How have surface NO2 concentrations changed as a result of the UK's COVID-19 travel restrictions?

Restrictions as a result of the COVID-19 pandemic have led to fewer vehicles on UK roads. Since fuel combustion is responsible for a large fraction of UK emissions it is expected that surface NO2 concentrations would reduce as a result. However, over parts of the UK, surface NO2 concentrations have increased following the implementation of travel restrictions. NO2 measurements from 142 Automatic Urban and Rural Network sites are combined with meteorological data from the Met Office high-resolution weather prediction model to build site specific models. These models predict NO2 concentrations given no change in emissions. It is found that both meteorological and emission changes contribute to the observed changes in NO2 concentrations. Given no change in emissions, changes in meteorology between pre- and post-lockdown periods would have led to a mean increase in NO2 concentrations of +6%. Conversely, changes in emissions would have led to a mean reduction in NO2 concentrations of -18%, resulting in the observed total change in NO2 concentrations of -12%. However at some sites the reduction in emissions is smaller than the increase in NO2 concentrations due to meteorology. The largest increases associated with changes in the meteorology are seen at rural sites (+20%) where NO2 measurements are representative of large areas and thus dominated by the regional advection of secondary NO2 from Europe. Conversely, the largest decreases associated with reduced emissions are found at urban traffic and urban background sites (-27% and -14% respectively) where NO2 concentrations are representative of local areas and thus dominated by local reduction in emissions from vehicles. As lockdown measures are relaxed, NO2 concentrations are likely to return to pre-COVID levels, but these results demonstrate that changes in our behaviour can result in positive impacts on air quality and illustrate the effectiveness of travel-reducing strategies in urban area

A mixed methods study to assess the impact of COVID-19 on maternal, newborn, child health and nutrition in fragile and conflict-affected settings.

BACKGROUND: The impacts of COVID-19 are unprecedented globally. The pandemic is reversing decades of progress in maternal, newborn, child health and nutrition (MNCHN), especially fragile and conflict-affected settings (FCAS) whose populations were already facing challenges in accessing basic health and nutrition services. This study aimed to investigate the collateral impact of COVID-19 on funding, services and MNCHN outcomes in FCAS, as well as adaptations used in the field to continue activities. METHODS: A scoping review of peer-reviewed and grey literature published between 1st March 2020-31st January 2021 was conducted. We analysed 103 publications using a narrative synthesis approach. 39 remote semi-structured key informant interviews with humanitarian actors and donor staff within 12 FCAS were conducted between October 2020 and February 2021. Thematic analysis was undertaken independently by two researchers on interview transcripts and supporting documents provided by key informants, and triangulated with literature review findings. RESULTS: Funding for MNCHN has been reduced or suspended with increase in cost of continuing the same activities, and diversion of MNCHN funding to COVID-19 activities. Disruption in supply and demand of interventions was reported across different settings which, despite data evidence still being missing, points towards likely increased maternal and child morbidity and mortality. Some positive adaptations including use of technology and decentralisation of services have been reported, however overall adaptation strategies have been insufficient to equitably meet additional challenges posed by the pandemic, and have not been evaluated for their effectiveness. CONCLUSIONS: COVID-19 is further exacerbating negative women's and children's health outcomes in FCAS. Increased funding is urgently required to re-establish MNCHN activities which have been deprioritised or halted. Improved planning to sustain routine health services and enable surge planning for emergencies with focus on the community/service users throughout adaptations is vital for improved MNCHN outcomes in FCAS

Community health workers adherence to referral guidelines: evidence from studies introducing RDTs in two malaria transmission settings in Uganda.

BACKGROUND: Many malaria-endemic countries have implemented national community health worker (CHW) programmes to serve remote populations that have poor access to malaria diagnosis and treatment. Despite mounting evidence of CHWs' ability to adhere to malaria rapid diagnostic tests (RDTs) and treatment guidelines, there is limited evidence whether CHWs adhere to the referral guidelines and refer severely ill children for further management. In southwest Uganda, this study examined whether CHWs referred children according to training guidelines and described factors associated with adherence to the referral guideline. METHODS: A secondary analysis was undertaken of data collected during two cluster-randomized trials conducted between January 2010 and July 2011, one in a moderate-to-high malaria transmission setting and the other in a low malaria transmission setting. All CHWs were trained to prescribe artemisinin-based combination therapy (ACT) and recognize symptoms in children that required immediate referral to the nearest health centre. Intervention arm CHWs had additional training on how to conduct an RDT; CHWs in the control arm used a presumptive diagnosis for malaria using clinical signs and symptoms. CHW treatment registers were reviewed to identify children eligible for referral according to training guidelines (temperature of ≥38.5 °C), to assess whether CHWs adhered to the guidelines and referred them. Factors associated with adherence were examined with logistic regression models. RESULTS: CHWs failed to refer 58.8% of children eligible in the moderate-to-high transmission and 31.2% of children in the low transmission setting. CHWs using RDTs adhered to the referral guidelines more frequently than CHWs not using RDTs (moderate-to-high transmission: 50.1 vs 18.0%, p = 0.003; low transmission: 88.5 vs 44.1%, p < 0.001). In both settings, fewer than 20% of eligible children received pre-referral treatment with rectal artesunate. Children who were prescribed ACT were very unlikely to be referred in both settings (97.7 and 73.3% were not referred in the moderate-to-high and low transmission settings, respectively). In the moderate-to-high transmission setting, day and season of visit were also associated with the likelihood of adherence to the referral guidelines, but not in the low transmission setting. CONCLUSIONS: CHW adherence to referral guidelines was poor in both transmission settings. However, training CHWs to use RDT improved correct referral of children with a high fever compared to a presumptive diagnosis using sign and symptoms. As many countries scale up CHW programmes, routine monitoring of reported data should be examined carefully to assess whether CHWs adhere to referral guidelines and take remedial actions where required

Caregivers' compliance with referral advice: evidence from two studies introducing mRDTs into community case management of malaria in Uganda.

BACKGROUND: Several malaria endemic countries have implemented community health worker (CHW) programmes to increase access to populations underserved by health care. There is considerable evidence on CHW adherence to case management guidelines, however, there is limited evidence on the compliance to referral advice and the outcomes of children under-5 referred by CHWs. This analysis examined whether caregivers complied with CHWs referral advice. METHODS: Data from two cluster (village) randomised trials, one in a moderate-to-high malaria transmission setting, another in a low-transmission setting conducted between January 2010-July 2011 were analysed. CHW were trained to recognise signs and symptoms that required referral to a health centre. CHW in the intervention arm also had training on; malaria rapid diagnostic tests (mRDT) and administering artemisinin based combination therapy (ACT); CHW in the control arm were trained to treat malaria with ACTs based on fever symptoms. Caregivers' referral forms were linked with CHW treatment forms to determine whether caregivers complied with the referral advice. Factors associated with compliance were examined with logistic regression. RESULTS: CHW saw 18,497 child visits in the moderate-to-high transmission setting and referred 15.2% (2815/18,497) of all visits; in the low-transmission setting, 35.0% (1135/3223) of all visits were referred. Compliance to referral was low, in both settings < 10% of caregivers complied with referral advice. In the moderate-to-high transmission setting compliance was higher if children were tested with mRDT compared to children who were not tested with mRDT. In both settings, nearly all children treated with pre-referral rectal artesunate failed to comply with referral and compliance was independently associated with factors such as health centre distance and day of referral by a CHW. In the moderate-to-high transmission setting, time of presentation, severity of referral were also associated with compliance, whilst in the low-transmission setting, compliance was low if an ACT was prescribed. CONCLUSIONS: This analysis suggests there are several barriers to comply with CHWs referral advice by caregivers. This is concerning for children who received rectal artesunate. As CHW programmes continue scale-up, barriers to referral compliance need to be addressed to ensure a continuum of care from the community to the health centre. TRIAL REGISTRATION: The study was registered with ClinicalTrials.gov. Identifier NCT01048801 , 13th January 2010

Referral patterns of community health workers diagnosing and treating malaria:Cluster-randomized trials in two areas of high- and low-malaria transmission in southwestern Uganda

Malaria-endemic countries have implemented community health worker (CHW) programs to provide malaria diagnosis and treatment to populations living beyond the reach of health systems. However, there is limited evidence describing the referral practices of CHWs. We examined the impact of malaria rapid diagnostic tests (mRDTs) on CHW referral in two cluster-randomized trials, one conducted in a moderate-to-high malaria transmission setting and one in a low-transmission setting in Uganda, between January 2010 and July 2012. All CHWs were trained to prescribe artemisinin-based combination therapy (ACT) for malaria and recognize signs and symptoms for referral to health centers. CHWs in the control arm used a presumptive diagnosis for malaria based on clinical symptoms, whereas intervention arm CHWs used mRDTs. CHWs recorded ACT prescriptions, mRDT results, and referral in patient registers. An intention-to-treat analysis was undertaken using multivariable logistic regression. Referral was more frequent in the intervention arm versus the control arm (moderate-to-high transmission, P < 0.001; low transmission, P < 0.001). Despite this increase, referral advice was not always given when ACTs or prereferral rectal artesunate were prescribed: 14% prescribed rectal artesunate in the moderate-to-high setting were not referred. In addition, CHWs considered factors alongside mRDTs when referring. Child visits during the weekends or the rainy season were less likely to be referred, whereas visits to CHWs more distant from health centers were more likely to be referred (low transmission only). CHWs using mRDTs and ACTs increased referral compared with CHWs using a presumptive diagnosis. To address these concerns, referral training should be emphasized in CHW programs as they are scaled-up

Future air pollution related health burdens associated with RCP emission changes in the UK

Intergovernmental Panel on Climate Change (IPCC) Representative Concentration Pathways (RCPs) are used to simulate future ozone (O3), nitrogen dioxide (NO2), and fine particulate matter (PM2.5) in the United Kingdom (UK) for the 2050s relative to the 2000s with an air quality model (AQUM) at a 12 km horizontal resolution. The present-day and future attributable fractions (AF) of mortality associated with long-term exposure to annual mean O3, NO2 and PM2.5 have accordingly been estimated for the first time for regions across England, Scotland and Wales. Across the three RCPs (RCP2.6, RCP6.0 and RCP8.5), simulated annual mean of the daily maximum 8-hr mean (MDA8) O3 concentrations increase compared to present-day, likely due to decreases in NOx (nitrogen oxides) emissions, leading to less titration of O3 by NO. Annual mean NO2 and PM2.5 concentrations decrease under all RCPs for the 2050s, mostly driven by decreases in NOx and sulphur dioxide (SO2) emissions, respectively. The AF of mortality associated with long-term exposure to annual mean MDA8 O3 is estimated to increase in the future across all the regions and for all RCPs. Reductions in NO2 and PM2.5 concentrations lead to reductions in the AF estimated for future periods under all RCPs, for both pollutants. Total mortality burdens are also highly sensitive to future population projections. Accounting for population projections exacerbates differences in total UK-wide MDA8 O3-health burdens between present-day and future by up to a factor of ~3 but diminishes differences in NO2-health burdens. For PM2.5, accounting for future population projections results in additional UK-wide deaths brought forward compared to present-day under RCP2.6 and RCP6.0, even though the simulated PM2.5 concentrations for the 2050s are estimated to decrease. Thus, these results highlight the sensitivity of future health burdens in the UK to future trends in atmospheric emissions over the UK as well as future population projections

Bayesian reconstruction of the cosmological large-scale structure: methodology, inverse algorithms and numerical optimization

We address the inverse problem of cosmic large-scale structure reconstruction from a Bayesian perspective. For a linear data model, a number of known and novel reconstruction schemes, which differ in terms of the underlying signal prior, data likelihood, and numerical inverse extra-regularization schemes are derived and classified. The Bayesian methodology presented in this paper tries to unify and extend the following methods: Wiener-filtering, Tikhonov regularization, Ridge regression, Maximum Entropy, and inverse regularization techniques. The inverse techniques considered here are the asymptotic regularization, the Jacobi, Steepest Descent, Newton-Raphson, Landweber-Fridman, and both linear and non-linear Krylov methods based on Fletcher-Reeves, Polak-Ribiere, and Hestenes-Stiefel Conjugate Gradients. The structures of the up-to-date highest-performing algorithms are presented, based on an operator scheme, which permits one to exploit the power of fast Fourier transforms. Using such an implementation of the generalized Wiener-filter in the novel ARGO-software package, the different numerical schemes are benchmarked with 1-, 2-, and 3-dimensional problems including structured white and Poissonian noise, data windowing and blurring effects. A novel numerical Krylov scheme is shown to be superior in terms of performance and fidelity. These fast inverse methods ultimately will enable the application of sampling techniques to explore complex joint posterior distributions. We outline how the space of the dark-matter density field, the peculiar velocity field, and the power spectrum can jointly be investigated by a Gibbs-sampling process. Such a method can be applied for the redshift distortions correction of the observed galaxies and for time-reversal reconstructions of the initial density field.Comment: 40 pages, 11 figure

Serum neurofilament dynamics predicts neurodegeneration and clinical progression in presymptomatic Alzheimer's disease

Neurofilament light chain (NfL) is a promising fluid biomarker of disease progression for various cerebral proteopathies. Here we leverage the unique characteristics of the Dominantly Inherited Alzheimer Network and ultrasensitive immunoassay technology to demonstrate that NfL levels in the cerebrospinal fluid (n = 187) and serum (n = 405) are correlated with one another and are elevated at the presymptomatic stages of familial Alzheimer's disease. Longitudinal, within-person analysis of serum NfL dynamics (n = 196) confirmed this elevation and further revealed that the rate of change of serum NfL could discriminate mutation carriers from non-mutation carriers almost a decade earlier than cross-sectional absolute NfL levels (that is, 16.2 versus 6.8 years before the estimated symptom onset). Serum NfL rate of change peaked in participants converting from the presymptomatic to the symptomatic stage and was associated with cortical thinning assessed by magnetic resonance imaging, but less so with amyloid-β deposition or glucose metabolism (assessed by positron emission tomography). Serum NfL was predictive for both the rate of cortical thinning and cognitive changes assessed by the Mini-Mental State Examination and Logical Memory test. Thus, NfL dynamics in serum predict disease progression and brain neurodegeneration at the early presymptomatic stages of familial Alzheimer's disease, which supports its potential utility as a clinically useful biomarker

Improving the deterministic skill of air quality ensembles

&lt;p&gt;&lt;strong&gt;Abstract.&lt;/strong&gt; Forecasts from chemical weather models are subject to uncertainties in the input data (e.g. emission inventory, initial and boundary conditions) as well as the model itself (e.g. physical parameterization, chemical mechanism). Multi-model ensemble forecasts can improve the forecast skill provided that certain mathematical conditions are fulfilled. We demonstrate through an intercomparison of two dissimilar air quality ensembles that unconditional raw forecast averaging, although generally successful, is far from optimum. One way to achieve an optimum ensemble is also presented. The basic idea is to either add optimum weights to members or constrain the ensemble to those members that meet certain conditions in time or frequency domain. The methods are evaluated against ground level observations collected from the EMEP and Airbase databases.&lt;br&gt;&lt;br&gt; The two ensembles were created for the first and second phase of the Air Quality Model Evaluation International Initiative (AQMEII). Verification statistics shows that the deterministic models simulate better O&lt;sub&gt;3&lt;/sub&gt; than NO&lt;sub&gt;2&lt;/sub&gt; and PM&lt;sub&gt;10&lt;/sub&gt;, linked to different levels of complexity in the represented processes. The ensemble mean achieves higher skill compared to each station's best deterministic model at 39&amp;#8201;%&amp;#8211;63&amp;#8201;% of the sites. The skill gained from the favourable ensemble averaging has at least double the forecast skill compared to using the full ensemble. The method proved robust for the 3-monthly examined time-series if the training phase comprises 60 days. Further development of the method is discussed in the conclusion.&lt;/p&gt

Analysis of the genetic phylogeny of multifocal prostate cancer identifies multiple independent clonal expansions in neoplastic and morphologically normal prostate tissue.

Genome-wide DNA sequencing was used to decrypt the phylogeny of multiple samples from distinct areas of cancer and morphologically normal tissue taken from the prostates of three men. Mutations were present at high levels in morphologically normal tissue distant from the cancer, reflecting clonal expansions, and the underlying mutational processes at work in morphologically normal tissue were also at work in cancer. Our observations demonstrate the existence of ongoing abnormal mutational processes, consistent with field effects, underlying carcinogenesis. This mechanism gives rise to extensive branching evolution and cancer clone mixing, as exemplified by the coexistence of multiple cancer lineages harboring distinct ERG fusions within a single cancer nodule. Subsets of mutations were shared either by morphologically normal and malignant tissues or between different ERG lineages, indicating earlier or separate clonal cell expansions. Our observations inform on the origin of multifocal disease and have implications for prostate cancer therapy in individual cases