Late diagnosis of HIV in the United Kingdom: an evidence review.

•Late diagnosis of HIV remains an important public health issue in the UK, with 40% of newly diagnosed individuals in 2014 diagnosed late •Reducing the number of people presenting to care at a late stage of HIV infection is a key public health priority in the United Kingdom. It is one of only three sexual health indicators included on the Public Health Outcomes Framework for England and a key ambition of the Framework for Sexual Health Improvement in England •Late diagnosis of HIV is defined as having a CD4 count of less than 350 cells per mm3 within 3 months of diagnosis and is associated with significantly heightened levels of HIV related morbidity and mortality, increased risk of onward HIV transmission (Halve it, 2011) and higher healthcare costs •Evidence suggests that certain groups are disproportionally affected by late diagnosis, namely older adults, heterosexuals and non-national populations, in particular black Africans •Evidence suggest that the majority of individuals have lowered perceptions of their risk of acquiring HIV and for those who have recent high risk behaviour, fear of disease is an important barrier to testing. Amongst black African populations, there are additional barriers to testing including a heightened fear of disclosure due to stigma •Amongst healthcare professionals, missed diagnostic opportunities are well documented and are linked to clinician’s own perceptions of risk and a lack of knowledge of HIV and testing procedures •Interventions to expand testing beyond routine settings have been shown as both acceptable and feasible to patients and staff and, cost effective. Pilots to expand testing in hospital and primary care settings have found varying levels of testing activity among clinicians suggesting that support and training for healthcare staff is necessary and effective in increasing testing •Community outreach testing has been found particularly effective among MSM and black African populations. Research suggests that effective interventions must be: grounded in community mobilisation and outreach settings; normalise both testing and treatment for HIV and, address HIV related stigma. Emerging evidence also suggests that new home sampling and home testing methods will be particularly effective in accessing harder to reach groups particularly among MS

Ambition for soil organic carbon sequestration in the new and updated nationally determined contributions 2020- 2021: Analysis of agricultural sub-sectors in national climate change strategies

Key messages - The share of countries that referenced soil organic carbon (SOC) in new and updated NDCs has increased since the previous round of NDCs. - Among the top 10 countries with the highest mitigation potential for SOC in croplands and grasslands, 6 referred to SOC in mitigation measures. - Among the top 10 countries with the highest mitigation potential in wetlands, 5 referred to wetlands in mitigation measures. - SOC commitments that demonstrated high standards, which may indicate options for other countries, included quantified outcomes, information on reference levels of indicators, mitigation potentials, and policies. - Specification of sub-sector actions in NDCs can improve eligibility for climate finance, but this level of detail can reduce countries’ flexibility for meeting their NDC targets and countries often lack affordable, robust monitoring, reporting, and verification (MRV) systems

Rice cultivation ambition in the new and updated Nationally Determined Contributions: 2020-2021: Analysis of agricultural sub-sectors in countries’ climate change strategies

The share of countries that referenced rice cultivation actions in new and updated NDCs has increased since the previous round of NDCs. Among the top 10 countries with the highest mitigation potential for rice cultivation, 4 countries mentioned rice mitigation actions. Seventeen countries quantified measures for rice cultivation in their new and updated NDCs, for the first time. 14% of the countries that have signed the US- EU Methane Reduction Pledge have rice mitigation actions in their NDC (15 countries out of 105). A number of countries mentioned limitations in GHG measurement and inventory as well as methods and data for calculating mitigation potential of different actions in rice, leading to the lack of specifying tangible actions and indicators in the rice sub-sector. 16% of countries included rice-specific mitigation actions (11 countries specified mitigation only and 13 specified combined mitigation and adaptation for a total of 24 out of 148) in new and updated NDCs compared to 9% of previous NDCs (18 out of 192). 3% specified only rice-specific adaptation actions in new and updated NDCs (5 out of 148) compared to only 0.5% in the previous round of NDCs (1 out of 192 countries). 50% of the countries mentioning rice mitigation actions prioritized water management (12 of 24 countries), 33% mentioned rice management packages (8), 33% mentioned land use management (8), and 33% mentioned by-product and residue management (8). 56% of countries mentioning adaptation actions in rice prioritized water management (10 of 18 countries), 33% mentioned System of Rice Intensification (SRI) (6), and 33% mentioned variety development (6)

Livestock management ambition in the new and updated nationally determined contributions: 2020-2021: Analysis of agricultural sub-sectors in national climate change strategies

Key messages 1) The share of countries with livestock measures in new and updated NDCs has not significantly changed since the previous round of NDCs. 2) 34% of countries included livestock mitigation measures in new and updated NDCs (50 of 148 countries) compared to 35% in the previous NDCs (68 of 192 countries). 3) 36% of countries included livestock adaptation measures in new and updated NDCs (53 of 148 countries) compared to 35% in the previous NDCs (67 of 192 countries). 4) Mitigation priorities included manure management (18% of 148 countries), feed management (16%) and silvopastoralism (10%). Adaptation priorities included breed management (14%), feed management (10%) and silvopastoralism (9%). 5) Among the top 10 countries with the highest mitigation potential for enteric fermentation and manure management, 7 referred to livestock in mitigation measures. 6) Specification of sub-sector actions in NDCs can improve eligibility for climate finance, but this level of detail can reduce countries’ flexibility for meeting their NDC targets and countries often lack affordable, robust monitoring, reporting, and verification (MRV) systems. 7) Livestock commitments that demonstrated high standards, which may indicate options for other countries, included quantified outcomes, reference levels of indicators, mitigation potentials, and policies.Updated 1 March 2022 by Sabrina Ros

Associations of Air Pollution and Pediatric Asthma in Cleveland, Ohio

Air pollution has been associated with poor health outcomes and continues to be a risk factor for respiratory health in children. While higher particulate matter (PM) levels are associated with increased frequency of symptoms, lower lung function, and increase airway inflammation from asthma, the precise composition of the particles that are more highly associated with poor health outcomes or healthcare utilization are not fully elucidated. PM is measured quantifiably by current air pollution monitoring systems. To better determine sources of PM and speciation of such sources, a particulate matter (PM) source apportionment study, the Cleveland Multiple Air Pollutant Study (CMAPS), was conducted in Cleveland, Ohio, in 2009–2010, which allowed more refined assessment of associations with health outcomes. This article presents an evaluation of short-term (daily) and long-term associations between motor vehicle and industrial air pollution components and pediatric asthma emergency department (ED) visits by evaluating two sets of air quality data with healthcare utilization for pediatric asthma. Exposure estimates were developed using land use regression models for long-term exposures for nitrogen dioxide (NO2) and coarse (i.e., with aerodynamic diameters between 2.5 and 10 μm) particulate matter (PM) and the US EPA Positive Matrix Factorization receptor model for short-term exposures to fine (μm) and coarse PM components. Exposure metrics from these two approaches were used in asthma ED visit prevalence and time series analyses to investigate seasonal-averaged short- and long-term impacts of both motor vehicles and industry emissions. Increased pediatric asthma ED visits were found for LUR coarse PM and NO2 estimates, which were primarily contributed by motor vehicles. Consistent, statistically significant associations with pediatric asthma visits were observed, with short-term exposures to components of fine and coarse iron PM associated with steel production. Our study is the first to combine spatial and time series analysis of ED visits for asthma using the same periods and shows that PM related to motor vehicle emissions and iron/steel production are associated with increased pediatric asthma visits

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Purine Nucleoside Phosphorylase mediated molecular chemotherapy and conventional chemotherapy: A tangible union against chemoresistant cancer

Background Late stage Ovarian Cancer is essentially incurable primarily due to late diagnosis and its inherent heterogeneity. Single agent treatments are inadequate and generally lead to severe side effects at therapeutic doses. It is crucial to develop clinically relevant novel combination regimens involving synergistic modalities that target a wider repertoire of cells and lead to lowered individual doses. Stemming from this premise, this is the first report of two- and three-way synergies between Adenovirus-mediated Purine Nucleoside Phosphorylase based gene directed enzyme prodrug therapy (PNP-GDEPT), docetaxel and/or carboplatin in multidrug-resistant ovarian cancer cells. Methods The effects of PNP-GDEPT on different cellular processes were determined using Shotgun Proteomics analyses. The in vitro cell growth inhibition in differentially treated drug resistant human ovarian cancer cell lines was established using a cell-viability assay. The extent of synergy, additivity, or antagonism between treatments was evaluated using CalcuSyn statistical analyses. The involvement of apoptosis and implicated proteins in effects of different treatments was established using flow cytometry based detection of M30 (an early marker of apoptosis), cell cycle analyses and finally western blot based analyses. Results Efficacy of the trimodal treatment was significantly greater than that achieved with bimodal- or individual treatments with potential for 10-50 fold dose reduction compared to that required for individual treatments. Of note was the marked enhancement in apoptosis that specifically accompanied the combinations that included PNP-GDEPT and accordingly correlated with a shift in the expression of anti- and pro-apoptotic proteins. PNP-GDEPT mediated enhancement of apoptosis was reinforced by cell cycle analyses. Proteomic analyses of PNP-GDEPT treated cells indicated a dowregulation of proteins involved in oncogenesis or cancer drug resistance in treated cells with accompanying upregulation of apoptotic- and tumour- suppressor proteins. Conclusion Inclusion of PNP-GDEPT in regular chemotherapy regimens can lead to significant enhancement of the cancer cell susceptibility to the combined treatment. Overall, these data will underpin the development of regimens that can benefit patients with late stage ovarian cancer leading to significantly improved efficacy and increased quality of life

Improving local health through community health workers in Cambodia: challenges and solutions

Volunteer community health workers (CHWs) are an important link between the public health system and the community. The ‘Community Participation Policy for Health’ in Cambodia identifies CHWs as key to local health promotion and as a critical link between district health centres and the community. However, research on the challenges CHWs face and identifying what is required to optimise their performance is limited in the Cambodian context. This research explores the views of CHWs in rural Cambodia, on the challenges they face when implementing health initiatives

Thalamic Activation Modulates the Responses of Neurons in Rat Primary Auditory Cortex: An In Vivo Intracellular Recording Study

Auditory cortical plasticity can be induced through various approaches. The medial geniculate body (MGB) of the auditory thalamus gates the ascending auditory inputs to the cortex. The thalamocortical system has been proposed to play a critical role in the responses of the auditory cortex (AC). In the present study, we investigated the cellular mechanism of the cortical activity, adopting an in vivo intracellular recording technique, recording from the primary auditory cortex (AI) while presenting an acoustic stimulus to the rat and electrically stimulating its MGB. We found that low-frequency stimuli enhanced the amplitudes of sound-evoked excitatory postsynaptic potentials (EPSPs) in AI neurons, whereas high-frequency stimuli depressed these auditory responses. The degree of this modulation depended on the intensities of the train stimuli as well as the intervals between the electrical stimulations and their paired sound stimulations. These findings may have implications regarding the basic mechanisms of MGB activation of auditory cortical plasticity and cortical signal processing

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication