organizations that seek to change their daily practices and worldviews. However, many students face constrained choices or structural barriers that prevent the conversion from being completed. Our research has important implications for conceptualizing conversion and for understanding the role of organizational context in conversions.
Contribution of specific pathogens to bloodstream infection mortality in neutropenic patients with hematologic malignancies: Results from a multicentric surveillance cohort study
Authors: Kern Winfried V. , Roth Jan A. , Bertz Hartmut , Götting Tim , Dettenkofer Markus , Widmer Andreas F. , Theilacker Christian ,   the Hospital Infection Surveillance System for Patients with Hematologic/Oncologic Malignancies Study Group (ONKO‐KISS)
Published: October 2019

Bloodstream infection (BSI) remains a serious complication in patients with hematologic malignancies and neutropenia. The risk factors for mortality after BSI and the contributions of BSI pathogens to mortality remain incompletely understood. We evaluated first BSI among adult neutropenic patients undergoing high‐dose chemotherapy for hematologic malignancies in the setting of (a) an early disease stage of autologous (auto‐HSCT) or allogeneic (allo‐HSCT) hematopoietic stem cell transplantation or (b) for acute leukemia. Risk factors for intensive care admission and all‐cause mortality were analyzed by multivariable logistic regression 7 and 30 days after onset of the first BSI in the first neutropenic episode. Between 2002 and 2015, 9080 patients met the study inclusion criteria, and 1424 (16%) developed BSIs, most of them during the first week of neutropenia. Mortality during neutropenia within 7 days and 30 days after BSI onset was 2.5% and 5.1%, respectively, and differed considerably between BSI pathogens. Both 7‐day and 30‐day mortalities were highest for Pseudomonas aeruginosa BSI (16.7% and 26.7%, respectively) and lowest for BSI due to coagulase‐negative Staphylococcus spp. (CoNS) and Streptococcus spp. BSI pathogens were independently associated with 7‐day mortality included P aeruginosa, Klebsiella spp., Enterobacter spp., Serratia spp., and enterococci. Only gram‐negative BSI and candidemia were associated with admission to intensive care within 7 days after BSI onset. BSI caused by P aeruginosa continues to carry a particularly poor prognosis in neutropenic patients. The unexpected association between enterococcal BSI and increased mortality needs further study.
Variation in phosphorus and sulfur content shapes the genetic architecture and phenotypic associations within the wheat grain ionome
Authors: Fatiukha Andrii , Klymiuk Valentyna , Peleg Zvi , Saranga Yehoshua , Cakmak Ismail , Krugman Tamar , Korol Abraham B. , Fahima Tzion
Published: October 2019

Dissection of the genetic basis of wheat ionome is crucial for understanding the physiological and biochemical processes underlying mineral accumulation in seeds, as well as for efficient crop breeding. Most of the elements essential for plants are metals stored in seeds as chelate complexes with phytic acid or sulfur‐containing compounds. We assume that the involvement of phosphorus and sulfur in metal chelation is the reason for strong phenotypic correlations within ionome. Adjustment of element concentrations for the effect of variation in phosphorus and sulfur seed content resulted in drastic change of phenotypic correlations between the elements. The genetic architecture of wheat grain ionome was characterized by quantitative trait loci (QTL) analysis using a cross between durum and wild emmer wheat. QTL analysis of the adjusted traits and two‐trait analysis of the initial traits paired with either P or S considerably improved QTL detection power and accuracy, resulting in the identification of 105 QTLs and 617 QTL effects for 11 elements. Candidate gene search revealed some potential functional associations between QTLs and corresponding genes within their intervals. Thus, we have shown that accounting for variation in P and S is crucial for understanding of the physiological and genetic regulation of mineral composition of wheat grain ionome and can be implemented for other plants.
Tariffs and formation of free trade agreements networks
Authors: Hur Jung , Qiu Larry D.
Published: October 2019

This paper examines the formation of bilateral free trade agreements (FTAs) on the basis of country heterogeneity in the tariff level. We demonstrate that a country's unilateral incentive to form an FTA depends on the relative magnitudes of the (negative) market concession effect and the (positive) market expansion effect, both of which are determined by the tariff levels of the two FTA partner countries. Global welfare is maximised when all country pairs form FTAs. Two countries in equilibrium are more likely to form an FTA when their tariff gap is smaller or when their tariff levels are neither very high nor very low. This finding is robust to several extensions of the model. Our preliminary empirical analysis provides some evidence for the finding.
Amperometric detection of triclosan with screen-printed carbon nanotube electrodes modified with Guinea Grass (Panicum maximum) peroxidase
Authors: Orduz Angie E , Gutierrez Jorge A , Blanco Sergio I , Castillo John J
Published: October 2019

Triclosan is a compound with antimicrobial activity broadly used in consumer products. Because of its well documented toxicity, the amount of triclosan present in different products needs to be tightly controlled. This paper outlines a new amperometric sensor for triclosan detection consisting of a screen-printed carbon nanotube electrode (SPCNE) modified w ith Guinea grass peroxidase (GGP). The GGP-modified S PCNE was a ble t o d etect an enhanced electrochemical response of triclosan, unlike the bare SPCNE. The cyclic voltammograms of the GGP-modified SPCNE in a solution of potassium ferrocyanide showed an increase in the current values and linearity between scan rates and oxidation peak currents, suggesting a surface controlled process. The GGP-modified SPCNEs howed an excellent electrocatalytic activity to triclosan oxidation, at a redox potential of 370 mV, in the presence of hydrogen peroxide, exhibiting a linear response between 20 mM to 80 mM and a detection limit of 3 µM. This new amperometry system, based on carbon nanotubes integrated with GGP, becomes a potential tool for environmental analysis and food quality control.
Non-radial functions, nonlocal operators and Markov processes over p-adic numbers
Authors: Chacón-Cortés Leonardo Fabio , Casas-Sánchez Oscar Francisco
Published: October 2019

The main goal of this article is to study a new class of nonlocal operators and the Cauchy problem for certain parabolic-type pseudodifferential equations naturally associated with them. The fundamental solutions of these equations are transition functions of Markov processes on an n-dimensional vector space over the p-adic numbers. We also study some properties of these Markov processes, including the first passage time problem.