Recent Archeological Work in Kachemak Bay, Gulf of Alaska

Excavations since 1974 have built upon de Laguna's pioneering classification of Pacific Eskimo prehistory. The Chugachik site (SEL 033) yielded abundant artifactual and paleoenvironmental information dated mainly between c. 350 B.C. and 250 A.D. While artifacts were scarce at Cottonwood Creek (SEL 030), dated at about 200 A.D., data on human biology, paleopathology, social stratification and mortuary ceremonialism were recovered. The Yukon Island Fox Farm Bluff site (SEL 041) dates to c. 500-900 A.D. and yielded a new culture showing connections with the Alaska Peninsula. Future research should focus on the earlier prehistory of the bay, the classic problem of the Pacific Eskimo-Tanaina Athapaskan transition, and the paleoenvironmental record

Analysis of queries from nurses to the South African National HIV & TB Health Care Worker Hotline

Background. Since 2008, the Medicines Information Centre (MIC) has run the South African National HIV & TB Health Care Worker Hotline which provides free information on patient treatment to all healthcare workers in South Africa. With the introduction of nurse-initiated management of antiretroviral therapy (NIMART) in the public sector, the need for easy access to HIV and tuberculosis (TB) information has increased, especially among nurses. The hotline aims to provide this, most importantly to nurses in rural areas, where clinical staff often have little access to peer review. Objective. To describe the queries received from nurses by the hotline between 1 March and 31 May 2012 and identify problem areas and knowledge gaps where nurses may require further training. Methods. All queries received from nurses during the study period were analysed. An experienced information pharmacist reviewed all queries to identify knowledge gaps. Results. During the study period, the hotline received a total of 1 479 HIV- and TB-related queries from healthcare workers. Of these, 386 were received from nurses, of which 254 (66%) were NIMART-trained. The most common query subtopic was initiating antiretroviral therapy (ART) (20%), followed by adverse drug reactions (18%). The most common knowledge gap identified was the ability to interpret laboratory results before initiating ART (10%). Discussion. We conclude that the hotline is providing clinical help to an increasing number of nurses on the topic of treating HIV and TB throughout South Africa. In addition, queries directed to the hotline may assist in identifying knowledge gaps for the further training of nurses

An examination of the perceived impact of a continuing interprofessional education experience on opiate prescribing practices

Chronic pain is increasingly recognized as a public health problem. We assessed the effectiveness of a multi-modal, interprofessional educational approach aimed at empowering healthcare professionals to make deliberative changes, especially in opiate prescribing practices. Education activities included enduring webcasts, regional interprofessional roundtable events, and state-level conference presentations within targeted Kentucky and West Virginia regions of the United States. Over 1,000 participants accessed the various activities. For the live events, the largest groups reached included nurses (38.1%), nurse practitioners (31.2%), and physicians (22.1%). In addition to our reach, higher levels of educational effectiveness were measured, specifically, learner’s intentions to change practice patterns, confidence in meeting patient’s needs, and knowledge of pain management guidelines. The majority of the conference (58%) and roundtable (69%) participants stated they intend to make a practice change in one or more areas of chronic pain patient management in post-event evaluation. Differences in pre- and post-activity responses on the measures of confidence and knowledge, with additional comparison to a control population who were not in attendance, were analyzed using non-parametric tests of significance. While neither activity produced significant changes in confidence from pre-activity, participants were more confident post-activity than their control group peers. There were significant changes in knowledge for both live event and webcast participants. Impactful chronic pain continuing the education that emphasizes collaborative care is greatly needed; these results show that the approaches taken here can impact learner’s knowledge and confidence, and hold potential for creating change in how opioid prescribing is managed

Subgenual activation and the finger of blame: individual differences and depression vulnerability.

BACKGROUND: Subgenual cingulate cortex (SCC) responses to self-blaming emotion-evoking stimuli were previously found in individuals prone to self-blame with and without a history of major depressive disorder (MDD). This suggested SCC activation reflects self-blaming emotions such as guilt, which are central to models of MDD vulnerability. METHOD: Here, we re-examined these hypotheses in an independent larger sample. A total of 109 medication-free participants (70 with remitted MDD and 39 healthy controls) underwent fMRI whilst judging self- and other-blaming emotion-evoking statements. They also completed validated questionnaires of proneness to self-blaming emotions including those related to internal (autonomy) and external (sociotropy) evaluation, which were subjected to factor analysis. RESULTS: An interaction between group (remitted MDD v. Control) and condition (self- v. other-blame) was observed in the right SCC (BA24). This was due to higher SCC signal for self-blame in remitted MDD and higher other-blame-selective activation in Control participants. Across the whole sample, extracted SCC activation cluster averages for self- v. other-blame were predicted by a regression model which included the reliable components derived from our factor analysis of measures of proneness to self-blaming emotions. Interestingly, this prediction was solely driven by autonomy/self-criticism, and adaptive guilt factors, with no effect of sociotropy/dependency. CONCLUSIONS: Despite confirming the prediction of SCC activation in self-blame-prone individuals and those vulnerable to MDD, our results suggest that SCC activation reflects blame irrespective of where it is directed rather than selective for self. We speculate that self-critical individuals have more extended SCC representations for blame in the context of self-agency

A DNA-binding-site landscape and regulatory network analysis for NAC transcription factors in Arabidopsis thaliana.

Target gene identification for transcription factors is a prerequisite for the systems wide understanding of organismal behaviour. NAM-ATAF1/2-CUC2 (NAC) transcription factors are amongst the largest transcription factor families in plants, yet limited data exist from unbiased approaches to resolve the DNA-binding preferences of individual members. Here, we present a TF-target gene identification workflow based on the integration of novel protein binding microarray data with gene expression and multi-species promoter sequence conservation to identify the DNA-binding specificities and the gene regulatory networks of 12 NAC transcription factors. Our data offer specific single-base resolution fingerprints for most TFs studied and indicate that NAC DNA-binding specificities might be predicted from their DNA-binding domain's sequence. The developed methodology, including the application of complementary functional genomics filters, makes it possible to translate, for each TF, protein binding microarray data into a set of high-quality target genes. With this approach, we confirm NAC target genes reported from independent in vivo analyses. We emphasize that candidate target gene sets together with the workflow associated with functional modules offer a strong resource to unravel the regulatory potential of NAC genes and that this workflow could be used to study other families of transcription factors

Safety and tolerability of single low-dose primaquine in a low-intensity transmission area in South Africa: an open-label, randomized controlled trial

Abstract Background To reduce onward falciparum malaria transmission, the World Health Organization recommends adding single low-dose (SLD) primaquine to artemisinin-based combination treatment in low transmission areas. However, uptake of this recommendation has been relatively slow given concerns about whether individual risks justify potential community benefit. This study was undertaken to generate comprehensive local data on the risk–benefit profile of SLD primaquine deployment in a pre-elimination area in South Africa. Methods This randomized, controlled open-label trial investigated adding a single low primaquine dose on day 3 to standard artemether–lumefantrine treatment for uncomplicated falciparum malaria. Efficacy, safety and tolerability of artemether–lumefantrine and primaquine treatment were assessed on days 3, 7, 14, 28 and 42. Lumefantrine concentrations were assayed from dried blood spot samples collected on day 7. Results Of 217 patients screened, 166 were enrolled with 140 randomized on day 3, 70 to each study arm (primaquine and no primaquine). No gametocytes were detected by either microscopy or PCR in any of the follow-up samples collected after randomization on day 3, precluding assessment of primaquine efficacy. Prevalence of the CYP2D6*4, CYP2D6*10 and CYP2D6*17 mutant alleles was low with allelic frequencies of 0.02, 0.11 and 0.16, respectively; none had the CYP2D6*4/*4 variant associated with null activity. Among 172 RDT-positive patients G6PD-genotyped, 24 (14%) carried the G6PD deficient (A−) variant. Median haemoglobin concentrations were similar between treatment arms throughout follow-up. A third of participants had a haemoglobin drop > 2 g/dL; this was not associated with primaquine treatment but may be associated with G6PD genotype [52.9% (9/17) with A− genotype vs. 31% (36/116) with other genotypes (p = 0.075)]. Day 7 lumefantrine concentrations and the number and nature of adverse events were similar between study arms; only one serious adverse event occurred (renal impairment in the no primaquine arm). The artemether–lumefantrine PCR-corrected adequate clinical and parasitological response rate was 100%, with only one re-infection found among the 128 patients who completed 42-day follow-up. Conclusions Safety, tolerability, CYP2D6 and G6PD variant data from this study support the deployment of the WHO-recommended SLD primaquine without G6PD testing to advance malaria elimination in South African districts with low-intensity residual transmission. Trial registration Pan African Clinical Trial Registry, PACTR201611001859416. Registered 11 November 2016, https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=185

Population Pharmacokinetic Properties of Piperaquine in Falciparum Malaria: An Individual Participant Data Meta-Analysis.

BACKGROUND: Artemisinin-based combination therapies (ACTs) are the mainstay of the current treatment of uncomplicated Plasmodium falciparum malaria, but ACT resistance is spreading across Southeast Asia. Dihydroartemisinin-piperaquine is one of the five ACTs currently recommended by the World Health Organization. Previous studies suggest that young children (<5 y) with malaria are under-dosed. This study utilised a population-based pharmacokinetic approach to optimise the antimalarial treatment regimen for piperaquine. METHODS AND FINDINGS: Published pharmacokinetic studies on piperaquine were identified through a systematic literature review of articles published between 1 January 1960 and 15 February 2013. Individual plasma piperaquine concentration-time data from 11 clinical studies (8,776 samples from 728 individuals) in adults and children with uncomplicated malaria and healthy volunteers were collated and standardised by the WorldWide Antimalarial Resistance Network. Data were pooled and analysed using nonlinear mixed-effects modelling. Piperaquine pharmacokinetics were described successfully by a three-compartment disposition model with flexible absorption. Body weight influenced clearance and volume parameters significantly, resulting in lower piperaquine exposures in small children (<25 kg) compared to larger children and adults (≥25 kg) after administration of the manufacturers' currently recommended dose regimens. Simulated median (interquartile range) day 7 plasma concentration was 29.4 (19.3-44.3) ng/ml in small children compared to 38.1 (25.8-56.3) ng/ml in larger children and adults, with the recommended dose regimen. The final model identified a mean (95% confidence interval) increase of 23.7% (15.8%-32.5%) in piperaquine bioavailability between each piperaquine dose occasion. The model also described an enzyme maturation function in very young children, resulting in 50% maturation at 0.575 (0.413-0.711) y of age. An evidence-based optimised dose regimen was constructed that would provide piperaquine exposures across all ages comparable to the exposure currently seen in a typical adult with standard treatment, without exceeding the concentration range observed with the manufacturers' recommended regimen. Limited data were available in infants and pregnant women with malaria as well as in healthy individuals. CONCLUSIONS: The derived population pharmacokinetic model was used to develop a revised dose regimen of dihydroartemisinin-piperaquine that is expected to provide equivalent piperaquine exposures safely in all patients, including in small children with malaria. Use of this dose regimen is expected to prolong the useful therapeutic life of dihydroartemisinin-piperaquine by increasing cure rates and thereby slowing resistance development. This work was part of the evidence that informed the World Health Organization technical guidelines development group in the development of the recently published treatment guidelines (2015)