bluuebunny/crossref_metadata_2025_split huggingface dataset:
Duration and exclusiveness of breastfeeding and risk of childhood atopic diseases
Authors: Elbert N. J. , van Meel E. R. , den Dekker H. T. , de Jong N. W. , Nijsten T. E. C. , Jaddoe V. W. V. , de Jongste J. C. , Pasmans S. G. M. A. , Duijts L. 
Published: April 2017

AbstractBackgroundBreastfeeding may have immune modulatory effects that influence the development of childhood allergic sensitization and atopic diseases. We aimed to examine the associations of breastfeeding with childhood allergic sensitization, inhalant or food allergy and eczema, and whether any association was affected by disease‐related modification of the exposure or modified by maternal history of allergy, eczema, or asthma.MethodsThis study among 5828 children was performed in a population‐based prospective cohort from fetal life onwards. We collected information on duration (<2 months, 2‐4 months, 4‐6 months, and ≥6 months) and exclusiveness (nonexclusive vs exclusive for 4 months) of breastfeeding in infancy by postal questionnaires. At age 10 years, inhalant allergic sensitization and food‐allergic sensitization were measured by skin prick tests, and physician‐diagnosed inhalant and food allergy by a postal questionnaire. Data on parental‐reported eczema were available from birth until age 10 years.ResultsWe observed no association of breastfeeding with any allergic sensitization, physician‐diagnosed allergy, or combination of these outcomes. Shorter breastfeeding duration was associated with an overall increased risk of eczema (P‐value for trend <.05). Nonexclusively breastfed children had an overall increased risk of eczema (adjusted odds ratio [95% confidence interval]: 1.11 [1.01, 1.23]), compared with children exclusively breastfed for 4 months. Risk period‐specific sensitivity analyses, additional adjustment for ointment use for eczema at age 2 months, and cross‐lagged modeling showed no consistent results for disease‐related modification of the exposure. Results were not modified by maternal history of allergy, eczema, or asthma (lowest P‐value for interaction=.13).ConclusionShorter duration or nonexclusiveness of breastfeeding is associated with a weak overall increased risk of eczema but not allergic sensitization or physician‐diagnosed allergy at age 10 years.
Systematic review: the safety of vedolizumab for the treatment of inflammatory bowel disease
Authors: Bye W. A. , Jairath V. , Travis S. P. L. 
Published: April 2017

SummaryBackgroundVedolizumab specifically recognises the α4β7 integrin and selectively blocks gut lymphocyte trafficking: potentially, it offers gut‐specific immunosuppression.AimTo review the safety of vedolizumab and summarise post‐marketing data to assess if any safety concerns that differ from registration trials have emerged.MethodA systematic bibliographic search identified six registration trials and nine cohort studies.ResultsIntegrated data from registration trials included 2830 vedolizumab‐exposed patients (4811 person‐years exposure [PYs]) and 513 placebo patients. This reported lower exposure‐adjusted incidence rates of infection (63.5/100 PYs; 95% CI: 59.6‐67.3) and serious adverse events (20.0/100 PYs; 95% CI: 18.5‐21.5) compared to placebo (82.9/100 PYs; 95% CI: 68.3‐97.5) and (28.3/100 PYs 95% CI: 20.6‐35.9) respectively. Higher, but statistically insignificant rates of enteric infections occurred in vedolizumab‐exposed patients (7.4/100 PYs; 95% CI: 6.6‐8.3) compared to placebo (6.7 PYs; 95% CI: 3.2‐10.1). Six post‐marketing cohort studies (1049 patients, 403 PYs) demonstrated rates of infection of 8% (82/1049); enteric infection of 2% (21/1049) and adverse events of 16% (166/1049). Multivariate analysis in one cohort study suggested increased risk of surgical site infection with perioperative VDZ. Human experience in pregnancy is limited.ConclusionsPost‐marketing data confirm the excellent safety of vedolizumab observed in registration trials. The signal of post‐operative complications should be interpreted with caution, but warrants further study. Although comparative studies are needed, Vedolizumab may be a safe alternative in patients who best avoid systematic immunosuppression, including those pre‐disposed to infection, malignancy or the elderly.
The risk of gastric cancer in patients with gastric intestinal metaplasia in 5‐year follow‐up
Authors: Pittayanon R. , Rerknimitr R. , Klaikaew N. , Sanpavat A. , Chaithongrat S. , Mahachai V. , Kullavanijaya P. , Barkun A. 
Published: April 2017

SummaryBackgroundGastric intestinal metaplasia (GIM) is the premalignant stage of gastric cancer; however, consensus on its management has not been established.AimTo determine the risk factors for gastric cancer in a population of patients with GIM to guide the appropriate clinical recommendations in a low prevalence area for gastric cancer.MethodsThis was a retrospective cohort study. Ninety‐one patients with GIM diagnosed between 2004 and 2014 were recruited for surveillance EGD every 6‐12 months until a diagnosis of gastric cancer or completion of the planned 5‐year follow‐up duration. Possible risk factors for gastric cancer were assessed.ResultsAt initial presentation, 81 of the 91 patients (89%) had complete GIM, whereas the remaining 11% had a study entry diagnosis of incomplete GIM. No cancer developed amongst patients with complete GIM. In contrast, five of the 10 patients exhibiting incomplete GIM (50%) progressed to high‐grade dysplasia (n=2) or cancer (n=3). Male gender (P=.027), and incomplete GIM (P=.001) were associated with high‐risk histology (dysplasia or cancer) by study end. A trend suggested a possible association with smoking (P=.08).ConclusionMale patients and those with incomplete GIM are at greatest risk of developing dysplasia or early gastric cancer. Further studies in determining optimal surveillance intervals and impact on cancer incidence and mortality are still required.
Safety, pharmacokinetics and pharmacological effects of the selective androgen receptor modulator, GSK2881078, in healthy men and postmenopausal women
Authors: Clark Richard V. , Walker Ann C. , Andrews Susan , Turnbull Philip , Wald Jeffrey A. , Magee Mindy H. 
Published: April 2017

AimSelective androgen receptor modulators (SARMs) induce anabolic effects on muscle without the adverse effects of androgenic steroids. In this first‐in‐human study, we report the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics of the SARM GSK2881078.MethodsIn Part A, healthy young men (n = 10) received a single dose of study drug (0 mg, 0.05 mg, 0.1 mg, 0.2 mg GSK2881078 or matching‐placebo). In Part B, repeat‐dose cohorts in men (n = 65) were 0.05 mg, 0.2 mg then 0.08 mg, 0.24 mg, 0.48 mg, 0.75 mg, or placebo; in women (n = 24) they were 0.24 mg, 0.35 mg, or placebo (7 days for 0.5 mg, 14 days for other doses).ResultsPK analysis showed dose‐proportional increases in exposure and a long >100‐h half‐life. No significant effects on vital signs, electrocardiograms, cardiac telemetry or standard clinical laboratory studies were observed. A dose–response effect was observed on lowering both high‐density lipoprotein and sex hormone‐binding globulin. In females at 0.35 mg, differences from placebo were −0.518 (95% confidence interval: –0.703, −0.334) mmol l–1 and −39.1 (−48.5, −29.7) nmol l–1, respectively. Women showed greater sensitivity to these parameters at lower doses than men. Drug‐related adverse events (AEs) were mild. One woman developed a drug rash and was withdrawn. Two men had elevated creatine phosphokinase after physical exertion during follow‐up. A serious AE occurred in a subject on placebo.ConclusionsThese data demonstrate pharmacodynamic effects with acceptable tolerability and support further clinical evaluation of this SARM.
Prescribing Safety Assessment 2016: Delivery of a national prescribing assessment to 7343 UK final‐year medical students
Authors: Maxwell Simon R. J. , Coleman Jamie J. , Bollington Lynne , Taylor Celia , Webb David J. 
Published: April 2017

AimsNewly graduated doctors write a large proportion of prescriptions in UK hospitals but recent studies have shown that they frequently make prescribing errors. The prescribing safety assessment (PSA) has been developed as an assessment of competence in relation to prescribing and supervising the use of medicines. This report describes the delivery of the PSA to all UK final‐year medical students in 2016 (PSA2016).MethodsThe PSA is a 2‐hour online assessment comprising eight sections which cover various aspects of prescribing defined within the outcomes of undergraduate education identified by the UK General Medical Council. Students sat one of four PSA ‘papers’, which had been standard‐set using a modified Angoff process.ResultsA total of 7343 final‐year medical students in all 31 UK medical schools sat the PSA. The overall pass rate was 95% with the pass rates for the individual papers ranging from 93 to 97%. The PSA was re‐sat by 261 students who had failed and 80% of those candidates passed. The internal consistency (Cronbach's alpha) of the four papers ranged from 0.74 to 0.77 (standard error of measurement 4.13–4.24%). There was a statistically significant variation in performance between medical school cohorts (F = 32.6,P < 0.001) and a strongly positive correlation in performance for individual schools between PSA2015 and PSA2016 (r = 0.79, 95% CI 0.61–0.90;P < 0.01).ConclusionsPSA2016 demonstrated the feasibility of delivering a standardized national prescribing assessment online. The vast majority of UK final‐year medical students were able to meet a prespecified standard of prescribing competence.
Targeting anti‐apoptotic BCL2 family proteins in haematological malignancies – from pathogenesis to treatment
Authors: Vogler Meike , Walter Harriet S. , Dyer Martin J. S. 
Published: April 2017

SummaryThe B‐cell lymphoma 2 (BCL2) family of proteins comprise key regulators of apoptosis and are implicated in the pathogenesis of many malignancies, including lymphomas and leukaemias. Targeting of BCL2 proteins can be directly toxic to tumour cells or render them more sensitive to chemotherapy. Inhibition of the anti‐apoptotic functions of BCL2 proteins using structure‐based design to produce specific inhibitors of protein–protein interactions has been achieved for BCL2, MCL1 and BCL‐XL (also termed BCL2L1), providing an armamentarium of new targeted therapies called BH3‐mimetics. The first BCL2‐specific inhibitor, venetoclax, has shown extraordinary single agent activity in chronic lymphocytic leukaemia (CLL), with surprisingly little toxicity given the expression of BCL2 in normal tissues. Despite success in CLL, where sensitivity to BCL2 inhibition is seen in nearly all cases, key questions have not yet been addressed. For example, responses to venetoclax in other B‐cell and myeloid malignancies are heterogeneous, highlighting the need to identify biomarkers that correlate with response and, secondly, to identify/develop other specific compounds that synergise with BCL2 inhibition. In this review, we summarise the biology of BCL2 proteins, the mechanism of action of BH3‐mimetics and the status of their clinical development in haematological malignancies.
The Lateglacial to early Holocene tephrochronological record from Lake Hämelsee, Germany: a key site within the European tephra framework
Authors: Jones Gwydion , Lane Christine S. , Brauer Achim , Davies Siwan M. , de Bruijn Renée , Engels Stefan , Haliuc Aritina , Hoek Wim Z. , Merkt Josef , Sachse Dirk , Turner Falko , Wagner‐Cremer Friederike 
Published: April 2017

Here we present the results of a detailed cryptotephra investigation through the Lateglacial to early Holocene transition, from a new sediment core record obtained from Lake Hämelsee, Germany. Two tephra horizons, the Laacher See Tephra (Eifel Volcanic Field) and the Saksunarvatn Ash (Iceland), have been previously described in this partially varved sediment record, indicating the potential of the location as an important Lateglacial tephrochronological site in northwest Europe. We have identified three further tephra horizons, which we correlate to: the c. 12.1 ka BP Vedde Ash (Iceland), the c. 11 ka BP Ulmener Maar tephra (Eifel Volcanic Field) and the c. 10.8 ka BP Askja‐S tephra (Iceland). Three additional cryptotephra deposits have been found (locally named HÄM_T1616, HÄM_T1470 and HÄM_T1456‐1455), which cannot be correlated to any known eruption at present. Geochemical analysis of the deposits suggests that these cryptotephras most likely have an Icelandic origin. Our discoveries provide age constraints for the new sediment records from Lake Hämelsee and enable direct stratigraphical correlations to be made with other tephra‐bearing sites across Europe. The new tephrostratigraphical record, within a partially varved Lateglacial sediment record, highlights the importance of Lake Hämelsee as a key site within the European tephra lattice.
Recent progress in the understanding of relaxin family peptides and their receptors
Authors: Summers R J 
Published: April 2017

Linked ArticlesThis article is part of a themed section on Recent Progress in the Understanding of Relaxin Family Peptides and their Receptors. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.10/issuetoc
Predictive mechanisms linking brain opioids to chronic pain vulnerability and resilience
Authors: Jones Anthony Kenneth Peter , Brown Christopher Andrew 
Published: April 2017

Chronic pain is a major global healthcare problem that is currently inadequately treated. In addition, the current use of opioids for treatment has reached far beyond the paucity of evidence for long‐term benefits relative to risks. Benefit–risk models for opioid and non‐opioid treatments would benefit from a rational, mechanism‐based understanding of neuroplastic and neurochemical contributions to chronic pain. Here, we evaluate the findings and limitations of representative research investigating brain neuroplasticity and neurochemistry in chronic pain. In sum, the mechanisms of pain‐related neuroplasticity in the brain remain poorly understood because neuroimaging studies have been largely descriptive. We argue that definition is needed of optimal (pain‐resilient) and suboptimal (pain‐vulnerable) functioning of the endogenous opioid system in order to identify neurochemical contributions to aberrant neuroplasticity in chronic pain. We outline the potential benefits of computational approaches that utilize evolutionary and statistical optimality principles, illustrating this approach with mechanistic hypotheses on opioid function. In particular, we discuss the role of predictive mechanisms in perceptual and associative plasticity and evidence for their modulation by endogenous opioids. Future research should attempt to utilize formal computational models to provide evidence for the clinical validity of this approach, thereby providing a rational basis for future treatment and, ideally, prevention.Linked ArticlesThis article is part of a themed section on Emerging Areas of Opioid Pharmacology. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.14/issuetoc
How to manage chronic urticaria ‘beyond’ guidelines: a practical algorithm
Authors: Rutkowski K. , Grattan C. E. H. 
Published: April 2017

SummaryChronic urticaria (CU) is a disease characterized by pruritic weals, angio‐oedema or both occurring for at least 6 weeks. It encompasses spontaneous and inducible urticarias. The national and international guidelines outline the principles of treatment. Omalizumab, an anti‐immunoglobulin E monoclonal antibody, has transformed the management of many severe and treatment‐refractory patients. However, current UK guidance on its use does not address the needs of those with less severe disease, inducible urticarias, idiopathic histaminergic angio‐oedema without weals as a presentation of CU and omalizumab non‐responders. Our algorithm and a summary of the evidence to support its principles offers guidance and a more systematic targeted approach to using a range of ‘off‐label’ agents for specific phenotypes of CU. It will be of use when guideline‐recommended mast cell mediator antagonists fail to control symptoms and/or using omalizumab is ineffective, not practical or unfunded.
Development, validation and testing of a skin sampling method for assessment of metal exposure
Authors: Erfani Behnaz , Midander Klara , Lidén Carola , Julander Anneli 
Published: April 2017

SummaryBackgroundNickel, cobalt and chromium are frequent skin sensitizers. Skin exposure results in eczema in sensitized individuals, the risk being related to the skin dose.ObjectivesTo develop a self‐sampling method for quantification of skin exposure to metals, to validate the method, and to assess its feasibility.MethodsDefined metal doses (0.01–5 µg) were applied to the fingers of 5 participants. Skin areas (2 cm2) were sampled with 1% HNO3, either as 0.1 ml on a swab, or as 0.5 ml on a wipe. Furthermore, 17 participants performed self‐sampling by swab after 2 h of leisure activity. Samples were extracted in 1% HNO3 and analysed by inductively coupled plasma mass spectrometry.ResultsThe sampling efficiency by swab was 46%, as compared with 93% for acid wipe sampling, for all tested doses. Most metal from the skin dose was detected in the first swab (33–43%). Despite lower sampling efficiency by swab, skin doses of metals following 2 h of leisure activity without hand washing were quantified in all participants, and ranged from 0.0016 to 0.15 µg/cm2, from 0.00014 to −0.0020 µg/cm2 and from 0.00048 to −0.027 µg/cm2 for nickel, cobalt, and chromium, respectively.ConclusionsThe results indicate a future potential of skin sampling by swab to detect and monitor metals on skin by self‐sampling. This will contribute to better knowledge of metal skin exposure among dermatitis patients, workers, and the general population.
Does urbanization lead to taxonomic and functional homogenization in riparian forests?
Authors: Brice Marie‐Hélène , Pellerin Stéphanie , Poulin Monique 
Published: April 2017

AbstractAimIn urbanized areas, exotic invasions, native extinctions, and the alteration of habitats and natural processes drive homogenization, which is a form of biotic impoverishment. This study examines whether urbanization and flooding induce homogenization of herbaceous communities in riparian forests and quantifies the relationships between taxonomic and functional β‐diversity.LocationMontréal, Québec, Canada.MethodsInventories were conducted in 56 riparian forests. Taxonomic and functional β‐diversity were calculated as between‐site similarities in species or trait composition for three levels of urbanization and flooding. Differences among the disturbance levels were compared using tests for homogeneity in multivariate dispersions. We quantified the correlation between local species richness, exotic proportion, taxonomic and functional β‐diversity. We also partitioned taxonomic β‐diversity into species turnover and richness difference.ResultsUrbanization led to taxonomic and functional differentiation, while increased flooding led to taxonomic and functional homogenization. We found a significant correlation between taxonomic and functional β‐diversity. Changes in β‐diversity were associated with species and trait turnover among both urbanization and flood levels, and with changes in species richness. Differentiation was associated with low species richness, and homogenization with high species richness. Exotic invasions tended to favour differentiation, but only at a low urbanization level.Main ConclusionsThe effect of urbanization on plant diversity in riparian forests was twofold: first, it directly induced taxonomic and functional differentiation through its effect on species loss and turnover (higher β‐diversity at high urbanization level); second, differentiation was indirectly favoured through the reduction in flooding (higher β‐diversity at low flood level). Taxonomic and functional β‐diversity followed similar patterns, likely because species invasions and extinctions are not random, but are related to species traits. Our results underline the need to move our focus from exotic species to the true underlying factors of biodiversity loss and homogenization, notably land use changes and human disturbances.
Depression symptoms are persistent in Type 2 diabetes: risk factors and outcomes of 5‐year depression trajectories using latent class growth analysis
Authors: Whitworth S. R. , Bruce D. G. , Starkstein S. E. , Davis W. A. , Davis T. M. E. , Skinner T. C. , Bucks R. S. 
Published: April 2017

AbstractAimsTo describe the long‐term trajectories of depression symptom severity in people with Type 2 diabetes, and to identify predictors and associates of these trajectories.MethodsA community‐dwelling cohort of 1201 individuals with Type 2 diabetes from the Fremantle Diabetes Study Phase II was followed for 5 years. The nine‐item version of the Patient Health Questionnaire was administered annually to assess depression symptoms, and biomedical and psychosocial measures were assessed at baseline and biennially. Latent class growth analysis was used to identify classes of depression severity trajectories and associated outcomes, and logistic regression models were used to determine predictors of class membership.ResultsThree trajectories of depression symptoms were identified: continuously low depression symptoms (85.2%); gradually worsening symptoms that then began to improve (persistent depression – low‐start; 7.3%); and gradually improving symptoms which later worsened (persistent depression – high‐start; 7.5%). Younger age, being a woman, and a lifetime history of major depressive disorder, were associated with greater risk of persistent depression symptoms. Persistent depression was associated with consistently higher BMI over time, but not with changes in HbA1c or self‐monitoring of blood glucose.ConclusionsA subset of individuals with Type 2 diabetes is at risk of depression symptoms that remain elevated over time. Younger, overweight individuals with a history of depression may benefit from early and intensive depression management and ongoing follow‐up as part of routine Type 2 diabetes care.
Reliable estimation of inhibitory efficiency: to anticipate, choose or simply react?
Authors: Leunissen Inge , Zandbelt Bram B. , Potocanac Zrinka , Swinnen Stephan P. , Coxon James P. 
Published: April 2017

AbstractResponse inhibition is an important executive process studied by clinical and experimental psychologists, neurophysiologists and cognitive neuroscientists alike. Stop‐signal paradigms are popular because they are grounded in a theory that provides methods to estimate the latency of an unobservable process: the stop‐signal reaction time (SSRT). Critically, SSRT estimates can be biased by skew of the response time distribution and gradual slowing over the course of the experiment. Here, we present a series of experiments that directly compare three common stop‐signal paradigms that differ in the distribution of response times. The results show that the widely used choice response (CR) and simple response (SR) time versions of the stop‐signal paradigm are particularly susceptible to skew of the response time distribution and response slowing, and that using the anticipated response (AR) paradigm based on the Slater‐Hammel task offers a viable alternative to obtain more reliable SSRT estimates.