bluuebunny/crossref_metadata_2025_split huggingface dataset:
The French reporting system for drug shortages: description and trends from 2012 to 2018: an observational retrospective study
Authors: Benhabib Amine , Ioughlissen Saïd , Ratignier-Carbonneil Christelle , Maison Patrick 
Published: March 2020

ObjectivesThe aim was to provide figures for drug shortages in France and describe their characteristics, causes and trends between 2012 and 2018.MethodsData from the national reporting system from the Agency of Medicine and Health Product Safety (ANSM) was analysed. This database contains information regarding effective and predicted shortages of major therapeutic of interest drugs (ie, drugs whose shortage would be life-threatening or representing a loss of treatment opportunity for patients with a severe disease) which are mandatory reported by marketing authorisation holders to the ANSM. Data are presented as numbers or percentages of pharmaceutical products (ie, the product name and its formulation) reported on shortage between 2012 and 2018.ResultsThere were 3530 pharmaceutical products reported on shortage during the period, including 1833 different active substances. Drugs on shortage were mostly old products (63.4%) with national marketing authorisation procedures (62.8%), as well as injectable and oral forms (47.5% and 43.3%, respectively). Anti-infectives for systemic use ranked first (18%), followed by nervous and cardiovascular system drugs and by antineoplastic and immunomodulating agents (17.4%, 12.5% and 10.4%, respectively). The number of reported shortages presented a fourfold increase between 2012 and 2018 and a sharp rise in 2017 and 2018, along with a rise in the number of active substances on shortage. The therapeutic classes concerned remained similar over time. Manufacturing and material supply issues were the main reported reasons for the shortage each year (30%) and there was an overall rise of pharmaceutical market reasons.ConclusionDrug shortages were increasingly reported in France. Preventive measures should specifically target the products most on shortage, in particular old drugs, injectable, anti-infective, nervous system and cardiovascular system drugs as well as antineoplastic and immunomodulating agents.
Severity of coeliac disease and clinical management study when using a CYP3A4 metabolised medication: a phase I pharmacokinetic study
Authors: Chretien Marc L , Bailey David G , Asher Linda , Parfitt Jeremy , Driman David , Gregor Jamie , Dresser George K 
Published: March 2020

ObjectiveSeverity of coeliac disease depends in part on the extent of small intestinal mucosa injury. Patients with the most abnormal pathology have loss of duodenal villi CYP3A4, a drug-metabolising enzyme that inactivates many drugs. These patients are hypothesised to have greater systemic concentrations of felodipine, a drug which normally has low oral bioavailability secondary to intestinal CYP3A4-mediated metabolism. It serves as a representative for a class containing many medications.DesignA phase I, open-label, single-dose, pharmacokinetic study.SettingLondon, Ontario, Canada.ParticipantsPatients with coeliac disease (n=47) with positive serology and healthy individuals (n=68).Main outcome measuresPatients with coeliac disease—upper gastrointestinal endoscopy and oral felodipine pharmacokinetics study within a 3-week period. Healthy individuals—oral felodipine pharmacokinetics study with water and grapefruit juice.ResultsCoeliac stratification categories: Group A (n=15, normal), B+C (n=16, intraepithelial lymphocytosis with/without mild villous blunting) and D (n=16, moderate/severe villous blunting). Groups A, B+C and D had linear trends of increasing felodipine AUC0–8; mean±SEM, 14.4±2.1, 17.6±2.8, 25.7±5.0; p<0.05) and Cmax (3.5±0.5, 4.0±0.6, 6.4±1.1; p<0.02), respectively. Healthy subjects receiving water had lower felodipine AUC0–8(11.9±0.9 vs 26.9±0.9, p=0.0001) and Cmax (2.9±0.2 vs 7.7±0.2, p=0.0001) relative to those receiving grapefruit juice.ConclusionsIncreased felodipine concentrations in patients with coeliac disease were most probably secondary to decreased small intestinal CYP3A4 expression. Patients with severe coeliac disease and healthy individuals with grapefruit juice had equivalently enhanced effect. Thus, patients with severe coeliac disease would probably experience similarly altered drug response, including overdose toxicity, from many important medications known to be metabolised by CYP3A4. Patients with coeliac disease with severe disease should be considered for other clinical drug management, particularly when there is the potential for serious drug toxicity.
Awareness and bispectral index (BIS) monitoring in mechanically ventilated patients in the emergency department and intensive care unit: a systematic review protocol
Authors: Pappal Ryan D , Roberts Brian W , Winkler Winston , Yaegar Lauren H , Stephens Robert J , Fuller Brian M 
Published: March 2020

IntroductionAccidental awareness with recall is one of the most feared complications for patients undergoing general anaesthesia and can lead to post-traumatic stress disorder in up to 70% of patients experiencing it. To reduce the incidence of awareness with recall, the bispectral index monitor is recommended for patients receiving total intravenous anaesthetics, especially those receiving neuromuscular blockers. While extensive investigation into awareness and bispectral index monitoring has occurred for operating room patients, this has not extended to other clinical arenas where sedated and mechanically ventilated patients are cared for, namely the intensive care unit and emergency department. The purpose of this systematic review is to assess the world’s literature to determine the incidence of awareness with paralysis in mechanically ventilated patients and the impact of bispectral index monitoring for reducing this complication.Methods and analysisRandomised trials and non-randomised studies are eligible for inclusion. With aid from a medical librarian, an electronic search will include Ovid Medline, Embase.com, Scopus, Cochrane Database of Systematic Reviews and Cochrane Central Register of Controlled Trials. To find data published in abstract form, literature from professional society conferences (2010–2019) will be manually searched. Two authors will independently review search results and consensus will be reached with assistance from a third author, as needed. Heterogeneity and publication bias will be assessed and reported. If possible and appropriate, a meta-analysis of the data will be conducted for quantitative data analysis.Ethics and disseminationThe proposed systematic review does not require ethical approval, as it is conducted at the study level and does not involve individual patient-level data. Results will be disseminated by data sharing via academically established means, presentation at local and national scientific meetings and publication as a peer-reviewed manuscript.PROSPERO registration numberThe protocol has been submitted to International Prospective Register of Systematic Reviews and is awaiting registration.
Bayesian methods in palliative care research: cancer-induced bone pain
Authors: Parker Richard A , Sande Tonje A , Laird Barry , Hoskin Peter , Fallon Marie , Colvin Lesley 
Published: March 2020

ObjectiveTo show how a simple Bayesian analysis method can be used to improve the evidence base in patient populations where recruitment and retention are challenging.MethodsA Bayesian conjugate analysis method was applied to binary data from the Thermal testing in Bone Pain (TiBoP) study: a prospective diagnostic accuracy/predictive study in patients with cancer-induced bone pain (CIBP). This study aimed to evaluate the clinical utility of a simple bedside tool to identify who was most likely to benefit from palliative radiotherapy (XRT) for CIBP.ResultsRecruitment and retention of patients were challenging due to the frail population, with only 27 patients available for the primary analysis. The Bayesian method allowed us to make use of prior work done in this area and combine it with the TiBoP data to maximise the informativeness of the results. Positive and negative predictive values were estimated with greater precision, and interpretation of results was facilitated by use of direct probability statements. In particular, there was only 7% probability that the true positive predictive value was above 80%.ConclusionsSeveral advantages of using Bayesian analysis are illustrated in this article. The Bayesian method allowed us to gain greater confidence in our interpretation of the results despite the small sample size by allowing us to incorporate data from a previous similar study. We suggest that this method is likely to be useful for the analysis of small diagnostic or predictive studies when prior information is available.
New therapies for canine atopic dermatitis
Authors: Forsythe Peter , Jackson Hilary 
Published: March 2020

Background: Canine atopic dermatitis (CAD) is an incurable inflammatory and pruritic allergic skin disease that starts in young dogs and requires lifelong management. There have been limited choices for the management of CAD, but over the past few years two, more‐targeted, therapies have been developed.Aim of the article: This article aims to review the use of these newer therapies and how they fit into the management of this complex disease.
Characteristics and sexual health service use of MSM engaging in chemsex: results from a large online survey in England
Authors: Blomquist Paula Bianca , Mohammed Hamish , Mikhail Amy , Weatherburn Peter , Reid David , Wayal Sonali , Hughes Gwenda , Mercer Catherine H 
Published: March 2020

BackgroundChemsex, the use of select psychoactive drugs to enhance sexual experience, typically among men who have sex with men (MSM), is associated with sexual behaviours with higher STI risk. Understanding patterns of chemsex among MSM as well as the characteristics and sexual health service engagement of chemsex participants is important for developing interventions.MethodsBetween 5/2016 to 5/2017, 3933 MSM completed an online survey, recruited in sexual health clinics (SHCs) in England (n=421) and via four social networking/dating apps (n=3512). We described patterns of chemsex in the past year and used multivariable logistic regression to investigate differences in demographics and sexual behaviours by chemsex history. We described history of SHC attendance and STI test in the past year among app-recruited chemsex participants.ResultsChemsex in the past year was reported by 10% of respondents; 19% of SHC-recruited and 9% of app-recruited. Among chemsex participants, 74% had used ≥2 chemsex drugs. In the multivariable model, MSM engaging in chemsex had a raised odds of being HIV-positive (adjusted OR (aOR): 3.6; 95% CI 2.1 to 6.1), aged 30–44 (aOR 1.5 vs <30 years; 95% CI 1.0 to 2.1), being born outside the UK and having engaged in higher risk sexual behaviours in the past 3 months. Chemsex participants also had higher odds of condomless anal sex with partners of different or unknown HIV status, but only among HIV-negative/untested. In the past year, 66% of app-recruited chemsex participants had attended a SHC and 81% had had an STI test.ConclusionOne in 10 MSM recruited through community and clinical settings across England had engaged in chemsex in the past year. Those that did appear to be at greater STI risk but engaged more actively with sexual health services. This highlights the need and opportunity for chemsex-related services in SHCs and robust referral pathways to drug treatment services.
Electroweak baryogenesis and electron EDM in the B-LSSM
Authors: Yang Jin-Lei , Feng Tai-Fu , Zhang Hai-Bin 
Published: March 2020

AbstractElectroweak baryogenesis (EWB) and electric dipole moment (EDM) have close relation with the new physics beyond the standard model (SM), because the SM CP-violating (CPV) interactions are not sufficient to provide the baryon asymmetry of the universe by many orders of magnitude, and the theoretical predictions for the EDM of electron ($$d_e$$de) in the SM are too tiny to be detected in near future. In this work, we explore the CPV effects on EWB and the electron EDM in the minimal supersymmetric extension (MSSM) of the SM with local $$B-L$$B-L gauge symmetry (B-LSSM). And the two-step transition via tree-effects in this model is discussed. Including two-loop corrections to $$d_e$$de and considering the constrains from updated experimental data, the numerical results show that the B-LSSM can account for the observed baryon asymmetry. In addition, when the cancellation between different contributions to $$d_e$$de takes place, the region favored by EWB can be compatible with the corresponding EDM bound.
Relativistic quantum oscillators in the global monopole spacetime
Authors: Bragança E. A. F. , Vitória R. L. L. , Belich H. , de Mello E. R. Bezerra 
Published: March 2020

AbstractWe investigated the effects of the global monopole spacetime on the Dirac and Klein–Gordon relativistic quantum oscillators. In order to do this, we solve the Dirac and Klein–Gordon equations analytically and discuss the influence of this background, which is characterised by the curvature of the spacetime, on the energy profiles of these oscillators. In addition, we introduce a hard-wall potential and, for a particular case, determine the energy spectrum for relativistic quantum oscillators in this background.
Effectiveness of hamstring stretching using a pressure biofeedback unit for 4 weeks: A randomized controlled trial
Authors: Ahn Jin-Oh , Weon Jong-Hyuck , Koh Eun-Kyung , Jung Do-Young 
Published: March 2020

Background: Stretching and length test of hamstring muscles have been performed commonly to manage lower back pain (LBP) in sports rehabilitation. Previous literatures addressed that stretching techniques and length test of hamstring muscles should be performed with the pelvic maintained in an anterior tilt position. However, there is no study to determine the effectiveness of pressure biofeedback unit (PBU) to maintain in anterior pelvic tilting (APT) on length test and stretching of hamstring muscles. Objective: To determine the effectiveness of hamstring muscles stretching using a PBU. Methods: Forty participants with shortness of hamstrings randomized into two groups. Participants performed the active knee extension (AKE) stretching without (control group) or with PBU (intervention group) for four weeks. AKE tests without and with PBU were administered three times before and after hamstrings stretching by each group. Results: The AKE test without PBU showed a significant main effect of time ([Formula: see text]) but not of group ([Formula: see text]) on the AKE angle. The AKE test with PBU showed a significant increase in the AKE angle in the post-intervention compared to the pre-intervention assessments in both groups ([Formula: see text]). The difference of AKE angle between the pre- and post-intervention results was significantly greater in the intervention group than in the control group ([Formula: see text]). Conclusion: We recommend the use of a PBU to maintain the pelvic anterior tilting position when performing the AKE test or AKE stretching.
Do lizards (Podarcis siculus) react to whip snake (Hierophis viridiflavus) scents? A comparative test on odour stimuli recognition
Authors: Cerini Francesco , Mattei Giacomo , Luiselli Luca , Vignoli Leonardo 
Published: March 2020

Abstract
We tested the ability in the ruin lizard (Podarcis siculus) to discriminate between odour of a predator (the whip snake Hierophis viridiflavus) and those from harmless sources. We analysed two lizard populations: one (PP) predated by snakes and another (PNP) where no snakes occur. We tested the rate of tongue flick directed to cotton-tips impregnated with odours, and the rate of tongue flick, the time spent in immobility, escaping and exploring the terrarium containing a diffuse odour. We used the smell of the snake as dangerous stimulus, water as blank control, and cologne as complex control. Both populations did not discriminate snake cue from complex odour in both the experiments. PP individuals were more active and prone to analysing and exploring the stimuli and the environment than PNP lizards. In PP, the higher interest towards cologne and snake scents could be triggered just by their complexity that requires more tongue flicks to be ‘analysed’, with no apparent adaptive anti-predatory value. Overall, we observed a total responsiveness and activity pattern higher in the PP respect to PNP.
The Philosophia ad Athenienses in the Light of Genuine Paracelsian Cosmology
Authors: Kahn Didier 
Published: March 2020

Abstract
The pseudo-Paracelsian Philosophia ad Athenienses (1564) draws upon many of the ideas of Paracelsus but combines them with many other elements not found in the genuine works of the Swiss physician. After discussing the details of its edition, we summarize its content, then examine its possible sources, including the authentic texts of Paracelsus by which the unknown author will have taken inspiration. We discuss specifically the question of uncreated prime matter and provide a number of criteria allowing us to consider the treatise as spurious. Finally, we argue that the unknown author wrote this text and ascribed it to Paracelsus in order to produce a more Platonist Paracelsian cosmology than that of the genuine treatises of Paracelsus, which apparently disappointed the unknown author in this regard.
Paracelsus, the Plague, and De Pestilitate
Authors: Gunnoe, Jr. Charles D. 
Published: March 2020

Abstract
While De Pestilitate is generally regarded as pseudepigraphic by modern scholarship, the treatise occupied a prominent place in Johann Huser’s definitive edition of Paracelsus’ Bücher und Schrifften (1589-1591). The text offers a compelling and generally reliable guide to Paracelsian plague theory with clear resemblances to the authentic Zwey Bücher von der Pestilentz und ihren zufällen and De Peste Libri tres. The text emphasizes the astrological transmission of the disease, describes a large role for divine retribution and demonological agency, and promotes the utility of folkloric cures. While the plague theory reflects Paracelsus’ own thought and is well synthesized with his tria prima chemical philosophy, there are sufficient dissonances between the text and the corpus of his accepted writings to maintain its pseudepigraphic status, even if it displays some indications of a reworking of genuine Paracelsica.
Fictional Dreams and Harsh Realities
Authors: Baas Renzo 
Published: March 2020

Abstract
This paper looks at the novels by Joseph Diescho (Born of the Sun, 1988), Kaleni Hiyalwa (Meekulu’s Children, 2000), and Neshani Andreas (The Purple Violet of Oshaantu, 2001) with a special focus on the access to education and land, but also problems such as Gender Based Violence and poverty. By comparing how an independent Namibia is imagined during South African apartheid rule, during the Liberation Struggle, and post-independence, the novels open up perspectives that empirical studies may overlook or decide not to emphasise. Furthermore, this comparison also allows for a linear, yet non-chronological, view on how the literary visions evolve with concepts such as nation and liberation, but also modernity and nationalism as they ‘enter’ into the characters’ every day. With the protagonists deeply involved in the make-up of their respective villages, they can also be considered prototypical Namibians in their value systems and networks. Through their eyes, it is possible to trace how political promises that were envisioned and imagined prior to 1990 are either realised or disappointed.
Development and Evaluation of an Evolutionary Programming-Based Tropical Cyclone Intensity Model
Authors: Schaffer Jesse D. , Roebber Paul J. , Evans Clark 
Published: March 2020

AbstractA statistical–dynamical tropical cyclone (TC) intensity model is developed from a large ensemble of algorithms through evolutionary programming (EP). EP mimics the evolutionary principles of genetic information, reproduction, and mutation to develop a population of algorithms with skillful predictor combinations. From this evolutionary process the 100 most skillful algorithms as determined by root-mean square error on validation data are kept and bias corrected. Bayesian model combination is used to assign weights to a subset of 10 skillful yet diverse algorithms from this list. The resulting algorithm combination produces a forecast superior in skill to that from any individual algorithm. Using these methods, two models are developed to give deterministic and probabilistic forecasts for TC intensity every 12 h out to 120 h: one each for the North Atlantic and eastern and central North Pacific basins. Deterministic performance, as defined by MAE, exceeds that of a “no skill” forecast in the North Atlantic to 96 h and is competitive with the operational Statistical Hurricane Intensity Prediction Scheme and Logistic Growth Equation Model at these times. In the eastern and central North Pacific, deterministic skill is comparable to the blended 5-day climatology and persistence (CLP5) track and decay-SHIFOR (DSHF) intensity forecast (OCD5) only to 24 h, after which time it is generally less skillful than OCD5 and all operational guidance. Probabilistic rapid intensification forecasts at the 25–30 kt (24 h)−1 thresholds, particularly in the Atlantic, are skillful relative to climatology and competitive with operational guidance when subjectively calibrated; however, probabilistic rapid weakening forecasts are not skillful relative to climatology at any threshold in either basin. Case studies are analyzed to give more insight into model behavior and performance.
Comparison of Leukocyte-Rich Platelet-Rich Plasma and Leukocyte-Poor Platelet-Rich Plasma on Achilles Tendinopathy at an Early Stage in a Rabbit Model
Authors: Jiang Guangyao , Wu Yifan , Meng Jiahong , Wu Fengfeng , Li Sihao , Lin Mu , Gao Xin , Hong Jianqiao , Chen Weishan , Yan Shigui , Yan Ruijian , Feng Gang , Cheng Zhiyuan 
Published: March 2020

Background:Tendinopathy is still a great challenge in clinical practice, and the role of platelet-rich plasma (PRP) is controversial. The influence of leukocytes on tendinopathy at an early stage has not been defined so far.Purpose:To compare the effects of leukocyte-rich PRP (Lr-PRP) and leukocyte-poor PRP (Lp-PRP) on Achilles tendinopathy when applied at an early stage.Study Design:Controlled laboratory study.Methods:A rabbit Achilles tendinopathy model was induced by a collagenase injection. A week later, treatments were applied randomly on local Achilles tendon lesions: (1) 200 μL of Lr-PRP (16 legs), (2) 200 μL of Lp-PRP (16 legs), and (3) 200 μL of saline (16 legs). At 3 and 6 weeks after the collagenase injection, outcomes were evaluated by histology, magnetic resonance imaging (MRI), real-time polymerase chain reaction analysis, immunohistochemistry, and transmission electron microscopy (TEM).Results:The Lr-PRP group had a lower T2 signal intensity ( P = .0377) and smaller diameter ( P = .0193) and cross-sectional area ( P = .0194) than the Lp-PRP group on MRI. Histologically, the Lr-PRP group had better scores than the Lp-PRP group ( P = .0284 and P = .0188, respectively). Compared with the Lp-PRP group, higher gene expression and more protein synthesis of collagen I ( P = .0160 and P = .0309, respectively) and CD163 ( P < .0001 and P = .0411, respectively) were found in the Lr-PRP group. Considering TEM and biomechanical testing, the Lr-PRP group demonstrated more mature collagen fibers ( P < .0001), a larger fiber diameter ( P = .0005), a higher failure load ( P = .00417), and higher tensile stress ( P < .0001) than the Lp-PRP group.Conclusion:Lr-PRP had more beneficial effects than Lp-PRP when delivered at an early stage during tendon repair.Clinical Relevance:Here, we showed that tendinopathy influenced the curative effects of PRP in vivo. An early-stage application of Lr-PRP had more benefits for the repair of tendinopathy than Lp-PRP in a rabbit model, which will supplement guidelines of PRP treatment on tendinopathy clinically.