bluuebunny/crossref_metadata_2025 huggingface dataset:
Cultural values, institutional arrangements and stakeholder management culture
Authors: Kumar Kamalesh , Boesso Giacomo , Yao Jun
Published: October 2017

Purpose

This study draws upon the cultural values model, institutional theory and comparative capitalism to investigate differences in organizations’ approach to stakeholder management across country boundaries.

Design/methodology/approach

The authors developed a multi-dimensional scale, following the stakeholder culture framework (Joneset al., 2007) to identify differences in the prevalent stakeholder cultures in the USA, Italy and Japan. Data were collected in form of a questionnaire from managers of 530 companies in the USA, Italy and Japan.

Findings

Results show that there are important differences in the extent to which different stakeholder cultures exist in each of these three countries, and that the prevalence of stakeholder culture types in each country is influenced by the country’s cultural values and institutional arrangements.

Originality/value

Understanding stakeholder management beyond the conventional firm level to a wider institutional setting has important implications for the dissemination of corporate social responsibility (CSR) practices across cultures. Developing an understanding of how organizations’ stakeholder management approaches are embedded in the context of the institutional arrangements that exist in a particular country will lead to CSR practices that are better suited to the specific national context. It may also help in a more widespread acceptance of these concepts and practices.
Inward retail internationalization and exogenous – based outshopping on the US-Mexico border
Authors: Hadjimarcou John , Herrera Jessica , Salazar Dalila
Published: October 2017

Purpose

Previous research on the internationalization of retailing typically focused on retail companies crossing borders to enter other countries. Yet, a large number of people cross country borders to outshop in neighboring countries. This form of inward retail internationalization has received little attention in the literature. To address this void, the purpose of this paper is to investigate the strategies of retailers in a border zone setting.

Design/methodology/approach

The authors collected data from 109 US retailers on the USA–Mexico border. The survey instrument included questions that captured the participants’ opinions regarding the importance of Mexican consumers, retail mix strategies, performance issues and overall retailer characteristics.

Findings

The findings show that US retailers perceive cross-border consumers as important to their performance. Interestingly, the findings also suggest that border zone retailers do not adapt their retail mix strategies with this target market in mind.

Research limitations/implications

The research was conducted at one particular border zone with its own unique characteristics. It is not clear whether the authors’ findings would apply in other inward internationalization contexts (e.g. medical tourism) or border zones. Future research should delve much more deeply into understanding outshopping motivations in border zones, but also the reasons why retailers do not actively engage in marketing their establishments to this target market.

Practical implications

The authors’ findings have interesting implications for retail managers in border zones. While exogenous and uncontrollable advantages on one side of the border may attract customers away from the other side of the border, retail mix customization under the control of retail managers may actually stimulate similar or better results. Border zone retailers are encouraged to engage in efforts to understand the border zone consumer and engage in programs directly targeted at them.

Originality/value

The study is grounded in theory and empirically assesses the retailers’ own contributions to enhancing their inward internationalization performance. By using the model of secondary boundary effects developed by Clark (1994) as their theoretical prism, the authors have put forward hypotheses, which address the aforementioned issues.
Dementia peer support: service delivery for the people, by the people
Authors: Femiola Clementine , Tilki Mary
Published: October 2017

Purpose

The purpose of this paper is to describe a community-based peer support project in the London borough of Brent, led by people living with dementia for people living with dementia.

Design/methodology/approach

The Brent Dementia Peer Support Project is a collaboration between a social movement Community Action on Dementia Brent, Brent CCG, Brent Council, third-sector organisations and faith communities.

Findings

Stakeholder workshops, ethnographic research highlighted the need to support people living with dementia, especially by people who understand that experience. The findings also demonstrated the abilities and skills retained by people living with dementia, their wish to help others to contribute and to remain connected with their communities.

Research limitations/implications

This is an account of one pilot project in a London borough, but is broadly applicable elsewhere. Further research is needed into the values and practicalities of peer support by and for people living with dementia.

Practical implications

People with dementia and their carers lack accessible information and empathetic support to cope with the condition and live independently. This can be offered through dementia peer support services.

Social implications

There are growing numbers of people living with dementia who are motivated to share their knowledge, skills and experiences to improve the lives of other people with dementia.

Originality/value

This paper describes how people with dementia can be enabled to design, inform and deliver support to other people with the condition.
Causal narratives in public health: the difference between mechanisms of aetiology and mechanisms of prevention in non‐communicable diseases
Authors: Kelly Michael P. , Russo Federica
Published: October 2017

Research in the health sciences has been highly successful in revealing the aetiologies of many morbidities, particularly those involving the microbiology of communicable disease. This success has helped form a narrative to be found in numerous public health documents, about interventions to reduce the burden of non‐communicable diseases (e.g., obesity or alcohol related pathologies). These focus on tackling the purported pathogenic factors causing the diseases as a means of prevention. In this paper, we argue that this approach has been sub‐optimal. The mechanisms of aetiology and of prevention are sometimes significantly different and failure to make this distinction has hindered efforts at preventing non‐communicable diseases linked to diet, exercise and alcohol consumption. We propose a sociological approach as an alternative based on social practice theory. (A virtual abstract for this paper can be found at:https://www.youtube.com/channel/UC_979cmCmR9rLrKuD7z0ycA).
Exploring parkrun as a social context for collective health practices: running with and against the moral imperatives of health responsibilisation
Authors: Wiltshire G. R. , Fullagar Simone , Stevinson Clare
Published: October 2017

Critiques of public health policies to reduce physical inactivity have led to calls for practice‐led research and the need to reduce the individualising effects of health promotion discourse. The purpose of this paper is to examine how parkrun – an increasingly popular, regular, community‐based 5 km running event – comes to be understood as a ‘health practice’ that allows individuals to enact contemporary desires for better health in a collective social context. Taking a reflexive analytical approach, we use interview data from a geographically diverse sample of previously inactive parkrun participants (N = 19) to explore two themes. First, we argue that parkrun offers a space for ‘collective bodywork’ whereby participants simultaneously enact personal body projects while they also experience a sense of being ‘all in this together’ which works to ameliorate certain individualising effects of health responsibilisation. Second, we examine how parkrun figures as a health practice that makes available the subject position of the ‘parkrunner’. In doing so, parkrun enables newly active participants to negotiate discourses of embodied risk to reconcile the otherwise paradoxical experience of being an ‘unfit‐runner’. Findings contribute to sociological understandings of health and illness through new insights into the relation between health practices and emerging physical cultures, such as parkrun.
Magnetic resonance imaging of the prostate and targeted biopsy, Comparison of PIRADS and Gleason grading
Authors: Bastian‐Jordan Matthew
Published: October 2017

Introduction

Multiparametric magnetic resonance imaging (mpMRI) of the prostate has become integral in the investigation of suspected prostate cancer. Regions of interest are graded using the PIRADS scoring system, and in our institution, lesions graded as PIRADS 3–5 undergo sampling by MRI‐guided biopsy. Limited data currently exists on PIRADS grading and biopsy results.

Methods

Retrospective review of 343 MRI‐guided biopsies (MRGB) performed between April 2013 and December 2016 was conducted. This included patients irrespective of whether they were biopsy naïve, biopsy negative or known low‐grade malignancy. A Gleason score (G) >= 3+4 was considered to reflect clinically significant disease (CSD).

Results

Of the 18 PIRADS 2 cases (at referrer request) who went to biopsy, 16 were negative and two had small volume Gleason 6 cancer. A total of 75 PIRADS 3 cases were biopsied with 88% negative or small volume Gleason 6 cancer, only 12% yielded ≥ G 3+4. Of the 133 PIRADS 4 lesions, 24% were negative, 25% were G6 and 51% were ≥ G 3+4. A total of 117 PIRADS 5 cases were biopsied with 7% negative, 13% Gleason 6 and 80% considered significant (≥ G 3+4). Of all biopsies, 230 (67%) had a positive result (≥ G6) with 171 of these (75%) being considered CSD, with overall CSD of 50% (171/343).

Conclusions

This paper demonstrates the incidence of CSD for different PIRADS grades. The low incidence of CSD in PIRADS 3 lesions suggests that in low clinical risk men, follow up in priority to biopsy may be an alternative treatment pathway.
MRI findings in deep infiltrating endometriosis: A pictorial essay
Authors: Thalluri Anitha L , Knox Steven , Nguyen Thi
Published: October 2017

Endometriosis is an important gynaecological disorder which can impact significantly on an individual's quality of life and has major implications on fertility. Deep infiltrating endometriosis is a severe form of endometriosis which can cause obliteration of anatomic compartments. Laparoscopy remains the gold standard for diagnosis of endometriosis, although is an invasive procedure that has the potential to be hindered by obliterative disease. Ultrasound is often employed as the first‐line imaging modality when endometriosis is suspected, however, MRI is more accurate in assessment of complex disease. Pre‐operative MRI is highly specific in the diagnosis of endometriosis and characterization of disease extent, and plays a key role in guiding surgical management. MRI findings in deep infiltrating endometriosis are described.
Evaluation of kidney motion with and without a pneumatic abdominal compression belt: Considerations for stereotactic radiotherapy
Authors: West Kimberley , Russo Majella , Brown Elizabeth , Barry Tamara , Hargrave Cathy , Pryor David
Published: October 2017

Introduction

The optimal delivery of stereotactic radiotherapy for kidney tumours requires an effective motion management strategy. This study assessed the effectiveness of a pneumatic abdominal compression belt in reducing kidney motion during free breathing.

Methods

Thirteen patients, with four‐dimensional computed tomography (4DCT) of the abdomen in free breathing with and without a pneumatic abdominal compression belt, were retrospectively reviewed. Points of Interest (POI) were placed on each kidney to determine the greatest magnitude of displacement in all directions.

Results

Without compression, all patients had >5.0 mm motion in the craniocaudal (CC) direction in at least one kidney. Median CC excursion of the left superior pole was reduced with compression from 8.0 mm (range 2.0 mm–18.0 mm) to 4.0 mm (range 2.0 mm–10.0 mm, P = 0.047) and right superior pole from 10.0 mm (range 4.0 mm–16.0 mm) to 6.0 mm (range 2.0 mm–10.0 mm, P=value 0.051). A benefit was less evident for the left and right inferior poles with median CC excursion of 6.0 mm versus 4.0 mm and 5.0 mm versus 4.0 mm without and with compression, respectively. Median displacement in the anteroposterior direction (≤3.2 mm) and lateral directions (≤1.3 mm) was similar for left and right kidneys and not significantly altered by compression. Overall, seven patients had kidney motion reduced by >5.0 mm with two reduced by 10.0 mm.

Conclusion

A pneumatic abdominal compression belt reduced kidney motion by >5.0 mm in seven of thirteen patients. The relative benefit is patient and location specific and should be assessed on an individual basis.
AcuityView: An r package for portraying the effects of visual acuity on scenes observed by an animal
Authors: Caves Eleanor M. , Johnsen Sönke
Published: October 2017

Visual acuity is one of three basic parameters that characterize a visual system. However, few comparative studies of signals, camouflage and ecology in general have considered visual acuity. This is unfortunate, because humans have high acuity, and thus researchers may focus on visual details of animals and habitats that are not actually visible to the relevant species.

Here we present AcuityView, a package for use in the software r which uses Fourier methods, measures of a viewer's acuity, viewing distance and the size of an image to modify images.

AcuityView renders an image in a way that preserves only the information that an animal with a given visual acuity can detect at a certain distance, thus displaying an image that shows only the visual information available to that viewer.

Ultimately, this will allow for a more informed analysis of what aspects of an animal's visual world may be detectable, and thus relevant to their ecology.
What's Next for Acute Heart Failure Research?
Authors: Collins Sean P. , Levy Phillip D. , Fermann Gregory J. , Givertz Michael M. , Martindale Jennifer M. , Pang Peter S. , Storrow Alan B. , Diercks Deborah D. , Michael Felker G. , Fonarow Gregg C. , Lanfear David J. , Lenihan Daniel J. , Lindenfeld JoAnn M. , Frank Peacock W. , Sawyer Douglas M. , Teerlink John R. , Butler Javed
Published: October 2017

Each year over one million patients with acute heart failure (AHF) present to a United States emergency department (ED). The vast majority are hospitalized for further management. The length of stay and high postdischarge event rate in this cohort have changed little over the past decade. Therapeutic trials have failed to yield substantive improvement in postdischarge outcomes; subsequently, AHF care has changed little in the past 40 years. Prior research studies have been fragmented as either “inpatient” or “ED‐based.” Recognizing the challenges in identification and enrollment of ED patients with AHF, and the lack of robust evidence to guide management, an AHF clinical trials network was developed. This network has demonstrated, through organized collaboration between cardiology and emergency medicine, that many of the hurdles in AHF research can be overcome. The development of a network that supports the collaboration of acute care and HF researchers, combined with the availability of federally funded infrastructure, will facilitate more efficient conduct of both explanatory and pragmatic trials in AHF. Yet many important questions remain, and in this document our group of emergency medicine and cardiology investigators have identified four high‐priority research areas.
Behavioral Changes in Children After Emergency Department Procedural Sedation
Authors: Pearce Jean I. , Brousseau David C. , Yan Ke , Hainsworth Keri R. , Hoffmann Raymond G. , Drendel Amy L.
Published: October 2017

Objective

The purpose of this study was to determine the proportion of children undergoing procedural sedation for fracture reduction in the emergency department (ED) observed to experience negative postdischarge behaviors. Predictors of negative behaviors were evaluated, including anxiety.

Methods

This was a prospective cohort study of children receiving intravenous ketamine sedation for ED fracture reduction. The child's anxiety prior to sedation was measured with the Modified Yale Preoperative Anxiety Scale. Negative behavioral changes were measured with the Post‐Hospitalization Behavior Questionnaire 1 to 2 weeks after discharge. Descriptive statistics and odds ratios (ORs) were calculated. Chi‐square test was used for comparisons between groups. Multivariable logistic regression models evaluated predictors of negative behavioral change after discharge.

Results

Ninety‐seven patients were enrolled; 82 (85%) completed follow‐up. Overall, 33 (40%) children were observed to be highly anxious presedation and 18 (22%) had significant negative behavior changes after ED discharge. Independent predictors for negative behaviors were high anxiety (OR = 9.0, 95% confidence interval [CI] = 2.3–35.7) and nonwhite race (OR = 6.5, 95% CI = 1.7–25.0).

Conclusion

For children undergoing procedural sedation in the ED, two in five children have high preprocedure anxiety and almost one in four have significant negative behaviors 1 to 2 weeks after discharge. Highly anxious and nonwhite children have increased risk of negative behavioral changes that have not been previously recognized in the ED setting.
Impact of Social Cognition on Alcohol Dependence Treatment Outcome: Poorer Facial Emotion Recognition Predicts Relapse/Dropout
Authors: Rupp Claudia I. , Derntl Birgit , Osthaus Friederike , Kemmler Georg , Fleischhacker W. Wolfgang
Published: October 2017

Background

Despite growing evidence for neurobehavioral deficits in social cognition in alcohol use disorder (AUD), the clinical relevance remains unclear, and little is known about its impact on treatment outcome. This study prospectively investigated the impact of neurocognitive social abilities at treatment onset on treatment completion.

Methods

Fifty‐nine alcohol‐dependent patients were assessed with measures of social cognition including 3 core components of empathy via paradigms measuring: (i) emotion recognition (the ability to recognize emotions via facial expression), (ii) emotional perspective taking, and (iii) affective responsiveness at the beginning of inpatient treatment for alcohol dependence. Subjective measures were also obtained, including estimates of task performance and a self‐report measure of empathic abilities (Interpersonal Reactivity Index). According to treatment outcomes, patients were divided into a patient group with a regular treatment course (e.g., with planned discharge and without relapse during treatment) or an irregular treatment course (e.g., relapse and/or premature and unplanned termination of treatment, “dropout”).

Results

Compared with patients completing treatment in a regular fashion, patients with relapse and/or dropout of treatment had significantly poorer facial emotion recognition ability at treatment onset. Additional logistic regression analyses confirmed these results and identified poor emotion recognition performance as a significant predictor for relapse/dropout. Self‐report (subjective) measures did not correspond with neurobehavioral social cognition measures, respectively objective task performance. Analyses of individual subtypes of facial emotions revealed poorer recognition particularly of disgust, anger, and no (neutral faces) emotion in patients with relapse/dropout.

Conclusions

Social cognition in AUD is clinically relevant. Less successful treatment outcome was associated with poorer facial emotion recognition ability at the beginning of treatment. Impaired facial emotion recognition represents a neurocognitive risk factor that should be taken into account in alcohol dependence treatment. Treatments targeting the improvement of these social cognition deficits in AUD may offer a promising future approach.
Maternal adherence with recommendations for folic acid and iodine supplements: A cross‐sectional survey
Authors: Reynolds Andrew N. , Skeaff Sheila A.
Published: October 2017

We conducted a survey of 535 New Zealand women to determine supplement use pre‐pregnancy, during pregnancy and while breastfeeding to evaluate adherence with national recommendations for folic acid and iodine supplementation. Our findings suggest that despite these women being well‐educated and motivated to complete an online survey, there was low adherence to recommendations for folic acid and iodine supplements. Only 38% of women reported supplement intake that met both folic acid and iodine recommendations. This cross‐sectional survey provides information useful to policy makers, clinicians and researchers seeking to protect and promote maternal and infant health.
Real‐time ultrasound‐guided axillary vein cannulation in children: a randomised controlled trial
Authors: Kim E.‐H. , Lee J.‐H. , Song I.‐K. , Kim H.‐S. , Jang Y.‐E. , Choi S.‐N. , Kim J.‐T.
Published: October 2017

The axillary vein is a good site for ultrasound‐guided central venous cannulation in terms of infection rate, patient comfort and its anatomical relationship with the clavicle and lungs. We compared real‐time ultrasound‐guided axillary vein cannulation with conventional infraclavicular landmark‐guided subclavian vein cannulation in children. A total of 132 paediatric patients were randomly allocated to either ultrasound‐guided axillary vein (axillary group) or landmark‐guided subclavian vein (landmark group). The outcomes measured were success rate after two attempts, first‐attempt success rate, time to cannulation and complication rate. The success rate after two attempts was 83% in the axillary group compared with 63% in the landmark group (odds ratio 2.85, 95%CI 1.25–6.48, p = 0.010). The first‐attempt success rate was 46% for the axillary group and 40% for the landmark group (p = 0.274) and median time to cannulation was 156 s for the axillary group and 180 s for the landmark group (p = 0.286). There were no differences in complication rates between the two groups, although three episodes of subclavian artery puncture occurred in the landmark group (p = 0.08). We conclude that axillary vein cannulation using a real‐time ultrasound‐guided in‐plane technique is useful and effective in paediatric patients.
Possible involvement of the glucocorticoid receptor (NR3C1) and selected NR3C1 gene variants in regulation of human testicular function
Authors: Nordkap L. , Almstrup K. , Nielsen J. E. , Bang A. K. , Priskorn L. , Krause M. , Holmboe S. A. , Winge S. B. , Egeberg Palme D. L. , Mørup N. , Petersen J. H. , Juul A. , Skakkebæk N. E. , Rajpert‐De Meyts E. , Jørgensen N.
Published: October 2017

Perceived stress has been associated with decreased semen quality but the mechanisms have not been elucidated. It is not known whether cortisol, the major stress hormone in humans, can act directly via receptors in the testis, and whether variants in the gene encoding the glucocorticoid receptor (NR3C1) can possibly modulate the effect. To address these questions, we investigated the expression of the glucocorticoid receptor in human testicular tissue, including adult and fetal samples (n = 20) by immunohistochemical staining, and in silico analysis of publicly available datasets. In the adult testis NR3C1 protein was detected in peritubular cells, a subset of Leydig cells, Sertoli cells (weak), and spermatogonia, but not in spermatids. The NR3C1 expression pattern in fetal testis samples differed by a notably stronger reaction in Sertoli cells, lack of staining in gonocytes but the presence in a subset of pro‐spermatogonia, and the almost absent reaction in nascent peritubular cells. In parallel, we explored the association between adult testicular function and three single nucleotide NR3C1 polymorphisms (BcII [rs41423247], 9β [rs6198], and Tth111I [rs10052957]) affecting glucocorticoid sensitivity. Testicular function was determined by semen analysis and reproductive hormone profiling in 893 men from the general population. The NR3C1 SNP BclI was associated with semen quality in an over‐dominant manner with heterozygotes having better semen parameters compared to both homozygote constellations, and with sperm motility showing the strongest association. This association was supported by a higher inhibin B and inhibin B/FSH ratio, as well as a lower FSH in BclI heterozygotes. The SNPs 9β and Tth111I were not associated with semen parameters. Although the clinical impact of the findings is limited, the results substantiate a suggested link between stress and testicular function. Hence this investigation should be regarded as a discovery study generating hypotheses for future studies.
Norepinephrine infusion improves haemodynamics in the preterm infants during septic shock
Authors: Rizk MY , Lapointe A , Lefebvre F , Barrington KJ
Published: October 2017

Aim

This study evaluated the clinical and haemodynamic effects of norepinephrine infusion in preterm infants.

Methods

The effects of norepinephrine therapy for refractory hypotension were evaluated in preterm infants between April 2009 and April 2011 at the neonatal intensive care unit of Sainte‐Justine Hospital, Montreal, Quebec. Changes in haemodynamics and clinical parameters were analysed eight hours before and eight hours after the start of norepinephrine infusion, and eight hours after its cessation.

Results

During the study, 30 preterm infants at a mean gestational age of 26.5 ± 2.6 weeks (median: 25.7, 23.4–34) and birthweight of 903 ± 437 g (median 827, 450–2550) received norepinephrine infusion for neonatal septic shock. After eight hours of treatment, mean blood pressure, urine output and FiO2 significantly improved. Eight hours after cessation of norepinephrine infusion, the number of patients treated with other inotropes decreased significantly, 24 patients (80%) had normal mean blood pressure and 27 patients (90%) had normal urine output.

Conclusion

Norepinephrine therapy could be considered to improve blood pressure and urine output during neonatal septic shock in preterm infants. Further studies are needed to prove the efficacy and safety of norepinephrine infusion in neonates.
Severe obesity is a limitation for the use of body mass index standard deviation scores in children and adolescents
Authors: Júlíusson Pétur B. , Roelants Mathieu , Benestad Beate , Lekhal Samira , Danielsen Yngvild , Hjelmesæth Jøran , Hertel Jens K
Published: October 2017

Aim

We analysed the distribution of the body mass index standard deviation scores (BMI‐SDS) in children and adolescents seeking treatment for severe obesity, according to the International Obesity Task Force (IOTF), World Health Organization (WHO) and the national Norwegian Bergen Growth Study (BGS) BMI reference charts and the percentage above the International Obesity Task Force 25 cut‐off (IOTF‐25).

Methods

This was a cross‐sectional study of 396 children aged four to 17 years, who attended a tertiary care obesity centre in Norway from 2009 to 2015. Their BMI was converted to SDS using the three growth references and expressed as the percentage above IOTF‐25. The percentage of body fat was assessed by bioelectrical impedance analysis.

Results

Regardless of which BMI reference chart was used, the BMI‐SDS was significantly different between the age groups, with a wider range of higher values up to 10 years of age and a more narrow range of lower values thereafter. The distributions of the percentage above IOTF‐25 and percentage of body fat were more consistent across age groups.

Conclusions

Our findings suggest that it may be more appropriate to use the percentage above a particular BMI cut‐off, such as the percentage above IOTF‐25, than the IOTF, WHO and BGS BMI‐SDS in paediatric patients with severe obesity.
Effects of Genetic Variants on Carboxylesterase 1 Gene Expression, and Clopidogrel Pharmacokinetics and Antiplatelet Effects
Authors: Neuvonen Mikko , Tarkiainen E. Katriina , Tornio Aleksi , Hirvensalo Päivi , Tapaninen Tuija , Paile‐Hyvärinen Maria , Itkonen Matti K. , Holmberg Mikko T. , Kärjä Vesa , Männistö Ville T. , Neuvonen Pertti J. , Pihlajamäki Jussi , Backman Janne T. , Niemi Mikko
Published: October 2017

Several single nucleotide variations (SNVs) affect carboxylesterase 1 (CES1) activity, but the effects of genetic variants on CES1 gene expression have not been systematically investigated. Therefore, our aim was to investigate effects of genetic variants on CES1 gene expression in two independent whole blood sample cohorts of 192 (discovery) and 88 (replication) healthy volunteers and in a liver sample cohort of 177 patients. Furthermore, we investigated possible effects of the found variants on clopidogrel pharmacokinetics (n = 106) and pharmacodynamics (n = 46) in healthy volunteers, who had ingested a single 300 mg or 600 mg dose of clopidogrel. Using massively parallel sequencing, we discovered two CES1 SNVs, rs12443580 and rs8192935, to be strongly and independently associated with a 39% (p = 4.0 × 10−13) and 31% (p = 2.5 × 10−8) reduction in CES1 whole blood expression per copy of the minor allele. These findings were replicated in the replication cohort. However, these SNVs did not affect CES1 liver expression, or clopidogrel pharmacokinetics or pharmacodynamics. Conversely, the CES1 c.428G>A missense SNV (rs71647871) impaired the hydrolysis of clopidogrel, increased exposure to clopidogrel active metabolite and enhanced its antiplatelet effects. In conclusion, the rs12443580 and rs8192935 variants reduce CES1 expression in whole blood but not in the liver. These tissue‐specific effects may result in substrate‐dependent effects of the two SNVs on CES1‐mediated drug metabolism.
Next‐Generation Magnetic Nanocomposites: Cytotoxic and Genotoxic Effects of Coated and Uncoated Ferric Cobalt Boron (FeCoB) Nanoparticles In Vitro
Authors: Netzer Katharina , Jordakieva Galateja , Girard Angelika M. , Budinsky Alexandra C. , Pilger Alexander , Richter Lukas , Kataeva Nadezhda , Schotter Joerg , Godnic‐Cvar Jasminka , Ertl Peter
Published: October 2017

Metal nanoparticles (NPs) have unique physicochemical properties and a widespread application scope depending on their composition and surface characteristics. Potential biomedical applications and the growing diversity of novel nanocomposites highlight the need for toxicological hazard assessment of next‐generation magnetic nanomaterials. Our study aimed to evaluate the cytotoxic and genotoxic properties of coated and uncoated ferric cobalt boron (FeCoB) NPs (5–15 nm particle size) in cultured normal human dermal fibroblasts. Cell proliferation was assessed via ATP bioluminescence kit, and DNA breakage and chromosomal damage were measured by alkaline comet assay and micronucleus test. Polyacryl acid‐coated FeCoB NPs [polyacrylic acid (PAA)‐FeCoB NPs) and uncoated FeCoB NPs inhibited cell proliferation at 10 μg/ml. DNA strand breaks were significantly increased by PAA‐coated FeCoB NPs, uncoated FeCoB NPs and l‐cysteine‐coated FeCoB NPs (Cys‐FeCoB NPs), although high concentrations (10 μg/ml) of coated NPs (Cys‐ and PAA‐FeCoB NPs) showed significantly more DNA breakage when compared to uncoated ones. Uncoated FeCoB NPs and coated NPs (PAA‐FeCoB NPs) also induced the formation of micronuclei. Additionally, PAA‐coated NPs and uncoated FeCoB NPs showed a negative correlation between cell proliferation and DNA strand breaks, suggesting a common pathomechanism, possibly by oxidation‐induced DNA damage. We conclude that uncoated FeCoB NPs are cytotoxic and genotoxic at in vitro conditions. Surface coating of FeCoB NPs with Cys and PAA does not prevent but rather aggravates DNA damage. Further safety assessment and a well‐considered choice of surface coating are needed prior to application of FeCoB nanocomposites in biomedicine.
Regularity of a Renewal Process Estimated from Binary Data
Authors: Rice John D. , Strawderman Robert L. , Johnson Brent A.
Published: October 2017

Assessment of the regularity of a sequence of events over time is important for clinical decision-making as well as informing public health policy. Our motivating example involves determining the effect of an intervention on the regularity of HIV self-testing behavior among high-risk individuals when exact self-testing times are not recorded. Assuming that these unobserved testing times follow a renewal process, the goals of this work are to develop suitable methods for estimating its distributional parameters when only the presence or absence of at least one event per subject in each of several observation windows is recorded. We propose two approaches to estimation and inference: a likelihood-based discrete survival model using only time to first event; and a potentially more efficient quasi-likelihood approach based on the forward recurrence time distribution using all available data. Regularity is quantified and estimated by the coefficient of variation (CV) of the interevent time distribution. Focusing on the gamma renewal process, where the shape parameter of the corresponding interevent time distribution has a monotone relationship with its CV, we conduct simulation studies to evaluate the performance of the proposed methods. We then apply them to our motivating example, concluding that the use of text message reminders significantly improves the regularity of self-testing, but not its frequency. A discussion on interesting directions for further research is provided.
A randomized waitlist control community study of Social Cognition and Interaction Training for people with schizophrenia
Authors: Gordon Anne , Davis Penelope J. , Patterson Susan , Pepping Christopher A. , Scott James G. , Salter Kerri , Connell Melissa
Published: October 2017

Objective

Social Cognition and Interaction Training (SCIT) has demonstrated effectiveness in improving social cognition and functioning of people with schizophrenia. This pilot study examines the acceptability, feasibility, and effectiveness of SCIT with individuals who have schizophrenia‐spectrum disorders and are receiving care through a public mental health service.

Method

In a pragmatic randomized waitlist controlled trial, 36 participants (aged 19–55 years) with a schizophrenia spectrum disorder were randomly allocated to SCIT or treatment as usual (TAU). Measures of theory of mind, emotion perception, attributional bias, social skills, quality of life, life skills, depression, anxiety, and stress were administered pre‐ and post‐intervention with follow‐up conducted 4 months later. All wait‐list controls subsequently received the intervention and a secondary within‐group analysis was conducted including these participants.

Results

While no significant differences were found between groups on any outcomes, there was strong engagement with the SCIT intervention. Of the 21 participants in the intervention group, the completion rate was 85.71% with a median attendance rate of 17 sessions. Within subject analyses of SCIT participants over time showed significant improvements in quality of life, emotion recognition, social skills, and a trend towards better life skills from pre‐ to post‐intervention. These gains were sustained at the 4‐month follow‐up time.

Conclusions and implications for practice

Although this study showed limited benefits in outcomes associated with SCIT compared with TAU, it demonstrated the acceptability of SCIT to participants in a real world public health setting shown by high retention, attendance, and positive feedback.

This pilot shows SCIT can be implemented in routine clinical practice and lays the foundation for a larger pragmatic study.

Practitioner points

SCIT can be implemented successfully in a real‐world community mental health setting.

SCIT had high levels of acceptability to these participants.

Limitations

The small sample size meant there was insufficient power to detect differences between groups on outcome measures.

The study did not include measures of psychiatric symptoms or neuropsychological functioning which may have influenced participants’ capacity to benefit from SCIT.
Optimization of rituximab for the treatment of DLBCL: increasing the dose for elderly male patients
Authors: Pfreundschuh Michael , Murawski Niels , Zeynalova Samira , Ziepert Marita , Loeffler M. , Hänel Matthias , Dierlamm Judith , Keller Ulrich , Dreyling Martin , Truemper Lorenz , Frickhofen Norbert , Hünerlitürkoglu Ali‐Nuri , Schmitz Norbert , Pöschel Viola , Rixecker Tanja , Berdel Christian , Rübe Christian , Held Gerhard , Zwick Carsten
Published: October 2017

Male sex is associated with unfavourable pharmacokinetics and prognosis in elderly patients with diffuse large B‐cell lymphoma (DLBCL). We investigated higher rituximab doses for elderly male DLBCL patients. Elderly patients (61–80 years) received 6 cycles CHOP‐14 (cyclophosphamide, doxorubicin, vincristine and prednisone at 14‐day intervals) and were randomized to 8 cycles rituximab (males 500 mg/m2, females 375 mg/m2) every 2 weeks or according to an upfront dose‐dense schedule. In 268 (120 females, 148 males) no difference between the standard and the upfront dose‐dense rituximab schedule was found (3‐year PFS 72% vs. 74%; OS 74% vs. 77%; P = 0.651). The 500 mg/m2 dose of rituximab for male patients was associated with serum levels and exposure times slightly better than in females and a male/female hazard ratio of 0.9 for progression‐free survival (PFS) and 0.8 for overall survival. For elderly males, 500 mg/m2 was not more toxic than 375 mg/m2 rituximab, but improved PFS by 32.5% (P = 0.039), with a trend for a (30%) better overall survival (P = 0.076) in a planned subgroup analysis adjusting for International Prognostic Index risk factors. We conclude that the higher rituximab dose for elderly male patients abrogated the adverse prognosis of male sex without increasing toxicity. In the era of personalized medicine, sex‐specific pharmacokinetics and toxicities should be investigated for all drugs where these parameters impact on outcome.
Control of GABARAP‐mediated autophagy by the Golgi complex, centrosome and centriolar satellites
Authors: Joachim Justin , Tooze Sharon A.
Published: October 2017

Within minutes of induction of autophagy by amino‐acid starvation in mammalian cells, multiple autophagosomes form throughout the cell cytoplasm. During their formation, the autophagosomes sequester cytoplasmic material and deliver it to lysosomes for degradation. How these organelles can be so rapidly formed and how their formation is acutely regulated are major questions in the autophagy field. Protein and lipid trafficking from diverse cell compartments contribute membrane to, or regulate the formation of the autophagosome. In addition, recruitment of Atg8 (in yeast), and the ATG8‐family members (in mammalian cells) to autophagosomes is required for efficient autophagy. Recently, it was discovered that the centrosome and centriolar satellites regulate autophagosome formation by delivery of an ATG8‐family member, GABARAP, to the forming autophagosome membrane, the phagophore. We propose that GABARAP regulates phagophore expansion by activating the ULK complex, the amino‐acid controlled initiator complex. This finding reveals a previously unknown link between the centrosome, centriolar satellites and autophagy.
Ecological and evolutionary legacy of megafauna extinctions
Authors: Galetti Mauro , Moleón Marcos , Jordano Pedro , Pires Mathias M. , Guimarães Paulo R. , Pape Thomas , Nichols Elizabeth , Hansen Dennis , Olesen Jens M. , Munk Michael , de Mattos Jacqueline S. , Schweiger Andreas H. , Owen‐Smith Norman , Johnson Christopher N. , Marquis Robert J. , Svenning Jens‐Christian
Published: October 2017

For hundreds of millions of years, large vertebrates (megafauna) have inhabited most of the ecosystems on our planet. During the late Quaternary, notably during the Late Pleistocene and the early Holocene, Earth experienced a rapid extinction of large, terrestrial vertebrates. While much attention has been paid to understanding the causes of this massive megafauna extinction, less attention has been given to understanding the impacts of loss of megafauna on other organisms with whom they interacted. In this review, we discuss how the loss of megafauna disrupted and reshaped ecological interactions, and explore the ecological consequences of the ongoing decline of large vertebrates. Numerous late Quaternary extinct species of predators, parasites, commensals and mutualistic partners were associated with megafauna and were probably lost due to their strict dependence upon them (co‐extinctions). Moreover, many extant species have megafauna‐adapted traits that provided evolutionary benefits under past megafauna‐rich conditions, but are now of no or limited use (anachronisms). Morphological evolution and behavioural changes allowed some of these species partially to overcome the absence of megafauna. Although the extinction of megafauna led to a number of co‐extinction events, several species that likely co‐evolved with megafauna established new interactions with humans and their domestic animals. Species that were highly specialized in interactions with megafauna, such as large predators, specialized parasites, and large commensalists (e.g. scavengers, dung beetles), and could not adapt to new hosts or prey were more likely to die out. Partners that were less megafauna dependent persisted because of behavioural plasticity or by shifting their dependency to humans via domestication, facilitation or pathogen spill‐over, or through interactions with domestic megafauna. We argue that the ongoing extinction of the extant megafauna in the Anthropocene will catalyse another wave of co‐extinctions due to the enormous diversity of key ecological interactions and functional roles provided by the megafauna.
Phylogenetic and functional underdispersion in Neotropical phyllostomid bat communities
Authors: Presley Steven J. , Cisneros Laura M. , Higgins Christopher L. , Klingbeil Brian T. , Scheiner Samuel M. , Willig Michael R.
Published: October 2017

Habitat conversion creates a mosaic of land cover types, which affect the spatial distribution, diversity, and abundance of resources. We used abundance, functional, and phylogenetic information to determine if Neotropical bat communities exhibited phylogenetic or functional overdispersion or underdispersion in response to habitat conversion. Overdispersion suggests the operation of intraclade competition, niche partitioning, limiting similarity, or character displacement, whereas underdispersion indicates the operation of interclade competition, abiotic filtering, or biotic filtering. We expected (1) biotic filtering in landscapes with extensive forest loss to result in underdispersion; (2) niche partitioning in heterogeneous landscapes with intermediate forest loss to result in overdispersion; and (3) intraclade competition during times of low resource abundance (i.e., dry season) to increase, resulting in overdispersion. Most bat communities exhibited phylogenetic or functional underdispersion; none exhibited overdispersion. Expectations were not met: underdispersion did not increase with forest loss, heterogeneous landscapes did not induce overdispersion, and no evidence supported the contention that intraclade competition changed with season. Empirical responses were season‐specific, likely because resource availability may affect relationships between forest cover and underdispersion and between biodiversity and underdispersion. During the dry season, only high diversity sites exhibited underdispersion (i.e., functional or phylogenetic redundancy), whereas underdispersion occurred in low, intermediate, or high diversity communities during the wet season; we suggest that this difference likely arises due to changes in resource abundance. Communities with high diversity and redundancy occupied heterogeneous sites during the dry season, but communities with high redundancy were restricted to large forest reserves during the wet season.
Measuring Early Care and Education Quality
Authors: Burchinal Margaret
Published: October 2017

High‐quality early care and education (ECE) programs are thought to increase opportunities for all children to succeed in school, but recent findings call into question whether these programs affect children as anticipated. In this article, I examine research relating the quality of ECE to children's outcomes, finding somewhat inconsistent and modest associations with widely used measures of process and structural quality, and more consistent and stronger associations with other dimensions of ECE such as curricula and type of ECE program. I discuss why the associations between ECE quality and outcomes are so modest, including limited children's outcomes, psychometric issues with quality measures, and a need to revise and expand measures of ECE quality. The evidence indicates that we need to focus on the content of instruction and teaching practices, as well as the extent to which teachers actively scaffold learning opportunities. We also need to continue to focus on the quality of interactions between teachers and children, and on children's access to age‐appropriate activities.
Threaded ensembles of autoencoders for stream learning
Authors: Dong Yue , Japkowicz Nathalie
Published: October 2017

Anomaly detection in streaming data is an important problem in numerous application domains. Most existing model‐based approaches to stream learning are based on decision trees due to their fast construction speed. This paper introduces streaming autoencoder (SA), a fast and novel anomaly detection algorithm based on ensembles of neural networks for evolving data streams. It is a one‐class learner, which only requires data from the positive class for training and is accurate even when anomalous training data are rare. It features an ensemble of threaded autoencoders with continuous learning capacity. Furthermore, the SA uses a 2‐step detection mechanism to ensure that real anomalies are detected with low false‐positive rates. The method is highly efficient because it processes data streams in parallel with multithreads and alternating buffers. Our analysis shows that SA has a linear runtime and requires constant memory space. Empirical comparisons to the state‐of‐the‐art methods on multiple benchmark data sets demonstrate that the proposed method detects anomalies efficiently with fewer false alarms.