Triplet energy transfer from quantum dots increases Ln(iii) photoluminescence, enabling excitation at visible wavelengths.

Europium(iii) complexes are promising for bioimaging because of their long-lived, narrow emission. The photoluminescence (PL) from europium(iii) complexes is usually low. Thus, the effective utilization of low-energy light >400 nm and enhancement of PL are long-standing goals. Here, we show for the first time that 1-naphthoic acid triplet transmitter ligands bound to CdS quantum dots (QDs) and europium(iii) complexes create an energy transfer cascade that takes advantage of the strong QD absorption. This is confirmed by transient absorption spectroscopy, which shows hole mediated triplet energy transfer from QDs to 1-NCA, followed by triplet transfer from 1-NCA to europium(iii) complexes with an efficiency of 65.9 ± 7.7%. Smaller CdS QDs with a larger driving force lead to higher triplet transfer efficiency, with Eu(iii) PL intensity enhanced up to 21.4 times, the highest value ever reported. This hybrid QD system introduces an innovative approach to enhance the brightness of europium complexes.

Halting the Canadian STRIDER randomised controlled trial of sildenafil for severe, early-onset fetal growth restriction: ethical, methodological, and pragmatic considerations.

OBJECTIVES: To determine the efficacy and safety of sildenafil citrate to improve outcomes in pregnancies complicated by early-onset, dismal prognosis, fetal growth restriction (FGR). Eligibility: women ≥ 18 years, singleton, 18 + 0-27 + 6 weeks' gestation, estimated fetal weight < 700 g, low PLFG, and ≥ 1 of (i) abdominal circumference < 10th percentile for gestational age (GA); or (ii) reduced growth velocity and either abnormal uterine artery Doppler or prior early-onset FGR with adverse outcome. Ineligibility criteria included: planned termination or reversed umbilical artery end-diastolic flow. Eligibility confirmed by placental growth factor (PLGF) < 5 th percentile for GA measured post randomization. Women randomly received (1:1) either sildenafil 25 mg three times daily or matched placebo until either delivery or 31 + 6 weeks. PRIMARY OUTCOME: delivery GA. The trial stopped early when Dutch STRIDER signalled potential harm; despite distinct eligibility criteria and IRB and DSMB support to continue, because of futility. NCT02442492 [registered 13/05/2015]. RESULTS: Between May 2017 and June 2018, 21 (90 planned) women were randomised [10 sildenafil; 11 placebo (1 withdrawal)]. Baseline characteristics, PLGF levels, maternal and perinatal outcomes, and adverse events did not differ. Delivery GA: 26 + 6 weeks (sildenafil) vs 29 + 2 weeks (placebo); p = 0.200. Data will contribute to an individual participant data meta-analysis.

UK B.1.1.7 variant exhibits increased respiratory replication and shedding in nonhuman primates

The continuing emergence of SARS-CoV-2 variants calls for regular assessment to identify differences in viral replication, shedding and associated disease. In this study, African green monkeys were infected intranasally with either a contemporary D614G or the UK B.1.1.7 variant. Both variants caused mild respiratory disease with no significant differences in clinical presentation. Significantly higher levels of viral RNA and infectious virus were found in upper and lower respiratory tract samples and tissues from B.1.1.7 infected animals. Interestingly, D614G infected animals showed significantly higher levels of viral RNA and infectious virus in rectal swabs and gastrointestinal tract tissues. Our results indicate that B.1.1.7 infection in African green monkeys is associated with increased respiratory replication and shedding but no disease enhancement similar to human B.1.1.7 cases. One-Sentence SummaryUK B.1.1.7 infection of African green monkeys exhibits increased respiratory replication and shedding but no disease enhancement

A single intranasal dose of chimpanzee adenovirus-vectored vaccine protects against SARS-CoV-2 infection in rhesus macaques

The deployment of a vaccine that limits transmission and disease likely will be required to end the Coronavirus Disease 2019 (COVID-19) pandemic. We recently described the protective activity of an intranasally-administered chimpanzee adenovirus-vectored vaccine encoding a pre-fusion stabilized spike (S) protein (ChAd-SARS-CoV-2-S) in the upper and lower respiratory tract of mice expressing the human angiotensin-converting enzyme 2 (ACE2) receptor. Here, we show the immunogenicity and protective efficacy of this vaccine in non-human primates. Rhesus macaques were immunized with ChAd-Control or ChAd-SARS-CoV-2-S and challenged one month later by combined intranasal and intrabronchial routes with SARS-CoV-2. A single intranasal dose of ChAd-SARS-CoV-2-S induced neutralizing antibodies and T cell responses and limited or prevented infection in the upper and lower respiratory tract after SARS-CoV-2 challenge. As this single intranasal dose vaccine confers protection against SARS-CoV-2 in non-human primates, it is a promising candidate for limiting SARS-CoV-2 infection and transmission in humans.

Long-Term Prognosis of Patients With Coronary Microvascular Disease Using Stress Perfusion Cardiac Magnetic Resonance.

OBJECTIVES: This study investigated the prognosis of coronary microvascular disease (CMD) as determined by stress perfusion cardiac magnetic resonance (CMR) in patients with ischemic symptoms but without significant coronary artery disease (CAD). BACKGROUND: Patients with CMD have poorer prognosis with various cardiac diseases. The myocardial perfusion reserve index (MPRI) derived from noninvasive stress perfusion CMR has been established to diagnose microvascular angina with a threshold MPRI <1.4. The prognosis of CMD as determined by MPRI is unknown. METHODS: Chest pain patients without epicardial CAD or myocardial disease from January 2009 to December 2017 were retrospectively included from 3 imaging centers in Hong Kong (HK). Stress perfusion CMR examinations were performed using either adenosine or adenosine triphosphate. Adequate stress was assessed by achieving splenic switch-off sign. Measurement of MPRI was performed in all stress perfusion CMR scans. Patients were followed for major adverse cardiovascular events defined as all-cause death, acute coronary syndrome (ACS), epicardial CAD development, heart failure hospitalization and non-fatal stroke. RESULTS: A total of 218 patients were studied (mean age 59 ± 12 years; 49.5% male) and the average MPRI of that cohort was 1.56 ± 0.33. Females and a history of hyperlipidemia were predictors of lower MPRI. Major adverse cardiovascular events (MACE) occurred in 15.6% of patients during a median follow-up of 5.5 years (interquartile range: 4.6 to 6.8 years). The optimal cutoff value of MPRI in predicting MACE was found with a threshold MPRI ≤1.47. Patients with MPRI ≤1.47 had three-fold increased risk of MACE compared with those with MPRI >1.47 (hazard ratio [HR]: 3.14; 95% confidence interval [CI]: 1.58 to 6.25; p = 0.001). Multivariate Cox regression after adjusting for age and hypertension demonstrated that MPRI was an independent predictor of MACE (HR: 0.10; 95% CI: 0.03 to 0.34; p < 0.001). CONCLUSIONS: Stress perfusion CMR-derived MPRI is an independent imaging marker that predicts MACE in patients with ischemic symptom and no overt CAD over the medium term.

Defining the Syrian hamster as a highly susceptible preclinical model for SARS-CoV-2 infection

Following emergence in late 2019, SARS-CoV-2 rapidly became pandemic and is presently responsible for millions of infections and hundreds of thousands of deaths worldwide. There is currently no approved vaccine to halt the spread of SARS-CoV-2 and only very few treatment options are available to manage COVID-19 patients. For development of preclinical countermeasures, reliable and well-characterized small animal disease models will be of paramount importance. Here we show that intranasal inoculation of SARS-CoV-2 into Syrian hamsters consistently caused moderate broncho-interstitial pneumonia, with high viral lung loads and extensive virus shedding, but animals only displayed transient mild disease. We determined the infectious dose 50 to be only five infectious particles, making the Syrian hamster a highly susceptible model for SARS-CoV-2 infection. Neither hamster age nor sex had any impact on the severity of disease or course of infection. Finally, prolonged viral persistence in interleukin 2 receptor gamma chain knockout hamsters revealed susceptibility of SARS-CoV-2 to adaptive immune control. In conclusion, the Syrian hamster is highly susceptible to SARS-CoV-2 making it a very suitable infection model for COVID-19 countermeasure development. One Sentence SummaryThe Syrian hamster is highly susceptible to SARS-CoV-2 making it an ideal infection model for COVID-19 countermeasure development.

The Community-Level Interventions for Pre-eclampsia (CLIP) cluster randomised trials in Mozambique, Pakistan, and India: an individual participant-level meta-analysis.

BACKGROUND: To overcome the three delays in triage, transport and treatment that underlie adverse pregnancy outcomes, we aimed to reduce all-cause adverse outcomes with community-level interventions targeting women with pregnancy hypertension in three low-income countries. METHODS: In this individual participant-level meta-analysis, we de-identified and pooled data from the Community-Level Interventions for Pre-eclampsia (CLIP) cluster randomised controlled trials in Mozambique, Pakistan, and India, which were run in 2014-17. Consenting pregnant women, aged 12-49 years, were recruited in their homes. Clusters, defined by local administrative units, were randomly assigned (1:1) to intervention or control groups. The control groups continued local standard of care. The intervention comprised community engagement and existing community health worker-led mobile health-supported early detection, initial treatment, and hospital referral of women with hypertension. For this meta-analysis, as for the original studies, the primary outcome was a composite of maternal or perinatal outcome (either maternal, fetal, or neonatal death, or severe morbidity for the mother or baby), assessed by unmasked trial surveillance personnel. For this analysis, we included all consenting participants who were followed up with completed pregnancies at trial end. We analysed the outcome data with multilevel modelling and present data with the summary statistic of adjusted odds ratios (ORs) with 95% CIs (fixed effects for maternal age, parity, maternal education, and random effects for country and cluster). This meta-analysis is registered with PROSPERO, CRD42018102564. FINDINGS: Overall, 44 clusters (69 330 pregnant women) were randomly assigned to intervention (22 clusters [36 008 pregnancies]) or control (22 clusters [33 322 pregnancies]) groups. 32 290 (89·7%) pregnancies in the intervention group and 29 698 (89·1%) in the control group were followed up successfully. Median maternal age of included women was 26 years (IQR 22-30). In the intervention clusters, 6990 group and 16 691 home-based community engagement sessions and 138 347 community health worker-led visits to 20 819 (57·8%) of 36 008 women (of whom 11 095 [53·3%] had a visit every 4 weeks) occurred. Blood pressure and dipstick proteinuria were assessed per protocol. Few women were eligible for methyldopa for severe hypertension (181 [1%] of 20 819) or intramuscular magnesium sulfate for pre-eclampsia (198 [1%]), of whom most accepted treatment (162 [89·5%] of 181 for severe hypertension and 133 [67·2%] of 198 for pre-eclampsia). 1255 (6%) were referred to a comprehensive emergency obstetric care facility, of whom 864 (82%) accepted the referral. The primary outcome was similar in the intervention (7871 [24%] of 32 290 pregnancies) and control clusters (6516 [22%] of 29 698; adjusted OR 1·17, 95% CI 0·90-1·51; p=0·24). No intervention-related serious adverse events occurred, and few adverse effects occurred after in-community treatment with methyldopa (one [2%] of 51; India only) and none occurred after in-community treatment with magnesium sulfate or during transport to facility. INTERPRETATION: The CLIP intervention did not reduce adverse pregnancy outcomes. Future community-level interventions should expand the community health worker workforce, assess general (rather than condition-specific) messaging, and include health system strengthening. FUNDING: University of British Columbia, a grantee of the Bill & Melinda Gates Foundation.

Community-level interventions for pre-eclampsia (CLIP) in Pakistan: A cluster randomised controlled trial.

OBJECTIVES: To reduce all-cause maternal and perinatal mortality and major morbidity through Lady Health Worker (LHW)-facilitated community engagement and early diagnosis, stabilization and referral of women with preeclampsia, an important contributor to adverse maternal and perinatal outcomes given delays in early detection and initial management. STUDY DESIGN: In the Pakistan Community-Level Interventions for Pre-eclampsia (CLIP) cluster randomized controlled trial (NCT01911494), LHWs engaged the community, recruited pregnant women from 20 union councils (clusters), undertook mobile health-guided clinical assessment for preeclampsia, and referral to facilities after stabilization. MAIN OUTCOME MEASURES: The primary outcome was a composite of maternal, fetal and newborn mortality and major morbidity. FINDINGS: We recruited 39,446 women in intervention (N = 20,264) and control clusters (N = 19,182) with minimal loss to follow-up (3∙7% vs. 4∙5%, respectively). The primary outcome did not differ between intervention (26·6%) and control (21·9%) clusters (adjusted odds ratio, aOR, 1∙20 [95% confidence interval 0∙84-1∙72]; p = 0∙31). There was reduction in stillbirths (0·89 [0·81-0·99]; p = 0·03), but no impact on maternal death (1·08 [0·69, 1·71]; p = 0·74) or morbidity (1·12 [0·57, 2·16]; p = 0·77); early (0·95 [0·82-1·09]; p = 0·46) or late neonatal deaths (1·23 [0·97-1·55]; p = 0·09); or neonatal morbidity (1·22 [0·77, 1·96]; p = 0·40). Improvements in outcome rates were observed with 4-7 (p = 0·015) and ≥8 (p < 0·001) (vs. 0) CLIP contacts. INTERPRETATION: The CLIP intervention was well accepted by the community and implemented by LHWs. Lack of effects on adverse outcomes could relate to quality care for mothers with pre-eclampsia in health facilities. Future strategies for community outreach must also be accompanied by health facility strengthening. FUNDING: The University of British Columbia (PRE-EMPT), a grantee of the Bill & Melinda Gates Foundation (OPP1017337).

The Community-Level Interventions for Pre-eclampsia (CLIP) cluster randomised trials in Mozambique, Pakistan, and India: an individual participant-level meta-analysis

To overcome the three delays in triage, transport and treatment that underlie adverse pregnancy outcomes, we aimed to reduce all-cause adverse outcomes with community-level interventions targeting women with pregnancy hypertension in three low-income countries. Methods: In this individual participant-level meta-analysis, we de-identified and pooled data from the Community-Level Interventions for Pre-eclampsia (CLIP) cluster randomised controlled trials in Mozambique, Pakistan, and India, which were run in 2014-17. Consenting pregnant women, aged 12-49 years, were recruited in their homes. Clusters, defined by local administrative units, were randomly assigned (1:1) to intervention or control groups. The control groups continued local standard of care. The intervention comprised community engagement and existing community health worker-led mobile health-supported early detection, initial treatment, and hospital referral of women with hypertension. For this meta-analysis, as for the original studies, the primary outcome was a composite of maternal or perinatal outcome (either maternal, fetal, or neonatal death, or severe morbidity for the mother or baby), assessed by unmasked trial surveillance personnel. For this analysis, we included all consenting participants who were followed up with completed pregnancies at trial end. We analysed the outcome data with multilevel modelling and present data with the summary statistic of adjusted odds ratios (ORs) with 95% CIs (fixed effects for maternal age, parity, maternal education, and random effects for country and cluster). This meta-analysis is registered with PROSPERO, CRD42018102564. Findings: Overall, 44 clusters (69 330 pregnant women) were randomly assigned to intervention (22 clusters [36 008 pregnancies]) or control (22 clusters [33 322 pregnancies]) groups. 32 290 (89·7%) pregnancies in the intervention group and 29 698 (89·1%) in the control group were followed up successfully. Median maternal age of included women was 26 years (IQR 22-30). In the intervention clusters, 6990 group and 16 691 home-based community engagement sessions and 138 347 community health worker-led visits to 20 819 (57·8%) of 36 008 women (of whom 11 095 [53·3%] had a visit every 4 weeks) occurred. Blood pressure and dipstick proteinuria were assessed per protocol. Few women were eligible for methyldopa for severe hypertension (181 [1%] of 20 819) or intramuscular magnesium sulfate for pre-eclampsia (198 [1%]), of whom most accepted treatment (162 [89·5%] of 181 for severe hypertension and 133 [67·2%] of 198 for pre-eclampsia). 1255 (6%) were referred to a comprehensive emergency obstetric care facility, of whom 864 (82%) accepted the referral. The primary outcome was similar in the intervention (7871 [24%] of 32 290 pregnancies) and control clusters (6516 [22%] of 29 698; adjusted OR 1·17, 95% CI 0·90-1·51; p=0·24). No intervention-related serious adverse events occurred, and few adverse effects occurred after in-community...

Community-level interventions for pre-eclampsia (CLIP) in Mozambique: A cluster randomised controlled trial

Objectives: Pregnancy hypertension is the third leading cause of maternal mortality in Mozambique and contributes significantly to fetal and neonatal mortality. The objective of this trial was to assess whether task-sharing care might reduce adverse pregnancy outcomes related to delays in triage, transport, and treatment. Study design: The Mozambique Community-Level Interventions for Pre-eclampsia (CLIP) cluster randomised controlled trial (NCT01911494) recruited pregnant women in 12 administrative posts (clusters) in Maputo and Gaza Provinces. The CLIP intervention (6 clusters) consisted of community engagement, community health worker-provided mobile health-guided clinical assessment, initial treatment, and referral to facility either urgently (<4hrs) or non-urgently (<24hrs), dependent on algorithm-defined risk. Treatment effect was estimated by multi-level logistic regression modelling, adjusted for prognostically-significant baseline variables. Predefined secondary analyses included safety and evaluation of the intensity of CLIP contacts. Main outcome measures: 20% reduction in composite of maternal, fetal, and newborn mortality and major morbidity. Results: 15,013 women (15,123 pregnancies) were recruited in intervention (N = 7930; 2·0% loss to follow-up (LTFU)) and control (N = 7190; 2·8% LTFU) clusters. The primary outcome did not differ between intervention and control clusters (adjusted odds ratio (aOR) 1·31, 95% confidence interval (CI) [0·70, 2·48]; p = 0·40). Compared with intervention arm women without CLIP contacts, those with ≥8 contacts experienced fewer primary outcomes (aOR 0·79 (95% CI 0·63, 0·99); p = 0·041), primarily due to improved maternal outcomes (aOR 0·72 (95% CI 0·53, 0·97); p = 0·033). Interpretation: As generally implemented, the CLIP intervention did not improve pregnancy outcomes; community implementation of the WHO eight contact model may be beneficial. Funding: The University of British Columbia (PRE-EMPT), a grantee of the Bill & Melinda Gates Foundation (OPP1017337).

Community level interventions for pre-eclampsia (CLIP) in India: A cluster randomised controlled trial.

OBJECTIVES: Pregnancy hypertension is associated with 7.1% of maternal deaths in India. The objective of this trial was to assess whether task-sharing care might reduce adverse pregnancy outcomes related to delays in triage, transport, and treatment. STUDY DESIGN: The Indian Community-Level Interventions for Pre-eclampsia (CLIP) open-label cluster randomised controlled trial (NCT01911494) recruited pregnant women in 12 clusters (initial four-cluster internal pilot) in Belagavi and Bagalkote, Karnataka. The CLIP intervention (6 clusters) consisted of community engagement, community health workers (CHW) provided mobile health (mHeath)-guided clinical assessment, initial treatment, and referral to facility either urgently (<4 h) or non-urgently (<24 h), dependent on algorithm-defined risk. Treatment effect was estimated by multi-level logistic regression modelling, adjusted for prognostically-significant baseline variables. Predefined secondary analyses included safety and evaluation of the intensity of mHealth-guided CHW-provided contacts. MAIN OUTCOME MEASURES: 20% reduction in composite of maternal, fetal, and newborn mortality and major morbidity. RESULTS: All 14,783 recruited pregnancies (7839 intervention, 6944 control) were followed-up. The primary outcome did not differ between intervention and control arms (adjusted odds ratio (aOR) 0.92 [95% confidence interval 0.74, 1.15]; p = 0.47; intraclass correlation coefficient 0.013). There were no intervention-related safety concerns following administration of either methyldopa or MgSO4, and 401 facility referrals. Compared with intervention arm women without CLIP contacts, those with ≥8 contacts suffered fewer stillbirths (aOR 0.19 [0.10, 0.35]; p < 0.001), at the probable expense of survivable neonatal morbidity (aOR 1.39 [0.97, 1.99]; p = 0.072). CONCLUSIONS: As implemented, solely community-level interventions focussed on pre-eclampsia did not improve outcomes in northwest Karnataka.

Hydroxychloroquine Proves Ineffective in Hamsters and Macaques Infected with SARS-CoV-2

We remain largely without effective prophylactic/therapeutic interventions for COVID-19. Although many human clinical trials are ongoing, there remains a deficiency of supportive preclinical drug efficacy studies. Here we assessed the prophylactic/therapeutic efficacy of hydroxychloroquine (HCQ), a drug of interest for COVID-19 management, in two animal models. When used for prophylaxis or treatment neither the standard human malaria dose (6.5 mg/kg) nor a high dose (50 mg/kg) of HCQ had any beneficial effect on clinical disease or SARS-CoV-2 kinetics (replication/shedding) in the Syrian hamster disease model. Similarly, HCQ prophylaxis/treatment (6.5 mg/kg) did not significantly benefit clinical outcome nor reduce SARS-CoV-2 replication/shedding in the upper and lower respiratory tract in the rhesus macaque disease model. In conclusion, our preclinical animal studies do not support the use of HCQ in prophylaxis/treatment of COVID-19.One Sentence Summary Hydroxychloroquine prophylaxis/treatment showed no beneficial effect in SARS-CoV-2 hamster and macaque disease models.Competing Interest StatementThe authors have declared no competing interest.View Full Text

Community-level interventions for pre-eclampsia (CLIP) in Mozambique: A cluster randomised controlled trial.

OBJECTIVES: Pregnancy hypertension is the third leading cause of maternal mortality in Mozambique and contributes significantly to fetal and neonatal mortality. The objective of this trial was to assess whether task-sharing care might reduce adverse pregnancy outcomes related to delays in triage, transport, and treatment. STUDY DESIGN: The Mozambique Community-Level Interventions for Pre-eclampsia (CLIP) cluster randomised controlled trial (NCT01911494) recruited pregnant women in 12 administrative posts (clusters) in Maputo and Gaza Provinces. The CLIP intervention (6 clusters) consisted of community engagement, community health worker-provided mobile health-guided clinical assessment, initial treatment, and referral to facility either urgently (<4hrs) or non-urgently (<24hrs), dependent on algorithm-defined risk. Treatment effect was estimated by multi-level logistic regression modelling, adjusted for prognostically-significant baseline variables. Predefined secondary analyses included safety and evaluation of the intensity of CLIP contacts. MAIN OUTCOME MEASURES: 20% reduction in composite of maternal, fetal, and newborn mortality and major morbidity. RESULTS: 15,013 women (15,123 pregnancies) were recruited in intervention (N = 7930; 2·0% loss to follow-up (LTFU)) and control (N = 7190; 2·8% LTFU) clusters. The primary outcome did not differ between intervention and control clusters (adjusted odds ratio (aOR) 1·31, 95% confidence interval (CI) [0·70, 2·48]; p = 0·40). Compared with intervention arm women without CLIP contacts, those with ≥8 contacts experienced fewer primary outcomes (aOR 0·79 (95% CI 0·63, 0·99); p = 0·041), primarily due to improved maternal outcomes (aOR 0·72 (95% CI 0·53, 0·97); p = 0·033). INTERPRETATION: As generally implemented, the CLIP intervention did not improve pregnancy outcomes; community implementation of the WHO eight contact model may be beneficial. FUNDING: The University of British Columbia (PRE-EMPT), a grantee of the Bill & Melinda Gates Foundation (OPP1017337).

Self-reported maternal morbidity: Results from the community level interventions for pre-eclampsia (CLIP) baseline survey in Sindh, Pakistan.

OBJECTIVE: Community-based data regarding maternal and perinatal morbidity and mortality are scarce in less-developed countries. The aim of the study was to collect representative community-level demographic health information to provide socio-demographic and health outcome data. METHODS: A retrospective household survey of women of reproductive age (15-49 years) living in two districts of Sindh Province, Pakistan was conducted. Pregnancy incidence over the past 12 months and during each woman's lifetime; maternal, fetal, infant and child deaths in the past 12 months; and rates of hypertension and seizures in pregnancy were calculated. RESULTS: From June to September 2013, 88,410 households were surveyed with 1.2 (±0.6) women of reproductive age per household. 19,584 women (11.9%) reported pregnancies in the preceding 12 months; 83.0% had live births, 3.5% resulting in stillbirths and 13.6% in miscarriages. 34.2% of deliveries occurred at home. Out of all women who reported a pregnancy in past 12 months, 62.1% reported high blood pressure and 11.9% reported seizures complicating her most recent pregnancy. Blood pressure was not measured during survey to confirm hypertension. The perinatal, neonatal and maternal mortality ratios were 64.7/1000, 39/1000 and 166/100,000 livebirths, respectively. CONCLUSION: This study estimated population-level mortality ratios that can be used for the planning of health interventions in these regions. Self-reported pregnancy hypertension and seizures was inaccurate, reflecting limited community understanding of these disorders. Mortality estimates are comparable to those reported by the World Health Organization for maternal mortality ratio and neonatal mortality rate of 170/100,000 and 36/1000 live births, respectively.

The incidence of pregnancy hypertension in India, Pakistan, Mozambique, and Nigeria: A prospective population-level analysis.

BACKGROUND: Most pregnancy hypertension estimates in less-developed countries are from cross-sectional hospital surveys and are considered overestimates. We estimated population-based rates by standardised methods in 27 intervention clusters of the Community-Level Interventions for Pre-eclampsia (CLIP) cluster randomised trials. METHODS AND FINDINGS: CLIP-eligible pregnant women identified in their homes or local primary health centres (2013-2017). Included here are women who had delivered by trial end and received a visit from a community health worker trained to provide supplementary hypertension-oriented care, including standardised blood pressure (BP) measurement. Hypertension (BP ≥ 140/90 mm Hg) was defined as chronic (first detected at <20 weeks gestation) or gestational (≥20 weeks); pre-eclampsia was gestational hypertension plus proteinuria or a pre-eclampsia-defining complication. A multi-level regression model compared hypertension rates and types between countries (p < 0.05 considered significant). In 28,420 pregnancies studied, women were usually young (median age 23-28 years), parous (53.7%-77.3%), with singletons (≥97.5%), and enrolled at a median gestational age of 10.4 (India) to 25.9 weeks (Mozambique). Basic education varied (22.8% in Pakistan to 57.9% in India). Pregnancy hypertension incidence was lower in Pakistan (9.3%) than India (10.3%), Mozambique (10.9%), or Nigeria (10.2%) (p = 0.001). Most hypertension was diastolic only (46.4% in India, 72.7% in Pakistan, 61.3% in Mozambique, and 63.3% in Nigeria). At first presentation with elevated BP, gestational hypertension was most common diagnosis (particularly in Mozambique [8.4%] versus India [6.9%], Pakistan [6.5%], and Nigeria [7.1%]; p < 0.001), followed by pre-eclampsia (India [3.8%], Nigeria [3.0%], Pakistan [2.4%], and Mozambique [2.3%]; p < 0.001) and chronic hypertension (especially in Mozambique [2.5%] and Nigeria [2.8%], compared with India [1.2%] and Pakistan [1.5%]; p < 0.001). Inclusion of additional diagnoses of hypertension and related complications, from household surveys or facility record review (unavailable in Nigeria), revealed higher hypertension incidence: 14.0% in India, 11.6% in Pakistan, and 16.8% in Mozambique; eclampsia was rare (<0.5%). CONCLUSIONS: Pregnancy hypertension is common in less-developed settings. Most women in this study presented with gestational hypertension amenable to surveillance and timed delivery to improve outcomes. TRIAL REGISTRATION: This study is a secondary analysis of a clinical trial - ClinicalTrials.gov registration number NCT01911494.

Temporal and external validation of the fullPIERS model for the prediction of adverse maternal outcomes in women with pre-eclampsia.

The fullPIERS model is a risk prediction model developed to predict adverse maternal outcomes within 48 h for women admitted with pre-eclampsia. External validation of the model is required before implementation for clinical use. We assessed the temporal and external validity of the fullPIERS model in high income settings using five cohorts collected between 2003 and 2016, from tertiary hospitals in Canada, the United States of America, Finland and the United Kingdom. The cohorts were grouped into three datasets for assessing the primary external, and temporal validity, and broader transportability of the model. The predicted risks of developing an adverse maternal outcome were calculated using the model equation and model performance was evaluated based on discrimination, calibration, and stratification. Our study included a total of 2429 women, with an adverse maternal outcome rate of 6.7%, 6.6%, and 7.0% in the primary external, temporal, and combined (broader) validation cohorts, respectively. The model had good discrimination in all datasets: 0.81 (95%CI 0.75-0.86), 0.82 (95%CI 0.76-0.87), and 0.75 (95%CI 0.71-0.80) for the primary external, temporal, and broader validation datasets, respectively. Calibration was best for the temporal cohort but poor in the broader validation dataset. The likelihood ratios estimated to rule in adverse maternal outcomes were high at a cut-off of ≥30% in all datasets. The fullPIERS model is temporally and externally valid and will be useful in the management of women with pre-eclampsia in high income settings although model recalibration is required to improve performance, specifically in the broader healthcare settings.

Place-specific factors associated with adverse maternal and perinatal outcomes in Southern Mozambique: a retrospective cohort study.

OBJECTIVES: To identify and measure the place-specific determinants that are associated with adverse maternal and perinatal outcomes in the southern region of Mozambique. DESIGN: Retrospective cohort study. Choice of variables informed by literature and Delphi consensus. SETTING: Study conducted during the baseline phase of a community level intervention for pre-eclampsia that was led by community health workers. PARTICIPANTS: A household census identified 50 493 households that were home to 80 483 women of reproductive age (age 12-49 years). Of these women, 14 617 had been pregnant in the 12 months prior to the census, of which 9172 (61.6%) had completed their pregnancies. PRIMARY AND SECONDARY OUTCOME MEASURES: A combined fetal, maternal and neonatal outcome was calculated for all women with completed pregnancies. RESULTS: A total of six variables were statistically significant (p≤0.05) in explaining the combined outcome. These included: geographic isolation, flood proneness, access to an improved latrine, average age of reproductive age woman, family support and fertility rates. The performance of the ordinary least squares model was an adjusted R2=0.69. Three of the variables (isolation, latrine score and family support) showed significant geographic variability in their effect on rates of adverse outcome. Accounting for this modest non-stationary effect through geographically weighted regression increased the adjusted R2 to 0.71. CONCLUSIONS: The community exploration was successful in identifying context-specific determinants of maternal health. The results highlight the need for designing targeted interventions that address the place-specific social determinants of maternal health in the study area. The geographic process of identifying and measuring these determinants, therefore, has implications for multisectoral collaboration. TRIAL REGISTRATION NUMBER: NCT01911494.

Semiconductor Nanocrystal Light Absorbers for Photon Upconversion.

Semiconductor nanocrystals (NCs) can initiate energy and charge transfer in multiple applications with their unique optical and electronic properties. In particular, NCs are excellent light absorbers for initiating triplet energy transfer (TET) to organic molecules, a key step in triplet-fusion-based photon upconversion. Triplet energy transfer across this inorganic-organic interface is one of the bottlenecks that currently limits the overall photon upconversion quantum yield. In this Perspective, we summarize the progress made in the past three years on this hybrid photon upconversion platform. We discuss the effects of NC size, composition, and surface states on TET. Nanocrystal surface engineering may address the loss mechanisms arising from defect states and exciton-phonon coupling. Alternative materials for NC triplet photosensitizers that do not contain toxic heavy metals will be especially useful for various biological applications.

The feasibility of task-sharing the identification, emergency treatment, and referral for women with pre-eclampsia by community health workers in India.

BACKGROUND: Hypertensive disorders are the second highest direct obstetric cause of maternal death after haemorrhage, accounting for 14% of maternal deaths globally. Pregnancy hypertension contributes to maternal deaths, particularly in low- and middle-income countries, due to a scarcity of doctors providing evidence-based emergency obstetric care. Task-sharing some obstetric responsibilities may help to reduce the mortality rates. This study was conducted to assess acceptability by the community and other healthcare providers, for task-sharing by community health workers (CHW) in the identification and initial care in hypertensive disorders in pregnancy. METHODS: This study was conducted in two districts of Karnataka state in south India. A total of 14 focus group discussions were convened with various community representatives: women of reproductive age (N = 6), male decision-makers (N = 2), female decision-makers (N = 3), and community leaders (N = 3). One-to-one interviews were held with medical officers (N = 2), private healthcare OBGYN specialists (N = 2), senior health administrators (N = 2), Taluka (county) health officers (N = 2), and obstetricians (N = 4). All data collection was facilitated by local researchers familiar with the setting and language. Data were subsequently transcribed, translated and analysed thematically using NVivo 10 software. RESULTS: There was strong community support for home visits by CHW to measure the blood pressure of pregnant women; however, respondents were concerned about their knowledge, training and effectiveness. The treatment with oral antihypertensive agents and magnesium sulphate in emergencies was accepted by community representatives but medical practitioners and health administrators had reservations, and insisted on emergency transport to a higher facility. The most important barriers for task-sharing were concerns regarding insufficient training, limited availability of medications, the questionable validity of blood pressure devices, and the ability of CHW to correctly diagnose and intervene in cases of hypertensive disorders of pregnancy. CONCLUSION: Task-sharing to community-based health workers has potential to facilitate early diagnosis of the hypertensive disorders of pregnancy and assist in the provision of emergency care. We identified some facilitators and barriers for successful task-sharing of emergency obstetric care aimed at reducing mortality and morbidity due to hypertensive disorders of pregnancy.

Health and socio-demographic profile of women of reproductive age in rural communities of southern Mozambique.

Reliable statistics on maternal morbidity and mortality are scarce in low and middle-income countries, especially in rural areas. This is the case in Mozambique where many births happen at home. Furthermore, a sizeable number of facility births have inadequate registration. Such information is crucial for developing effective national and global health policies for maternal and child health. The aim of this study was to generate reliable baseline socio-demographic information on women of reproductive age as well as to establish a demographic surveillance platform to support the planning and implementation of the Community Level Intervention for Pre-eclampsia (CLIP) study, a cluster randomized controlled trial. This study represents a census of all women of reproductive age (12-49 years) in twelve rural communities in Maputo and Gaza provinces of Mozambique. The data were collected through electronic forms implemented in Open Data Kit (ODK) (an app for android based tablets) and household and individual characteristics. Verbal autopsies were conducted on all reported maternal deaths to determine the underlying cause of death. Between March and October 2014, 50,493 households and 80,483 women of reproductive age (mean age 26.9 years) were surveyed. A total of 14,617 pregnancies were reported in the twelve months prior to the census, resulting in 9,029 completed pregnancies. Of completed pregnancies, 8,796 resulted in live births, 466 resulted in stillbirths and 288 resulted in miscarriages. The remaining pregnancies had not yet been completed during the time of the survey (5,588 pregnancies). The age specific fertility indicates that highest rate (188 live births per 1,000 women) occurs in the age 20-24 years old. The estimated stillbirth rate was 50.3/1,000 live and stillbirths; neonatal mortality rate was 13.3/1,000 live births and maternal mortality ratio was 204.6/100,000 live births. The most common direct cause of maternal death was eclampsia and tuberculosis was the most common indirect cause of death. This study found that fertility rate is high at age 20-24 years old. Pregnancy in the advanced age (>35 years of age) in this study was associated with higher poor outcomes such as miscarriage and stillbirth. The study also found high stillbirth rate indicating a need for increased attention to maternal health in southern Mozambique. Tuberculosis and HIV/AIDS are prominent indirect causes of maternal death, while eclampsia represents the number one direct obstetric cause of maternal deaths in these communities. Additional efforts to promote safe motherhood and improve child survival are crucial in these communities.