bluuebunny/crossref_metadata_2025 huggingface dataset:
A Pilot Follow‐Up Study of Older Alcohol‐Dependent COGA Adults
Authors: Chan Grace , Kramer John R. , Schuckit Marc A. , Hesselbrock Victor , Bucholz Kathleen K. , Edenberg Howard J. , Acion Laura , Langbehn Douglas , McCutcheon Vivia , Nurnberger John I. , Hesselbrock Michie , Porjesz Bernice , Bierut Laura , Marenna Bethany C. , Cookman Angella , Kuperman Samuel
Published: May 2019

Background

Alcohol consumption and problems are increasing among older adults, who are at elevated risk for alcohol‐related accidents and medical problems. This paper describes a pilot follow‐up of older adults with a history of alcohol dependence that was designed to determine the feasibility of conducting a more extensive investigation.

Methods

The sample consisted of previously assessed subjects in the Collaborative Studies on the Genetics of Alcoholism who: (i) were age 50+; (ii) had lifetime DSM‐IV AD; and (iii) had DNA available. Individuals were located through family contacts, Internet searches, and death registries. A brief telephone interview assessed demographics, health, and alcohol involvement.

Results

Of the total sample (N = 2,174), 36% were contacted, 24% were deceased, and 40% were not yet located. Most (89%) contacted subjects were interviewed, and 99% of them agreed to future evaluation. Thirty percent of interviewed subjects reported abstinence for 10+ years, 56% reported drinking within the past year, and 14% last drank between >1 and 10 years ago. There were no age‐related past‐year differences in weekly consumption (overall sample mean: 16 drinks), number of drinking weeks (30.8), maximum number of drinks in 24 hours (8.1), or prevalence of weekly risky drinking (19%). Among those who drank within the past 5 years, the 3 most common alcohol‐related problems were spending excessive time drinking or recovering (49%), drinking more/longer than intended (35%), and driving while intoxicated (35%); and about a third (32%) received some form of treatment.

Conclusions

Over a 1‐year period, we located 60% of individuals last seen an average of 23 years ago. The majority of contacted individuals were interviewed and willing to be evaluated again. Although the proportion of individuals currently drinking diminished with age, subjects exhibited troublesome levels of alcohol consumption and problems. Our findings suggest the importance and feasibility of a more comprehensive follow‐up.
Relationship between types of humour and stress response and well‐being among children in Japan
Authors: Tsukawaki Ryota , Kojima Nanae , Imura Tomoya , Furukawa Yoshiya , Ito Katsuhiro
Published: May 2019

This study examined the relationship between three types of children's humour (aggressive, self‐defeating, and playful) and the children's stress response and well‐being in the Japanese context, where a collectivistic culture is prevalent. To do so, 500 study participants (250 elementary and 250 junior high school students) were recruited. The participants reported the types of humour, stress responses, and level of well‐being that they experienced. After correlation analysis, aggressive humour and playful humour showed a positive correlation with stress responses; in addition, aggressive humour showed a negative correlation with well‐being. Self‐defeating humour showed a negative correlation with stress responses and a positive correlation with well‐being. We also conducted a cluster analysis using the scores for the three types of humour, analysing four groups: “aggressive humourists” (respondents who demonstrated above‐average aggressive humour and scored average for all other humours), “nonhumourists” (below‐average humour in all areas), “self‐deprecating humourists” (above‐average self‐defeating humour, below‐average aggressive humour, and average playful humour), and “multiple humourists” (above‐average humour in all areas). Upon comparing the results of stress responses and well‐being scores among the four groups, we found that self‐deprecating humourists reported the highest level of well‐being. These results show that in collectivistic cultures, self‐defeating humour may be adaptive.
There's an App for That: Telecom, Children's Rights, and Conflicting Logics of Corporate Social Responsibility
Authors: Campoamor Leigh M.
Published: May 2019

This article examines how a Spanish telecom giant legitimizes its market expansion through a corporate social responsibility (CSR) narrative that links generic notions of technological innovation and children's rights to projects of development and democracy. At a broad level, I explore how the neoliberal privatization of the telecommunications industry has involved a reconfiguration of corporate‐state relations rather than an erasure of the state in corporate discourse. I trace how Telefónica accrues currency as a digital pioneer and provider of a social good by incorporating consumers, state actors, and other corporations into its moral apparatus. My point of entry is a smartphone application that the company's Colombian subsidiary developed and subsequently gamified to empower consumer‐citizens to end street‐based child labor. Within a digital economy of “instant gratification” and national context of securitization, the process whereby consumers are interpellated as citizen‐activists highlights the thin line between profiling techniques and humanitarian action, and between surveillance and activism, while disguising the limits of the state bureaucracy and the company's own distance from its purported beneficiaries. Ultimately, I show how the company maintained its narrative about its innovative and sustainable commitment to children even when explaining the failures of its CSR strategy. [digital activism, corporate social responsibility, children's rights, corporate–state relations, urban Latin America]
Implementation and obstacles of pharmacogenetics in clinical practice: An international survey
Authors: Abou Diwan Elizabeth , Zeitoun Ralph I. , Abou Haidar Lea , Cascorbi Ingolf , Khoueiry Zgheib Nathalie
Published: May 2019

Aims

Eight years ago, a paper‐based survey was administered during the World Pharma 2010 meeting, asking about the challenges of implementing pharmacogenetics (PGx) in clinical practice. The data collected at the time gave an idea about the progress of this implementation and what still needs to be done. Since then, although there have been major initiatives to push PGx forward, PGx clinical implementation may still be facing different challenges in different parts of the world. Our aim was therefore to distribute a follow‐up international survey in electronic format to elucidate an overview on the current stage of implementation, acceptance and challenges of PGx in academic institutions around the world.

Methods

This is an online anonymous LimeSurvey‐based study launched on 11 November 2018. Survey questions were adapted from the initially published manuscript in 2010. An extensive web search for worldwide scientists potentially involved in PGx research resulted in a total of 1973 names. Countries were grouped based on the Human Development Index.

Results

There were 204 respondents from 43 countries. Despite the wide availability of PGx tests, the consistently positive attitude towards their applications and advances in the field, progress of the clinical implementation of PGx still faces many challenges all around the globe.

Conclusions

Clinical implementation of PGx started over a decade ago but there is a gap in progress around the globe and discrepancies between the challenges reported by different countries, despite some challenges being universal. Further studies on ways to overcome these challenges are warranted.
Predicting anaemia and transfusion dependency in severe alloimmune haemolytic disease of the fetus and newborn in the first 3 months after birth
Authors: Ree Isabelle M. C. , de Haas Masja , Middelburg Rutger A. , Zwiers Carolien , Oepkes Dick , van der Bom Johanna G. , Lopriore Enrico
Published: May 2019

Infants with haemolytic disease of the fetus and newborn (HDFN) often require erythrocyte transfusions in the first 3 months of life. We aimed to evaluate the incidence, timing and potential predictors of transfusion‐dependent anaemia. An observational cohort of 298 term and near‐term infants with severe HDFN treated with or without intrauterine transfusion (IUT) was evaluated. Transfusions were administered to 88% (169/193) of infants with IUT and 60% (63/105) without IUT. The following potential predictors were associated with less anaemia: K compared to D immunisation [odds ratio (OR) 0·13, 95% confidence interval (CI): 0·03–0·55], higher reticulocyte count at birth [per 10 parts per thousand (‰) higher, OR 0·99, CI: 0·97–1·00] and exchange transfusion (OR 0·11, 95% CI: 0·03–0·50). Without IUT, these variables were: lower reticulocyte count at birth (per 10‰ lower, OR 1·02, 95% CI: 1·00–1·03), lower maximum bilirubin after birth (per 10 μmol/l lower, OR 1·01, 95% CI: 1·01–1·02) and exchange transfusion (OR 0·07, 95% CI: 0·01–0·20). In conclusion, potential predictors for anaemia in infants with severe HDFN varied between infants treated with and without IUT and are useful for selecting subgroups of infants at increased risk of anaemia.
The effects of hydroxycarbamide on the plasma proteome of children with sickle cell anaemia
Authors: Brewin John , Tewari Sanjay , Menzel Stephan , Kirkham Fenella , Inusa Baba , Renney George , Ward Malcolm , Rees David C.
Published: May 2019

We investigated changes in the plasma proteome of children with sickle cell anaemia (SCA) associated with hydroxycarbamide (HC) use, to further characterize the actions of HC. Fifty‐one children with SCA consented to take part in this study. Eighteen were taking HC at a median dose of 22 mg/kg, and 33 were not on HC. Plasma was analysed using an unbiased proteomic approach and a panel of 92 neurological biomarkers. HC was associated with increased haemoglobin (Hb) (89·8 vs. 81·4 g/l, P = 0·007) and HbF (6·7 vs. 15·3%, P < 0·001). Seventeen proteins were decreased on HC compared to controls by a factor of <0·77, and six proteins showed >1·3 increased concentration. HC use was associated with reduced haemolysis (lower α, β, δ globin chains, haptoglobin‐related protein, complement C9; higher haemopexin), reduced inflammation (lower α‐1‐acid glycoprotein, CD5 antigen‐like protein, ceruloplasmin, factor XII, immunoglobulins, cysteine‐rich secretory protein 3, vitamin D‐binding protein) and decreased activation of coagulation (lower factor XII, carboxypeptidase B2, platelet basic protein). There was a significant correlation between the increase in HbF% on HC and haemopexin levels (r = 0·603, P = 0·023). This study demonstrated three ways in which HC may be beneficial in SCA, and identified novel proteins that may be useful to monitor therapeutic response.
Risk of metastatic disease on 68gallium‐prostate‐specific membrane antigen positron emission tomography/computed tomography scan for primary staging of 1253 men at the diagnosis of prostate cancer
Authors: Yaxley John W. , Raveenthiran Sheliyan , Nouhaud François‐Xavier , Samaratunga Hemamali , Yaxley William J. , Coughlin Geoff , Yaxley Anna J. , Gianduzzo Troy , Kua Boon , McEwan Louise , Wong David
Published: May 2019

Objective

To determine the number of men with 68gallium‐prostate‐specific membrane antigen positron emission tomography/computed tomography (68Ga‐PSMA PET/CT) avid metastasis at diagnosis, as most data on 68Ga‐PSMA PET/CT are for the evaluation of recurrent disease after primary treatment and to our knowledge this study is the largest series of primary prostate cancer staging with 68Ga‐PSMA PET/CT.

Patients and Methods

A retrospective review conducted on 1253 consecutive men referred by urologists or radiation oncologists to our tertiary referral centre for 68Ga‐PSMA PET/CT scan for staging at the initial diagnosis of prostate cancer between July 2014 and June 2018.

The primary outcome measure was to determine the risk of metastasis based on 68Ga‐PSMA PET/CT. Patients were risk stratified based on histological biopsy International Society of Urological Pathology (ISUP) grade, prostate‐specific antigen (PSA) level, and staging with pre‐biopsy multiparametric magnetic resonance imaging (mpMRI). Univariate and multivariate logistic regression were used to analyse results.

Results

The median PSA level was 6.5 ng/mL and median ISUP grade was 3, with high‐risk disease in 49.7%. The prostate primary was PSMA avid in 91.7% of men. Metastatic disease was identified in 12.1% of men, including 8.2% with a PSA level of <10 ng/mL and 43% with a PSA level of >20 ng/mL. Metastases were identified in 6.4% with ISUP grade 2–3 and 21% with ISUP grade 4–5. Pre‐biopsy mpMRI identified metastasis in 8.1% of T2 disease, increasing to 42.4% of T3b. Lymph node metastases were suspected in 107 men, with 47.7% outside the boundaries of an extended pelvic lymph node dissection. Skeletal metastases were identified in 4.7%. In men with intermediate‐risk prostate cancer, metastases were identified in 5.2%, compared to 19.9% with high‐risk disease.

Conclusions

These results support the use of 68Ga‐PSMA PET/CT for primary staging of prostate cancer. Increasing PSA level, ISUP grade and radiological staging with mpMRI were all statistically significant prognostic factors for metastasis on both univariate and multivariate analysis.
Use of multiparametric magnetic resonance imaging and fusion‐guided biopsies to properly select and follow African‐American men on active surveillance
Authors: Bloom Jonathan B. , Lebastchi Amir H. , Gold Samuel A. , Hale Graham R. , Sanford Thomas , Mehralivand Sherif , Ahdoot Michael , Rayn Kareem N. , Czarniecki Marcin , Smith Clayton , Valera Vladimir , Wood Bradford J. , Merino Maria J. , Choyke Peter L. , Parnes Howard L. , Turkbey Baris , Pinto Peter A.
Published: May 2019

Objectives

To determine the rate of Gleason Grade Group (GGG) upgrading in African‐American (AA) men with a prior diagnosis of low‐grade prostate cancer (GGG 1 or GGG 2) on 12‐core systematic biopsy (SB) after multiparametric magnetic resonance imaging (mpMRI) and fusion biopsy (FB); and whether AA men who continued active surveillance (AS) after mpMRI and FB fared differently than a predominantly Caucasian (non‐AA) population.

Patients and methods

A database of men who had undergone mpMRI and FB was queried to determine rates of upgrading by FB amongst men deemed to be AS candidates based on SB prior to referral. After FB, Kaplan–Meier curves were generated for AA men and non‐AA men who then elected AS. The time to GGG upgrading and time continuing AS were compared using the log‐rank test.

Results

AA men referred with GGG 1 disease on previous SB were upgraded to GGG ≥3 by FB more often than non‐AA men, 22.2% vs 12.7% (P = 0.01). A total of 32 AA men and 258 non‐AA men then continued AS, with a median (interquartile range) follow‐up of 39.19 (24.24–56.41) months. The median time to progression was 59.7 and 60.5 months, respectively (P = 0.26). The median time continuing AS was 61.9 months and not reached, respectively (P = 0.80).

Conclusions

AA men were more likely to be upgraded from GGG 1 on SB to GGG ≥3 on initial FB; however, AA and non‐AA men on AS subsequently progressed at similar rates following mpMRI and FB. A greater tendency for SB to underestimate tumour grade in AA men may explain prior studies that have shown AA men to be at higher risk of progression during AS.
Hydrogen sulfide lowers hyperhomocysteinemia dependent on cystathionine γ lyase S‐sulfhydration in ApoE‐knockout atherosclerotic mice
Authors: Fan Jinhui , Zheng Fengjiao , Li Shuangyue , Cui Cangting , Jiang Shan , Zhang Jun , Cai Jun , Cui Qinghua , Yang Jichun , Tang Xinjing , Xu Guoheng , Geng Bin
Published: May 2019

Background and Purpose

Hydrogen sulfide donors can block the cardiovascular injury of hyperhomocysteinemia. H2S also lowers serum homocysteine in rats with mild hyperhomocysteinemia, but the pharmacological mechanism is unknown. The present study investigated the mechanism(s) involved.

Experimental Approach

ApoE‐knockout mice were fed a Paigen diet and L‐methionine in drinking water for 16 weeks to create a mouse model of atherosclerosis with hyperhomocysteinemia. H2S donors (NaHS and GYY4137) were administered by intraperitoneal injection. We also assayed the H2S produced (by methylene blue assay and mito‐HS [H2S fluorescence probe]), cystathionine γ lyase (CSE) mRNA and protein expression, and CSE sulfhydration and nitrosylation and its activity.

Key Results

H2S donor treatment significantly lowered atherosclerotic plaque area, macrophage infiltration, and serum homocysteine level in the mouse model of atherosclerosis with co‐existing hyperhomocysteinemia. mRNA and protein levels of CSE, a key enzyme catalyzing homocysteine trans‐sulfuration, were down‐regulated with hyperhomocysteinemia, and CSE catalytic activity was inhibited. All these effects were reversed with H2S donor treatment. Hyperhomocysteinemia induced CSE nitrosylation, whereas H2S sulfhydrated CSE at the same cysteine residues. Nitrosylated CSE decreased and sulfhydrated CSE increased its catalytic and binding activities towards L‐homocysteine. Mutation of C252, C255, C307, and C310 residues in CSE abolished CSE nitrosylation or sulfhydration and prevented its binding to L‐homocysteine.

Conclusions and Implications

Sulfhydration or nitrosylation of CSE represents a yin/yang regulation of catalysis or binding to L‐homocysteine. H2S donor treatment enhanced CSE sulfhydration, thus lowering serum L‐homocysteine, which contributed in part to the anti‐atherosclerosis effects in ApoE‐knockout mice with hyperhomocysteinemia.
Base‐salt relief controls salt‐tectonic structural style, São Paulo Plateau, Santos Basin, Brazil
Authors: Pichel Leonardo M. , Jackson Christopher A.‐L. , Peel Frank , Dooley Tim P.
Published: May 2019

Base‐salt relief influences salt flow, producing three‐dimensionally complex strains and multiphase deformation within the salt and its overburden. Understanding how base‐salt relief influences salt‐related deformation is important to correctly interpret salt basin kinematics and distribution of structural domains, which have important implications to understand the development of key petroleum system elements. The São Paulo Plateau, Santos Basin, Brazil is characterized by a >2 km thick, mechanically layered Aptian salt layer deposited above prominent base‐salt relief. We use 3D seismic reflection data, and physical and conceptual kinematic models to investigate how gravity‐driven translation above thick salt, underlain by complex base‐salt relief, generated a complex framework of salt structures and minibasins. We show that ramp‐syncline basins developed above and downdip of the main pre‐salt highs record c. 30 km of Late Cretaceous‐Paleocene basinward translation. As salt and overburden translated downdip, salt flux variations caused by the base‐salt relief resulted in non‐uniform motion of the cover, and the simultaneous development of extensional and contractional structures. Contraction preferentially occurred where salt flow locally decelerated, above landward‐dipping base‐salt and downdip of basinward‐dipping ramps. Extension occurred at the top of basinward‐dipping ramps and base‐salt plateaus, where salt flow locally accelerated. Where the base of the salt layer was broadly flat, structures evolved primarily by load‐driven passive diapirism. At the edge of or around smaller base‐salt highs, salt structures were affected by plan‐view rotation, shearing and divergent flow. The magnitude of translation (c. 30 km) and the style of salt‐related deformation observed on the São Paulo Plateau afford an improved kinematic model for the enigmatic Albian Gap, suggesting this structure formed by a combination of basinward salt expulsion and regional extension. These observations contribute to the long‐lived debate regarding the mechanisms of salt tectonics on the São Paulo Plateau, ultimately improving our general understanding of the effects of base‐salt relief on salt tectonics in other basins.
Cities and places in provincial policy agendas
Authors: Peterson Jacqueline , Lucas Jack , Klain Andrew
Published: May 2019

This article uses a new dataset of coded Alberta Throne Speeches from 1906 to 2017 to identify patterns of provincial policy attention to place and urban place across policy issues and time. We discuss three main findings. First, provincial attention to place and urban place is influenced by policy domain: place‐based attention is generally absent in some policy domains, such as macroeconomic policy, and prevalent in others, such as health care. Second, place‐based attention is patterned over time, with a noticeable peak in the post‐war “province‐building” years and distinct troughs in other periods. Finally, we discuss the related but distinct patterns of attention to place and urban place across policy domains and time.
Cultural Underpinnings of Gender Development: Studying Gender Among Children of Immigrants
Authors: Schroeder Kingsley M. , Bámaca‐Colbert Mayra Y.
Published: May 2019

This article addresses the historical divide between gender development researchers and developmental researchers working with immigrant populations, advocating for the benefits gained by bridging research approaches and interests. For gender researchers, the immigrant context allows for the examination of how children embedded in multiple cultures navigate the potentially conflicting information about appropriate gendered behaviors and attitudes. Furthermore, research focusing on immigrant development can move beyond examining gender differences and benefit from understanding the ways in which gender differences develop. This bridging seems particularly relevant in middle childhood, given (a) the exposure to multiple contexts which increase the salience of cultural differences between home and outside‐of‐home environments and (b) greater awareness and internalization of collective identities (i.e., gender, ethnicity).
Should testing be initiated prior to amoxicillin challenge in children?
Authors: Abrams Elissa M. , Ben‐Shoshan Moshe
Published: May 2019

Amoxicillin is the most common antibiotic prescribed in children with increasing use over time. While up to 10% of children are labelled as amoxicillin allergic, most children can tolerate amoxicillin after allergy evaluation. It is well documented that the label of amoxicillin allergy in children is associated with adverse health outcomes such as antibiotic‐resistant infections. However, it remains controversial how best to assess children for amoxicillin allergy. While in general it is recommended that skin testing be done prior to drug provocation test in the evaluation of amoxicillin allergy, there is increasing evidence that drug provocation testing could be done in lower risk children without skin testing prior. The goal of this article as a narrative review is to review the strengths and limitations of skin testing prior to drug provocation test in children who have a history of either immediate or non‐immediate, reactions to amoxicillin.
Typical practices of lesson study in East Asia
Authors: Chen Xiangming , Zhang Yurong
Published: May 2019

As countries worldwide aim to reform their education systems and improve teaching and learning, lesson study (LS), which originated in East Asia, has recently attracted great attention. In order for international educators and policy makers to better understand the history and the state of the art of LS in East Asia, this article introduces three typical models in Japan, Mainland China and Hong Kong. First, they are described with regard to their distinct features, historical origin and development, goals and objectives, mechanisms of implementation, actual achievements, and structural constraints. Their commonalities and differences are then compared, and especially how and why these differences emerge in the specific sociocultural contexts of the regions. Finally, policy implications are discussed to provide insights for the other education systems in their policy making and implementation of similar reform practices.
Lesson study in teacher development: A paradigm shift from a culture of receiving to a culture of acting and reflecting
Authors: Mewald Claudia , Mürwald‐Scheifinger Elisabeth
Published: May 2019

This article describes how lesson study creates a process of teacher learning whilst developing student learning through collaborative planning, guided observation and reflection. It presents a framework for conducting lesson study in a teacher development programme in Lower Austria. The role of knowledgeable others in the development of ownership for educational change towards competence‐oriented teaching and learning is explored and an overview of the organisational requirements and practical effects in the implementation of professional learning communities is given. In doing so, the article sheds light on training strategies and material development. Thus, insights on a paradigm shift in teacher development towards learning focused on discourse and reflected action are presented.
Lesson and learning studies—An edifying story
Authors: Gordon Győri János
Published: May 2019

It would be difficult to find any pedagogical story that is comparable to that of jugyou kenkyuu (or lesson study in English) that has been practised for over a century in Japan in isolation and became a method that was used worldwide in less than 10 years. Because of its uniqueness and its history, it is an irrefutable challenge to understand what it is really about, how its basic aspects such as a lesson or teachers' knowledge and its development, the culture of education, the measurability of educational activities and other main aspects of education are or can be conceptualised and in which ways these can travel in a globalised arena of education. In this article, we try to give answers to these and some other relevant issues related to lesson study via the author's subjective view and individually‐constructed narrative.
Enhancing decision making by providing a unified system for computer‐interpretable guideline management
Authors: Silva António , Oliveira Tiago , Gonçalves Filipe , Novais Paulo
Published: May 2019

The need for integration of clinical practice guidelines (CPGs) in daily clinical practice calls for computational systems able to operationalise their knowledge and provide an enhanced experience in their enactment. Current approaches lack in functionalities such as scheduling and temporal management of CPGs, the combination of CPGs, and user‐friendly systems for computer‐interpretable guideline (CIG) creation and editing. This paper presents a comprehensive architecture for the deployment of CIGs, featuring components that allow the following: the creation and manipulation of clinical practice guideline knowledge elements, execution of CIGs with the temporal verification of clinical tasks, and drug conflict identification and resolution. This comprehensive approach provides a step‐by‐step assistant for health care professionals in the form of an agenda of activities that detects drug interactions when they are prescribed simultaneously and applies a mitigation algorithm to select possible and conflict‐free alternatives. This work addresses the lack of a unified pipeline and mitigation features shown in approaches to CIG conflict mitigation in use.
Spiral ganglion cell degeneration‐induced deafness as a consequence of reduced GATA factor activity
Authors: Hoshino Tomofumi , Terunuma Tsumoru , Takai Jun , Uemura Satoshi , Nakamura Yasuhiro , Hamada Michito , Takahashi Satoru , Yamamoto Masayuki , Engel James Douglas , Moriguchi Takashi
Published: May 2019

Zinc‐finger transcription factors GATA2 and GATA3 are both expressed in the developing inner ear, although their overlapping versus distinct activities in adult definitive inner ear are not well understood. We show here that GATA2 and GATA3 are co‐expressed in cochlear spiral ganglion cells and redundantly function in the maintenance of spiral ganglion cells and auditory neural circuitry. Notably, Gata2 and Gata3 compound heterozygous mutant mice had a diminished number of spiral ganglion cells due to enhanced apoptosis, which resulted in progressive hearing loss. The decrease in spiral ganglion cellularity was associated with lowered expression of neurotrophin receptor TrkC that is an essential factor for spiral ganglion cell survival. We further show that Gata2 null mutants that additionally bear a Gata2 YAC (yeast artificial chromosome) that counteracts the lethal hematopoietic deficiency due to complete Gata2 loss nonetheless failed to complement the deficiency in neonatal spiral ganglion neurons. Furthermore, cochlea‐specific Gata2 deletion mice also had fewer spiral ganglion cells and resultant hearing impairment. These results show that GATA2 and GATA3 redundantly function to maintain spiral ganglion cells and hearing. We propose possible mechanisms underlying hearing loss in human GATA2‐ or GATA3‐related genetic disorders.
Population uptake and effectiveness of test‐and‐treat antiretroviral therapy guidelines for preventing the global spread of HIV: an ecological cross‐national analysis
Authors: Mendez‐Lopez A , McKee M , Stuckler D , Granich R , Gupta S , Noori T , Semenza JC
Published: May 2019

Objectives

Although the benefits of adopting test‐and‐treat antiretroviral therapy (ART) guidelines that recommend initiation of ART regardless of CD4 cell counts have been demonstrated at the individual level, there is uncertainty about how this translates to the population level. Here, we explored whether adopting ART guidelines recommending earlier treatment initiation improves population ART access and viral suppression and reduces overall disease transmission.

Methods

Data on ART initiation guidelines and treatment coverage, viral suppression, and HIV incidence from 37 European and Central Asian countries were collected from the European Centre for Disease Prevention and Control and the Global HIV Policy Watch and HIV 90‐90‐90 Watch databases. We used multivariate linear regression models to quantify the association of ART initiation guidelines with population ART access, viral suppression, and HIV incidence, adjusting for potential confounding factors.

Results

Test‐and‐treat policies were associated with 15.2 percentage points (pp) [95% confidence interval (CI) 0.8–29.6 pp; P = 0.039] greater treatment coverage (proportion of HIV‐positive people on ART) compared with countries with ART initiation at CD4 cell counts ≤ 350 cells/μL. The presence of test‐and‐treat policies was associated with 15.8 pp (95% CI 2.4–29.1 pp; P = 0.023) higher viral suppression rates (people on ART virally suppressed) compared with countries with treatment initiation at CD4 counts ≤ 350 cells/μL. ART initiation at CD4 counts ≤ 500 cells/μL did not significantly improve ART coverage compared to initiation at CD4 counts ≤ 350 cells/μL but achieved similar degrees of viral suppression as test‐and‐treat.

Conclusions

Test‐and‐treat was found to be associated with substantial improvements in population‐level access to ART and viral suppression, further strengthening evidence that rapid initiation of treatment will help curb the spread of HIV.
Angiotensin‐converting enzyme inhibitory activity of hydrolysates generated from whey protein fortified with salal fruits (Galtheria shallon) by enzymatic treatment with Pronase from Streptomyces griseus
Authors: Raikos Vassilios , Hays Helen , Stead David , Ni He
Published: May 2019

Whey proteins mixed with salal fruits extract (0–20% w/w) were hydrolysed with Pronase E from Streptomyces griseus for a period of 8 h. The angiotensin‐converting enzyme (ACE) inhibitory activity of the hydrolysates was highest (IC50: 0.087 mg mL−1) for samples fortified with the highest extract concentration (20%). Peptides (>7 amino acids) with documented ACE inhibitory activity (DAQSAPLRVY, ALPMHIR, DKVGINY, LHLPLPL, YPFPGPI, YPFPGPIPN, VYPFPGPIPN) were identified bv LC‐MS/MS data analysis using a database search approach. Fluorescence spectra of the whey proteins mixed with salal fruits extract indicates fluorescence quenching for α‐lactalbumin. SDS‐PAGE analysis suggests that α‐lactalbumin is less susceptible to proteolysis when the extract is included in the formula. Data indicate that α‐lactalbumin may be interacting with phenolic compounds naturally present in salal fruits. These interactions and the formation of complexes between a‐Lac and phenolic compounds may affect the hydrolysis pattern of whey protein and the release of peptides with ACE‐inhibitory activity.
Does Drug Use Lead to Homelessness for Young, Disadvantaged People?
Authors: McVicar Duncan , Moschion Julie , van Ours Jan
Published: May 2019

Drug use among homeless young people tends to be higher than drug use among those who are not homeless. Is that because drug use causes homelessness, as is often assumed? Duncan McVicar, Julie Moschion and Jan van Ours investigate.
The Tukeyg-and-hDistribution
Authors: Yan Yuan , Genton Marc G.
Published: May 2019

Yuan Yan and Marc G. Genton explain this boosted log-normal distribution, which can be used to model wind speed data and stock market returns, among other things
Ask a Statistician: Does Manchester United Really Have 100 Million Followers in China?
Authors: Mastrodomenico Rob
Published: May 2019

A reader writes: I was interested to see a Times article about some new Manchester United-themed centres that will be built in China. In the football club's associated press release, it claims to have “100 million followers” in China. This is, interestingly, 8 million fewer than the figure it claimed to have back in 2012. Is there any truth to these figures?
Graphical Interpretations of Data: A Hole Lot of Questions
Authors: Reese R. Allan
Published: May 2019

R. Allan Reese reviews one of the most dramatic scientific images of our age
Bortezomib attenuates renal interstitial fibrosis in kidney transplantation via regulating the EMT induced by TNF‐α‐Smurf1‐Akt‐mTOR‐P70S6K pathway
Authors: Zhou Jiajun , Cheng Hong , Wang Zijie , Chen Hao , Suo Chuanjian , Zhang Hengcheng , Zhang Jiayi , Yang Yanhao , Geng Liang , Gu Ming , Tan Ruoyun
Published: May 2019

Allograft interstitial fibrosis was characterized by massive extracellular matrix deposition caused by activated fibroblasts and myofibroblasts. Epithelial‐mesenchymal transition (EMT) is recognized as an important source of myofibroblasts contributing to the pathogenesis of allograft interstitial fibrosis. Smad ubiquitination regulatory factor 1 (Smurf1) has been recently reported to be involved in the progression of EMT. Our study was to detect the effect of Bortezomib and Smurf1 in the EMT and allograft interstitial fibrosis. Biomarkers of EMT, as well as Smurf1, were examined in human proximal tubular epithelial cells (HK‐2) treated with tumour necrosis factor‐alpha (TNF‐α) in various doses or at various time points by Western Blotting or qRT‐PCR. We knockdown or overexpressed Smurf1 in HK‐2 cells. Furthermore, rat renal transplant model was established and intervened by Bortezomib. Allograft tissues from human and rats were also collected and prepared for HE, Masson's trichrome, immunohistochemical staining and western blotting assays. As a result, we found that TNF‐α significantly promoted the development of EMT in a time‐dependent and dose‐dependent manner through Smurf1/Akt/mTOR/P70S6K signalling pathway. More importantly, Bortezomib alleviated the progression of EMT and allograft interstitial fibrosis in vivo and in vitro by inhibiting the production of TNF‐α and expression of Smurf1. In conclusion, Smurf1 plays a critical role in the development of EMT induced by TNF‐α. Bortezomib can attenuate the Sumrf1‐mediated progression of EMT and renal allograft interstitial fibrosis, which could be suggested as a novel choice for the prevention and treatment of renal allograft interstitial fibrosis.
Reply to comments made by M. Donnarumma et al. Comment on “Acne and nutrition: hypotheses, myths and facts” published by our expert group in 2018
Authors: Claudel J.P. , Auffret N. , Leccia M.T. , Poli F. , Dréno B.
Published: May 2019

Linked article: M. Donnarumma. J Eur Acad Dermatol Venereol 2019; 33: e418–e419. https://doi.org/10.1111/jdv.15723.
Fitness of reciprocal F1 hybrids between Rhinanthus minor and Rhinanthus major under controlled conditions and in the field
Authors: Wesselingh Renate A. , Hořčicová Šárka , Mirzaei Khaled
Published: May 2019

The performance of first‐generation hybrids determines to a large extent the long‐term outcome of hybridization in natural populations. F1 hybrids can facilitate further gene flow between the two parental species, especially in animal‐pollinated flowering plants. We studied the performance of reciprocal F1 hybrids between Rhinanthus minor and R. major, two hemiparasitic, annual, self‐compatible plant species, from seed germination to seed production under controlled conditions and in the field. We sowed seeds with known ancestry outdoors before winter and followed the complete life cycle until plant death in July the following season. Germination under laboratory conditions was much lower for the F1 hybrid formed on R. major compared with the reciprocal hybrid formed on R. minor, and this confirmed previous results from similar experiments. However, this difference was not found under field conditions, which seems to indicate that the experimental conditions used for germination in the laboratory are not representative for the germination behaviour of the hybrids under more natural conditions. The earlier interpretation that F1 hybrid seeds formed on R. major face intrinsic genetic incompatibilities therefore appears to be incorrect. Both F1 hybrids performed at least as well as and sometimes better than R. minor, which had a higher fitness than R. major in one of the two years in the greenhouse and in the field transplant experiment. The high fitness of the F1 hybrids confirms findings from naturally mixed populations, where F1 hybrids appear in the first year after the two species meet, which leads to extensive advanced‐hybrid formation and introgression in subsequent generations.
Maternal influence on early lipid content in an introduced partially anadromous population of Oncorhynchus mykiss
Authors: Liberoff Ana L. , Leal Alejandra A. , Díaz De Vivar María E. , Riva‐Rossi Carla M. , Pascual Miguel A.
Published: May 2019

This study evaluated how the maternal migratory tactic in a partially anadromous population of Oncorhynchus mykiss may influence the early energetic status of their offspring. Total lipid content variation (% dry mass) of recently emerged fry caught in the Santa Cruz River, Argentina, was evaluated as a function of their maternal origin (anadromous v. resident) and fork length (LF). Lipid content of fry decreased with LF and was higher for offspring of anadromous mothers.
Pumpkin (Cucurbita maxima) by‐products: Obtaining seed oil enriched with active compounds from the peel by ultrasonic‐assisted extraction
Authors: Massa Thainara Bovo , Stevanato Natália , Cardozo‐Filho Lúcio , da Silva Camila
Published: May 2019

Ultrasonic‐assisted extraction (UAE) of the oil from the seeds/peel mixture of pumpkin using ethanol as solvent was investigated. The effects of the ultrasound, solvent volume, time, and temperature on the oil yield were evaluated. Oil extraction from the seeds by ultrasound and the mixture by Soxhlet extraction (SE) was also performed. The use of ultrasound and higher availability of ethanol (up to 6 mL g−1 sample) favored the oil removal. In the extraction kinetics, the washing step was verified in the first 20 min, corresponding to 79–89% of the total oil yield. The diffusion coefficient increased from 30 to 75°C, as well as the spontaneity of the extraction, achieving 71% of the SE. Linoleic and oleic acids were found in higher concentrations in the oils. UAE made possible the greater extraction of β‐carotene, tocopherols, and fistosterois, and the peel addition provided higher contents of these compounds.

Practical application

The simultaneous extraction of compounds from the pumpkin by‐products arouses interest, for obtaining an oil of the seeds enriched with the active compounds present in the peel. Ultrasound‐assisted extraction was employed because it showed relevant benefits in relation to Soxhlet extraction, such as operations with reduced time, mild temperatures, and low amounts of solvent. Aiming at the use of solvents considered as “green,” in the present study we opted for the use of ethanol, since it is considered a safe solvent and comes from renewable sources. In addition, the determination of the diffusion coefficient and the thermodynamic properties of the process helped to understand the mechanisms that characterize the extraction.
Antidepressant Treatment for Late‐Life Depression: Considering Risks and Benefits
Authors: Lenze Eric J. , Ajam Oughli Hanadi
Published: May 2019

This editorial comments on the article by Sobieraj et al.
Training and confidence in undertaking child protection work as reported by New Zealand paediatricians
Authors: Neels Aimee , Tuohy Pat , Elder Dawn ,   on behalf of the Child Protection Clinical Network of the Paediatric Society of New Zealand
Published: May 2019

Aim

In New Zealand and rural Australia, general paediatricians undertake the majority of child protection (CP) medical assessments. This study aimed to document what New Zealand paediatricians think about their role in CP and their perceived preparedness for this work.

Methods

A 43‐item SurveyMonkey questionnaire was sent to paediatricians working in CP. Questions explored demographic detail, CP work undertaken clinically and with regard to teaching and paediatrician confidence and experience in areas of CP. A separate questionnaire documented organisational CP work.

Results

A total of 79 paediatricians, 45 (57%) female, responded from 15 of 20 District Health Boards. For 73%, CP was less than 10% of their weekly workload, with 42% indicating they had been the lead paediatrician for fewer than five cases in the preceding 12 months. Paediatricians were more confident managing physical abuse than sexual abuse cases with regard to initial assessments, report writing and appearances in court. Just over a third reported at least once feeling personally threatened or unsafe while involved in a CP case. Only 29% were satisfied with their level of training, and 73% agreed they would like more CP training.

Conclusions

Paediatricians undertake a number of roles in CP but do not feel confident in all these roles. More attention needs to be given to training in CP in general paediatric physician training in New Zealand.
In‐Hospital mortality varies by procedure type among cirrhosis surgery admissions
Authors: Mahmud Nadim , Fricker Zachary , Serper Marina , Kaplan David E. , Rothstein Kenneth D. , Goldberg David S.
Published: May 2019

Background

Patients with cirrhosis have increased peri‐operative mortality risk relative to non‐cirrhotic patients, however, the impact of surgical procedure category on this risk is poorly understood.

Methods

We performed a retrospective cohort study of cirrhosis surgery admissions using the National Inpatient Sample between 2012 and 2014 to estimate the adjusted odds of in‐hospital mortality by surgical procedure category.

Results

In‐hospital mortality differed by surgical procedure category. Relative to major orthopedic surgeries, major abdominal surgeries had the highest odds of in‐hospital mortality (odds ratio [OR] 8.27, 95% confidence interval [CI] 5.96‐11.49), followed by major cardiovascular surgeries (OR 3.45, 95% CI 2.33‐5.09). There was also a significant interaction term, whereby elective/non‐elective admission status impacted in‐hospital mortality risk differently for each surgical procedure category (P < 0.001).

Conclusion

In‐hospital mortality varies substantially by surgical procedure type. Accounting for procedure type in models may improve risk prediction for peri‐operative mortality in patients with cirrhosis.
A decomposition scheme for parallelization of system optimal dynamic traffic assignment on urban networks with multiple origins and destinations
Authors: Mehrabipour Mehrzad , Hajibabai Leila , Hajbabaie Ali
Published: May 2019

This paper presents a decomposition scheme to find near‐optimal solutions to a cell transmission model‐based system optimal dynamic traffic assignment problem with multiple origin‐destination pairs. A linear and convex formulation is used to define the problem characteristics. The decomposition is designed based on the Dantzig–Wolfe technique that splits the set of decision variables into subsets through the construction of a master problem and subproblems. Each subproblem includes only a single origin‐destination pair with significantly less computational burden compared to the original problem. The master problem represents the coordination between subproblems through the design of interactive flows between the pairs. The proposed methodology is implemented in two case study networks of 20 and 40 intersections with up to 25 origin‐destination pairs. The numerical results show that the decomposition scheme converges to the optimal solution, within 2.0% gap, in substantially less time compared to a benchmark solution, which confirms the computational efficiency of the proposed algorithm. Various network performance measures have been assessed based on different traffic state scenarios to draw managerial insights.
The sedation practices of paediatric intensive care unit nurses and the influencing factors in China
Authors: Liu Zuojia , Ge Xiaohua
Published: May 2019

Nurses play a key role in administering sedation to mechanically ventilated children, which impacts children's psychological, physiological and cognitive changes in the paediatric intensive care unit. This study aimed to survey the sedation practices of paediatric intensive care unit nurses on mechanically ventilated children in China and explored the influencing factors. A cross‐sectional survey was conducted based on electronic questionnaires comprised of the Nurse Sedation Practices Scale (Chinese version) in 14 different types of paediatric intensive care units of 11 academic hospitals in China from 15 February to 15 April 2017. A convenience sample of 495 nurses [73·4% response rate, (674)] completed the survey. Seven units applied Ramsay Sedation Scale as a sedative assessment tool. The majority of the nurses used observed behaviours and physiological changes of the ventilated children as indicators to assess the sedation level, and they had a positive attitude and intention, which may influence practice positively, whereas high clinical workload and the lack of communication between the nurses and families might hinder practice. The practice of sedation varied greatly in different regions, and the respondents of the northwest region scored lower. Paediatric nurses in China rarely used a validated paediatric instrument to assess sedation, and most nurses relied on physiological and behavioural cues. The quality of sedation training, nursing workload and regional economic disparity affected the sedation practice. The restricted visiting policy and lack of clearly defined nursing responsibilities around sedation may hinder effective sedation assessment and management. This study found that there was no paediatric‐validated tool popularized in paediatric intensive care units in China and explored influencing factors. We suggest that a validated tool, high‐quality training and hospital's policy, such as visiting regulation, should be promoted to improve the sedation practice.