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Abstract Background Minority stress from racism and heterosexism may uniquely interact to impact the mental health of racialized sexual minorities. We examined variations in anxiety and depressive symptoms by reported by ethno-racial identity among gay, bisexual, and other men who have sex with men (gbMSM) in Vancouver, Canada. Methods We recruited gbMSM aged ≥ 16 years from February 2012 to February 2015 using respondent-driven sampling (RDS). Participants completed computer assisted self-interviews (CASI) at enrollment and every 6 months until February 2017. We examined factors associated with moderate/severe anxiety and depression scores (> 10) on the Hospital Anxiety and Depression Scale (HADS) and differences in key explanatory variables including sociodemographic, psychosocial, and substance use factors. We used multivariable mixed effects models to assess whether moderate/severe scores were associated with ethno-racial identity across all visits. Results After RDS-adjustment, of 774 participants, 79.9% of participants identified as gay. 68.6% identified as white, 9.2% as Asian, 9.8% as Indigenous, 7.3% as Latin American, and 5.1% as other ethno-racial identities. Participants contributed a median of 6 follow-up visits (Q1-Q3: 4–7). In the multivariable analysis, Asian participants had decreased odds of moderate/severe anxiety scores compared to white participants (aOR = 0.39; 95% CI: 0.18–0.86), and Latin American participants had decreased odds of moderate/severe depression scores compared to both white (aOR = 0.17; 95% CI: 0.08–0.36) and Asian (aOR = 0.07; 95% CI: 0.02–0.20) participants. Conclusion Asian and Latino gbMSM reported decreased mental health symptoms compared to white participants. Asian and Latino gbMSM in Vancouver appear to manage multiple minority stressors without adversely affecting their mental health.

The adverse effects of coal and gas energy production with the subsequent rapid increase in energy consumption emphasize the importance for Australia to adopt more renewable energy sources to counteract these dismissive contributions to climate change. This work presents a data mining approach for optimally selecting the best locations for installing a distributed hybrid renewable energy generation system for rural regions in Western Australia. The K-Means and K-Medoids clustering algorithms were used to divide the constructed dataset into clusters. In total, 69 locations were selected for the overall dataset, proceeding with the filtering process. The returned cluster data were graphically rendered on a Western Australia map for the region. The clustering algorithms were evaluated using the Dunn index, such that K-Means performed to a higher degree than K-Medoids, given our dataset's nature. After passing the generated clusters to HOMER software to generate the potential wind and solar energy output for each centroid, K-Medoids produced a set of locations that generated higher solar and wind energy on average. However, due to the reduced internal validation, K-Medoids might not be as valuable as K-Means, it does not cluster the data points very well, and within-cluster location energy requirements are not considered in our study.

Abstract Background Young gay, bisexual, and other men who have sex with men (YGBM) may have reduced engagement and knowledge of HIV care and biomedical HIV prevention strategies, such as pre-exposure prophylaxis (PrEP), post-exposure prophylaxis (PEP), and Treatment as Prevention (TasP), compared with adult GBM. We sought to understand differences in HIV prevention awareness, health care access, and service utilization between youth (16–29 years) and adult (≥30 year) GBM, as well as factors associated with attendance in HIV leadership programming among YGBM living in the publicly funded PrEP setting of Vancouver, Canada. Methods Sexually-active GBM were recruited using respondent-driven sampling (RDS) from February 2012 to February 2015. Participants completed an in-person computer-assisted self-interview every 6 months, up to February 2017, with questions on sociodemographic factors, awareness of biomedical HIV prevention strategies, and an HIV treatment optimism-skepticism scale. Participants were asked if they had ever attended either of two HIV-leadership programs designed for YGBM. Both programs involve multiple GBM-led education and social networking sessions operated by community-based organizations in Vancouver. Multivariable Glimmix confounder models assessed differences between youth and adult GBM. Among younger men, bivariate analyses examined factors associated with HIV-leadership program attendance. Results Of 698 GBM who enrolled in the longitudinal study, 36.8% were less than 30 years old at the first study visit. After controlling for gender identification, sexual orientation, HIV status, and income in the past 6 months, younger GBM (n = 257/698) had lower awareness of biomedical HIV prevention strategies and less HIV treatment optimism compared with older GBM (n = 441/698). Among younger GBM who attended HIV-leadership programs (n = 50), greater awareness of biomedical HIV prevention strategies and higher HIV treatment optimism were reported, compared with non-attendees. Conclusion Younger GBM, who are disproportionately affected by the HIV epidemic, are less aware of new prevention technologies than older GBM, but attending peer-based HIV-leadership programs ameliorates age-disparities in HIV-prevention knowledge and treatment optimism.

The nuclear fuel cycle forms the basis for producing special nuclear materials used in nuclear weapons via a series of interdependent industrial operations. These industrial operations each produce characteristic emanations that can be gathered to ascertain signatures of facility operations. Machine learning and deep learning techniques were applied to time series magnetic field sensor data collected at the High Flux Isotope Reactor (HFIR) to assess the feasibility of determining the ON/OFF operational state of the reactor. When data collected by the sensor near the cooling fans, position 9, are transformed to the frequency domain, it was found that both machine and deep learning methods were able to classify the operational state of the reactor with a balanced accuracy of over 90%. This result suggests that the utilized methods show promise for application as techniques to verify declared activities involving nuclear reactors. Additional effort is recommended to develop models and architectures that will more fully capitalize on the data’s temporal nature by incorporating the magnetic field’s time dependence to improve the model’s robustness and classification performance.

Objective Mathematical models have gained traction when estimating cases of foodborne illness. Model structures vary due to differences in data availability. This begs the question as to whether differences in foodborne illness rates internationally are real or due to differences in modelling approaches.Difficulties in comparing illness rates have come into focus with COVID-19 infection rates being contrasted between countries. Furthermore, with post-EU Exit trade talks ongoing, being able to understand and compare foodborne illness rates internationally is a vital part of risk assessments related to trade in food commodities.Design We compared foodborne illness estimates for the United Kingdom (UK) with those from Australia, Canada and the USA. We then undertook sensitivity analysis, by recreating the mathematical models used in each country, to understand the impact of some of the key differences in approach and to enable more like-for-like comparisons.Results Published estimates of overall foodborne illness rates in the UK were lower than the other countries. However, when UK estimates were adjusted to a more like-for-like approach to the other countries, differences were smaller and often had overlapping credible intervals. When comparing rates by specific pathogens, there were fewer differences between countries. The few large differences found, such as virus rates in Canada, could at least partly be traced to methodological differences.Conclusion Foodborne illness estimation models are country specific, making international comparisons problematic. Some of the disparities in estimated rates between countries can be shown to be attributed to differences in methodology rather than real differences in risk.

Abstract Background DNA repair deficiencies are characteristic of cancer and homologous recombination deficiency (HRD) is the most common. HRD sensitizes tumour cells to PARP inhibitors so it is important to understand the landscape of HRD across different solid tumour types. Methods Germline and somatic BRCA mutations in breast and ovarian cancers were evaluated using sequencing data from The Cancer Genome Atlas (TCGA) database. Secondly, a larger independent genomic dataset was analysed to validate the TCGA results and determine the frequency of germline and somatic mutations across 15 different candidate homologous recombination repair (HRR) genes, and their relationship with the genetic events of bi-allelic loss, loss of heterozygosity (LOH) and tumour mutation burden (TMB). Results Approximately one-third of breast and ovarian cancer BRCA mutations were somatic. These showed a similar degree of bi-allelic loss and clinical outcomes to germline mutations, identifying potentially 50% more patients that may benefit from precision treatments. HRR mutations were present in sizable proportions in all tumour types analysed and were associated with high TMB and LOH scores. We also identified numerous BRCA reversion mutations across all tumour types. Conclusions Our results will facilitate future research into the efficacy of precision oncology treatments, including PARP and immune checkpoint inhibitors.

BackgroundGreenness exposure is beneficial to human health, but its potential mechanisms through which the risk for metabolic syndrome (MetS) could be reduced have been poorly studied. We aimed to estimate the greenness-MetS association in southeast China and investigate the independent and joint mediation effects of physical activity (PA), body mass index (BMI), and air pollutants on the association.MethodsA cross-sectional study was conducted among the 38,288 adults based on the Fujian Behavior and Disease Surveillance (FBDS), established in 2018. MetS was defined as the presence of three or more of the five components: abdominal obesity, elevated triglyceride, reduced high-density lipoprotein cholesterol (HDL-C), high blood pressure, and elevated fasting glucose. The residential greenness exposure was measured as the 3-year mean values of the normalized difference vegetation index (NDVI) and enhanced vegetation index (EVI) within the 250, 500, and 1,000 meters (m) buffer zones around the residential address of each participant. Logistic regression models were used to estimate the greenness-MetS association. The causal mediation analysis was used to estimate the independent and joint mediation effects of PA, BMI, particulate matter with an aerodynamic diameter of 2.5 μm (PM2.5), particulate matter with an aerodynamic diameter ≤ 10 μm (PM10), nitrogen dioxide (NO2), and sulfur dioxide (SO2).ResultsEach interquartile range (IQR) increase in greenness was associated with a decrease of 13% (OR = 0.87 [95%CI: 0.83, 0.92] for NDVI500m and OR = 0.87 [95%CI: 0.82, 0.91] for EVI500m) in MetS risk after adjusting for covariates. This association was stronger in those aged < 60 years (e.g., OR = 0.86 [95%CI: 0.81, 0.92] for NDVI500m), males (e.g., OR = 0.73 [95%CI: 0.67, 0.80] for NDVI500m), having an educational level of primary school or above (OR = 0.81 [95%CI: 0.74, 0.89] for NDVI500m), married/cohabitation (OR = 0.86 [95%CI: 0.81, 0.91] for NDVI500m), businessman (OR = 0.82 [95%CI: 0.68, 0.99] for NDVI500m), other laborers (OR = 0.77 [95%CI: 0.68, 0.88] for NDVI500m), and non-smokers (OR = 0.77 [95%CI: 0.70, 0.85] for NDVI500m). The joint effect of all six mediators mediated about 48.1% and 44.6% of the total effect of NDVI500m and EVI500m on the MetS risk, respectively. Among them, BMI showed the strongest independent mediation effect (25.0% for NDVI500m), followed by NO2 and PM10.ConclusionExposure to residential greenness was associated with a decreased risk for MetS. PA, BMI, and the four air pollutants jointly interpreted nearly half of the mediation effects on the greenness-MetS association.

Abstract Background In high grade serous ovarian cancer (HGSOC), there is a spectrum of sensitivity to first line platinum‐based chemotherapy. This study molecularly characterizes HGSOC patients from two distinct groups of chemotherapy responders (good vs. poor). Methods Following primary debulking surgery and intravenous carboplatin/paclitaxel, women with stage III–IV HGSOC were grouped by response. Patients in the good response (GR) and poor response (PR) groups respectively had a progression‐free intervals (PFI) of ≥12 and ≤6 months. Analysis of surgical specimens interrogated genomic and immunologic features using whole exome sequencing. RNA‐sequencing detected gene expression outliers and inference of immune infiltrate, with validation by targeted NanoString arrays. PD‐L1 expression was scored by immunohistochemistry (IHC). Results A total of 39 patient samples were analyzed (GR = 20; PR = 19). Median PFI for GR and PR patient cohorts was 32 and 3 months, respectively. GR tumors were enriched for loss‐of‐function BRCA2 mutations and had a significantly higher nonsynonymous mutation rate compared to PR tumors (p = 0.001). Samples from the PR cohort were characterized by mutations in MGA and RAD51B and trended towards a greater rate of amplification of PIK3CA, MECOM, and ATR in comparison to GR tumors. Gene expression analysis by NanoString correlated increased PARP4 with PR and increased PD‐L1 and EMSY with GR. There was greater tumor immune cell infiltration and higher immune cell PD‐L1 protein expression in the GR group. Conclusions Our research demonstrates that tumors from HGSOC patients responding poorly to first line chemotherapy have a distinct molecular profile characterized by actionable drug targets including PARP4.

Although two years have passed since the coronavirus disease 2019 (COVID-19) outbreak, various variants are still rampant across the globe. The Omicron variant, in particular, is rapidly gained dominance through its ability to spread. In this study, we elucidated the spatial distribution pattern of Omicron from a global perspective. We used the cumulative number of notified COVID-19 cases per country spanning four weeks up to February 10, 2022, and the proportion of the Omicron variant genomic sequences from the Global Initiative on Sharing Avian Influenza Data (GISAID). The global spatial distribution of Omicron was investigated by analyzing Global & Local Moran’s I and Getis- Ord General G. The spatial weight matrix was defined by combining K-Nearest neighbour and flight connectivity between countries. The results showed that the epidemic is relatively severe in Europe, countries with a high number of Omicron cases and incidence tended to be clustered spatially. In contrast, there are relatively fewer Omicron cases in Asia and Africa, with few hotspots identified. Furthermore, some noted spatial outliers, such as a lowvalue area surrounded by high-value areas, deserve special attention. This study has improved our awareness of the global distribution of Omicron. The findings can provide helpful information for deploying targeted epidemic preparedness for the subsequent COVID-19 variant and future epidemics.

In a global and highly competitive world, the importance of creativity is increasing as it supports adaptability, health, and actualization. Yet, because most research focuses on what it takes to produce creative artifacts, interventions supporting growth in creative potential remains underexplored. To address this limitation, the first goal of this paper is to review the creativity science literature to identify the elements that underpin the realization of an individual’s creative potential. The summary of the literature is presented using a framework which highlights the interactions between environmental elements (i.e., cultural values, social interactions, and material world) and actors’ elements (i.e., affective attributes and states, cognitive skills, and physical expression). Using a systemic perspective, the framework illustrates ‘what’ creativity enhancement interventions should aim for, to facilitate the emergence of creative actions. Given the current lack of holistic, embodied, and interactive evidence-based interventions to nurture the creative potential elements identified, the second part of this review builds on movement sciences literature and physical literacy conceptualization to suggest that enriched movement activities are promising avenues to explore. Specifically, following non-linear pedagogy approaches, an intervention called movement improvisation is introduced. Ecological dynamics principles are used to explain how improvising with movement in a risk-friendly environment can lead to cognitive, affective, social, and cultural repertoire expansion. To interrogate this argument further, the review concludes with possible solutions to withstand research challenges and raises future study questions. Overall, combining creativity and movement sciences in this review demonstrates the potential for well-designed movement interventions to ignite creative potential for individuals and overcome the tendency to remain anchored in a state of inertia.

The Cameron Highlands has experienced multiple land encroachment activities and repeated deforestation, leading to extensive land-use and land-cover change (LULCC) during the past six decades. This study aims to determine the LULCC against topography in Cameron Highlands between 2009 and 2019 by using geospatial techniques to analyze Landsat 7 (ETM+) and 8 (OLI/TIRS), ASTER GDEM and MODIS imaging sensors. The results showed a decline of 35.98 km2 in primary forests over ten years across the Cameron Highlands, while agricultural lands and urban areas flourished by a rise of 51.61 km2 and 11.00 km2 respectively. It can be noted that the elevation most affected is between 1000 and 1500 m, across all classes. Further results showed the expansion of both agriculture and urban development onto slopes above 35°, leading to an instability of soil structure. In a comparison of the base years of 2009 with 2019, mean LST results have shown temperatures rising by 7.5°C, while an average between 3 and 4°C across the region is recorded. The results obtained provide new information for government bodies and land planners to coordinate their actions without further jeopardizing the environment of the Cameron Highlands.

Objective To estimate the number of deaths from foodborne disease in the UK from 11 key pathogens.Design Four different models were developed using data from a range of sources. These included enhanced surveillance, outbreaks, death certificates and hospital episode statistics data. For each model, median estimates were produced with 95% credible intervals (CrI). The results from the different models were compared.Results The estimates for foodborne deaths for each pathogen from the different models were consistent, with CrIs largely overlapping. Based on the preferred model for each pathogen, foodborne norovirus is estimated to cause 56 deaths per year (95% CrI 32 to 92), foodborne Salmonella 33 deaths (95% CrI 7 to 159), foodborne Listeria monocytogenes 26 deaths (95% CrI 24 to 28), foodborne Clostridium perfringens 25 deaths (95% CrI 1 to 163) and foodborne Campylobacter 21 deaths (95% CrI 8 to 47). The considerable overlap in the CrIs means it is not possible to make any firm conclusions on ranking. Most of these deaths occur in those aged over 75 years. Foodborne deaths from Shigella, Cryptosporidium, Giardia, adenovirus, astrovirus and rotavirus are all rare.Conclusions We estimate that there are 180 deaths per year in the UK (95% CrI 113 to 359) caused by foodborne disease based on these 11 pathogens. While this is a small fraction of the estimated 2.4 million cases of foodborne illness per year it still illustrates the potential severity of these illnesses demonstrating the importance in continuing efforts to reduce these infections.

Laser balloon (LB) has emerged as an interesting strategy for pulmonary vein isolation in paroxysmal atrial fibrillation (AF). A third-generation LB has recently been developed, allowing a continuous ablation set. We aimed to compare the results from our center’s experience with second and third-generation LBs to a cohort of matched patients who had undergone radiofrequency ablation (RFA) with contact-force catheters. This retrospective monocenter case-control study included our first 50 LB paroxysmal AF ablations (26 second and 24 third-generation LB) and 50 RFA controls, matched on age, sex and left atrial dilation. The two groups had similar baseline parameters. LB procedures were significantly shorter than RFA (129 (110–160) vs. 160 (119–198) min, p = 0.007). During AF ablation, two major complications occurred in each group. At the one-year follow-up, AF recurrence was diagnosed in 7 (14%) of the LB group vs. 14 (28%) of the RFA group (p = 0.14). Moreover, we observed that third-generation LB procedures were associated with shorter laser applications (22 (19–29) vs. 69 (55–76) min, p < 0.001) and procedural durations (111 (100–128) vs. 151.5 (128.5–167) min, p < 0.001) compared to second-generation LB procedures. In the context of the major increase in the number of AF ablations, LB demonstrated consistent results in terms of clinical success, complications and also reduced procedure durations compared to RFA.

This update reflects upon the outcomes of the UNFCCC (United Nations Framework Convention on Climate Change) negotiations held in Paris in December 2015 (COP21). As the dust settles, this update explores the temperature targets, loss and damage, climate justice and what the agreement might mean for small island states.

The latest and most significant round of multilateral climate negotiations (COP21) takes place in Paris (30/11 to 11/12/2015). Like other participants and signatories to the United Nations Framework Convention on Climate Change, small island states have submitted contributions (INDCs) towards reducing emissions as a precursor to the creation of a post-Kyoto global emissions framework. This reflection outlines their contributions and examines the underlying dynamics of small island INDCs as they attempt to engage with the process of international negotiation. Preliminary findings confirm the need for small island states to be supported financially and technically by global institutional mechanisms in order to develop the capacity to deal with climate change.

Mountainous regions are more sensitive to climatic condition changes and are susceptible to recent increases in temperature. Due to urbanization and land use/land cover (LULC) issues, Cameron Highlands has been impacted by rising land surface temperature (LST) variation. Thus, this study was carried out to explore the impact of the LULC change on LST in the Cameron Highlands from 2009 to 2019 using remote sensing images acquired from Landsat 7 ETM+, Landsat 8 Operational Land Imager (OLI/TIRS), and Moderate Resolution Imaging Spectroradiometer (MODIS) 11A Thermal sensors. A split-window algorithm was applied to Landsat 8 images (2013–2019) to derive the LST. Air temperature data of the study area were also obtained to cross-validate data sources. Based on the validation results, the accuracy of LULC and LST outputs were more than 94.6% and 80.0%, respectively. The results show that the current trend of urban growth continues at a rate of 0.16% per year, and the area experienced an LST increase of 2 °C between 2009 and 2019. This study is crucial for land planners and environmentalists to understand the impacts of LULC change on LST and to propose appropriate policy measures to control development in Cameron Highlands.

AF is a heterogeneous rhythm disorder that is related to a wide spectrum of etiologies and has broad clinical presentations. Mechanisms underlying AF are complex and remain incompletely understood despite extensive research. They associate interactions between triggers, substrate and modulators including ionic and anatomic remodeling, genetic predisposition and neuro-humoral contributors. The pulmonary veins play a key role in the pathogenesis of AF and their isolation is associated to high rates of AF freedom in patients with paroxysmal AF. However, ablation of persistent AF remains less effective, mainly limited by the difficulty to identify the sources sustaining AF. Many theories were advanced to explain the perpetuation of this form of AF, ranging from a single localized focal and reentrant source to diffuse bi-atrial multiple wavelets. Translating these mechanisms to the clinical practice remains challenging and limited by the spatio-temporal resolution of the mapping techniques. AF is driven by focal or reentrant activities that are initially clustered in a relatively limited atrial surface then disseminate everywhere in both atria. Evidence for structural remodeling, mainly represented by atrial fibrosis suggests that reentrant activities using anatomical substrate are the key mechanism sustaining AF. These reentries can be endocardial, epicardial, and intramural which makes them less accessible for mapping and for ablation. Subsequently, early interventions before irreversible remodeling are of major importance. Circumferential pulmonary vein isolation remains the cornerstone of the treatment of AF, regardless of the AF form and of the AF duration. No ablation strategy consistently demonstrated superiority to pulmonary vein isolation in preventing long term recurrences of atrial arrhythmias. Further research that allows accurate identification of the mechanisms underlying AF and efficient ablation should improve the results of PsAF ablation.

Background: Excess weight is associated with poor health and increased health-care costs. However, a detailed understanding of the effects of excess weight on total hospital costs and costs for different health conditions is needed. Methods: Women in England aged 50–64 years were recruited into the prospective Million Women Study cohort in 1996–2001 through 60 NHS breast cancer screening centres. Participants were followed up and annual hospital costs and admission rates were estimated for April 1, 2006, to March 31, 2011, in relation to body-mass index (BMI) at recruitment, overall and for categories of health conditions defined by the International Classification of Diseases 10th revision chapter of the primary diagnosis at admission. Associations of BMI with hospital costs were projected to the 2013 population of women aged 55–79 years in England. Findings: 1 093 866 women who provided information on height and weight, had a BMI of at least 18·5 kg/m2, and had no previous cancer at recruitment, were followed up for an average of 4·9 years from April 1, 2006 (12·3 years from recruitment), during which time 1·84 million hospital admissions were recorded. Annual hospital costs were lowest for women with a BMI of 20·0 kg/m2 to less than 22·5 kg/m2 (£567 per woman per year, 99% CI 556–577). Every 2 kg/m2 increase in BMI above 20 kg/m2 was associated with a 7·4% (7·1–7·6) increase in annual hospital costs. Excess weight was associated with increased costs for all diagnostic categories, except respiratory conditions and fractures. £662 million (14·6%) of the estimated £4·5 billion of total annual hospital costs among all women aged 55–79 years in England was attributed to excess weight (BMI ≥25 kg/m2), of which £517 million (78%) arose from hospital admissions with procedures. £258 million (39%) of the costs attributed to excess weight were due to musculoskeletal admissions, mainly for knee replacement surgeries. Interpretation: Excess body weight is associated with increased hospital costs for middle-aged and older women in England across a broad range of conditions, especially knee replacement surgery and diabetes. These results provide reliable up-to-date estimates of the health-care costs of excess weight and emphasise the need for investment to tackle this public health issue. Funding: Cancer Research UK; Medical Research Council; National Institute for Health Research.

Leading a new network is a distinctive act, defined by a range of apparent paradoxes. The leader does not occupy a position of hierarchical power but needs influence if the network is to thrive. It is rooted in enquiry but uses advocacy to build its momentum. Networks cannot be managed, but they need management.

Mixed cryoglobulinemia is the most common extrahepatic disease manifestation of chronic hepatitis C virus (HCV) infection, where immunoglobulins precipitate at low temperatures and cause symptoms such as vasculitis, glomerulonephritis and arthralgia. HCV-associated cryoglobulinemia is also strongly linked with the development of B cell non-Hodgkin lymphoma. Abnormal B cell function in HCV infections can lead to the formation of HCV cryoglobulin complexes that usually comprise monoclonal rheumatoid factor and HCV-specific immune complexes. The aim of this study was to characterize the activation phenotype of B cells from patients with chronic HCV infection in comparison to healthy controls using flow cytometry. In addition, we determined how the activation status varies depending on the presence of cryoglobulinemia and advanced liver fibrosis. We found that only memory B cells, not naïve cells, were significantly activated in chronic HCV infection when compared with healthy controls. We also identified markers of memory B cell activation that were specific for HCV patients with cryoglobulinemia (CD86, CD71, HLA-DR) and advanced liver disease (CD86). Our results demonstrate that HCV infection has differential effects on B cells depending on the severity of hepatic and extrahepatic disease.

Although a cure for HCV is on the near horizon, emerging drug cocktails will be expensive, associated with side-effects and resistance making a global vaccine an urgent priority given the estimated high incidence of infection around the world. Due to the highly heterogeneous nature of HCV, an effective HCV vaccine which could elicit broadly cross-neutralizing antibodies has represented a major challenge. In this study, we tested for the presence of cross-neutralizing antibodies in human volunteers who were immunized with recombinant glycoproteins gpE1/gpE2 derived from a single HCV strain (HCV1 of genotype 1a). Cross neutralization was tested in Huh-7.5 human hepatoma cell cultures using infectious recombinant HCV (HCVcc) expressing structural proteins of heterologous HCV strains from all known major genotypes, 1-7. Vaccination induced significant neutralizing antibodies against heterologous HCV genotype 1a virus which represents the most common genotype in North America. Of the 16 vaccinees tested, 3 were selected on the basis of strong 1a virus neutralization for testing of broad cross-neutralizing responses. At least 1 vaccinee was shown to elicit broad cross-neutralization against all HCV genotypes. Although observed in only a minority of vaccinees, our results prove the key concept that a vaccine derived from a single strain of HCV can elicit broad cross-neutralizing antibodies against all known major genotypes of HCV and provide considerable encouragement for the further development of a human vaccine against this common, global pathogen.

The gammaretroviruses xenotropic murine leukemia virus (MLV)-related virus (XMRV) and MLV have been reported to be more prevalent in plasma and peripheral blood mononuclear cells of chronic fatigue syndrome (CFS) patients than in healthy controls. Here, we report the complex analysis of whole blood and plasma samples from 58 CFS patients and 57 controls from Canada for the presence of XMRV/MLV nucleic acids, infectious virus, and XMRV/MLV-specific antibodies. Multiple techniques were employed, including nested and qRT-PCR, cell culture, and immunoblotting. We found no evidence of XMRV or MLV in humans and conclude that CFS is not associated with these gammaretroviruses.