Seriation and Multidimensional Scaling: A Data Analysis Approach to Scaling Asymmetric Proximity Matrices

A number of model-based scaling methods have been developed that apply to asymmetric proximity matrices. A flexible data analysis approach is pro posed that combines two psychometric procedures— seriation and multidimensional scaling (MDS). The method uses seriation to define an empirical order ing of the stimuli, and then uses MDS to scale the two separate triangles of the proximity matrix defined by this ordering. The MDS solution con tains directed distances, which define an "extra" dimension that would not otherwise be portrayed, because the dimension comes from relations between the two triangles rather than within triangles. The method is particularly appropriate for the analysis of proximities containing temporal information. A major difficulty is the computa tional intensity of existing seriation algorithms, which is handled by defining a nonmetric seriation algorithm that requires only one complete itera tion. The procedure is illustrated using a matrix of co-citations between recent presidents of the Psychometric Society.Yeshttps://us.sagepub.com/en-us/nam/manuscript-submission-guideline

The Depsipeptide Romidepsin Reverses HIV-1 Latency In Vivo.

UNLABELLED: Pharmacologically-induced activation of replication competent proviruses from latency in the presence of antiretroviral treatment (ART) has been proposed as a step towards curing HIV-1 infection. However, until now, approaches to reverse HIV-1 latency in humans have yielded mixed results. Here, we report a proof-of-concept phase Ib/IIa trial where 6 aviremic HIV-1 infected adults received intravenous 5 mg/m2 romidepsin (Celgene) once weekly for 3 weeks while maintaining ART. Lymphocyte histone H3 acetylation, a cellular measure of the pharmacodynamic response to romidepsin, increased rapidly (maximum fold range: 3.7-7.7 relative to baseline) within the first hours following each romidepsin administration. Concurrently, HIV-1 transcription quantified as copies of cell-associated un-spliced HIV-1 RNA increased significantly from baseline during treatment (range of fold-increase: 2.4-5.0; p = 0.03). Plasma HIV-1 RNA increased from <20 copies/mL at baseline to readily quantifiable levels at multiple post-infusion time-points in 5 of 6 patients (range 46-103 copies/mL following the second infusion, p = 0.04). Importantly, romidepsin did not decrease the number of HIV-specific T cells or inhibit T cell cytokine production. Adverse events (all grade 1-2) were consistent with the known side effects of romidepsin. In conclusion, romidepsin safely induced HIV-1 transcription resulting in plasma HIV-1 RNA that was readily detected with standard commercial assays demonstrating that significant reversal of HIV-1 latency in vivo is possible without blunting T cell-mediated immune responses. These finding have major implications for future trials aiming to eradicate the HIV-1 reservoir. TRIAL REGISTRATION: clinicaltrials.gov NTC02092116

Recent Asian origin of chytrid fungi causing global amphibian declines

Globalized infectious diseases are causing species declines worldwide, but their source often remains elusive. We used whole-genome sequencing to solve the spatiotemporal origins of the most devastating panzootic to date, caused by the fungus Batrachochytrium dendrobatidis, a proximate driver of global amphibian declines. We traced the source of B. dendrobatidis to the Korean peninsula, where one lineage, BdASIA-1, exhibits the genetic hallmarks of an ancestral population that seeded the panzootic. We date the emergence of this pathogen to the early 20th century, coinciding with the global expansion of commercial trade in amphibians, and we show that intercontinental transmission is ongoing. Our findings point to East Asia as a geographic hotspot for B. dendrobatidis biodiversity and the original source of these lineages that now parasitize amphibians worldwide

OpenSAFELY: The impact of COVID‐19 on azathioprine, leflunomide and methotrexate monitoring, and factors associated with change in monitoring rate

Aims The COVID-19 pandemic created unprecedented pressure on healthcare services. This study investigates whether disease-modifying antirheumatic drug (DMARD) safety monitoring was affected during the COVID-19 pandemic. Methods A population-based cohort study was conducted using the OpenSAFELY platform to access electronic health record data from 24.2 million patients registered at general practices using TPP's SystmOne software. Patients were included for further analysis if prescribed azathioprine, leflunomide or methotrexate between November 2019 and July 2022. Outcomes were assessed as monthly trends and variation between various sociodemographic and clinical groups for adherence with standard safety monitoring recommendations. Results An acute increase in the rate of missed monitoring occurred across the study population (+12.4 percentage points) when lockdown measures were implemented in March 2020. This increase was more pronounced for some patient groups (70–79 year-olds: +13.7 percentage points; females: +12.8 percentage points), regions (North West: +17.0 percentage points), medications (leflunomide: +20.7 percentage points) and monitoring tests (blood pressure: +24.5 percentage points). Missed monitoring rates decreased substantially for all groups by July 2022. Consistent differences were observed in overall missed monitoring rates between several groups throughout the study. Conclusion DMARD monitoring rates temporarily deteriorated during the COVID-19 pandemic. Deterioration coincided with the onset of lockdown measures, with monitoring rates recovering rapidly as lockdown measures were eased. Differences observed in monitoring rates between medications, tests, regions and patient groups highlight opportunities to tackle potential inequalities in the provision or uptake of monitoring services. Further research should evaluate the causes of the differences identified between groups

O período da contaminação com petróleo influencia a rebrota de Echinochloa polystachya (H.B.K.) Hitchcock em solo de várzea da Amazônia central?

Several factors may influence the impact of oil on the environment. However, although it is understood that the effect of pollutants may change throughout the year according to seasonal variations in environmental parameters, this effect is poorly studied in the tropical region. The effects of Urucu's crude oil on the vegetative propagation and growth of Echinochloa polystachya were evaluated in a 63 days period, in two experiments, "A" (July-September) and "B" (September-November) planting the species in a greenhouse. In both experiments parts of stems were placed in 2 L of várzea soil contaminated by 6 oil doses, ranging from 0 to 0.231 L oil m-2 soil. In response to dosage increase there was a decrease of total biomass, ratio of live /total biomass, the leaf length and number of leaves. The period of planting influenced the response of plants to the dosage applied due to climate change, with negative effects in the "B" period of higher temperatures. We concluded that the exposure period influence the vegetative propagation and growth of the seedlings, being a spill in the period of the higher temperatures more dangerous for this specie