A Cross-Sectional Survey of the Knowledge, Attitudes, and Practices of Antimicrobial Users and Providers in an Area of High-Density Livestock-Human Population in Western Kenya.

Background: Antimicrobial resistance (AMR) is one of the most important global health crises in recent times and is driven primarily by antimicrobial consumption. In East Africa, there is a paucity of data regarding the knowledge, attitudes, and practices (KAP) related to antimicrobial use (AMU). We investigate the ways in which antimicrobial users in the veterinary sector accessed veterinary antimicrobials, and common behaviors of veterinary antimicrobial users and prescribers associated with AMU and AMR. Methods: In total, 70 farmers, staff at 49 agricultural-veterinary antimicrobial shops (agrovet staff) and 28 veterinary animal healthcare workers or veterinary surgeons (veterinary professionals) were interviewed in Busia county, western Kenya in 2016 using a standard questionnaire as a framework for structured interviews. Data recorded included participant demographics, level of education, access to and sources of veterinary antimicrobials, prescribing patterns, and knowledge of AMR and antimicrobial withdrawal periods. Results: The majority of antimicrobials were accessed through informal means, purchased from agroveterinary shops; more than half of staff did not hold nationally mandated qualifications to advise on or sell veterinary antimicrobials. Approximately 40% of veterinary antimicrobials were sold without a prescription and it was noted that both price and customer preference were important factors when selling antimicrobials in almost all agrovet shops. Knowledge of the dangers associated with AMR and AMU were mostly superficial. Treatment failure occurred often, and there was a lack of differentiation between AMR and simply treatment failure. Conclusion: In this study area in East Africa with high-density human and livestock populations, AMU was primarily for maintenance of livestock health. These findings have highlighted several aspects surrounding inappropriate access to antimicrobials, and as such require attention from policy makers concerned with AMR in both livestock and human medicine sectors. Improving prescribing practices and ensuring a minimum level of general education and awareness of prescribers, as well as expanding the role of agrovet staff in antimicrobial stewardship programmes, may help begin to mitigate the maintenance and transmission of AMR, particularly amongst livestock

Evidence from Detrital Zircon Ages for Middle Pennsylvanian Uplift and Drainage in the Source Area of the Chariton Conglomerate and Marmaton Group Sandstones, Southern Iowa and Northern Missouri

The Chariton Conglomerate is a quartz/limestone conglomerate of Middle Pennsylvanian age sparsely exposed in southern Iowa and northern Missouri. In Iowa it is characterized by quartz granules and rounded crinoid columnals. The objective of this study was to use detrital zircon ages to determine the provenance of the Chariton Conglomerate and possibly associated Marmaton Group sandstone beds. Detrital zircon ages were obtained for five conglomerate and two sandstone beds of the Chariton Conglomerate in Iowa, three conglomerate beds of the Chariton Conglomerate in Missouri, and two sandstone beds of the Marmaton Group in Iowa. According to the Kolmogorov-Smirnoff Test, the 12 detrital zircon age spectra were statistically indistinguishable, consistent with a common provenance for all beds. The combined age spectrum (879 zircons) showed both a young cluster (1.1 % of zircons) in the range 320-364 Ma (Late Devonian Period - Late Mississippian Subperiod) and a much older cluster (0.3% of zircons) in the range 3198-3269 Ma (Paleoarchean - Mesoarchean Eras). The Devonian Period - Mississippian Subperiod (318--416 Ma) and the Paleoarchean-Mesoarchean Eras (2800-3600 Ma) accounted for 2.8% and 3.6% of zircon ages, respectively. A model consistent with the above ages and the paleocurrent directions in the Chariton Conglomerate is an Early - Middle Pennsylvanian river originating in the Devonian - Mississippian crystalline rocks of New England and entering Minnesota - Wisconsin from the northeast to collect sediments from crystalline rocks of Paleoarchean - Mesoarchean age. However, a Middle Pennsylvanian uplift in the Minnesota - Wisconsin region is also required to produce the headwaters necessary for the production of quartz granules, which is consistent with the model of hotspot epeirogen

Cellular Models of Aggregation-Dependent Template-Directed Proteolysis to Characterize Tau Aggregation Inhibitors for Treatment of Alzheimer's Disease

Copyright © 2015, The American Society for Biochemistry and Molecular Biology. Acknowledgements-We thank Drs Timo Rager and Rolf Hilfiker (Solvias, Switzerland) for polymorph analyses.Peer reviewedPublisher PD

Raising argument strength using negative evidence: A constraint on models of induction

Both intuitively, and according to similarity-based theories of induction, relevant evidence raises argument strength when it is positive and lowers it when it is negative. In three experiments, we tested the hypothesis that argument strength can actually increase when negative evidence is introduced. Two kinds of argument were compared through forced choice or sequential evaluation: single positive arguments (e.g., “Shostakovich’s music causes alpha waves in the brain; therefore, Bach’s music causes alpha waves in the brain”) and double mixed arguments (e.g., “Shostakovich’s music causes alpha waves in the brain, X’s music DOES NOT; therefore, Bach’s music causes alpha waves in the brain”). Negative evidence in the second premise lowered credence when it applied to an item X from the same subcategory (e.g., Haydn) and raised it when it applied to a different subcategory (e.g., AC/DC). The results constitute a new constraint on models of induction

HIV-1 Evolutionary Dynamics under Nonsuppressive Antiretroviral Therapy

Prolonged virologic failure on 2nd-line protease inhibitor (PI)-based antiretroviral therapy (ART) without emergence of major protease mutations is well recognized and provides an opportunity to study within-host evolution in long-term viremic individuals. Using next-generation sequencing and in silico haplotype reconstruction, we analyzed whole-genome sequences from longitudinal plasma samples of eight chronically infected HIV-1-positive individuals failing 2nd-line regimens from the French National Agency for AIDS and Viral Hepatitis Research (ANRS) 12249 Treatment as Prevention (TasP) trial. On nonsuppressive ART, there were large fluctuations in synonymous and nonsynonymous variant frequencies despite stable viremia. Reconstructed haplotypes provided evidence for selective sweeps during periods of partial adherence, and viral haplotype competition, during periods of low drug exposure. Drug resistance mutations in reverse transcriptase (RT) were used as markers of viral haplotypes in the reservoir, and their distribution over time indicated recombination. We independently observed linkage disequilibrium decay, indicative of recombination. These data highlight dramatic changes in virus population structure that occur during stable viremia under nonsuppressive ART. IMPORTANCE HIV-1 infections are most commonly initiated with a single founder virus and are characterized by extensive inter- and intraparticipant genetic diversity. However, existing literature on HIV-1 intrahost population dynamics is largely limited to untreated infections, predominantly in subtype B-infected individuals. The manuscript characterizes viral population dynamics in long-term viremic treatment-experienced individuals, which has not been previously characterized. These data are particularly relevant for understanding HIV dynamics but can also be applied to other RNA viruses. With this unique data set we propose that the virus is highly unstable, and we have found compelling evidence of HIV-1 within-host viral diversification, recombination, and haplotype competition during nonsuppressive ART

HIV transmission dynamics and population-wide drug resistance in rural South Africa

Despite expanded antiretroviral therapy (ART) in South Africa, HIV-1 transmission persists. Integrase strand transfer inhibitors (INSTI) and long-acting injectables offer potential for superior viral suppression, but pre-existing drug resistance could threaten their effectiveness. In a community-based study in rural KwaZulu-Natal, prior to widespread INSTI usage, we enroled 18,025 individuals to characterise HIV-1 drug resistance and transmission networks to inform public health strategies. HIV testing and reflex viral load quantification were performed, with deep sequencing (20% variant threshold) used to detect resistance mutations. Phylogenetic and geospatial analyses characterised transmission clusters. One-third of participants were HIV-positive, with 21.7% having detectable viral loads; 62.1% of those with detectable viral loads were ART-naïve. Resistance to older reverse transcriptase (RT)-targeting drugs was found, but INSTI resistance remained low (<1%). Non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance, particularly to rilpivirine (RPV) even in ART-naïve individuals, was concerning. Twenty percent of sequenced individuals belonged to transmission clusters, with geographic analysis highlighting higher clustering in peripheral and rural areas. Our findings suggest promise for INSTI-based strategies in this setting but underscore the need for RPV resistance screening before implementing long-acting cabotegravir (CAB) + RPV. The significant clustering emphasises the importance of geographically targeted interventions to effectively curb HIV-1 transmission

High prevalence of integrase mutation L74I in West African HIV-1 subtypes prior to integrase inhibitor treatment.

OBJECTIVES: HIV-1 integrase inhibitors are recommended as first-line therapy by WHO, though efficacy and resistance data for non-B subtypes are limited. Two recent trials have identified the integrase L74I mutation to be associated with integrase inhibitor treatment failure in HIV-1 non-B subtypes. We sought to define the prevalence of integrase resistance mutations, including L74I, in West Africa. METHODS: We studied a Nigerian cohort of recipients prior to and during receipt of second-line PI-based therapy, who were integrase inhibitor-naive. Illumina next-generation sequencing with target enrichment was used on stored plasma samples. Drug resistance was interpreted using the Stanford Resistance Database and the IAS-USA 2019 mutation lists. RESULTS: Of 115 individuals, 59.1% harboured CRF02_AG HIV-1 and 40.9% harboured subtype G HIV-1. Four participants had major IAS-USA integrase resistance-associated mutations detected at low levels (2%-5% frequency). Two had Q148K minority variants and two had R263K (one of whom also had L74I). L74I was detected in plasma samples at over 2% frequency in 40% (46/115). Twelve (26.1%) had low-level minority variants of between 2% and 20% of the viral population sampled. The remaining 34 (73.9%) had L74I present at >20% frequency. L74I was more common among those with subtype G infection (55.3%, 26/47) than those with CRF02_AG infection (29.4%, 20/68) (P = 0.005). CONCLUSIONS: HIV-1 subtypes circulating in West Africa appear to have very low prevalence of major integrase mutations, but significant prevalence of L74I. A combination of in vitro and clinical studies is warranted to understand the potential implications.K.E.B. is supported by Wellcome Trust award number 170461. N.N. is supported by NIH R01 AI147331-01. R.K.G. is supported by a Wellcome Trust Senior Fellowship in Clinical Science (WT108082AIA). This study was supported by the President’s Emergency Plan for AIDS Relief (PEPFAR) through the Centers for Disease Control and Prevention (CDC) under the terms of U2G GH002099-01 and PA GH17-1753 (ACHIEVE)

Acoustic and oceanographic observations and configuration information for the WHOI moorings from the SW06 experiment

This document describes data, sensors, and other useful information pertaining to the moorings that were deployed from the R/V Knorr from July 24th to August 4th, 2006 in support of the SW06 experiment. The SW06 experiment was a large, multi-disciplinary effort performed 100 miles east of the New Jersey coast. A total of 62 acoustic and oceanographic moorings were deployed and recovered. The moorings were deployed in a “T” geometry to create an along-shelf path along the 80 meter isobath and an across-shelf path starting at 600 meters depth and going shoreward to a depth of 60 meters. A cluster of moorings was placed at the intersection of the two paths to create a dense sensor-populated area to measure a 3-dimensional physical oceanography. Environmental moorings were deployed along both along-shelf and across-shelf paths to measure the physical oceanography along those paths. Moorings with acoustic sources were placed at the outer ends of the “T” to propagate various signals along these paths. Five single hydrophone receivers were positioned on the across shelf path and a vertical and horizontal hydrophone array was positioned at the intersection of the “T” to get receptions from all the acoustics assets that were used during SW06.Funding was provided by the Office of Naval Research under Contract No. N00014-04-1014

Organism-sediment interactions govern post-hypoxia recovery of ecosystem functioning

Hypoxia represents one of the major causes of biodiversity and ecosystem functioning loss for coastal waters. Since eutrophication-induced hypoxic events are becoming increasingly frequent and intense, understanding the response of ecosystems to hypoxia is of primary importance to understand and predict the stability of ecosystem functioning. Such ecological stability may greatly depend on the recovery patterns of communities and the return time of the system properties associated to these patterns. Here, we have examined how the reassembly of a benthic community contributed to the recovery of ecosystem functioning following experimentally-induced hypoxia in a tidal flat. We demonstrate that organism-sediment interactions that depend on organism size and relate to mobility traits and sediment reworking capacities are generally more important than recovering species richness to set the return time of the measured sediment processes and properties. Specifically, increasing macrofauna bioturbation potential during community reassembly significantly contributed to the recovery of sediment processes and properties such as denitrification, bedload sediment transport, primary production and deep pore water ammonium concentration. Such bioturbation potential was due to the replacement of the small-sized organisms that recolonised at early stages by large-sized bioturbating organisms, which had a disproportionately stronger influence on sediment. This study suggests that the complete recovery of organism-sediment interactions is a necessary condition for ecosystem functioning recovery, and that such process requires long periods after disturbance due to the slow growth of juveniles into adult stages involved in these interactions. Consequently, repeated episodes of disturbance at intervals smaller than the time needed for the system to fully recover organism-sediment interactions may greatly impair the resilience of ecosystem functioning.