bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical and laboratory correlates of lung disease and cancer in adults with idiopathic hypogammaglobulinaemia
Authors: Brent J , Guzman D , Bangs C , Grimbacher B , Fayolle C , Huissoon A , Bethune C , Thomas M , Patel S , Jolles S , Alachkar H , Kumaratne D , Baxendale H , Edgar J D , Helbert M , Hambleton S , Arkwright P D 
Published: December 2015

Summary
Idiopathic hypogammaglobulinaemia, including common variable immune deficiency (CVID), has a heterogeneous clinical phenotype. This study used data from the national UK Primary Immune Deficiency (UKPID) registry to examine factors associated with adverse outcomes, particularly lung damage and malignancy. A total of 801 adults labelled with idiopathic hypogammaglobulinaemia and CVID aged 18–96 years from 10 UK cities were recruited using the UKPID registry database. Clinical and laboratory data (leucocyte numbers and serum immunoglobulin concentrations) were collated and analysed using uni- and multivariate statistics. Low serum immunoglobulin (Ig)G pre-immunoglobulin replacement therapy was the key factor associated with lower respiratory tract infections (LRTI) and history of LRTI was the main factor associated with bronchiectasis. History of overt LRTI was also associated with a significantly shorter delay in diagnosis and commencing immunoglobulin replacement therapy [5 (range 1–13 years) versus 9 (range 2–24) years]. Patients with bronchiectasis started immunoglobulin replacement therapy significantly later than those without this complication [7 (range 2–22) years versus 5 (range 1–13) years]. Patients with a history of LRTI had higher serum IgG concentrations on therapy and were twice as likely to be on prophylactic antibiotics. Ensuring prompt commencement of immunoglobulin therapy in patients with idiopathic hypogammaglobulinaemia is likely to help prevent LRTI and subsequent bronchiectasis. Cancer was the only factor associated with mortality. Overt cancer, both haematological and non-haematological, was associated with significantly lower absolute CD8+ T cell but not natural killer (NK) cell numbers, raising the question as to what extent immune senescence, particularly of CD8+ T cells, might contribute to the increased risk of cancers as individuals age.
Clinically occult primary fallopian tube carcinoma presenting as a malignant pleural effusion
Authors: Hiensch Robert , Meinhof Klaus , Leytin Anatoly , Hagopian George , Szemraj Eva , Epelbaum Oleg 
Published: December 2015

AbstractWe report the first known case of malignant pleural effusion (MPE) as the sole presenting feature of clinically occult primary fallopian tube carcinoma (PFTC). A 57‐year‐old healthy woman was admitted with dyspnea. Evaluation demonstrated a right pleural effusion, fluid of which was malignant. The immunohistochemical profile, including negative calretinin, favored metastatic adenocarcinoma over mesothelioma but could not identify the primary tumour site. Pleural biopsy was not pursued as it would not have helped localize the primary. Chest, abdomen and pelvic computed tomography (CT) demonstrated only borderline lymphadenopathy in the left para‐aortic lymph node chain that was hypermetabolic on positron emission tomography. Ultrasound and CT showed normal adnexal anatomy. These findings, coupled with an elevated serum CA‐125, prompted empiric neoadjuvant chemotherapy targeting epithelial ovarian carcinoma (EOC) followed by surgery, which revealed a tiny left PFTC with negative peritoneal washings. Sampled left para‐aortic lymph nodes were positive. The pleural effusion resolved after chemotherapy. Malignant pleural disease without peritoneal involvement is more characteristic of PFTC than of EOC, in which MPE is common but almost always accompanies peritoneal carcinomatosis. The extensive lymphatic supply of the fallopian tube promotes distant metastasis of small, seemingly localized tumours. This case is a reminder that the clinician should not be dissuaded from considering carcinoma of Müllerian origin, especially PFTC, as the cause of a MPE even in the face of normal gynecologic imaging. Appropriately broad immunohistochemical staining and careful attention to even minimal lymphadenopathy can be invaluable in pinpointing the primary tumour site in such patients.
Research START: A Multimethod Study of Barriers and Accelerators of Recruiting Research Participants
Authors: Stein Mark A. , Shaffer Michele , Echo‐Hawk Abigail , Smith Jody , Stapleton Ann , Melvin Ann 
Published: December 2015

AbstractUnder‐recruitment into clinical trials is a common and costly problem that undermines medical research. To better understand barriers to recruitment into clinical trials in our region, we conducted a multimethod descriptive study. We initially surveyed investigators who had conducted or were currently conducting studies that utilized an adult or pediatric clinical research center (n = 92). We then conducted focus groups and key informant interviews with investigators, coordinators, and other stakeholders in clinical and translational research (n = 32 individuals). Only 41% of respondents reported that they had or were successfully meeting recruitment goals and 24% of the closed studies actually met their targeted recruitment goals. Varied reasons were identified for poor recruitment but there was not a single investigator or study “phenotype” that predicted enrollment outcome. Investigators commonly recruited from their own practice or clinic, and 29% used a manual electronic medical record search. The majority of investigators would utilize a service that provides recruitment advice, including feasibility assessment and consultation, easier access to the electronic health record and assistance with institutional review board and other regulatory requirements. Our findings suggest potential benefits providing assistance across a range of services that can be individualized to the varied needs of clinical and translational investigators.
Children with autism are impaired in the understanding of teaching
Authors: Knutsen John , Mandell David S. , Frye Douglas 
Published: December 2015

AbstractChildren learn novel information using various methods, and one of the most common is human pedagogical communication or teaching – the purposeful imparting of information from one person to another. Neuro‐typically developing (TD) children gain the ability to recognize and understand teaching as a core method for acquiring knowledge from others. However, it is not known when children with Autism Spectrum Disorder (ASD) acquire the ability to recognize and understand teaching. This study (total N = 70) examined whether children with ASD recognize the two central elements that define teaching: (1) that teaching is an intentional activity; and (2) that teaching requires a knowledge difference between teacher and learner. Theory of mind understanding was also tested. Compared to individually matched TD children, high cognitively functioning children with ASD were impaired in their comprehension of both components of teaching understanding, and their performance was correlated with theory of mind understanding. These findings could have broad implications for explaining learning in children with autism, and could help in designing more effective interventions, which could ultimately lead to improved learning outcomes for everyday life skills, school performance, health, and overall well‐being.
Cortical speech and non‐speech discrimination in relation to cognitive measures in preschool children
Authors: Kuuluvainen Soila , Alku Paavo , Makkonen Tommi , Lipsanen Jari , Kujala Teija 
Published: December 2015

AbstractEffective speech sound discrimination at preschool age is known to be a prerequisite for the development of language skills and later literacy acquisition. However, the speech specificity of cortical discrimination skills in small children is currently not known, as previous research has either studied speech functions without comparison with non‐speech sounds, or used much simpler sounds such as harmonic or sinusoidal tones as control stimuli. We investigated the cortical discrimination of five syllable features (consonant, vowel, vowel duration, fundamental frequency, and intensity), covering both segmental and prosodic phonetic changes, and their acoustically matched non‐speech counterparts in 63 6‐year‐old typically developed children, by using a multi‐feature mismatch negativity (MMN) paradigm. Each of the five investigated features elicited a unique pattern of differentiating negativities: an early differentiating negativity, MMN, and a late differentiating negativity. All five studied features showed speech‐related enhancement of at least one of these responses, suggesting experience‐related neural commitment in both phonetic and prosodic speech processing. In addition, the cognitive performance and language skills of the children were tested extensively. The speech‐related neural enhancement was positively associated with the level of performance in several neurocognitive tasks, indicating a relationship between successful establishment of cortical memory traces for speech and enhanced cognitive functioning. The results contribute to the understanding of typical developmental trajectories of linguistic vs. non‐linguistic auditory skills, and provide a reference for future studies investigating deficits in language‐related disorders at preschool age.
Unexplained early onset epileptic encephalopathy: Exome screening and phenotype expansion
Authors: Allen Nicholas M. , Conroy Judith , Shahwan Amre , Lynch Bryan , Correa Raony G. , Pena Sergio D. J. , McCreary Dara , Magalhães Tiago R. , Ennis Sean , Lynch Sally A. , King Mary D. 
Published: December 2015

SummaryEarly onset epileptic encephalopathies (EOEEs) represent a significant diagnostic challenge. Newer genomic approaches have begun to elucidate an increasing number of responsible single genes as well as emerging diagnostic strategies. In this single‐center study, we aimed to investigate a cohort of children with unexplained EOEE. We performed whole‐exome sequencing (WES), targeting a list of 137 epilepsy‐associated genes on 50 children with unexplained EOEE. We characterized all phenotypes in detail and classified children according to known electroclinical syndromes where possible. Infants with previous genetic diagnoses, causative brain malformations, or inborn errors of metabolism were excluded. We identified disease‐causing variants in 11 children (22%) in the following genes: STXBP1 (n = 3), KCNB1 (n = 2), KCNT1, SCN1A, SCN2A, GRIN2A, DNM1, and KCNA2. We also identified two further variants (in GRIA3 and CPA6) in two children requiring further investigation. Eleven variants were de novo, and in one paternal testing was not possible. Phenotypes were broadened for some variants identified. This study demonstrates that WES is a clinically useful screening tool for previously investigated unexplained EOEE and allows for reanalysis of data as new genes are being discovered. Detailed phenotyping allows for expansion of specific gene disorders leading to epileptic encephalopathy and emerging sub‐phenotypes.
Targeting glycolysis in the malaria parasite Plasmodium falciparum
Authors: van Niekerk David D. , Penkler Gerald P. , du Toit Francois , Snoep Jacky L. 
Published: December 2015

Glycolysis is the main pathway for ATP production in the malaria parasite Plasmodium falciparum and essential for its survival. Following a sensitivity analysis of a detailed kinetic model for glycolysis in the parasite, the glucose transport reaction was identified as the step whose activity needed to be inhibited to the least extent to result in a 50% reduction in glycolytic flux. In a subsequent inhibitor titration with cytochalasin B, we confirmed the model analysis experimentally and measured a flux control coefficient of 0.3 for the glucose transporter. In addition to the glucose transporter, the glucokinase and phosphofructokinase had high flux control coefficients, while for the ATPase a small negative flux control coefficient was predicted. In a broader comparative analysis of glycolytic models, we identified a weakness in the P. falciparum pathway design with respect to stability towards perturbations in the ATP demand.DatabaseThe mathematical model described here has been submitted to the JWS Online Cellular Systems Modelling Database and can be accessed at http://jjj.bio.vu.nl/database/vanniekerk1. The SEEK‐study including the experimental data set is available at DOI 10.15490/seek.1.investigation.56 (http://dx.doi.org/10.15490/seek.1.investigation.56).
Multiple stressors, nonlinear effects and the implications of climate change impacts on marine coastal ecosystems
Authors: Hewitt Judi E. , Ellis Joanne I. , Thrush Simon F. 
Published: December 2015

AbstractGlobal climate change will undoubtedly be a pressure on coastal marine ecosystems, affecting not only species distributions and physiology but also ecosystem functioning. In the coastal zone, the environmental variables that may drive ecological responses to climate change include temperature, wave energy, upwelling events and freshwater inputs, and all act and interact at a variety of spatial and temporal scales. To date, we have a poor understanding of how climate‐related environmental changes may affect coastal marine ecosystems or which environmental variables are likely to produce priority effects. Here we use time series data (17 years) of coastal benthic macrofauna to investigate responses to a range of climate‐influenced variables including sea‐surface temperature, southern oscillation indices (SOI, Z4), wind‐wave exposure, freshwater inputs and rainfall. We investigate responses from the abundances of individual species to abundances of functional traits and test whether species that are near the edge of their tolerance to another stressor (in this case sedimentation) may exhibit stronger responses. The responses we observed were all nonlinear and some exhibited thresholds. While temperature was most frequently an important predictor, wave exposure and ENSO‐related variables were also frequently important and most ecological variables responded to interactions between environmental variables. There were also indications that species sensitive to another stressor responded more strongly to weaker climate‐related environmental change at the stressed site than the unstressed site. The observed interactions between climate variables, effects on key species or functional traits, and synergistic effects of additional anthropogenic stressors have important implications for understanding and predicting the ecological consequences of climate change to coastal ecosystems.
Plant roots and GHG mitigation in native perennial bioenergy cropping systems
Authors: Jungers Jacob M. , Eckberg James O. , Betts Kevin , Mangan Margaret E. , Wyse Donald L. , Sheaffer Craig C. 
Published: December 2015

AbstractNative perennial bioenergy crops can mitigate greenhouse gases (GHG) by displacing fossil fuels with renewable energy and sequestering atmospheric carbon (C) in soil and roots. The relative contribution of root C to net GHG mitigation potential has not been compared in perennial bioenergy crops ranging in species diversity and N fertility. We measured root biomass, C, nitrogen (N), and soil organic carbon (SOC) in the upper 90 cm of soil for five native perennial bioenergy crops managed with and without N fertilizer. Bioenergy crops ranged in species composition and were annually harvested for 6 (one location) and 7 years (three locations) following the seeding year. Total root biomass was 84% greater in switchgrass (Panicum virgatum L.) and a four‐species grass polyculture compared to high‐diversity polycultures; the difference was driven by more biomass at shallow soil depth (0–30 cm). Total root C (0–90 cm) ranged from 3.7 Mg C ha−1 for a 12‐species mixture to 7.6 Mg C ha−1 for switchgrass. On average, standing root C accounted for 41% of net GHG mitigation potential. After accounting for farm and ethanol production emissions, net GHG mitigation potential from fossil fuel offsets and root C was greatest for switchgrass (−8.4 Mg CO2e ha−1 yr−1) and lowest for high‐diversity mixtures (−4.5 Mg CO2e ha−1 yr−1). Nitrogen fertilizer did not affect net GHG mitigation potential or the contribution of roots to GHG mitigation for any bioenergy crop. SOC did not change and therefore did not contribute to GHG mitigation potential. However, associations among SOC, root biomass, and root C : N ratio suggest greater long‐term C storage in diverse polycultures vs. switchgrass. Carbon pools in roots have a greater effect on net GHG mitigation than SOC in the short‐term, yet variation in root characteristics may alter patterns in long‐term C storage among bioenergy crops.
Relationship between cardiac autonomic function and cognitive function in Alzheimer's disease
Authors: Nonogaki Zen , Umegaki Hiroyuki , Makino Taeko , Suzuki Yusuke , Kuzuya Masafumi 
Published: December 2015

AimAlzheimer's disease (AD) affects many central nervous structures and neurotransmitter systems. These changes affect not only cognitive function, but also cardiac autonomic function. However, the functional relationship between cardiac autonomic function and cognition in AD has not yet been investigated. The objective of the present study was to evaluate the association between cardiac autonomic function measured by heart rate variability and cognitive function in AD.MethodsA total of 78 AD patients were recruited for this study. Cardiac autonomic function was evaluated using heart rate variability analysis. Multiple linear regression analysis was used to model the association between heart rate variability and cognitive function (global cognitive function, memory, executive function and processing speed), after adjustment for covariates.ResultsGlobal cognitive function was negatively associated with sympathetic modulation (low‐to‐high frequency power ratio). Memory performance was positively associated with parasympathetic modulation (high frequency power) and negatively associated with sympathetic modulation (low‐to‐high frequency power ratio). These associations were independent of age, sex, educational years, diabetes, hypertension and cholinesterase inhibitor use.ConclusionsCognitive function, especially in the areas of memory, is associated with cardiac autonomic function in AD. Specifically, lower cognitive performance was found to be associated with significantly higher cardiac sympathetic and lower parasympathetic function in AD. Geriatr Gerontol Int 2017; 17: 92–98.
Alcohol use disorder hospitalisations over the last two decades: a population‐based cohort study
Authors: Liang W. , Chikritzhs T. 
Published: December 2015

BackgroundAlcohol use disorders are risk factors for almost all health conditions due to heavy alcohol use. The epidemiology of alcohol use disorders can be used to monitor harm from heavy alcohol consumption.AimTo estimate changes in the risk of alcohol use disorders over the last two decades among the Western Australian adult population.MethodsThis population‐based cohort study used hospital separation records for Western Australian residents aged 18 years and older that occurred between 1990 and 2013 with a primary diagnosis of alcohol use disorder and annual estimated residential population to estimate the annual gender‐ and age‐specific incidence rate. A random sample of emergency presentations to public hospitals in Western Australia between 2002 and 2013 was used to account for confounding effects, such as changes in patient access to medical care and overall improvement in healthcare service in the multivariable Poisson regression model.ResultsThe risk of alcohol use disorder hospitalisations among the Western Australia population has increased considerably since 1998 with a decline in 2012 and 2013. The average rate remained significantly higher from 2010 to 2013 compared with previous years.ConclusionsThe trend of alcohol use disorder hospitalisations is indicative of an increase in harm due to heavy alcohol use in the population.
Experience with Company Unions and their Treatment under the Wagner Act: A Four Frames of Reference Analysis
Authors: Kaufman Bruce E. 
Published: December 2015

This paper reexamines American experience with company unions (also known as nonunion employee representation plans) before they were banned by the Wagner Act (1935). For the half‐century following the passage of the act, labor historians and industrial relations scholars painted a bleak portrait of company unions as anti‐union sham organizations. Since the 1980s, additional research has documented a more positive side; similarly, concern has grown that the Wagner Act's ban is stifling legitimate employee participation programs. This paper brings new theoretical and empirical evidence to both historical and legal parts of this debate, including examination of company unions through individualist, unitarist, pluralist, and radical frames; demonstration that the pluralists’ view of company unions was more diverse and positive than conventionally portrayed; presentation of new historical evidence and testimony on the company union experience; and a substantially revisionist assessment of the merits of the Wagner Act's ban. In particular, the conclusion is that, given any reasonable weighting of the four frames, the company union ban is overly restrictive and should be modified so companies can implement the positive side of nonunion employee committees but not the negative. The paper ends by noting that the unbalanced and narrowly critical treatment of company unions in the mainline industrial relations tradition is a case study of the field's perhaps fatal post–World WarIIcore intellectual‐normative contradiction—professed inclusiveness of all frames of employment relations but, in practice, attention to and preference for a narrow union‐centric version of one frame.
Periodontitis prevalence and serum antibody reactivity to periodontal bacteria in primary Sjögren's syndrome: a pilot study
Authors: Lugonja Bozo , Yeo Lorraine , Milward Michael R. , Smith Diana , Dietrich Thomas , Chapple Iain L. C. , Rauz Saaeha , Williams Geraint P. , Barone Francesca , de Pablo Paola , Buckley Chris , Hamburger John , Richards Andrea , Poveda‐Gallego Ana , Scheel‐Toellner Dagmar , Bowman Simon J. 
Published: December 2015

AbstractAimsThe aims of this study were as follows: (i) To assess the prevalence of periodontitis among patients with primary Sjögren's syndrome (pSS) and comparator groups of patients with rheumatoid arthritis (RA) and osteoarthritis (OA). (ii) To perform a pilot study to compare serum antibody responses to 10 oral/periodontal bacteria in these patient groups and a historical comparator group of patients with periodontitis.Materials and MethodsStandard clinical periodontal assessments were performed on 39 pSS, 36 RA and 23 OA patients and “In‐house” antibody ELISAs for serum antibodies against 10 oral/periodontal bacteria were performed in these groups.ResultsForty‐six percent of the pSS group, 64% of the RA group and 48% of the OA group had moderate/severe periodontitis. These frequencies did not reach statistical significance between groups. Raised antibody levels to Prevotella denticola were found in the pSS, RA and periodontitis groups compared to the OA group. Significant between group differences were seen for Aggregatibacter actinomycetemcomitans, Prevotella intermedia and Campylobacter showae. None of these differences were specifically associated with pSS.ConclusionThis study showed no increase in periodontitis in pSS patients. Although the P. denticola data are of interest, identifying bacterial triggering factors for pSS will likely require alternative strategies including modern techniques such as microbiome analysis.