Minkowski distances and standardisation for clustering and classification of high dimensional data

There are many distance-based methods for classification and clustering, and for data with a high number of dimensions and a lower number of observations, processing distances is computationally advantageous compared to the raw data matrix. Euclidean distances are used as a default for continuous multivariate data, but there are alternatives. Here the so-called Minkowski distances, $L_1$ (city block)-, $L_2$ (Euclidean)-, $L_3$-, $L_4$-, and maximum distances are combined with different schemes of standardisation of the variables before aggregating them. Boxplot transformation is proposed, a new transformation method for a single variable that standardises the majority of observations but brings outliers closer to the main bulk of the data. Distances are compared in simulations for clustering by partitioning around medoids, complete and average linkage, and classification by nearest neighbours, of data with a low number of observations but high dimensionality. The $L_1$-distance and the boxplot transformation show good results.Comment: Preliminary version; final version to be published by Springer, using Springer's svmult LATEX styl

Prioritising prevention strategies for patients in antiretroviral treatment programmes in resource-limited settings

Expanded access to antiretroviral therapy (ART) offers opportunities to strengthen HIV prevention in resource-limited settings. We invited 27 ART programmes from urban settings in Africa, Asia and South America to participate in a survey, with the aim to examine what preventive services had been integrated in ART programmes. Twenty-two programmes participated; eight (36%) from South Africa, two from Brazil, two from Zambia and one each from Argentina, India, Thailand, Botswana, Ivory Coast, Malawi, Morocco, Uganda and Zimbabwe and one occupational programme of a brewery company included five countries (Nigeria, Republic of Congo, Democratic Republic of Congo, Rwanda and Burundi). Twenty-one sites (96%) provided health education and social support, and 18 (82%) provided HIV testing and counselling. All sites encouraged disclosure of HIV infection to spouses and partners, but only 11 (50%) had a protocol for partner notification. Twenty-one sites (96%) supplied male condoms, seven (32%) female condoms and 20 (91%) provided prophylactic ART for the prevention of mother-to child transmission. Seven sites (33%) regularly screened for sexually transmitted infections (STI). Twelve sites (55%) were involved in activities aimed at women or adolescents, and 10 sites (46%) in activities aimed at serodiscordant couples. Stigma and discrimination, gender roles and funding constraints were perceived as the main obstacles to effective prevention in ART programmes. We conclude that preventive services in ART programmes in lower income countries focus on health education and the provision of social support and male condoms. Strategies that might be equally or more important in this setting, including partner notification, prompt diagnosis and treatment of STI and reduction of stigma in the community, have not been implemented widely

Electroreduction of CO2/CO to C2 products: process modeling, downstream separation, system integration, and economic analysis.

Direct electrochemical reduction of CO2 to C2 products such as ethylene is more efficient in alkaline media, but it suffers from parasitic loss of reactants due to (bi)carbonate formation. A two-step process where the CO2 is first electrochemically reduced to CO and subsequently converted to desired C2 products has the potential to overcome the limitations posed by direct CO2 electroreduction. In this study, we investigated the technical and economic feasibility of the direct and indirect CO2 conversion routes to C2 products. For the indirect route, CO2 to CO conversion in a high temperature solid oxide electrolysis cell (SOEC) or a low temperature electrolyzer has been considered. The product distribution, conversion, selectivities, current densities, and cell potentials are different for both CO2 conversion routes, which affects the downstream processing and the economics. A detailed process design and techno-economic analysis of both CO2 conversion pathways are presented, which includes CO2 capture, CO2 (and CO) conversion, CO2 (and CO) recycling, and product separation. Our economic analysis shows that both conversion routes are not profitable under the base case scenario, but the economics can be improved significantly by reducing the cell voltage, the capital cost of the electrolyzers, and the electricity price. For both routes, a cell voltage of 2.5 V, a capital cost of $10,000/m2, and an electricity price of <$20/MWh will yield a positive net present value and payback times of less than 15 years. Overall, the high temperature (SOEC-based) two-step conversion process has a greater potential for scale-up than the direct electrochemical conversion route. Strategies for integrating the electrochemical CO2/CO conversion process into the existing gas and oil infrastructure are outlined. Current barriers for industrialization of CO2 electrolyzers and possible solutions are discussed as well

An expanded diversity of oomycetes in Carboniferous forests: Reinterpretation of Oochytrium lepidodendri (Renault 1894) from the Esnost chert, Massif Central, France

335–330 million-year-old cherts from the Massif Central, France, contain exceptionally well-preserved remains of an early forest ecosystem, including plants, fungi and other microorganisms. Here we reinvestigate the original material prepared by Renault and Roche from collections of the Muséum National d’Histoire Naturelle, Paris, and present a re-evaluation of Oochytrium lepidodendri (Renault 1894), originally described as a zoosporic fungus. Confocal laser scanning microscopy (CLSM) was used to study the microfossils, enabling us in software to digitally reconstruct them in three-dimensional detail. We reinterpret O. lepidodendri as a pseudofungus and favour placement within the oomycetes, a diverse clade of saprotrophs and both animal and plant parasites. Phylogenetically, O. lepidodendri appears to belong to a group of oomycetes distinct from those previously described from Paleozoic rocks and most likely related to the Peronosporales s.l. This study adds to our knowledge of Paleozoic eukaryotic diversity and reinforces the view that oomycetes were early and diverse constituents of terrestrial biotas, playing similar ecological roles to those they perform in modern ecosystems

Accurate reconstruction of insertion-deletion histories by statistical phylogenetics

The Multiple Sequence Alignment (MSA) is a computational abstraction that represents a partial summary either of indel history, or of structural similarity. Taking the former view (indel history), it is possible to use formal automata theory to generalize the phylogenetic likelihood framework for finite substitution models (Dayhoff's probability matrices and Felsenstein's pruning algorithm) to arbitrary-length sequences. In this paper, we report results of a simulation-based benchmark of several methods for reconstruction of indel history. The methods tested include a relatively new algorithm for statistical marginalization of MSAs that sums over a stochastically-sampled ensemble of the most probable evolutionary histories. For mammalian evolutionary parameters on several different trees, the single most likely history sampled by our algorithm appears less biased than histories reconstructed by other MSA methods. The algorithm can also be used for alignment-free inference, where the MSA is explicitly summed out of the analysis. As an illustration of our method, we discuss reconstruction of the evolutionary histories of human protein-coding genes.Comment: 28 pages, 15 figures. arXiv admin note: text overlap with arXiv:1103.434

Provision of antiretroviral treatment in conflict settings: the experience of Médecins Sans Frontières

ABSTRACT: INTRODUCTION: Many countries ravaged by conflict have substantial morbidity and mortality attributed to HIV/AIDS yet HIV treatment is uncommonly available. Universal access to HIV care cannot be achieved unless the needs of populations in conflict-affected areas are addressed. METHODS: From 2003 Médecins Sans Frontières introduced HIV care, including antiretroviral therapy, into 24 programmes in conflict or post-conflict settings, mainly in sub-Saharan Africa. HIV care and treatment activities were usually integrated within other medical activities. Project data collected in the Fuchia software system were analysed and outcomes compared with ART-LINC data. Programme reports and other relevant documents and interviews with local and headquarters staff were used to develop lessons learned. RESULTS: In the 22 programmes where ART was initiated, more than 10,500 people were diagnosed with HIV and received medical care, and 4555 commenced antiretroviral therapy, including 348 children. Complete data were available for adults in 20 programmes (n = 4145). At analysis, 2645 (64%) remained on ART, 422 (10%) had died, 466 (11%) lost to follow-up, 417 (10%) transferred to another programme, and 195 (5%) had an unclear outcome. Median 12-month mortality and loss to follow-up were 9% and 11% respectively, and median 6-month CD4 gain was 129 cells/mm 3.Patient outcomes on treatment were comparable to those in stable resource-limited settings, and individuals and communities obtained significant benefits from access to HIV treatment. Programme disruption through instability was uncommon with only one program experiencing interruption to services, and programs were adapted to allow for disruption and population movements. Integration of HIV activities strengthened other health activities contributing to health benefits for all victims of conflict and increasing the potential sustainability for implemented activities. CONCLUSIONS: With commitment, simplified treatment and monitoring, and adaptations for potential instability, HIV treatment can be feasibly and effectively provided in conflict or post-conflict settings

Postapproval trials versus patient registries:comparability of advanced melanoma patients with brain metastases

Postapproval trials and patient registries have their pros and cons in the generation of postapproval data. No direct comparison between clinical outcomes of these data sources currently exists for advanced melanoma patients. We aimed to investigate whether a patient registry can complement or even replace postapproval trials. Postapproval single-arm clinical trial data from the Medicines Evaluation Board and real-world data from the Dutch Melanoma Treatment Registry were used. The study population consisted of advanced melanoma patients with brain metastases treated with targeted therapies (BRAF- or BRAF-MEK inhibitors) in the first line. A Cox hazard regression model and a propensity score matching (PSM) model were used to compare the two patient populations. Compared to patients treated in postapproval trials (n = 467), real-world patients (n = 602) had significantly higher age, higher ECOG performance status, more often ≥3 organ involvement and more symptomatic brain metastases. Lactate dehydrogenase levels were similar between both groups. The unadjusted median overall survival (mOS) in postapproval clinical trial patients was 8.7 (95% CI, 8.1-10.4) months compared to 7.2 (95% CI, 6.5-7.7) months (P < 0.01) in real-world patients. With the Cox hazard regression model, survival was adjusted for prognostic factors, which led to a statistically insignificant difference in mOS for trial and real-world patients of 8.7 (95% CI, 7.9-10.4) months compared to 7.3 (95% CI, 6.3-7.9) months, respectively. The PSM model resulted in 310 matched patients with similar survival (P = 0.9). Clinical outcomes of both data sources were similar. Registries could be a complementary data source to postapproval clinical trials to establish information on clinical outcomes in specific subpopulations

Perceptions of involvement in advance care planning and emotional functioning in patients with advanced cancer

Purpose: Advance Care Planning (ACP) is positively associated with the quality of care, but its impact on emotional functioning is ambiguous. This study investigated the association between perceptions of ACP involvement and emotional functioning in patients with advanced cancer. Methods: This study analyzed baseline data of 1,001 patients of the eQuiPe study, a prospective, longitudinal, multicenter, observational study on quality of care and quality of life in patients with advanced cancer in the Netherlands. Patients with metastatic solid cancer were asked to participate between November 2017 and January 2020. Patients’ perceptions of ACP involvement were measured by three self-administered statements. Emotional functioning was measured by the EORTC-QLQ-C30. A linear multivariable regression analysis was performed while taking gender, age, migrant background, education, marital status, and symptom burden into account. Results: The majority of patients (87%) reported that they were as much involved as they wanted to be in decisions about their future medical treatment and care. Most patients felt that their relatives (81%) and physicians (75%) were familiar with their preferences for future medical treatment and care. A positive association was found between patients’ perceptions of ACP involvement and their emotional functioning (b=0.162, p<0.001, 95%CI[0.095;0.229]) while controlling for relevant confounders. Conclusions: Perceptions of involvement in ACP are positively associated with emotional functioning in patients with advanced cancer. Future studies are needed to further investigate the effect of ACP on emotional functioning. Trial registration number: NTR6584 Date of registration: 30 June 2017 Implications for Cancer Survivors: Patients’ emotional functioning might improve from routine discussions regarding goals of future care. Therefore, integration of ACP into palliative might be promising

US Cosmic Visions: New Ideas in Dark Matter 2017: Community Report

This white paper summarizes the workshop "U.S. Cosmic Visions: New Ideas in Dark Matter" held at University of Maryland on March 23-25, 2017.Comment: 102 pages + reference

Advances in GPCR modeling evaluated by the GPCR Dock 2013 assessment: Meeting new challenges

© 2014 Elsevier Ltd All rights reserved. Despite tremendous successes of GPCR crystallography, the receptors with available structures represent only a small fraction of human GPCRs. An important role of the modeling community is to maximize structural insights for the remaining receptors and complexes. The community-wide GPCR Dock assessment was established to stimulate and monitor the progress in molecular modeling and ligand docking for GPCRs. The four targets in the present third assessment round presented new and diverse challenges for modelers, including prediction of allosteric ligand interaction and activation states in 5-hydroxytryptamine receptors 1B and 2B, and modeling by extremely distant homology for smoothened receptor. Forty-four modeling groups participated in the assessment. State-of-the-art modeling approaches achieved close-to-experimental accuracy for small rigid orthosteric ligands and models built by close homology, and they correctly predicted protein fold for distant homology targets. Predictions of long loops and GPCR activation states remain unsolved problems