HIV-1 Evolutionary Patterns Associated with Metastatic Kaposi's Sarcoma during AIDS.

Kaposi's sarcoma (KS) in HIV-infected individuals can have a wide range of clinical outcomes, from indolent skin tumors to a life-threatening visceral cancer. KS tumors contain endothelial-related cells and inflammatory cells that may be HIV-infected. In this study we tested if HIV evolutionary patterns distinguish KS tumor relatedness and progression. Multisite autopsies from participants who died from HIV-AIDS with KS prior to the availability of antiretroviral therapy were identified at the AIDS and Cancer Specimen Resource (ACSR). Two patients (KS1 and KS2) died predominantly from non-KS-associated disease and KS3 died due to aggressive and metastatic KS within one month of diagnosis. Skin and visceral tumor and nontumor autopsy tissues were obtained (n = 12). Single genome sequencing was used to amplify HIV RNA and DNA, which was present in all tumors. Independent HIV tumor clades in phylogenies differentiated KS1 and KS2 from KS3, whose sequences were interrelated by both phylogeny and selection. HIV compartmentalization was confirmed in KS1 and KS2 tumors; however, in KS3, no compartmentalization was observed among sampled tissues. While the sample size is small, the HIV evolutionary patterns observed in all patients suggest an interplay between tumor cells and HIV-infected cells which provides a selective advantage and could promote KS progression

A CMOS TDI image sensor for Earth observation

Time Delay and Integration (TDI) is used to increase the Signal to Noise Ratio (SNR) in image sensors when imaging fast moving objects. One important TDI application is in Earth observation from space. In order to operate in the space radiation environment, the effect that radiation damage has on the performance of the image sensors must be understood. This work looks at prototype TDI sensor pixel designs, produced by e2v technologies. The sensor is a CCD-like charge transfer device, allowing in-pixel charge summation, produced on a CMOS process. The use of a CMOS process allows potential advantages such as lower power consumption, smaller pixels, higher line rate and extra on-chip functionality which can simplify system design. CMOS also allows a dedicated output amplifier per column allowing fewer charge transfers and helping to facilitate higher line rates than CCDs. In this work the effect on the pixels of radiation damage from high energy protons, at doses relevant to a low Earth orbit mission, is presented. This includes the resulting changes in Charge Transfer inefficiency (CTI) and dark signal

HIV-1 Evolutionary Patterns Associated with Metastatic Kaposi’s Sarcoma during AIDS

Kaposi’s sarcoma (KS) in HIV-infected individuals can have a wide range of clinical outcomes, from indolent skin tumors to a life-threatening visceral cancer. KS tumors contain endothelial-related cells and inflammatory cells that may be HIV-infected. In this study we tested if HIV evolutionary patterns distinguish KS tumor relatedness and progression. Multisite autopsies from participants who died from HIV-AIDS with KS prior to the availability of antiretroviral therapy were identified at the AIDS and Cancer Specimen Resource (ACSR). Two patients (KS1 and KS2) died predominantly from non-KS-associated disease and KS3 died due to aggressive and metastatic KS within one month of diagnosis. Skin and visceral tumor and nontumor autopsy tissues were obtained (n=12). Single genome sequencing was used to amplify HIV RNA and DNA, which was present in all tumors. Independent HIV tumor clades in phylogenies differentiated KS1 and KS2 from KS3, whose sequences were interrelated by both phylogeny and selection. HIV compartmentalization was confirmed in KS1 and KS2 tumors; however, in KS3, no compartmentalization was observed among sampled tissues. While the sample size is small, the HIV evolutionary patterns observed in all patients suggest an interplay between tumor cells and HIV-infected cells which provides a selective advantage and could promote KS progression

Silk garments plus standard care compared with standard care for treating eczema in children: a randomised controlled, observer blind, pragmatic trial (CLOTHES Trial)

Background The role of clothing in the management of eczema (syn. atopic dermatitis, atopic eczema) is poorly understood. This trial evaluated the effectiveness and cost-effectiveness of silk garments (in addition to standard care) for the management of eczema in children with moderate to severe disease. Methods and findings This was a parallel group randomised controlled, observer-blind trial. Children aged 1 to 15 years with moderate to severe eczema were recruited from secondary care and the community in five UK centres. Participants were allocated using on-line randomisation (1:1) to standard care, or standard care plus silk garments; stratified by age and recruiting centre. Silk garments were worn for 6 months. Primary outcome (eczema severity) was assessed at baseline, 2, 4 and 6 months, by nurses blinded to treatment allocation using the Eczema Area and Severity Index (EASI), which was log-transformed for analysis (intention-to-treat analysis). Safety outcome: number of skin infections. Three hundred children were randomised (26th Nov 2013 to 5th May 2015): 42% girls, 79% white, mean age 5 years. Primary analysis included 282/300 (94%) children (n = 141 in each group). The garments were worn more often at night than in the day (median of 81% of nights (25th to 75th centile 57% to 96%) and 34% of days (25th to 75th centile 10% to 76%)). Geometric mean EASI scores at baseline, 2, 4 and 6 months were 9·2, 6·4, 5·8, 5·4 for silk clothing and 8·4, 6·6, 6·0, 5·4 for standard care. There was no evidence of any difference between the groups in EASI score averaged over all follow up visits adjusted for baseline EASI score, age and centre (adjusted ratio of geometric means: 0·95, 95% CI 0·85 to 1·07). This confidence interval is equivalent to a difference of -1·5 to 0·5 in the original EASI scale units which is not clinically important. Skin infections occurred in 36/142 (25%) and 39/141 (28%) for silk clothing and standard care respectively. Even if the small observed treatment effect was genuine, the incremental cost per QALY was £56,881 in the base case analysis from an NHS perspective, suggesting that silk garments are unlikely to be cost-effective within currently accepted thresholds. Main limitations: whilst minimising detection bias, use of an objective primary outcome may have underestimated treatment effects. Conclusions Silk clothing is unlikely to provide additional benefit over standard care in children with moderate to severe eczema

Whole-Community Facilitation Regulates Biodiversity on Patagonian Rocky Shores

Understanding the factors that generate and maintain biodiversity is a central goal in ecology. While positive species interactions (i.e., facilitation) have historically been underemphasized in ecological research, they are increasingly recognized as playing important roles in the evolution and maintenance of biodiversity. Dominant habitat-forming species (foundation species) buffer environmental conditions and can therefore facilitate myriad associated species. Theory predicts that facilitation will be the dominant community-structuring force under harsh environmental conditions, where organisms depend on shelter for survival and predation is diminished. Wind-swept, arid Patagonian rocky shores are one of the most desiccating intertidal rocky shores ever studied, providing an opportunity to test this theory and elucidate the context-dependency of facilitation.Surveys across 2100 km of southern Argentinean coastline and experimental manipulations both supported theoretical predictions, with 43 out of 46 species in the animal assemblage obligated to living within the matrices of mussels for protection from potentially lethal desiccation stress and predators having no detectable impact on diversity.These results provide the first experimental support of long-standing theoretical predictions and reveal that in extreme climates, maintenance of whole-community diversity can be maintained by positive interactions that ameliorate physical stress. These findings have important conservation implications and emphasize that preserving foundation species should be a priority in remediating the biodiversity consequences of global climate change

Genetic and Computational Identification of a Conserved Bacterial Metabolic Module

We have experimentally and computationally defined a set of genes that form a conserved metabolic module in the α-proteobacterium Caulobacter crescentus and used this module to illustrate a schema for the propagation of pathway-level annotation across bacterial genera. Applying comprehensive forward and reverse genetic methods and genome-wide transcriptional analysis, we (1) confirmed the presence of genes involved in catabolism of the abundant environmental sugar myo-inositol, (2) defined an operon encoding an ABC-family myo-inositol transmembrane transporter, and (3) identified a novel myo-inositol regulator protein and cis-acting regulatory motif that control expression of genes in this metabolic module. Despite being encoded from non-contiguous loci on the C. crescentus chromosome, these myo-inositol catabolic enzymes and transporter proteins form a tightly linked functional group in a computationally inferred network of protein associations. Primary sequence comparison was not sufficient to confidently extend annotation of all components of this novel metabolic module to related bacterial genera. Consequently, we implemented the Graemlin multiple-network alignment algorithm to generate cross-species predictions of genes involved in myo-inositol transport and catabolism in other α-proteobacteria. Although the chromosomal organization of genes in this functional module varied between species, the upstream regions of genes in this aligned network were enriched for the same palindromic cis-regulatory motif identified experimentally in C. crescentus. Transposon disruption of the operon encoding the computationally predicted ABC myo-inositol transporter of Sinorhizobium meliloti abolished growth on myo-inositol as the sole carbon source, confirming our cross-genera functional prediction. Thus, we have defined regulatory, transport, and catabolic genes and a cis-acting regulatory sequence that form a conserved module required for myo-inositol metabolism in select α-proteobacteria. Moreover, this study describes a forward validation of gene-network alignment, and illustrates a strategy for reliably transferring pathway-level annotation across bacterial species

Ecosystem development after mangrove wetland creation : plant–soil change across a 20-year chronosequence

This paper is not subject to U.S. copyright. The definitive version was published in Ecosystems 15 (2012): 848-866, doi:10.1007/s10021-012-9551-1.Mangrove wetland restoration and creation efforts are increasingly proposed as mechanisms to compensate for mangrove wetland losses. However, ecosystem development and functional equivalence in restored and created mangrove wetlands are poorly understood. We compared a 20-year chronosequence of created tidal wetland sites in Tampa Bay, Florida (USA) to natural reference mangrove wetlands. Across the chronosequence, our sites represent the succession from salt marsh to mangrove forest communities. Our results identify important soil and plant structural differences between the created and natural reference wetland sites; however, they also depict a positive developmental trajectory for the created wetland sites that reflects tightly coupled plant-soil development. Because upland soils and/or dredge spoils were used to create the new mangrove habitats, the soils at younger created sites and at lower depths (10–30 cm) had higher bulk densities, higher sand content, lower soil organic matter (SOM), lower total carbon (TC), and lower total nitrogen (TN) than did natural reference wetland soils. However, in the upper soil layer (0–10 cm), SOM, TC, and TN increased with created wetland site age simultaneously with mangrove forest growth. The rate of created wetland soil C accumulation was comparable to literature values for natural mangrove wetlands. Notably, the time to equivalence for the upper soil layer of created mangrove wetlands appears to be faster than for many other wetland ecosystem types. Collectively, our findings characterize the rate and trajectory of above- and below-ground changes associated with ecosystem development in created mangrove wetlands; this is valuable information for environmental managers planning to sustain existing mangrove wetlands or mitigate for mangrove wetland losses

Aboveground biomass density models for NASA's Global Ecosystem Dynamics Investigation (GEDI) lidar mission

NASA's Global Ecosystem Dynamics Investigation (GEDI) is collecting spaceborne full waveform lidar data with a primary science goal of producing accurate estimates of forest aboveground biomass density (AGBD). This paper presents the development of the models used to create GEDI's footprint-level (similar to 25 m) AGBD (GEDI04_A) product, including a description of the datasets used and the procedure for final model selection. The data used to fit our models are from a compilation of globally distributed spatially and temporally coincident field and airborne lidar datasets, whereby we simulated GEDI-like waveforms from airborne lidar to build a calibration database. We used this database to expand the geographic extent of past waveform lidar studies, and divided the globe into four broad strata by Plant Functional Type (PFT) and six geographic regions. GEDI's waveform-to-biomass models take the form of parametric Ordinary Least Squares (OLS) models with simulated Relative Height (RH) metrics as predictor variables. From an exhaustive set of candidate models, we selected the best input predictor variables, and data transformations for each geographic stratum in the GEDI domain to produce a set of comprehensive predictive footprint-level models. We found that model selection frequently favored combinations of RH metrics at the 98th, 90th, 50th, and 10th height above ground-level percentiles (RH98, RH90, RH50, and RH10, respectively), but that inclusion of lower RH metrics (e.g. RH10) did not markedly improve model performance. Second, forced inclusion of RH98 in all models was important and did not degrade model performance, and the best performing models were parsimonious, typically having only 1-3 predictors. Third, stratification by geographic domain (PFT, geographic region) improved model performance in comparison to global models without stratification. Fourth, for the vast majority of strata, the best performing models were fit using square root transformation of field AGBD and/or height metrics. There was considerable variability in model performance across geographic strata, and areas with sparse training data and/or high AGBD values had the poorest performance. These models are used to produce global predictions of AGBD, but will be improved in the future as more and better training data become available

A united statement of the global chiropractic research community against the pseudoscientific claim that chiropractic care boosts immunity.

BACKGROUND: In the midst of the coronavirus pandemic, the International Chiropractors Association (ICA) posted reports claiming that chiropractic care can impact the immune system. These claims clash with recommendations from the World Health Organization and World Federation of Chiropractic. We discuss the scientific validity of the claims made in these ICA reports. MAIN BODY: We reviewed the two reports posted by the ICA on their website on March 20 and March 28, 2020. We explored the method used to develop the claim that chiropractic adjustments impact the immune system and discuss the scientific merit of that claim. We provide a response to the ICA reports and explain why this claim lacks scientific credibility and is dangerous to the public. More than 150 researchers from 11 countries reviewed and endorsed our response. CONCLUSION: In their reports, the ICA provided no valid clinical scientific evidence that chiropractic care can impact the immune system. We call on regulatory authorities and professional leaders to take robust political and regulatory action against those claiming that chiropractic adjustments have a clinical impact on the immune system

Model for screening of resonant magnetic perturbations by plasma in a realistic tokamak geometry and its impact on divertor strike points

This work addresses the question of the relation between strike-point splitting and magnetic stochasticity at the edge of a poloidally diverted tokamak in the presence of externally imposed magnetic perturbations. More specifically, ad-hoc helical current sheets are introduced in order to mimic a hypothetical screening of the external resonant magnetic perturbations by the plasma. These current sheets, which suppress magnetic islands, are found to reduce the amount of splitting expected at the target, which suggests that screening effects should be observable experimentally. Multiple screening current sheets reinforce each other, i.e. less current relative to the case of only one current sheet is required to screen the perturbation.Comment: Accepted in the Proceedings of the 19th International Conference on Plasma Surface Interactions, to be published in Journal of Nuclear Materials. Version 2: minor formatting and text improvements, more results mentioned in the conclusion and abstrac