Variation in C - reactive protein response according to host and mycobacterial characteristics in active tuberculosis

BACKGROUND: The C - reactive protein (CRP) response is often measured in patients with active tuberculosis (TB) yet little is known about its relationship to clinical features in TB, or whether responses differ between ethnic groups or with different Mycobacterium tuberculosis (M.tb) strain types. We report the relationship between baseline serum CRP prior to treatment and disease characteristics in a metropolitan population with TB resident in a low TB incidence region. METHODS: People treated for TB at four London, UK sites between 2003 and 2014 were assessed and data collected on the following characteristics: baseline CRP level; demographics (ethnicity, gender and age); HIV status; site of TB disease; sputum smear (in pulmonary cases) and culture results. The effect of TB strain-type was also assessed in culture-positive pulmonary cases using VNTR typing data. RESULTS: Three thousands two hundred twenty-two patients were included in the analysis of which 72 % had a baseline CRP at or within 4 weeks prior to starting TB treatment. CRP results were significantly higher in culture positive cases compared to culture negative cases: median 49 mg/L (16-103 mg/L) vs 19 mg/L (IQR 5-72 mg/L), p = <0.001. In those with pulmonary disease, smear positive cases had a higher CRP than smear negative cases: 67 mg/L (31-122 mg/L) vs 24 mg/L (7-72 mg/L), p < 0.001. HIV positive cases had higher baseline CRPs than HIV negative cases: 75 mg/L (26-136 mg/L) vs 37 mg/L (10-88 mg/L), p <0.001. Differing sites of disease were associated with differences in baseline CRP: locations that might be expected to have a high mycobacterial load (e.g. pulmonary disease and disseminated disease) had a significantly higher CRP than those such as skin, lymph node or CNS disease, where the mycobacterial load is typically low in HIV negative subjects. In a multivariable log-scale linear regression model adjusting for host characteristics and M.tb strain type, infection with the East African Indian strain was associated with significantly lower baseline-CRP (fold-change in CRP 0.51 (0.34-0.77), p < 0.01). CONCLUSIONS: Host and mycobacterial factors are strongly associated with baseline CRP response in tuberculosis. This analysis suggests that there are important differences in innate immune response according to ethnicity, Mtb strain type and site of disease. This may reflect differing mycobacterial loads or host immune responses

Terrorists, rioters and crocodiles: The political symbolism of an Olympic monster

This is a post-peer-review, pre-copyedit version of an article published in British Politics. The definitive publisher-authenticated version - British Politics, 2014, 9(2), pp. 161-181 - is available online at: http://www.palgrave-journals.com/bp/journal/v9/n2/full/bp201317a.htmlIn August 2005, just a month after the announcement that London had succeeded in its bid to host the 2012 Olympic Games, the UK national press witnessed a brief rash of stories alleging the presence of a crocodile or similar water monster lurking beneath the surface of the River Lea – the river that runs from the town of Luton in Bedfordshire down to join the Thames adjacent to the Olympic site. This story re-emerged in November 2011 when a campaigner against the environmental impact of the Olympics on the river area claimed to have seen further evidence of crocodilian activity. This paper will explore the reasons for the proliferation of this story, in terms both of its function as a metonymic news-hook (it opened up directly related concerns as to the impact, organization and security of the Games) and of its metaphorical significance (its incarnation of a superstructure’s fears of an emerging threat of a monstrous underclass – one which might at once comprise terrorists, rioters and anti-establishment campaigners). It will conclude by suggesting that this monstrous myth might hold within it the possibility of the convergence of populist news media and popular democracy

Fatal COVID-19 infection in a patient with long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency: A case report

Long-chain fatty-acyl CoA dehydrogenase deficiency (LCHADD) is an inborn error of long chain fatty acid oxidation with various features including hypoketotic hypoglycemia, recurrent rhabdomyolysis, pigmentary retinopathy, peripheral neuropathy, cardiomyopathy, and arrhythmias. Various stresses trigger metabolic decompensation. Coronavirus disease 2019 (COVID-19) is a pandemic caused by the RNA virus SARS-CoV-2 with diverse presentations ranging from respiratory symptoms to myocarditis. We report a case of a patient with LCHADD who initially presented with typical metabolic decompensation symptoms including nausea, vomiting, and rhabdomyolysis in addition to mild cough, and was found to have COVID-19. She developed acute respiratory failure and refractory hypotension from severe cardiomyopathy which progressed to multiple organ failure and death. Our case illustrates the need for close monitoring of cardiac function in patients with a long-chain fatty acid oxidation disorder

How Do You Identify m⁶A Methylation in Transcriptomes at High Resolution? A Comparison of Recent Datasets

A flurry of methods has been developed in recent years to identify N6-methyladenosine (m⁶A) sites across transcriptomes at high resolution. This raises the need to understand both the common features and those that are unique to each method. Here, we complement the analyses presented in the original papers by reviewing their various technical aspects and comparing the overlap between m⁶A-methylated messenger RNAs (mRNAs) identified by each. Specifically, we examine eight different methods that identify m⁶A sites in human cells with high resolution: two antibody-based crosslinking and immunoprecipitation (CLIP) approaches, two using endoribonuclease MazF, one based on deamination, two using Nanopore direct RNA sequencing, and finally, one based on computational predictions. We contrast the respective datasets and discuss the challenges in interpreting the overlap between them, including a prominent expression bias in detected genes. This overview will help guide researchers in making informed choices about using the available data and assist with the design of future experiments to expand our understanding of m⁶A and its regulation

A systematic review and narrative synthesis of antenatal interventions to improve maternal and neonatal health in Nepal

BACKGROUND: Maternal and neonatal mortality rates remain high in many economically underdeveloped countries, including Nepal, and good quality antenatal care can reduce adverse pregnancy outcomes. However, identifying how to best improve antenatal care can be challenging.OBJECTIVE: To identify the interventions that have been investigated in the antenatal period in Nepal for maternal or neonatal benefit. We wanted to understand their scale, location, cost, and effectiveness.STUDY DESIGN: Online bibliographic databases (Cochrane Central, MEDLINE, Embase, CINAHL Plus, British Nursing Index, PsycInfo, Allied and Complementary Medicine) and trial registries (ClinicalTrials.gov and the World Health Organization Clinical Trials Registry Platform) were searched from their inception till May 24, 2020. We included all studies reporting any maternal or neonatal outcome after an intervention in the antenatal period. We screened the studies and extracted the data in duplicate. A meta-analysis was not possible because of the heterogeneity of the interventions and outcomes, so we performed a narrative synthesis of the included studies.RESULTS: A total of 25 studies met our inclusion criteria. These studies showed a variety of approaches toward improving antenatal care (eg, educational programs, incentive schemes, micronutrient supplementation) in different settings (home, community, or hospital-based) and with a wide variety of outcomes. Less than a quarter of the studies were randomized controlled trials, and many were single-site or reported only short-term outcomes. All studies reported having made a positive impact on antenatal care in some way, but only 3 provided a cost-benefit analysis to support implementation. None of these studies focused on the most remote communities in Nepal.CONCLUSION: Our systematic review found good quality evidence that micronutrient supplementation and educational interventions can bring important clinical benefits. Iron and folic acid supplementation significantly reduces neonatal mortality and maternal anemia, whereas birth preparedness classes increase the uptake of antenatal and postnatal care, compliance with micronutrient supplementation, and awareness of the danger signs in pregnancy.</p

Environmental impact assessment in health technology assessment: principles, approaches, and challenges

To reduce harm to the environment resulting from the production, use, and disposal of health technologies, there are different options for how health technology assessment (HTA) agencies can consider environmental information. We identified four approaches that HTA agencies can use to take environmental information into account in healthcare decision making and the challenges associated with each approach. Republishing data that is in the public domain or has been submitted to an HTA agency we term the “information conduit” approach. Analyzing and presenting environmental data separately from established health economic analyses is described as “parallel evaluation.” Integrating environmental impact into HTAs by identifying or creating new methods that allow clinical, financial, and environmental information to be combined in a single quantitative analysis is “integrated evaluation.” Finally, evidence synthesis and analysis of health technologies that are not expected to improve health-related outcomes but claim to have relative environmental benefits are termed “environment-focused evaluation.

A green solvent system for precursor phase-engineered sequential deposition of stable formamidinium lead triiodide for perovskite solar cells

Perovskite solar cells (PSCs) offer an efficient, inexpensive alternative to current photovoltaic technologies, with the potential for manufacture via high-throughput coating methods. However, challenges for commercial-scale solution-processing of metal-halide perovskites include the use of harmful solvents, the expense of maintaining controlled atmospheric conditions, and the inherent instabilities of PSCs under operation. Here, we address these challenges by introducing a high volatility, low toxicity, biorenewable solvent system to fabricate a range of 2D perovskites, which highly effective precursor phases for subsequent transformation to alpha-formamidinium lead triiodide (FAPbI3), fully processed under ambient conditions. PSCs utilising our FAPbI3 reproducibly show remarkable stability under illumination and elevated temperature (ISOS-L-2) and "damp heat" (ISOS-D-3) stressing, surpassing other state-of-the-art perovskite compositions. We determine that this enhancement is a consequence of the 2D precursor phase crystallisation route, which simultaneously avoids retention of residual low-volatility solvents (such as DMF and DMSO) and reduces the rate of degradation of FA+ in the material. Our findings highlight both the critical role of the initial crystallisation process in determining the operational stability of perovskite materials, and that neat FA+-based perovskites can be competitively stable despite the inherent metastability of the alpha-phase

Strong intermodel differences and biases in CMIP6 simulations of PM2.5, aerosol optical depth, and precipitation over Africa

Poor air quality and precipitation change are strong, rapidly changing, and possibly linked drivers of physical hazards in sub-Saharan Africa. Future projections of sub-Saharan air quality and precipitation remain uncertain due to differences in model representations of aerosol, aerosol–precipitation interactions, and unclear future aerosol emission pathways. In this study, we evaluate the performance of CMIP6 models in simulating PM2.5, aerosol optical depth (AOD), and precipitation over Africa relative to a range of observational and re- analysis products, including novel observational datasets, over the 1981–2023 period. While models accurately capture the seasonal cycle of PM2.5 concentrations over most regions, the concentration magnitudes show strong intermodel diversity. Dust AOD shows a generally accurate seasonal spatial distribution, with multi-model mean (MMM) pattern correlation coefficients within 0.77–0.94, despite strong intermodel diversity in magnitude. Sea- sonal spatial patterns of non-dust AOD are poorly represented, with MMM pattern correlation coefficients of 0.25–0.58 and the poorest performance during September through November. Emission inventory inaccuracies may explain systematic biases for non-dust AOD fields, with differences in circulation and precipitation patterns, as well as aerosol treatment causing intermodel diversity. The magnitude and annual progression of precipitation over both the east and west African monsoon regions are well captured, though there is poorer performance in simulating the east African monsoon. Biases found relate to the intertropical convergence zone, more apparent over east Africa, and rainfall magnitude, more apparent over west Africa. This evaluation highlights strong in- termodel diversity in the representation of African air quality and climate and identifies model performance over sub-Saharan Africa and the reasons behind the biases as critical gaps to address for improving confidence in climate projections