The UK register of HIV seroconverters: Methods and analytical issues

A Register of HIV-infected persons who have had a negative antibody test within 3 years of their first antibody positive test (seroconverters) is being set up in the UK to monitor the distribution of times from HIV seroconversion to AIDS (the incubation period) and to death. It will also provide a national resource for use by those designing studies in this group of individuals. Clinicians caring for HIV-positive persons in Genito-Urinary Medicine, Infectious Disease and other departments throughout the UK were asked to participate by providing information on eligible subjects. Most laboratories undertaking HIV antibody testing were also contacted and asked to provide the name of the attending clinician for all seroconverters identified through the HIV laboratory reporting systems of the PHLS Communicable Disease Surveillance Centre (CDSC) and the Scottish Centre for Infection and Environmental Health (SCIEH) and for any other seroconverters known to them but not identified by CDSC or SCIEH. Data items sought for the Register include: sex, ethnic group, probable route of HIV transmission, annual CD4 counts, details of therapy and prophylaxis prescribed, AIDS-defining events and vital status. Follow up information is collected annually. Wherever possible, all seroconverters known to a clinic have been identified, whether currently alive or dead, either from clinic records or laboratory reporting or both. The objective is to establish and update a complete register of seroconverters on a long-term basis to provide reliable estimates of the incubation period on which future projections of AIDS cases in the UK can be made

High temperature superconductors for magnetic suspension applications

High temperature superconductors (HTS) hold the promise for applications in magnetic levitation bearings, vibration damping, and torque coupling. Traditional magnetic suspension systems require active feedback and vibration controls in which power consumption and low frequency vibration are among the major engineering concerns. HTS materials have been demonstrated to be an enabling approach towards such problems due to their flux trapping properties. In our laboratory at TCSUH, we have been conducting a series of experiments to explore various mechanical applications using HTS. We have constructed a 30 lb. model flywheel levitated by a hybrid superconducting magnetic bearing (HSMB). We are also developing a levitated and vibration-dampled platform for high precision instrumentation. These applications would be ideal for space usages where ambient temperature is adequate for HTS to operate properly under greatly reduced cryogenic requirements. We will give a general overview of these potential applications and discuss the operating principles of the HTS devices we have developed

Obesity is not associated with disease-free interval, melanoma-specific survival, or overall survival in patients with clinical stage IB-II melanoma after SLNB

BACKGROUND AND OBJECTIVES: Clinicopathologic characteristics have prognostic value in clinical stage IB‐II patients with melanoma. Little is known about the prognostic value of obesity that has been associated with an increased risk for several cancer types and worsened prognosis after diagnosis. This study aims to examine effects of obesity on outcome in patients with clinical stage IB‐II melanoma. METHODS: Prospectively recorded data of patients with clinical stage IB‐II melanoma who underwent sentinel lymph node biopsy (SLNB) between 1995 and 2018 at the University Medical Center of Groningen were collected from medical files and retrospectively analyzed. Cox‐regression analyses were used to determine associations between obesity (body mass index> 30), tumor (location, histology, Breslow‐thickness, ulceration, mitotic rate, SLN‐status) and patient‐related variables (gender, age, and social‐economic‐status [SES]) and disease‐free interval (DFI), melanoma‐specific survival (MSS), and overall survival (OS). RESULTS: Of the 715 patients, 355 (49.7%) were women, median age was 55 (range 18.6‐89) years, 149 (20.8%) were obese. Obesity did not significantly affect DFI (adjusted hazard ratio [HR] = 1.40; 95% confidence interval [CI] = 0.98–2.00; p = 0.06), MSS (adjusted HR = 1.48;95%CI = 0.97–2.25; p = 0.07), and OS (adjusted HR = 1.25; 95% CI = 0.85–1.85; p = 0.25). Increased age, arm location, increased Breslow‐thickness, ulceration, increased mitotic rate, and positive SLN‐status were significantly associated with decreased DFI, MSS, and OS. Histology, sex, and SES were not associated. CONCLUSION: Obesity was not associated with DFI, MSS, or OS in patients with clinical stage IB‐II melanoma who underwent SLNB

Accounting Problems Under the Excess Profits Tax

DNA vaccines based on subunits from pathogens have several advantages over other vaccine strategies. DNA vaccines can easily be modified, they show good safety profiles, are stable and inexpensive to produce, and the immune response can be focused to the antigen of interest. However, the immunogenicity of DNA vaccines which is generally quite low needs to be improved. Electroporation and co-delivery of genetically encoded immune adjuvants are two strategies aiming at increasing the efficacy of DNA vaccines. Here, we have examined whether targeting to antigen-presenting cells (APC) could increase the immune response to surface envelope glycoprotein (Env) gp120 from Human Immunodeficiency Virus type 1 (HIV- 1). To target APC, we utilized a homodimeric vaccine format denoted vaccibody, which enables covalent fusion of gp120 to molecules that can target APC. Two molecules were tested for their efficiency as targeting units: the antibody-derived single chain Fragment variable (scFv) specific for the major histocompatilibility complex (MHC) class II I-E molecules, and the CC chemokine ligand 3 (CCL3). The vaccines were delivered as DNA into muscle of mice with or without electroporation. Targeting of gp120 to MHC class II molecules induced antibodies that neutralized HIV-1 and that persisted for more than a year after one single immunization with electroporation. Targeting by CCL3 significantly increased the number of HIV-1 gp120-reactive CD8(+) T cells compared to non-targeted vaccines and gp120 delivered alone in the absence of electroporation. The data suggest that chemokines are promising molecular adjuvants because small amounts can attract immune cells and promote immune responses without advanced equipment such as electroporation.Funding Agencies|Research Council of Norway; Odd Fellow</p

The effectiveness of public health interventions to reduce the health impact of climate change:a systematic review of systematic reviews

Climate change is likely to be one of the most important threats to public health in the coming years. Yet despite the large number of papers considering the health impact of climate change, few have considered what public health interventions may be of most value in reducing the disease burden. We aimed to evaluate the effectiveness of public health interventions to reduce the disease burden of high priority climate sensitive diseases

Polymeric hydrogel coating for modulating the shape of keratin fiber

Hydrogel coating was explored to modulate the shape of keratin hair fiber. The motivation was the development of an eco-friendly methodology with non-toxic chemicals to modulate keratin fiber. Polymeric hydrogel of acrylic acid and N-N-dimethylacrylamide was prepared by free-radical polymerization in aqueous solution, using nano-alumina particles as crosslinker and potassium persulfate as an initiator. Physico-chemical properties of the hydrogel was investigated by Fourier transformer infrared spectrum (FTIR), thermal analysis and swelling ratio behavior. After hydrogel coating, morphological modification was observed from straight to curly hair effect. The influence of hydrogel coating on hair fiber was evaluated by perming efficiency supported by X-ray diffraction and morphological characterization (SEM and AFM). The durability of hydrogel coating was tested until four wash processes maintaining around 65% the new configuration of the hair fiber.This study was supported by the Portuguese Foundationfor Science and Technology (FCT) under the scope of thestrategic funding of UID/BIO/04469/2019 unit and BioTecNorte operation (NORTE-01-0145-FEDER-000004) funded by theEuropean Regional Development Fund under the scope ofNorte2020—Programa Operacional Regional do Norte. Thisstudy was also supported by the Natural Science Foundation ofJiangsu Province (Grant No. BK20180631).info:eu-repo/semantics/publishedVersio

Urban Area Disadvantage and Under-5 Mortality in Nigeria: The Effect of Rapid Urbanization

Background: Living in socioeconomically disadvantaged areas is associated with increased -childhood mortality risks. As city living becomes the predominant social context in low- and middle-income countries, the resulting rapid urbanization together with the poor economic circumstances of these countries greatly increases the risks of mortality for children < 5 years of age (under-5 mortality). Objective: In this study we examined the trends in urban population growth and urban under-5 mortality between 1983 and 2003 in Nigeria. We assessed whether urban area socioeconomic dis-advantage has an impact on under-5 mortality. Methods: Urban under-5 mortality rates were directly estimated from the 1990, 1999, and 2003 Nigeria Demographic and Health Surveys. Multilevel logistic regression analysis was performed on data for 2,118 children nested within data for 1,350 mothers, who were in turn nested within data for 165 communities. Results: Urban under-5 mortality increased as urban population steadily increased between 1983 and 2003. Urban area disadvantage was significantly associated with under-5 mortality after adjusting for individual child- and mother-level demographic and socioeconomic characteristics. Conclusions: Significant relative risks of under-5 deaths at both individual and community levels underscore the need for interventions tailored toward community- and individual-level inter-ventions. We stress the need for further studies on community-level determinants of under-5 mortality in disadvantaged urban areas

Metastatic eccrine porocarcinoma: report of a case and review of the literature

Eccrine porocarcinoma (EPC) is a rare type of skin cancer arising from the intraepidermal portion of eccrine sweat glands or acrosyringium, representing 0.005-0.01% of all cutaneous tumors. About 20% of EPC will recur and about 20% will metastasize to regional lymph nodes. There is a mortality rate of 67% in patients with lymph node metastases. Although rare, the occurrence of distant metastases has been reported

High Pro-Inflammatory Cytokine Secretion and Loss of High Avidity Cross-Reactive Cytotoxic T-Cells during the Course of Secondary Dengue Virus Infection

BACKGROUND: Dengue is one of the most important human diseases transmitted by an arthropod vector and the incidence of dengue virus infection has been increasing - over half the world's population now live in areas at risk of infection. Most infections are asymptomatic, but a subset of patients experience a potentially fatal shock syndrome characterised by plasma leakage. Severe forms of dengue are epidemiologically associated with repeated infection by more than one of the four dengue virus serotypes. Generally attributed to the phenomenon of antibody-dependent enhancement, recent observations indicate that T-cells may also influence disease phenotype. METHODS AND FINDINGS: Virus-specific cytotoxic T lymphocytes (CTL) showing high level cross reactivity between dengue serotypes could be expanded from blood samples taken during the acute phase of secondary dengue infection. These could not be detected in convalescence when only CTL populations demonstrating significant serotype specificity were identified. Dengue cross-reactive CTL clones derived from these patients were of higher avidity than serotype-specific clones and produced much higher levels of both type 1 and certain type 2 cytokines, many previously implicated in dengue pathogenesis. CONCLUSION: Dengue serotype cross-reactive CTL clones showing high avidity for antigen produce higher levels of inflammatory cytokines than serotype-specific clones. That such cells cannot be expanded from convalescent samples suggests that they may be depleted, perhaps as a consequence of activation-induced cell death. Such high avidity cross-reactive memory CTL may produce inflammatory cytokines during the course of secondary infection, contributing to the pathogenesis of vascular leak. These cells appear to be subsequently deleted leaving a more serotype-specific memory CTL pool. Further studies are needed to relate these cellular observations to disease phenotype in a large group of patients. If confirmed they have significant implications for understanding the role of virus-specific CTL in pathogenesis of dengue disease

Prior immunity helps to explain wave-like behaviour of pandemic influenza in 1918-9

<p>Abstract</p> <p>Background</p> <p>The ecology of influenza may be more complex than is usually assumed. For example, despite multiple waves in the influenza pandemic of 1918-19, many people in urban locations were apparently unaffected. Were they unexposed, or protected by pre-existing cross-immunity in the first wave, by acquired immunity in later waves, or were their infections asymptomatic?</p> <p>Methods</p> <p>We modelled all these possibilities to estimate parameters to best explain patterns of repeat attacks in 24,706 individuals potentially exposed to summer, autumn and winter waves in 12 English populations during the 1918-9 pandemic.</p> <p>Results</p> <p>Before the summer wave, we estimated that only 52% of persons (95% credibility estimates 41-66%) were susceptible, with the remainder protected by prior immunity. Most people were exposed, as virus transmissibility was high with R₀credibility estimates of 3.10-6.74. Because of prior immunity, estimates of effective R at the start of the summer wave were lower at 1.57-3.96. Only 25-66% of exposed and susceptible persons reported symptoms. After each wave, 33-65% of protected persons became susceptible again before the next wave through waning immunity or antigenic drift. Estimated rates of prior immunity were less in younger populations (19-59%) than in adult populations (38-66%), and tended to lapse more frequently in the young (49-92%) than in adults (34-76%).</p> <p>Conclusions</p> <p>Our model for pandemic influenza in 1918-9 suggests that pre-existing immune protection, presumably induced by prior exposure to seasonal influenza, may have limited the pandemic attack-rate in urban populations, while the waning of that protection likely contributed to recurrence of pandemic waves in exposed cities. In contrast, in isolated populations, pandemic attack rates in 1918-9 were much higher than in cities, presumably because prior immunity was less in populations with infrequent prior exposure to seasonal influenza. Although these conclusions cannot be verified by direct measurements of historical immune mechanisms, our modelling inferences from 1918-9 suggest that the spread of the influenza A (H1N1) 2009 pandemic has also been limited by immunity from prior exposure to seasonal influenza. Components of that immunity, which are measurable, may be short-lived, and not necessarily correlated with levels of HI antibody.</p