Metamorphism of the Sierra de Maz and implications for the tectonic evolution of the MARA terrane

The Mesoproterozoic MARA terrane of western South America is a composite igneous-metamorphic complex that is important for Paleozoic paleogeographic reconstructions and the relative positions of Laurentia and Gondwana. The magmatic and detrital records of the MARA terrane are consistent with a Laurentian origin; however, the metamorphic and deformation records lack sufficient detail to constrain the correlation of units within the MARA terrane and the timing and mechanisms of accretion to the Gondwana margin. Combined regional mapping, metamorphic petrology, and garnet and monazite geochronology from the Sierra de Maz of northwest Argentina suggest that the region preserves four distinct litho-tectonic units of varying age and metamorphic conditions that are separated by middle- to lower-crustal ductile shear zones. The Zaino and Maz Complexes preserve Barrovian metamorphism and ages that are distinct from other units within the region. The Zaino and Maz Complexes both record metamorphism ca. 430–410 Ma and show no evidence of the regional Famatinian orogeny (ca. 490–455 Ma). In addition, the Maz Complex records an earlier granulite facies event at ca. 1.2 Ga. The Taco and Ramaditas Complexes, in contrast, experienced medium- and low-pressure upper amphibolite to granulite facies metamorphism, respectively, between ca. 470–460 Ma and were later deformed at ca. 440–420 Ma. The Maz shear zone that bounds the Zaino and Maz Complexes records sinistral oblique to sinistral deformation between ca. 430–410 Ma. The data suggest that at least some units in the MARA terrane were accreted by translation, and the Gondwana margin of northwest Argentina transitioned from a dominantly convergent margin to a highly oblique margin in the Silurian

Being Ready to Treat Ebola Virus Disease Patients

As the outbreak of Ebola virus disease (EVD) in West Africa continues, clinical preparedness is needed in countries at risk for EVD (e.g., United States) and more fully equipped and supported clinical teams in those countries with epidemic spread of EVD in Africa. Clinical staff must approach the patient with a very deliberate focus on providing effective care while assuring personal safety. To do this, both individual health care providers and health systems must improve EVD care. Although formal guidance toward these goals exists from the World Health Organization, Medecin Sans Frontières, the Centers for Disease Control and Prevention, and other groups, some of the most critical lessons come from personal experience. In this narrative, clinicians deployed by the World Health Organization into a wide range of clinical settings in West Africa distill key, practical considerations for working safely and effectively with patients with EVD

Can modeling of HIV treatment processes improve outcomes? Capitalizing on an operations research approach to the global pandemic

<p>Abstract</p> <p>Background</p> <p>Mathematical modeling has been applied to a range of policy-level decisions on resource allocation for HIV care and treatment. We describe the application of classic operations research (OR) techniques to address logistical and resource management challenges in HIV treatment scale-up activities in resource-limited countries.</p> <p>Methods</p> <p>We review and categorize several of the major logistical and operational problems encountered over the last decade in the global scale-up of HIV care and antiretroviral treatment for people with AIDS. While there are unique features of HIV care and treatment that pose significant challenges to effective modeling and service improvement, we identify several analogous OR-based solutions that have been developed in the service, industrial, and health sectors.</p> <p>Results</p> <p>HIV treatment scale-up includes many processes that are amenable to mathematical and simulation modeling, including forecasting future demand for services; locating and sizing facilities for maximal efficiency; and determining optimal staffing levels at clinical centers. Optimization of clinical and logistical processes through modeling may improve outcomes, but successful OR-based interventions will require contextualization of response strategies, including appreciation of both existing health care systems and limitations in local health workforces.</p> <p>Conclusion</p> <p>The modeling techniques developed in the engineering field of operations research have wide potential application to the variety of logistical problems encountered in HIV treatment scale-up in resource-limited settings. Increasing the number of cross-disciplinary collaborations between engineering and public health will help speed the appropriate development and application of these tools.</p

Evolutionary conserved longevity genes and human cognitive abilities in elderly cohorts

Genetic influences have an important role in the ageing process. The genetic factors that influence success in bodily ageing may also contribute to the successful ageing of cognitive abilities. A comparative genomics approach found longevity genes conserved between yeast Saccharomyces cerevisiae and nematode Caenorhabditis elegans. We hypothesised that these longevity genes influence variance in cognitive ability and age-related cognitive decline in humans. Here, we investigated six of these genes that have human orthologs and show expression in the brain. We tested AFG3L2 (MIM: 604581, AFG3 ATPase family gene 3-like 2 (yeast)), FRAP1 (MIM: 601231, a FK506 binding protein 12-rapamycin associated protein), MAT1A, MAT2A (MIM: 610550 and 601468, methionine adenosyltransferases I alpha and II alpha, respectively), SYNJ1 and SYNJ2 (MIM: 604297 and 609410, synaptojanin-1 and synaptojanin-2, respectively) in approximately 1000 healthy older Scots: the Lothian Birth Cohort 1936 (LBC1936). They were tested on general cognitive ability at age 11 years. At a mean age of 70 years, they re-sat the same general cognitive ability test and underwent an additional battery of diverse cognitive tests. In all, 70 tag and functional SNPs in the six longevity genes were genotyped and tested for association with cognition and cognitive ageing in LBC1936. Suggestive associations were detected between SNPs in SYNJ2, MAT1A, AFG3L2 and SYNJ1 and a general memory factor and general cognitive ability at age 11 and 70 years. Replication studies for cognitive ability associations were performed in 2506 samples from the Cognitive Ageing Genetics in England and Scotland consortium. A meta-analysis replicated the SYNJ2 association with cognitive abilities (lowest P=0.00077). SYNJ2 is a novel gene in which variation is potentially associated with cognitive abilities

Impacts of fire and prospects for recovery in a tropical peat forest ecosystem

Uncontrolled fires place considerable burdens on forest ecosystems, compromising our ability to meet conservation and restoration goals. A poor understanding of the impacts of fire on ecosystems and their biodiversity exacerbates this challenge, particularly in tropical regions where few studies have applied consistent analytical techniques to examine a broad range of ecological impacts over multiyear time frames. We compiled 16 y of data on ecosystem properties (17 variables) and biodiversity (21 variables) from a tropical peatland in Indonesia to assess fire impacts and infer the potential for recovery. Burned forest experienced altered structural and microclimatic conditions, resulting in a proliferation of nonforest vegetation and erosion of forest ecosystem properties and biodiversity. Compared to unburned forest, habitat structure, tree density, and canopy cover deteriorated by 58 to 98%, while declines in species diversity and abundance were most pronounced for trees, damselflies, and butterflies, particularly for forest specialist species. Tracking ecosystem property and biodiversity datasets over time revealed most to be sensitive to recurrent high-intensity fires within the wider landscape. These megafires immediately compromised water quality and tree reproductive phenology, crashing commercially valuable fish populations within 3 mo and driving a gradual decline in threatened vertebrates over 9 mo. Burned forest remained structurally compromised long after a burn event, but vegetation showed some signs of recovery over a 12-y period. Our findings demonstrate that, if left uncontrolled, fire may be a pervasive threat to the ecological functioning of tropical forests, underscoring the importance of fire prevention and long-term restoration efforts, as exemplified in Indonesia

New filovirus disease classification and nomenclature.

The recent large outbreak of Ebola virus disease (EVD) in Western Africa resulted in greatly increased accumulation of human genotypic, phenotypic and clinical data, and improved our understanding of the spectrum of clinical manifestations. As a result, the WHO disease classification of EVD underwent major revision

SARS-CoV-2 Omicron is an immune escape variant with an altered cell entry pathway

Vaccines based on the spike protein of SARS-CoV-2 are a cornerstone of the public health response to COVID-19. The emergence of hypermutated, increasingly transmissible variants of concern (VOCs) threaten this strategy. Omicron (B.1.1.529), the fifth VOC to be described, harbours multiple amino acid mutations in spike, half of which lie within the receptor-binding domain. Here we demonstrate substantial evasion of neutralization by Omicron BA.1 and BA.2 variants in vitro using sera from individuals vaccinated with ChAdOx1, BNT162b2 and mRNA-1273. These data were mirrored by a substantial reduction in real-world vaccine effectiveness that was partially restored by booster vaccination. The Omicron variants BA.1 and BA.2 did not induce cell syncytia in vitro and favoured a TMPRSS2-independent endosomal entry pathway, these phenotypes mapping to distinct regions of the spike protein. Impaired cell fusion was determined by the receptor-binding domain, while endosomal entry mapped to the S2 domain. Such marked changes in antigenicity and replicative biology may underlie the rapid global spread and altered pathogenicity of the Omicron variant

Investigation of hospital discharge cases and SARS-CoV-2 introduction into Lothian care homes

Background The first epidemic wave of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in Scotland resulted in high case numbers and mortality in care homes. In Lothian, over one-third of care homes reported an outbreak, while there was limited testing of hospital patients discharged to care homes. Aim To investigate patients discharged from hospitals as a source of SARS-CoV-2 introduction into care homes during the first epidemic wave. Methods A clinical review was performed for all patients discharges from hospitals to care homes from 1st March 2020 to 31st May 2020. Episodes were ruled out based on coronavirus disease 2019 (COVID-19) test history, clinical assessment at discharge, whole-genome sequencing (WGS) data and an infectious period of 14 days. Clinical samples were processed for WGS, and consensus genomes generated were used for analysis using Cluster Investigation and Virus Epidemiological Tool software. Patient timelines were obtained using electronic hospital records. Findings In total, 787 patients discharged from hospitals to care homes were identified. Of these, 776 (99%) were ruled out for subsequent introduction of SARS-CoV-2 into care homes. However, for 10 episodes, the results were inconclusive as there was low genomic diversity in consensus genomes or no sequencing data were available. Only one discharge episode had a genomic, time and location link to positive cases during hospital admission, leading to 10 positive cases in their care home. Conclusion The majority of patients discharged from hospitals were ruled out for introduction of SARS-CoV-2 into care homes, highlighting the importance of screening all new admissions when faced with a novel emerging virus and no available vaccine

Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK.

BACKGROUND: A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials. METHODS: This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 1010 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674. FINDINGS: Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0-75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4-97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; pinteraction=0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8-80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3-4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation. INTERPRETATION: ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials. FUNDING: UK Research and Innovation, National Institutes for Health Research (NIHR), Coalition for Epidemic Preparedness Innovations, Bill & Melinda Gates Foundation, Lemann Foundation, Rede D'Or, Brava and Telles Foundation, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland's NIHR Clinical Research Network, and AstraZeneca

Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK

Background A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials. Methods This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 1010 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674. Findings Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0–75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4–97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; pinteraction=0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8–80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3–4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation. Interpretation ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials