bluuebunny/crossref_metadata_2025 huggingface dataset:
Investigating the readiness of people in manufacturing SMEs to embark on Lean Six Sigma projects
Authors: Shokri Alireza , Waring Teresa Shirley , Nabhani Farhad
Published: July 2016

Purpose

– The purpose of this paper is to focus on three fundamental human-related behaviour factors associated with Lean Six Sigma (LSS) projects in German manufacturing small-and medium-sized enterprises (SMEs) on the readiness of people (managers and their staff) to commence LSS projects. These are core personal competence, strategic vision of the people and the organisational culture of the specific organisation.

Design/methodology/approach

– Based on a thorough review of the academic literature a set of hypotheses were constructed to examine the level of association between people’s competence, vision and culture with LSS readiness within SMEs. This was done using correlation and regression analysis. Data collection were carried out in seven different German manufacturing SMEs involved in aerospace supply and agro-food manufacturing using a survey instrument.

Findings

– It was found that there is a strong positive association between the core competence of people and organisational culture with readiness for commencing LSS in the manufacturing SMEs studied. The core values of people, education level and the vision of making continuous quality improvement were identified as key variables in promoting LSS readiness in these manufacturing SMEs. This study indicates that these “softer” variables can be essential to successful LSS implementation and need to be explored further before undertaking the process.

Practical implications

– From the perspective of the implementers of LSS the results of this research could be of interest to different manufacturing SMEs intending to embark upon an LSS journey as it highlights the significance of human-related behavioural factors in the process. SME organisations may consider carrying out development or training with their managers and employees around personal and organisational values, addressing core competence and strengthening organisational culture in order to facilitate LSS readiness and enhance the prospect of its success.

Originality/value

– It would appear that this LSS research has not been carried out within the German manufacturing SME context before and although discrete in nature has surfaced the “softer” variables of core competence of staff and organisational culture as important readiness issues to address when undertaking LSS. This integrated approach of human behavioural factors, organisational culture, LSS and manufacturing SMEs demonstrates the originality of the research.
Supply-side resilience as practice bundles: a critical incident study
Authors: Dabhilkar Mandar , Birkie Seyoum Eshetu , Kaulio Matti
Published: July 2016

Purpose

– The purpose of this paper is to conceptualize a typology of supply-side resilience capabilities and empirically validates these capabilities and their constituent bundles of practices.

Design/methodology/approach

– The study is primarily qualitative, employing the critical incident technique to collect data across 22 firms and seeking to validate how and why practice bundles form and relate to operations performance. It contains a frequency of occurrence analysis for the purpose of triangulation, a minor statistical part to provide some additional evidence of bundle formation and correlation between adoption of bundles of practices and recovered operations performance after upstream supply chain disruptions.

Findings

– Four supply-side resilience capabilities are conceptualized along two dichotomous dimensions – “proactive/reactive” and “internal/external” – in a 2×2 matrix as proactive-internal, proactive-external, reactive-internal and reactive-external resilience capabilities. Empirical support for the conceptualized typology is found. Bundles of specific practices that can be associated with each capability are identified. Moreover, the study finds a relationship between these practice bundles and recovered operations performance.

Research limitations/implications

– The statistical part is used just to provide some additional evidence through factor and regression analyses that these capabilities exist and do benefit adopting firms.

Practical implications

– Specifies practices that lead to recovered operations performance in the event of supply disruptions.

Originality/value

– Advances current theory by operationalizing resilience as a set of dynamic capabilities in terms of practice bundles that aid in recovering operations performance upon supply disruptions.
Enhancing sustainability curricula through faculty learning communities
Authors: Natkin Lisa W. , Kolbe Tammy
Published: July 2016

Purpose

Although the number of higher education institutions adopting sustainability-focused faculty learning communities (FLCs) has grown, very few of these programs have published evaluation research. This paper aims to report findings from an evaluation of the University of Vermont’s (UVM’s) sustainability faculty fellows (SFF) program. It discusses how utilization-focused program evaluation is an important tool for developing and improving sustainability-focused FLCs. The SFF program aims to enhance sustainability education by bringing faculty members together to expand their knowledge of sustainability concepts and offer pedagogical support for integrating those concepts in higher education curricula.

Design/methodology/approach

A utilization-focused evaluation framework guided the evaluation’s design and implementation. Multiple methods were used to collect evaluation data, including in-person interviews and an online survey with SFF program participants.

Findings

The evaluation’s findings suggest that UVM’s SFF program expanded faculty understanding of sustainability concepts, encouraged curricular and instructional reform and made progress toward developing a community of faculty interested in sustainability education. The evaluation’s utilization focus was instrumental in providing useful information for improving the SFF program.

Originality/value

Evaluation findings expand what we know about the potential effectiveness of sustainability-focused FLCs, as well as challenges institutions might encounter when adopting such an approach to faculty development. Findings also point to ways in which utilization-focused evaluations can inform program development and improvement efforts.
The alternative “Marketing Revolution”
Authors: Tadajewski Mark
Published: July 2016

Purpose

This paper reviews the contributions of Harry Tosdal, a pioneer of sales and marketing management. It serves to puncture a variety of marketing myths and illuminate a completely neglected concept of the consumer.

Design/methodology/approach

This account is based on a close reading of Tosdal’s publications.

Findings

Tosdal articulated a highly nuanced interpretation of marketing management, market research and sales force management. Each of these elements was keyed into fostering goodwill between firm and customer. Perhaps most importantly, he provides a counterpoint to the idea that the consumer is sovereign in the marketplace. Instead, he makes a case that the ontology of the market is riven by compromise.

Originality/value

This paper highlights the concept of the compromising consumer. Arguably, this is a much more empirically realistic conception of the agency we possess in the marketplace than the idea that we move markets in ways absolutely consistent with our desires.
Gay guys using gay language: friendship, shared values and the intent‐context‐effect matrix
Authors: McCormack Mark , Wignall Liam , Morris Max
Published: July 2016

This article draws on in‐depth interviews with 35 openly gay male undergraduates from four universities in England to develop an understanding of the changing nature of language related to homosexuality. In addition to finding a diminution in the prevalence of homophobic language, we demonstrate that participants maintain complex and nuanced understandings of phrases that do not use homophobic pejoratives, such as ‘that's so gay’. The majority of participants rejected the notion that these phrases are inherently homophobic, instead arguing that the intent with which they are said and the context in which they are used are vital in understanding their meaning and effect. We conceptualize an intent‐context‐effect matrix to understand the interdependency of these variables. Highlighting the situated nature of this matrix, we also demonstrate the importance of the existence of shared norms between those saying and hearing the phrase when interpreting such language.
Factors associated with maternal mortality at advanced maternal age: a population‐based case–control study
Authors: McCall SJ , Nair M , Knight M
Published: July 2016

Objective

This study aimed to examine the factors associated with maternal mortality among women aged ≥35 years.

Design

Unmatched population based case–control study.

Setting

United Kingdom.

Population

Between 2009 and 2012, 105 cases of maternal deaths aged ≥35 years were extracted from the surveillance database of the MBRRACE‐UK confidential enquiries into maternal deaths in the UK. In addition, 766 controls aged ≥35 years were identified from the UK Obstetric Surveillance System (2005–2012).

Methods

Risk factors known to be associated with maternal mortality and morbidity and for which data were available were examined for their association with maternal mortality among women ≥35 years using logistic regression analysis.

Main outcome measures

Odds ratios and 95% confidence intervals associated with maternal death.

Results

Five factors were found to be significantly associated with increased odds of death among women aged ≥35 years: smoking during pregnancy (adjusted odds ratio (aOR) 2.06, 95% CI 1.13–3.75), inadequate use of antenatal care (aOR 23.62, 95% CI 8.79–63.45), medical co‐morbidities (aOR 5.92, 95% CI 3.56–9.86) and previous pregnancy problems (aOR 2.06, 95% CI 1.23–3.45). The odds associated with death increased by 12% per year increase in age (aOR 1.12, 95% CI 1.02–1.22).

Conclusion

Age was associated with maternal mortality even after adjusting for other known risk factors. Importantly, this study showed an association between maternal mortality and smoking among women aged 35 years or older. It emphasises the importance of public health action to reduce smoking levels and address trends in rising maternal age.

Tweetable abstract

Smoking is a risk factor for maternal death for those aged over 35 years.
Feeding and parasitism of adultStenoperlaspp. (Plecoptera: Eustheniidae) in New Zealand
Authors: Winterbourn Michael J , Pohe Stephen R
Published: July 2016

The adult diets of two species of stonefly,Stenoperla prasina(Newman, 1845) andStenoperla maclellaniZwick, 1979 were investigated by gut content analysis. Adults were collected throughout New Zealand by light‐trapping at 77 streamside sites most of which were located in native forest.S. prasinawas widely distributed and collected at 43 sites, whereasS. maclellaniwas sampled at 10 sites in the South Island only. Of 200 S. prasinaand 42 S. maclellanidissected, 36% and 69% respectively, contained food. Microscopic examination of a subset of individuals indicated that the gut contents of both species were dominated by sooty mould fungi with lesser contributions made by plant tissue, pollen grains and the spores of tree ferns. These findings suggest that stoneflies had been feeding on the trunks, branches and foliage of trees and perhaps on fronds of tree ferns. As the abdomens of most females were packed with eggs, which mature in late‐instar nymphs it is likely that feeding provides adults with a source of immediately available energy for mating and flight. Encysted larval stages of hairworms (Nematomorpha) and a trematode were also found in both stonefly species. Metacercarial cysts of the trematode are the first records of larval flukes parasitising New Zealand stoneflies. They were found in about 43% of dissected adults of each species with up to 40 cysts present in some individuals. It is possible that the parasite's definitive host is one of New Zealand's native bats (Chiroptera), which are known to eatStenoperlaand inhabit streamside forests at some of the localities where parasitised stoneflies were taken. Overall, our results provide further evidence for the importance of sooty mould fungi as a food source for New Zealand insects and highlight the role ofStenoperlaas a vector of larval parasites from aquatic to terrestrial hosts.
Navigating the Range of Statistical Tools for Inferential Network Analysis
Authors: Cranmer Skyler J. , Leifeld Philip , McClurg Scott D. , Rolfe Meredith
Published: July 2016

The last decade has seen substantial advances in statistical techniques for the analysis of network data, as well as a major increase in the frequency with which these tools are used. These techniques are designed to accomplish the same broad goal, statistically valid inference in the presence of highly interdependent relationships, but important differences remain between them. We review three approaches commonly used for inferential network analysis—the quadratic assignment procedure, exponential random graph models, and latent space network models—highlighting the strengths and weaknesses of the techniques relative to one another. An illustrative example using climate change policy network data shows that all three network models outperform standard logit estimates on multiple criteria. This article introduces political scientists to a class of network techniques beyond simple descriptive measures of network structure, and it helps researchers choose which model to use in their own research.
Inequality, Labor Market Segmentation, and Preferences for Redistribution
Authors: Alt James , Iversen Torben
Published: July 2016

We formalize and examine two overlapping models that show how rising inequality combined with ethnic and racial heterogeneity can explain why many advanced industrial countries have experienced a drop in support for redistribution as inequality has risen. One model, based on altruism and homophily, focuses on the effect of increasing “social distance” between the poor and the middle class, especially when minorities are increasingly overrepresented among the very poor. The other, based on self‐interest, combines an “insurance” model of preferences for redistribution with increasingly segmented labor markets, in which immigration of workers without recognized skills leaves most native workers better off but intensifies competition for low‐end jobs. Empirically, when we estimate parameters from the two models using data from multiple waves of ISSP surveys, we find that labor market segmentation, previously omitted in this literature, has more consistent effects than social distance.
Delays during the administration of acetylcysteine for the treatment of paracetamol overdose
Authors: Bailey George P. , Najafi Javad , Elamin Muhammad E. M. O. , Waring W. Stephen , Thomas Simon H. L. , Archer John R. H. , Wood David M. , Dargan Paul I.
Published: July 2016

Background

The licensed intravenous acetylcysteine regimen for treating paracetamol overdose in most countries uses three separate infusions over 21 h. This complex regimen, requiring different infusion concentrations and rates, has been associated with administration errors. The aim of the present study was to assess the extent of administration delays occurring during this acetylcysteine regimen.

Method

A 6‐month retrospective observational study was conducted at three English teaching hospitals with clinical toxicology services from October 2014. Patients aged 16 years and over, treated with intravenous acetylcysteine for paracetamol overdose, were included. The start times for infusions were recorded and the delays compared with the prescribed infusion times were calculated. Anaphylactoid reactions, intravenous cannula problems, overdose intent and smoking status were recorded to assess their contribution to delays.

Results

From 263 cases identified, 198 met the study inclusion criteria. The median time between the start of infusions 1 and 3 was delayed from the intended 5 h by a median (interquartile range) of 90 (50–163) min, with 135 (68%) cases delayed by more than 1 h. Significantly longer delays were observed in patients with anaphylactoid reactions [median delay 267 (217–413) min, n = 8] and accidental/supratherapeutic overdose [median delay 170 (95–260) min, n = 29]. There were no significant differences between smokers and nonsmokers, or for patients with intravenous cannula problems.

Conclusion

Long delays were identified during the three‐infusion acetylcysteine regimen for the treatment of paracetamol overdose. These were of clinical significance and could lead to periods of subtherapeutic plasma acetylcysteine concentrations and potentially avoidable hepatotoxicity, as well as delaying hospital discharge.
GBT440 increases haemoglobin oxygen affinity, reduces sickling and prolongs RBC half‐life in a murine model of sickle cell disease
Authors: Ferrone Frank A.
Published: July 2016

The article by Oksenberg et al., cited in this Editorial Comment, is published in issue 175:1 (http://onlinelibrary.wiley.com/doi/10.1111/bjh.14214/full).
Multiple myeloma: patient outcomes in real‐world practice
Authors: Yong Kwee , Delforge Michel , Driessen Christoph , Fink Leah , Flinois Alain , Gonzalez‐McQuire Sebastian , Safaei Reza , Karlin Lionel , Mateos Maria‐Victoria , Raab Marc S. , Schoen Paul , Cavo Michele
Published: July 2016

With increasing number of therapies available for the treatment of multiple myeloma, it is timely to examine the course of patients' journeys. We investigated patient characteristics, treatment durations and outcomes, and symptom burden across the treatment pathway in Belgium, France, Germany, Italy, Spain, Switzerland and the UK. In total, 435 physicians retrospectively reviewed 4997 patient charts. Profiles of patients diagnosed with multiple myeloma during the last 12 months were similar across countries; bone pain was the most common presentation. Median duration of first‐line therapy was 6 months, followed by a median treatment‐free interval of 10 months; both these decreased with increasing lines of therapy, as did time to progression. Depth of response, as assessed by the treating physician, also decreased with each additional line of therapy: 74% of patients achieved at least a very good partial response at first line, compared with only 11% at fifth line. Deeper responses were associated with longer time to progression, although these were physician‐judged. Toxicities and co‐morbidities increased with later treatment lines, and were more likely to have led to discontinuation of treatment. These real‐world data provide an insight into patient outcomes and treatment decisions being made in clinical practice.
Patient‐reported outcomes in the ProtecT randomized trial of clinically localized prostate cancer treatments: study design, and baseline urinary, bowel and sexual function and quality of life
Authors: Lane Athene , Metcalfe Chris , Young Grace J. , Peters Tim J. , Blazeby Jane , Avery Kerry N. L. , Dedman Daniel , Down Liz , Mason Malcolm D. , Neal David E. , Hamdy Freddie C. , Donovan Jenny L. ,   the ProtecT Study group
Published: July 2016

Objectives

To present the baseline patient‐reported outcome measures (PROMs) in the Prostate Testing for Cancer and Treatment (ProtecT) randomized trial comparing active monitoring, radical prostatectomy and external‐beam conformal radiotherapy for localized prostate cancer and to compare results with other populations.

Materials and Methods

A total of 1643 randomized men, aged 50–69 years and diagnosed with clinically localized disease identified by prostate‐specific antigen (PSA) testing, in nine UK cities in the period 1999–2009 were included. Validated PROMs for disease‐specific (urinary, bowel and sexual function) and condition‐specific impact on quality of life (Expanded Prostate Index Composite [EPIC], 2005 onwards; International Consultation on Incontinence Questionnaire‐Urinary Incontinence [ICIQ‐UI], 2001 onwards; the International Continence Society short‐form male survey [ICSmaleSF]; anxiety and depression (Hospital Anxiety and Depression Scale [HADS]), generic mental and physical health (12‐item short‐form health survey [SF‐12]; EuroQol quality‐of‐life survey, the EQ‐5D‐3L) were assessed at prostate biopsy clinics before randomization. Descriptive statistics are presented by treatment allocation and by men's age at biopsy and PSA testing time points for selected measures.

Results

A total of 1438 participants completed biopsy questionnaires (88%) and 77–88% of these were analysed for individual PROMs. Fewer than 1% of participants were using pads daily (5/754). Storage lower urinary tract symptoms were frequent (e.g. nocturia 22%, 312/1423). Bowel symptoms were rare, except for loose stools (16%, 118/754). One third of participants reported erectile dysfunction (241/735) and for 16% (118/731) this was a moderate or large problem. Depression was infrequent (80/1399, 6%) but 20% of participants (278/1403) reported anxiety. Sexual function and bother were markedly worse in older men (65–70 years), whilst urinary bother and physical health were somewhat worse than in younger men (49–54 years, all P < 0.001). Bowel health, urinary function and depression were unaltered by age, whilst mental health and anxiety were better in older men (P < 0.001). Only minor differences existed in mental or physical health, anxiety and depression between PSA testing and biopsy assessments.

Conclusion

The ProtecT trial baseline PROMs response rates were high. Symptom frequencies and generic quality of life were similar to those observed in populations screened for prostate cancer and control subjects without cancer.
Analysis of nucleophosmin–anaplastic lymphoma kinase (NPM-ALK)-reactive CD8+ T cell responses in children with NPM-ALK+ anaplastic large cell lymphoma
Authors: Singh V K , Werner S , Hackstein H , Lennerz V , Reiter A , Wölfel T , Damm-Welk C , Woessmann W
Published: July 2016

Cellular immune responses against the oncoantigen anaplastic lymphoma kinase (ALK) in patients with ALK-positive anaplastic large cell lymphoma (ALCL) have been detected using peptide-based approaches in individuals preselected for human leucocyte antigen (HLA)-A*02:01. In this study, we aimed to evaluate nucleophosmin (NPM)-ALK-specific CD8+ T cell responses in ALCL patients ensuring endogenous peptide processing of ALK antigens and avoiding HLA preselection. We also examined the HLA class I restriction of ALK-specific CD8+ T cells. Autologous dendritic cells (DCs) transfected with in-vitro-transcribed RNA (IVT-RNA) encoding NPM–ALK were used as antigen-presenting cells for T cell stimulation. Responder T lymphocytes were tested in interferon-gamma enzyme-linked immunospot (ELISPOT) assays with NPM–ALK-transfected autologous DCs as well as CV-1 in Origin with SV40 genes (COS-7) cells co-transfected with genes encoding the patients’ HLA class I alleles and with NPM–ALK encoding cDNA to verify responses and define the HLA restrictions of specific T cell responses. NPM–ALK-specific CD8+ T cell responses were detected in three of five ALK-positive ALCL patients tested between 1 and 13 years after diagnosis. The three patients had also maintained anti-ALK antibody responses. No reactivity was detected in samples from five healthy donors. The NPM–ALK-specific CD8+ T cell responses were restricted by HLA-C-alleles (C*06:02 and C*12:02) in all three cases. This approach allowed for the detection of NPM–ALK-reactive T cells, irrespective of the individual HLA status, up to 9 years after ALCL diagnosis.
The induction of autoimmune hepatitis in the human leucocyte antigen-DR4 non-obese diabetic mice autoimmune hepatitis mouse model
Authors: Yuksel M , Xiao X , Tai N , Vijay G M , Gülden E , Beland K , Lapierre P , Alvarez F , Hu Z , Colle I , Ma Y , Wen L
Published: July 2016

Autoimmune hepatitis (AIH) is a chronic liver disease characterized by progressive inflammation, female preponderance and seropositivity for autoantibodies such as anti-smooth muscle actin and/or anti-nuclear, anti-liver kidney microsomal type 1 (anti-LKM1) and anti-liver cytosol type 1 (anti-LC1) in more than 80% of cases. AIH is linked strongly to several major histocompatibility complex (MHC) alleles, including human leucocyte antigen (HLA)-DR3, -DR7 and -DR13. HLA-DR4 has the second strongest association with adult AIH, after HLA-DR3. We investigated the role of HLA-DR4 in the development of AIH by immunization of HLA-DR4 (DR4) transgenic non-obese diabetic (NOD) mice with DNA coding for human CYP2D6/FTCD fusion autoantigen. Immunization of DR4 mice leads to sustained mild liver injury, as assessed biochemically by elevated alanine aminotransferase, histologically by interface hepatitis, plasma cell infiltration and mild fibrosis and immunologically by the development of anti-LKM1/anti-LC1 antibodies. In addition, livers from DR4 mice had fewer regulatory T cells (Tregs), which had decreased programmed death (PD)-1 expression. Splenic Tregs from these mice also showed impaired inhibitory capacity. Furthermore, DR4 expression enhanced the activation status of CD8+ T cells, macrophages and dendritic cells in naive DR4 mice compared to naive wild-type (WT) NOD mice. Our results demonstrate that HLA-DR4 is a susceptibility factor for the development of AIH. Impaired suppressive function of Tregs and reduced PD-1 expression may result in spontaneous activation of key immune cell subsets, such as antigen-presenting cells and CD8+ T effectors, facilitating the induction of AIH and persistent liver damage.
Hypoxia‐induced vascular endothelial growth factor secretion by retinal pigment epithelial cells is inhibited by melatonin via decreased accumulation of hypoxia‐inducible factors‐1α protein
Authors: Lai Yu‐Hung , Hu Dan‐Ning , Rosen Richard , Sassoon Jodi , Chuang Lea‐Yea , Wu Kwou‐Yeung , Wu Wen‐Chuan
Published: July 2016

Background

Hypoxia is the most important stimulus leading to up‐regulation of vascular endothelial growth factor (VEGF) in the retina via elevation of hypoxia‐inducible factors‐1α (HIF‐1α) protein. The purpose of this study was to test the effects of melatonin on the expression of VEGF and HIF‐1α in the cultured human retinal pigment epithelial (RPE) cells under normoxia and hypoxia.

Method

An in vitro RPE cell hypoxia model was established by placing cells under 1% oxygen pressure or by adding cobalt chloride (CoCl2) to the culture medium. RPE cells and conditioned media were collected from cultures treated with and without melatonin under normoxia and hypoxia. The protein and RNA levels of VEGF and HIF‐1α were measured by ELISA kits and RT‐PCR, respectively.

Result

Hypoxia induced a significant increase of expression and secretion of VEGF and accumulation of HIF‐1α protein in RPE cells (P < 0.05). Melatonin at 10−5 to 10−8 M significantly inhibited hypoxia‐induced expression, the secretion of VEGF and the accumulation of HIF‐1α protein (P < 0.05), but not affected expression of VEGF and HIF‐1α under normoxia (P > 0.05).

Conclusion

This study suggests that melatonin may have potential value in the prevention and treatment of various retinal diseases associated with increase of VEGF, vascular leakage and angiogenesis.
KIF5A de novo mutation associated with myoclonic seizures and neonatal onset progressive leukoencephalopathy
Authors: Rydzanicz M. , Jagła M. , Kosinska J. , Tomasik T. , Sobczak A. , Pollak A. , Herman‐Sucharska I. , Walczak A. , Kwinta P. , Płoski R.
Published: July 2016

The KIF5A gene (OMIM 602821) encodes a neuron‐specific kinesin heavy chain involved in intracellular transport of mitochondria and other cargoes. KIF5A protein comprises the N terminal motor domain, the stalk domain and the C‐terminal cargo binding domain. The binding between KIF5A and its cargoes is mediated by kinesin adaptor proteins such as TRAK1 and TRAK2. Numerous missense KIF5A mutations in the motor and stalk domains cause spastic paraplegia type 10 (SPG10, OMIM 604187). Conversely, the role of loss‐of‐function mutations, especially those affecting the cargo binding domain, is unclear. We describe a novel de novo KIF5A p.Ser974fs/c.2921delC mutation found by whole exome sequencing in a patient with a congenital severe disease characterized by myoclonic seizures and progressive leukoencephalopathy. Since this phenotype differs considerably from the KIF5A/SPG10 disease spectrum we propose that the KIF5A p.Ser974fs and possibly other mutations which lead to truncation of the C‐terminal tail of the protein cause a novel disorder. We speculate that the unique effect of the C‐terminal truncating KIF5A mutations may result from the previously described complex role of this protein domain in binding of the TRAK2 and possibly other kinesin adaptor protein(s).
Comprehensive population screening in the Ashkenazi Jewish population for recurrent disease‐causing variants
Authors: Shi L. , Webb B.D. , Birch A.H. , Elkhoury L. , McCarthy J. , Cai X. , Oishi K. , Mehta L. , Diaz G.A. , Edelmann L. , Kornreich R.
Published: July 2016

The Ashkenazi Jewish (AJ) population has an increased risk for a variety of recessive diseases due to historical founder effects and genetic drift. For some, the disease‐causing founder mutations have been identified and well‐characterized, but for others, further study is necessary. The purpose of this study is to assess the carrier frequencies of 85 pathogenic variants causative of 29 recessive conditions in the AJ population. Up to 3000 AJ individuals were genotyped by Luminex MagPlex®‐TAG™ bead array or Agena Bioscience™ MassARRAY assays. We identified seven conditions with carrier frequencies higher than 1 in 100, nine between 1 in 100 and 1 in 200, and four between 1 in 200 and 1 in 500. Variants in nine conditions had a detected carrier rate of less than 1 in 500 or were not identified in approximately 2000 AJ individuals. We assessed the combined AJ carrier frequency for 18 relatively prevalent diseases to be 1 in 6, and the risk of AJ individuals to be a carrier couple for one of these 18 diseases as 1 in 441. We note additional recessive genetic conditions should be considered for AJ carrier screening panels.
Oral health‐related quality of life and esthetic outcome in single anterior maxillary implants
Authors: Angkaew Chayanuch , Serichetaphongse Pravej , Krisdapong Sudaduang , Dart Michel M. , Pimkhaokham Atiphan
Published: July 2016

Objectives

The aim of this study is twofold: to assess the esthetic outcome of single dental implant restorations in the anterior maxillary area after up to 3 years of function, and to evaluate the relationship between the esthetic outcome and oral health‐related quality of life.

Materials and methods

Twenty patients who were treated with an anterior maxillary single implant restoration were recalled for esthetic outcome evaluation using pink and white esthetic scores (PES/WES). All patients completed a questionnaire regarding satisfaction of treatment outcome and quality of life related to the implant restorations. Patient satisfaction was assessed by visual analog scales (VAS) analysis, whereas oral impact on daily life performances (OIDP) was used to evaluate the quality of life of patients.

Results

The esthetic outcome assessed by PES/WES showed favorable results. The median PES/WES scores were 16.00 (maximum possible score = 20). The median PES scores and WES scores were 7.50 and 8.00, respectively. Patient satisfaction rated in VAS scale ranged from 8 to 10. OIDP assessment showed an impact on daily life performance in 45% of patients. The most common impacts were eating (n = 5) and cleaning teeth (n = 4). No significant difference in PES/WES scores was found between the patients who perceived and did not perceive oral impacts.

Conclusions

There was some discrepancy between the dentist's evaluation and patient's perception but a strong positive satisfaction was reported from all patients which let suppose that the psychosocial factors that involve patient's perspective should be further investigated.
The long‐term efficacy of combining nucleos(t)ide analog and low‐dose hepatitis B immunoglobulin on post‐transplant hepatitis B virus recurrence
Authors: Idilman Ramazan , Akyildiz Murat , Keskin Onur , Gungor Gokhan , Yilmaz Tonguc U. , Kalkan Cagdas , Dayangac Murat , Cinar Kubilay , Balci Deniz , Hazinedaroglu Selcuk , Tokat Yaman
Published: July 2016

Background

The aim of this study was to determine the long‐term efficacy of nucleos(t)ide analog (NA) and low‐dose hepatitis B immunoglobulin (HBIG) combination treatment for preventing post‐transplant hepatitis B virus (HBV) recurrence.

Methods

A total of 296 patients with HBV‐associated liver disease who underwent liver transplantation (LT) were enrolled. A combination of a daily NA and low‐dose HBIG was used after LT.

Results

The median follow‐up period was 46 months. HBV recurrence occurred in eight patients. The cumulative probability of HBV recurrence at 1, 3, 5, and 7 years was 1%, 3%, 3%, and 4%, respectively. Seven were on lamivudine (LMV) or adefovir dipivoxil (ADV), or LMV and ADV and HBIG combination treatment and one entecavir (ETV) and HBIG. With Cox regression analysis, HBV recurrence was determined to be associated with the presence of hepatocellular cancer (HCC) prior to LT (HR: 12.3, P=.02). Overall, 44 patients died. Survival was significantly better in the ETV or tenofovir disoproxil fumarate (TDF) and HBIG group than the other group (P<.001).

Conclusion

The combination of ETV or TDF and low‐dose HBIG achieved a more favorable prophylaxis against HBV recurrence after LT. The presence of HCC prior to LT was associated with post‐transplant HBV recurrence.
Reading skill–fractional anisotropy relationships in visuospatial tracts diverge depending on socioeconomic status
Authors: Gullick Margaret M. , Demir‐Lira Özlem Ece , Booth James R.
Published: July 2016

Low socioeconomic status (SES) has been repeatedly linked with decreased academic achievement, including lower reading outcomes. Some lower SES children do show skills and scores commensurate with those of their higher SES peers, but whether their abilities stem from the same systems as high SES children or are based on divergent strategies is unknown. We here investigated a potential interactive relationship between SES and real‐word reading skill in the white matter in 42 typically developing children. SES was determined based on parental education; reading skill and age were not significantly related to SES. There was a significant neural interaction: Clusters in the bilateral inferior longitudinal fasciculus (ILF), left superior longitudinal fasciculus, and left corticospinal tract demonstrated interactive skill–SES relationships in fractional anisotropy. Follow‐up analyses demonstrated that higher SES children showed a positive relationship between fractional anisotropy, reflecting tract coherence, and reading skill in left hemisphere tract clusters, whereas lower SES children showed a positive relationship in the right hemisphere homologues. Broadly, the ILF has been demonstrated to support orthographic skill on the left and more general visuospatial processing on the right, so high reading achievement in lower SES children may rely on supplementary visuospatial processing more than for higher SES readers. This pattern is consistent with previous work reporting low SES children's environments to include less rich verbal experience, which may lead them to disproportionately draw on visuospatial skills for success. Further, these results indicate that group SES differences may be best described by an adaptive, not a deficit, model.
Altered functional connectivity of the default mode network in Williams syndrome: a multimodal approach
Authors: Sampaio Adriana , Moreira Pedro Silva , Osório Ana , Magalhães Ricardo , Vasconcelos Cristiana , Férnandez Montse , Carracedo Angel , Alegria Joana , Gonçalves Óscar F. , Soares José Miguel
Published: July 2016

Resting state brain networks are implicated in a variety of relevant brain functions. Importantly, abnormal patterns of functional connectivity (FC) have been reported in several neurodevelopmental disorders. In particular, the Default Mode Network (DMN) has been found to be associated with social cognition. We hypothesize that the DMN may be altered in Williams syndrome (WS), a neurodevelopmental genetic disorder characterized by an unique cognitive and behavioral phenotype. In this study, we assessed the architecture of the DMN using fMRI in WS patients and typically developing matched controls (sex and age) in terms of FC and volumetry of the DMN. Moreover, we complemented the analysis with a functional connectome approach. After excluding participants due to movement artifacts (n = 3), seven participants with WS and their respective matched controls were included in the analyses. A decreased FC between the DMN regions was observed in the WS group when compared with the typically developing group. Specifically, we found a decreased FC in a posterior hub of the DMN including the precuneus, calcarine and the posterior cingulate of the left hemisphere. The functional connectome approach showed a focalized and global increased FC connectome in the WS group. The reduced FC of the posterior hub of the DMN in the WS group is consistent with immaturity of the brain FC patterns and may be associated with the singularity of their visual spatial phenotype.
A theoretical rut: revisiting and critically evaluating the generalized under/over‐connectivity hypothesis of autism
Authors: Picci Giorgia , Gotts Stephen J. , Scherf K. Suzanne
Published: July 2016

In 2004, two papers proposed that pervasive functional under‐connectivity (Just et al., ) or a trade‐off between excessive local connectivity at the cost of distal under‐connectivity (Belmonte et al., ) characterizes atypical brain organization in autism. Here, we take stock of the most recent and rigorous functional and structural connectivity findings with a careful eye toward evaluating the extent to which they support these original hypotheses. Indeed, the empirical data do not support them. From rsfMRI studies in adolescents and adults, there is an emerging consensus regarding long‐range functional connections indicating cortico‐cortical under‐connectivity, specifically involving the temporal lobes, combined with subcortical‐cortical over‐connectivity. In contrast, there is little to no consensus regarding local functional connectivity or findings from task‐based functional connectivity studies. The structural connectivity data suggest that white matter tracts are pervasively weak, particularly in the temporal lobe. Together, these findings are revealing how deeply complex the story is regarding atypical neural network organization in autism. In other words, distance and strength of connectivity as individual factors or as interacting factors do not consistently explain the patterns of atypical neural connectivity in autism. Therefore, we make several methodological recommendations and highlight developmental considerations that will help researchers in the field cultivate new hypotheses about the nature and mechanisms of potentially aberrant functional and structural connectivity in autism.
Patient‐level predictors of achieving early glycaemic control in Type 2 diabetes mellitus: a population‐based study
Authors: Svensson E. , Baggesen L. M. , Thomsen R. W. , Lyngaa T. , Pedersen L. , Nørrelund H. , Buhl E. S. , Haase C. L. , Johnsen S. P.
Published: July 2016

Aims

To identify individual predictors of early glycaemic control in people with Type 2 diabetes mellitus after initiation of first glucose‐lowering drug treatment in everyday clinical practice.

Methods

Using medical registries, we identified a population‐based cohort of people with a first‐time glucose‐lowering drug prescription in Northern Denmark in the period 2000–2012. We used Poisson regression analysis to examine patient‐level predictors of success in reaching early glycaemic control [HbA1c target of < 53 mmol/mol (7%)] < 6 months after treatment start.

Results

Among the 38 418 people (median age 63 years), 27 545 (72%) achieved early glycaemic control. The strongest predictor of achieving early control was pre‐treatment HbA1c level; compared with a pre‐treatment HbA1c level of ≤ 58 mmol/mol (7.5%), the adjusted relative risks of attaining early control were 0.63 (95% CI 0.61–0.64) for baseline HbA1c levels of > 58 and ≤ 75 mmol/mol (> 7.5 and ≤ 9%), and 0.58 (95% CI 0.57–0.59) for a baseline HbA1c level of > 9% (> 75 mmol/mol). All other examined predictors were only weakly associated with the chance of achieving early control. After adjustment, the only characteristics that remained independently associated with early control (in addition to high baseline HbA1c) were being widowed (adjusted relative risk 0.95; 95% CI 0.93–0.97) and having a high Charlson comorbidity index score (score ≥ 3; adjusted relative risk 0.94; 95% CI 0.90–0.97).

Conclusions

In a real‐world clinical setting, people with Type 2 diabetes mellitus initiating glucose‐lowering medication had a similar likelihood of achieving glycaemic control, regardless of sex, age, comorbidities and other individual factors; the only strong and potentially modifiable predictor was HbA1c before therapy start.
Efficacy and safety of liraglutide, a once‐daily human glucagon‐like peptide‐1 receptor agonist, in African‐American people with Type 2 diabetes: a meta‐analysis of sub‐population data from seven phase III trials
Authors: Shomali M. E. , Ørsted D. D. , Cannon A. J.
Published: July 2016

Aim

To evaluate the efficacy and safety of the glucagon‐like peptide‐1 (GLP‐1) receptor agonist liraglutide in African‐American people with Type 2 diabetes.

Methods

Analyses were performed on patient‐level data from individuals self‐defined as African‐American or non‐African‐American in seven phase III studies. Endpoints included change in HbA1c level, fasting plasma glucose level and body weight from baseline, proportion of patients reaching HbA1c target [< 53 mmol/mol (< 7.0%)], and incidence of hypoglycaemia and nausea. Analyses used data obtained after 26 weeks. Within‐population comparisons of liraglutide were performed vs placebo for African‐American and non‐African‐American patient groups. In addition, between‐population comparisons with non‐African‐American patients were performed for each treatment.

Results

In African‐American patients (n = 225), HbA1c was significantly reduced at 26 weeks with liraglutide 1.2 and 1.8 mg (−11 and −14 mmol/mol, respectively compared with placebo; P < 0.0001). There were also significant reductions in fasting plasma glucose (−2.4 and −3.1 mmol/l, respectively, compared with placebo; P < 0.0001). Statistically significant reductions in body weight were observed with 1.8 mg liraglutide (−2.1 kg compared with placebo; P = 0.0056), but not with 1.2 mg liraglutide (−0.26 kg; P = 0.7307). The P value for interaction between treatment and race was significant for body weight (P = 0.0355). The incidence of non‐severe hypoglycaemia with liraglutide was low (11–15% of patients), and < 25% of patients receiving liraglutide experienced nausea.

Conclusions

This meta‐analysis suggests that liraglutide is well tolerated and efficacious for treatment of Type 2 diabetes in African‐American patients, with an efficacy that was shown not to differ from that observed in non‐African‐American patients over 26 weeks.
Natural enemy impacts on Bemisia tabaci (MEAM1) dominate plant quality effects in the cotton system
Authors: ASIIMWE PETER , ELLSWORTH PETER C. , NARANJO STEVEN E.
Published: July 2016

1. Plant quality (bottom‐up effects) and natural enemies (top‐down effects) affect herbivore performance. Furthermore, plant quality can also influence the impact of natural enemies.

2. Lower plant quality through reduced irrigation increased the abundance of the cryptic species from the Bemisia tabaci complex [hereafter B. tabaci Middle East Asia Minor 1 (MEAM1)], but not its natural enemies on cotton. It was therefore predicted that lower plant quality would diminish the impact of natural enemies in regulating this herbivore.

3. Over three cotton seasons, plant quality was manipulated via differential irrigation and natural enemy abundance with insecticides. Life tables were used to evaluate the impact of these factors on mortality of immature B. tabaci (MEAM1) over nine generations.

4. Mortality of B. tabaci (MEAM1) was consistently affected by natural enemies but not by plant quality. This pattern was driven by high levels of sucking predation, which was the primary (key) factor associated with changes in immature mortality across all irrigation and natural enemy treatments. Dislodgement (chewing predation and weather) and parasitism contributed as key factors in some cases. Analyses also showed that elimination of sucking predation and dislodgement would have the greatest effect on overall mortality.

5. The top‐down effects of natural enemies had dominant effects on populations of B. tabaci (MEAM1) relative to the bottom‐up effects of plant quality. Effects were primarily due to native generalist arthropod predators and not more host‐specific aphelinid parasitoids. The findings of this study demonstrate the important role of arthropod predators in population suppression and validate the importance of conservation biological control in this system for effective pest control.
Impact of ASPECTS on computed tomography angiography source images on outcome after thrombolysis or endovascular therapy in large vessel occlusions
Authors: Wasser K. , Papanagiotou P. , Brunner F. , Hildebrandt H. , Winterhalter M. , Roth C. , Kastrup A.
Published: July 2016

Background and purpose

Endovascular therapy (ET) is superior to intravenous thrombolysis (IVT) in selected patients with anterior circulation large vessel occlusions. However, it is unclear if this positive effect also applies to patients with extensive early ischaemic changes. The aim of this study was to analyze the impact of the Alberta Stroke Program Early Computed Tomography Score (ASPECTS) on the CT angiography source images (SI) on outcome after ET or IVT.

Methods

Using our prospectively obtained stroke database and the admission SI‐ASPECTS divided into three groups (0–5, 6–7 and 8–10), primarily the rates of good outcome [modified Rankin Scale (mRS) ≤2 at discharge] after either ET (n = 255) or IVT (n = 479) were compared.

Results

A favorable SI‐ASPECTS (8–10) was present in 501 patients, 132 patients had a moderately favorable SI‐ASPECTS (6–7) and 101 patients had an unfavorable SI‐ASPECTS (0–5). Irrespective of the treatment modality, no patient with an unfavorable SI‐ASPECTS had a good outcome and 38% died during hospital stay. Whilst significantly more patients with a favorable SI‐ASPECTS had a good outcome after ET than after IVT (51% vs. 35%, P < 0.01), there was only a non‐significant trend towards a good outcome after ET than after IVT in patients with a moderately favorable ASPECTS (25% vs. 14%, P = 0.1).

Conclusion

Patients with extensive early ischaemic changes on CT scans (SI‐ ASPECTS ≤5) might not profit from ET. The impact of ET on outcome in patients with moderately favorable SI‐ASPECTS should be addressed in further trials.