Vascular Endothelial Growth Factor Level as a Predictor of Hepatocellular Carcinoma in Liver Cirrhosis Patients

BACKGROUND: Alpha-fetoprotein (AFP) has been used for hepatocellular carcinoma (HCC) diagnosis and screening, however, AFP has poor specificity. The extensive hypervascularity associated with HCC could be driven in part by the pro-angiogenic factor known as vascular endothelial growth factor (VEGF). Furthermore, invasiveness of certain HCC lesions has recently been linked to high levels of VEGF. Therefore, circulating VEGF levels of patients with liver cirrhosis (LC) and HCC were investigated and analysed.METHODS: An analytical cross sectional study was designed. Diagnosis of HCC and LC was performed using clinical criteria and findings obtained from B-mode ultrasonography (USG), computed tomography (CT) angiography, or magnetic resonance imaging (MRI). Blood were collected intravenously from all subjects. Obtained serum and plasma were stored in -80°C for following analyses: hepatitis B surface antigen (HBSAg), hepatitis C virus (HCV), alanine aminotransferase (ALT), total bilirubin, albumin, VEGF and AFP.RESULTS: Levels of VEGF and AFP were significantly higher in HCC group compared with LC group with p = 3.05 x 10-6 and p = 8.74 x 10-5, respectively. There was a significant positive correlation (p=0.029, r=0.309) between VEGF level and tumor size in HCC group. The area under curve (AUC) for VEGF level in HCC and LC groups was 0.771. In the level of median 435.6 pg/mL VEGF, the sensitivity was 50% and specificity was 86%. In the level of 199.99 pg/mL VEGF the sensitivity was 74% and specificity was 76%.CONCLUSION: The present findings suggested that VEGF level could be a useful marker for the presence of HCC in patients with LC

Malaria mortality in Africa and Asia: evidence from INDEPTH health and demographic surveillance system sites.

BACKGROUND: Malaria continues to be a major cause of infectious disease mortality in tropical regions. However, deaths from malaria are most often not individually documented, and as a result overall understanding of malaria epidemiology is inadequate. INDEPTH Network members maintain population surveillance in Health and Demographic Surveillance System sites across Africa and Asia, in which individual deaths are followed up with verbal autopsies. OBJECTIVE: To present patterns of malaria mortality determined by verbal autopsy from INDEPTH sites across Africa and Asia, comparing these findings with other relevant information on malaria in the same regions. DESIGN: From a database covering 111,910 deaths over 12,204,043 person-years in 22 sites, in which verbal autopsy data were handled according to the WHO 2012 standard and processed using the InterVA-4 model, over 6,000 deaths were attributed to malaria. The overall period covered was 1992-2012, but two-thirds of the observations related to 2006-2012. These deaths were analysed by site, time period, age group and sex to investigate epidemiological differences in malaria mortality. RESULTS: Rates of malaria mortality varied by 1:10,000 across the sites, with generally low rates in Asia (one site recording no malaria deaths over 0.5 million person-years) and some of the highest rates in West Africa (Nouna, Burkina Faso: 2.47 per 1,000 person-years). Childhood malaria mortality rates were strongly correlated with Malaria Atlas Project estimates of Plasmodium falciparum parasite rates for the same locations. Adult malaria mortality rates, while lower than corresponding childhood rates, were strongly correlated with childhood rates at the site level. CONCLUSIONS: The wide variations observed in malaria mortality, which were nevertheless consistent with various other estimates, suggest that population-based registration of deaths using verbal autopsy is a useful approach to understanding the details of malaria epidemiology

High-mass X-ray binaries and OB-runaway stars

High-mass X-ray binaries (HMXBs) represent an important phase in the evolution of massive binary systems. HMXBs provide unique diagnostics to test massive-star evolution, to probe the physics of radiation-driven winds, to study the process of mass accretion, and to measure fundamental parameters of compact objects. As a consequence of the supernova explosion that produced the neutron star (or black hole) in these systems, HMXBs have high space velocities and thus are runaways. Alternatively, OB-runaway stars can be ejected from a cluster through dynamical interactions. Observations obtained with the Hipparcos satellite indicate that both scenarios are at work. Only for a minority of the OB runaways (and HMXBs) a wind bow shock has been detected. This might be explained by the varying local conditions of the interstellar medium.Comment: 15 pages, latex (sty file included) with 5 embedded figures (one in jpg format), to appear in Proc. "Influence of binaries on stellar population studies", Eds. Vanbeveren, Van Rensberge

LES-based Study of the Roughness Effects on the Wake of a Circular Cylinder from Subcritical to Transcritical Reynolds Numbers

This paper investigates the effects of surface roughness on the flow past a circular cylinder at subcritical to transcritical Reynolds numbers. Large eddy simulations of the flow for sand grain roughness of size k/D = 0.02 are performed (D is the cylinder diameter). Results show that surface roughness triggers the transition to turbulence in the boundary layer at all Reynolds numbers, thus leading to an early separation caused by the increased momentum deficit, especially at transcritical Reynolds numbers. Even at subcritical Reynolds numbers, boundary layer instabilities are triggered in the roughness sublayer and eventually lead to the transition to turbulence. The early separation at transcritical Reynolds numbers leads to a wake topology similar to that of the subcritical regime, resulting in an increased drag coefficient and lower Strouhal number. Turbulent statistics in the wake are also affected by roughness; the Reynolds stresses are larger due to the increased turbulent kinetic energy production in the boundary layer and separated shear layers close to the cylinder shoulders.We acknowledge “Red Española de Surpercomputación” (RES) for awarding us access to the MareNostrum III machine based in Barcelona, Spain (Ref. FI-2015-2-0026 and FI-2015-3-0011). We also acknowledge PRACE for awarding us access to Fermi and Marconi Supercomputers at Cineca, Italy (Ref. 2015133120). Oriol Lehmkuhl acknowledges a PDJ 2014 Grant by AGAUR (Generalitat de Catalunya). Ugo Piomelli acknowledges the support of the Natural Sciences and Engineering Research Council (NSERC) of Canada under the Discovery Grant Programme (Grant No. RGPIN-2016-04391). Ricard Borrell acknowledges a Juan de la Cierva postdoctoral grant (IJCI-2014-21034). Ivette Rodriguez, Oriol Lehmkuhl, Ricard Borrell and Assensi Oliva acknowledge Ministerio de Economía y Competitividad, Secretaría de Estado de Investigación, Desarrollo e Innovación, Spain (ref. ENE2014-60577-R).Peer ReviewedPostprint (author's final draft

Adult non-communicable disease mortality in Africa and Asia: evidence from INDEPTH Health and Demographic Surveillance System sites.

BACKGROUND: Mortality from non-communicable diseases (NCDs) is a major global issue, as other categories of mortality have diminished and life expectancy has increased. The World Health Organization's Member States have called for a 25% reduction in premature NCD mortality by 2025, which can only be achieved by substantial reductions in risk factors and improvements in the management of chronic conditions. A high burden of NCD mortality among much older people, who have survived other hazards, is inevitable. The INDEPTH Network collects detailed individual data within defined Health and Demographic Surveillance sites. By registering deaths and carrying out verbal autopsies to determine cause of death across many such sites, using standardised methods, the Network seeks to generate population-based mortality statistics that are not otherwise available. OBJECTIVE: To describe patterns of adult NCD mortality from INDEPTH Network sites across Africa and Asia, according to the WHO 2012 verbal autopsy (VA) cause categories, with separate consideration of premature (15-64 years) and older (65+ years) NCD mortality. DESIGN: All adult deaths at INDEPTH sites are routinely registered and followed up with VA interviews. For this study, VA archives were transformed into the WHO 2012 VA standard format and processed using the InterVA-4 model to assign cause of death. Routine surveillance data also provide person-time denominators for mortality rates. RESULTS: A total of 80,726 adult (over 15 years) deaths were documented over 7,423,497 person-years of observation. NCDs were attributed as the cause for 35.6% of these deaths. Slightly less than half of adult NCD deaths occurred in the 15-64 age group. Detailed results are presented by age and sex for leading causes of NCD mortality. Per-site rates of NCD mortality were significantly correlated with rates of HIV/AIDS-related mortality. CONCLUSIONS: These findings present important evidence on the distribution of NCD mortality across a wide range of African and Asian settings. This comes against a background of global concern about the burden of NCD mortality, especially among adults aged under 70, and provides an important baseline for future work

"It's a can of worms": understanding primary care practitioners' behaviours in relation to HPV using the Theoretical Domains Framework

Background: The relationship between infection with high-risk human papillomavirus (HPV) and cervical cancer is transforming cervical cancer prevention. HPV tests and vaccinations have recently become available. In Ireland, as elsewhere, primary care practitioners play a key role in prevention. ATHENS (A Trial of HPV Education and Support) aims to develop a theorybased intervention to support primary care practitioners in their HPV-related practice. This study, the first step in the intervention development process, aimed to: identify HPV-related clinical behaviours that the intervention will target; clarify general practitioners’ (GPs’) and practice nurses’ roles and responsibilities; and determine factors that potentially influence clinical behaviour. A secondary objective was to informally assess the utility of the Theoretical Domains Framework (TDF) in understanding clinical behaviours in an area with an evolving evidence-base. Methods: In-depth semi-structured telephone interviews were conducted with GPs and practice nurses. The topic guide, which contained open questions and HPV-related clinical scenarios, was developed through literature review and clinical experience. Interview transcripts were content-analysed using the TDF as the coding framework. Results: 19 GPs and 14 practice nurses were interviewed. The major HPV-related clinical behaviours were: initiating a discussion about HPV infection with female patients; offering/recommending HPV vaccination to appropriate patients; and answering patients’ questions about HPV testing. While the responsibility for taking smears was considered a female role, both male and female practitioners dealt with HPV-related issues. All 12 theoretical domains arose in relation to HPV infection; the domains judged to be most important were: knowledge, emotion, social influences, beliefs about capabilities and beliefs about consequences. Eleven domains emerged in relation to HPV vaccination, with beliefs about consequences, social influences, knowledge and environmental context and resources judged to be the most important. Nine domains were relevant to HPV testing, with knowledge and beliefs about capabilities judged to be the most important. Conclusions: The findings confirm the need for an intervention to support primary care practitioners around HPV and suggest it should target a range of theoretical domains. The TDF proved valuable in analysing qualitative data collected using a topic guide not specifically designed to capture TDF domains and understanding clinical behaviours in an area with an evolving evidence-base

From policy to practice: exploring the implementation of antiretroviral therapy access and retention policies between 2013 and 2016 in six sub-Saharan African countries

Background: Understanding the implementation of 2013 World Health Organization (WHO) consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection at the facility level provides important lessons for the roll-out of future HIV policies. Methods: A national policy review was conducted in six sub-Saharan African countries to map the inclusion of the 2013 WHO HIV treatment recommendations. Twenty indicators of policy adoption were selected to measure ART access (n = 12) and retention (n = 8). Two sequential cross-sectional surveys were conducted in facilities between 2013/2015 (round 1) and 2015/2016 (round 2) from ten health and demographic surveillance sites in Kenya, Malawi, South Africa, Tanzania, Uganda and Zimbabwe. Using standardised questionnaires, facility managers were interviewed. Descriptive analyses were used to assess the change in the proportion of facilities that implemented these policy indicators between rounds. Results: Although, expansion of ART access was explicitly stated in all countries’ policies, most lacked policies that enhanced retention. Overall, 145 facilities were included in both rounds. The proportion of facilities that initiated ART at CD4 counts of 500 or less cells/μL increased between round 1 and 2 from 12 to 68%, and facilities initiating patients on 2013 WHO recommended ART regimen increased from 42 to 87%. There were no changes in the proportion of facilities reporting stock-outs of first-line ART in the past year (18 to 11%) nor in the provision of three-month supply of ART (43 to 38%). None of the facilities provided community-based ART delivery. Conclusion: The increase in ART initiation CD4 threshold in most countries, and substantial improvements made in the provision of WHO recommended first-line ART regimens demonstrates that rapid adoption of WHO recommendations is possible. However, improved logistics and resources and/or changes in policy are required to further minimise ART stock-outs and allow lay cadres to dispense ART in the community. Increased efforts are needed to offer longer durations between clinic visits, a strategy purported to improve retention. These changes will be important as countries move to implement the revised 2015 WHO guidelines to initiate all HIV positive people onto ART regardless of their immune statu

Kaposi's Sarcoma-Associated Herpesvirus ORF45 Interacts with Kinesin-2 Transporting Viral Capsid-Tegument Complexes along Microtubules

Open reading frame (ORF) 45 of Kaposi's sarcoma-associated herpesvirus (KSHV) is a tegument protein. A genetic analysis with a null mutant suggested a possible role for this protein in the events leading to viral egress. In this study, ORF45 was found to interact with KIF3A, a kinesin-2 motor protein that transports cargoes along microtubules to cell periphery in a yeast two-hybrid screen. The association was confirmed by both co-immunoprecipitation and immunoflorescence approaches in primary effusion lymphoma cells following virus reactivation. ORF45 principally mediated the docking of entire viral capsid-tegument complexes onto the cargo-binding domain of KIF3A. Microtubules served as the major highways for transportation of these complexes as evidenced by drastically reduced viral titers upon treatment of cells with a microtubule depolymerizer, nocodazole. Confocal microscopic images further revealed close association of viral particles with microtubules. Inhibition of KIF3A–ORF45 interaction either by the use of a headless dominant negative (DN) mutant of KIF3A or through shRNA-mediated silencing of endogenous KIF3A expression noticeably decreased KSHV egress reflecting as appreciable reductions in the release of extracellular virions. Both these approaches, however, failed to impact HSV-1 egress, demonstrating the specificity of KIF3A in KSHV transportation. This study thus reports on transportation of KSHV viral complexes on microtubules by KIF3A, a kinesin motor thus far not implicated in virus transportation. All these findings shed light on the understudied but significant events in the KSHV life cycle, delineating a crucial role of a KSHV tegument protein in cellular transport of viral particles