Background: Vaccination refusal exacerbates global COVID-19 vaccination inequities. No studies in East Africa have examined temporal trends in vaccination refusal, precluding addressing refusal. We assessed vaccine refusal over time in Kenya, and characterized factors associated with changes in vaccination refusal.
View Article and Find Full Text PDFDespite numerous journalistic accounts, systematic quantitative evidence on economic conditions during the ongoing COVID-19 pandemic remains scarce for most low- and middle-income countries, partly due to limitations of official economic statistics in environments with large informal sectors and subsistence agriculture. We assemble evidence from over 30,000 respondents in 16 original household surveys from nine countries in Africa (Burkina Faso, Ghana, Kenya, Rwanda, Sierra Leone), Asia (Bangladesh, Nepal, Philippines), and Latin America (Colombia). We document declines in employment and income in all settings beginning March 2020.
View Article and Find Full Text PDFBackground: The health burden caused by seasonal influenza is substantial. We sought to examine the effectiveness of influenza vaccination against admission to hospital for acute cardiovascular and respiratory conditions and all-cause death in people with type 2 diabetes.
Methods: We conducted a retrospective cohort study using primary and secondary care data from the Clinical Practice Research Datalink in England, over a 7-year period between 2003/04 and 2009/10.
Background: Understanding how urbanisation and rural-urban migration influence risk-factors for non-communicable disease (NCD) is crucial for developing effective preventative strategies globally. This study compares NCD risk-factor prevalence in urban, rural and migrant populations in China, Ghana, India, Mexico, Russia and South Africa.
Methods: Study participants were 39,436 adults within the WHO Study on global AGEing and adult health (SAGE), surveyed 2007-2010.
Pay-for-performance programs are often aimed to improve the management of chronic diseases. We evaluate the impact of a local pay for performance programme (QOF+), which rewarded financially more ambitious quality targets ('stretch targets') than those used nationally in the Quality and Outcomes Framework (QOF). We focus on targets for intermediate outcomes in patients with cardiovascular disease and diabetes.
View Article and Find Full Text PDFBackground: In England, the National Institute for Health and Care Excellence (NICE) produces guidelines for the management of hypertension. In 2006, the NICE guidelines introduced an ethnic-age group algorithm based on the 2004 British Hypertension Society guidelines to guide antihypertensive drug prescription.
Methods: A longitudinal retrospective study with 15933 hypertensive patients aged 18 years or over and registered with 28 general practices in Wandsworth, London in 2007 was conducted to assess variations in antihypertensive prescribing.
Proc Natl Acad Sci U S A
January 2014
Dioxygenases of the Ten-Eleven Translocation (TET) family are 5-methylcytosine oxidases that convert 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) and further oxidation products in DNA. We show that Tet1 and Tet2 have distinct roles in regulating 5hmC in mouse embryonic stem cells (mESC). Tet1 depletion diminishes 5hmC levels at transcription start sites (TSS), whereas Tet2 depletion is predominantly associated with decreased 5hmC in gene bodies.
View Article and Find Full Text PDFBackground: The objective of this review was to assess the uptake of WHO recommended integrated perinatal prevention of mother-to-child transmission (PMTCT) of HIV interventions in low- and middle-income countries.
Methods And Findings: We searched 21 databases for observational studies presenting uptake of integrated PMTCT programs in low- and middle-income countries. Forty-one studies on programs implemented between 1997 and 2006, met inclusion criteria.
Objectives: To examine differences in blood pressure control using the 2006 National Institute for Health and Clinical Excellence (NICE) guidelines and the 2007 Quality and Outcome Framework (QOF) standards.
Design: Cross-sectional study.
Setting: 28 general practices located in Wandsworth, London.
Background: Patients are increasingly rating their family physicians on the Internet in the same way as they might rate a hotel on TripAdvisor or a seller on eBay, despite physicians' concerns about this process.
Objective: This study aims to examine the usage of NHS Choices, a government website that encourages patients to rate the quality of family practices in England, and associations between web-based patient ratings and conventional measures of patient experience and clinical quality in primary care.
Methods: We obtained all (16,952) ratings of family practices posted on NHS Choices between October 2009 and December 2010.
B cells and plasma cells possess distinct RNA processing environments that respectively promote the expression of membrane-associated Ig by B cells versus the secretion of Ig by plasma cells. Through a combination of transcriptional profiling and screening using a lentiviral short-hairpin RNA interference library, we show that both the splicing factor hnRNPLL and the transcription elongation factor ELL2 modulate the ratio of secreted versus membrane-encoding Ighg2b transcripts in MPC11 plasmacytoma cell lines. hnRNPLL and ELL2 are both highly expressed in primary plasma cells relative to B cells, but hnRNPLL binds Ighg2b mRNA transcripts and promotes an increase in levels of the membrane-encoding Ighg2b isoform at the expense of the secreted Ighg2b isoform, whereas ELL2 counteracts this effect and drives Ig secretion by increasing the frequency of the secreted Ighg2b isoform.
View Article and Find Full Text PDFObjective: To examine the effect of systolic and diastolic blood pressure achieved in the first year of treatment on all cause mortality in patients newly diagnosed with type 2 diabetes, with and without established cardiovascular disease.
Design: Retrospective cohort study.
Setting: United Kingdom General Practice Research Database, between 1990 and 2005.
Objective: Unsolicited web-based comments by patients regarding their healthcare are increasing, but controversial. The relationship between such online patient reports and conventional measures of patient experience (obtained via survey) is not known. The authors examined hospital level associations between web-based patient ratings on the National Health Service (NHS) Choices website, introduced in England during 2008, and paper-based survey measures of patient experience.
View Article and Find Full Text PDFBackground: The ideal population size of healthcare commissioning organisations is not known.
Aim: To investigate whether there is a relationship between the size of commissioning organisations and how well they perform on a range of performance measures.
Design And Setting: Cross-sectional, observational study of performance in all 152 primary care trusts (PCTs) in England.
Amid international concerns about health care safety and quality, there has been an escalation of investigations by health care regulators into adverse events. England has a powerful central health care regulator, the Care Quality Commission, which conducts occasional high-profile investigations into major lapses in quality at individual hospitals. The results have sometimes garnered considerable attention from the news media, but it is not known what effect the investigations have had on patients' behavior.
View Article and Find Full Text PDFBackground: The UK introduced an ambitious national strategy to reduce population levels of salt intake in 2003. The aim of this study was to evaluate the impact of this strategy on salt intake in England, including potential effects on health inequalities.
Methods: Secondary analysis of data from the Health Survey for England.
The increasing volume of ChIP-chip and ChIP-seq data being generated creates a challenge for standard, integrative and reproducible bioinformatics data analysis platforms. We developed a web-based application called Cistrome, based on the Galaxy open source framework. In addition to the standard Galaxy functions, Cistrome has 29 ChIP-chip- and ChIP-seq-specific tools in three major categories, from preliminary peak calling and correlation analyses to downstream genome feature association, gene expression analyses, and motif discovery.
View Article and Find Full Text PDFBackground: Not enough is known about the association between practice size and clinical outcomes in primary care. We examined this association between 1997 and 2005, in addition to the impact of the Quality and Outcomes Framework, a pay-for-performance incentive scheme introduced in the United Kingdom in 2004, on diabetes management.
Methods: We conducted a retrospective open-cohort study using data from the General Practice Research Database.
5-hydroxymethylcytosine (5hmC) is a modified base present at low levels in diverse cell types in mammals. 5hmC is generated by the TET family of Fe(II) and 2-oxoglutarate-dependent enzymes through oxidation of 5-methylcytosine (5mC). 5hmC and TET proteins have been implicated in stem cell biology and cancer, but information on the genome-wide distribution of 5hmC is limited.
View Article and Find Full Text PDFTET2 is a close relative of TET1, an enzyme that converts 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) in DNA. The gene encoding TET2 resides at chromosome 4q24, in a region showing recurrent microdeletions and copy-neutral loss of heterozygosity (CN-LOH) in patients with diverse myeloid malignancies. Somatic TET2 mutations are frequently observed in myelodysplastic syndromes (MDS), myeloproliferative neoplasms (MPN), MDS/MPN overlap syndromes including chronic myelomonocytic leukaemia (CMML), acute myeloid leukaemias (AML) and secondary AML (sAML).
View Article and Find Full Text PDFBackground: Cell functions depend on molecules organized in the cellular society. Two basic components are mRNA molecules and proteins. The interactions within and between those two components are crucial for carrying out sophisticated cell functions.
View Article and Find Full Text PDFMotivation: Statistical assessment of cis-regulatory modules (CRMs) is a crucial task in computational biology. Usually, one concludes from exceptional co-occurrences of DNA motifs that the corresponding transcription factors (TFs) are cooperative. However, similar DNA motifs tend to co-occur in random sequences due to high probability of overlapping occurrences.
View Article and Find Full Text PDFTranscription factors play a key role in gene regulation by interacting with specific binding sites or motifs. Therefore, enrichment of binding motifs is important for genome annotation and efficient computation of the statistical significance, the p-value, of the enrichment of motifs is crucial. We propose an efficient approximation to compute the significance.
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