2,356 research outputs found

    What is meant by validity in maternal and newborn health measurement? A conceptual framework for understanding indicator validation.

    Get PDF
    BACKGROUND: Rigorous monitoring supports progress in achieving maternal and newborn mortality and morbidity reductions. Recent work to strengthen measurement for maternal and newborn health highlights the existence of a large number of indicators being used for this purpose. The definitions and data sources used to produce indicator estimates vary and challenges exist with completeness, accuracy, transparency, and timeliness of data. The objective of this study is to create a conceptual overview of how indicator validity is defined and understood by those who develop and use maternal and newborn health indicators. METHODS: A conceptual framework of validity was developed using mixed methods. We were guided by principles for conceptual frameworks and by a review of the literature and key maternal and newborn health indicator guidance documents. We also conducted qualitative semi-structured interviews with 32 key informants chosen through purposive sampling. RESULTS: We categorised indicator validity into three main types: criterion, convergent, and construct. Criterion or diagnostic validity, comparing a measure with a gold standard, has predominantly been used to assess indicators of care coverage and content. Studies assessing convergent validity quantify the extent to which two or more indicator measurement approaches, none of which is a gold-standard, relate. Key informants considered construct validity, or the accuracy of the operationalisation of a concept or phenomenon, a critical part of the overall assessment of indicator validity. CONCLUSION: Given concerns about the large number of maternal and newborn health indicators currently in use, a more consistent understanding of validity can help guide prioritization of key indicators and inform development of new indicators. All three types of validity are relevant for evaluating the performance of maternal and newborn health indicators. We highlight the need to establish a common language and understanding of indicator validity among the various global and local stakeholders working within maternal and newborn health

    Tonic Activation of GluN2C/GluN2D-Containing NMDA Receptors by Ambient Glutamate Facilitates Cortical Interneuron Maturation

    Get PDF
    Developing cortical GABAergic interneurons rely on genetic programs, neuronal activity, and environmental cuesto construct inhibitory circuits during early postnatal development. Disruption of these events can cause long-term changes in cortical inhibition and may be involved in neurological disorders associated with inhibitory circuit dysfunction. We hypothesized that tonic glutamate signaling in the neonatal cortex contributesto, and is necessary for,the maturation of cortical interneurons. Totestthis hypothesis, we used mice of both sexes to quantify extracellular glutamate concentrations in the cortex during development, measure ambient glutamate-mediated activation of developing cortical interneurons, and manipulatetonic glutamate signaling using subtype-specific NMDA receptor antagonists in vitro and in vivo. We report that ambient glutamate levels are high (100 nM) in the neonatal cortex and decrease (to 50 nM) during the first weeks of life, coincident with increases in astrocytic glutamate uptake. Consistent with elevated ambient glutamate, putative parvalbumin-positive interneurons in the cortex (identified using G42:GAD1-eGFP reporter mice) exhibit a transient, tonic NMDA current at the end of the first postnatal week. GluN2C/GluN2D-containing NMDA receptors mediate the majority of this current and contribute to the resting membrane potential and intrinsic properties of developing putative parvalbumin interneurons. Pharmacological blockade of GluN2C/GluN2D-containing NMDA receptors in vivo during the period of tonic interneuron activation, but not later, leads to lasting decreases in interneuron morphological complexity and causes deficits in cortical inhibition later in life. These results demonstrate that dynamic ambient glutamate signaling contributes to cortical interneuron maturation via tonic activation of GluN2C/ GluN2D-containing NMDA receptor

    A multi-center study on the attitudes of Malaysian emergency health care staff towards allowing family presence during resuscitation of adult patients

    Get PDF
    BACKGROUND The practice of allowing family members to witness on-going active resuscitation has been gaining ground in many developed countries since it was first introduced in the early 1990s. In many Asian countries, the acceptability of this practice has not been well studied. AIM We conducted a multi-center questionnaire study to determine the attitudes of health care professionals in Malaysia towards family presence to witness ongoing medical procedures during resuscitation. METHODS Using a bilingual questionnaire (in Malay and English language), we asked our respondents about their attitudes towards allowing family presence (FP) as well as their actual experience of requests from families to be allowed to witness resuscitations. Multiple logistic regression was used to analyze the association between the many variables and a positive attitude towards FP. RESULTS Out of 300 health care professionals who received forms, 270 responded (a 90% response rate). Generally only 15.8% of our respondents agreed to allow relatives to witness resuscitations, although more than twice the number (38.5%) agreed that relatives do have a right to be around during resuscitation. Health care providers are significantly more likely to allow FP if the procedures are perceived as likely to be successful (e.g., intravenous cannulation and blood taking as compared to chest tube insertion). Doctors were more than twice as likely as paramedics to agree to FP (p-value = 0.002). This is probably due to the Malaysian work culture in our health care systems in which paramedics usually adopt a 'follow-the-leader' attitude in their daily practice. CONCLUSION The concept of allowing FP is not well accepted among our Malaysian health care providers

    Denitrification and nitrous oxide emissions from riparian forests soils exposed to prolonged nitrogen runoff

    Get PDF
    Compared to upland forests, riparian forest soils have greater potential to remove nitrate (NO3) from agricultural run-off through denitrification. It is unclear, however, whether prolonged exposure of riparian soils to nitrogen (N) loading will affect the rate of denitrification and its end products. This research assesses the rate of denitrification and nitrous oxide (N2O) emissions from riparian forest soils exposed to prolonged nutrient run-off from plant nurseries and compares these to similar forest soils not exposed to nutrient run-off. Nursery run-off also contains high levels of phosphate (PO4). Since there are conflicting reports on the impact of PO4 on the activity of denitrifying microbes, the impact of PO4 on such activity was also investigated. Bulk and intact soil cores were collected from N-exposed and non-exposed forests to determine denitrification and N2O emission rates, whereas denitrification potential was determined using soil slurries. Compared to the non-amended treatment, denitrification rate increased 2.7- and 3.4-fold when soil cores collected from both N-exposed and non-exposed sites were amended with 30 and 60 μg NO3-N g-1 soil, respectively. Net N2O emissions were 1.5 and 1.7 times higher from the N-exposed sites compared to the non-exposed sites at 30 and 60 μg NO3-N g-1 soil amendment rates, respectively. Similarly, denitrification potential increased 17 times in response to addition of 15 μg NO3-N g-1 in soil slurries. The addition of PO4 (5 μg PO4–P g-1) to soil slurries and intact cores did not affect denitrification rates. These observations suggest that prolonged N loading did not affect the denitrification potential of the riparian forest soils; however, it did result in higher N2O emissions compared to emission rates from non-exposed forests

    Utility of polygenic risk scores in UK cancer screening: a modelling analysis

    Get PDF
    BACKGROUND: It is proposed that, through restriction to individuals delineated as high risk, polygenic risk scores (PRSs) might enable more efficient targeting of existing cancer screening programmes and enable extension into new age ranges and disease types. To address this proposition, we present an overview of the performance of PRS tools (ie, models and sets of single nucleotide polymorphisms) alongside harms and benefits of PRS-stratified cancer screening for eight example cancers (breast, prostate, colorectal, pancreas, ovary, kidney, lung, and testicular cancer). METHODS: For this modelling analysis, we used age-stratified cancer incidences for the UK population from the National Cancer Registration Dataset (2016–18) and published estimates of the area under the receiver operating characteristic curve for current, future, and optimised PRS for each of the eight cancer types. For each of five PRS-defined high-risk quantiles (ie, the top 50%, 20%, 10%, 5%, and 1%) and according to each of the three PRS tools (ie, current, future, and optimised) for the eight cancers, we calculated the relative proportion of cancers arising, the odds ratios of a cancer arising compared with the UK population average, and the lifetime cancer risk. We examined maximal attainable rates of cancer detection by age stratum from combining PRS-based stratification with cancer screening tools and modelled the maximal impact on cancer-specific survival of hypothetical new UK programmes of PRS-stratified screening. FINDINGS: The PRS-defined high-risk quintile (20%) of the population was estimated to capture 37% of breast cancer cases, 46% of prostate cancer cases, 34% of colorectal cancer cases, 29% of pancreatic cancer cases, 26% of ovarian cancer cases, 22% of renal cancer cases, 26% of lung cancer cases, and 47% of testicular cancer cases. Extending UK screening programmes to a PRS-defined high-risk quintile including people aged 40–49 years for breast cancer, 50–59 years for colorectal cancer, and 60–69 years for prostate cancer has the potential to avert, respectively, a maximum of 102, 188, and 158 deaths annually. Unstratified screening of the full population aged 48–49 years for breast cancer, 58–59 years for colorectal cancer, and 68–69 years for prostate cancer would use equivalent resources and avert, respectively, an estimated maximum of 80, 155, and 95 deaths annually. These maximal modelled numbers will be substantially attenuated by incomplete population uptake of PRS profiling and cancer screening, interval cancers, non-European ancestry, and other factors. INTERPRETATION: Under favourable assumptions, our modelling suggests modest potential efficiency gain in cancer case detection and deaths averted for hypothetical new PRS-stratified screening programmes for breast, prostate, and colorectal cancer. Restriction of screening to high-risk quantiles means many or most incident cancers will arise in those assigned as being low-risk. To quantify real-world clinical impact, costs, and harms, UK-specific cluster-randomised trials are required. FUNDING: The Wellcome Trust

    Health System Support for Childbirth care in Southern Tanzania: Results from a Health Facility Census.

    Get PDF
    Progress towards reaching Millennium Development Goals four (child health) and five (maternal health) is lagging behind, particularly in sub-Saharan Africa, despite increasing efforts to scale up high impact interventions. Increasing the proportion of birth attended by a skilled attendant is a main indicator of progress, but not much is known about the quality of childbirth care delivered by these skilled attendants. With a view to reducing maternal mortality through health systems improvement we describe the care routinely offered in childbirth offered at dispensaries, health centres and hospitals in five districts in rural Southern Tanzania. We use data from a health facility census assessing 159 facilities in five districts in early 2009. A structural and operational assessment was undertaken based on staff reports using a modular questionnaire assessing staffing, work load, equipment and supplies as well as interventions routinely implemented during childbirth. Health centres and dispensaries attended a median of eight and four deliveries every month respectively. Dispensaries had a median of 2.5 (IQR 2--3) health workers including auxiliary staff instead of the recommended four clinical officer and certified nurses. Only 28% of first-line facilities (dispensaries and health centres) reported offering active management in the third stage of labour (AMTSL). Essential childbirth care comprising eight interventions including AMTSL, infection prevention, partograph use including foetal monitoring and newborn care including early breastfeeding, thermal care at birth and prevention of ophthalmia neonatorum was offered by 5% of dispensaries, 38% of health centres and 50% of hospitals consistently. No first-line facility had provided all signal functions for emergency obstetric complications in the previous six months. Essential interventions for childbirth care are not routinely implemented in first-line facilities or hospitals. Dispensaries have both low staffing and low caseload which constraints the ability to provide high-quality childbirth care. Improvements in quality of care are essential so that women delivering in facility receive "skilled attendance" and adequate care for common obstetric complications such as post-partum haemorrhage

    Transient peak-strain matching partially recovers the age-impaired mechanoadaptive cortical bone response

    Get PDF
    Mechanoadaptation maintains bone mass and architecture; its failure underlies age-related decline in bone strength. It is unclear whether this is due to failure of osteocytes to sense strain, osteoblasts to form bone or insufficient mechanical stimulus. Mechanoadaptation can be restored to aged bone by surgical neurectomy, suggesting that changes in loading history can rescue mechanoadaptation. We use non-biased, whole-bone tibial analyses, along with characterisation of surface strains and ensuing mechanoadaptive responses in mice at a range of ages, to explore whether sufficient load magnitude can activate mechanoadaptation in aged bone. We find that younger mice adapt when imposed strains are lower than in mature and aged bone. Intriguingly, imposition of short-term, high magnitude loading effectively primes cortical but not trabecular bone of aged mice to respond. This response was regionally-matched to highest strains measured by digital image correlation and to osteocytic mechanoactivation. These data indicate that aged bone’s loading response can be partially recovered, non-invasively by transient, focal high strain regions. Our results indicate that old murine bone does respond to load when the loading is of sufficient magnitude, and bones’ age-related adaptation failure may be due to insufficient mechanical stimulus to trigger mechanoadaptation
    • …
    corecore