Miracle-dz/UniFAR-FTUs huggingface dataset:
CCR5 Antagonists: Host-Targeted Antivirals for the Treatment of HIV Infection

The human chemokine receptors, CCR5 and CXCR4, are potential host targets for exogenous, small-molecule antagonists for the inhibition of HIV-1 infection. HIV-1 strains can be categorised by co-receptor tropism — their ability to utilise CCR5 (CCR5-tropic), CXCR4 (CXCR4-tropic) or both (dual-tropic) as a co-receptor for entry into susceptible cells. CCR5 may be the more suitable co-receptor target for small-molecule antagonists because a natural deletion in the CCR5 gene preventing its expression on the cell surface is not associated with any obvious phenotype, but can confer resistance to infection by CCR5-tropic strains — the most frequently sexually-transmitted strains. The current leading CCR5 antagonists in clinical development include maraviroc (UK-427,857, Pfizer), aplaviroc (873140, GlaxoSmithKline) and vicriviroc (SCH-D, Schering-Plough), which have demonstrated efficacy and tolerability in HIV-infected patients. Pharmacodynamic data also suggest that these compounds have a long plasma half-life and/or prolonged CCR5 occupancy, which may explain the delay in viral rebound observed following compound withdrawal in short-term monotherapy studies. A switch from CCR5 to CXCR4 tropism occurs spontaneously in approximately 50% of HIV-infected patients and has been associated with, but is not required for, disease progression. The possibility of a co-receptor tropism switch occurring under selection pressure by CCR5 antagonists is discussed. The completion of ongoing Phase IIb/III studies of maraviroc, aplaviroc and vicriviroc will provide further insight into co-receptor tropism, HIV pathogenesis and the suitability of CCR5 antagonists as a potent new class of antivirals for the treatment of HIV infection.
Econometric analysis of the real exchange rate, energy consumption and instrumental variables

The present thesis consists of four chapters: the introduction (Chapter 1), and three econometrics-based research papers (Chapters 2 through 4). The introduction sets out the research questions explored in the subsequent chapters and previews the results. Chapter 2 uses Monte Carlo studies to investigate a pre-test bias problem potentially associated with using Stock and Yogo’s (2005) critical values to determine whether the instrumental variables in the model are strong or weak. A solution is proposed based on Angrist and Krueger’s (1995) Split-Sample IV estimator. Chapter 3 tests the Balassa-Samuelson hypothesis using a new dataset, and with a focus on oil-producing countries. A relationship between oil rents, which represent productivity measure in the tradable sector of oil exporters, and the real exchange rates are examined using unique data constructed from Wood Mackenzie’s Global Economic Model. The results provide evidence in favour of the Balassa-Samuelson effect in most countries in the sample, apart from OPEC countries. Chapter 4 investigates the long-run relationship between GDP per capita, energy consumption and energy prices in a set of 28 OECD countries using newer econometric techniques than have been prevalent in the prior literature. The results of the analysis suggest that the long-run bi-directional relationship exists, but is likely to be heterogeneous across countries. Also, the bi-directionality is not symmetric: energy consumption was found to be more strongly affected by economic growth than vice versa. In a narrative sense, the three research papers reflect the progression of my interests over the past several years: from a work focused on econometric theory (‘how should we do IV pre-testing? ’), to a work of applied econometrics testing a piece of economic theory (‘does the Balassa-Samuelson hypothesis account for real exchange rate movements in oil exporters? ’), and finally to a work of applied econometrics which is oriented more towards answering policy-relevant questions (‘if we cut our energy usage to meet climate targets, will we choke off economic growth? ’).
Exaggerated activation of dorsal anterior cingulate cortex during cognitive interference: a monozygotic twin study of posttraumatic stress disorder.

OBJECTIVE Neuroimaging studies have revealed functional abnormalities in the anterior cingulate cortex in posttraumatic stress disorder (PTSD). The goal of this study was to determine whether hyperresponsivity of the dorsal anterior cingulate in PTSD is an acquired characteristic or a familial risk factor. METHOD Using a case-control twin design, the authors studied combat-exposed veterans with PTSD (N=12) and their identical combat-unexposed co-twins (N=12), as well as combat-exposed veterans without PTSD (N=14) and their identical combat-unexposed co-twins (N=14). Participants underwent functional MRI during completion of the Multi-Source Interference Task, which reliably activates the dorsal anterior cingulate. RESULTS Combat-exposed veterans with PTSD and their unexposed co-twins had significantly greater activation in the dorsal anterior cingulate and tended to have larger response time difference scores, as compared to combat-exposed veterans without PTSD and their co-twins. Dorsal anterior cingulate activation in the exposed twins was positively correlated with their PTSD symptom severity. Dorsal anterior cingulate activation in the unexposed twins was positively correlated with their combat-exposed co-twins' PTSD symptom severity, but not with depression or alcohol use severity in the combat-exposed co-twins. CONCLUSIONS Hyperresponsivity in the dorsal anterior cingulate appears to be a familial risk factor for the development of PTSD following psychological trauma.
Assessment of the Implementation of Trade/Entrepreneurship Curricula in Senior Secondary Schools as a Veritable Tool towards Youth Empowerment in Kano State, Nigeria

This descriptive study assessed the implementation of Trade/Entrepreneurship curricula in senior secondary schools in Kano State, Nigeria with the aim of assessing the extent to which such implementation empowered students for self-employment. The objectives of the study were to assess the entrepreneurship skills that students had acquired and identify the products they had successfully produced for sale in Kano State. The population of the study was the entire senior secondary school three (SS3) students offering Trade/Entrepreneurship in Kano State, which are 43,154. A sample of 380 students was selected using simple one-way cluster sampling techniques. The data was collected using a questionnaire entitled Questionnaire for Assessment of the Implementation of Trade/Entrepreneurship Curriculums in Senior Secondary Schools (QAITECSSS). The descriptive statistics of arithmetic mean, standard deviation, and bar chart were used to answer the research questions; while for inferential analysis, chi square was used to test the research hypotheses at 0.05 level of significance. Findings revealed that students had learnt significant skills and knowledge in all of the four trade/ entrepreneurship subjects offered to them in Kano State. In addition, the quantity of products students produced for sale was identified as limited/small. This study recommends, among other things, that the government should provide enough practical facilities to boost students’ production for sale.
Estimation of the flexibility range in the transmission-distribution boundary

The smart grid concept increases the observability and controllability of the distribution system, which creates conditions for bi-directional control of Distributed Energy Resources (DER). The high penetration of Renewable Energy Resources (RES) in the distribution grid may create technical problems (e.g., voltage problems, branch congestion) in both transmission and distribution systems. The flexibility from DER can be explored to minimize RES curtailment and increase its hosting capacity. This paper explores the use of the Monte Carlo Simulation to estimate the flexibility range of active and reactive power at the boundary nodes between transmission and distribution systems, considering the available flexibility at the distribution grid level (e.g., demand response, on-load tap changer transformers). The obtained results suggest the formulation of an optimization problem in order to overcome the limitations of the Monte Carlo Simulation, increasing the capability to find extreme points of the flexibility map and reducing the computational effort.
Soluble SLAMF6 Receptor Induces Strong CD8+ T-cell Effector Function and Improves Anti-Melanoma Activity In Vivo

Treatment of tumor-bearing mice with the ectodomain of SLAMF6, an immune receptor, improved tumor-infiltrating CD8+ lymphocyte persistence and function. Ectodomain-treated mice had enhanced tumor clearance, suggesting that converting the SLAMF6 interaction from inhibitory to stimulatory could be therapeutic. SLAMF6, a member of the SLAM (signaling lymphocyte activation molecules) family, is a homotypic-binding immune receptor expressed on NK, T, and B lymphocytes. Phosphorylation variance between T-cell subclones prompted us to explore its role in anti melanoma immunity. Using a 203-amino acid sequence of the human SLAMF6 (seSLAMF6) ectodomain, we found that seSLAMF6 reduced activation-induced cell death and had an antiapoptotic effect on tumor-infiltrating lymphocytes. CD8+ T cells costimulated with seSLAMF6 secreted more IFNγ and displayed augmented cytolytic activity. The systemic administration of seSLAMF6 to mice sustained adoptively transferred transgenic CD8+ T cells in comparable numbers to high doses of IL2. In a therapeutic model, lymphocytes activated by seSLAMF6 delayed tumor growth, and when further supported in vivo with seSLAMF6, induced complete tumor clearance. The ectodomain expedites the loss of phosphorylation on SLAMF6 that occurs in response to T-cell receptor triggering. Our findings suggest that seSLAMF6 is a costimulator that could be used in melanoma immunotherapy. Cancer Immunol Res; 6(2); 127–38. ©2018 AACR.
Optimal Incentive Contracts in Project Management

Motivated by the ever‐growing complexity of projects and the consistent trend of outsourcing of individual tasks or components, we study the contract‐design problem faced by a firm (or organization) for executing a project consisting of multiple tasks, each of which is performed by an individual contractor whose efforts (work‐rates) are not observable. While the contractors incur costs continuously during the course of their tasks, the firm realizes its reward or revenue only when the entire project is (i.e., all tasks are) completed. The firm’s contract‐design decisions and the contractors’ effort‐level decisions are all governed by the goals of maximizing the respective party’s expected discounted profit. We adopt the framework in Kwon et al. (2010a) and Chen et al. (2015), and derive optimal contracts for both parallel projects (tasks can be performed in parallel) and sequential projects (tasks have to be performed sequentially). The simplicity of the contracts we obtain suggests that there is potential for designing profit‐maximizing contracts without paying a price in terms of contract complexity.
The prevalence and incidence of diabetic foot ulcers among five countries in the Arab world: a systematic review.

OBJECTIVE There is a rising incidence of diabetes worldwide; however there seems to be a higher incidence and prevalence rates in the Arab world when compared with the global average. 1 Out of the top 10 countries with the highest prevalence rates, six are Arab countries and almost 20.5 million people in that part of the world live with diabetes. Despite this, published scientific research from the 22 Arab countries is limited and seems to be of lower quality when compared with the rest of the developed world. 2 Therefore, our aim was to explore the contribution of the different Arab countries in the world literature, to identify the diabetic foot ulcer (DFU) prevalence and incidence rates and to quality appraise these studies. METHOD A systematic review, following PRISMA guidelines, was undertaken to identify the incidence and prevalence of DFUs in the Arab world. The following databases were searched: PubMed, Embase CINAHL, Web of Science (Scopus), Global Health and EBSCO Results: A total of nine papers were identified. The mean prevalence of DFU in Saudi Arabia was 11.85% (4.7-19%), in Egypt was 4.2% (1-7.4%), in Jordan was 4.65% (4-5.3%), in Bahrain was 5.9% and in Iraq was 2.7%. A single study identified DFU incidence in Saudi Arabia as 1.8% between 2009-2010. CONCLUSION The mean prevalence rates of DFU were highest in Saudi Arabia and Bahrain and lowest in Iraq. Saudi Arabia had the only reported incidence study, thus findings could not be compared to other countries of the Arab world. There were no studies identified during our search reporting prevalence rates of DFU in 17 of the 22 Arab countries. It is clear that further research is required to determine the incidence and prevalance of DFUs in the Arab world and that progress is needed in order to improve the quality of research conducted in those countries.
Cycles of Declines and Reversals following Overnight Market Declines

This paper uncovers and explains the emergence of cycles of intraday declines and overnight reversals in the U.S. stock market in the 21st century. Using quote midpoints for the past 24 years of common stocks traded in the three main exchanges, I show that the cross-sectional association between average intraday and overnight returns has steadily shifted from a direct association into a strong inverse association over the years. I explain this shift by showing that after 2001, consistent with theoretical models in which binding capital constraints lead to liquidity dry-ups, an overnight decline in the stock market is followed by a further intraday decline for volatile stocks and their reversal over the next overnight period. Moreover, I show that market liquidity of volatile stocks further deteriorates following an overnight market decline, which confirms my proposed explanation. Finally, I show that idiosyncratic volatility, compared with systematic risk, better explains the cross section of the documented systematic intraday declines and overnight reversals.
Effect of videotape feedback on anaesthetists' performance while managing simulated anaesthetic crises: a multicentre study

The aim of this study was to examine the performance of anaesthetists while managing simulated anaesthetic crises and to see whether their performance was improved by reviewing their own performances recorded on videotape. Thirty‐two subjects from four hospitals were allocated randomly to one of two groups, with each subject completing five simulations in a single session. Individuals in the first group completed five simulations with only a short discussion between each simulation. Those in the second group were allowed to review their own performance on videotape between each of the simulations. Performance was measured by both ‘time to solve the problem’ and mental workload, using anaesthetic chart error as a secondary task. Those trainees exposed to videotape feedback had a shorter median ‘time to solve’ and a smaller decrease in chart error when compared to those not exposed to video feedback. However, the differences were not statistically significant, confirming the difficulties encountered by other groups in designing valid tests of the performance of anaesthetists.
Cost-effectiveness of carotid artery stent placement versus endarterectomy in patients with carotid artery stenosis.

OBJECT The Carotid Revascularization Endarterectomy versus Stenting Trial (CREST) demonstrated that the risk of the primary composite outcome of stroke, myocardial infarction (MI), or death did not differ significantly in patients with an average surgical risk undergoing carotid artery stenting (CAS) and those undergoing carotid endarterectomy (CEA). However, the cost associated with CAS may limit its broad applicability. The authors' goal in this paper was to determine the cost-effectiveness of CAS with an embolic-protection device versus CEA in patients with moderate to severe carotid artery stenosis who are at average surgical risk. METHODS The probability of the primary outcome was obtained from the results of the CREST trial. The quality-adjusted life years (QALYs) associated with each treatment modality were estimated by adjusting for the incidence of each quality-adjusted outcome (QALY weights of ipsilateral stroke, MI, death, and postprocedure QALYs). The total cost associated with each intervention was derived from hospitalization cost and cost associated with primary outcomes including stroke, MI, and death in each group. Costs are expressed in US dollars accounting for inflation up to October 2010. Incremental cost-effectiveness ratios (ICERs) were estimated for the 4-year period after the procedure. All values are expressed as means and 95% confidence intervals. RESULTS The estimated net costs for patients after treatment with CAS and CEA after consideration of the primary outcome were $18,335 and $13,276, respectively, from the definitive presimulation analysis. Postsimulation values were $19,210 (range $18,264-$20,156) and $14,080 (range $13,076-$15,084), respectively. Overall, QALYs for the CAS and CEA groups were 0.712 and 0.702, respectively (ranging from 0.0 [death] to 0.815 [no adverse events]). The estimated ICER for CAS versus CEA treatment was $229,429. CONCLUSIONS Although the CREST demonstrated equivalent results with CAS (compared with CEA) in patients at average surgical risk with severe carotid artery stenosis, broad applicability of CAS might be limited by the higher cost associated with this procedure.
Vasectomy and the risk of prostate cancer: a meta-analysis of cohort studies.

BACKGROUND The relationship of vasectomy to prostate cancer has great public health significance. However, the results of observational studies were conflicting. To determine whether vasectomy is associated with the risk of prostate cancer, we performed a meta-analysis of cohort studies. METHODS A literature search was carried out using Pubmed, Embase, Cochrane Libraryl, and China National Knowledge Infrastructure (CNKI) between January 1966 and July 2013. Before meta-analysis, between-study heterogeneity and publication bias were assessed using adequate statistical tests. Fixed-effect and random-effect models were used to estimate summary relative risks (RR) and the corresponding 95% confidence intervals (CIs). Potential sources of heterogeneity were detected by meta-regression. Subgroup analyses and sensitivity analysis were also performed. RESULTS A total of nine cohort studies contributed to the analysis. There was heterogeneity among the studies but no publication bias. Pooled results indicated that vasectomy was not associated with a significant increase of total prostate cancer risk (RR = 1.07, 95% CI [0.79, 1.46]). When stratified the various studies by geographic location, we found a significant association between vasectomy and increased PCa risk among studies conducted in the USA (RR = 1.54, 95% CI [1.23, 1.93]), however, there was no significant association between vasectomy and PCa risk among studies conducted in non-USA countries (RR = 0.74, 95% CI [0.50, 1.09]). Furthermore, sensitivity analysis confirmed the stability of the results. CONCLUSIONS In conclusion, the present meta-analysis of cohort studies suggested that vasectomy was not associated with increased risk of prostate cancer. More in-depth studies are warranted to report more detailed results, including stratified results by age at vasectomy, tumor grade, and tumor stage.
Cardiac responses to maximal upright cycle exercise in healthy boys and men.

Previous investigations have indicated that children demonstrate a lower cardiac output at a given oxygen uptake during exercise compared with adults. This study compared cardiac responses with maximal upright cycle exercise in 15 boys (mean age 10.9 yr) and 16 men (mean age 30.7 yr) to determine whether this observation reflects differences in size or age-related influences on myocardial function. Stroke volume, aortic peak velocity, and systolic ejection time were measured to peak exercise in all subjects using Doppler ultrasound techniques. No significant differences were observed in resting, submaximal, or peak mean values for these variables relative to body size between the boys and men. Average values for peak stroke index, cardiac index, and peak aortic velocity were 59 (+/-11) mL.m-2, 11.33 (+/-2.32) L.min-1.m-2, and 152 (+/-30) cm.s-1, respectively, for the boys. Respective values for the men were 61 (+/-14) mL.m-2, 11.08 (+/-2.52) L.min-1.m-2, and 144 (+/-24) cm.s-1 (P > 0.05). This study failed to demonstrate evidence of impaired cardiac responses to maximal exercise in prepubertal boys compared with that in adult males.
Nd:Yag goniopuncture after deep sclerectomy with collagen implant.

BACKGROUND AND OBJECTIVE To study the need, the safety and the success rate of Nd:Yag goniopuncture in eyes that underwent deep sclerectomy with collagen implant. PATIENTS AND METHODS The first 100 patients that underwent deep sclerectomy with collagen implant were prospectively followed. Deep sclerectomy with collagen implant is a non-penetrating filtering surgery which allows filtration of aqueous from the anterior chamber to the subconjunctival space through a remaining trabeculo-Descemet's membrane without opening the anterior chamber. Goniopunctures with Nd:Yag laser were performed at the site of surgery when the filtration through the trabeculo-Descemet's membrane was considered to be insufficient with elevated intraocular pressure. The laser treatment was performed using a Lasag 15 gonioscopy contact lens (CGA1). Goniopunctures were performed using the free-running Q-switched mode with an energy ranging from 2 to 4 mJ. RESULTS Of 100 patients who underwent deep sclerectomy with collagen implant, goniopunctures with Nd:Yag laser were performed in 41 patients (41%). The mean time between deep sclerectomy with collagen implant and goniopuncture was 9.9 months +/-1.2 months (+/-SE). The mean IOP before laser treatment was 22.2 mm +/-7.0 mm Hg and decreased to 12.5 mm +/-5.8 mm Hg immediately after laser treatment and remained stable for the next 2 years of follow-up. The immediate success rate of goniopuncture was 83%. Choroidal detachment occurred in two patients (5%). CONCLUSION Nd:Yag goniopuncture is an efficient and safe treatment for low filtration through the trabeculo-Descemet's membrane after deep sclerectomy with collagen implant.