Summary In this Series paper, we review trends since the 2005 Lancet Series on Neonatal Survival to inform acceleration of progress for newborn health post-2015. On the basis of multicountry analyses ...and multi-stakeholder consultations, we propose national targets for 2035 of no more than 10 stillbirths per 1000 total births, and no more than 10 neonatal deaths per 1000 livebirths, compatible with the under-5 mortality targets of no more than 20 per 1000 livebirths. We also give targets for 2030. Reduction of neonatal mortality has been slower than that for maternal and child (1–59 months) mortality, slowest in the highest burden countries, especially in Africa, and reduction is even slower for stillbirth rates. Birth is the time of highest risk, when more than 40% of maternal deaths (total about 290 000) and stillbirths or neonatal deaths (5·5 million) occur every year. These deaths happen rapidly, needing a rapid response by health-care workers. The 2·9 million annual neonatal deaths worldwide are attributable to three main causes: infections (0·6 million), intrapartum conditions (0·7 million), and preterm birth complications (1·0 million). Boys have a higher biological risk of neonatal death, but girls often have a higher social risk. Small size at birth—due to preterm birth or small-for-gestational-age (SGA), or both—is the biggest risk factor for more than 80% of neonatal deaths and increases risk of post-neonatal mortality, growth failure, and adult-onset non-communicable diseases. South Asia has the highest SGA rates and sub-Saharan Africa has the highest preterm birth rates. Babies who are term SGA low birthweight (10·4 million in these regions) are at risk of stunting and adult-onset metabolic conditions. 15 million preterm births, especially of those younger than 32 weeks' gestation, are at the highest risk of neonatal death, with ongoing post-neonatal mortality risk, and important risk of long-term neurodevelopmental impairment, stunting, and non-communicable conditions. 4 million neonates annually have other life-threatening or disabling conditions including intrapartum-related brain injury, severe bacterial infections, or pathological jaundice. Half of the world's newborn babies do not get a birth certificate, and most neonatal deaths and almost all stillbirths have no death certificate. To count deaths is crucial to change them. Failure to improve birth outcomes by 2035 will result in an estimated 116 million deaths, 99 million survivors with disability or lost development potential, and millions of adults at increased risk of non-communicable diseases after low birthweight. In the post-2015 era, improvements in child survival, development, and human capital depend on ensuring a healthy start for every newborn baby—the citizens and workforce of the future.
We report on the discovery of WASP-12b, a new transiting extrasolar planet with R pl = 1.79+0.09 -0.09 RJ and M pl = 1.41+0.10 -0.10 M J. The planet and host star properties were derived from a Monte ...Carlo Markov Chain analysis of the transit photometry and radial velocity data. Furthermore, by comparing the stellar spectrum with theoretical spectra and stellar evolution models, we determined that the host star is a supersolar metallicity (M/H = 0.3+0.05 -0.15), late-F (T eff = 6300+200 -100 K) star which is evolving off the zero-age main sequence. The planet has an equilibrium temperature of T eq = 2516 K caused by its very short period orbit (P = 1.09 days) around the hot, twelfth magnitude host star. WASP-12b has the largest radius of any transiting planet yet detected. It is also the most heavily irradiated and the shortest period planet in the literature.
Background Care institutions are recognised to be a high-risk setting for the emergence and spread of infections and antimicrobial-resistant organisms, which stresses the importance of infection ...prevention and control (IPC). Accurate implementation is crucial for optimal IPC practice. Despite the wide promotion of IPC and research thereof in the hospital and nursing home setting, similar efforts are lacking in disability care settings. Therefore, this study aimed to assess perceived barriers and facilitators to IPC among professionals working at residential care facilities (RCFs) for people with intellectual and developmental disabilities (IDD), as well as to identify professional-reported recommendations to improve IPC. Methods This qualitative study involved semi-structured interviews (before COVID-19) with twelve professionals from five Dutch RCFs for people with IDD. An integrated theoretical approach was used to inform data collection and analysis. Thematic analysis using inductive and deductive approaches was conducted. This study followed the COnsolidated criteria for REporting Qualitative research (COREQ) guidelines. Results Our findings revealed barriers and facilitators at the guideline, client, professional, professional interaction, professional client interaction, client interaction, organisational, community, and societal level. Six main themes covering multiple barriers and facilitators were identified: (1) guidelines' applicability to (work)setting; (2) professionals' cognitions and attitude towards IPC (related to educational background); (3) organisational support and priority; (4) educational system; (5) time availability and staff capacity; and (6) task division and change coaches. The main professional-reported recommendations were the introduction of tailored and practical IPC guidelines, structural IPC education and training among all professionals, and client participation. Conclusions To promote IPC, multifaceted and multilevel strategies should be implemented, with a preliminary need for improvements on the guideline, professional, and organisational level. Given the heterogeneous character, i.e., different professionals, clients and care needs, there is a need for a tailored approach to implement IPC and sustain it successfully in disability care. Our findings can inform future IPC practice improvements.
Patients with advanced urothelial carcinoma that progresses after platinum-based chemotherapy have a poor prognosis and limited treatment options.
In this open-label, international, phase 3 trial, we ...randomly assigned 542 patients with advanced urothelial cancer that recurred or progressed after platinum-based chemotherapy to receive pembrolizumab (a highly selective, humanized monoclonal IgG4κ isotype antibody against programmed death 1 PD-1) at a dose of 200 mg every 3 weeks or the investigator's choice of chemotherapy with paclitaxel, docetaxel, or vinflunine. The coprimary end points were overall survival and progression-free survival, which were assessed among all patients and among patients who had a tumor PD-1 ligand (PD-L1) combined positive score (the percentage of PD-L1-expressing tumor and infiltrating immune cells relative to the total number of tumor cells) of 10% or more.
The median overall survival in the total population was 10.3 months (95% confidence interval CI, 8.0 to 11.8) in the pembrolizumab group, as compared with 7.4 months (95% CI, 6.1 to 8.3) in the chemotherapy group (hazard ratio for death, 0.73; 95% CI, 0.59 to 0.91; P=0.002). The median overall survival among patients who had a tumor PD-L1 combined positive score of 10% or more was 8.0 months (95% CI, 5.0 to 12.3) in the pembrolizumab group, as compared with 5.2 months (95% CI, 4.0 to 7.4) in the chemotherapy group (hazard ratio, 0.57; 95% CI, 0.37 to 0.88; P=0.005). There was no significant between-group difference in the duration of progression-free survival in the total population (hazard ratio for death or disease progression, 0.98; 95% CI, 0.81 to 1.19; P=0.42) or among patients who had a tumor PD-L1 combined positive score of 10% or more (hazard ratio, 0.89; 95% CI, 0.61 to 1.28; P=0.24). Fewer treatment-related adverse events of any grade were reported in the pembrolizumab group than in the chemotherapy group (60.9% vs. 90.2%); there were also fewer events of grade 3, 4, or 5 severity reported in the pembrolizumab group than in the chemotherapy group (15.0% vs. 49.4%).
Pembrolizumab was associated with significantly longer overall survival (by approximately 3 months) and with a lower rate of treatment-related adverse events than chemotherapy as second-line therapy for platinum-refractory advanced urothelial carcinoma. (Funded by Merck; KEYNOTE-045 ClinicalTrials.gov number, NCT02256436 .).
Neocortical choline acetyltransferase (ChAT)-expressing interneurons are a subclass of vasoactive intestinal peptide (ChAT-VIP) neurons of which circuit and behavioural function are unknown. Here, we ...show that ChAT-VIP neurons directly excite neighbouring neurons in several layers through fast synaptic transmission of acetylcholine (ACh) in rodent medial prefrontal cortex (mPFC). Both interneurons in layers (L)1-3 as well as pyramidal neurons in L2/3 and L6 receive direct inputs from ChAT-VIP neurons mediated by fast cholinergic transmission. A fraction (10-20%) of postsynaptic neurons that received cholinergic input from ChAT-VIP interneurons also received GABAergic input from these neurons. In contrast to regular VIP interneurons, ChAT-VIP neurons did not disinhibit pyramidal neurons. Finally, we show that activity of these neurons is relevant for behaviour and they control attention behaviour distinctly from basal forebrain ACh inputs. Thus, ChAT-VIP neurons are a local source of cortical ACh that directly excite neurons throughout cortical layers and contribute to attention.
The availability of valid Severe Acute Respiratory Syndrome Coronvirus-2 (SARS-CoV-2) serological tests overcome the problem of underestimated cumulative Coronavirus Disease 2019 (COVID-19) cases ...during the first months of the pandemic in The Netherlands. The possibility to reliably determine the number of truly infected persons, enabled us to study initial drivers for exposure risk in the absence of routine testing. Numerous activities or circumstances can accelerate virus spread, here defined as exposure factors. Hence, we aimed to evaluate a wide variety of demographic, behavioural and social exposure factors associated with seropositivity during the first eight months of the pandemic in Limburg, The Netherlands.
SARS-CoV-2 point-seroprevalence was determined cross-sectionally to indicate previous infection in a convenience sample of minimal 10,000 inhabitants of the study province. All adult (18+ years) inhabitants of the study province were eligible to register themselves for participation. Once the initial 10,000 registrations were reached, a reserve list was kept to ensure sufficient participants. Possible exposure factors were mapped by means of an extensive questionnaire. Associated exposure factors were determined using univariable and multivariable logistic regression models.
Seropositivity was established in 19.5% (n = 1,948) of the 10,001 participants (on average 49 years old (SD = 15; range 18-90 years), majority women (n = 5,829; 58.3%). Exposure factors associated with seropositivity included current education, working in healthcare and not working from home, and being a member of three or four associations or clubs. Specifically for February-March 2020, visiting an après-ski bar during winter sports in Austria, travelling to Spain, celebrating carnival, and participating in a singing activity or ball sport were associated with seropositivity.
Our results confirm that relevant COVID-19 exposure factors generally reflected circumstances where social distancing was impossible, and the number and duration of contacts was high, in particular for indoor activities.
The regional integrity of brain subcortical structures has been implicated in sleep-wake regulation, however, their associations with sleep parameters remain largely unexplored. Here, we assessed ...association between quantitative Magnetic Resonance Imaging (qMRI)-derived marker of the myelin content of the brainstem and the variability in the sleep electrophysiology in a large sample of 18-to-31 years healthy young men (N = 321; ~ 22 years). Separate Generalized Additive Model for Location, Scale and Shape (GAMLSS) revealed that sleep onset latency and slow wave energy were significantly associated with MTsat estimates in the brainstem (p
≤ 0.03), with overall higher MTsat value associated with values reflecting better sleep quality. The association changed with age, however (MTsat-by-age interaction-p
≤ 0.03), with higher MTsat value linked to better values in the two sleep metrics in the younger individuals of our sample aged ~ 18 to 20 years. Similar associations were detected across different parts of the brainstem (p
≤ 0.03), suggesting that the overall maturation and integrity of the brainstem was associated with both sleep metrics. Our results suggest that myelination of the brainstem nuclei essential to regulation of sleep is associated with inter-individual differences in sleep characteristics during early adulthood. They may have implications for sleep disorders or neurological diseases related to myelin.
Abstract On 2022 September 5, Parker Solar Probe (Parker) observed a large solar energetic particle (SEP) event at the unprecedented distance of only 15 R S from the Sun. The observations from the ...Integrated Science Investigation of the Sun (IS⊙IS) obtained over the course of this event are remarkably rich, and an overview is presented here. IS⊙IS is capable of measuring ions from 20 keV to over 100 MeV nuc −1 and electrons from 30 keV to 6 MeV; here, we primarily focus on the proton and helium measurements above 80 keV. Among the surprising results are evidence of inverse velocity dispersion at energies above 1 MeV during the onset of the event, a sharp decrease in the energetic particle intensities at all energies at the interplanetary shock crossing, and repeated short durations of highly anisotropic sunward flow. Many changes in the SEP intensities, anisotropy, and spectral steepness are coincident with solar wind structure boundaries identified using the Parker solar wind magnetic field and plasma data. However, there are significant changes that are not correlated with any clearly visible solar wind variation. The observations presented here serve as an introduction to a complex event with numerous opportunities for future, more in-depth studies.
Context.
The observation of numerous magnetic switchbacks and associated plasma jets in Parker Solar Probe (PSP) during its first five orbits, particularly near the Sun, has attracted considerable ...attention. Switchbacks have been found to be systematically associated with correlated reversals in the direction of the propagation of Alfvénic fluctuations, as well as similar reversals of the electron strahl.
Aims.
Here we aim to see whether the energetic particles change direction at the magnetic field switchbacks.
Methods.
We use magnetic field data from the MAG suite’s fluxgate magnetometer instrument to identify switchback regions. We examine the radial anisotropy of the energetic particles measured by the EPI-Lo instrument of the IS⊙IS suite.
Results.
We find that energetic particles measured by EPI-Lo generally do not preferentially change their directionality from that of the background magnetic field to that of the switchbacks.
Conclusions.
A reasonable hypothesis is that particles with smaller gyroradii, such as strahl electrons, can reverse direction by following the magnetic field in switchbacks, but that larger gyroradii particles cannot. This provides the possibility of setting a constraint on the radius of the curvature of the magnetic field in switchbacks, a property not otherwise observed by PSP. We expect that particles at higher energies than those detectable by EPI-Lo will also not respond to switchbacks. The observed reversals of radial energetic particle flux are separate phenomena, likely associated with source locations or other propagation effects occurring at greater radial distances.
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