Chemical Characterization and Source Apportionment of Household Fine Particulate Matter in Rural, Peri-urban, and Urban West Africa

Household air pollution in sub-Saharan Africa and other developing regions is an important cause of disease burden. Little is known about the chemical composition and sources of household air pollution in sub-Saharan Africa, and how they differ between rural and urban homes. We analyzed the chemical composition and sources of fine particles (PM2.5) in household cooking areas of multiple neighborhoods in Accra, Ghana, and in peri-urban (Banjul) and rural (Basse) areas in The Gambia. In Accra, biomass burning accounted for 39–62% of total PM2.5 mass in the cooking area in different neighborhoods; the absolute contributions were 10–45 μg/m3. Road dust and vehicle emissions comprised 12–33% of PM2.5 mass. Solid waste burning was also a significant contributor to household PM2.5 in a low-income neighborhood but not for those living in better-off areas. In Banjul and Basse, biomass burning was the single dominant source of cooking-area PM2.5, accounting for 74–87% of its total mass; the relative and absolute contributions of biomass smoke to PM2.5 mass were larger in households that used firewood than in those using charcoal, reaching as high as 463 μg/m3 in Basse homes that used firewood for cooking. Our findings demonstrate the need for policies that enhance access to cleaner fuels in both rural and urban areas, and for controlling traffic emissions in cities in sub-Saharan Africa

Rapid evolution of virulence and drug resistance in the emerging zoonotic pathogen Streptococcus suis

Background: Streptococcus suis is a zoonotic pathogen that infects pigs and can occasionally cause serious infections in humans. S. suis infections occur sporadically in human Europe and North America, but a recent major outbreak has been described in China with high levels of mortality. The mechanisms of S. suis pathogenesis in humans and pigs are poorly understood. Methodology/Principal Findings: The sequencing of whole genomes of S. suis isolates provides opportunities to investigate the genetic basis of infection. Here we describe whole genome sequences of three S. suis strains from the same lineage: one from European pigs, and two from human cases from China and Vietnam. Comparative genomic analysis was used to investigate the variability of these strains. S. suis is phylogenetically distinct from other Streptococcus species for which genome sequences are currently available. Accordingly, ,40% of the ,2 Mb genome is unique in comparison to other Streptococcus species. Finer genomic comparisons within the species showed a high level of sequence conservation; virtually all of the genome is common to the S. suis strains. The only exceptions are three ,90 kb regions, present in the two isolates from humans, composed of integrative conjugative elements and transposons. Carried in these regions are coding sequences associated with drug resistance. In addition, small-scale sequence variation has generated pseudogenes in putative virulence and colonization factors. Conclusions/Significance: The genomic inventories of genetically related S. suis strains, isolated from distinct hosts and diseases, exhibit high levels of conservation. However, the genomes provide evidence that horizontal gene transfer has contributed to the evolution of drug resistance

Dicer regulates Xist promoter methylation in ES cells indirectly through transcriptional control of Dnmt3a

<p>Abstract</p> <p>Background</p> <p>X chromosome inactivation is the mechanism used in mammals to achieve dosage compensation of X-linked genes in XX females relative to XY males. Chromosome silencing is triggered in <it>cis </it>by expression of the non-coding RNA <it>Xist</it>. As such, correct regulation of the <it>Xist </it>gene promoter is required to establish appropriate X chromosome activity both in males and females. Studies to date have demonstrated co-transcription of an antisense RNA <it>Tsix </it>and low-level sense transcription prior to onset of X inactivation. The balance of sense and antisense RNA is important in determining the probability that a given <it>Xist </it>allele will be expressed, termed the X inactivation choice, when X inactivation commences.</p> <p>Results</p> <p>Here we investigate further the mechanism of <it>Xist </it>promoter regulation. We demonstrate that both sense and antisense transcription modulate <it>Xist </it>promoter DNA methylation in undifferentiated embryonic stem (ES) cells, suggesting a possible mechanistic basis for influencing X chromosome choice. Given the involvement of sense and antisense RNAs in promoter methylation, we investigate a possible role for the RNA interference (RNAi) pathway. We show that the <it>Xist </it>promoter is hypomethylated in ES cells deficient for the essential RNAi enzyme Dicer, but that this effect is probably a secondary consequence of reduced levels of <it>de novo </it>DNA methyltransferases in these cells. Consistent with this we find that Dicer-deficient XY and XX embryos show appropriate <it>Xist </it>expression patterns, indicating that Xist gene regulation has not been perturbed.</p> <p>Conclusion</p> <p>We conclude that <it>Xist </it>promoter methylation prior to the onset of random X chromosome inactivation is influenced by relative levels of sense and antisense transcription but that this probably occurs independent of the RNAi pathway. We discuss the implications for this data in terms of understanding <it>Xist </it>gene regulation and X chromosome choice in random X chromosome inactivation.</p

Climate change adaptation in European river basins

This paper contains an assessment and standardized comparative analysis of the current water management regimes in four case-studies in three European river basins: the Hungarian part of the Upper Tisza, the Ukrainian part of the Upper Tisza (also called Zacarpathian Tisza), Alentejo Region (including the Alqueva Reservoir) in the Lower Guadiana in Portugal, and Rivierenland in the Netherlands. The analysis comprises several regime elements considered to be important in adaptive and integrated water management: agency, awareness raising and education, type of governance and cooperation structures, information management and—exchange, policy development and—implementation, risk management, and finances and cost recovery. This comparative analysis has an explorative character intended to identify general patterns in adaptive and integrated water management and to determine its role in coping with the impacts of climate change on floods and droughts. The results show that there is a strong interdependence of the elements within a water management regime, and as such this interdependence is a stabilizing factor in current management regimes. For example, this research provides evidence that a lack of joint/participative knowledge is an important obstacle for cooperation, or vice versa. We argue that there is a two-way relationship between information management and collaboration. Moreover, this research suggests that bottom-up governance is not a straightforward solution to water management problems in large-scale, complex, multiple-use systems, such as river basins. Instead, all the regimes being analyzed are in a process of finding a balance between bottom-up and top–down governance. Finally, this research shows that in a basin where one type of extreme is dominant—like droughts in the Alentejo (Portugal) and floods in Rivierenland (Netherlands)—the potential impacts of other extremes are somehow ignored or not perceived with the urgency they might deserv

Die Ballon-Okklusionsangiographie der Pulmonalarterien bei chronischer pulmonaler Hypertonie

Die chronische pulmonale Hypertonie ist eine seltene Erkrankung, die heute noch als unheilbar gilt. Die therapeutischen Möglichkeiten haben sich in den letzten Jahren rasant weiterentwickelt und orientieren sich an der Pathogenese und an den Befunden aus der bildgebenden Diagnostik. Diese muss in ihren Möglichkeiten der differentialdiagnostischen Eingrenzung zugrundeliegender Ursachen der pulmonalen Hypertonie Schritt halten. Insbesondere die Ergebnisse der intraarteriellen Pulmonalisangiographie als Referenzmethode in der Bildgebung der Lungen-strombahn haben meist unmittelbare therapeutische Konsequenz, z.B. ob ein Patient für eine pulmonale Thrombendarteriektomie gegeignet ist oder nicht. Wir haben überprüft, ob die selektive pulmonale Ballon-Okklusionsangiographie als Erweiterung der standardisierten Übersichtsangiographie die Differentialdiagnose z.B. der embolischen (CTEPH) gegenüber der nichtembolischen (NoCTEPH) Erkrankung verbessert. Zu diesem Zweck wurden Untersuchungen von 50 Patienten bestehend aus jeweils einer konventionellen Übersichtsangiographie und der ergänzenden Ballon-Okklusionsangiographie retrospektiv nach einem standardisierten Studienprotokoll ausgewertet. Zunächst wurde eine digitale Subtraktionsangiographie der Pulmonalarterien angefertigt. Anschließend führten wir einen weichen Latex-Ballonkatheter in Segment- oder Subsegmentarterien ein. Dann entfalteten wir den Ballon, um die sondierte Arterie zu verschließen und injizierten jeweils 10 bis 15 ml Kontrastmittel, um die kleinen peripheren Gefäße sichtbar zu machen. 13 Patienten litten an einer nichtthrombembolischen Form der chronischen pulmonalen Hypertonie. Bei 36 von 37 Patienten mit CTEPH fanden wir organisiertes embolisches Material als irreguläre Stenosen, Verschlüsse oder Strickleitersysteme (Webs und Bands). In der Darstellung dieser pathologischen Befunde war die Ballon-Okklusionsangiographie der Übersichtsangiographie sowohl qualitativ als auch quantitativ überlegen. Nach unseren Daten entdeckt die Ballon-Okklusionsangiographie in etwa bei jedem fünften Patienten mit negativer Übersichtsangiographie wenigstens ein thrombembolisches Residuum, sie steigert somit als Verfeinerung der Methode die Sensitivität der Pulmonalisangiographie. Generell stellte sie 2,7 bis 3,6 Aufteilungsgenerationen der peripheren Gefäße mehr dar als die konventionelle selektive DSA. Außerdem fanden wir bei 17 Patienten Kollateralgefäße zu den peripheren Segmenten von zentral verschlossenen Pulmonal-arterien. Dieses Phänomen war nur in der Ballon-Okklusionsangiographie zu beobachten und erwies sich als spezifisch für Patienten mit thrombembolischer pulmonaler Hypertonie. Der Befund ist insofern erstaunlich, als dass Pulmonalarterien eigentlich als funktionelle Endarterien ohne Anastomosen zu Nachbararterien beschrieben werden. Bei 11 Patienten fanden sich Anastomosen zu subpleuralen Bronchialarterien. Dieses bereits bekannte Phänomen steht nach unseren Daten in keinem Zusammenhang mit einer bestimmten Erkrankung und ist somit als unspezifisches Merkmal der chronischen pulmonalen Hypertonie zu deuten. In drei Fällen konnten histologisch postkapilläre Formen der pulmonalen Hypertonie (zweimal pulmonale veno-okklusive Erkrankung (PVOD), einmal primäre kapilläre Hämangiomatose) gesichert werden. Bei diesen Patienten zeigte die Ballon-Okklusionsangiographie eine Füllung der Lungenvenen ohne angiographisch sichtbare Anfärbung des Kapillarbettes (fehlende Parenchymanfärbung). Die geschilderten Erkenntnisse aus unserer Studie lassen sich für die Praxis wie folgt zusammenfassen: 1. Die Ballon-Okklusionsangiographie verbessert die Visualisierung der peripheren Pulmonalarterien. 2. Sie erleichtert die Detektion und Lokalisation thrombembolischer Residuen 3. Sie hilft bei der Differentialdiagnose zwischen thrombembolischer und nicht-thrombembolischer chronischer pulmonaler Hypertonie. 4. Vorher unsichtbare Anastomosen und Kollateralgefäße werden sichtbar. 5. Venöse Füllung ohne Parenchymanfärbung ist offensichtlich ein Zeichen der Parenchymerkrankung; diese Konstellation ist bei Patienten mit chronischer pulmonaler Hypertonie möglicherweise ein Hinweis auf das Vorliegen der pulmonalen venookklusiven Erkrankung (PVOD) oder der primären kapillären Hämangiomatose (PCH). 6. Die selektive Ballon-Okklusionsangiographie segmentaler Pulmonalarterien verbessert in Zusammenschau mit der Computertomographie die Zuverlässigkeit in der Selektion von Kandidaten für eine pulmonale Thrombendarteriektomie oder eine Prostazyklintherapie.Purpose: Test the ability of selective balloon occlusion angiography of pulmonary segmental arteries in the differential diagnosis of chronic pulmonary hypertension: embolic vs. non-embolic disease, pulmonary capillary hemangiomatosis, and venoocclusive disease. Methods and Materials: In 50 patients with pulmonary hypertension, digital subtraction angiography (DSA) of pulmonary arteries were used to assist in the selection of candidates appropriate for thrombo-endarterectomy. In addition to these standard methods, we introduced a soft latex balloon catheter into segmental arteries, inflated the balloon to occlude the artery, and injected 10 to 15 ml contrast medium to visualize small peripheral vessels as completely as possible. Results: 13 patients suffered from non-embolic pulmonary hypertension. In 36 of 37 patients with embolic pulmonary hypertension organizing embolic material was depicted as irregular narrowing or occlusion of pulmonary arteries, and weblike strictures. In all of these patients occlusion technique revealed more tiny webs or organized micro emboli in small peripheral arteries. According to our data balloon occlusion angiography discovers in every fifth patient showing a negative conventional pulmonary angiography at least one thromboembolic residuum and thus increases as a sophisticated method the sensitivity of the pulmonary angiography. Generally, occlusion technique revealed additional 2,7 to 3,6 ramifications of peripheral vessels in comparison to conventional selective DSA. Unexpectedly, we found in 11 patients anastomoses to bronchial arteries and in 17 patients collateral vessels to the peripheral segments of centrally occluded pulmonary arteries. These findings are astonishing, because pulmonary arteries are believed ramifying dichotomically without anastomoses. Obviously, there are alterations of pulmonary perfusion, which overcome normal anatomy. 3 patients with characteristic CT signs of interstitial disease (poorly defined nodular opacities and septal lines) underwent lung biopsy: 2 cases of venoocclusive disease, 1 case of pulmonary capillary hemangiomatosis. Occlusion angiography in these 3 patients revealed filling of veins without opacification of capillaries (failing parenchymal phase). Conclusion: Balloon occlusion technique improves the visualization of peripheral pulmonary arteries. Differential diagnosis of embolic and non-embolic pulmonary hypertension is facilitated. Previously invisible anastomoses and collateral vessels become visible. Venous filling without capillary opacification is apparently a sign of parenchymal disease; in patients with chronic pulmonary hypertension it might be a hint at venoocclusive disease or pulmonary capillary hemangiomatosi

The Terebridae and teretoxins: Combining phylogeny and anatomy for concerted discovery of bioactive compounds

The Conoidea superfamily, comprised of cone snails, terebrids, and turrids, is an exceptionally promising group for the discovery of natural peptide toxins. The potential of conoidean toxins has been realized with the distribution of the first Conus (cone snail) drug, Prialt (ziconotide), an analgesic used to alleviate chronic pain in HIV and cancer patients. Cone snail toxins (conotoxins) are highly variable, a consequence of a high mutation rate associated to duplication events and positive selection. As Conus and terebrids diverged in the early Paleocene, the toxins from terebrids (teretoxins) may demonstrate highly divergent and unique functionalities. Recent analyses of the Terebridae, a largely distributed family with more than 300 described species, indicate they have evolutionary and pharmacological potential. Based on a three gene (COI, 12S and 16S) molecular phylogeny, including ~50 species from the West-Pacific, five main terebrid lineages were discriminated: two of these lineages independently lost their venom apparatus, and one venomous lineage was previously unknown. Knowing the phylogenetic relationships within the Terebridae aids in effectively targeting divergent lineages with novel peptide toxins. Preliminary results indicate that teretoxins are similar in structure and composition to conotoxins, suggesting teretoxins are an attractive line of research to discover and develop new therapeutics that target ion channels and receptors. Using conotoxins as a guideline, and innovative natural products discovery strategies, such as the Concerted Discovery Strategy, the potential of the Terebridae and their toxins are explored as a pioneering pharmacological resource

Acupressure for smoking cessation – a pilot study

BACKGROUND: Tobacco smoking is a serious risk to health: several therapies are available to assist those who wish to stop. Smokers who approach publicly funded stop-smoking clinics in the UK are currently offered nicotine replacement therapy (NRT) or bupropion, and group behaviour therapy, for which there is evidence of effectiveness. Acupuncture and acupressure are also used to help smokers, though a systematic review of the evidence of their effectiveness was inconclusive. The aim of this pilot project was to determine the feasibility of a study to test acupressure as an adjunct to one anti-smoking treatment currently offered, and to inform the design of the study. METHODS: An open randomised controlled pilot study was conducted within the six week group programme offered by the Smoking Advice Service in Plymouth, UK. All participants received the usual treatment with NRT and group behavioural therapy, and were randomised into three groups: group A with two auricular acupressure beads, group B with one bead, and group C with no additional therapy. Participants were taught to press the beads when they experienced cravings. Beads were worn in one ear for four weeks, being replaced as necessary. The main outcome measures assessed in the pilot were success at quitting (expired CO ≤ 9 ppm), the dose of NRT used, and the rating of withdrawal symptoms using the Mood and Symptoms Scale. RESULTS: From 49 smokers attending four clinics, 24 volunteered to participate, 19 attended at least once after quitting, and seven remained to the final week. Participants who dropped out reported significantly fewer previous quit attempts, but no other significant differences. Participants reported stimulating the beads as expected during the initial days after quitting, but most soon reduced the frequency of stimulation. The discomfort caused by the beads was minor, and there were no significant side effects. There were technical problems with adhesiveness of the dressing. Reporting of NRT consumption was poor, with much missing data, but reporting of ratings of withdrawal symptom scores was nearly complete. However, these showed no significant changes or differences between groups for any week. CONCLUSION: Any effects of acupressure on smoking withdrawal, as an adjunct to the use of NRT and behavioural intervention, are unlikely to be detectable by the methods used here and further preliminary studies are required before the hypothesis can be tested

Estimating the number of infections and the impact of non-pharmaceutical interventions on COVID-19 in European countries: technical description update

Following the emergence of a novel coronavirus (SARS-CoV-2) and its spread outside of China, Europe has experienced large epidemics. In response, many European countries have implemented unprecedented non-pharmaceutical interventions including case isolation, the closure of schools and universities, banning of mass gatherings and/or public events, and most recently, wide-scale social distancing including local and national lockdowns. In this technical update, we extend a semi-mechanistic Bayesian hierarchical model that infers the impact of these interventions and estimates the number of infections over time. Our methods assume that changes in the reproductive number - a measure of transmission - are an immediate response to these interventions being implemented rather than broader gradual changes in behaviour. Our model estimates these changes by calculating backwards from temporal data on observed to estimate the number of infections and rate of transmission that occurred several weeks prior, allowing for a probabilistic time lag between infection and death. In this update we extend our original model [Flaxman, Mishra, Gandy et al 2020, Report #13, Imperial College London] to include (a) population saturation effects, (b) prior uncertainty on the infection fatality ratio, (c) a more balanced prior on intervention effects and (d) partial pooling of the lockdown intervention covariate. We also (e) included another 3 countries (Greece, the Netherlands and Portugal). The model code is available at https://github.com/ImperialCollegeLondon/covid19model/ We are now reporting the results of our updated model online at https://mrc-ide.github.io/covid19estimates/ We estimated parameters jointly for all M=14 countries in a single hierarchical model. Inference is performed in the probabilistic programming language Stan using an adaptive Hamiltonian Monte Carlo (HMC) sampler