bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lymphopaenia in the diagnosis of paediatric appendicitis: a false sense of security?
Authors: Greer Douglas , Bennett Peter , Wagstaff Benjamin , Croaker David 
Published: August 2019

AbstractBackgroundAppendicitis is a common indication for emergent surgery in children; however, it is a small proportion of presentations with abdominal pain. As viral illness is a common differential diagnosis, lymphopaenia is used by some as a predictor against appendicitis. Furthermore, neutrophil–lymphocyte ratio (NLR) has been found to predict appendicitis. We aimed to verify if lymphopaenia predicted against appendicitis in children.MethodsRetrospective review was conducted for all patients aged 15 years and under presenting with abdominal pain to our institution in 2017, and data including age, white cell count, neutrophil and lymphocyte count, NLR, C‐reactive protein and diagnosis of appendicitis were recorded. Statistical analysis was performed using Stata©. Receiver operating characteristic curves for various tests were formed and areas under curve (AUC) compared using regression, P < 0.05 was considered significant.ResultsA total of 1263 patients were presented, of whom 546 had their blood performed and were included, 86 had appendicitis and 460 did not. Neutrophilia was the best predictor for appendicitis (AUC = 0.86), significantly higher than NLR (0.81), P < 0.05. Lymphopaenia was a poor negative predictor of appendicitis (AUC = 0.46), and while isolated lymphopaenia was more predictive (AUC = 0.23) this was inferior to the positive prediction of neutrophilia, P < 0.05.ConclusionThe value of isolated lymphopaenia to predict against appendicitis is largely accounted for inherently normal neutrophils, independently lymphopaenia has little value. NLR, while predictive, is a weaker predictor than neutrophilia.
Impacts of USAID and development assistance toward counterterrorism efforts: Empirical evidence in context of Pakistan
Authors: Shahzad Umer , Farooq Muhammad Umar , Qin Fengming 
Published: August 2019

AbstractThis article studies whether the pursuit of foreign aid for counterterrorism purposes militarizes or mitigates terrorism. It focuses on the USAID and official development assistance (ODA) flows to Pakistan, which recently has experienced an increase due to the presence of deadliest terrorist organizations. By using the time series data from 1985 to 2016, the paper investigated the foreign aid and terrorism nexus for pre‐9/11 and post‐9/11 periods. The empirical estimations of autoregressive distributed lag bound testing approach reported that an increase in military expenditures fuels terrorism in post‐9/11 period and the ODA helps to control terrorism from the country. On the contrary, USAID reported insignificant response toward terrorist attacks in pre‐ and post‐9/11 periods, suggesting that the foreign aid from the United States has no significant impact on counterterrorism policies for Pakistan. The outcomes of the current study can be utilized in policymaking of counterterrorism and to explore the nexus between foreign aid, terrorism, and military expenditures. The paper concludes that the concerns about the use of foreign aid as counterterrorism tool are warranted, but that actual manifestations are nuanced.
Longitudinal exposure of English primary care patients to pharmacogenomic drugs: An analysis to inform design of pre‐emptive pharmacogenomic testing
Authors: Kimpton James E. , Carey Iain M. , Threapleton Christopher J.D. , Robinson Alexandra , Harris Tess , Cook Derek G. , DeWilde Stephen , Baker Emma H. 
Published: August 2019

AimsTo investigate the longitudinal exposure of English primary care patients to pharmacogenomic drugs to inform design of pre‐emptive testing.MethodsSixty‐three drugs were identified with dosing guidelines based on variants of 19 pharmacogenes in the Pharmacogenomics Knowledgebase on 01 September 2018. Prescribing of these pharmacogenomic drugs between 1993 and 2017 was summarised for a sample of 648 141 English patients aged 50–99 years on 01 January 2013, registered with Clinical Practice Research Datalink practices during 2011–12. Exposure of patients to pharmacogenomic drugs retrospectively (2, 10, 20 y) and prospectively (5 y) was described.ResultsDuring 2011–12, 58% of patients were prescribed at least 1 pharmacogenomic drug, increasing to 80% over the previous 20 years. Multiple exposure was common, with 47% patients prescribed ≥2 pharmacogenomic drugs and 7% prescribed ≥5 pharmacogenomic drugs over the next 5 years. The likelihood of exposure to pharmacogenomic drugs increased with age, with 89% patients ≥70 years prescribed at least 1 pharmacogenomic drug over the previous 20 years. Even among those aged 50–59 years, 71% were prescribed at least 1 pharmacogenomic drug over the previous 20 years. The pharmacogenomic drugs prescribed to the most patients were for pain relief, gastroprotection, psychiatric and cardiovascular conditions. Three pharmacogenes (CYP2D6, CYP2C19 and SLCO1B1) accounted for >95% pharmacogenomic drugs prescribed.ConclusionsIn primary care patients, exposure to pharmacogenomic drugs is extremely common, multiplicitous and has commenced by relatively early adulthood. A small number of pharmacogenes account for the majority of drugs prescribed. These findings could inform design of pre‐emptive pharmacogenomic testing for implementation in primary care.
CD4+ count‐dependent concentration–effect relationship of rituximab in rheumatoid arthritis
Authors: Bensalem Amina , Mulleman Denis , Thibault Gilles , Azzopardi Nicolas , Goupille Philippe , Paintaud Gilles , Ternant David 
Published: August 2019

AimsRituximab is approved in rheumatoid arthritis (RA). A substantial decrease in CD4+ count was observed in responders after a single cycle of treatment. This study aimed to describe and quantifying the influence of CD4+ count depletion on the concentration–response relationship of rituximab in RA patients.MethodsIn this retrospective monocentric observational study, 52 patients were assessed. Repeated measurements of rituximab concentrations (pharmacokinetics), CD4+ counts (biomarker) and disease activity score in 28 joints (DAS28, clinical response) were made. Rituximab pharmacokinetics was described using a 2‐compartment model, and CD4+ cell counts and DAS28 measurements were described using indirect turnover and direct Emax pharmacokinetic–pharmacodynamic models, respectively. Delay between rituximab concentrations and responses was accounted for by including biophase compartments.ResultsElimination half‐life of rituximab was 18 days. The pharmacokinetic–pharmacodynamic model showed that DAS28 response to rituximab was partly associated with CD4+ cell depletion. At 6 months, a deeper DAS28 decrease was observed in patients when CD4+ cell count is decreased: median [interquartile range] of DAS28 was 3.7 [2.9–4.4] and 4.5 [3.7–5.3] in patients with and without CD4+ decrease, respectively.ConclusionsThis is the first study to quantify the relationship between rituximab concentrations, CD4+ count and DAS28 in RA patients. This model showed that approximately 75% of patients had CD4+ count decrease, and that the clinical improvement is 2‐fold higher in patients with CD4+ cells decrease than in others.
The somatic integration definition of the beginning of life
Authors: Brown Mark T. 
Published: August 2019

AbstractThe somatic integration definition of life is familiar from the debate on the determination of death, with some bioethicists arguing that it supports brain death while others argue that some brain‐dead bodies exhibit sufficient somatic integration for biological life. I argue that on either interpretation, the somatic integration definition of life implies that neither the preimplantation embryo nor the postimplantation embryo meet the somatic integration threshold condition for organismal human life. The earliest point at which a somatic integration determination of life could be made would be the beginning of the fetal stage, 9 weeks postfertilization. Bioethical implications are considered, specifically with respect to the moral status of the postimplantation embryo in embryo research and abortion.
Design, synthesis, and in vitro antitumor activity of a transferrin receptor‐targeted peptide–doxorubicin conjugate
Authors: Li Songtao , Zhao Hongling , Fan Yanfang , Zhao Guiqin , Wang Ruxing , Wen Fuyu , Wang Jianping , Wang Xiaohui , Wang Yu , Gao Yang 
Published: August 2019

AbstractIn this study, a peptide–drug conjugate was designed and synthesized by connecting a transferrin receptor (TfR)‐targeted binding peptide analog BP9a (CAHLHNRS) with doxorubicin (DOX) through N‐succinimidyl‐3‐maleimidopropionate (SMP) as the cross‐linker. Confocal laser scanning microscopy results indicated that free DOX mainly accumulated in the nuclei of both TfR overexpressed HepG2 hepatoma cells and L‐O2 normal liver cells expressing low level of TfR; most of the BP9a‐DOX conjugate displayed cytoplasmic location, and its cellular uptake by HepG2 cells was obviously reduced by TfR blockage test. Nevertheless, the cellular uptake of this conjugate by L‐O2 cells was much less than that of free DOX. Meanwhile, the BP9a‐DOX conjugate exhibited lower in vitro antiproliferative activity against HepG2 cells than free DOX, but its cytotoxic effect on L‐O2 cells was decreased compared with that of free DOX. These results suggest that BP9a could be applied as a potential TfR‐targeted peptide vector for selective drug delivery.
Preschool Self‐Regulation and Preacademic Skills as Mediators of the Long‐Term Impacts of an Early Intervention
Authors: McCoy Dana C. , Gonzalez Kathryn , Jones Stephanie 
Published: August 2019

This study explores children's early academic and self‐regulatory skills as potential pathways through which a preschool enrichment program—the Chicago School Readiness Project (CSRP)—may contribute to low‐income children's long‐term outcomes (N = 466; Mage at baseline = 4.10 years). We find that CSRP's impact on high school grades may be partially explained by early gains in vocabulary and math skills. Although impacts on high school executive function (EF) were more equivocal, our results suggest that early improvements in math skills attributable to the intervention may, in turn, predict long‐term gains in EF skills. These results complement the existing literature on preschool fade out, while also shedding light on the cross‐domain relations between academic and self‐regulatory skills.
Psychological services for food allergy: The unmet need for patients and families in the United Kingdom
Authors: Knibb Rebecca , Halsey Mary , James Polly , du Toit George , Young Judith 
Published: August 2019

AbstractResearch over the past 20 years has demonstrated the significant impact food allergy can have on quality of life and mental health of patients and their families, yet there is a paucity of psychological services to support families in coping with this condition. This paper provides a short overview of the psychological impact of food allergy, followed by a discussion of the use of paediatric psychological services for long‐term conditions. To our knowledge, few paediatric allergy clinics in the UK have funding for dedicated clinical psychology services. Two such services are based at Southampton General Hospital and the Evelina London Children's Hospital. This paper includes descriptions of these services and how they are currently being used by patients and families. This is followed by an allergy clinician's perspective on the use of psychological services. Recommendations are made for allergy services to work with hospital psychology services to develop, integrate and deliver psychological services for all patients with allergy and their families who are in need. Future research also needs to focus on the efficacy of psychological therapies and group interventions in food allergy.
Practitioner insights as a means of setting a context for conservation
Authors: Sanders Michele Jeanette , Miller Laura , Bhagwat Shonil A. , van der Grient Jesse Marije Anne , Rogers Alex David 
Published: August 2019

AbstractA key obstacle to conservation success is the tendency of conservation professionals to tackle each challenge individually rather than collectively and in context. We sought to prioritize barriers to conservation previously described in the conservation literature. We undertook an online survey of 154 practitioners from over 70 countries to ascertain the most important barriers to conservation they faced. We used statistical analyses to identify the key impediments to conservation success and to examine whether these were affected by organizational attributes. Twenty‐one barriers were identified. The importance ascribed to those was influenced by continent of operation and organization size, but not by organization age or autonomy (from larger parent organizations). We found the most important barriers to consider when undertaking conservation action were wider issues (e.g., population growth, consumerism, favoring development, and industrial‐scale activity), operating environment (e.g., lack of political will, ineffective law enforcement, weak governments, corruption, safety and security), community attributes (e.g., dynamics, conflicts, and education levels), and the way conservation is undertaken (overconfidence, lack of funding, and externally set agendas). However, we advise against applying a one‐size‐fits‐all approach. We propose that conservationists account for the complex socioecological systems they operate in if they are to achieve success.
912. PETROCOSMEA THERMOPUNCTA
Authors: Shaw Julian M. H. 
Published: August 2019

SummaryPetrocosmea thermopuncta, a probable hybrid species from Yunnan, is described and illustrated. Formerly known in cultivation as P. grandiflora, this taxon is named thermopuncta (hotspot) with reference to the dark spot in the corolla tube and its growing in a biodiversity hotspot, (though of uncertain geographical provenance).
Impact of dietary protein on postprandial glycaemic control and insulin requirements in Type 1 diabetes: a systematic review
Authors: Paterson M. A. , King B. R. , Smart C. E. M. , Smith T. , Rafferty J. , Lopez P. E. 
Published: August 2019

AbstractAimPostprandial hyperglycaemia is a challenge for people living with Type 1 diabetes. In addition to carbohydrate, dietary protein has been shown to contribute to postprandial glycaemic excursions with recommendations to consider protein when calculating mealtime insulin doses. The aim of this review is to identify and synthesize evidence about the glycaemic impact of dietary protein and insulin requirements for individuals with Type 1 diabetes.MethodsA systematic literature search of relevant biomedical databases was performed to identify research on the glycaemic impact of dietary protein when consumed alone, and in combination with other macronutrients in individuals with Type 1 diabetes.ResultsThe review included 14 published studies dated from 1992 to 2018, and included studies that researched the impact of protein alone (n = 2) and protein in a mixed meal (n = 12). When protein was consumed alone a glycaemic effect was not seen until ≥ 75 g. In a carbohydrate‐containing meal ≥ 12.5 g of protein impacted the postprandial glucose. Inclusion of fat in a high‐protein meal enhanced the glycaemic response and further increased insulin requirements. The timing of the glycaemic effect from dietary protein ranged from 90 to 240 min. Studies indicate that the postprandial glycaemic response and insulin requirements for protein are different when protein is consumed alone or with carbohydrate and/or fat.ConclusionsThis systematic review provides evidence that dietary protein contributes to postprandial glycaemic excursions and insulin requirements. These insights have important implications for the education of people with Type 1 diabetes and highlights the need for more effective insulin dosing strategies for mixed macronutrient meals.
Prevalence and characteristics of renal artery fibromuscular dysplasia in hypertensive women below 50 years old
Authors: Di Monaco Silvia , Lengelé Jean‐Philippe , Heenaye Sheik , Danse Etienne , Hammer Frank , Lopez‐Sublet Marilucy , Toubiana Laurent , Rabbia Franco , Persu Alexandre 
Published: August 2019

AbstractBackgroundRenal fibromuscular dysplasia (FMD) is typically diagnosed in young hypertensive women. The 2014 European FMD Consensus recommended screening in all hypertensive women <30 yo. However, the prevalence of renal FMD in young/middle‐aged hypertensive women remains unclear. The aim of this work was to assess the prevalence and characteristics of renal FMD in hypertensive women ≤50 yo.MethodsWe retrospectively included all consecutive women aged ≤50 years referred to our Hypertension Unit from 2014 to 2017 and collected standardized information on patient characteristics and screening modalities.ResultsOf 1083 incident hypertensive patients, 157 patients fitted with inclusion criteria. The prevalence of renal FMD varied between 3.2% in the whole sample and 7.5% in patients explored by CTA and/or MRA (n = 67). In the subgroup of patients ≤30 yo (n = 32), the corresponding figures were 3.1% and 5.6%. The yearly prevalence of FMD tended to increase over time, in parallel with increased use of CTA/MRA as a first‐line imaging modality. Out of 5 patients with renal FMD, 2 were revascularized and 1 had extra‐renal FMD.ConclusionsThe prevalence of renal FMD in young/middle‐aged hypertensive women is probably one order of magnitude higher than previously assumed, in the range of 3%‐8%, depending on imaging modalities. While the diagnosis of FMD does not influence short‐term management in all patients, it may allow close monitoring and prevention of complications of the disease over time. This analysis provides the rationale for a prospective, multicentre study aiming at determining the cost‐effectiveness of systematic screening for renal FMD.
Microglia cytoarchitecture in the brain of adenosine A2A receptor knockout mice: Brain region and sex specificities
Authors: Simões-Henriques Carla , Mateus‐Pinheiro Miguel , Gaspar Rita , Pinheiro Helena , Mendes Duarte Joana , Baptista Filipa I. , Canas Paula M. , Fontes-Ribeiro Carlos Alberto , Cunha Rodrigo A. , Ambrósio António F. , Gomes Catarina A. 
Published: August 2019

AbstractMicroglia cells exert a critical role in brain development, mainly supported by their immune functions, which predicts an impact on the genesis of psychiatric disorders. In fact, microglia stress during gestation is, for instance, associated with chronic anxiety and cognitive deficits accompanied by long‐lasting, region‐ and sex‐specific changes in microglia morphology. We recently reported that the pattern of microglia morphologic plasticity, which is sex‐determined, impacts on anxious‐like behaviour and cognition. We also reported that the pharmacologic blockade of adenosine A2A receptors (A2AR) is able to reshape microglia morphology, in a sex‐specific manner and with behavioural sequelae. In order to better understand the role of A2AR in the sex differentiation of microglia, we now compared their morphology in wild‐type and A2AR knockout male and female C57BL/6 mice in two cardinal brain regions implicated in anxiety‐like behaviour and cognition, the prefrontal cortex (PFC) and the dorsal hippocampus (dHIP). We report interregional differences between PFC and dHIP in a sex‐specific manner: while males presented more complex microglia in the dHIP, microglia from females had a more complex morphology in the PFC. Surprisingly, the genetic deletion of A2AR did not alter these sex differences, but promoted the exclusive remodelling (increase in complexity) in PFC microglia from females. These findings further support the existence of a heterogeneous microglial network, distinct between sexes and brain regions, and help characterizing the role of A2AR in the sex‐ and brain region‐specific morphologic differentiation of microglia.
Pathological responses to single‐pulse electrical stimuli in epilepsy: The role of feedforward inhibition
Authors: Hebbink Jurgen , Huiskamp Geertjan , van Gils Stephan A. , Leijten Frans S. S. , Meijer Hil G. E. 
Published: August 2019

AbstractDelineation of epileptogenic cortex in focal epilepsy patients may profit from single‐pulse electrical stimulation during intracranialEEGrecordings. Single‐pulse electrical stimulation evokes early and delayed responses. Early responses represent connectivity. Delayed responses are a biomarker for epileptogenic cortex, but up till now, the precise mechanism generating delayed responses remains elusive. We used a data‐driven modelling approach to study early and delayed responses. We hypothesized that delayed responses represent indirect responses triggered by early response activity and investigated this for 11 patients. Using two coupled neural masses, we modelled early and delayed responses by combining simulations and bifurcation analysis. An important feature of the model is the inclusion of feedforward inhibitory connections. The waveform of early responses can be explained by feedforward inhibition. Delayed responses can be viewed as second‐order responses in the early response network which appear when input to a neural mass falls below a threshold forcing it temporarily to a spiking state. The combination of the threshold with noisy background input explains the typical stochastic appearance of delayed responses. The intrinsic excitability of a neural mass and the strength of its input influence the probability at which delayed responses to occur. Our work gives a theoretical basis for the use of delayed responses as a biomarker for the epileptogenic zone, confirming earlier clinical observations. The combination of early responses revealing effective connectivity, and delayed responses showing intrinsic excitability, makes single‐pulse electrical stimulation an interesting tool to obtain data for computational models of epilepsy surgery.
Does Parkinson's disease increase the risk of cardiovascular events? A systematic review and meta‐analysis
Authors: Alves M. , Caldeira D. , Ferro J. M. , Ferreira J. J. 
Published: August 2019

Background and purposeThe impact of Parkinson's disease (PD) on the risk of cardiovascular disease is poorly known. The aim was to systematically review observational studies evaluating the association between PD and cardiovascular events.MethodsMEDLINE through PubMed, the Web of Science and Cochrane Central Register of Controlled Trials with conference proceedings were searched from inception to 4 July 2019. Two reviewers independently selected studies comparing cardiovascular events between Parkinson's disease and control groups. Ischaemic stroke, myocardial infarction and cardiovascular mortality were the outcomes of interest. Pooled estimates of odds ratios (ORs) and 95% confidence intervals (CIs) were derived by random effects meta‐analysis. Heterogeneity was assessed using the I2 test. The study protocol was registered at PROSPERO: CRD42017076527.ResultsEleven studies were included: nine cohort studies and two case–control studies. PD was associated with a significantly increased risk of stroke (nine studies: OR 1.66, 95% CI 1.19, 2.34; I2 = 50%). No significant differences were detected regarding myocardial infarction risks (eight studies: OR 1.15, 95% CI 0.72, 1.83; I2 = 76%) nor cardiovascular mortality risks (seven studies: OR 1.11, 95% CI 0.85, 1.45; I2 = 47%) in PD patients.ConclusionsThe best evidence available showed an association between PD and increased risk of stroke. The risk of myocardial infarction and cardiovascular mortality was not different in PD and non‐PD individuals.