bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exploring global and country-level barriers to an effective supply of leishmaniasis medicines and diagnostics in eastern Africa: a qualitative study
Authors: Sunyoto Temmy , Potet Julien , den Boer Margriet , Ritmeijer Koert , Postigo Jose A R , Ravinetto Raffaella , Alves Fabiana , Picado Albert , Boelaert Marleen 
Published: May 2019

ObjectivesTo understand stakeholders’ perceptions of the access barriers to quality-assured diagnostics and medicines for leishmaniasis in the high-burden region of eastern Africa, and to identify key bottlenecks to improve the supply of commodities for neglected tropical diseases.DesignDesk reviews and qualitative in-depth interview study with purposive sampling.MethodsA landscape analysis through literature and desk review was performed. Next, 29 representatives from international organisations, non-governmental agencies, national control programmes from six countries (Ethiopia, Kenya, Somalia, South Sudan, Sudan and Uganda) and manufacturers were interviewed between May and July 2018. Participants were selected purposively and expanded through a snowballing technique.Data analysis was aided by NVivo, applying the framework method as a part of the thematic content analysis approach.ResultsThe barriers along the visceral leishmaniasis (VL) supply chain were identified as emerging themes, grouped across supply chain activities and health systems component(s). Stakeholders expressed the perception of progress, but bottlenecks persist. VL medicines, in general, lack multisource production capacity and with small market volume, expansion of suppliers is difficult. Procurement is plagued by forecasting difficulties, complex regulatory policies and procedures, and distribution challenges. Weak communication and coordination across different levels resulted in shortages and loss of trust among different actors. Cross-cutting issues spanned from limited political and resource commitment due to low awareness and limited in-country capacity. However, study respondents were optimistic to pursue several remedies, most importantly to build bridges between supply and demand sides through continued dialogue and collaborations. Diagnostics supply has mostly been overlooked; thus, improved investment in this area is needed.ConclusionsAddressing supply barriers in eastern Africa requires consistent, specific efforts at the global and national levels, progressing from current partnerships and agreements. Priority actions include pooled procurement, improved forecast, and increased commitment and resources. Sustainability remains an elusive goal, yet to be integrated into discussions moving forward.
New alumni EXperiences of Training and independent Unsupervised Practice (NEXT-UP): protocol for a cross-sectional study of early career general practitioners
Authors: Magin Parker , Moad Dominica , Tapley Amanda , Holliday L , Davey Andrew , Spike Neil , FitzGerald Kristen , Kirby Catherine , Bentley Michael , Turnock Allison , van Driel Mieke L , Fielding Alison 
Published: May 2019

IntroductionGeneral practice in Australia, as in many countries, faces challenges in the areas of workforce capacity and workforce distribution. General practice vocational training in Australia not only addresses the training of competent independent general practitioners (GPs) but also addresses these workforce issues. This study aims to establish the prevalence and associations of early career (within 2 years of completion of vocational training) GPs’ practice characteristics; and also to establish their perceptions of utility of their training in preparing them for independent practice.Methods and analysisThis will be a cross-sectional questionnaire study. Participants will be former registrars (‘alumni’) of three regional training organisations (RTOs) who achieved general practice Fellowship (qualifying them for independent practice) between January 2016 and July 2018 inclusive. The questionnaire data will be linked to data collected as part of the participants’ educational programme with the RTOs. Outcomes will include alumni rurality of practice; socioeconomic status of practice; retention within their RTO’s geographic footprint; workload; provision of nursing home care, after-hours care and home visits; and involvement in general practice teaching and supervision. Associations of these outcomes will be established with logistic regression. The utility of RTO-provided training versus in-practice training in preparing the early career GP for unsupervised post-Ffellowship practice in particular aspects of practice will be assessed with χ2tests.Ethics and disseminationEthics approval is by the University of Newcastle Human Research Ethics Committee, approval numbers H-2018-0333 and H-2009-0323. The findings of this study will be widely disseminated via conference presentations and publication in peer-reviewed journals, educational practice translational workshops and the GP Synergy Research subwebsite.
Small head circumference at birth: an 8-year retrospective cohort study in China
Authors: Liu Shiliang , Pan Yanmei , Auger Nathalie , Sun Wen , Dai Lijuan , Li Sihui , Xie Sushan , Wen Shi Wu , Chen Dunjin 
Published: May 2019

ObjectiveHead circumference is considered a reliable assessment of the volume of the underlying brain. We sought to identify risk factors (maternal factors or antenatal antecedents) for microcephaly and to assess the effects of microcephaly on neonatal outcomes.DesignRetrospective cohort study.SettingData for all births in 2009-2017 were obtained from the Guangzhou Maternal-Fetal Care Database.ParticipantsAll singleton liveborn infants between 33 and 42 weeks’ gestation (n=45 663) were categorised using the Intergrowth-21st standard for microcephaly.Main outcome measuresPrevalence of mild, absolute and relative microcephaly at birth. We estimated associations of (1) maternal characteristics including Cantonese origin, parity, exposure to teratogens, TORCH infections (ie,Toxoplasmagondii, rubella virus, cytomegalovirus, herpes simplex virus), in vitro fertilisation conception, pre-eclampsia and maternal congenital anomalies with risk of each category of microcephaly, and (2) microcephaly with risk of in-hospital mortality and severe morbidity.ResultsA total of 2709 infants had a head circumference z-score >2 SD, resulting in an overall prevalence of microcephaly of 59.3 per 1000 infants, consisting of mild (54.1 per 1000), absolute (2.8 per 1000) and relative microcephaly (2.4 per 1000). In multiple logistic regression, absolute microcephaly was associated with in utero exposure to teratogens (OR 4.2, 95% CI 2.0 to 8.8) and TORCH agents (OR 3.2, 95% CI 1.1 to 9.5). Mild microcephaly was associated with Cantonese descent (OR) 1.5, 95% CI 1.3 to 1.7) and primiparity (OR 1.7, 95% CI 1.5 to 2.0). Absolute microcephaly was associated with a significantly higher odds of neonatal seizure (OR 8.7, 95% CI 1.1 to 69.1). Mild microcephaly was not associated with adverse neonatal outcomes overall.ConclusionsCantonese origin, exposure to teratogens, pre-eclampsia and TORCH infection may be risk factors for microcephaly. The high prevalence of relative microcephaly and associated poor outcomes suggests that high-risk women merit closer clinical management and follow-up to maximise fetal head development during pregnancy.
Cross-country comparison of cigarette and vaping product marketing exposure and use: findings from 2016 ITC Four Country Smoking and Vaping Survey
Authors: Cho Yoo Jin , Thrasher James , Cummings Michael , Yong Hua H , Hitchman Sara C , McNeill Ann , Fong Geoffrey T , Hammond David , Hardin James , Li Lin , Lindblom Eric N 
Published: May 2019

ObjectiveTo compare exposure to and use of certain cigarette and vaping product marketing among adult smokers and vapers in four countries with contrasting regulations—Australia (AU), Canada, England and the USA.Data sourcesAdult smokers and vapers (n=12 294) from the 2016 International Tobacco Control (ITC) Four Country Smoking and Vaping Survey (4CV1).AnalysisSelf-reported exposure to cigarette and vaping product advertising through point-of-sale, websites/social media, emails/texts, as well as exposure to and use of price offers were assessed for country differences using logistic regression models adjusted for multiple covariates.ResultsReported exposure to cigarette advertising exposure at point-of-sale was higher in the USA (52.1%) than in AU, Canada and England (10.5%–18.5%). Exposure to cigarette advertising on websites/social media and emails/texts was low overall (1.5%–10.4%). Reported exposure to vaping ads at point-of-sale was higher in England (49.3%) and USA (45.9%) than in Canada (32.5%), but vaping ad exposure on websites/social media in Canada (15.1%) was similar with England (18.4%) and the USA (12.1%). Exposure to vaping ads via emails/texts was low overall (3.1%–9.9%). Exposure to, and use of, cigarette price offers was highest in the USA (34.0 % and 17.8 %, respectively), but the use rate among those exposed was highest in AU (64.9%). Exposure to, and use of, price offers for vaping products was higher in the USA (42.3 % and 21.7 %) than in AU, Canada and England (25.9%–31.5 % and 7.4%–10.3 %).ConclusionsPatterns of cigarette and vaping product marketing exposure generally reflected country-specific policies, except for online vaping ads. Implications for research and policy are discussed.
A potential degradation mechanism in RF MEMS ohmic switches
Authors: Huang Qinwen , Dong Xianshan , Zhu Junhua , Yang Shaohua , Wang Yunhui 
Published: May 2019

A study of electrical breakdown across bias and top electrodes and its effect on the reliability of RF MEMS ohmic switches is presented. Tests under two situations were applied to study the electrical breakdown characteristic between bias and top electrodes, the first is the 10 h continuous stress under on state and the second is the voltage sweep from 0 V to 80 V. During the test, the switch ohmic contact resistance and current across bias and top electrodes were monitored simultaneously. Current across bias and top electrodes is observed in both of the two situations. Further analysis by FIB and SEM shows the breakdown damage on the surface of the bias electrode, which leads to the pull-in voltage shift of the RF MEMS ohmic switches.
Mini-dental implants for definitive prosthesis retention — A synopsis of the current evidence
Authors: Wang Ben , Ho Kok Sen , Neo Tee Khin , Cheng Ansgar C. 
Published: May 2019

Background: This narrative review provides an evidence-based overview of the comparison between mini-dental implants (MDI) and conventional dental implants for definitive prosthesis retention. In addition, recommendations are made on whether the use of reduced diameter dental implants is more appropriate.Method: A literature review was conducted via electronic search addressing the following topics: (1) osseointegration, (2) peri-implant soft tissue characteristics, (3) biomechanics, (4) implant survival and (5) implant success.Conclusion: The procedure for dental implant prosthetic rehabilitation should preferentially include conventional dental implants (i.e. [Formula: see text][Formula: see text]mm fixture diameter). Small (3–3.25[Formula: see text]mm) and narrow (3.3–3.5[Formula: see text]mm) dental implants should primarily be used in non-load-bearing regions. MDI ([Formula: see text][Formula: see text]mm) should be considered to retain definitive prosthesis, only for reasons of anatomy or patient-centred preferences and as a last resort. If MDI are to be used, patients should be made aware of the lack of long-term, high-quality evidence as a part of the informed consent process and that most of the prospective data available pertain to MDI retaining complete dentures.
CRONOS
Authors: Shaabana Ala , Zheng Rong 
Published: May 2019

Data synchronization is crucial in ubiquitous computing systems, where heterogeneous sensor devices, modalities, and different communication capabilities and protocols are the norm. A common notion of time among devices is required to make sense of their sensing data. Traditional synchronization methods rely on wireless communication between devices to synchronize, potentially incurring computational and power costs. Furthermore, they are unsuitable for synchronizing data streams that have already been collected. We present CRONOS: a post-hoc, data-driven framework for sensor data synchronization for wearable and Internet-of-Things devices that takes advantage of independent, omni-present motion events in the data streams of two or more sensors. Experimental results on pairwise and multi-sensor synchronization show a drift improvement as high as 98% and a mean absolute synchronization error of approximately 6ms for multi-sensor synchronization with sensors sampling at 100Hz.
Exploiting Concurrency for Opportunistic Forwarding in Duty-Cycled IoT Networks
Authors: Liu Daibo , Cao Zhichao , He Yuan , Ji Xiaoyu , Hou Mengshu , Jiang Hongbo 
Published: May 2019

Due to limited energy supply of Internet of Things (Zhao et al. 2018) (IoT) devices, asynchronous duty cycle radio management is widely adopted to save energy. Since the sleep schedules of nodes are unsynchronized, a sender has to repeatedly send frames to coordinate with its receiver or keep sleeping until the receiver’s wake-up time will come according to receiver’s sleep-wake schedule. In such contexts, opportunistic forwarding, which takes the earliest forwarding opportunity instead of a deterministic forwarder, shows great advantage in utilizing channel resource for duty-cycled IoT networks. The multiple forwarding choices with temporal and spatial diversity increase the chance of collision tolerance in opportunistic forwarding, potentially enhancing the overall performance of duty-cycled multi-hop networks. However, since the current channel contention mechanisms mainly focus on collision avoidance, it is too conservative to exploit concurrency.
To address this problem, in this article, we propose COF to fully exploit the potential Concurrency for Opportunistic Forwarding in duty-cycled IoT networks. COF achieves concurrent transmission by: (i) measuring conditional link quality under the interference of on-going transmissions, and then (ii) further modeling the benefit of potential concurrency opportunities. According to the expected benefit of concurrency, COF decides whether or not to transmit in concurrent way. COF also adopts concurrency flag and signal features to avoid data collision caused by disordered concurrent transmissions and enhance the accuracy of conditional link quality estimation. COF can be easily integrated into the conventional unsynchronized and duty-cycled protocols. We have implemented COF and evaluated its performance on a 40-node testbed. The results show that COF can effectively exploit potential concurrency in opportunistic forwarding and COF outperforms the state-of-art protocols under diverse traffic load and network density.
Estrogen determines sex differences in adrenergic vessel tone by regulation of endothelial β-adrenoceptor expression
Authors: Riedel Kristin , Deussen Andreas Johannes , Tolkmitt Josephine , Weber Silvio , Schlinkert Pia , Zatschler Birgit , Friebel Carmen , Müller Bianca , El-Armouche Ali , Morawietz Henning , Matschke Klaus , Kopaliani Irakli 
Published: May 2019

Vessels of female rats constrict less and relax more to adrenergic stimulation than vessels of males. Although we have reported that these sex-specific differences rely on endothelial β-adrenoceptors, the role of sex hormones in β-adrenoceptor expression and related vessel tone regulation is unknown. We investigated the role of estrogen, progesterone and testosterone on β-adrenoceptor expression and adrenergic vessel tone regulation, along with sex-specific differences in human mammary arteries. The sex-specific differences in vasoconstriction and vasorelaxation in rat vessels were eliminated after ovariectomy in females. Ovariectomy increased vessel vasoconstriction to norepinephrine more than twofold. Vasorelaxations by isoprenaline and a β3-agonist were reduced after ovariectomy. Estrogen, but not progesterone substitution, restored sex-specific differences in vasoconstriction and vasorelaxation. Vascular mRNA levels of β1- and β3- but not β2-adrenoreceptors were higher in vessels of females compared with males. Ovariectomy reduced these differences by decreasing β1- and β3- but not β2-adrenoreceptor expression in females. Consistently, estrogen substitution restored β1- and β3-adrenoreceptor expression. Orchiectomy or testosterone treatment affected neither vasoconstriction and vasorelaxation nor β-adrenoceptor expression in vessels of male rats. In human mammary arteries, sex-specific differences in vasoconstriction and vasorelaxation were reduced after removal of endothelium or treatment with l-NMMA. Vessels of women showed higher levels of β1- and β3-adrenoceptors than in men. In conclusion, the sex-specific differences in vasoconstriction and vasorelaxation are common for rat and human vessels. In rats, these differences are estrogen but not testosterone or progesterone dependent. Estrogen determines these differences via regulation of vascular endothelial β1- and β3-adrenoreceptor expression. NEW & NOTEWORTHY This study proposes a mechanistic concept regulating sex-specific differences in adrenergic vasoconstriction and vasorelaxation. Estrogen increases vascular β1- and β3-adrenoceptor expression in female rats. This and our previous studies demonstrate that these receptors are located primarily on endothelium and when activated by norepinephrine act via nitric oxide (NO). Therefore, β-adrenergic stimulation leads to a more pronounced vasorelaxation in females. Coactivation of endothelial β1- and β3-adrenoreceptors leads to higher NO release in vessels of females, ultimately blunting vasoconstriction triggered by activation of smooth muscle α-adrenoceptors.
Elevated bone marrow sympathetic drive precedes systemic inflammation in angiotensin II hypertension
Authors: Ahmari Niousha , Santisteban Monica M. , Miller Douglas R. , Geis Natalie M. , Larkin Riley , Redler Ty , Denson Heather , Khoshbouei Habibeh , Baekey David M. , Raizada Mohan K. , Zubcevic Jasenka 
Published: May 2019

Increased sympathetic nervous system activity is a hallmark of hypertension (HTN), and it is implicated in altered immune system responses in its pathophysiology. However, the precise mechanisms of neural-immune interaction in HTN remain elusive. We have previously shown an association between elevated sympathetic drive to the bone marrow (BM) and activated BM immune cells in rodent models of HTN. Moreover, microglial-dependent neuroinflammation is also seen in rodent models of HTN. However, the cause-effect relationship between central and systemic inflammatory responses and the sympathetic drive remains unknown. These observations led us to hypothesize that increase in the femoral BM sympathetic nerve activity (fSNA) initiates a cascade of events leading to increase in blood pressure (BP). Here, we investigated the temporal relationship between the BM sympathetic drive, activation of the central and peripheral immune system, and increase in BP in the events leading to established HTN. The present study demonstrates that central infusion of angiotensin II (ANG II) induces early microglial activation in the paraventricular nucleus of hypothalamus, which preceded increase in the fSNA. In turn, activation of fSNA correlated with the timing of increased production and release of CD4+.IL17+T cells and other proinflammatory cells into circulation and elevation in BP, whereas infiltration of CD4+cells to the paraventricular nucleus marked establishment of ANG II HTN. This study identifies cellular and molecular mechanisms involved in neural-immune interactions in early and established stages of rodent ANG II HTN.NEW & NOTEWORTHY Early microglia activation in paraventricular nucleus precedes sympathetic activation of the bone marrow. This leads to increased bone marrow immune cells and their release into circulation and an increase in blood pressure. Infiltration of CD4+ T cells into paraventricular nucleus paraventricular nucleus marks late hypertension.
Urinary Metabolomics to Identify a Unique Biomarker Panel for Detecting Colorectal Cancer: A Multicenter Study
Authors: Deng Lu , Ismond Kathleen , Liu Zhengjun , Constable Jeremy , Wang Haili , Alatise Olusegun I. , Weiser Martin R. , Kingham T.P. , Chang David 
Published: May 2019

Abstract

Background:
Population-based screening programs are credited with earlier colorectal cancer diagnoses and treatment initiation, which reduce mortality rates and improve patient health outcomes. However, recommended screening methods are unsatisfactory as they are invasive, are resource intensive, suffer from low uptake, or have poor diagnostic performance. Our goal was to identify a urine metabolomic-based biomarker panel for the detection of colorectal cancer that has the potential for global population-based screening.

Methods:
Prospective urine samples were collected from study participants. Based upon colonoscopy and histopathology results, 342 participants (colorectal cancer, 171; healthy controls, 171) from two study sites (Canada, United States) were included in the analyses. Targeted liquid chromatography-mass spectrometry (LC-MS) was performed to quantify 140 highly valuable metabolites in each urine sample. Potential biomarkers for colorectal cancer were identified by comparing the metabolomic profiles from colorectal cancer versus controls. Multiple models were constructed leading to a good separation of colorectal cancer from controls.

Results:
A panel of 17 metabolites was identified as possible biomarkers for colorectal cancer. Using only two of the selected metabolites, namely diacetylspermine and kynurenine, a predictor for detecting colorectal cancer was developed with an AUC of 0.864, a specificity of 80.0%, and a sensitivity of 80.0%.

Conclusions:
We present a potentially “universal” metabolomic biomarker panel for colorectal cancer independent of cohort clinical features based on a North American population. Further research is needed to confirm the utility of the profile in a prospective, population-based colorectal cancer screening trial.

Impact:
A urinary metabolomic biomarker panel was identified for colorectal cancer with the potential of clinical application.
HPV Epitope Processing Differences Correlate with ERAP1 Allotype and Extent of CD8+ T-cell Tumor Infiltration in OPSCC
Authors: Reeves Emma , Wood Oliver , Ottensmeier Christian H. , King Emma V. , Thomas Gareth J. , Elliott Tim , James Edward 
Published: May 2019

AbstractPresence of tumor-infiltrating lymphocytes (TIL) predicts survival in many cancer types. In HPV-driven cancers, cervical and oropharyngeal squamous cell carcinomas (CSCC and OPSCC, respectively), numbers of infiltrating T cells, particularly CD8+ T cells, and presentation of HPV E6/E7 epitopes are associated with improved prognosis. Endoplasmic reticulum aminopeptidase 1 (ERAP1) regulates the presented peptide repertoire, trimming peptide precursors prior to MHC I loading. ERAP1 is polymorphic, and allotypic variation of ERAP1 enzyme activity has an impact on the presented peptide repertoire. Individual SNPs are associated with incidence and outcome in a number of diseases, including CSCC. Here, we highlight the requirement for ERAP1 in the generation of HPV E6/E7 epitopes and show that the functional activity of ERAP1 allotype combinations identified in OPSCC correlate with tumor-infiltrating CD8+ T-cell (CD8)/TIL (CD8/TIL) status of the tumor. Functional analyses revealed that ERAP1 allotype combinations associated with CD8/TILlow tumors have a reduced capacity to generate both a model antigen SIINFEHL and the HPV-16 E782-90 epitope LLMGTLGIV from N-terminally extended precursor peptides. In contrast, ERAP1 allotypes from CD8/TILhigh tumors generated the epitopes efficiently. These data reveal that ERAP1 function correlates with CD8/TIL numbers and, by implication, prognosis, suggesting that the presentation of HPV-16 epitopes at the cell surface, resulting in an anti-HPV T-cell response, may depend on the ERAP1 allotype combinations expressed within an individual.