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

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

Agricultural services support programme and socio-economic empowerment of rural women in Zanzibar, Tanzania

Women in Zanzibar are socially and economically disadvantaged in many aspects. In view of this, the government made efforts to ensure women empowerment through development programmes such as Agriculture Services Support Programme (ASSP). However, the extent of socio-economic empowerment on women in rural areas is scanty. Therefore, this study aimed at assessing the contribution of ASSP intervention to socio- economic empowerment of rural women in Zanzibar. Specifically, the study assessed the ASSP empowerment strategies, women participation levels and attitude towards ASSP. The study also compared empowerment levels between programme and non-programme members. Primary data were collected using a structured questionnaire from 200 women in ten shehia of Mkoani district. Women empowerment levels were measured by using a Women Empowerment Index (WEI). The hypothesis to demonstrate the differences of women empowerment between programme and non-programme members was tested using Mann-Whitney U-test. The results showed high extent of women participation in study visits, training and regular meetings and moderate participation was noted on Participatory Action Research (PAR) and Participatory Rural Appraisal (PRA). Women benefited socially and economically due to their participation in ASSP. The results suggested high level of empowerment for women in the ASSP programme. This was confirmed by Mann-Whitney U-test, which revealed increased in women decision making on production resources, increase in income and contribution on household expenses. However, mobility decision and asset ownership did not differ among ASSP and non- ASSP members due to Islamic socialization culture. Women’s attitude towards ASSP was positive indicating that strategies used to empower women were appropriate, while the lack of investment capital and time constraints hampered women's participation in the programme. Based on these findings, it is concluded that the initiative taken by theiii government through ASSP left significant change on rural women's socio-economic status in Mkoani district. However, consideration of the women financial support is among other things recommended for other coming women empowerment programmes

'I have made children, so what's the problem?' Retrospective self-circumcision and the sexual and urological needs of some Somali men in Sweden

Unskilled traditional healers are widely blamed for complications to male circumcision performed in low- and middle-income settings. However, attributions of culpability are mostly anecdotal. We identify self-circumcision in adults that was performed during adolescence, hereby termed retrospective self-circumcision, and unexpectedly discovered during interviews with Somali men in Sweden in 2010. This study explores the phenomenon with the aim to increase our understanding about the health needs of this group. Two focus group discussions (six and seven participants), one informal discussion with three participants, and 27 individual interviews were conducted in 2010 and 2011 with Somali-Swedish fathers, guided by a hermeneutic, comparative natural inquiry method. Eight participants had performed retrospective self-circumcision while living in rural Somalia. Actions were justified according to strong faith in Islam. Genital physiology was described as adequate for producing children, but physical sensation or characteristics were implied as less than optimal. Few had heard about penile reconstruction. There was hesitation to openly discuss concerns, but men nevertheless encouraged each other to seek care options. Presently no medical platform is available for retrospective self-circumcision. Further systematic exploration is recommended in sexual, reproductive and urological health to increase interest in this phenomenon. Our findings suggest approachability if health communication is enabled within an Islamic context

Advanced Tracheal Adenoid Cystic Carcinoma with Thyroid Invasion Mimicking Thyroid Cancer Treated with Definitive Radiation: Case Report and Review of the Literature

A 54-year-old female patient, a breast cancer survivor and a case of unresectable adenoid cystic carcinoma of the trachea, with thyroid invasion, presented with suprasternal neck swelling mimicking thyroid primary. A literature search was undertaken to highlight this rare presentation. There have been few reports in the literature describing tracheal adenoid cystic carcinoma involving the thyroid