Birthweight measurement processes and perceived value: qualitative research in one EN-BIRTH study hospital in Tanzania.

BACKGROUND: Globally an estimated 20.5 million liveborn babies are low birthweight (LBW) each year, weighing less than 2500 g. LBW babies have increased risk of mortality even beyond the neonatal period, with an ongoing risk of stunting and non-communicable diseases. LBW is a priority global health indicator. Now almost 80% of births are in facilities, yet birthweight data are lacking in most high-mortality burden countries and are of poor quality, notably with heaping especially on values ending in 00. We aimed to undertake qualitative research in a regional hospital in Dar es Salaam, Tanzania, observing birthweight weighing scales, exploring barriers and enablers to weighing at birth as well as perceived value of birthweight data to health workers, women and stakeholders. METHODS: Observations were undertaken on type of birthweight scale availability in hospital wards. In-depth semi-structured interviews (n = 21) were conducted with three groups: women in postnatal and kangaroo mother care wards, health workers involved in birthweight measurement and recording, and stakeholders involved in data aggregation in Temeke Hospital, Tanzania, a site in the EN-BIRTH study. An inductive thematic analysis was undertaken of translated interview transcripts. RESULTS: Of five wards that were expected to have scales, three had functional scales, and only one of the functional scales was digital. The labour ward weighed the most newborns using an analogue scale that was not consistently zeroed. Hospital birthweight data were aggregated monthly for reporting into the health management information system. Birthweight measurement was highly valued by all respondents, notably families and healthcare workers, and local use of data was considered an enabler. Perceived barriers to high quality birthweight data included: gaps in availability of precise weighing devices, adequate health workers and imprecise measurement practices. CONCLUSION: Birthweight measurement is valued by families and health workers. There are opportunities to close the gap between the percentage of babies born in facilities and the percentage accurately weighed at birth by providing accurate scales, improving skills training and increasing local use of data. More accurate birthweight data are vitally important for all babies and specifically to track progress in preventing and improving immediate and long-term care for low birthweight children

Counting on birth registration: mixed-methods research in two EN-BIRTH study hospitals in Tanzania.

BACKGROUND: Birth registration marks a child's right to identity and is the first step to establishing citizenship and access to services. At the population level, birth registration data can inform effective programming and planning. In Tanzania, almost two-thirds of births are in health facilities, yet only 26% of children under 5 years have their births registered. Our mixed-methods research explores the gap between hospital birth and birth registration in Dar es Salaam, Tanzania. METHODS: The study was conducted in the two Tanzanian hospital sites of the Every Newborn-Birth Indicators Research Tracking in Hospitals (EN-BIRTH) multi-country study (July 2017-2018). We described the business processes for birth notification and registration and collected quantitative data from women's exit surveys after giving birth (n = 8038). We conducted in-depth interviews (n = 21) to identify barriers and enablers to birth registration among four groups of participants: women who recently gave birth, women waiting for a birth certificate at Temeke Hospital, hospital employees, and stakeholders involved in the national birth registration process. We synthesized findings to identify opportunities to improve birth registration. RESULTS: Standard national birth registration procedures were followed at Muhimbili Hospital; families received birth notification and were advised to obtain a birth certificate from the Registration, Insolvency, and Trusteeship Agency (RITA) after 2 months, for a fee. A pilot programme to improve birth registration coverage included Temeke Hospital; hand-written birth certificates were issued free of charge on a return hospital visit after 42 days. Among 2500 women exit-surveyed at Muhimbili Hospital, 96.3% reported receiving a birth notification form and nearly half misunderstood this to be a birth certificate. Of the 5538 women interviewed at Temeke Hospital, 33.0% reported receiving any documentation confirming the birth of their child. In-depth interview respondents perceived birth registration to be important but considered both the standard and pilot processes in Tanzania complex, burdensome and costly to both families and health workers. CONCLUSION: Birth registration coverage in Tanzania could be improved by further streamlining between health facilities, where most babies are born, and the civil registry. Families and health workers need support to navigate processes to register every child

Aquaporin expression in the human and canine intervertebral disc during maturation and degeneration

The intervertebral disc (IVD) is a highly hydrated tissue, the rich proteoglycan matrix imbibes water, enabling the disc to withstand compressive loads. During ageing and degeneration increased matrix degradation leads to dehydration and loss of function. Aquaporins (AQP) are a family of transmembrane channel proteins that selectively allow the passage of water in and out of cells and are responsible for maintaining water homeostasis in many tissues. Here, the expression of all 13 AQPs at gene and protein level was investigated in human and canine non‐degenerate and degenerate IVDs to develop an understanding of the role of AQPs during degeneration. Furthermore, in order to explore the transition of notochordal cells (NCs) towards nucleus pulposus (NP) cells, AQP expression was investigated in canine IVDs enriched in NCs to understand the role of AQPs in IVD maturation. AQP0, 1, 2, 3, 4, 5, 6, 7 and 9 were expressed at gene and protein level in both non‐degenerate and degenerate human NP tissue. AQP2 and 7 immunopositivity increased with degeneration in human NP tissue, whereas AQP4 expression decreased with degeneration in a similar way to AQP 1 and 5 shown previously. All AQP proteins that were identified in human NP tissue were also expressed in canine NP tissue. AQP2, 5, 6 and 9 were found to localise to vacuole‐like membranes and cell membranes in NC cells. In conclusion, AQPs were abundantly expressed in human and canine IVDs. The expression of many AQP isotypes potentially alludes to multi‐faceted functions related to adaption of NP cells to the conditions they encounter within their microenvironment in health and degeneration. The presence of AQPs within the IVD may suggest an adaptive role for these water channels during the development and maintenance of the healthy, mature IVD

Stillbirths including intrapartum timing: EN-BIRTH multi-country validation study.

BACKGROUND: An estimated >2 million babies stillborn around the world each year lack visibility. Low- and middle-income countries carry 84% of the burden yet have the least data. Most births are now in facilities, hence routine register-recording presents an opportunity to improve counting of stillbirths, but research is limited, particularly regarding accuracy. This paper evaluates register-recorded measurement of hospital stillbirths, classification accuracy, and barriers and enablers to routine recording. METHODS: The EN-BIRTH mixed-methods, observational study took place in five hospitals in Bangladesh, Nepal and Tanzania (2017-2018). Clinical observers collected time-stamped data on perinatal care and birth outcomes as gold standard. To assess accuracy of routine register-recorded stillbirth rates, we compared birth outcomes recorded in labour ward registers to observation data. We calculated absolute rate differences and individual-level validation metrics (sensitivity, specificity, percent agreement). We assessed misclassification of stillbirths with neonatal deaths. To examine stillbirth appearance (fresh/macerated) as a proxy for timing of death, we compared appearance to observed timing of intrauterine death based on heart rate at admission. RESULTS: 23,072 births were observed including 550 stillbirths. Register-recorded completeness of birth outcomes was > 90%. The observed study stillbirth rate ranged from 3.8 (95%CI = 2.0,7.0) to 50.3 (95%CI = 43.6,58.0)/1000 total births and was under-estimated in routine registers by 1.1 to 7.3 /1000 total births (register: observed ratio 0.9-0.7). Specificity of register-recorded birth outcomes was > 99% and sensitivity varied between hospitals, ranging from 77.7-86.1%. Percent agreement between observer-assessed birth outcome and register-recorded birth outcome was very high across all hospitals and all modes of birth (> 98%). Fresh or macerated stillbirth appearance was a poor proxy for timing of stillbirth. While there were similar numbers of stillbirths misclassified as neonatal deaths (17/430) and neonatal deaths misclassified as stillbirths (21/36), neonatal deaths were proportionately more likely to be misclassified as stillbirths (58.3% vs 4.0%). Enablers to more accurate register-recording of birth outcome included supervision and data use. CONCLUSIONS: Our results show these routine registers accurately recorded stillbirths. Fresh/macerated appearance was a poor proxy for intrapartum stillbirths, hence more focus on measuring fetal heart rate is crucial to classification and importantly reduction in these preventable deaths

Single-mode instability in standing-wave lasers: The quantum cascade laser as a self-pumped parametric oscillator

We report the observation of a clear single-mode instability threshold in continuous-wave Fabry-Perot quantum cascade lasers (QCLs). The instability is characterized by the appearance of sidebands separated by tens of free spectral ranges (FSR) from the first lasing mode, at a pump current not much higher than the lasing threshold. As the current is increased, higher-order sidebands appear that preserve the initial spacing, and the spectra are suggestive of harmonically phase-locked waveforms. We present a theory of the instability that applies to all homogeneously broadened standing-wave lasers. The low instability threshold and the large sideband spacing can be explained by the combination of an unclamped, incoherent Lorentzian gain due to the population grating, and a coherent parametric gain caused by temporal population pulsations that changes the spectral gain line shape. The parametric term suppresses the gain of sidebands whose separation is much smaller than the reciprocal gain recovery time, while enhancing the gain of more distant sidebands. The large gain recovery frequency of the QCL compared to the FSR is essential to observe this parametric effect, which is responsible for the multiple-FSR sideband separation. We predict that by tuning the strength of the incoherent gain contribution, for example by engineering the modal overlap factors and the carrier diffusion, both amplitude-modulated (AM) or frequency-modulated emission can be achieved from QCLs. We provide initial evidence of an AM waveform emitted by a QCL with highly asymmetric facet reflectivities, thereby opening a promising route to ultrashort pulse generation in the mid-infrared. Together, the experiments and theory clarify a deep connection between parametric oscillation in optically pumped microresonators and the single-mode instability of lasers, tying together literature from the last 60 years.United States. Defense Advanced Research Projects Agency. Spectral Combs from UV to THz Program (Grant W31P4Q-16-1-0002)National Science Foundation (U.S.) (Awards ECCS-1230477, ECCS-1614631 and ECCS- 1614531)United States. Dept. of Defense. Assistant Secretary of Defense for Research & Engineering (Air Force Contracts FA8721-05-C- 0002 and No. FA8702-15-D-0001

A comparison between radiolabeled fluorodeoxyglucose uptake and hyperpolarized (13)C-labeled pyruvate utilization as methods for detecting tumor response to treatment.

Published versio

Barriers and enablers to routine register data collection for newborns and mothers: EN-BIRTH multi-country validation study.

BACKGROUND: Policymakers need regular high-quality coverage data on care around the time of birth to accelerate progress for ending preventable maternal and newborn deaths and stillbirths. With increasing facility births, routine Health Management Information System (HMIS) data have potential to track coverage. Identifying barriers and enablers faced by frontline health workers recording HMIS source data in registers is important to improve data for use. METHODS: The EN-BIRTH study was a mixed-methods observational study in five hospitals in Bangladesh, Nepal and Tanzania to assess measurement validity for selected Every Newborn coverage indicators. We described data elements required in labour ward registers to track these indicators. To evaluate barriers and enablers for correct recording of data in registers, we designed three interview tools: a) semi-structured in-depth interview (IDI) guide b) semi-structured focus group discussion (FGD) guide, and c) checklist assessing care-to-documentation. We interviewed two groups of respondents (January 2018-March 2019): hospital nurse-midwives and doctors who fill ward registers after birth (n = 40 IDI and n = 5 FGD); and data collectors (n = 65). Qualitative data were analysed thematically by categorising pre-identified codes. Common emerging themes of barriers or enablers across all five hospitals were identified relating to three conceptual framework categories. RESULTS: Similar themes emerged as both barriers and enablers. First, register design was recognised as crucial, yet perceived as complex, and not always standardised for necessary data elements. Second, register filling was performed by over-stretched nurse-midwives with variable training, limited supervision, and availability of logistical resources. Documentation complexity across parallel documents was time-consuming and delayed because of low staff numbers. Complete data were valued more than correct data. Third, use of register data included clinical handover and monthly reporting, but little feedback was given from data users. CONCLUSION: Health workers invest major time recording register data for maternal and newborn core health indicators. Improving data quality requires standardised register designs streamlined to capture only necessary data elements. Consistent implementation processes are also needed. Two-way feedback between HMIS levels is critical to improve performance and accurately track progress towards agreed health goals

Survey of women's report for 33 maternal and newborn indicators: EN-BIRTH multi-country validation study.

BACKGROUND: Population-based household surveys, notably the Demographic and Health Surveys (DHS) and Multiple Indicator Cluster Surveys (MICS), remain the main source of maternal and newborn health data for many low- and middle-income countries. As part of the Every Newborn Birth Indicators Research Tracking in Hospitals (EN-BIRTH) study, this paper focuses on testing validity of measurement of maternal and newborn indicators around the time of birth (intrapartum and postnatal) in survey-report. METHODS: EN-BIRTH was an observational study testing the validity of measurement for selected maternal and newborn indicators in five secondary/tertiary hospitals in Bangladesh, Nepal and Tanzania, conducted from July 2017 to July 2018. We compared women's report at exit survey with the gold standard of direct observation or verification from clinical records for women with vaginal births. Population-level validity was assessed by validity ratios (survey-reported coverage: observer-assessed coverage). Individual-level accuracy was assessed by sensitivity, specificity and percent agreement. We tested indicators already in DHS/MICS as well as indicators with potential to be included in population-based surveys, notably the first validation for small and sick newborn care indicators. RESULTS: 33 maternal and newborn indicators were evaluated. Amongst nine indicators already present in DHS/MICS, validity ratios for baby dried or wiped, birthweight measured, low birthweight, and sex of baby (female) were between 0.90-1.10. Instrumental birth, skin-to-skin contact, and early initiation of breastfeeding were highly overestimated by survey-report (2.04-4.83) while umbilical cord care indicators were massively underestimated (0.14-0.22). Amongst 24 indicators not currently in DHS/MICS, two newborn contact indicators (kangaroo mother care 1.00, admission to neonatal unit 1.01) had high survey-reported coverage amongst admitted newborns and high sensitivity. The remaining indicators did not perform well and some had very high "don't know" responses. CONCLUSIONS: Our study revealed low validity for collecting many maternal and newborn indicators through an exit survey instrument, even with short recall periods among women with vaginal births. Household surveys are already at risk of overload, and some specific clinical care indicators do not perform well and may be under-powered. Given that approximately 80% of births worldwide occur in facilities, routine registers should also be explored to track coverage of key maternal and newborn health interventions, particularly for clinical care

Carbonic Anhydrase Activity Monitored In Vivo by Hyperpolarized 13C-Magnetic Resonance Spectroscopy Demonstrates Its Importance for pH Regulation in Tumors.

Carbonic anhydrase buffers tissue pH by catalyzing the rapid interconversion of carbon dioxide (CO2) and bicarbonate (HCO3 (-)). We assessed the functional activity of CAIX in two colorectal tumor models, expressing different levels of the enzyme, by measuring the rate of exchange of hyperpolarized (13)C label between bicarbonate (H(13)CO3(-)) and carbon dioxide ((13)CO2), following injection of hyperpolarized H(13)CO3(-), using (13)C-magnetic resonance spectroscopy ((13)C-MRS) magnetization transfer measurements. (31)P-MRS measurements of the chemical shift of the pH probe, 3-aminopropylphosphonate, and (13)C-MRS measurements of the H(13)CO3(-)/(13)CO2 peak intensity ratio showed that CAIX overexpression lowered extracellular pH in these tumors. However, the (13)C measurements overestimated pH due to incomplete equilibration of the hyperpolarized (13)C label between the H(13)CO3(-) and (13)CO2 pools. Paradoxically, tumors overexpressing CAIX showed lower enzyme activity using magnetization transfer measurements, which can be explained by the more acidic extracellular pH in these tumors and the decreased activity of the enzyme at low pH. This explanation was confirmed by administration of bicarbonate in the drinking water, which elevated tumor extracellular pH and restored enzyme activity to control levels. These results suggest that CAIX expression is increased in hypoxia to compensate for the decrease in its activity produced by a low extracellular pH and supports the hypothesis that a major function of CAIX is to lower the extracellular pH.The authors acknowledge funding support from Cancer Research UK (CRUK; C19212/A16628; C19212/A911376), the National Institute for Health Research Cambridge Biomedical Research Centre and the School of Clinical Medicine at the University of Cambridge, the CRUK and Engineering and Physical Sciences Research Council (EPSRC) Cancer Imaging Centre in Cambridge and Manchester. E.M.S. is a recipient of funding from the European Union Seventh Framework Programme (FP7/2007-2013) under the Marie Curie Initial Training Network METAFLUX and has support from the Calouste Gulbenkian Foundation, Champalimaud Foundation, Ministerio de Saude and Fundacao para a Ciencia e Tecnologia, Portugal.This is the author accepted manuscript. The final version is available from American Association for Cancer Research via http://dx.doi.org/10.1158/0008-5472.CAN-15-085

Neonatal resuscitation: EN-BIRTH multi-country validation study.

BACKGROUND: Annually, 14 million newborns require stimulation to initiate breathing at birth and 6 million require bag-mask-ventilation (BMV). Many countries have invested in facility-based neonatal resuscitation equipment and training. However, there is no consistent tracking for neonatal resuscitation coverage. METHODS: The EN-BIRTH study, in five hospitals in Bangladesh, Nepal, and Tanzania (2017-2018), collected time-stamped data for care around birth, including neonatal resuscitation. Researchers surveyed women and extracted data from routine labour ward registers. To assess accuracy, we compared gold standard observed coverage to survey-reported and register-recorded coverage, using absolute difference, validity ratios, and individual-level validation metrics (sensitivity, specificity, percent agreement). We analysed two resuscitation numerators (stimulation, BMV) and three denominators (live births and fresh stillbirths, non-crying, non-breathing). We also examined timeliness of BMV. Qualitative data were collected from health workers and data collectors regarding barriers and enablers to routine recording of resuscitation. RESULTS: Among 22,752 observed births, 5330 (23.4%) babies did not cry and 3860 (17.0%) did not breathe in the first minute after birth. 16.2% (n = 3688) of babies were stimulated and 4.4% (n = 998) received BMV. Survey-report underestimated coverage of stimulation and BMV. Four of five labour ward registers captured resuscitation numerators. Stimulation had variable accuracy (sensitivity 7.5-40.8%, specificity 66.8-99.5%), BMV accuracy was higher (sensitivity 12.4-48.4%, specificity > 93%), with small absolute differences between observed and recorded BMV. Accuracy did not vary by denominator option. < 1% of BMV was initiated within 1 min of birth. Enablers to register recording included training and data use while barriers included register design, documentation burden, and time pressure. CONCLUSIONS: Population-based surveys are unlikely to be useful for measuring resuscitation coverage given low validity of exit-survey report. Routine labour ward registers have potential to accurately capture BMV as the numerator. Measuring the true denominator for clinical need is complex; newborns may require BMV if breathing ineffectively or experiencing apnoea after initial drying/stimulation or subsequently at any time. Further denominator research is required to evaluate non-crying as a potential alternative in the context of respectful care. Measuring quality gaps, notably timely provision of resuscitation, is crucial for programme improvement and impact, but unlikely to be feasible in routine systems, requiring audits and special studies