"I think it is right": a qualitative exploration of the acceptability and desired future use of oral swab and finger-prick HIV self-tests by lay users in KwaZulu-Natal, South Africa.

The uptake of HIV testing has increased in sub-Saharan Africa over the past three decades. However, the proportion of people aware of their HIV status remains lower than required to change the pandemic. HIV self-testing (HIVST) may meet this gap. Assessment of readiness for and the acceptability of HIVST by lay users in South Africa is limited. This paper presents results from a formative study designed to assess the perceived usability and acceptability of HIVST among lay users using several self-test prototypes. Fifty lay users were purposively selected from rural and peri-urban KwaZulu-Natal, South Africa. Acceptability of HIVST was assessed using a simple post-test quantitative assessment tool addressing confidence, ease-of-use, intended future use and willingness to pay. In-depth qualitative interviews explored what participants felt about the HIVST and why, their willingness to recommend and how much they would pay for a test. The key finding is that there is high acceptability regardless of self-test prototype. Acceptability is framed by two domains: usability and perceived need. Perceived usability was explored through perceived ease of use, which, regardless of actual correct usage, was reported by many of the respondents. Acceptability is influenced by perceived need, expressed by many who felt that the need for the self-test to protect privacy and autonomy. Ease of access and widespread availability of the test, not at a significant cost, were also important factors. Many participants would recommend self-test use to others and also indicated that they would choose to conduct the test again if it was free while some also indicated being willing to buy a test. The positive response and readiness amongst lay users for an HIVST in this context prototype suggests that there would be a ready and willing market for HIVST. For scalability and sustainability usability, including access and availability that are here independent indications of acceptability, should be considered. So too should the desire for future use, as an additional factor pointing to acceptability. The results show high acceptability in all of these areas domains and a general interest in HIVST amongst lay users in a community in KwaZulu-Natal

Understanding the treatment benefit of hyperimmune anti-influenza intravenous immunoglobulin (Flu-IVIG) for severe human influenza

Background: Antibody-based therapies for respiratory viruses are of increasing importance. The INSIGHT 006 trial administered anti-influenza hyperimmune intravenous immunoglobulin (Flu-IVIG) to patients hospitalized with influenza. Flu-IVIG treatment improved outcomes in patients with influenza B but showed no benefit for influenza A. Methods: To probe potential mechanisms of Flu-IVIG utility, sera collected from patients hospitalized with influenza A or B viruses (IAV or IBV) were analyzed for antibody isotype/subclass and Fcγ receptor (FcγR) binding by ELISA, bead-based multiplex, and NK cell activation assays. Results: Influenza-specific FcγR-binding antibodies were elevated in Flu-IVIG–infused IBV- and IAV-infected patients. In IBV-infected participants (n = 62), increased IgG3 and FcγR binding were associated with more favorable outcomes. Flu-IVIG therapy also improved the odds of a more favorable outcome in patients with low levels of anti-IBV Fc-functional antibody. Higher FcγR-binding antibody was associated with less favorable outcomes in IAV-infected patients (n = 50), and Flu-IVIG worsened the odds of a favorable outcome in participants with low levels of anti-IAV Fc-functional antibody. Conclusion: These detailed serological analyses provide insights into antibody features and mechanisms required for a successful humoral response against influenza, suggesting that IBV-specific, but not IAV-specific, antibodies with Fc-mediated functions may assist in improving influenza outcome. This work will inform development of improved influenza immunotherapies

Epidermal Growth Factor Receptor Activation in Glioblastoma through Novel Missense Mutations in the Extracellular Domain

Background: Protein tyrosine kinases are important regulators of cellular homeostasis with tightly controlled catalytic activity. Mutations in kinase-encoding genes can relieve the autoinhibitory constraints on kinase activity, can promote malignant transformation, and appear to be a major determinant of response to kinase inhibitor therapy. Missense mutations in the EGFR kinase domain, for example, have recently been identified in patients who showed clinical responses to EGFR kinase inhibitor therapy. Methods and Findings: Encouraged by the promising clinical activity of epidermal growth factor receptor (EGFR) kinase inhibitors in treating glioblastoma in humans, we have sequenced the complete EGFR coding sequence in glioma tumor samples and cell lines. We identified novel missense mutations in the extracellular domain of EGFR in 13.6% (18/132) of glioblastomas and 12.5% (1/ 8) of glioblastoma cell lines. These EGFR mutations were associated with increased EGFR gene dosage and conferred anchorage-independent growth and tumorigenicity to NIH-3T3 cells. Cells transformed by expression of these EGFR mutants were sensitive to small-molecule EGFR kinase inhibitors. Conclusions: Our results suggest extracellular missense mutations as a novel mechanism for oncogenic EGFR activation and may help identify patients who can benefit from EGFR kinase inhibitors for treatment of glioblastoma

Genetic and Antigenic Characterization of an Influenza A(H3N2) Outbreak in Cambodia and the Greater Mekong Subregion during the COVID-19 Pandemic, 2020

Introduction of non-pharmaceutical interventions to control COVID-19 in early 2020 coincided with a global decrease in active influenza circulation. However, between July and November 2020, an influenza A(H3N2) epidemic occurred in Cambodia and in other neighboring countries in the Greater Mekong Subregion in Southeast Asia. We characterized the genetic and antigenic evolution of A(H3N2) in Cambodia and found that the 2020 epidemic comprised genetically and antigenically similar viruses of Clade3C2a1b/131K/94N, but they were distinct from the WHO recommended influenza A(H3N2) vaccine virus components for 2020-2021 Northern Hemisphere season. Phylogenetic analysis revealed multiple virus migration events between Cambodia and bordering countries, with Laos PDR and Vietnam also reporting similar A(H3N2) epidemics immediately following the Cambodia outbreak: however, there was limited circulation of these viruses elsewhere globally. In February 2021, a virus from the Cambodian outbreak was recommended by WHO as the prototype virus for inclusion in the 2021-2022 Northern Hemisphere influenza vaccine. IMPORTANCE The 2019 coronavirus disease (COVID-19) pandemic has significantly altered the circulation patterns of respiratory diseases worldwide and disrupted continued surveillance in many countries. Introduction of control measures in early 2020 against Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection has resulted in a remarkable reduction in the circulation of many respiratory diseases. Influenza activity has remained at historically low levels globally since March 2020, even when increased influenza testing was performed in some countries. Maintenance of the influenza surveillance system in Cambodia in 2020 allowed for the detection and response to an influenza A(H3N2) outbreak in late 2020, resulting in the inclusion of this virus in the 2021-2022 Northern Hemisphere influenza vaccine

The Age-Specific Cumulative Incidence of Infection with Pandemic Influenza H1N1 2009 Was Similar in Various Countries Prior to Vaccination

Background: During the influenza pandemic of 2009 estimates of symptomatic and asymptomatic infection were needed to guide vaccination policies and inform other control measures. Serological studies are the most reliable way to measure influenza infection independent of symptoms. We reviewed all published serological studies that estimated the cumulative incidence of infection with pandemic influenza H1N1 2009 prior to the initiation of population-based vaccination against the pandemic strain. Methodology and Principal Findings: We searched for studies that estimated the cumulative incidence of pandemic influenza infection in the wider community. We excluded studies that did not include both pre- and post-pandemic serological sampling and studies that included response to vaccination. We identified 47 potentially eligible studies and included 12 of them in the review. Where there had been a significant first wave, the cumulative incidence of pandemic influenza infection was reported in the range 16%-28% in pre-school aged children, 34%-43% in school aged children and 12%-15% in young adults. Only 2%-3% of older adults were infected. The proportion of the entire population infected ranged from 11%-18%. We re-estimated the cumulative incidence to account for the small proportion of infections that may not have been detected by serology, and performed direct age-standardisation to the study population. For those countries where it could be calculated, this suggested a population cumulative incidence in the range 11%-21%. Conclusions and Significance: Around the world, the cumulative incidence of infection (which is higher than the cumulative incidence of clinical disease) was below that anticipated prior to the pandemic. Serological studies need to be routine in order to be sufficiently timely to provide support for decisions about vaccination. © 2011 Kelly et al.published_or_final_versio

Epidermal Growth Factor Receptor Activation in Glioblastoma through Novel Missense Mutations in the Extracellular Domain

BACKGROUND: Protein tyrosine kinases are important regulators of cellular homeostasis with tightly controlled catalytic activity. Mutations in kinase-encoding genes can relieve the autoinhibitory constraints on kinase activity, can promote malignant transformation, and appear to be a major determinant of response to kinase inhibitor therapy. Missense mutations in the EGFR kinase domain, for example, have recently been identified in patients who showed clinical responses to EGFR kinase inhibitor therapy. METHODS AND FINDINGS: Encouraged by the promising clinical activity of epidermal growth factor receptor (EGFR) kinase inhibitors in treating glioblastoma in humans, we have sequenced the complete EGFR coding sequence in glioma tumor samples and cell lines. We identified novel missense mutations in the extracellular domain of EGFR in 13.6% (18/132) of glioblastomas and 12.5% (1/8) of glioblastoma cell lines. These EGFR mutations were associated with increased EGFR gene dosage and conferred anchorage-independent growth and tumorigenicity to NIH-3T3 cells. Cells transformed by expression of these EGFR mutants were sensitive to small-molecule EGFR kinase inhibitors. CONCLUSIONS: Our results suggest extracellular missense mutations as a novel mechanism for oncogenic EGFR activation and may help identify patients who can benefit from EGFR kinase inhibitors for treatment of glioblastoma

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Habitat restoration plan and programmatic biological assessment for Potamilus capax (green 1832) in Arkansas

The fat pocketbook, Potamilus capax (Mollusca: Unionidae), was designated as “Endangered” in June 1976 by the USFWS in the entire range of the species. The present general distribution of P. capax has been reported from the upper Mississippi River on the boarders of Minnesota, Wisconsin, Iowa, Illinois, and Missouri, the Ohio River System on the borders of Indiana, Illinois, and Kentucky, especially its tributary the Wabash River in Indiana and Illinois, the White River of Missouri and Arkansas, and the St. Francis River system in Arkansas. Relocation of freshwater mussels prior to large-scale bridge construction, repair, or replacement has been broadly utilized for conventional management of construction impact. The success of that practice related to long-term viability of relocated specimens, however, has not been fully validated. This research was jointly funded by the Federal Highway Administration (FHWA) and the Arkansas State Highway and Transportation Department (AHTD) in 2003 as an Environmental Streamlining Initiative to provide more information regarding the likelihood of specific impacts to mussels attributed to sediment plumes downstream of highway construction activities. The research proposes to support a programmatic Biological Opinion for P. capax, which will provide a protocol for highway projects that may impact the species. Relocation can then be assessed for its ability to minimize loss of endangered freshwater mussel species, and in particular, P. capax. The objectives of this project are: 1) to determine the success of relocation efforts for P. capax associated with highway construction projects by investigating survival, movements, mortality, fitness (as indicated by condition factor), and fecundity of relocated and non-relocated adults and sub-adults, 2) to determine the success of propagation efforts resulting from highway construction projects by investigating the survival of juveniles returned to identified habitats and used for population enhancement (recruitment), and 3) to determine relative impacts at highway construction sites to P. capax and associated mussel assemblage by comparing pre- and post-construction abundance and composition, sediment deposition downstream of the construction, and individual mussel fitness. Data acquired will be submitted to the Fish and Wildlife Service as documentation of the likelihood of impacts for the programmatic Biological Assessment. These data will be utilized by the Fish and Wildlife Service in crafting the programmatic Biological Opinion. Initial observations have indicated relocated P. capax and Quadrula quadrula exhibit very different movement patterns post-relocation. For example, many resident and relocated P. capax are capable of moving 10 miles or more over a 12-hour period, while resident and relocated Q. quadrula have remained stationary up to four months after relocation. A continuation of this pattern may reveal that species-specific life history characteristics potentially influence movement patterns following relocation. Fatalities have occurred in the resident, relocated, and propagation animals of both species, though time to and cause of fatality are not known