bluuebunny/crossref_metadata_2025 huggingface dataset:
Tobacco control policies and smoking among older adults: a longitudinal analysis of 10 European countries
Authors: Serrano‐Alarcón Manuel , Kunst Anton E. , Bosdriesz Jizzo R. , Perelman Julian
Published: March 2019

Background and Aims

The impact of tobacco control on European older adults has not been studied, despite evidence that smoking cessation at old age can bring significant life expectancy gains. Our aim was to evaluate the impact of tobacco control policies on smoking among older adults in Europe from 2004 to 2013.

Design

We used longitudinal data from the Survey of Health, Ageing and Retirement in Europe (SHARE, aged 50+ years) from four waves from 2004 to 2013. We used logistic regression models with clustered standard errors to determine whether the implementation of tobacco control policies was associated with changes in smoking status. Furthermore, we studied whether these associations varied by socio‐demographic characteristics. Regression coefficients were converted to changes the probability of smoking [marginal effects (ME)].

Measurements

Smoking status was the dependent variable, and the Tobacco Control Scale (TCS) was the explanatory variable, overall and by its main policy components (pricing and smoke‐free policies). Covariates included age, sex, education and country and wave fixed‐effects.

Findings

A 10‐point increase in TCS was associated with a lower probability of smoking by 1.6 percentage points [95% confidence interval (CI) = −3.208, −0.056] for those aged 50–65, but not for older Europeans. Among those with primary school or no education, the associated drop was of 1.5 percentage points (95% CI = –2.751, −0.253). By contrast, no significant relation between TCS and smoking was observed among those with high education. Higher TCS scores for pricing (ME = –0.636, 95% CI = –0.998, −0.275) and smoke‐free policies (ME = –0.243, 95% CI = –0.445, −0.041) were associated with a significantly lower probability of smoking (P = 0.001 and P = 0.018, respectively).

Conclusion

Increases in tobacco taxes and smoke‐free policies are significantly related with a reduction in smoking among European older adults, suggesting potential health gains for this rising share of the population. These policies may be more effective among the lowest educated.
Glass beads and pendants from Meroitic and Nobadian Lower Nubia, Sudan: Chemical compositional analysis using laser ablation‐inductively coupled plasma‐mass spectrometry
Authors: Then‐Obłuska J. , Wagner B.
Published: March 2019

This paper presents a detailed elemental analysis of 64 glass beads and pendants dated to the Meroitic period (first–third centuries ad) and the Nobadian period (fourth–sixth centuries) from burial sites in the Lower Nubian Nile Valley region. Laser ablation‐inductively coupled plasma‐mass spectrometry (LA‐ICP‐MS) was used to determine the chemical composition of the glass and to gain knowledge about its origin. Four main glass types were identified: low‐alumina soda‐lime glass, high‐alumina glass, plant‐ash soda‐lime glass, and mixed‐alkali glass. Mineral soda‐lime glass (m‐Na‐Ca) of East Mediterranean/Egyptian provenance is dominant within the low‐alumina glass group from Meroitic and Nobadian periods. Mineral soda high‐alumina glass (m‐Na‐Al) appeared in the Nobadian bead assemblages, and the m‐Na‐Al 1 subtype was produced in Sri Lanka/South India. An initial insight into the origin of the glass beads in Nubia from the first to sixth centuries is described, indicating the first evidence for the presence of Asian objects in Nubia. The data obtained for the bead trade in North‐east Africa in this study has allowed a new light to be shed on the westward flow of Asian glass during a time of intensive maritime trade contacts with the wider Indian Ocean world.
Lessons from exome sequencing in prenatally diagnosed heart defects: A basis for prenatal testing
Authors: Westphal Dominik S. , Leszinski Gloria S. , Rieger‐Fackeldey Esther , Graf Elisabeth , Weirich Gregor , Meitinger Thomas , Ostermayer Eva , Oberhoffer Renate , Wagner Matias
Published: March 2019

Congenital heart defects (CHDs) are the most common birth defect with 30%‐40% being explained by genetic aberrations. With next generation sequencing becoming widely available, we sought to evaluate the clinical utility of exome sequencing (ES) in prenatally diagnosed CHD.

We retrospectively analyzed the diagnostic yield as well as non‐conclusive and incidental findings in 30 cases with prenatally diagnosed CHDs using ES, mostly as parent‐child trios.

A genetic diagnosis was established in 20% (6/30). Non‐conclusive results were found in 13% (4/30) and incidental findings in 10% (3/30). There was a phenotypic discrepancy between reported prenatal and postnatal extracardiac findings in 40% (8/20). However, none of these additional, postnatal findings altered the genetic diagnosis.

Herein, ES in prenatally diagnosed CHDs results in a comparably high diagnostic yield. There was a significant proportion of incidental findings and variants of unknown significance as well as potentially pathogenic variants in novel disease genes. Such findings can bedevil genetic counseling and decision making for pregnancy termination. Despite the small cohort size, our data serve as a first basis to evaluate the value of prenatal ES in CHD for further studies emerging in the near future.
Quantifying the burden of managing wildlife diseases in multiple host species
Authors: Canessa Stefano , Bozzuto Claudio , Pasmans Frank , Martel An
Published: March 2019

Mitigation of infectious wildlife diseases is especially challenging where pathogens affect communities of multiple host species. Although most ecological studies recognize the challenge posed by multiple‐species pathogens, the implications for management are typically assessed only qualitatively. Translating the intuitive understanding that multiple host species are important into practice requires a quantitative assessment of whether and how secondary host species should also be targeted by management and the effort this will require. Using a multiple‐species compartmental model, we determined analytically whether and how intensively secondary host species should be managed to prevent outbreaks in focal hosts based on the reproduction number of individual host species and between‐species transmission rates. We applied the model to the invasive pathogenic fungus Batrachochytrium salamandrivorans in a 2‐host system in northern Europe. Avoiding a disease outbreak in the focal host (fire salamanders [Salamandra salamandra]) was impossible unless management also heavily targeted the secondary host (alpine newts [Ichthyosaura alpestris]). Preventing an outbreak in the community required targeted removal of at least 80% of each species. This proportion increased to 90% in the presence of an environmental reservoir of B. salamandrivorans and when the proportion of individuals removed could not be adjusted for different host species (e.g., when using traps that are not species specific). We recommend the focus of disease‐mitigation plans should shift from focal species to the community level and calculate explicitly the management efforts required on secondary host species to move beyond the simple intuitive understanding that multiple host species may all influence the system. Failure to do so may lead to underestimating the magnitude of the effort required and ultimately to suboptimal or futile management attempts.
Effects of colchicine in adults with metabolic syndrome: A pilot randomized controlled trial
Authors: Demidowich Andrew P. , Levine Jordan A. , Onyekaba Ginikanwa I. , Khan Shahzaib M. , Chen Kong Y. , Brady Sheila M. , Broadney Miranda M. , Yanovski Jack A.
Published: March 2019

Aim

To evaluate the efficacy and safety of colchicine for improving metabolic and inflammatory outcomes in people with obesity and metabolic syndrome (MetS).

Materials and methods

Adults with obesity and MetS, but who did not have diabetes, were randomized to colchicine 0.6 mg or placebo capsules twice daily for 3 months. The primary outcome was change in insulin sensitivity (SI) as estimated by insulin‐modified frequently sampled intravenous glucose tolerance tests. Secondary outcomes included changes in other metabolic variables and inflammatory markers.

Results

Of 40 participants randomized (21 colchicine, 19 placebo), 37 completed the trial. Compared with placebo, colchicine significantly reduced C‐reactive protein (P <0.005), erythrocyte sedimentation rate (P <0.01), white blood cell count (P <0.005), and absolute neutrophil count (P <0.001). Change in SI was not significantly different between colchicine and placebo arms (difference: +0.21 × 10−5; CI −1.70 to +2.13 × 10−5 min−1 mU−1 mL; P = 0.82). However, changes in some secondary outcomes, including homeostatic model assessment of insulin resistance (P = 0.0499), fasting insulin (P = 0.07) and glucose effectiveness (P = 0.08), suggested metabolic improvements in the colchicine versus placebo group. Adverse events were generally mild and similar in both groups.

Conclusions

This pilot study found colchicine significantly improved obesity‐associated inflammatory variables and showed a good safety profile among adults with obesity and MetS who did not have diabetes. These results suggest a larger, adequately powered study should be conducted to determine whether colchicine improves insulin resistance and other measures of metabolic health in at‐risk individuals.
Efficacy, safety, and tolerability of perampanel in Asian and non‐Asian patients with epilepsy
Authors: Tsai Jing‐Jane , Ikeda Akio , Hong Seung Bong , Likasitwattanakul Surachai , Dash Amitabh
Published: March 2019

People of different ethnic or racial backgrounds may experience variations in pharmacokinetic and pharmacodynamic responses to drug therapies. Our post hoc analysis evaluated the efficacy, safety, and tolerability of perampanel in Asian and non‐Asian populations with refractory focal seizures with or without focal to bilateral tonic‐clonic (FBTC) seizures. This analysis pooled data from 4 randomized, placebo‐controlled, phase‐3 studies involving patients aged ≥12 years who have focal seizures with or without FBTC seizures. Patients were receiving 2, 4, 8, or 12 mg perampanel (or placebo) by the end of a 6‐week titration period and for a further 13 weeks during the maintenance phase. Efficacy endpoints included median percent change in seizure frequency per 28 days, and 50% and seizure‐freedom responder rates relative to baseline. The median percent change in seizure frequency per 28 days from baseline was significantly greater than placebo for perampanel 8 and 12 mg (−31.1% and −38.1% change, respectively; each P < 0.0001) in the Asian population, and for perampanel 4, 8, and 12 mg (−21.1% [P = 0.0001], −26.3% [P < 0.0001], and −27.7% [P = 0.0001] change, respectively) in the non‐Asian population. The 50% responder rate relative to baseline was significantly greater than placebo for perampanel 8 and 12 mg (40.1% and 43.8%, respectively; each P < 0.0001) in the Asian population, and for perampanel 4, 8, and 12 mg (29.4% [P = 0.0002], 32.8% [P < 0.0001] and 34.5% [P = 0.0001]), respectively, in the non‐Asian population. Seizure‐freedom rate among all patients was 4.9%‐11.7% for perampanel 2, 4, 8, and 12 mg. The most frequently reported treatment‐emergent adverse events (TEAEs) across both populations were dizziness, somnolence, irritability, headache, and fatigue. The most common psychiatric TEAEs were aggression and irritability. Perampanel demonstrated a favorable and similar risk‐benefit profile in both Asian and non‐Asian populations with refractory focal seizures.
Efficacy and safety of perampanel in generalized and focal to bilateral tonic‐clonic seizures: A comparative study of Asian and non‐Asian populations
Authors: Nishida Takuji , Lee Sang Kun , Wu Tony , Tiamkao Somsak , Dash Amitabh
Published: March 2019

Perampanel is an approved adjunctive treatment for focal seizures with or without focal to bilateral tonic‐clonic (FBTC) seizures and generalized tonic‐clonic (GTC) seizures. We compared efficacy and safety of perampanel vs placebo in Asian and non‐Asian populations in a post hoc analysis of pooled data from 5 randomized phase 3 studies. Patients (≥12 years old) with focal + FBTCseizures received perampanel 2, 4, 8, or 12 mg or placebo; patients withGTCseizures received perampanel 8 mg or placebo (titration: 4‐6 weeks; maintenance: 13 weeks). Efficacy endpoints included median percentage change inFBTCorGTCseizure frequency per 28 days and 50% responder rate relative to baseline. Median percentage change inFBTCseizure frequency was significantly greater for perampanel 8 and 12 mg than placebo in the Asian population (median difference from placebo: −30.32%,P = 0.0017; −30.06%,P = 0.0008, respectively) and perampanel 4, 8, and 12 mg in the non‐Asian population (−35.07%,P = 0.0001; −37.78%,P < 0.0001; −34.53%,P < 0.0001, respectively). In both populations, median percentage change inGTCseizure frequency was significantly greater for perampanel 8 mg than placebo (median difference from placebo: Asian, −37.37%,P = 0.0139; non‐Asian, −27.04%,P = 0.0006). The 50% responder rates were significantly greater than placebo for perampanel 8 and 12 mg forFBTCseizures (Asian: 58.0%,P = 0.0017 and 58.6%,P = 0.0013, respectively; non‐Asian: 59.3%,P < 0.0001 and 54.3%,P = 0.0050, respectively) and perampanel 8 mg forGTCseizures (Asian: 57.6%,P = 0.0209; non‐Asian: 68.8%,P = 0.0329). PooledFBTC/GTCseizure data showed generally similar patterns of response to perampanel in both populations. The most frequent treatment‐related adverse events were fatigue, irritability, dizziness, somnolence, and headache. Perampanel was effective, well tolerated, and can be considered a therapeutic option forFBTC/GTCseizures in Asian populations.
Trends in mortality from cutaneous malignant melanoma in Spain (1982–2016): sex‐specific age‐cohort‐period effects
Authors: Gutiérrez‐González E. , López‐Abente G. , Aragonés N. , Pollán M. , Pastor‐Barriuso R. , Sánchez M.J. , Pérez‐Gómez B.
Published: March 2019

Background

Mortality from malignant cutaneous melanoma increased alarmingly during the second half of the 20th century in Spain and other European countries.

Objective

The aim was to analyse sex‐ and age‐specific trends in melanoma mortality in Spain in the period 1982–2016.

Methods

European age‐standardized melanoma mortality rates during the period 1982–2016 were calculated from mortality figures provided by the National Statistics Institute. Joinpoint regressions were used to identify significant points of change in trends and to compute average annual per cent change (AAPC). Age‐cohort‐period models were fitted to explore the effect of these variables on mortality.

Results

During the period 1982–2016, age‐standardized melanoma mortality rates increased in Spain from 0.90 to 1.80 deaths per 100 000 people in men and from 0.64 to 1.11 per 100 000 in women, rising noticeably from 1982 to 1995 in both sexes and in all age groups. From the mid‐90s different trends were observed depending on sex and age: there was a decrease in mortality in the population younger than 45 years (AAPC ‐2 in both sexes) and aged 45–64 years (AAPC ‐1 among men and ‐0.2 among women), but in the group over 64 years rates continued to increase (AAPC 1.7 and 0.2, respectively, for men and women). The mortality sex ratio decreased in the younger population but increased in older individuals. A cohort effect was observed with lower mortality in the cohorts born after 1943 in men and 1956 in women. There was also a period effect with decreased mortality rates at the beginning of the 1990s.

Conclusions

Melanoma mortality rates in Spain increased during the last decades of the 20th century; however, later they stabilized in women and began to decrease in younger cohorts and middle‐aged men. Promotion of primary and secondary prevention measures should continue, with particular emphasis on males over 65 years.
Exploring the Influence of Judge Proficiency on Standard‐Setting Judgments
Authors: Peabody Michael R. , Wind Stefanie A.
Published: March 2019

Setting performance standards is a judgmental process involving human opinions and values as well as technical and empirical considerations. Although all cut score decisions are by nature somewhat arbitrary, they should not be capricious. Judges selected for standard‐setting panels should have the proper qualifications to make the judgments asked of them; however, even qualified judges vary in expertise and in some cases, such as highly specialized areas or when members of the public are involved, it may be difficult to ensure that each member of a standard‐setting panel has the requisite expertise to make qualified judgments. Given the subjective nature of these types of judgments, and that a large part of the validity argument for an exam lies in the robustness of its passing standard, an examination of the influence of judge proficiency on the judgments is warranted. This study explores the use of the many‐facet Rasch model as a method for adjusting modified Angoff standard‐setting ratings based on judges’ proficiency levels. The results suggest differences in the severity and quality of standard‐setting judgments across levels of judge proficiency, such that judges who answered easy items incorrectly tended to perceive them as easier, but those who answered correctly tended to provide ratings within normal stochastic limits.
Bias and Bias Correction Method for Nonproportional Abilities Requirement (NPAR) Tests
Authors: Ip Edward H. , Strachan Tyler , Fu Yanyan , Lay Alexandra , Willse John T. , Chen Shyh‐Huei , Rutkowski Leslie , Ackerman Terry
Published: March 2019

Test items must often be broad in scope to be ecologically valid. It is therefore almost inevitable that secondary dimensions are introduced into a test during test development. A cognitive test may require one or more abilities besides the primary ability to correctly respond to an item, in which case a unidimensional test score overestimates the primary ability and creates interpretability problems. In this article, we demonstrate the nonproportional abilities requirement, a phenomenon with which secondary abilities are more required for difficult items. A novel and practical method for correcting bias in the primary ability is proposed and illustrated using a real data set from an international assessment. Simulation data are also used to evaluate the performance of the method.
Interdisciplinary Work Is Essential for Research on Puberty: Complexity and Dynamism in Action
Authors: Susman Elizabeth J. , Marceau Kristine , Dockray Samantha , Ram Nilam
Published: March 2019

Puberty is associated with changes in behavior and psychosocial well‐being, and is important in lifelong health. We present five different facets regarding interdisciplinary research that are important to puberty. A short history of philosophical issues instrumental in promoting early interdisciplinary research is first presented. We discuss then what is hard and what is easy about interdisciplinary research, the purpose of which is to alert scientists to challenges and opportunities for interdisciplinary research on puberty. Readers then are introduced to advances and obstacles in interdisciplinary research on development. Recommendations for tailoring graduate education toward interdisciplinarity are introduced. Finally, issues related to publication, education of scientists, and policy makers are described. The report concludes with a discussion of funding and policy issues.
Association between ultrasonographic appearance of urine and urinalysis in dogs and cats
Authors: Valls Sanchez F. , Puig J. , Olivares G. , Holloway A. , Seth M.
Published: March 2019

Objective

To evaluate association between ultrasonographic urine echogenicity and sediment examination in dogs and cats.

Materials and Methods

Dogs and cats undergoing ultrasound‐guided cystocentesis at a multidisciplinary referral hospital. Ultrasonographic images were stored and reviewed by a single, blinded, board‐certified radiologist. Urine appearance was described as “echoic” or “anechoic”. Urine sediment was examined for bacteriuria, pyuria, haematuria, crystalluria and urine‐specific gravity and then classified as “active” or “inactive.”

Results

Of the 194 cases included in this study, urine was echoic in 52 and anechoic in 142. Sediment was active in 52 and inactive in 142 samples. Sensitivity and specificity of echoic urine for active sediment were 40% (95% CI: 27 to 55%) and 78% (95% CI: 70 to 85%), respectively. Positive predictive value and negative predictive value of echoic urine for active sediment were 40% (CI 30 to 52%) and 78% (CI 74 to 82%), respectively. If urine‐specific gravity was <1.015 urine was always described ultrasonographically as anechoic.

Clinical Significance

Association between sediment analysis and ultrasonographic appearance of urine is poor. Echoic urine had low positive predictive value for active sediment in this study, suggesting that echoic urine alone should not prompt urinary investigations in the absence of other clinical suspicion. Despite a negative predictive value of 78%, urinalysis is still indicated for anechoic urine, especially if urine specific gravity is low.
Acute and chronic toxicity of nitrate to fat greenling (Hexagrammos otakii) juveniles
Authors: Yang Xiaohan , Peng Lei , Hu Fawen , Guo Wen , Hallerman Eric , Huang Zhitao
Published: March 2019

We evaluated the acute and chronic toxicity of nitrate to juvenile fat greenlingHexagrammos otakii. The 24‐, 48‐, 72‐, and 96‐hr LC50s of nitrate to 1.91 ± 0.7 g greenlings were 2,741, 2,413.5, 2,357.6, or 2,339.2 mg/L nitrate‐N, respectively. Greenlings (6.55 ± 1.83 g) were exposed to 5 mg/L (control) and 157 mg/L for 4 weeks in a recirculating aquaculture system. After 4 weeks, length, weight, feed conversion ratio, and specific growth rate were significantly (p < 0.05) lower for nitrate‐exposed fish than for control fish. Elevated nitrate exposure was associated with decreased plasma hemoglobin concentration and red blood cell count. Our results demonstrate that nitrate poses a threat to greenlings and provide information that is useful for establishing water quality criteria for early life stages of this cultured fish. The sensitivity of greenlings to elevated NO3−should be evaluated at other life stages to determine how chronic exposure might impact survival, growth, health, reproductive success, and harvest quality.
Mast cell infiltration associated with loss of interstitial cells of Cajal and neuronal degeneration in achalasia
Authors: Liu Zu‐Qiang , Chen Wei‐Feng , Wang Yun , Xu Xiao‐Yue , Zeng Yi‐Gang , Lee Dillon Dustin , Cheng Jing , Xu Mei‐Dong , Zhong Yun‐Shi , Zhang Yi‐Qun , Yao Li‐Qing , Zhou Ping‐Hong , Li Quan‐Lin
Published: March 2019

Background

Achalasia is a motility disorder of unknown etiology. Previous studies supported the hypothesis that autoimmune‐mediated inflammatory responses produce inhibitory neuronal degeneration. This study was designed to explore the role of mast cells in achalasia.

Methods

We collected information from 116 patients with achalasia who underwent peroral endoscopic myotomy between December 2016 and May 2017. Lower esophageal sphincter (LES) muscle biopsy was performed in all patients with achalasia, as well as 20 control subjects. The number of mast cells, interstitial cells of Cajal (ICCs), nNOS‐positive cells, and S‐100‐positive cells in the LES were evaluated by immunohistochemistry. Pathological and clinical data were compared between groups.

Key Results

Compared with controls, the LES of patients with achalasia had significantly fewer ICCs, nNOS‐positive cells, and S‐100‐positive cells and a higher number of mast cells (all P < 0.001). Furthermore, the increased mast cell infiltration was significantly associated with decreased ICCs, nNOS‐positive cells, and S‐100‐positive cells in patients with achalasia (all P < 0.05). Clinically, the number of strongly positive mast cells was highest in patients with type I achalasia and lowest in those with type III achalasia (P < 0.001). In addition, patients with a history of autoimmune disease or viral infection had greater mast cell infiltration in the LES muscle (P = 0.040).

Conclusions & Inferences

In patients with achalasia, mast cell infiltration in the LES muscle is increased, in association with loss of ICCs and neuronal degeneration. Mast cells may thereby play a crucial role in the development of achalasia.
Automatic lesion border selection in dermoscopy images using morphology and color features
Authors: Mishra Nabin K. , Kaur Ravneet , Kasmi Reda , Hagerty Jason R. , LeAnder Robert , Stanley Ronald J. , Moss Randy H. , Stoecker William V.
Published: March 2019

Purpose

We present a classifier for automatically selecting a lesion border for dermoscopy skin lesion images, to aid in computer‐aided diagnosis of melanoma. Variation in photographic technique of dermoscopy images makes segmentation of skin lesions a difficult problem. No single algorithm provides an acceptable lesion border to allow further processing of skin lesions.

Methods

We present a random forests border classifier model to select a lesion border from 12 segmentation algorithm borders, graded on a “good‐enough” border basis. Morphology and color features inside and outside the automatic border are used to build the model.

Results

For a random forests classifier applied to an 802‐lesion test set, the model predicts a satisfactory border in 96.38% of cases, in comparison to the best single border algorithm, which detects a satisfactory border in 85.91% of cases.

Conclusion

The performance of the classifier‐based automatic skin lesion finder is found to be better than any single algorithm used in this research.
Regulatory actors and alternative routes for Arabidopsis seed germination are revealed using a pathway‐based analysis of transcriptomic datasets
Authors: Ponnaiah Maharajah , Gilard Françoise , Gakière Bertrand , El‐Maarouf‐Bouteau Hayat , Bailly Christophe
Published: March 2019

Regulation of seed germination by dormancy relies on a complex network of transcriptional and post‐transcriptional modifications during seed imbibition that controls seed adaptive responses to environmental cues. High‐throughput technologies have brought significant progress in the understanding of this phenomenon and have led to identify major regulators of seed germination, mostly by studying the behaviour of highly differentially expressed genes. However, the actual models of transcriptome analysis cannot catch additive effects of small variations of gene expression in individual signalling or metabolic pathways, which are also likely to control germination. Therefore, the comprehension of the molecular mechanism regulating germination is still incomplete and to gain knowledge about this process we have developed a pathway‐based analysis of transcriptomic Arabidopsis datasets, to identify regulatory actors of seed germination. The method allowed quantifying the level of deregulation of a wide range of pathways in dormant versus non‐dormant seeds. Clustering pathway deregulation scores of germinating and dormant seed samples permitted the identification of mechanisms involved in seed germination such as RNA transport or vitamin B6 metabolism, for example. Using this method, which was validated by metabolomics analysis, we also demonstrated that Col and Cvi seeds follow different metabolic routes for completing germination, demonstrating the genetic plasticity of this process. We finally provided an extensive basis of analysed transcriptomic datasets that will allow further identification of mechanisms controlling seed germination.
Social Studies Preservice Teachers’ Views on and Experiences with WebQuest
Authors: Gürgil Fitnat , Ünal Mertcan , Aksoy Bülent
Published: March 2019

The current study aims to determine prospective teachers’ opinions about WebQuest applications by both introducing them to the WebQuest teaching materials and obtaining their experiences in the WebQuest design process. This study employs phenomenology as a qualitative research approach. The study was conducted in the spring semester of the 2017-2018 academic year with the third year undergraduate students in the social studies education department of a state university in Ankara. Two different data collection tools, a Peer Evaluation Form and an Interview Form, were used. Content analysis was used to analyze the data obtained. According to the findings of the study, social studies preservice teachers think that teacher supervision of Webquest teaching activities is advantageous. Preservice teachers defined the specific principles of WebQuest teaching activities as a weak factor. Additionally, preservice teachers emphasized that WebQuest teaching activities are difficult to implement in environments where Internet and computer facilities are not available. Even though almost half of the participants stated that they wanted to include WebQuest teaching activities in their classes when they started the teaching profession, they expressed about their concerns.
Pierre Pasquier, l’inventeur d’une « politique des sports » en Indochine
Authors: Fossard Brice
Published: March 2019

Les sports occidentaux font partie des activités de loisirs qui ont été transférées en Indochine par les conquérants français. D’abord réservées à ces derniers, ces activités sont ensuite pratiquées par certaines fractions des élites locales en quête de transformation individuelle et collective. Un gouverneur général a joué un rôle essentiel dans ce processus d’acculturation: Pierre Pasquier a ainsi utilisé les sports pour rapprocher les élites indochinoises de la France dès 1929. Il a donc élaboré la première politique des sports en Indochine. Cet article analyse les motivations et les moyens utilisés par ce haut fonctionnaire entre 1929 et 1934.
Hypoxia induces rapid changes to histone methylation and reprograms chromatin
Authors: Batie Michael , Frost Julianty , Frost Mark , Wilson James W. , Schofield Pieta , Rocha Sonia
Published: March 2019

Oxygen sensing revisited

The cellular response to hypoxia (oxygen deficiency) is a contributing factor in many human diseases. Previous studies examining the way in which hypoxia alters gene expression have focused on oxygen-sensing enzymes that regulate the activity of a transcription factor called hypoxia-inducible factor (see the Perspective by Gallipoli and Huntly). Chakraborty
et al.
and Batie
et al.
now show that hypoxia can also affect gene expression through direct effects on chromatin regulators. Certain histone demethylases, such as KDM6A and KDM5A, were found to be direct sensors of oxygen. In cell-culture models, hypoxia diminished the activity of these enzymes and caused changes in the expression of genes that govern cell fate.

Science
, this issue p.
1217
, p.
1222
; see also p.
1148
A rights revolution for nature
Authors: Chapron Guillaume , Epstein Yaffa , López-Bao José Vicente
Published: March 2019

Introduction of legal rights for nature could protect natural systems from destruction
Architecture of the heteromeric GluA1/2 AMPA receptor in complex with the auxiliary subunit TARP γ8
Authors: Herguedas Beatriz , Watson Jake F. , Ho Hinze , Cais Ondrej , García-Nafría Javier , Greger Ingo H.
Published: March 2019

Regulating signals at synapses

At excitatory synapses in the brain, tetrameric cation channels called AMPA-type glutamate receptors (AMPARs) play a key role in the cellular processes that underlie learning and memory. AMPARs are heterotetramers comprising various compositions of the subunits GluA1 to 4. Herguedas
et al.
used cryo–electron microscopy to determine the structure of the most prevalent form of AMPAR in the hippocampus, the GluA1/2 heteromer in complex with its regulatory subunit TARPγ8. The structure shows the architecture of the complex and provides insight into how conductance is controlled and modulated by auxiliary subunits.

Science
, this issue p.
eaav9011
Ushering in the next generation of precision trials for pediatric cancer
Authors: DuBois Steven G. , Corson Laura B. , Stegmaier Kimberly , Janeway Katherine A.
Published: March 2019

Cancer treatment decisions are increasingly based on the genomic profile of the patient’s tumor, a strategy called “precision oncology.” Over the past few years, a growing number of clinical trials and case reports have provided evidence that precision oncology is an effective approach for at least some children with cancer. Here, we review key factors influencing pediatric drug development in the era of precision oncology. We describe an emerging regulatory framework that is accelerating the pace of clinical trials in children as well as design challenges that are specific to trials that involve young cancer patients. Last, we discuss new drug development approaches for pediatric cancers whose growth relies on proteins that are difficult to target therapeutically, such as transcription factors.
Outer Membrane Protein Insertion by the β-barrel Assembly Machine
Authors: Ricci Dante P. , Silhavy Thomas J.
Published: March 2019

Like all outer membrane (OM) constituents, integral OM β-barrel proteins in Gram-negative bacteria are synthesized in the cytoplasm and trafficked to the OM, where they are locally assembled into the growing OM by the ubiquitous β-barrel assembly machine (Bam). While the identities and structures of all essential and accessory Bam components have been determined, the basic mechanism of Bam-assisted OM protein integration remains elusive. Here we review mechanistic analyses of OM β-barrel protein folding and Bam dynamics and summarize recent insights that inform a general model for OM protein recognition and assembly by the Bam complex.
Contribution of the Cytoplasmic Determinants of Vpu to the Expansion of Virus-Containing Compartments in HIV-1-Infected Macrophages
Authors: Leymarie Olivier , Lepont Leslie , Versapuech Margaux , Judith Delphine , Abelanet Sophie , Janvier Katy , Berlioz-Torrent Clarisse
Published: March 2019

HIV-1 infection of macrophages leads to the sequestration of newly formed viruses in virus-containing compartments (VCCs), where virions remain infectious and hidden from immune surveillance. The restriction factor BST2, which prevents HIV-1 dissemination by tethering budding viral particles, can be found in VCCs. The HIV-1 Vpu protein counteracts BST2. This study explores the interplay between Vpu and BST2 in the viral protein functions on HIV-1 release and viral particle sequestration in VCCs in macrophages. The results show that Vpu controls the volume of VCCs and favors viral particle release. These Vpu functions partly depend on Vpu’s ability to antagonize BST2. This study highlights that the transmembrane domain of Vpu and two motifs of the Vpu cytoplasmic domain are required for these functions. These motifs were notably involved in the control of the volume of VCCs by Vpu but were dispensable for the prevention of the specific accumulation of BST2 in these structures.
Tuberculous Addison’s disease with increased hydrocortisone requirements due to administration of rifampicin
Authors: Kusuki Kazuhisa , Watanabe Satoshi , Mizuno Yuzo
Published: March 2019

A 58-year-old man was referred to our hospital for darkened skin, general fatigue and weight loss. His adrenocorticotropic hormone and cortisol levels indicated a primary adrenal insufficiency.18Fluorodeoxyglucose positron emission tomography/CT showed bilateral enlargement of the adrenal glands, with18fluorodeoxyglucose accumulation. Loop-mediated isothermal amplification assays of bronchoalveolar lavage fluid were positive forMycobacterium tuberculosis. The patient was diagnosed with tuberculous Addison’s disease and treated with antituberculosis agents, including rifampicin. The patient’s fatigue worsened gradually after initiation of rifampicin, and the dosage of hydrocortisone was increased. Serum cortisol level monitoring at 2 hours after administration of hydrocortisone was shown to be clinically useful for determining the optimal dose, especially with concurrent use of rifampicin.
Development of an online secondary prevention programme for stroke survivors: Prevent 2nd Stroke
Authors: Denham Alexandra M J , Guillaumier Ashleigh , McCrabb Sam , Turner Alyna , Baker Amanda L , Spratt Neil J , Pollack Michael , Magin Parker , Oldmeadow Christopher , Collins Clare , Callister Robin , Wallis Mark , Wynne Olivia , Bonevski Billie
Published: March 2019

Background

Stroke events often result in long-term negative health outcomes. People who experience a first stroke event are 30%–40% more likely to experience a second stroke event within 5 years. An online secondary prevention programme for stroke survivors may help stroke survivors improve their health risk behaviours and lower their risk of a second stroke.

Objectives

This paper describes the development and early iteration testing of the usability and acceptability of an online secondary prevention programme for stroke survivors (Prevent 2nd Stroke, P2S). P2S aims to address six modifiable health risk behaviours of stroke: blood pressure, physical activity, nutrition, depression and anxiety, smoking, and alcohol consumption.

Methods

P2S was developed as an eight-module online secondary prevention programme for stroke survivors. Modelled on the DoTTI (Design and development, Testing early iterations, Testing for effectiveness, Integration and implementation) framework for the development of online programmes, the following stages were followed during programme development: (1) content development and design; and (2) testing early iteration. The programme was pilot-tested with 15 stroke survivors who assessed P2S on usability and acceptability.

Results

In stage 1, experts provided input for the content development of P2S. In stage 2, 15 stroke survivors were recruited for usability testing of P2S. They reported high ratings of usability and acceptability of P2S. P2S was generally regarded as ‘easy to use’ and ‘relevant to stroke survivors’. Participants also largely agreed that it was appropriate to offer lifestyle advice to stroke survivors through the internet.

Conclusions

The study found that an online secondary prevention programme was acceptable and easily usable by stroke survivors. The next step is to conduct a randomised controlled trial to assess the effectiveness of the programme regarding behaviour change and determine the cost-effectiveness of the intervention.
Lateral episiotomy versus no episiotomy to reduce obstetric anal sphincter injury in vacuum-assisted delivery in nulliparous women: study protocol on a randomised controlled trial
Authors: Bergendahl Sandra , Ankarcrona Victoria , Leijonhufvud Åsa , Hesselman Susanne , Karlström Sofie , Kopp Kallner Helena , Brismar Wendel Sophia
Published: March 2019

Introduction

Obstetric anal sphincter injury (OASIS) occurs in 5%–7% of normal deliveries and increases with vacuum extraction (VE) to 12%–14% in nulliparous women in Sweden. Lateral/mediolateral episiotomy may reduce the prevalence of OASIS at VE in nulliparous women. The current use of episiotomy is restrictive. The protective effect and consequences are uncertain. This trial will investigate if lateral episiotomy can reduce the prevalence of OASIS and assess short-term and long-term effects.

Methods and analysis

This is a multicentre randomised controlled trial of lateral episiotomy versus no episiotomy in nulliparous women with a singleton, live fetus, after gestational week 34+0 with indication for VE. A lateral episiotomy of 4 cm is cut at crowning, 1–3 cm from the midline, at a 60° angle. The primary outcome is OASIS by clinical diagnosis analysed according to intention to treat. To demonstrate a 50% reduction in OASIS prevalence (from 12.4% to 6.2%), 710 women will be randomised at a 1:1 ratio. Secondary outcomes are pain, blood loss, other perineal injuries, perineal complications, Apgar score, cord pH and neonatal complications. Web-based questionnaires at baseline, 2 months, 1 and 5 years will be used to assess pain, incontinence, prolapse, sexual function, quality of life and childbirth experience. A subset of women will receive follow-up by pelvic floor sonography and pelvic examination. Mode of delivery and recurrence of OASIS/episiotomy in subsequent pregnancies will be assessed at 5 and 10 years using register data.

Ethics and dissemination

The trial is open for enrolment. The trial has received ethical approval from the Regional Ethical Review Board of Stockholm and full funding from the Swedish Research Council. Women are interested in participation. The predominant restrictive view on episiotomy may limit recruitment. Results are of global interest and will be disseminated in peer-reviewed journals and at international congresses.

Trial registration number

NCT02643108; Pre-results.
Randomised controlled trial of a video intervention and behaviour contract to improve medication adherence after renal transplantation: the VECTOR study protocol
Authors: Mansell Holly , Rosaasen Nicola , West-Thielke Patricia , Wichart Jenny , Daley Christopher , Mainra Rahul , Shoker Ahmed , Liu Juxin , Blackburn David
Published: March 2019

Introduction

Non-adherence after kidney transplantation contributes to increased rejections, hospitalisations and healthcare expenditures. Although effective adherence interventions are sorely needed, increasing education and support to transplant recipients demands greater use of care providers’ time and resources in a healthcare system that is stretched. The objective of this clinical trial is to determine the effectiveness of an electronically delivered video series and adherence behaviour contract on improving medication adherence to immunosuppressant medications.

Methods and analysis

A multicentre, parallel arm, randomised controlled trial will be conducted with four sites across North America (Saskatoon, Calgary, Halifax, Chicago). Adult patients will be randomised (1:1) to either the intervention (ie, home-based video education +behaviour contract plus usual care) or usual care alone. De novo transplant recipients will be enrolled prior to their hospital discharge and will be provided with electronic access to the video intervention (immediately) and adherence contract (1 month post-transplant). Follow-up electronic surveys will be provided at 3 and 12 months postenrolment. The primary outcome will be adherence at 12 months post-transplant, as measured by self-report Basel Assessment of Adherence to Immunosuppressive medications and immunosuppressant levels. Secondary outcomes include the difference in knowledge score between the intervention and control in groups (measured by the Kidney Transplant Understanding Tool); differences in self-efficacy (Generalised Self-efficacy Scale), Beliefs of Medicine Questionnaire (BMQ), quality of life (Short Form-12), patient satisfaction and cost utilisation. The study aims to recruit at least 200 participants across participating sites.

Ethics and dissemination

Ethical approval was obtained from the University of Saskatchewan Behavioural Ethics Committee (Beh 18–63), and all patients provide informed consent prior to participating. This educational intervention aims to improve information retention and self-efficacy, leading to improved medication adherence after kidney transplantation, at low cost, with little impact to existing healthcare personnel. If proven beneficial, delivery can be easily implemented into standard of care.

Trial registration number

NCT03540121; Pre-results.
Exercise and incidence of myocardial infarction, stroke, hypertension, type 2 diabetes and site-specific cancers: prospective cohort study of 257 854 adults in South Korea
Authors: Kim Youngwon , Sharp Stephen , Hwang Semi , Jee Sun Ha
Published: March 2019

Objective

The objective of this study was to examine the longitudinal associations of exercise frequency with the incidence of myocardial infarction, stroke, hypertension, type 2 diabetes and 10 different cancer outcomes.

Design

A prospective cohort study.

Setting

Physical examination data linked with the entire South Korean population’s health insurance system: from 2002 to 2015.

Participants

257 854 South Korean adults who provided up to 7 repeat measures of exercise (defined as exercises causing sweat) and confounders.

Primary outcome measures

Each disease incidence was defined using both fatal and non-fatal health records (a median follow-up period of 13 years).

Results

Compared with no exercise category, the middle categories of exercise frequency (3–4 or 5–6 times/week) showed the lowest risk of myocardial infarction (HR 0.79; 95% CI 0.70 to 0.90), stroke (HR 0.80; 95% CI 0.73 to 0.89), hypertension (HR 0.86; 95% CI 0.85 to 0.88), type 2 diabetes (HR 0.87; 95% CI 0.84 to 0.89), stomach (HR 0.87; 95% CI 0.79 to 0.96), lung (HR 0.80; 95% CI 0.71 to 0.91), liver (HR 0.85; 95% CI 0.75 to 0.98) and head and neck cancers (HR 0.76; 95% CI 0.63 to 0.93; for 1–2 times/week), exhibiting J-shaped associations. There was, in general, little evidence of effect modification by body mass index, smoking, alcohol consumption, family history of disease and sex in these associations.

Conclusions

Moderate levels of sweat-inducing exercise showed the lowest risk of myocardial infarction, stroke, hypertension, type 2 diabetes, stomach, lung, liver and head and neck cancers. Public health and lifestyle interventions should, therefore, promote moderate levels of sweat-causing exercise as a behavioural prevention strategy for non-communicable diseases in a wider population of East Asians.
The Triscapular Block: A New Application of Therapy of Periscapular Pain and Glenohumeral Restriction
Authors: Long Jim , Peer Gerald , Cwik John
Published: March 2019

After a series of 1-10 triscapular nerve blocks, significant subjective pain relief lasting longer than 1 month was verified by chart review in 30 of 50 patients with chronic pain who had periscapular myofascial pain syndromes. The triscapular block is the combination of suprascapular and infrascapular nerve blocks with subscapular infiltration of local anesthetic. The triscapular block provides shoulder capsule analgesia and offers relief of arm and chest wall pain. When impaired, glenohumeral range of motion is often improved, especially when the block is combined with physical therapy.
Interscalene Approach to the Brachial Plexus: Paresthesiae Versus Nerve Stimulator
Authors: McClain Deborah A. , Finucane Brendan T.
Published: March 2019

Thirty-eight patients (ASA class I-III), scheduled for hand or forearm surgery, were randomly assigned to either the paresthesia or nerve stimulator group. After injection of 5.5 mg/kg of 1% mepivacaine, motor and sensory function was evaluated by testing over the distribution of the three major nerve trunks in the hand. The results showed that the overall success rate in the paresthesia group, when paresthesia could be elicited, was 82%. The success rate in the stimulator group was 75%. There was no statistical difference between the two groups. It appears that both techniques are equally effective and predictable.
Pulmonary rehabilitation, physical activity, respiratory failure and palliative respiratory care
Authors: Spruit Martijn A , Rochester Carolyn L , Pitta Fabio , Kenn Klaus , Schols Annemie M W J , Hart Nicholas , Wouters Emiel F M , Nava Stefano , Dreher Michael , Janssen Daisy J A , Johnson Miriam J , Curtis Randall J , Sastry Manuel , Franssen Frits M E
Published: March 2019

The CIRO Academy in Horn (the Netherlands) organised a 2-day meeting to present and discuss the studies published in 2017 pertaining to key priority areas of respiratory and critical care medicine. This review summarises studies focussing on pulmonary rehabilitation and exercise training, physical activity, chronic respiratory failure and palliative respiratory care published in 2017.
Paul Guy Hall
Authors: Hall Hazel
Published: March 2019

A vet and wildlife enthusiast, his passions included fishing in the River Tyne near his home in Northumberland and enjoying Newcastle's cultural and sporting opportunities.