bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Reform of the International Investment Regime: An African Perspective
Authors: El-Kady Hamed , De Gama Mustaqeem 
Published: September 2019

Abstract
The international legal framework for investment in Africa is complex, consisting of a large number of bilateral investment treaties (BITs) and regional investment agreements. This is in addition to a number of non-binding regional investment instruments and models that influence African countries' investment policy directions. Looking at the numbers, African countries have concluded over 860 BITs of which 160 are intra-African treaties. This represents around 28 percent of the BIT universe. For over 50 years African countries have been signing BITs that have core elements developed by third countries. Little attention has been given to the implications of these treaties on African countries’ right and duty to regulate investment in their territories. The result is a web of legally binding and broadly formulated commitments on investment protection. Today, African countries are taking a more active approach in the formulation of their international investment commitments at the national, bilateral and regional levels. Africa is becoming a laboratory for innovative and sustainable development-oriented investment policymaking. While these reform efforts occur in parallel and sometimes overlap with one another, they all converge in their attempt to formulate a new approach to investment policies that aims at safeguarding the right and duty of African countries to regulate and to reflect emerging sustainable development imperatives. The challenge remains in the existing stock of outdated African BITs and in the investor–State dispute system. Tribunals have broadly interpreted BIT commitments in ways that were not foreseen by African countries. The system that was originally developed to foster legal predictability in investment relations between countries has today become a source of legal uncertainty, debate and controversy. So far, African countries have been observing proposals and discussions for the reform of the ISDS system, including through the establishment of a Multilateral Investment Court (MIC) from a distance. They have been allowed to raise concerns, propose ideas and suggestions, but were not included in the original construction of the concepts and structures of any of the proposed solutions.
Improvements in patient safety culture: a national Taiwanese survey, 2009–16
Authors: Yu Brian , Wen Cheng-Fan , Lo Heng-Lien , Liao Hsun-Hsiang , Wang Pa-Chun 
Published: September 2019

Abstract

Objective
To assess national trends in patient safety culture in Taiwan.

Design
A safety attitudes questionnaire (SAQ) was distributed to 144 hospitals from 2009 to 2016 (n = 392 341).

Setting
Taiwan’s medical centers, regional hospitals and community hospitals.

Participants
Hospital staff in Taiwan.

Interventions
None.

Main Outcome Measures
5-point Likert scale to assess changes in patient safety culture dimensions (teamwork, safety climate, job satisfaction, stress recognition, management and working conditions) converted to positive response rate (percentage of respondents who answered slightly agree or strongly agree on Likert scale).

Results
Dimensions for patient safety culture significantly increased in Taiwan over a period of 8 years, with an all-composite improvement in positive response rate of 4.6% (P &lt; 0.001). Regional hospitals and community hospitals registered an all-composite improvement of 6.7 and 7.0%, respectively, while medical centers improved by 4.0%. Improvements for regional and community hospitals primarily occurred in teamwork (regional hospitals, 10.4% [95% confidence interval [CI], 10.2–10.6]; community hospitals, 8.5% [95% CI, 8.0–9.0]) and safety climate (regional hospitals, 11.1% [95% [CI], 10.9–11.4]; community hospitals, 11.3% [95% CI, 10.7–11.8]) (P &lt; 0.001, all differences). Compared with nurses (5.1%) and pharmaceutical staff (10.6%), physicians improved the least (2.0%). Improvements for nurses and pharmacists were driven by increases in perceptions of teamwork (nurses, 9.8% [95% CI, 9.7–10.0]; pharmaceutical staff, 14.2% [95% CI, 13.4–14.9]) and safety climate (nurses, 9.0% [95% CI, 8.8–9.1]; pharmaceutical staff, 16.4% [95% CI, 15.7–17.2]) (P &lt; 0.001, all differences). At study end, medical centers (55.1%) had greater all-composite measurements of safety culture than regional hospitals (52.4%) and community hospitals (52.2%) while physicians (63.7%) maintained greater measurements of safety culture than nurses (52.1%) and pharmaceutical staff (56.6%).

Conclusion
These results suggest patient safety culture improved in Taiwan from 2009 to 2016.
Improving the Lifetime Efficiency of Trimedlure-Dispensing System in Trapping the Fruit Fly Ceratitis capitata Using Polyethylene Matrix
Authors: Bayoumy Mohamed H , El-Metwally Mostafa M , El-Adly Refaat A , Majerus Tamsin M O 
Published: September 2019

AbstractDetection of the Mediterranean fruit fly, Ceratitis capitata (Wiedemann), is highly reliant on traps loaded with trimedlure (TML), a male-specific attractant. The successful application of attractants requires that constituents are placed in a suitable dispensing system to reduce volatilization and increase the effective field longevity of the attractant. A series of trials were conducted in different fruit orchards to test 1) the efficiency of a polyethylene-matrix plug in regulating the emission rate of TML 2) and the lifetime attractiveness of the plug compared to the cotton wick dispenser. Cotton dispensers containing the recommended dose of TML (0.75 cm3) and with a double dose (1.5 cm3) remained active for 6 and 8 wk, respectively. The increase in TML dose from 0.75 cm3 to 1.5 cm3 led to an increase in the longevity of the cotton dispenser, but there was no significant difference between the doses in biological activity. In all trials, TML-polyethylene matrix dispensers were more efficient under field conditions as they attracted more males for up to 12 wk and prolonged the release of TML more than the cotton wick dispensers. The TML-loaded polyethylene matrix dispensers might be useful in 1) minimizing the losses of the liquid TML from cotton wicks, 2) avoiding the damage that occurs when using other dispensers, 3) prolonging the TML lifetime in the field through regulating its release rates, 4) potentially minimizing the adverse effect of high temperatures on release rate, and, finally, 5) minimizing the costs of using large amounts of expensive TML solutions.
Extreme value theory in the solar wind: the role of current sheets
Authors: Gomes Tiago F P , Rempel Erico L , Ramos Fernando M , Silva Suzana S A , Muñoz Pablo R 
Published: September 2019

ABSTRACTThis article provides observational evidence for the direct relation between current sheets, multifractality and fully developed turbulence in the solar wind. In order to study the role of current sheets in extreme-value statistics in the solar wind, the use of magnetic volatility is proposed. The statistical fits of extreme events are based on the peaks-over-threshold (POT) modelling of Cluster 1 magnetic field data. The results reveal that current sheets are the main factor responsible for the behaviour of the tail of the magnetic volatility distributions. In the presence of current sheets, the distributions display a positive shape parameter, which means that the distribution is unbounded in the right tail. Thus the appearance of larger current sheets is to be expected and magnetic reconnection events are more likely to occur. The volatility analysis confirms that current sheets are responsible for the −5/3 Kolmogorov power spectra and the increase in multifractality and non-Gaussianity in solar wind statistics. In the absence of current sheets, the power spectra display a −3/2 Iroshnikov–Kraichnan law. The implications of these findings for the understanding of intermittent turbulence in the solar wind are discussed.
Stability in the most external region of the Oort Cloud: evolution of the ejected comets
Authors: Correa-Otto J A , Calandra M F 
Published: September 2019

ABSTRACTIn this paper, we present a study of the dynamical effects of the Galaxy on the external region of the Oort Cloud. The aims of this paper are: (i) to determine an outer limit for the Oort Cloud; and (ii) to analyse the dynamical behaviour of the most external objects of the Oort Cloud and how they are ejected from the Solar system. To achieve these aims, we follow the temporal evolution of massless test particles in the Galactic environment of the solar neighbourhood. We show that the effect of the perturbations from the Galactic tide in the particles is similar to that found for the evolution of the population of wide binary stars. Moreover, in the Oort Cloud, we find a dynamical structure around 105 au conformed by objects unbound from the Sun. This structure allows us to define a transition region of stability and an outer boundary for the Oort Cloud, and it is also in agreement with previous results about the disruption of wide binary stars.
Sox2+ cells in Sonic Hedgehog-subtype medulloblastoma resist p53-mediated cell-cycle arrest response and drive therapy-induced recurrence
Authors: Treisman Daniel M , Li Yinghua , Pierce Brianna R , Li Chaoyang , Chervenak Andrew P , Tomasek Gerald J , Lozano Guillermina , Zheng Xiaoyan , Kool Marcel , Zhu Yuan 
Published: September 2019

Abstract

Background
High-intensity therapy effectively treats most TP53 wild-type (TP53-WT) Sonic Hedgehog-subgroup medulloblastomas (SHH-MBs), but often cause long-term deleterious neurotoxicities in children. Recent clinical trials investigating reduction/de-escalation of therapy for TP53-WT SHH-MBs caused poor overall survival. Here, we investigated whether reduced levels of p53-pathway activation by low-intensity therapy potentially contribute to diminished therapeutic efficacy.

Methods
Using mouse SHH-MB models with different p53 activities, we investigated therapeutic efficacy by activating p53-mediated cell-cycle arrest versus p53-mediated apoptosis on radiation-induced recurrence.

Results
Upon radiation treatment, p53WT-mediated apoptosis was sufficient to eliminate all SHH-MB cells, including Sox2+ cells. The same treatment eliminated most Sox2− bulk tumor cells in SHH-MBs harboring p53R172P, an apoptosis-defective allele with cell-cycle arrest activity, via inducing robust neuronal differentiation. Rare quiescent Sox2+ cells survived radiation-enhanced p53R172P activation and entered a proliferative state, regenerating tumors. Transcriptomes of Sox2+ cells resembled quiescent Nestin-expressing progenitors in the developing cerebellum, expressing Olig2 known to suppress p53 and p21 expression. Importantly, high SOX2 expression is associated with poor survival of all four SHH-MB subgroups, independent of TP53 mutational status.

Conclusions
Quiescent Sox2+ cells are efficiently eliminated by p53-mediated apoptosis, but not cell-cycle arrest and differentiation. Their survival contributes to tumor recurrence due to insufficient p53-pathway activation.
Newborn Screening for Five Conditions in a Tertiary Care Government Hospital in Bengaluru, South India—Three Years Experience
Authors: Kommalur Anitha , Devadas Sahana , Kariyappa Mallesh , Sabapathy Sarala , Benakappa Asha , Gagandeep Vijayalaxmi , Veranna Sajjan Sushma , Krishnapura Lakshminarayana Shilpa , Dakshayani B , Devi Chinnappa Gayathri 
Published: September 2019

Abstract

Purpose
Newborn screening is the need of the hour in a developing country like India as there is paucity of data from studies conducted in government hospitals with large sample size. The purpose of the study is to estimate incidence rate and recall rates for five conditions screened in the neonatal period namely congenital hypothyroidism, congenital adrenal hyperplasia, glucose-6-phosphate dehydrogenase (G6PD) deficiency, galactosemia and phenyl ketonuria (PKU).

Methods
The study was conducted at VaniVilas Hospital attached to Bangalore Medical College and Research Institute. A retrospective analysis of the results of newborn screening programme during a 3-year period between January 2016 and December 2018 was done. There were 47 623 livebirths during this period out of which 41 027 babies were screened (coverage—86% of total livebirths). Heelprick samples after 48 h of life and prior to discharge were analysed by quantitative assessment. Neonates having positive screening results were recalled by telephonic call for repeat screening and confirmatory tests.

Results
G6PD deficiency was the most common disorder with an incidence of 1:414, followed by congenital hypothyroidism and Congenital Adrenal Hyperplasia with an incidence of 1:2735 and 1:4102, respectively. Galactosemia and PKU were found to be rare in our population. The overall average recall rate was 0.6% which meant that 24 normal newborns were recalled for testing for one confirmed case. The recall rate was relatively higher for galactosemia and G6PD deficiency which was at 0.25% each compared to the other conditions where it was below 0.05%.

Conclusion
The results of the study emphasize the need for universal newborn screening especially in all government hospitals with large birth cohorts.
Epigenomic prediction of cardiovascular disease risk and interactions with traditional risk metrics
Authors: Westerman Kenneth , Fernández-Sanlés Alba , Patil Prasad , Sebastiani Paola , Jacques Paul , Starr John M. , Deary Ian , Liu Qing , Liu Simin , Elosua Roberto , DeMeo Dawn L. , Ordovás José M. 
Published: September 2019

AbstractEpigenome-wide association studies for cardiometabolic risk factors have discovered multiple loci associated with incident cardiovascular disease (CVD). However, few studies have sought to directly optimize a predictor of CVD risk. Furthermore, it is challenging to train multivariate models across multiple studies in the presence of study- or batch effects. Here, we analyzed existing DNA methylation data collected using the Illumina HumanMethylation450 microarray to create a predictor of CVD risk across three cohorts: Women’s Health Initiative, Framingham Heart Study Offspring Cohort, and Lothian Birth Cohorts. We trained Cox proportional hazards-based elastic net regressions for incident CVD separately in each cohort, and used a recently-introduced cross-study learning approach to integrate these individual predictions into an ensemble predictor. The methylation-based risk score (MRS) predicted CVD time-to-event in a held-out fraction of the Framingham dataset (HR per SD = 1.28, p = 2e-3) and predicted myocardial infarction status in the independent REGICOR dataset (OR per SD = 2.14, p = 9e-7). These associations remained after adjustment for traditional cardiovascular risk factors and were similar to those from elastic net models trained on a directly merged dataset. Additionally, we investigated interactions between the MRS and both genetic and biochemical CVD risk, showing preliminary evidence of an enhanced predictive power in those with less traditional risk factor elevation. This investigation provides proof-of-concept for a genome-wide, CVD-specific epigenomic risk score and suggests that the DNA methylation data may enable the discovery of high-risk individuals that would be missed by alternative risk metrics.
“Multimorbidity and consultation time: a systematic review”
Authors: Reis Tadeu Ana Carolina , e Silva Caetano Inês Rosendo Carvalho , de Figueiredo Inês Jorge , Santiago Luiz Miguel 
Published: September 2019

ABSTRACTBackgroundMultimorbidity (MM) is one of the major challenges health systems currently face. Management of time length of a medical consultation with a patient with MM is a matter of concern for doctors.ObjectivesTo describe the impact of MM on the average time of a medical consultation.MethodsA systematic review was performed considering the Preferred Reporting Items for Systematic Review and Meta-analyses (PRISMA) guidelines. The systematic online searches of the Embase and PubMed databases were undertaken, from January 2000 to August 2018. The studies were independently screened by two reviewers to decide which ones met the inclusion criteria. (Kappa=0.84 and Kappa=0.82). Differing opinions were solved by a third person. This systematic review included people with MM criteria as participants (two or more chronic conditions in the same individual). The type of outcome included was explicitly defined – the length of medical appointments with patients with MM. Any strategies aiming to analyse the impact of MM on the average consultation time were considered. The length of time of medical appointment for patients without MM was the comparator criteria. Experimental and observational studies were included.ResultsOf 85 articles identified, only 1 observational study was included, showing a clear trend for patients with MM to have longer consultations than patients without MM criteria (p<0.001).ConclusionsMore studies are necessary to assess better allocation length-time for patients with MM and to measure other characteristics like doctors workload.
Weight loss reduces head motion: re-visiting a major confound in neuroimaging
Authors: Beyer F. , Prehn K. , Wüsten KA , Villringer A. , Ordemann J. , Flöel A. , Witte AV 
Published: September 2019

AbstractHead motion during magnetic resonance imaging (MRI) induces image artifacts that affect virtually every brain measure. In parallel, cross-sectional observations indicate a correlation of head motion with age, psychiatric disease status and obesity, raising the possibility of a systematic artifact-induced bias in neuroimaging outcomes in these conditions, due to the differences in head motion. Yet, a causal link between obesity and head motion has not been tested in an experimental design. Here, we show that a change in body mass index (i.e., weight loss after bariatric surgery) systematically decreases head motion during MRI. In this setting, reduced imaging artifacts due to lower head motion might result in biased estimates of neural differences induced by changes in BMI. Overall, our finding urges the need to rigorously control for within-scanner head motion to enable valid results of neuroimaging outcomes in populations that differ in head motion due to obesity or other conditions.
TRANSCUP: a scalable workflow for predicting cancer of unknown primary based on next-generation transcriptome profiling
Authors: Li Peng 
Published: September 2019

AbstractSummaryCancer of unknown primary site (CUP) accounts for 5% of all cancer diagnoses. These patients may benefit from more precise treatment when primary cancer site was identified. Advances in high-throughput sequencing have enabled cost-effective sequencing the transcriptome for clinical application. Here, we present a free, scalable and extendable software for CUP predication called TRANSCUP, which enables (1) raw data processing, (2) read mapping, (3) quality re-port, (4) gene expression quantification, (5) random forest machine learning model building for cancer type classification. TRANSCUP achieved high accuracy, sensitivity and specificity for tumor type classification based on external RNA-seq datasets. It has potential for broad clinical application for solving the CUP problem.AvailabilityTRANSCUP is open-source and freely available at https://github.com/plsysu/TRANSCUPContactpeng-li@outlook.com
How the forest interacts with the trees: Multiscale shape integration explains global and local processing
Authors: Jacob Georgin , Arun S. P. 
Published: September 2019

ABSTRACTHierarchical stimuli (such as a circle made of diamonds) have been widely used to study global and local processing. Two classic phenomena have been observed using these stimuli: the global advantage effect (that we identify the circle faster than the diamonds) and the incongruence effect (that we identify the circle faster when both global and local shapes are circles). Understanding them has been difficult because they occur during shape detection, where an unknown categorical judgement is made on an unknown feature representation.Here we report two essential findings. First, these phenomena are present both in a general same-different task and a visual search task, suggesting that they may be intrinsic properties of the underlying representation. Second, in both tasks, responses were explained using linear models that combined multiscale shape differences and shape distinctiveness. Thus, global and local processing can be understood as properties of a systematic underlying feature representation.
A multifaceted cellular damage repair and prevention pathway promotes high level tolerance to β-lactam antibiotics
Authors: Shin Jung-Ho , Choe Donghui , Ransegnola Brett , Hong Hye-Rim , Onyekwere Ikenna , Cross Trevor , Shi Qiaojuan , Cho Byung-Kwan , Westblade Lars F. , Brito Ilana L. , Dörr Tobias 
Published: September 2019

AbstractBactericidal antibiotics are powerful agents due to their ability to convert essential bacterial functions into lethal processes. However, many important bacterial pathogens are remarkably tolerant against bactericidal antibiotics due to inducible damage repair responses. The cell wall damage response two-component system VxrAB of the gastrointestinal pathogen Vibrio cholerae promotes high-level β-lactam tolerance and controls a gene network encoding highly diverse functions, including negative control over multiple iron uptake systems. How this system contributes to tolerance is poorly understood. Here, we show that β-lactam antibiotics cause an increase in intracellular free iron levels and collateral oxidative damage, which is exacerbated in the ΔvxrAB mutant. Mutating major iron uptake systems drastically increased ΔvxrAB tolerance to β-lactams. We propose that VxrAB reduces antibiotic-induced toxic iron and concomitant metabolic perturbations by downregulating iron uptake transporters and show that iron sequestration enhances tolerance against β-lactam therapy in a mouse model of cholera infection. Our results suggest that a microorganism’s ability to counteract diverse antibiotic-induced stresses promotes high-level antibiotic tolerance, and highlights the complex secondary responses elicited by antibiotics.
The genomic landscape of metastasis in treatment-naïve breast cancer models
Authors: Ross Christina , Szczepanek Karol , Lee Maxwell , Yang Howard , Qiu Tinghu , Sanford Jack , Hunter Kent 
Published: September 2019

AbstractMetastasis remains the principle cause of mortality for breast cancer and presents a critical challenge because secondary lesions are often refractory to conventional treatments. While specific genetic alterations are tightly linked to primary tumour development and progression, the role of genetic alteration in the metastatic process is not well-understood. To investigate how somatic evolution might contribute to breast cancer metastasis, we performed exome, whole genome, and RNA sequencing of matched metastatic and primary tumours from pre-clinical mouse models of breast cancer. Here we show that in a treatment-naïve setting, recurrent single nucleotide variants and copy number variation, but not gene fusion events, play key metastasis-driving roles in breast cancer. For instance, we identified recurrent mutations inKras, a known driver of tumorigenesis that has not been previously implicated in breast cancer metastasis. The strategy presented here represents a novel framework to identify actionable metastasis-targeted therapies.