bluuebunny/crossref_metadata_2025 huggingface dataset:
Phase I trial of a standalone internet social anxiety treatment for adolescents who stutter: iBroadway
Authors: Gunn Anthony , Menzies Ross G. , Onslow Mark , O'Brian Sue , Packman Ann , Lowe Robyn , Helgadóttir Fjóla Dögg , Jones Mark
Published: July 2019

Background

iGlebe is a fully automated internet treatment program for adults who stutter that has been shown, in some cases, to reduce anxiety and effectively manage social anxiety disorder for many participants. No such automated internet treatment program exists for adolescents who stutter.

Aims

The present paper reports a Phase I trial of an adolescent version of the adult program: iBroadway.

Methods & Procedures

Participants were 29 adolescents in the age range 12–17 years who were seeking cognitive–behaviour therapy (CBT) for anxiety associated with stuttering. The design was a non‐randomized Phase I trial with outcome assessments at pre‐treatment and immediately post‐treatment after 5 months of access to the program. No contact by a clinical psychologist occurred during participant use of the program. Outcomes were a range of psychological, quality‐of‐life and stuttering severity measures.

Outcomes & Results

The compliance rate for the seven iBroadway modules over 5 months was extremely favourable for internet CBT, at 52.4%. There was evidence of treatment effects for (1) the number of DSM‐IV mental health diagnoses with the Diagnostic Interview Schedule for Children; (2) the Unhelpful Thoughts and Beliefs About Stuttering scale; (3) the Subjective Units of Distress Scale; and (4) parent‐reported speech satisfaction.

Conclusions & Implications

Further development of iBroadway, the adolescent version of iGlebe, with Phase II trialling is warranted.
The price of going green: the role of greenness in green bond markets
Authors: Hyun Suk , Park Donghyun , Tian Shu
Published: July 2019

In this paper, we empirically investigate how greenness information is priced in the green bond market. Our comparison of liquidity‐adjusted yield premiums of green bonds versus synthetic conventional bonds indicates that, on average, there is no robust and significant yield premium or discount on green bonds. However, green bonds certified by an external reviewer enjoy a discount of about 6 bps. Furthermore, green bonds that obtain a Climate Bonds Initiative certificate show a discount of around 15 bps. The findings suggest that a universally accepted greenness measure can benefit the development of the green bond market.
Compound heterozygosity for TNXB genetic variants in a mixed‐breed dog with Ehlers‐Danlos syndrome
Authors: Bauer A. , de Lucia M. , Leuthard F. , Jagannathan V. , Leeb T.
Published: July 2019

The Ehlers‐Danlos syndromes (EDSs) are a heterogeneous group of inherited connective tissue disorders characterized by skin hyperextensibility, joint hypermobility and tissue fragility. Inherited disorders similar to human EDS have been reported in different mammalian species. In the present study, we investigated a female mixed‐breed dog with clinical signs of EDS. Whole‐genome sequencing of the affected dog revealed two missense variants in the TNXB gene, encoding the extracellular matrix protein tenascin XB. In humans, TNXB genetic variants cause classical‐like EDS or the milder hypermobile EDS. The affected dog was heterozygous at both identified variants. Each variant allele was transmitted from one of the case's parents, consistent with compound heterozygosity. Although one of the variant alleles, XM_003431680.3:c.2012G>A, p.(Ser671Asn), was private to the family of the affected dog and absent from whole‐genome sequencing data of 599 control dogs, the second variant allele, XM_003431680.3:c.2900G>A, p.(Gly967Asp), is present at a low frequency in the Chihuahua and Poodle population. Given that TNXB is a functional candidate gene for EDS, we suggest that compound heterozygosity for the identified TNXB variants may have caused the EDS‐like phenotype in the affected dog. Chihuahuas and Poodles should be monitored for EDS cases, which might confirm the hypothesized pathogenic effect of the segregating TNXB variant.
Does Public Support Help Democracy Survive?
Authors: Claassen Christopher
Published: July 2019

It is widely believed that democracy requires public support to survive. The empirical evidence for this hypothesis is weak, however, with existing tests resting on small cross‐sectional samples and producing contradictory results. The underlying problem is that survey measures of support for democracy are fragmented across time, space, and different survey questions. In response, this article uses a Bayesian latent variable model to estimate a smooth country‐year panel of democratic support for 135 countries and up to 29 years. The article then demonstrates a positive effect of support on subsequent democratic change, while adjusting for the possible confounding effects of prior levels of democracy and unobservable time‐invariant factors. Support is, moreover, more robustly linked with the endurance of democracy than its emergence in the first place. As Lipset (1959) and Easton (1965) hypothesized over 50 years ago, public support does indeed help democracy survive.
Predicting the prognosis of undifferentiated pleomorphic soft tissue sarcoma: a 20‐year experience of 266 cases
Authors: Vodanovich Domagoj A. , Spelman Tim , May Deborah , Slavin John , Choong Peter F. M.
Published: July 2019

Background

Undifferentiated pleomorphic sarcoma (UPS) is a rare malignant tumour of mesenchymal origin, which was conceived following re‐classification of malignant fibrous histiocytoma (MFH). The objective of this study is to determine prognostic factors for the outcome of UPS, following multi‐modal treatment.

Methods

Data of UPS tumours from 1996 to 2016 were collected, totalling 266 unique UPS patients. Median follow‐up was 7.8 years. All tumours were retrospectively analysed for prognostic factors of the disease, including local recurrence (LR) and metastatic disease (MD) at diagnosis, tumour size, grade, location and depth, patient age, adjuvant therapy and surgical margin. Overall survival (OS), post‐treatment LR and metastatic‐free survival were assessed as outcomes.

Results

The 5‐ and 10‐year OS rates for all ages were 60% and 48%, respectively, with a median survival time of 10.1 years. Multivariate analysis revealed that the adverse prognostic factors associated with decreased OS were older age (P < 0.001; hazard ratio 1.03) and MD at diagnosis (P = 0.001; 2.89), with upper extremity tumours being favourable (P = 0.043; 2.30). Poor prognosis for post‐operative LR was associated with older age (P = 0.046; 1.03) and positive surgical margins (P = 0.028; 2.68). Increased post‐treatment MD was seen in patients with large tumours (5–9 cm (P < 0.001; 4.42), ≥10 cm (P < 0.001; 6.80)) and MD at diagnosis (P < 0.001; 3.99), adjuvant therapy was favourable, shown to reduce MD (P < 0.001; 0.34).

Conclusions

UPS is a high‐grade soft tissue sarcoma, for which surgery striving for negative margins, with radiotherapy, is the treatment of choice. Older age, lower extremity location, MD at presentation, large size and positive surgical margins, were unfavourable.
Meta‐analysis of unplanned readmission to hospital post‐appendectomy: an opportunity for a new benchmark
Authors: Bailey Kate , Choynowski Michelle , Kabir Syed Mohammad Umar , Lawler Jack , Badrin Adibah , Sugrue Michael
Published: July 2019

Background

Appendicitis is the most common cause of acute abdominal pain requiring surgical intervention. While many studies report readmission, a meta‐analysis of readmission post‐appendectomy has not been published. This meta‐analysis was undertaken to determine rates and predictors of hospital readmission following appendectomy and to potentially provide a metric benchmark.

Methods

An ethically approved PROSPERO‐registered (ID CRD42017069040) meta‐analysis following Preferred Reporting Items for Systematic Reviews and Meta‐Analyses guidelines, using databases PubMed and Scopus, was undertaken for studies published between January 2012 and June 2017. Articles relating to outcomes and readmissions after appendectomy were identified. Those scoring >15 for comparative studies and >10 for non‐comparative studies, using Methodological Index for Non‐Randomized Studies criteria were included in the final analysis. The odds ratios (OR) using random‐effects, Mantel–Haenszel method with 95% confidence intervals (CI), were computed for each risk factor with RevMan5.

Results

A total of 1757 articles reviewed were reduced to 45 qualifying studies for a final analysis of 836 921 appendectomies. 4.3% (range 0.0–14.4%) of patients were readmitted within 30 days. Significant preoperative patient factors for increased readmission were diabetes mellitus (OR 1.93, CI 1.63–2.28, P < 0.00001), complicated appendicitis (OR 3.6, CI 2.43–5.34, P < 0.00001) and open surgical technique (OR 1.39, CI 1.08–1.79, P < 0.00001). Increased readmission was not associated with gender, obesity or paediatric versus general surgeons or centres.

Conclusion

This meta‐analysis identified that readmission is not uncommon post‐appendectomy, occurring in one in 25 cases. The mean readmission rate of 4.3% may act as a quality benchmark for improving emergency surgical care. Targeting high‐risk groups with diabetes or complicated appendicitis and increasing use of laparoscopic technique may help reduce readmission rates.
Advances in understanding the pathogenesis of red cell membrane disorders
Authors: Iolascon Achille , Andolfo Immacolata , Russo Roberta
Published: July 2019

Hereditary erythrocyte membrane disorders are caused by mutations in genes encoding various transmembrane or cytoskeletal proteins of red blood cells. The main consequences of these genetic alterations are decreased cell deformability and shortened erythrocyte survival. Red blood cell membrane defects encompass a heterogeneous group of haemolytic anaemias caused by either (i) altered membrane structural organisation (hereditary spherocytosis, hereditary elliptocytosis, hereditary pyropoikilocytosis and Southeast Asian ovalocytosis) or (ii) altered membrane transport function (overhydrated hereditary stomatocytosis, dehydrated hereditary stomatocytosis or xerocytosis, familial pseudohyperkalaemia and cryohydrocytosis). Herein we provide a comprehensive review of the recent literature on the molecular genetics of erythrocyte membrane defects and their reported clinical consequences. We also describe the effect of low‐expression genetic variants on the high inter‐ and intra‐familial phenotype variability of erythrocyte structural defects.
A non‐covalent inhibitor XMU‐MP‐3 overrides ibrutinib‐resistant BtkC481S mutation in B‐cell malignancies
Authors: Gui Fu , Jiang Jie , He Zhixiang , Li Li , Li Yunzhan , Deng Zhou , Lu Yue , Wu Xinrui , Chen Guyue , Su Jingyi , Song Siyang , Zhang Yue‐Ming , Yun Cai‐Hong , Huang Xin , Weisberg Ellen , Zhang Jianming , Deng Xianming
Published: July 2019

Background and Purpose

Bruton's tyrosine kinase (BTK) plays a key role in B‐cell receptor signalling by regulating cell proliferation and survival in various B‐cell malignancies. Covalent low‐MW BTK kinase inhibitors have shown impressive clinical efficacy in B‐cell malignancies. However, the mutant BtkC481S poses a major challenge in the management of B‐cell malignancies by disrupting the formation of the covalent bond between BTK and irreversible inhibitors, such as ibrutinib. The present studies were designed to develop novel BTK inhibitors targeting ibrutinib‐resistant BtkC481S mutation.

Experimental Approach

BTK‐Ba/F3, BTK(C481S)‐Ba/F3 cells, and human malignant B‐cells JeKo‐1, Ramos, and NALM‐6 were used to evaluate cellular potency of BTK inhibitors. The in vitro pharmacological efficacy and compound selectivity were assayed via cell viability, colony formation, and BTK‐mediated signalling. A tumour xenograft model with BTK‐Ba/F3, Ramos and BTK(C481S)‐Ba/F3 cells in Nu/nu BALB/c mice was used to assess in vivo efficacy of XMU‐MP‐3.

Key Results

XMU‐MP‐3 is one of a group of low MW compounds that are potent non‐covalent BTK inhibitors. XMU‐MP‐3 inhibited both BTK and the acquired mutant BTKC481S, in vitro and in vivo. Further computational modelling, site‐directed mutagenesis analysis, and structure–activity relationships studies indicated that XMU‐MP‐3 displayed a typical Type‐II inhibitor binding mode.

Conclusion and Implications

XMU‐MP‐3 directly targets the BTK signalling pathway in B‐cell lymphoma. These findings establish XMU‐MP‐3 as a novel inhibitor of BTK, which could serve as both a tool compound and a lead for further drug development in BTK relevant B‐cell malignancies, especially those with the acquired ibrutinib‐resistant C481S mutation.
Aquaporin 4 deletion exacerbates brain impairments in a mouse model of chronic sleep disruption
Authors: Zhang Rui , Liu Yun , Chen Yan , Li Qian , Marshall Charles , Wu Ting , Hu Gang , Xiao Ming
Published: July 2019

Aims

As a normal physiological process, sleep has recently been shown to facilitate clearance of macromolecular metabolic wastes from the brain via the glymphatic system. The aim of the present study was to investigate pathophysiological roles of astroglial aquaporin 4 (AQP4), a functional regulator of glymphatic clearance, in a mouse model of chronic sleep disruption (SD).

Methods

Adult AQP4 null mice and wild‐type (WT) mice were given 7 days of SD using the improved rotating rod method, and then received behavioral, neuropathological, and neurochemical analyses.

Results

Aquaporin 4 deletion resulted in an impairment of glymphatic transport and accumulation of β‐amyloid and Tau proteins in the brain following SD. AQP4 null SD mice exhibited severe activation of microglia, neuroinflammation, and synaptic protein loss in the hippocampus, as well as decreased working memory, compared with WT‐SD mice.

Conclusion

These results demonstrate that AQP4‐mediated glymphatic clearance ameliorates brain impairments caused by abnormal accumulation of metabolic wastes following chronic SD, thus serving as a potential target for sleep‐related disorders.
Therapeutische Patientenschulungsprogramme und Unterstützung beim Selbstmanagement für Patienten mit Psoriasis – eine systematische Übersicht
Authors: Dressler Corinna , Lambert Jo , Grine Lynda , Galdas Paul , Paul Carle , Zidane Miriam , Nast Alexander
Published: July 2019

Psoriasis ist eine chronisch‐entzündliche Hautkrankheit. Patientenschulungen könnten eine Möglichkeit sein, die Adhärenz und die Bewältigungsstrategien (Coping) zu verbessern. Das Ziel dieser systematischen Übersichtsarbeit ist es, Studien zu ermitteln, in denen Schulungsinterventionen für Psoriasis‐Patienten evaluiert werden. Die Übersichtsarbeit wurde im Einklang mit den von Cochrane empfohlenen Methoden erstellt. Wir durchsuchten sieben Datenbanken, ein Studienregister und drei Repositorien für graue Literatur. Die Sichtung und Extraktion der Daten wurden von zwei unabhängigen Untersuchern durchgeführt. Es wurden die Instrumente Risk of Bias 2.0, ROBINS‐I und Instrumente des NIH verwendet. Zusätzlich wurden die APEASE‐Kriterien angewendet. Sechzehn Studien wurden von uns ausgewertet. In zwei RCT (randomized clinical trials) wurden Eins‐zu‐Eins‐Interventionen (Patient/Arzt, Patient/Pflegekraft), in einer RCT wurde eine Web‐basierte Intervention, in drei RCT wurden öfter stattfindende Gruppeninterventionen und in einem RCT wurde eine einmalig stattfindende Gruppensitzung untersucht. Eine RCT stellte einen Vergleich an zwischen den beteiligten medizinischen Fachkräften. Die Bewertung des Verzerrungsrisikos (Risk of Bias; RoB) reichte von „gewisse Bedenken“ bis „hoch“. Drei RCT fanden einen Effekt. Wir schlossen vier CCT (controlled clinical trials) ein, in einer konnte ein Effekt gezeigt werden. Eine der vier Vorher‐Nachher‐Studien rechtfertigt weitere Untersuchungen. Trotz gewisser Ähnlichkeiten zwischen den Interventionen in der Art der Vermittlung waren Patientenselektion und Setting, in denen die Interventionen durchgeführt wurden, verschieden. Interventionen, die eine individuelle (Eins‐zu‐Eins) Sitzung beinhalteten, schienen erfolgreich zu sein. Nach Anwendung der APEASE‐Kriterien scheinen zwei Interventionen für eine Adaptation geeignet zu sein: das Programm zur Optimierung der topischen Therapie und die motivierende Gesprächsführung (motivational interviewing) nach einer Klimatherapie.
Inducing remission of Type 2 diabetes in the Caribbean: findings from a mixed methods feasibility study of a low‐calorie liquid diet‐based intervention in Barbados
Authors: Bynoe K. , Unwin N. , Taylor C. , Murphy M. M. , Bartholomew L. , Greenidge A. , Abed M. , Jeyaseelan S. , Cobelli C. , Dalla Man C. , Taylor R.
Published: July 2019

Aim

In a high proportion of people with recently diagnosed Type 2 diabetes, a short (2–3‐month) low‐calorie diet is able to restore normal glucose and insulin metabolism. The aim of this study was to determine the feasibility of this approach in Barbados.

Methods

Twenty‐five individuals with Type 2 diabetes diagnosed within past 6 years, not on insulin, BMI ≥ 27 kg/m2 were recruited. Hypoglycaemic medication was stopped on commencement of the 8‐week liquid (760 calorie) diet. Insulin response was assessed in meal tests at baseline, 8 weeks and 8 months. Semi‐structured interviews, analysed thematically, explored participants’ experiences. ‘Responders’ were those with fasting plasma glucose (FPG) < 7 mmol/l at 8 weeks.

Results

Ten men and 15 women (mean age 48, range 26–68 years) participated. Mean (sd) BMI was 34.2 kg/m2 (6.0); FPG 9.2 mmol/l (2.2). Mean weight loss at 8 weeks and 8 months was 10.1 kg [95% confidence interval (CI) 8.1, 12.0] and 8.2 kg (95% CI 5.8, 10.6); FPG was lower by 2.2 mmol/l (95% CI 1.2, 3.2) and 1.7 mmol/l (95% CI 0.8, 2.7) respectively. Nine of 11 (82%) of those who lost ≥ 10 kg were ‘responders’ compared with 6 of 14 (43%) who lost < 10 kg (P = 0.048). The 30‐min insulin increment was higher in responders at baseline and follow‐up (P ≤ 0.01). A food culture based on starchy foods and pressures to eat large amounts at social events were among the challenges identified by participants.

Conclusions

The feasibility of this approach to weight loss and diabetes remission in a predominantly black population in Barbados was demonstrated.
First report of Ceratocystis huliohia causing mortality of Metrosideros polymorpha trees on the Island of Kauaʻi, Hawaiʻi USA
Authors: Heller Wade P. , Hughes Marc A. , Luiz Blaine C. , Brill Eva , Friday James B. , Williams Adam M. , Keith Lisa M.
Published: July 2019

The fungus Ceratocystis huliohia was detected for the first time in dead and dying Metrosideros polymorpha trees on the Island of Kauaʻi, Hawaiʻi, U.S.A. Fungal isolates were recovered from diseased trees into culture, and identities were confirmed by diagnostic qPCR assay and DNA sequencing. Growth chamber inoculations confirmed C. huliohia pathogenicity on M. polymorpha seedlings and subsequently the same fungus was recovered, completing Koch's postulates. DNA sequence analysis revealed a unique ITS haplotype for Kauaʻi isolates of C. huliohia that has not been found on Hawaiʻi Island.
On Natural Variation in Grades in Higher Education, and Its Implications for Assessing Effectiveness of Educational Innovations
Authors: Boevé Anja J. , Meijer Rob R. , Beldhuis Hans J. A. , Bosker Roel J. , Albers Casper J.
Published: July 2019

To investigate the effect of innovations in the teaching–learning environment, researchers often compare study results from different cohorts across years. However, variance in scores can be attributed to both random fluctuation and systematic changes due to the innovation, complicating cohort comparisons. In the present study, we illustrate how using information about the variation in course grades over time can help researchers and practitioners better compare the grades and pass rates of different cohorts of students. To this end, all 375,093 grades from all 40,087 first‐year students at a Dutch university during a period of six consecutive years were examined. Overall, about 17% of the variation in grades could be attributed to random variation between years and courses. With respect to passing courses, this percentage was almost 40%. Nonsignificant improvements in grades could be flagged as highly significant when this is ignored, thus leading to an overrepresentation of significant effects in educational literature. As a consequence, too many educational innovations are claimed to be effective.
The effect of grazing versus cutting on dry matter production of multispecies and perennial ryegrass‐only swards
Authors: Grace Cornelia , Boland Tommy M. , Sheridan Helen , Brennan Eugene , Fritch Rochelle , Lynch Mary Bridget
Published: July 2019

Dry matter (DM) production of multispecies swards compared to perennial ryegrass (Lolium perenne; PRG) swards under intensive grazing warrants investigation as it is relatively unknown. A 5 × 2 factorial experiment, with five sward types and two defoliation methods, was used to investigate the effect of grazing versus cutting on dry matter (DM) production of multispecies and PRG‐only swards. Five sward types were established namely: a PRG‐only sward, receiving 250 kg N ha−1 year−1 (PRG250), and a PRG‐only sward (PRG90), a two‐species sward with PRG and white clover (Trifolium repens; PRGWC), a six‐species sward (6S) and a nine‐species sward (9S), each receiving 90 kg N ha−1 year−1. Cutting plots measured 1.95 × 10 m and grazing plots measured 10 × 10 m. All plots were harvested concurrently every 21–30 days from April‐November for two years (2015 and 2016). A strip from the grazing plots was cut for DM yield determination prior to turning in cattle for grazing. There was an interaction between sward type and defoliation method (p < .01), whereby there was no effect of defoliation method on the PRG‐only swards, however, the annual DM production of PRGWC, 6S and 9S swards reduced under grazing compared to cutting (p < .001; on average 1,929 kg DM/ha lower). Multispecies swards had lower DM production under grazing compared to cutting, while the DM yield of PRG‐only swards was unaffected by defoliation method.
Infectious differential diagnosis of chronic generalized pruritus without primary cutaneous lesions: a review of the literature
Authors: Molkara Sara , Sabourirad Sara , Molooghi Kasra
Published: July 2019

Pruritus is one of the most common complaints among patients referred to a dermatology clinic. “Chronic generalized pruritus” is described as the sensation of itching on the entire body surface, which lasts at least 6 or more weeks. This symptom can be a disabling phenomenon for patients and may sometimes interfere with daily activities such as sleep. If specific dermatological findings are observed, the physician easily comes to a diagnosis and treats the condition, whereas, when primary lesions are not detected, the diagnosis can become challenging, and some patients have to undergo extensive evaluations. The association between some systemic disorders and chronic generalized pruritus is widely known and confirmed. Many infections have been associated with pruritus, but few are considered to cause chronic generalized pruritus without any characteristic skin lesions. We aimed to gather all the available data on infectious causes of chronic generalized pruritus with no diagnostic cutaneous lesions to assist fellow physicians in the process of evaluation of these challenging cases.
Consumption of ultra‐processed foods and its association with added sugar content in the diets of US children, NHANES 2009‐2014
Authors: Neri Daniela , Martinez‐Steele Euridice , Monteiro Carlos Augusto , Levy Renata Bertazzi
Published: July 2019

Background

There is cumulative recognition that increases in the dietary share of ultra‐processed foods result in deterioration of the nutritional quality of the overall diet and adverse health outcomes.

Objective

The purpose of this study was to assess the consumption of ultra‐processed foods and to examine its association with added sugar content in the diet of US children aged 2 to 19 years.

Methods

We classified all food items according to the NOVA food classification system and looked at the consumption of ultra‐processed foods, measured as percentage of total energy intake. We assessed dietary added sugar content by estimating its contribution to total energy intake and the proportion of individuals with diets exceeding the recommended limit of 10% of total energy intake from added sugars. We also examined the proportion of those who surpassed twice that limit. Gaussian and Poisson regressions estimated the association between consumption of ultra‐processed foods and estimates of added sugar content.

Results

Ultra‐processed foods contributed to 65% of total energy intake and to 92% of energy from added sugars in the diet of US children. The mean percent energy provided by added sugars in the observed period was 14.3%. Most individuals (70.9%) had diets exceeding the recommended limit of added sugar (<10% of total energy intake), and 18.4% of the population had diets surpassing twice the recommended level (20% of total energy intake). A 5.5% point increase in the dietary share of ultra‐processed foods determined a 1 percentage point increase in the dietary content of added sugars, with stronger adjusted associations among younger children.

Conclusions

Public health efforts to reduce added sugars in the diet of US children must put greater emphasis on decreasing the consumption of ultra‐processed foods.
Serial cross‐sectional study for the association between urinary bisphenol A and paediatric obesity: Recent updates using NHANES 2003‐2014
Authors: Okubo Yusuke , Handa Atsuhiko , Belin Thomas
Published: July 2019

Background

Several studies have reported bisphenol A (BPA) as a potential risk factor for paediatric obesity, but the findings were inconsistent among these studies.

Methods

Using data from the National Health and Nutrition Examination Survey from 2003 to 2014, we conducted a serial cross‐sectional study to examine the association between urinary BPA and paediatric obesity among children aged 6 and 19 years. The association between paediatric obesity and urinary BPA concentrations with or without urinary creatinine adjustments was assessed using multivariable regression and cubic spline models fitted for regression models.

Results

We observed decreasing trends in urinary BPA concentrations from 2003 to 2014. The associations between urinary BPA concentrations and obesity were inconsistent across the years of survey and even after different models for urinary creatinine adjustments were used. Children with obesity were positively associated with urinary creatinine concentrations, but was not with creatinine‐adjusted models. Furthermore, children with higher urinary BPA concentrations had elevated odds of obesity during 2003 to 2008, whereas these associations were inconsistent during 2009 to 2014.

Conclusions

The associations between paediatric obesity and urinary BPA concentrations differed across the years of survey and creatinine adjustments. Further studies are required to assess these discrepancies.
Reducing seclusion and restraints on the inpatient child and adolescent behavioral health unit: A quality improvement study
Authors: Eblin Amanda
Published: July 2019

Background

The utilization of seclusion and restraint during psychiatric inpatient treatment increases the risk of trauma, humiliation, physical injuries, psychological distress, and even death. Compared to adult patients, pediatric patients are more likely to be placed in seclusion and restraints. In a short‐term child and adolescent behavioral health unit, the average seclusion and restraint rate was 0.031. The hospital's goal was to achieve a zero seclusion and restraint rate.

Purpose

The purpose of this project was to decrease the rate of seclusion and restraints at the study site.

Method

A quality improvement study was implemented based on a bundled intervention strategy. The intervention included a decision‐making algorithm for initiation of seclusion and restraints, behavioral modification plans for patients at risk of seclusion and restraints, and a patient‐debriefing tool to be used post a seclusion and restraint event. Post implementation, data were collected over a 3‐month period.

Results

The implementation of a seclusion and restraint decision‐making algorithm, behavioral modification, and patient debriefing successfully decreased the seclusion and restraint rate by 55% on an inpatient pediatric behavioral health unit.

Conclusion

Although, the project resulted in a successful reduction in the rates for seclusion and restraint, continued quality improvement efforts are indicated to achieve zero restraint/seclusions on the unit.
A randomised controlled trial of treatments of childhood anxiety disorder in the context of maternal anxiety disorder: clinical and cost‐effectiveness outcomes
Authors: Creswell Cathy , Violato Mara , Cruddace Susan , Gerry Stephen , Murray Lynne , Shafran Roz , Stein Alan , Willetts Lucy , McIntosh Emma , Cooper Peter J.
Published: July 2019

Background

This study evaluated whether clinical and economic outcomes from CBT for child anxiety disorders in the context of maternal anxiety disorders are improved by adding treatment focused on (a) maternal anxiety disorders or (b) mother–child interactions.

Methods

Two hundred and eleven children (7–12 years, 85% White British, 52% female) with a primary anxiety disorder, whose mothers also had a current anxiety disorder, were randomised to receive (a) child‐focused CBT with nonspecific control interventions (CCBT+Con), (b) CCBT with CBT for the maternal anxiety disorder (CCBT+MCBT), or (c) CCBT with an intervention targeting the mother–child interaction (CCBT+MCI). A cost‐utility analysis from a societal perspective was conducted using mother/child combined quality‐adjusted life years (QALYs). [Trial registration: https://doi.org/10.1186/isrctn19762288].

Results

MCBT was associated with immediate reductions in maternal anxiety compared to the nonspecific control; however, after children had also received CCBT, maternal outcomes in the CCBT+MCI and CCBT+Con arms improved and CCBT+MCBT was no longer superior. Neither CCBT+MCBT nor CCBT+MCI conferred a benefit over CCBT+Con in terms of child anxiety disorder diagnoses post‐treatment [primary outcome] (adj RR: 1.22 (95% CI: 0.88, 1.67), p = .23; adj RR: 1.21 (95% CI: 0.88, 1.65), p = .24, respectively) or global improvement ratings (adj RR: 1.25 (95% CI: 0.99, 1.57), p = .06; adj RR: 1.18 (95% CI: 0.93, 1.50), p = .17) or six and 12 months later. No significant differences between the groups were found on the main economic outcome measures (child/mother combined QALY mean difference: CCBT+MCBT vs. CCBT+Con: −0.04 (95% CI: −0.12, 0.04), p = .29; CCBT+MCI vs. CCBT+Con: 0.02 (95% CI: −0.05, −0.09), p = .54). CCBT+MCI was associated with nonsignificantly higher costs than CCBT (mean difference: £154 (95% CI: −£1,239, £1,547), p = .83) but, when taking into account sampling uncertainty, it may be cost‐effective compared with CCBT alone.

Conclusions

Good outcomes were achieved for children and their mothers across treatment arms. There was no evidence of significant clinical benefit from supplementing CCBT with either CBT for the maternal anxiety disorder or treatment focussed on mother–child interactions, but the addition of MCI (and not MCBT) may be cost‐effective.
Noncomprehensive and Intermittent Obesity‐Related School Programs and Policies May Not Work: Evidence from the COMPASS Study
Authors: Laxer Rachel E. , Dubin Joel A. , Brownson Ross C. , Cooke Martin , Chaurasia Ashok , Leatherdale Scott T.
Published: July 2019

BACKGROUND

The school environment has the potential to influence student body mass index (BMI) through programs and policies. Our objective was to examine the effect of modifying obesity‐related school policies and programs on youths' BMI trajectories.

METHODS

Obesity‐related school policies and programs related to physical activity and healthy eating were collected from 41 schools across Ontario at baseline (2012‐2013) and year 2 (2013‐2014) of the COMPASS study. Self‐reported height and weight were collected from the 4951 grades 9 and 10 students who attended those schools for 3 years. Linear mixed effects regression models examined the effect of modifying obesity‐related school policies and programs on youths' BMI trajectories.

RESULTS

Between Y1 and Y2, 26 of the 41 schools implemented distinct new obesity‐related programs or policies related to physical activity or healthy eating. Five of the interventions were associated with BMI trajectories of students attending those schools compared to students attending a pooled sample of control schools, predicting a higher BMI trajectory.

CONCLUSIONS

Isolated programs and policies may not successfully improve youths' BMI trajectories. Further research is required to test the implementation of policies and programs that follow a comprehensive school health (CSH) approach, targeting BMI and associated behaviors.
The RNA‐binding protein SORBS2 suppresses hepatocellular carcinoma tumourigenesis and metastasis by stabilizing RORA mRNA
Authors: Han Lili , Huang Chen , Zhang Shuqun
Published: July 2019

Background

Numerous studies have revealed that dysregulation of RNA‐binding protein (RBP) expression is causally linked with human cancer tumourigenesis. However, the detailed biological effect and underlying mechanisms of most RBPs remain unclear.

Methods

Expression of sorbin and SH3 domain‐containing 2 (SORBS2) in hepatocellular carcinoma (HCC) was detected by qRT‐PCR, immunohistochemistry assay and Western blot assay. Proliferation, migration, invasion and cell cycle progression of HCC cells were measured by 3‐(4,5‐Dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assay, colony‐forming assay, Transwell assay and flow cytometry assay respectively. A xenograft model and metastatic model were established to evaluate the proliferation and metastasis of HCC cells in vivo. Western blot assays were performed to assess the expression of epithelial‐mesenchymal transition markers. Luciferase reporter assay, RNA immunoprecipitation and pull‐down assay elucidated the effect of SORBS2 on one of its downstream genes.

Results

The expression of SORBS2 was significantly decreased in HCC and was associated with metastasis, advanced TNM clinical stage and poor clinical outcome of HCC patients. Furthermore, our results suggested that SORBS2 inhibited HCC cell proliferation, invasion, migration and EMT both in vivo and in vitro. Mechanistically, we revealed that retinoic acid receptor‐related orphan receptor (RORA) was a major target of SORBS2 and was critical to sustaining the antitumour effect of SORBS2 on HCC cells. SORBS2 reduced RORA mRNA degradation by directly binding to the 3′UTR of RORA mRNA.

Conclusions

In this study, we found for the first time that SORBS2 contributed to the suppression of HCC tumourigenesis and metastasis via post‐transcriptional regulation of RORA expression as an RBP.
Management of human immunodeficiency virus–associated cryptococcal meningitis: Current status and future directions
Authors: Wu Xueyun , Shen Yinzhong
Published: July 2019

Cryptococcal meningitis (CM) is one of the most common opportunistic infections of acquired immunodeficiency syndrome (AIDS), as well as an important cause of hospitalisation and death. In recent years, the mortality of CM has remained high in HIV/AIDS population, with up to 30%, including within developed countries. The treatment usually encompasses controls of Cryptococcus, HIV, and increased intracranial pressure. Recent progress on the management of HIV‐associated CM mainly centres in optimising induction regimens, looking for appropriate timing of initiating antiretroviral therapy and prevention of symptomatic onset and adverse consequences. This review compared several international guidelines combined with the results from some clinical researches to illustrate the similarities, differences and potential in CM treatment. The present practice is still far from satisfactory, and there remains much to explore due to our limited understanding of the pathogenesis of HIV‐associated CM. Thus, screening and monitoring should be strengthened, and better therapies in line with the actual situation of each country should be discovered.
NADPH oxidase regulates chemotropic growth of the fungal pathogen Fusarium oxysporum towards the host plant
Authors: Nordzieke Daniela Elisabeth , Fernandes Tânia R. , El Ghalid Mennat , Turrà David , Di Pietro Antonio
Published: July 2019

Soil‐inhabiting fungal pathogens use chemical signals to locate and colonise the host plant. In the vascular wilt fungus Fusarium oxysporum, hyphal chemotropism towards tomato roots is triggered by secreted plant peroxidases (Prx), which catalyse the reductive cleavage of reactive oxygen species (ROS).

Here we show that this chemotropic response requires the regulated synthesis of ROS by the conserved fungal NADPH oxidase B (NoxB) complex, and their transformation into hydrogen peroxide (H2O2) by superoxide dismutase (SOD). Deletion of NoxB or the regulatory subunit NoxR, or pharmacological inhibition of SOD, specifically abolished chemotropism of F. oxysporum towards Prx gradients.

Addition of isotropic concentrations of H2O2 rescued chemotropic growth in the noxBΔ and noxRΔ mutants, but not in a mutant lacking the G protein‐coupled receptor Ste2. Prx‐triggered rapid Nox‐ and Ste2‐dependent phosphorylation of the cell wall integrity mitogen‐activated protein kinase (CWI MAPK) Mpk1, an essential component of the chemotropic response. These results suggest that Ste2 and the CWI MAPK cascade function downstream of NoxB in Prx chemosensing.

Our findings reveal a new role for Nox enzymes in directed hyphal growth of a filamentous pathogen towards its host and might be of broad interest for chemotropic interactions between plants and root‐colonising fungi.
Rehabilitating Statistical Evidence
Authors: Ross Lewis
Published: July 2019

Recently, the practice of deciding legal cases on purely statistical evidence has been widely criticised. Many feel uncomfortable with finding someone guilty on the basis of bare probabilities, even though the chance of error might be stupendously small. This is an important issue: with the rise of DNA profiling, courts are increasingly faced with purely statistical evidence. A prominent line of argument—endorsed by Blome‐Tillmann 2017; Smith 2018; and Littlejohn 2018 rejects the use of such evidence by appealing to epistemic norms that apply to individual inquirers. My aim in this paper is to rehabilitate purely statistical evidence by arguing that, given the broader aims of legal systems, there are scenarios in which relying on such evidence is appropriate. Along the way I explain why popular arguments appealing to individual epistemic norms to reject legal reliance on bare statistics are unconvincing, by showing that courts and individuals face different epistemic predicaments (in short, individuals can hedge when confronted with statistical evidence, while legal tribunals cannot). I also correct some misconceptions about legal practice that have found their way into the recent literature.
Mesenchymal stem cells reduce ER stress via PERK‐Nrf2 pathway in an aged mouse model
Authors: Lee Eun Joo , Cárdenes Nayra , Álvarez Diana , Sellarés Jacobo , Sembrat John , Aranda Paola , Peng Yating , Bullock Jordan , Nouraie Seyed M. , Mora Ana L. , Rojas Mauricio
Published: July 2019

Background and objective

Mesenchymal stem cells (MSC) have been shown to ameliorate the deleterious effects of bleomycin in murine models. However, the mechanism responsible for protection from pulmonary fibrosis by stem cell therapy is still poorly understood, especially in terms of endoplasmic reticulum (ER) stress. We hypothesized that during bleomycin‐induced lung injury, markers of ER stress, specifically the activation of the unfolded protein response (UPR), increase during injury, resembling the kinetics of collagen deposition in the lung described for the bleomycin model. We aimed to elucidate the possible role of MSC in ER stress modulation.

Methods

To determine the kinetics of ER stress in aged mice, the expression of ER stress markers after bleomycin lung injury was measured in old mice at different time points (days 0, 3, 7, 14 and 21). To evaluate the consequences of systemic delivery of MSC on lung ER stress in the bleomycin model, we evaluated changes in body weight, lung histology and protein expression of ER stress markers.

Results

The level of expression of UPR transcription factor XBP‐1 and its regulator BiP was elevated at day 7 and progressively increased up to day 21. MSC inhibited BiP expression in bleomycin‐induced ER stress, attenuating ER stress via the protein kinase RNA‐like ER kinase (PERK)‐Nrf2 pathway. The expression levels of other ER stress markers were not perturbed by MSC.

Conclusion

Our data suggest that MSC operate on ER stress via several pathways, but the PERK‐Nrf2 pathway revealed to be the main functioning pathway in our bleomycin model.
Dimension reduction for the conditional mean and variance functions in time series
Authors: Park Jin‐Hong , Samadi S. Yaser
Published: July 2019

This paper deals with the nonparametric estimation of the mean and variance functions of univariate time series data. We propose a nonparametric dimension reduction technique for both mean and variance functions of time series. This method does not require any model specification and instead we seek directions in both the mean and variance functions such that the conditional distribution of the current observation given the vector of past observations is the same as that of the current observation given a few linear combinations of the past observations without loss of inferential information. The directions of the mean and variance functions are estimated by maximizing the Kullback–Leibler distance function. The consistency of the proposed estimators is established. A computational procedure is introduced to detect lags of the conditional mean and variance functions in practice. Numerical examples and simulation studies are performed to illustrate and evaluate the performance of the proposed estimators.
Equine infectious keratitis in Finland: Associated microbial isolates and susceptibility profiles
Authors: Mustikka Minna P. , Grönthal Thomas S. C. , Pietilä Elina M.
Published: July 2019

Objective

To retrospectively describe laboratory findings, treatment, and outcome associated with equine infectious keratitis in Finland.

Animals and procedures

Medical records of horses diagnosed with infectious keratitis in University of Helsinki Equine Hospital from January 2007 to June 2018 were reviewed.

Results

Forty‐seven cases were included. Keratomycosis was diagnosed in 27 eyes and bacterial keratitis in 20 eyes.Aspergillus flavuswas the most frequent fungal isolate (9/17, 53%), followed byCylindrocarponsp. (3/17, 18%) andAspergillus fumigatus(2/17, 12%). Susceptibility was tested for 10/11Aspergillussp. isolates; all were susceptible to voriconazole while only two were susceptible to amphotericin B.Cylindrocarponsp. isolates were resistant to both agents.Streptococcus equisubsp.zooepidemicuswas the most frequent bacterial isolate (9/19, 47%), followed by other streptococci (4/19, 21%). All 13Streptococcussp. isolates were susceptible to penicillin, and all tested isolates (n = 11) were also susceptible to chloramphenicol. Mean duration of medical treatment was longer in fungal keratitis (38 days) than in bacterial keratitis (25 days) (P < .001). Twenty‐six of the eyes underwent globe‐sparing surgery in addition to medical therapy. Recovery was achieved in 66% (31/47) of all cases and in 59% (16/27) and 75% (15/20) (P = .264) of cases with keratomycosis and bacterial keratitis, respectively.

Conclusions

AlthoughAspergillussp. andS zooepidemicuswere the most frequently encountered isolates, cytology, culture, and susceptibility testing are essential to differentiate bacterial and fungal keratitis and guide the clinician to choose the most efficient treatment.
Some integral inequalities for multiplicatively geometrically P-functions
Authors: Kadakal Huriye
Published: July 2019

In this manuscript, by using a general identity for differentiable functions we can obtain new estimates on a generalization of Hadamard, Ostrowski and Simpson type inequalities for functions whose derivatives in absolute value at certain power are multiplicatively geometrically P-functions. Some applications to special means of real numbers are also given.
Stochastic tunneling across fitness valleys can give rise to a logarithmic long-term fitness trajectory
Authors: Guo Yipei , Vucelja Marija , Amir Ariel
Published: July 2019

Theoretical model suggests that gene interactions, known as epistasis, may dramatically slow down evolutionary dynamics.
Neural correlates of weighted reward prediction error during reinforcement learning classify response to cognitive behavioral therapy in depression
Authors: Queirazza Filippo , Fouragnan Elsa , Steele J. Douglas , Cavanagh Jonathan , Philiastides Marios G.
Published: July 2019

fMRI activity encoding acquisition and processing of feedback enables discrimination of response to self-help CBT in depression.
Treating ischemia via recruitment of antigen-specific T cells
Authors: Kwee Brian J. , Seo Bo Ri , Najibi Alexander J. , Li Aileen W. , Shih Ting-Yu , White Des , Mooney David J.
Published: July 2019

Recruitment of antigen-specific T cells promotes vascularization in ischemic injuries in mice.
Dynamic earthquake rupture in the lower crust
Authors: Petley-Ragan Arianne , Ben-Zion Yehuda , Austrheim Håkon , Ildefonse Benoit , Renard François , Jamtveit Bjørn
Published: July 2019

A lower crustal earthquake is initiated by dynamic rupturing with fragmentation of wall rock that precedes frictional melting.
Cyclooxygenase 2 augments osteoblastic but suppresses chondrocytic differentiation of CD90
+
skeletal stem cells in fracture sites
Authors: Wasnik Samiksha , Lakhan Ram , Baylink David J. , Rundle Charles H. , Xu Yi , Zhang Jintao , Qin Xuezhong , Lau Kin-Hing William , Carreon Edmundo E. , Tang Xiaolei
Published: July 2019

This study identifies that cyclooxygenase 2 targets CD90
+
skeletal stem cells in fracture sites to accelerate fracture repair.
Diversity of the Madden-Julian Oscillation
Authors: Wang Bin , Chen Guosen , Liu Fei
Published: July 2019

We report propagation diversity of the tropical convective systems with a time scale of 4 to 8 weeks and examine its causes.
Cancer likes it saturated
Authors: El-Kenawi Asmaa
Published: July 2019

Constitutively active EGFR drives glioblastoma progression by overproducing saturated phosphatidylcholine.
Whole-Genome Sequence of French Clinical Olivibacter jilunii Strain P8502
Authors: Anani Hussein , Khodor May , Raoult Didier , Fournier Pierre-Edouard
Published: July 2019

In 2013,
Olivibacter jilunii
was reported as a bacterial species isolated from contaminated soil. In 2018, a clinical strain from the same species was isolated from the rectal swab of a Hajj pilgrim. Genome sequencing yielded 6,704,032 bp, with 41.2% G+C content, 5,406 protein-coding genes, and 54 predicted RNA genes in strain P8502.