600 research outputs found
Diversity and the Civic Spirit in British Neighbourhoods: An Investigation with MCDS and EMBES 2010 Data
Recently, there has been a proliferation of studies investigating the relationship between diversity and outcomes such as social cohesion and civic mindedness. This article addresses several common problems in this field and, using data for British neighbourhoods, elaborates on the experiences of both white British and ethnic minority respondents. We conclude that, if anything, diversity should be encouraged to cement the integration progress of migrants and foster stronger identification with Britain in the second generation. Deprivation at the neighbourhood level along with individual factors such as fear of crime is a much stronger predictor of deterioration of the civic spirit than diversity. Bridging contacts have the expected strong positive association with cohesion outcomes; and contrary to policy concerns no strong negative impact is observed for associational bonding among minority ingroupers
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The metabolome regulates the epigenetic landscape during naive-to-primed human embryonic stem cell transition.
For nearly a century developmental biologists have recognized that cells from embryos can differ in their potential to differentiate into distinct cell types. Recently, it has been recognized that embryonic stem cells derived from both mice and humans exhibit two stable yet epigenetically distinct states of pluripotency: naive and primed. We now show that nicotinamide N-methyltransferase (NNMT) and the metabolic state regulate pluripotency in human embryonic stem cells (hESCs). Specifically, in naive hESCs, NNMT and its enzymatic product 1-methylnicotinamide are highly upregulated, and NNMT is required for low S-adenosyl methionine (SAM) levels and the H3K27me3 repressive state. NNMT consumes SAM in naive cells, making it unavailable for histone methylation that represses Wnt and activates the HIF pathway in primed hESCs. These data support the hypothesis that the metabolome regulates the epigenetic landscape of the earliest steps in human development
Combination of Sleeping Beauty transposition and chemically induced dimerization selection for robust production of engineered cells
The main methods for producing genetically engineered cells use viral vectors for which safety issues and manufacturing costs remain a concern. In addition, selection of desired cells typically relies on the use of cytotoxic drugs with long culture times. Here, we introduce an efficient non-viral approach combining the Sleeping Beauty (SB) Transposon System with selective proliferation of engineered cells by chemically induced dimerization (CID) of growth factor receptors. Minicircles carrying a SB transposon cassette containing a reporter transgene and a gene for the F36VFGFR1 fusion protein were delivered to the hematopoietic cell line Ba/F3. Stably-transduced Ba/F3 cell populations with >98% purity were obtained within 1 week using this positive selection strategy. Copy number analysis by quantitative PCR (qPCR) revealed that CID-selected cells contain on average higher copy numbers of transgenes than flow cytometry-selected cells, demonstrating selective advantage for cells with multiple transposon insertions. A diverse population of cells is present both before and after culture in CID media, although site-specific qPCR of transposon junctions show that population diversity is significantly reduced after selection due to preferential expansion of clones with multiple integration events. This non-viral, positive selection approach is an attractive alternative for producing engineered cells
Global regulation of alternative splicing during myogenic differentiation
Recent genome-wide analyses have elucidated the extent of alternative splicing (AS) in mammals, often focusing on comparisons of splice isoforms between differentiated tissues. However, regulated splicing changes are likely to be important in biological transitions such as cellular differentiation, or response to environmental stimuli. To assess the extent and significance of AS in myogenesis, we used splicing-sensitive microarray analysis of differentiating C2C12 myoblasts. We identified 95 AS events that undergo robust splicing transitions during C2C12 differentiation. More than half of the splicing transitions are conserved during differentiation of avian myoblasts, suggesting the products and timing of transitions are functionally significant. The majority of splicing transitions during C2C12 differentiation fall into four temporal patterns and were dependent on the myogenic program, suggesting that they are integral components of myogenic differentiation. Computational analyses revealed enrichment of many sequence motifs within the upstream and downstream intronic regions near the alternatively spliced regions corresponding to binding sites of splicing regulators. Western analyses demonstrated that several splicing regulators undergo dynamic changes in nuclear abundance during differentiation. These findings show that within a developmental context, AS is a highly regulated and conserved process, suggesting a major role for AS regulation in myogenic differentiation.National Institutes of Health (U.S.) (grant number R01GM076493)Ford Foundation (Predoctoral Diversity Fellowship)Baylor College of Medicine. Graduate School of Biomedical Sciences (Baylor Research Advocates for Student Scientists
A rhetoric-in-context approach to building commitment to multiple strategic goals
There are still few explanations of the micro-level practices by which top managers influence employee commitment to multiple strategic goals. This paper argues that, through their language, top managers can construct a context for commitment to multiple strategic goals. We therefore propose a rhetoric-in-context approach to illuminate some of the micro practices through which top managers influence employee commitment. Based upon an empirical study of the rhetorical practices through which top managers influence academic commitment to multiple strategic goals in university contexts, we demonstrate relationships between rhetoric and context. Specifically, we show that rhetorical influences over commitment to multiple goals are associated with the historical context for multiple goals, the degree to which top managers' rhetoric instantiates a change in that context, and the internal consistency of the rhetorical practices used by top managers. Copyright © 2007 SAGE Publications
Causes of stillbirth and death among children younger than 5 years in eastern Hararghe, Ethiopia: a population-based post-mortem study
Background
Child mortality is high in Ethiopia, but reliable data on the causes of death are scarce. We aimed to gather data for the contributory causes of stillbirth and child deaths in eastern Ethiopia.
Methods
In this population-based post-mortem study, we established a death-notification system in health facilities and in the community in Kersa (rural), Haramaya (rural) and Harar (urban) in eastern Ethiopia, at a new site of the Child Health and Mortality Prevention Surveillance (CHAMPS) network. We collected ante-mortem data, did verbal autopsies, and collected post-mortem samples via minimally invasive tissue sampling from stillbirths (weighing at least 1000 g or with an estimated gestational age of at least 28 weeks) and children who died younger than 5 years. Children—or their mothers, in the case of stillbirths and deaths in children younger than 6 months—had to have lived in the catchment area for the past 6 months to be included. Molecular, microbiological, and histopathological analyses were done in collected samples. Cause of death was established by an expert panel on the basis of these data and classified as underlying, comorbid, or immediate separately for stillbirths, neonatal deaths (deaths aged 0–27 days), and child deaths (aged 28 days to <5 years).
Findings
Between Feb 4, 2019, and Feb 3, 2021, 312 deaths were eligible for inclusion, and the families gave consent in 195 (63%) cases. Cause of death was established in 193 (99%) cases. Among 114 stillbirths, the underlying cause of death was perinatal asphyxia or hypoxia in 60 (53%) and birth defects in 24 (21%). Among 59 neonatal deaths, the most common underlying cause was perinatal asphyxia or hypoxia (17 [29%]) and the most common immediate cause of death was neonatal sepsis, which occurred in 27 (60%). Among 20 deaths in children aged 28 days to 59 months, malnutrition was the leading underlying cause (15 [75%]) and infections were common immediate and comorbid causes. Pathogens were identified in 19 (95%) child deaths, most commonly Klebsiella pneumoniae and Streptococcus pneumoniae.
Interpretation
Perinatal asphyxia or hypoxia, infections, and birth defects accounted for most stillbirths and child deaths. Most deaths could have been prevented with feasible interventions, such as improved maternity services, folate supplementation, and improved vaccine uptake.
Funding
Bill & Melinda Gates Foundation
Initial findings from a novel population-based child mortality surveillance approach: a descriptive study.
--- - Label: BACKGROUND NlmCategory: BACKGROUND content:
"Sub-Saharan Africa and south Asia contributed 81% of 5\xC2\xB79
million under-5 deaths and 77% of 2\xC2\xB76 million stillbirths
worldwide in 2015. Vital registration and verbal autopsy data
are mainstays for the estimation of leading causes of death, but
both are non-specific and focus on a single underlying cause. We
aimed to provide granular data on the contributory causes of
death in stillborn fetuses and in deceased neonates and children
younger than 5 years, to inform child mortality prevention
efforts." - Label: METHODS NlmCategory: METHODS content: "The
Child Health and Mortality Prevention Surveillance (CHAMPS)
Network was established at sites in seven countries (Baliakandi,
Bangladesh; Harar and Kersa, Ethiopia; Siaya and Kisumu, Kenya;
Bamako, Mali; Manhi\xC3\xA7a, Mozambique; Bombali, Sierra Leone;
and Soweto, South Africa) to collect standardised,
population-based, longitudinal data on under-5 mortality and
stillbirths in sub-Saharan Africa and south Asia, to improve the
accuracy of determining causes of death. Here, we analysed data
obtained in the first 2 years after the implementation of CHAMPS
at the first five operational sites, during which surveillance
and post-mortem diagnostics, including minimally invasive tissue
sampling (MITS), were used. Data were abstracted from all
available clinical records of deceased children, and relevant
maternal health records were also extracted for stillbirths and
neonatal deaths, to incorporate reported pregnancy or delivery
complications. Expert panels followed standardised procedures to
characterise causal chains leading to death, including
underlying, intermediate (comorbid or antecedent causes), and
immediate causes of death for stillbirths, neonatal deaths, and
child (age 1-59 months) deaths." - Label: FINDINGS NlmCategory:
RESULTS content: Between Dec 10, 2016, and Dec 31, 2018, MITS
procedures were implemented at five sites in Mozambique, South
Africa, Kenya, Mali, and Bangladesh. We screened 2385 death
notifications for inclusion eligibility, following which 1295
families were approached for consent; consent was provided for
MITS by 963 (74%) of 1295 eligible cases approached. At least
one cause of death was identified in 912 (98%) of 933 cases (180
stillbirths, 449 neonatal deaths, and 304 child deaths); two or
more conditions were identified in the causal chain for 585
(63%) of 933 cases. The most common underlying causes of
stillbirth were perinatal asphyxia or hypoxia (130 [72%] of 180
stillbirths) and congenital infection or sepsis (27 [15%]). The
most common underlying causes of neonatal death were preterm
birth complications (187 [42%] of 449 neonatal deaths),
perinatal asphyxia or hypoxia (98 [22%]), and neonatal sepsis
(50 [11%]). The most common underlying causes of child deaths
were congenital birth defects (39 [13%] of 304 deaths), lower
respiratory infection (37 [12%]), and HIV (35 [12%]). In 503
(54%) of 933 cases, at least one contributory pathogen was
identified. Cytomegalovirus, Escherichia coli, group B
Streptococcus, and other infections contributed to 30 (17%) of
180 stillbirths. Among neonatal deaths with underlying
prematurity, 60% were precipitated by other infectious causes.
Of the 275 child deaths with infectious causes, the most common
contributory pathogens were Klebsiella pneumoniae (86 [31%]),
Streptococcus pneumoniae (54 [20%]), HIV (40 [15%]), and
cytomegalovirus (34 [12%]), and multiple infections were common.
Lower respiratory tract infection contributed to 174 (57%) of
304 child deaths. - Label: INTERPRETATION NlmCategory:
CONCLUSIONS content: Cause of death determination using MITS
enabled detailed characterisation of contributing conditions.
Global estimates of child mortality aetiologies, which are
currently based on a single syndromic cause for each death, will
be strengthened by findings from CHAMPS. This approach adds
specificity and provides a more complete overview of the chain
of events leading to death, highlighting multiple potential
interventions to prevent under-5 mortality and stillbirths. -
Label: FUNDING NlmCategory: BACKGROUND content: Bill &
Melinda Gates Foundation
Provider adherence to clinical care recommendations for infants and children who died in seven low- and middle-income countries in the Child Health and Mortality Prevention Surveillance (CHAMPS) network
Background
Most childhood deaths globally are considered preventable through high-quality clinical care, which includes adherence to clinical care recommendations. Our objective was to describe adherence to World Health Organization recommendations for the management of leading causes of death among children.
Methods
We conducted a retrospective, descriptive study examining clinical data for children aged 1–59 months who were hospitalized and died in a Child Health and Mortality Prevention Surveillance (CHAMPS) catchment, December 2016–June 2021. Catchment areas included: Baliakandi and Faridpur, Bangladesh; Kersa, Haramaya, and Harar, Ethiopia; Kisumu and Siaya, Kenya; Bamako, Mali; Manhiça and Quelimane, Mozambique; Makeni, Sierra Leone; Soweto, South Africa. We reviewed medical records of those who died from lower respiratory tract infections, sepsis, malnutrition, malaria, and diarrheal diseases to determine the proportion who received recommended treatments and compared adherence by hospitalization duration.
Findings
CHAMPS enrolled 460 hospitalized children who died from the leading causes (median age 12 months, 53.0% male). Median hospital admission was 31 h. There were 51.0% (n = 127/249) of children who died from lower respiratory tract infections received supplemental oxygen. Administration of intravenous fluids for sepsis (15.9%, n = 36/226) and supplemental feeds for malnutrition (14.0%, n = 18/129) were uncommon. There were 51.4% (n = 55/107) of those who died from malaria received antimalarials. Of the 80 children who died from diarrheal diseases, 76.2% received intravenous fluids. Those admitted for ≥24 h more commonly received antibiotics for lower respiratory tract infections and sepsis, supplemental feeds for malnutrition, and intravenous fluids for sepsis than those admitted <24 h.
Interpretation
Provision of recommended clinical care for leading causes of death among young children was suboptimal. Further studies are needed to understand the reasons for deficits in clinical care recommendation adherence.
Funding
Bill & Melinda Gates Foundation
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