Profiling and identification of novel rpoB mutations in rifampicin-resistant Mycobacterium tuberculosis clinical isolates from Pakistan

Introduction: Rifampicin (RIF) is one of the most effective anti-tuberculosis first-line drugs prescribed along with isoniazid. However, the emergence of RIF resistance Mycobacterium tuberculosis (MTB) isolates is a major issue towards tuberculosis (TB) control program in high MDR TB-burdened countries including Pakistan. Molecular data behind phenotypic resistance is essential for better management of RIF resistance which has been linked with mutations in rpoB gene. Since molecular studies on RIF resistance is limited in Pakistan, the current study was aimed to investigate the molecular data of mutations in rpoB gene behind phenotypic RIF resistance isolates in Pakistan. / Method: A total of 322 phenotypically RIF-resistant isolates were randomly selected from National TB Reference Laboratory, Pakistan for sequencing while 380 RIF resistance whole-genome sequencing (WGS) of Pakistani isolates (BioProject PRJEB25972), were also analyzed for rpoB mutations. / Result: Among the 702 RIF resistance samples, 675 (96.1%) isolates harbored mutations in rpoB in which 663 (94.4%) were detected within the Rifampicin Resistance Determining Region (RRDR) also known as a mutation hot spot region, including three novel. Among these mutations, 657 (97.3%) were substitutions including 603 (89.3%) single nucleotide polymorphism, 49 (7.25%) double and five (0.8%) triple. About 94.4% of Phenotypic RIF resistance strains, exhibited mutations in RRDR, which were also detectable by GeneXpert. / Conclusion: Mutations in the RRDR region of rpoB is a major mechanism of RIF resistance in MTB circulating isolates in Pakistan. Molecular detection of drug resistance is a faster and better approach than phenotypic drug susceptibility testing to reduce the time for transmission of RIF resistance strains in population. Such insights will inform the deployment of anti-TB drug regimens and disease control tools and strategies in high burden settings, such as Pakistan

Mechanisms of rhinovirus neutralisation by antibodies

Antibodies are a critical immune correlate of protection for rhinoviruses, particularly those antibodies found in the secretory compartment. For nonenveloped viruses such as rhinoviruses, antibody binding to regions of the icosahedral capsid can neutralise infections by a number of different mechanisms. The purpose of this review is to address the neutralising mechanisms of antibodies to rhinoviruses that would help progress vaccine development. At least five mechanisms of antibody neutralisation have been identified which depend to some extent on the antibody binding footprints upon the capsid. The most studied mechanisms are virion aggregation, inhibition of attachment to cells, and stabilisation or destabilisation of the capsid structure. Newer mechanisms of degradation inside the cell through cytoplasmic antibody detection or outside by phagocytosis rely on what might have been previously considered as non-neutralising antibodies. We discuss these various approaches of antibody interference of rhinoviruses and offer suggestions as to how these could influence vaccine design

Standardising Marine Renewable Energy Testing: Gap Analysis and Recommendations for Development of Standards

Marine renewable energy (MRE) is still an emerging technology. As such, there is still a lack of mature standards and guidance for the development and testing of these devices. The sector covers a wide range of disciplines, so there is a need for more comprehensive guidance to cover these. This paper builds on a study undertaken in the MaRINET2 project to summarise recommendations and guidance for testing MRE devices and components, by reviewing the recently published guidance. Perceived gaps in the guidance are then discussed, expanding on the previous study. Results from an industry survey are also used to help quantify and validate these gaps. The main themes identified can be summarised as: the development progression from concept to commercialisation, including more complex environmental conditions in testing, accurately modelling and quantifying the power generated, including grid integration, plus modelling and testing of novel moorings and foundation solutions. A pathway to a standardised approach to MRE testing is presented, building on recommendations learnt from the MaRINET2 round-robin testing, showing how these recommendations are being incorporated into the guidance and ultimately feeding into the development of international standards for the marine renewable energy sector

Severity of COVID-19 after Vaccination among Hemodialysis Patients: An Observational Cohort Study

Background and objectives: Patients receiving hemodialysis are at high risk from coronavirus disease 2019 (COVID-19) and demonstrate impaired immune responses to vaccines. There have been several descriptions of their immunologic responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination, but few studies have described the clinical efficacy of vaccination in patients on hemodialysis. // Design, setting, participants, & measurements: In a multicenter observational study of the London hemodialysis population undergoing surveillance PCR testing during the period of vaccine rollout with BNT162b2 and AZD1222, all of those positive for SARS-CoV-2 were identified. Clinical outcomes were analyzed according to predictor variables, including vaccination status, using a mixed effects logistic regression model. Risk of infection was analyzed in a subgroup of the base population using a Cox proportional hazards model with vaccination status as a time-varying covariate. // Results: SARS-CoV-2 infection was identified in 1323 patients of different ethnicities (Asian/other, 30%; Black, 38%; and White, 32%), including 1047 (79%) unvaccinated, 86 (7%) after first-dose vaccination, and 190 (14%) after second-dose vaccination. The majority of patients had a mild course; however, 515 (39%) were hospitalized, and 172 (13%) died. Older age, diabetes, and immune suppression were associated with greater illness severity. In regression models adjusted for age, comorbidity, and time period, prior two-dose vaccination was associated with a 75% (95% confidence interval, 56 to 86) lower risk of admission and 88% (95% confidence interval, 70 to 95) fewer deaths compared with unvaccinated patients. No loss of protection was seen in patients over 65 years or with increasing time since vaccination, and no difference was seen between vaccine types. // Conclusions: These data demonstrate a substantially lower risk of severe COVID-19 after vaccination in patients on dialysis who become infected with SARS-CoV-2

Offshore aquaculture of finfish: Big expectations at sea

Offshore aquaculture has gained momentum in recent years, and the production of an increasing number of marine fish species is being relocated offshore. Initially, predictions of the advantages that offshore aquaculture would present over nearshore farming were made without enough science-based evidence. Now, with more scientific knowledge, this review revisits past predictions and expectations of offshore aquaculture. We analysed and explained the oceanographic features that define offshore and nearshore sites. Using Atlantic salmon (Salmo salar) as a case study, we focussed on sea lice, amoebic gill disease, and the risk of harmful algal blooms, as well as the direct effects of the oceanography on the health and physiology of fish. The operational and licencing challenges and advantages of offshore aquaculture are also considered. The lack of space in increasingly saturated sheltered areas will push new farms out to offshore locations and, if appropriate steps are followed, offshore aquaculture can be successful. Firstly, the physical capabilities of the farmed fish species and infrastructure must be fully understood. Secondly, the oceanography of potential sites must be carefully studied to confirm that they are compatible with the species-specific capabilities. And, thirdly, an economic plan considering the operational costs and licencing limitations of the site must be developed. This review will serve as a guide and a compilation of information for researchers and stakeholders

The Global Alliance for Infections in Surgery : defining a model for antimicrobial stewardship-results from an international cross-sectional survey

Background: Antimicrobial Stewardship Programs (ASPs) have been promoted to optimize antimicrobial usage and patient outcomes, and to reduce the emergence of antimicrobial-resistant organisms. However, the best strategies for an ASP are not definitively established and are likely to vary based on local culture, policy, and routine clinical practice, and probably limited resources in middle-income countries. The aim of this study is to evaluate structures and resources of antimicrobial stewardship teams (ASTs) in surgical departments from different regions of the world. Methods: A cross-sectional web-based survey was conducted in 2016 on 173 physicians who participated in the AGORA (Antimicrobials: A Global Alliance for Optimizing their Rational Use in Intra-Abdominal Infections) project and on 658 international experts in the fields of ASPs, infection control, and infections in surgery. Results: The response rate was 19.4%. One hundred fifty-six (98.7%) participants stated their hospital had a multidisciplinary AST. The median number of physicians working inside the team was five [interquartile range 4-6]. An infectious disease specialist, a microbiologist and an infection control specialist were, respectively, present in 80.1, 76.3, and 67.9% of the ASTs. A surgeon was a component in 59.0% of cases and was significantly more likely to be present in university hospitals (89.5%, p <0.05) compared to community teaching (83.3%) and community hospitals (66.7%). Protocols for pre-operative prophylaxis and for antimicrobial treatment of surgical infections were respectively implemented in 96.2 and 82.3% of the hospitals. The majority of the surgical departments implemented both persuasive and restrictive interventions (72.8%). The most common types of interventions in surgical departments were dissemination of educational materials (62.5%), expert approval (61.0%), audit and feedback (55.1%), educational outreach (53.7%), and compulsory order forms (51.5%). Conclusion: The survey showed a heterogeneous organization of ASPs worldwide, demonstrating the necessity of a multidisciplinary and collaborative approach in the battle against antimicrobial resistance in surgical infections, and the importance of educational efforts towards this goal.Peer reviewe

The LifeCycle Project-EU Child Cohort Network : a federated analysis infrastructure and harmonized data of more than 250,000 children and parents

Early life is an important window of opportunity to improve health across the full lifecycle. An accumulating body of evidence suggests that exposure to adverse stressors during early life leads to developmental adaptations, which subsequently affect disease risk in later life. Also, geographical, socio-economic, and ethnic differences are related to health inequalities from early life onwards. To address these important public health challenges, many European pregnancy and childhood cohorts have been established over the last 30 years. The enormous wealth of data of these cohorts has led to important new biological insights and important impact for health from early life onwards. The impact of these cohorts and their data could be further increased by combining data from different cohorts. Combining data will lead to the possibility of identifying smaller effect estimates, and the opportunity to better identify risk groups and risk factors leading to disease across the lifecycle across countries. Also, it enables research on better causal understanding and modelling of life course health trajectories. The EU Child Cohort Network, established by the Horizon2020-funded LifeCycle Project, brings together nineteen pregnancy and childhood cohorts, together including more than 250,000 children and their parents. A large set of variables has been harmonised and standardized across these cohorts. The harmonized data are kept within each institution and can be accessed by external researchers through a shared federated data analysis platform using the R-based platform DataSHIELD, which takes relevant national and international data regulations into account. The EU Child Cohort Network has an open character. All protocols for data harmonization and setting up the data analysis platform are available online. The EU Child Cohort Network creates great opportunities for researchers to use data from different cohorts, during and beyond the LifeCycle Project duration. It also provides a novel model for collaborative research in large research infrastructures with individual-level data. The LifeCycle Project will translate results from research using the EU Child Cohort Network into recommendations for targeted prevention strategies to improve health trajectories for current and future generations by optimizing their earliest phases of life.Peer reviewe

Global prevalence and genotype distribution of hepatitis C virus infection in 2015 : A modelling study

Publisher Copyright: © 2017 Elsevier LtdBackground The 69th World Health Assembly approved the Global Health Sector Strategy to eliminate hepatitis C virus (HCV) infection by 2030, which can become a reality with the recent launch of direct acting antiviral therapies. Reliable disease burden estimates are required for national strategies. This analysis estimates the global prevalence of viraemic HCV at the end of 2015, an update of—and expansion on—the 2014 analysis, which reported 80 million (95% CI 64–103) viraemic infections in 2013. Methods We developed country-level disease burden models following a systematic review of HCV prevalence (number of studies, n=6754) and genotype (n=11 342) studies published after 2013. A Delphi process was used to gain country expert consensus and validate inputs. Published estimates alone were used for countries where expert panel meetings could not be scheduled. Global prevalence was estimated using regional averages for countries without data. Findings Models were built for 100 countries, 59 of which were approved by country experts, with the remaining 41 estimated using published data alone. The remaining countries had insufficient data to create a model. The global prevalence of viraemic HCV is estimated to be 1·0% (95% uncertainty interval 0·8–1·1) in 2015, corresponding to 71·1 million (62·5–79·4) viraemic infections. Genotypes 1 and 3 were the most common cause of infections (44% and 25%, respectively). Interpretation The global estimate of viraemic infections is lower than previous estimates, largely due to more recent (lower) prevalence estimates in Africa. Additionally, increased mortality due to liver-related causes and an ageing population may have contributed to a reduction in infections. Funding John C Martin Foundation.publishersversionPeer reviewe