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Abstract SARS-CoV-2 has resulted in high levels of morbidity and mortality world-wide, and severe complications can occur in older populations. Humoral immunity induced by authorized vaccines wanes within 6 months, and frequent boosts may only offer transient protection. GRT-R910 is an investigational self-amplifying mRNA (samRNA)-based SARS-CoV-2 vaccine delivering full-length Spike and selected conserved non-Spike T cell epitopes. This study reports interim analyses for a phase I open-label dose-escalation trial evaluating GRT-R910 in previously vaccinated healthy older adults (NCT05148962). Primary endpoints of safety and tolerability were assessed. Most solicited local and systemic adverse events (AEs) following GRT-R910 dosing were mild to moderate and transient, and no treatment-related serious AEs were observed. The secondary endpoint of immunogenicity was assessed via IgG binding assays, neutralization assays, interferon-gamma ELISpot, and intracellular cytokine staining. Neutralizing antibody titers against ancestral Spike and variants of concern were boosted or induced by GRT-R910 and, contrasting to authorized vaccines, persisted through at least 6 months after the booster dose. GRT-R910 increased and/or broadened functional Spike-specific T cell responses and primed functional T cell responses to conserved non-Spike epitopes. This study is limited due to small sample size, and additional data from ongoing studies will be required to corroborate these interim findings.

The trial objective was to compare the performance and animal health parameters of pigs raised according to one of 3 antibiotic (AB) protocols: standard AB medication consisting of mass treatment on days 4 and 21 and judicious AB therapy given therapeutically thereafter as group medication in water and feed or by individual injection (group T1, N = 702); modified AB medication identical to group T1 but with mass treatment only on day 4 and without subsequent therapeutic feed medication (group T2, N = 675); or an antibiotic-free (ABF) regimen (group T3, N = 702). All pigs were vaccinated with a modified-live porcine reproductive and respiratory syndrome virus (PRRSV) vaccine 3 days after weaning. Using a seeder pig model to mimic endemic field infection dynamics, pigs were contact-challenged with virulent PRRSV lineage 1 strain 174 four weeks after vaccination. At finishing, average daily gain (ADG) and mean feed conversion ratio (FCR) were significantly better (p ≤ 0.05) for the T1 and T2 groups compared to the T3 group. There were no significant differences in post-weaning ADG and FCR between the T1 and T2 groups. Mortality and removals significantly favored (p ≤0.05) the T1 and T2 groups (20.94% and 24.89%, respectively) versus the T3 group (57.98%). Net revenue per pig was $105.43, $98.79, and $33.81 for the T1, T2 and T3 groups, respectively. Under the conditions of this study, these results indicate that in a PRRSV-endemic setting involving bacterial co-infections, an ABF production strategy may leave pigs at considerable risk of exposure to severe clinical disease and that judicious use of antibiotics can significantly improve animal health.

In this study, conducted in Nova Scotia, Canada, we surveyed people at farmers' markets, agricultural fairs, and other agricultural events to investigate the views of people who would likely be trying to incorporate local food into their everyday shopping habits. Survey respondents (N = 2,316) indicated strong positive beliefs, attitudes, and propensity toward buying local food. At the same time, however, they reported difficulty identifying whether food was local as well as a lack of opportunities to buy local food. The findings build upon the growing body of research surrounding the "buy local" movement in North America by providing insight into why people want to buy local and potential barriers that prevent stronger markets for local food products.

JUSTIFICATIVA E OBJETIVOS: O tromboembolismo venoso (TEV), que inclui a trombose venosa profunda (TVP) e o tromboembolismo pulmonar (TEP) são complicações comuns em pacientes críticos. A ocorrência de TEV acarreta um substancial aumento da morbimortalidade dos pacientes internados em unidades de terapia intensiva (UTI). CONTEÚDO: A maioria dos pacientes críticos apresenta alto risco para ocorrência de complicações tromboembólicas, entretanto, a prevenção do TEV muitas vezes não é realizada de maneira adequada para este grupo de pacientes. A heparina de baixo peso molecular (HBPM) parece ser o método mais eficiente para a prevenção do TEV em pacientes de UTI. Entretanto, é patente a escassez de estudos voltados para esta população, cujas particularidades levam a recomendações específicas em relação ao diagnóstico e tratamento. CONCLUSÕES: Esta revisão faz uma análise do risco, discute os principais trabalhos publicados a respeito da profilaxia e sugere estratégias para a diminuição da ocorrência de TEV nos pacientes críticos.BACKGROUND AND OBJECTIVES: Venous thromboembolism (VTE), with includes deep vein thrombosis (DVT) and pulmonary embolism (PE), is a common complication in critically ill patients, resulting in high morbidity and mortality. CONTENTS: Most patients treated in intensive care units (ICU) face a high risk of thromboembolic complications. Despite these considerations, the prevention of VTE may not be as high a priority in ICU patients as it is in other high-risk patient groups. Low molecular weight heparin (LMWH) may be the optimal prophylaxis in most ICU patients, but there is a lack of sufficient data including the paucity of VTE consensus and guidelines documents pertaining to critically ill patients. CONCLUSIONS: This article reviews background, current options, and recommendations regarding VTE in intensive care population emphasizing special diagnostic and treatment considerations in the ICU setting.

Early intramuscular administration of SARS-CoV-2-neutralising monoclonal antibody combination, tixagevimab–cilgavimab, to non-hospitalised adults with mild to moderate COVID-19 has potential to prevent disease progression. We aimed to evaluate the safety and efficacy of tixagevimab–cilgavimab in preventing progression to severe COVID-19 or death. TACKLE is an ongoing, phase 3, randomised, double-blind, placebo-controlled study conducted at 95 sites in the USA, Latin America, Europe, and Japan. Eligible participants were non-hospitalised adults aged 18 years or older with a laboratory-confirmed SARS-CoV-2 infection (determined by RT-PCR or an antigen test) from any respiratory tract specimen collected 3 days or less before enrolment and who had not received a COVID-19 vaccination. A WHO Clinical Progression Scale score from more than 1 to less than 4 was required for inclusion and participants had to receive the study drug 7 days or less from self-reported onset of mild to moderate COVID-19 symptoms or measured fever. Participants were randomly assigned (1:1) to receive either a single tixagevimab–cilgavimab 600 mg dose (two consecutive 3 mL intramuscular injections, one each of 300 mg tixagevimab and 300 mg cilgavimab) or placebo. Randomisation was stratified (using central blocked randomisation with randomly varying block sizes) by time from symptom onset, and high-risk versus low-risk of progression to severe COVID-19. Participants, investigators, and sponsor staff involved in the treatment or clinical evaluation and monitoring of the participants were masked to treatment-group assignments. The primary endpoints were severe COVID-19 or death from any cause through to day 29, and safety. This study is registered with ClinicalTrials.gov , NCT04723394. Between Jan 28, 2021, and July 22, 2021, 1014 participants were enrolled, of whom 910 were randomly assigned to a treatment group (456 to receive tixagevimab–cilgavimab and 454 to receive placebo). The mean age of participants was 46·1 years (SD 15·2). Severe COVID-19 or death occurred in 18 (4%) of 407 participants in the tixagevimab–cilgavimab group versus 37 (9%) of 415 participants in the placebo group (relative risk reduction 50·5% [95% CI 14·6–71·3]; p=0·0096). The absolute risk reduction was 4·5% (95% CI 1·1–8·0; p<0·0001). Adverse events occurred in 132 (29%) of 452 participants in the tixagevimab–cilgavimab group and 163 (36%) of 451 participants in the placebo group, and were mostly of mild or moderate severity. There were three COVID-19-reported deaths in the tixagevimab–cilgavimab group and six in the placebo group. A single intramuscular tixagevimab–cilgavimab dose provided statistically and clinically significant protection against progression to severe COVID-19 or death versus placebo in unvaccinated individuals and safety was favourable. Treating mild to moderate COVID-19 earlier in the disease course with tixagevimab–cilgavimab might lead to more favourable outcomes. AstraZeneca. [ABSTRACT FROM AUTHOR]

Apresenta-se um estudo retrospectivo bibligráfico sobre a transmissão sexual do HCV, listando as principais evidências que indicam a sua ocorrência e os principais pontos que não a favorecem. É feita uma revisão sobre a sua etiologia e epidemiologia, ressaltando-se a importância da via sexual na manutenção do HCV na natureza, principalmente em contextos de alta endemicidade e métodos de prevenção.

This article contends that researchers can and should be active participants in making sound archives more accessible. In fact, such advocacy can be consequential in setting up possibilities for creative research on race within radio history and sound studies. Using the example of NPR's All Things Considered archive spanning from 1971–1983, I demonstrate how academics and archivists can work together to make possible the preservation and accessibility of sound archives. This particular collaboration offers an opportunity to take a cultural approach to understanding newsroom diversity, more specifically: the cultural constraints of linguistic norms and the emergent cultures that arise as aberrations from such norms. The article reflects on this project's implications for other scholars who work with archives that wish to invest in sound archive preservation and use. [ABSTRACT FROM AUTHOR]

O sarcoma de Kaposi, até há alguns anos um tumor raro, adquiriu importância pela sua associação com a síndrome de imunodeficiência adquirida (SIDA). [...]

Based on a survey and face-to-face interview with 24 students who lived most of their lives on farms, this study extends the findings of previously reported research by examining similarities and differences between males' and females' beliefs, attitudes, and adoption offarm health and safety practices. The survey and interview asked participants to recall their experiences growing up on a farm and in particular how they learned tofarm safely. Data were analyzed qualitatively, focusing on two potentially gendered farm chores: tractor operation and livestock handling. Particular emphasis was placed on identifying similarities and differences between boys' and girls' childhood farm experiences and transfer of farm health and safety knowledge. Main findings indicated that although there may be some differences between how boys and girls perceive the operational aspects of the farm (particularly parental roles), there seems to be little difference between genders in terms of tasks they were permitted to do and in their health and safely practices. The current study adds to a small but growing literature suggesting that gender differences play a relatively small role in farm health and safety practices among individuals strongly committed to and engaged in agriculture. [ABSTRACT FROM AUTHOR]

Highlights: [•] Dengue is the fastest spreading vector borne viral disease. [•] A vaccine would provide an important public health tool. [•] Vaccine candidates must demonstrate safety and efficacy in clinical trials. [•] Study sites must ensure high quality, long term surveillance. [•] Appropriate preparation and community engagement are critical. [Copyright &y& Elsevier]

The article presents a study which evaluates the influence of apprentice farming on safety beliefs, attitudes, and farming practices of 24 farm youth attending the Nova Scotia Agricultural College. The study is conducted through semi-structured interviews designed to derive information regarding the respondents' memories of their involvement in farming. The results showed that early experience related to farming appears to be an integral part of the social context of the farming community.

An essay is presented on the life and works of composer Ester Mägi. It discusses the contributions of Mägi to the Estonian choral music, her Estonian national music style, and the awards and titles she received. It mentions the genres which she composed except for stage music and her compositional techniques by focusing on folk melodies harmonized in romantic style like her pice "Leidsid sõnad kalli viisi (Leaves Falling) and keeping her compositions fresh and modern.

SARS-CoV-2 has resulted in high levels of morbidity and mortality world-wide, and severe complications can occur in older populations. Humoral immunity induced by authorized vaccines wanes within 6 months, and frequent boosts may only offer transient protection. GRT-R910 is an investigational self-amplifying mRNA (samRNA)-based SARS-CoV-2 vaccine delivering full-length Spike and selected conserved non-Spike T cell epitopes. This study reports interim analyses for a phase I open-label dose-escalation trial evaluating GRT-R910 in previously vaccinated healthy older adults (NCT05148962). Primary endpoints of safety and tolerability were assessed. Most solicited local and systemic adverse events (AEs) following GRT-R910 dosing were mild to moderate and transient, and no treatment-related serious AEs were observed. The secondary endpoint of immunogenicity was assessed via IgG binding assays, neutralization assays, interferon-gamma ELISpot, and intracellular cytokine staining. Neutralizing antibody titers against ancestral Spike and variants of concern were boosted or induced by GRT-R910 and, contrasting to authorized vaccines, persisted through at least 6 months after the booster dose. GRT-R910 increased and/or broadened functional Spike-specific T cell responses and primed functional T cell responses to conserved non-Spike epitopes. This study is limited due to small sample size, and additional data from ongoing studies will be required to corroborate these interim findings., (© 2023. The Author(s).)

Background: This phase 3 trial assessed AZD7442 (tixagevimab/cilgavimab) for post-exposure prophylaxis against symptomatic coronavirus disease 2019 (COVID-19)., Methods: Adults without prior severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or COVID-19 vaccination were enrolled within 8 days of exposure to a SARS-CoV-2-infected individual and randomized 2:1 to a single 300-mg AZD7442 dose (one 1.5-mL intramuscular injection each of tixagevimab and cilgavimab) or placebo. Primary end points were safety and first post-dose SARS-CoV-2 reverse-transcription polymerase chain reaction (RT-PCR)-positive symptomatic COVID-19 event before day 183., Results: A total of 1121 participants were randomized and dosed (AZD7442, n = 749; placebo, n = 372). Median (range) follow-up was 49 (5-115) and 48 (20-113) days for AZD7442 and placebo, respectively. Adverse events occurred in 162 of 749 (21.6%) and 111 of 372 (29.8%) participants with AZD7442 and placebo, respectively, mostly mild/moderate. RT-PCR-positive symptomatic COVID-19 occurred in 23 of 749 (3.1%) and 17 of 372 (4.6%) AZD7442- and placebo-treated participants, respectively (relative risk reduction, 33.3%; 95% confidence interval [CI], -25.9 to 64.7; P = .21). In predefined subgroup analyses of 1073 (96%) participants who were SARS-CoV-2 RT-PCR-negative (n = 974, 87%) or missing an RT-PCR result (n = 99, 9%) at baseline, AZD7442 reduced RT-PCR-positive symptomatic COVID-19 by 73.2% (95% CI, 27.1 to 90.1) vs placebo., Conclusions: This study did not meet the primary efficacy end point of post-exposure prevention of symptomatic COVID-19. However, analysis of participants who were SARS-CoV-2 RT-PCR-negative or missing an RT-PCR result at baseline support a role for AZD7442 in preventing symptomatic COVID-19. Clinical Trials Registration. NCT04625972., Competing Interests: Potential conflicts of interest. M. J. L. reports research support from GSK, Johnson & Johnson, Moderna, and Novavax; consultancy for Dynavax, GSK, Merck & Co, Pfizer, and Seqirus; and participation on a data and safety monitoring board (DSMB)/advisory board for GSK. A. U. reports honoraria/speaker fees from Sanofi, Merck, Janssen, GSK, Roche, ViiV, and Gilead; advisory boards for Gilead, Merck, and ViiV/GSK; and participation on a DSMB for COV-Boost study, Flare study, and for Vicore. S. D. P. reports that the USU Infectious Diseases Clinical Research Program (IDCRP), a US Department of Defense institution, and HJF were funded under a cooperative research and development agreement to help conduct the STORM CHASER study, sponsored by AstraZeneca. The HJF, in support of the USU IDCRP, was also funded by the Department of Defense Joint Program Executive Office for Chemical, Biological, Radiological, and Nuclear Defense to augment the conduct of an unrelated phase 3 vaccine trial sponsored by AstraZeneca. Both of these trials were part of the US government COVID-19 response. M. T. E. reports patents planned, issued, or pending by AstraZeneca on AZD7442. P. G. reports consulting fees from Medicago and Takeda Vaccines as senior medical director; a leadership or fiduciary role as a full member of the Academy of Medicine in Rio de Janeiro, Brazil; and stock or stock options in Takeda Pharmaceuticals, AstraZeneca. All authors report medical writing assistance provided by Prime Global. S. T., A. T., Y. Y., S. S., R. H. A., R. B., K. D., P. G., E. J. K., G. C. K. W. K., S. I., K. A. N., A. S., K. S., M. N. P., and M. T. E. are employees of and hold or may hold stock in AstraZeneca. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: The monoclonal-antibody combination AZD7442 is composed of tixagevimab and cilgavimab, two neutralizing antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that have an extended half-life and have been shown to have prophylactic and therapeutic effects in animal models. Pharmacokinetic data in humans indicate that AZD7442 has an extended half-life of approximately 90 days., Methods: In an ongoing phase 3 trial, we enrolled adults (≥18 years of age) who had an increased risk of an inadequate response to vaccination against coronavirus disease 2019 (Covid-19), an increased risk of exposure to SARS-CoV-2, or both. Participants were randomly assigned in a 2:1 ratio to receive a single dose (two consecutive intramuscular injections, one containing tixagevimab and the other containing cilgavimab) of either 300 mg of AZD7442 or saline placebo, and they were followed for up to 183 days in the primary analysis. The primary safety end point was the incidence of adverse events after a single dose of AZD7442. The primary efficacy end point was symptomatic Covid-19 (SARS-CoV-2 infection confirmed by means of reverse-transcriptase-polymerase-chain-reaction assay) occurring after administration of AZD7442 or placebo and on or before day 183., Results: A total of 5197 participants underwent randomization and received one dose of AZD7442 or placebo (3460 in the AZD7442 group and 1737 in the placebo group). The primary analysis was conducted after 30% of the participants had become aware of their randomized assignment. In total, 1221 of 3461 participants (35.3%) in the AZD7442 group and 593 of 1736 participants (34.2%) in the placebo group reported having at least one adverse event, most of which were mild or moderate in severity. Symptomatic Covid-19 occurred in 8 of 3441 participants (0.2%) in the AZD7442 group and in 17 of 1731 participants (1.0%) in the placebo group (relative risk reduction, 76.7%; 95% confidence interval [CI], 46.0 to 90.0; P<0.001); extended follow-up at a median of 6 months showed a relative risk reduction of 82.8% (95% CI, 65.8 to 91.4). Five cases of severe or critical Covid-19 and two Covid-19-related deaths occurred, all in the placebo group., Conclusions: A single dose of AZD7442 had efficacy for the prevention of Covid-19, without evident safety concerns. (Funded by AstraZeneca and the U.S. government; PROVENT ClinicalTrials.gov number, NCT04625725.)., (Copyright © 2022 Massachusetts Medical Society.)

Background: Dengue is the most common mosquito-borne viral disease in human beings, and vector control has not halted its spread worldwide. A dengue vaccine for individuals aged 9 years and older has been licensed, but there remains urgent medical need for a vaccine that is safe and effective against all four dengue virus serotypes (DENV-1-4) in recipients of all ages. Here, we present the preplanned interim analyses at 6 months of a tetravalent dengue vaccine candidate (TDV), which is comprised of an attenuated DENV-2 virus strain (TDV-2) and three chimeric viruses containing the premembrane and envelope protein genes of DENV-1, DENV-3, and DENV-4 genetically engineered into the attenuated TDV-2 genome backbone (TDV-1, TDV-3, and TDV-4)., Methods: An ongoing phase 2, randomised, double-blind, placebo-controlled trial of a TDV is being done at three sites in dengue-endemic countries (Dominican Republic, Panama, and the Philippines) to determine its safety and immunogenicity over 48 months in healthy participants aged 2-17 years who were randomly assigned (1:2:5:1) using an interactive web response system (stratified by age) to subcutaneous TDV injection (one 0·5 mL dose containing 2·5 × 10 4 plaque-forming units [PFU] of TDV-1; 6·3 × 10 3 PFU of TDV-2; 3·2 × 10 4 PFU of TDV-3; and 4·0 × 10 5 PFU of TDV-4) in different dose schedules (two-dose regimen at 0 and 3 months, one dose at 0 months, or one dose at 0 months and a booster at 12 months) or placebo. The primary endpoint of this 6 month interim analysis was geometric mean titres (GMTs) of neutralising antibodies against DENV-1-4 in the per-protocol immunogenicity subset at 1 month, 3 months, and 6 months after the first injection. Safety was assessed as a secondary outcome as percentage of participants with serious adverse events in all participants who were injected (safety set), and solicited and unsolicited adverse events (immunogenicity subset). This trial is registered with ClinicalTrials.gov, number NCT02302066., Findings: 1800 participants were enrolled between Dec 5, 2014, and Feb 13, 2015. 1794 participants were given study injection as follows: 200 participants were given two-dose regimen at 0 and 3 months (group 1), 398 were given one dose at 0 months (group 2), 998 were given one dose at 0 months and will be given (trial ongoing) a booster at 12 months (group 3), and 198 were given placebo (group 4). These 1794 participants were included in the safety set; 562 participants were randomly assigned to the immunogenicity subset, of which 503 were included in the per-protocol set. TDV elicited neutralising antibodies against all DENV serotypes, which peaked at 1 month and remained elevated above baseline at 6 months. At 6 months, GMTs of neutralising antibodies against DENV-1 were 489 (95% CI 321-746) for group 1, 434 (306-615) for group 2, 532 (384-738) for group 3, and 62 (32-120) for group 4; GMTs of neutralising antibodies against DENV-2 were 1565 (1145-2140) for group 1, 1639 (1286-2088) for group 2, 1288 (1031-1610) for group 3, and 86 (44-169) for group 4; GMTs of neutralising antibodies against DENV-3 were 160 (104-248) for group 1, 151 (106-214) for group 2, 173 (124-240) for group 3, and 40 (23-71) for group 4; and GMTs of neutralising antibodies against DENV-4 were 117 (79-175) for group 1, 110 (80-149) for group 2, 93 (69-125) for group 3, and 24 (15-38) for group 4. No vaccine-related serious adverse events occurred; 15 (3%) of 562 participants in the immunogenicity subset reported vaccine-related unsolicited adverse events. The reactogenicity profile of TDV was acceptable, and similar to previous findings with TDV., Interpretation: TDV is safe and immunogenic in individuals aged 2-17 years, irrespective of previous dengue exposure. A second TDV dose induced enhanced immunogenicity against DENV-3 and DENV-4 in children who were seronegative before vaccination. These data supported the initiation of phase 3 evaluation of the efficacy and safety of TDV given in a two-dose schedule 3 months apart, with analyses that take into account baseline age and dengue serostatus., Funding: Takeda Vaccines., (Copyright © 2017 Elsevier Ltd. All rights reserved.)