Air Pollution and Climate Forcing of the Charcoal Industry in Africa

The demand for charcoal in Africa is growing rapidly, driven by urbanization and lack of access to electricity. Charcoal production and use, including plastic burning to initiate combustion, release large quantities of trace gases and particles that impact air quality and climate. Here, we develop an inventory of current (2014) and future (2030) emissions from the charcoal supply chain in Africa that we implement in the GEOS-Chem model to quantify the contribution of charcoal to surface concentrations of PM2.5 and ozone and direct radiative forcing due to aerosols and ozone. We estimate that the charcoal industry in 2014 required 140–460 Tg of biomass and 260 tonnes of plastic and that industry emissions could double by 2030, so that methane emissions from the charcoal industry could outcompete those from open fires by 2025. In 2014, the largest enhancements in PM2.5 (0.5–1.4 μg m–3) and ozone (0.4–0.7 ppbv) occur around the densely populated cities in East and West Africa. Cooling due to aerosols (−100 to −300 mW m–2) is concentrated over dense cities, whereas warming due to ozone is widespread, peaking at 4.2 mW m–2 over the Atlantic Ocean. These effects will worsen with ongoing dependence on this energy source, spurred by rapid urbanization and absence of viable cleaner alternatives

Hypertriglyceridaemia in adolescents may have serious complications

Acute pancreatitis is an often-overlooked cause of acute abdominal pain in children and adolescents. Severe hypertriglyceridaemia is an important cause of recurrent acute pancreatitis. Monogenic causes of hypertriglyceridaemia, such as familial chylomicronaemia caused by lipoprotein lipase deficiency, are more frequently encountered in children and adolescents, but remain rare. Polygenic hypertriglyceridaemia is more common, but may require a precipitant before manifesting. With the global increase in obesity and type 2 diabetes, secondary causes of hypertriglyceridaemia in children and adolescents are increasing. We report two cases of severe hypertriglyceridaemia and pancreatitis in adolescent females. Hypertriglyceridaemia improved markedly with restriction of dietary fat. An inhibitor to lipoprotein lipase was found to be the cause in one patient, while in the other limited genetic investigation excluded chylomicronaemia owing to deficiency of lipoprotein lipase, its activators and processing proteins

Preventing the spread of multidrug-resistant tuberculosis and protecting contacts of infectious cases

Prevention of multidrug-resistant and extensively drug-resistant tuberculosis (MDR/XDR-TB) is a top priority for global TB control, given the need to limit epidemic spread and considering the high cost, toxicity and poor treatment outcomes with available therapies. We performed a systematic literature review to evaluate the evidence for strategies to reduce MDR/XDR-TB transmission and disease progression. Rapid detection and timely initiation of effective treatment is critical to rendering MDR/XDR-TB cases non-infectious. The scale-up of rapid molecular testing has transformed the capacity of high-incidence settings to identify and treat patients with MDR/XDR-TB. Optimized infection control measures in hospitals and clinics are critical to protect other patients and healthcare workers, whereas creative measures to reduce transmission within community hotspots require consideration. Targeted screening of high-risk communities may enhance early case-detection and limit the spread of MDR/XDR-TB. Among infected contacts, preventive therapy promises to reduce the risk of disease progression. This is supported by observational cohort studies, but randomized trials are urgently needed to confirm these observations and guide policy formulation. Substantial investment in MDR/XDR-TB prevention and care will be critical if the ambitious global goal of TB elimination is to be realized

Clinical Evaluation of a Line-Probe Assay for Tuberculosis Detection and Drug-Resistance Prediction in Namibia.

Treatment of tuberculosis requires rapid information about Mycobacterium tuberculosis (Mtb) drug susceptibility to ensure effective therapy and optimal outcomes. At the tuberculosis referral hospital in Windhoek, Namibia, a country of high tuberculosis incidence, we evaluated the diagnostic accuracy of a line-probe-assay (LPA), GenID, for the molecular diagnosis of Mtb infection and drug resistance in patients with suspected tuberculosis (cohort 1) and confirmed rifampin (RIF)-resistant tuberculosis (cohort 2). GenID test results were compared to Xpert MTB/RIF and/or Mtb culture and antimicrobial suceptibilty testing. GenID LPA was applied to 79 and 55 samples from patients in cohort 1 and cohort 2, respectively. The overall sensitivity of GenID LPA for the detection of Mtb DNA in sputum from patients with detectable and undetectable acid-fast bacilli by sputum smear microscopy was 93.3% (56/60; 95% confidence interval = 83.8-98.2) and 22.7% (5/22; 7.8-45.4). The sensitivity/specificity for the detection of drug resistance was 84.2% (32/38; 68.7-94.0)/100% (19/19; 82.4-100.0) for RIF, 89.7% (26/29; 72.6-97.8)/91.7% (22/24; 73.0-99.0) for isoniazid, and 85.7% (6/7; 42.1-99.6)/94.7% (18/19; 74.0-99.9) for fluoroquinolones; 23.6% of tests for second-line injectable resistance were invalid despite repeat testing. The diagnosis of tuberculosis by detection of Mtb DNA in sputum by GenID LPA depends strongly on the detection of acid-fast bacilli in sputum specimen. Prediction of drug resistance by GenID did not reach the World Health Organization (WHO) target product profile. IMPORTANCE Mycobacterium tuberculosis (Mtb) drug-resistance detection is crucial for successful control of tuberculosis. Line-probe assays (LPA) are frequently used to detect resistance to rifampin, isoniazid, fluoroquinolones (FQs), and second-line injectables (SLIs). GenID RIF/isoniazid (INH), FQ, and SLI LPA have not been widely tested and used so far. This study tested the diagnostic performance of the GenID LPA in a high-incidence TB/HIV, real-world setting in Namibia. The LPA demonstrates only an acceptable diagnostic performance for Mtb and drug-resistance detection. The diagnostic sensitivity and specificity fall short of the WHO suggested target product profiles for LPA

Severe Hypertriglyceridaemia as a result of Familial Chylomicronaemia:

Lipoprotein lipase deficiency causes severe hypertriglyceridaemia due to chylomicronaemia, and leads to recurrent and potentially life-threatening pancreatitis. This disorder can only be managed by dietary fat restriction as drugs are ineffective. We review the experience with familial chylomicronaemia in patients who attended the lipid clinics at Groote Schuur Hospital and Red Cross Children's War Memorial Hospital in Cape Town. Criteria for inclusion were an initial plasma triglyceride concentration of >15 mmol/l and a typical type I Fredrickson hyperlipidaemia pattern on plasma lipoprotein electrophoresis. A total of 29 patients were seen over 25 years. The mean age of presentation was 10 years, but ranged from 0 to 43 years. The modes of presentation differed: pancreatitis (N=16), eruptive xanthomata (N=2), coincidental detection of hypertriglyceridaemia (N=2), screening relatives (N=7), and after death from pancreatitis (N=1). Plasma triglycerides responded rapidly and dramatically to dietary fat restriction, and some patients sustained good control of the hyperlipidaemia. The onset of pancreatitis was earlier in patients of Indian ancestry, suggesting a genotype/phenotype interaction within this disorder. Genetic work-up indicated founder effects in the Afrikaner and Indian patients. Lipaemic plasma should be taken seriously at all ages, and necessitates work-up at specialised clinics where the diagnosis of chylomicronaemia or type I hyperlipidaemia facilitates appropriate dietary management that can prevent pancreatitis. South African Medical Journal Vol. 98 (2) 2008: pp. 105-10

Global mortality from outdoor fine particle pollution generated by fossil fuel combustion: Results from GEOS-Chem

The burning of fossil fuels – especially coal, petrol, and diesel – is a major source of airborne fine particulate matter (PM2.5), and a key contributor to the global burden of mortality and disease. Previous risk assessments have examined the health response to total PM2.5, not just PM2.5 from fossil fuel combustion, and have used a concentration-response function with limited support from the literature and data at both high and low concentrations. This assessment examines mortality associated with PM2.5 from only fossil fuel combustion, making use of a recent meta-analysis of newer studies with a wider range of exposure. We also estimated mortality due to lower respiratory infections (LRI) among children under the age of five in the Americas and Europe, regions for which we have reliable data on the relative risk of this health outcome from PM2.5 exposure. We used the chemical transport model GEOS-Chem to estimate global exposure levels to fossil-fuel related PM2.5 in 2012. Relative risks of mortality were modeled using functions that link long-term exposure to PM2.5 and mortality, incorporating nonlinearity in the concentration response. We estimate a global total of 10.2 (95% CI: -47.1 to 17.0) million premature deaths annually attributable to the fossil-fuel component of PM2.5. The greatest mortality impact is estimated over regions with substantial fossil fuel related PM2.5, notably China (3.9 million), India (2.5 million) and parts of eastern US, Europe and Southeast Asia. The estimate for China predates substantial decline in fossil fuel emissions and decreases to 2.4 million premature deaths due to 43.7% reduction in fossil fuel PM2.5 from 2012 to 2018 bringing the global total to 8.7 (95% CI: -1.8 to 14.0) million premature deaths. We also estimated excess annual deaths due to LRI in children (0-4 years old) of 876 in North America, 747 in South America, and 605 in Europe. This study demonstrates that the fossil fuel component of PM2.5 contributes a large mortality burden. The steeper concentration-response function slope at lower concentrations leads to larger estimates than previously found in Europe and North America, and the slower drop-off in slope at higher concentrations results in larger estimates in Asia. Fossil fuel combustion can be more readily controlled than other sources and precursors of PM2.5 such as dust or wildfire smoke, so this is a clear message to policymakers and stakeholders to further incentivize a shift to clean sources of energy

Severe hypertriglyceridaemia as a result of familial chylomicronaemia:The Cape Town experience

Lipoprotein lipase deficiency causes severe hypertriglyceridaemia due to chylomicronaemia, and leads to recurrent and potentially life-threatening pancreatitis. This disorder can only be managed by dietary fat restriction as drugs are ineffective. We review the experience with familial chylomicronaemia in patients who attended the lipid clinics at Groote Schuur Hospital and Red Cross Children's War Memorial Hospital in Cape Town. Criteria for inclusion were an initial plasma triglyceride concentration of >15 mmol/l and a typical type I Fredrickson hyperlipidaemia pattern on plasma lipoprotein electrophoresis. A total of 29 patients were seen over 25 years. The mean age of presentation was 10 years, but ranged from 0 to 43 years. The modes of presentation differed: pancreatitis (N=16), eruptive xanthomata (N=2), coincidental detection of hypertriglyceridaemia (N=2), screening relatives (N=7), and after death from pancreatitis (N=1). Plasma triglycerides responded rapidly and dramatically to dietary fat restriction, and some patients sustained good control of the hyperlipidaemia. The onset of pancreatitis was earlier in patients of Indian ancestry, suggesting a genotype/phenotype interaction within this disorder. Genetic work-up indicated founder effects in the Afrikaner and Indian patients. Lipaemic plasma should be taken seriously at all ages, and necessitates work-up at specialised clinics where the diagnosis of chylomicronaemia or type I hyperlipidaemia facilitates appropriate dietary management that can prevent pancreatitis

Clustered bottlenecks in mRNA translation and protein synthesis

We construct an algorithm that generates large, band-diagonal transition matrices for a totally asymmetric exclusion process (TASEP) with local hopping rate inhomogeneities. The matrices are diagonalized numerically to find steady-state currents of TASEPs with local variations in hopping rate. The results are then used to investigate clustering of slow codons along mRNA. Ribosome density profiles near neighboring clusters of slow codons interact, enhancing suppression of ribosome throughput when such bottlenecks are closely spaced. Increasing the slow codon cluster size, beyond $\approx 3-4$, does not significantly reduce ribosome current. Our results are verified by extensive Monte-Carlo simulations and provide a biologically-motivated explanation for the experimentally-observed clustering of low-usage codons

Geometrical Optics Formalism to Model Contrast in Dark-Field X-ray Microscopy

Dark-field X-ray microscopy is a new full-field imaging technique that nondestructively maps the structure and local strain inside deeply embedded crystalline elements in three dimensions. Placing an objective lens in the diffracted beam generates a magnified projection image of a local volume. We provide a general formalism based on geometrical optics for the diffraction imaging, valid for any crystallographic space group. This allows simulation of diffraction images based on micro-mechanical models. We present example simulations with the formalism, demonstrating how it may be used to design new experiments or interpret existing ones. In particular, we show how modifications to the experimental design may tailor the reciprocal-space resolution function to map specific components of the deformation gradient tensor. The formalism supports multi-length scale experiments, as it enables DFXM to be interfaced with 3DXRD. The formalism is demonstrated by comparison to experimental images of the strain field around a straight dislocation

Chromosomal Redistribution of Male-Biased Genes in Mammalian Evolution with Two Bursts of Gene Gain on the X Chromosome

Mammalian X chromosomes evolved under various mechanisms including sexual antagonism, the faster-X process, and meiotic sex chromosome inactivation (MSCI). These forces may contribute to nonrandom chromosomal distribution of sex-biased genes. In order to understand the evolution of gene content on the X chromosome and autosome under these forces, we dated human and mouse protein-coding genes and miRNA genes on the vertebrate phylogenetic tree. We found that the X chromosome recently acquired a burst of young male-biased genes, which is consistent with fixation of recessive male-beneficial alleles by sexual antagonism. For genes originating earlier, however, this pattern diminishes and finally reverses with an overrepresentation of the oldest male-biased genes on autosomes. MSCI contributes to this dynamic since it silences X-linked old genes but not X-linked young genes. This demasculinization process seems to be associated with feminization of the X chromosome with more X-linked old genes expressed in ovaries. Moreover, we detected another burst of gene originations after the split of eutherian mammals and opossum, and these genes were quickly incorporated into transcriptional networks of multiple tissues. Preexisting X-linked genes also show significantly higher protein-level evolution during this period compared to autosomal genes, suggesting positive selection accompanied the early evolution of mammalian X chromosomes. These two findings cast new light on the evolutionary history of the mammalian X chromosome in terms of gene gain, sequence, and expressional evolution.</p