Group B streptococcal colonization in elderly women.

BACKGROUND In non-pregnant adults, the incidence of invasive Group B Streptococcus (GBS) disease is continuously increasing. Elderly and immunocompromised persons are at increased risk of infection. GBS commonly colonizes the vaginal tract, though data on colonization in the elderly are scarce. It is unknown whether the prevalence of GBS colonization is increasing in parallel to the observed rise of invasive infection. We conducted a three-year (2017-2019) prospective observational cross-sectional study in two teaching hospitals in Switzerland to determine the rate of GBS vaginal colonization in women over 60 years and i) to compare the proportions of known risk factors associated with invasive GBS diseases in colonized versus non-colonized women and ii) to evaluate the presence of GBS clusters with specific phenotypic and genotypic patterns in this population. METHODS GBS screening was performed by using vaginal swabs collected during routine examination from women willing to participate in the study and to complete a questionnaire for risk factors. Isolates were characterized for antibiotic resistance profile, serotype and sequence type (ST). RESULTS The GBS positivity rate in the elderly was 17% (44/255 positive samples), and similar to the one previously reported in pregnant women (around 20%). We could not find any association between participants' characteristics, previously published risk factors and GBS colonization. All strains were susceptible to penicillin, 22% (8/36) were not susceptible to erythromycin, 14% (5/36) were not susceptible to clindamycin and 8% (3/36) showed inducible clindamycin resistance. Both M and L phenotypes were each detected in one isolate. The most prevalent serotypes were III (33%, 12/36) and V (31%, 11/36). ST1 and ST19 accounted for 11% of isolates each (4/36); ST175 for 8% (3/36); and ST23, ST249 and ST297 for 6% each (2/36). Significantly higher rates of resistance to macrolides and clindamycin were associated with the ST1 genetic background of ST1. CONCLUSIONS Our findings indicate a similar colonization rate for pregnant and elderly women. TRIAL REGISTRATION Current Controlled Trial ISRCTN15468519 ; 06/01/2017

Emerging organic contaminants in the river Ganga and key tributaries in the middle Gangetic Plain, India:Characterization, distribution & controls

The presence and distribution of emerging organic contaminants (EOCs) in freshwater environments is a key issue in India and globally, particularly due to ecotoxicological and potential antimicrobial resistance concerns. Here we have investigated the composition and spatial distribution of EOCs in surface water along a ∼500 km segment of the iconic River Ganges (Ganga) and key tributaries in the middle Gangetic Plain of Northern India. Using a broad screening approach, in 11 surface water samples, we identified 51 EOCs, comprising of pharmaceuticals, agrochemicals, lifestyle and industrial chemicals. Whilst the majority of EOCs detected were a mixture of pharmaceuticals and agrochemicals, lifestyle chemicals (and particularly sucralose) occurred at the highest concentrations. Ten of the EOCs detected are priority compounds (e.g. sulfamethoxazole, diuron, atrazine, chlorpyrifos, perfluorooctane sulfonate (PFOS), perfluorobutane sulfonate, thiamethoxam, imidacloprid, clothianidin and diclofenac). In almost 50% of water samples, sulfamethoxazole concentrations exceeded predicted no-effect concentrations (PNECs) for ecological toxicity. A significant downstream reduction in EOCs was observed along the River Ganga between Varanasi (Uttar Pradesh) and Begusarai (Bihar), likely reflecting dilution effects associated with three major tributaries, all with considerably lower EOC concentrations than the main Ganga channel. Sorption and/or redox controls were observed for some compounds (e.g. clopidol), as well as a relatively high degree of mixing of EOCs within the river. We discuss the environmental relevance of the persistence of several parent compounds (notably atrazine, carbamazepine, metribuzin and fipronil) and associated transformation products. Associations between EOCs and other hydrochemical parameters including excitation emission matrix (EEM) fluorescence indicated positive, significant, and compound-specific correlations between EOCs and tryptophan-, fulvic- and humic-like fluorescence. This study expands the baseline characterization of EOCs in Indian surface water and contributes to an improved understanding of the potential sources and controls on EOC distribution in the River Ganga and other large river systems

Connectivity-based parcellation of the thalamus explains specific cognitive and behavioural symptoms in patients with bilateral thalamic infarct

A novel approach based on diffusion tractography was used here to characterise the cortico-thalamic connectivity in two patients, both presenting with an isolated bilateral infarct in the thalamus, but exhibiting partially different cognitive and behavioural profiles. Both patients (G.P. and R.F.) had a pervasive deficit in episodic memory, but only one of them (R.F.) suffered also from a dysexecutive syndrome. Both patients had an MRI scan at 3T, including a T1-weighted volume. Their lesions were manually segmented. T1-volumes were normalised to standard space, and the same transformations were applied to the lesion masks. Nineteen healthy controls underwent a diffusion-tensor imaging (DTI) scan. Their DTI data were normalised to standard space and averaged. An atlas of Brodmann areas was used to parcellate the prefrontal cortex. Probabilistic tractography was used to assess the probability of connection between each voxel of the thalamus and a set of prefrontal areas. The resulting map of corticothalamic connections was superimposed onto the patients' lesion masks, to assess whether the location of the thalamic lesions in R.F. (but not in G. P.) implied connections with prefrontal areas involved in dysexecutive syndromes. In G.P., the lesion fell within areas of the thalamus poorly connected with prefrontal areas, showing only a modest probability of connection with the anterior cingulate cortex (ACC). Conversely, R.F.'s lesion fell within thalamic areas extensively connected with the ACC bilaterally, with the right dorsolateral prefrontal cortex, and with the left supplementary motor area. Despite a similar, bilateral involvement of the thalamus, the use of connectivity-based segmentation clarified that R.F.'s lesions only were located within nuclei highly connected with the prefrontal cortical areas, thus explaining the patient's frontal syndrome. This study confirms that DTI tractography is a useful tool to examine in vivo the effect of focal lesions on interconnectivity brain patterns

Quantifying the impacts of groundwater abstraction on Ganges river water infiltration into shallow aquifers under the rapidly developing city of Patna, India

Study region Patna is located on the southern bank of the River Ganges in Bihar, India. Rapid population growth over the past few decades has driven an increase in groundwater abstraction from aquifers under the city. Study focus This study exeplores the pumping-induced water exchange between the River Ganges and groundwater under transient conditions between 2009 and 2015, using a numerical simulation. The deterministic water exchange model within an uncertainty quantification was used to reveal the controlling factors affecting river water infiltration. New hydrological insights for the region Modelling reveals that under baseline (eno pumping) conditions, the dominant (~ 91% of the year) flow direction is from the aquifer to the river, which reverses (~ 9% of the year) when the river stage is high. When a municipal pumping well is implemented, river water infiltration into the aquifer increases to 68% of the year. The groundwater pumping rate is found to be the most important factor affecting the river water infiltration, whilst the groundwater table level is most sensitive to the well distance from the river, followed by pumping rate. Optimizing the location, depth and pumping rate of new wells in the area could mitigate fluvial contamination of the aquifer and help maintain groundwater levels

Yielded to Christ or conformed to this world? Postwar Mennonite responses to labour activism

This is the accepted version of the manuscript.The urbanization of North American Mennonites after the Second World War necessitated a reconsideration of Mennonite religious beliefs. Post-war concerns for social justice led to a greater emphasis on non-violence and agape at the expense of Gelassenheit. The tenor of Mennonite church conference resolutions regarding labour union membership changed; while skepticism remained regarding the wisdom of union involvement, the door was left open for participation in unions. The labour militancy of the 1970s led Manitoba Mennonites to re-examine their engagement with the labour movement, a process that has continued to the present day. Without further research on Mennonite workplaces, it cannot be known exactly how the change in religious emphases has affected Mennonite identity.https://journals.sagepub.com/doi/abs/10.1177/00084298070360020

Inflation and Dark Energy from spectroscopy at z > 2

The expansion of the Universe is understood to have accelerated during two epochs: in its very first moments during a period of Inflation and much more recently, at z < 1, when Dark Energy is hypothesized to drive cosmic acceleration. The undiscovered mechanisms behind these two epochs represent some of the most important open problems in fundamental physics. The large cosmological volume at 2 < z < 5, together with the ability to efficiently target high-$z$ galaxies with known techniques, enables large gains in the study of Inflation and Dark Energy. A future spectroscopic survey can test the Gaussianity of the initial conditions up to a factor of ~50 better than our current bounds, crossing the crucial theoretical threshold of $\sigma(f_{NL}^{\rm local})$ of order unity that separates single field and multi-field models. Simultaneously, it can measure the fraction of Dark Energy at the percent level up to $z = 5$, thus serving as an unprecedented test of the standard model and opening up a tremendous discovery space

The biogeochemical impact of glacial meltwater from Southwest Greenland

Biogeochemical cycling in high-latitude regions has a disproportionate impact on global nutrient budgets. Here, we introduce a holistic, multi-disciplinary framework for elucidating the influence of glacial meltwaters, shelf currents, and biological production on biogeochemical cycling in high-latitude continental margins, with a focus on the silica cycle. Our findings highlight the impact of significant glacial discharge on nutrient supply to shelf and slope waters, as well as surface and benthic production in these regions, over a range of timescales from days to thousands of years. Whilst biological uptake in fjords and strong diatom activity in coastal waters maintains low dissolved silicon concentrations in surface waters, we find important but spatially heterogeneous additions of particulates into the system, which are transported rapidly away from the shore. We expect the glacially-derived particles – together with biogenic silica tests – to be cycled rapidly through shallow sediments, resulting in a strong benthic flux of dissolved silicon. Entrainment of this benthic silicon into boundary currents may supply an important source of this key nutrient into the Labrador Sea, and is also likely to recirculate back into the deep fjords inshore. This study illustrates how geochemical and oceanographic analyses can be used together to probe further into modern nutrient cycling in this region, as well as the palaeoclimatological approaches to investigating changes in glacial meltwater discharge through time, especially during periods of rapid climatic change in the Late Quaternary

Ancient genomes reveal complex patterns of population movement, interaction, and replacement in sub-Saharan Africa

Africa hosts the greatest human genetic diversity globally, but legacies of ancient population interactions and dispersals across the continent remain understudied. Here, we report genome-wide data from 20 ancient sub-Saharan African individuals, including the first reported ancient DNA from the DRC, Uganda, and Botswana. These data demonstrate the contraction of diverse, once contiguous hunter-gatherer populations, and suggest the resistance to interaction with incoming pastoralists of delayed-return foragers in aquatic environments. We refine models for the spread of food producers into eastern and southern Africa, demonstrating more complex trajectories of admixture than previously suggested. In Botswana, we show that Bantu ancestry post-dates admixture between pastoralists and foragers, suggesting an earlier spread of pastoralism than farming to southern Africa. Our findings demonstrate how processes of migration and admixture have markedly reshaped the genetic map of sub-Saharan Africa in the past few millennia and highlight the utility of combined archaeological and archaeogenetic approaches

NEMO reshapes the α-Synuclein aggregate interface and acts as an autophagy adapter by co-condensation with p62

NEMO is a ubiquitin-binding protein which regulates canonical NF-kappa B pathway activation in innate immune signaling, cell death regulation and host-pathogen interactions. Here we identify an NF-kappa B-independent function of NEMO in proteostasis regulation by promoting autophagosomal clearance of protein aggregates. NEMO-deficient cells accumulate misfolded proteins upon proteotoxic stress and are vulnerable to proteostasis challenges. Moreover, a patient with a mutation in the NEMO-encoding IKBKG gene resulting in defective binding of NEMO to linear ubiquitin chains, developed a widespread mixed brain proteinopathy, including alpha-synuclein, tau and TDP-43 pathology. NEMO amplifies linear ubiquitylation at alpha-synuclein aggregates and promotes the local concentration of p62 into foci. In vitro, NEMO lowers the threshold concentrations required for ubiquitin-dependent phase transition of p62. In summary, NEMO reshapes the aggregate surface for efficient autophagosomal clearance by providing a mobile phase at the aggregate interphase favoring co-condensation with p62. Selective autophagy helps to degrade aggregated proteins accumulating in neurodegenerative diseases. Here, the authors show that NEMO, a ubiquitin binding protein previously linked to innate immune signaling, is recruited to misfolded proteins and promotes their autophagic clearance by forming condensates with the autophagy receptor p62