289 research outputs found

    Predicting the Impact of Placing Pre-event Pharmaceuticals for Anthrax

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    Finding feasible strategies to distribute antibiotics quickly to the general public in response to an anthrax attack remains a difficult challenge. Among the proposed strategies is the pre-event placement of pharmaceuticals in individual households for use only as directed by public health authorities. These medications (known as ā€œMedKitsā€) would allow many exposed persons to begin treatment quickly while reducing the number who visit on points of dispensing, the primary distribution strategy. This paper describes a model that estimates the expected number of deaths in an anthrax attack by modeling the logistics of the response and the use of MedKits. The results show that increasing the number of MedKits distributed can reduce the expected number of deaths. When the population has more potential exposures, deploying MedKits is more effective. The MedKits reduce the number of potential exposures who seek prophylaxis, which allows those truly exposed (but without MedKits) to receive medication sooner, which saves lives. Beyond the scenarios considered here, the ability to predict this benefit in other scenarios will be valuable to public health officials who are considering this option

    Expressing gratitude and visualising oneā€™s best possible self: Assessing the effectiveness of a four-week intervention on affect and health behaviours during the COVID-19 lockdown

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    AbstractThis research examined affect and health behaviours over four weeks during consecutive COVID-19 lockdowns in the United Kingdom (UK), and the impact of expressing gratitude (EG) and visualising oneā€™s best possible self (BPS) on these outcomes compared to a control condition. Participants (Nā€‰=ā€‰145) took part in a 4-week intervention during lockdown and completed an EG, BPS, or control exercise and measures of affect and health behaviours once per week for four weeks. Results showed that participants reported increased positive affect and decreased negative affect, reduced food consumption, and lower levels of moderate and vigorous exercise, but no change in alcohol consumption and walking. There were, however, no significant effects of the interventions vs. control condition on any of the outcomes; these findings were also supported by Bayes factors. This research suggests that people changed their health behaviours and affect during the COVID-19 lockdown, but that BPS and EG interventions may not be viable interventions to promote these outcomes during intense crises such as COVID-19.</jats:p

    Comparing a mindfulness- and CBT-based guided self-help Internet- and mobile-based intervention against a waiting list control condition as treatment for adults with frequent cannabis use: a randomized controlled trial of CANreduce 3.0

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    Background: Though Internet- and mobile-based interventions (IMIs) and mindfulness-based interventions (generally delivered in-situ) appear effective for people with substance use disorders, IMIs incorporating mindfulness are largely missing, including those targeting frequent cannabis use. Methods: This paper details the protocol for a three-arm randomized controlled trial comparing a mindfulness-based self-help IMI (arm 1) and cognitive-behavioral therapy (CBT)-based self-help IMI (arm 2) versus being on a waiting list (arm 3) in their effectiveness reducing cannabis use in frequent cannabis users. Predictors of retention, adherence and treatment outcomes will be identified and similarities between the two active intervention arms explored. Both active interventions last six weeks and consist of eight modules designed to reduce cannabis use and common mental health symptoms. With a targeted sample size of n = 210 per treatment arm, data will be collected at baseline immediately before program use is initiated; at six weeks, immediately after program completion; and at three and six months post baseline assessment to assess the retention of any gains achieved during treatment. The primary outcome will be number of days of cannabis use over the preceding 30 days. Secondary outcomes will include further measures of cannabis use and use of other substances, changes in mental health symptoms and mindfulness, client satisfaction, intervention retention and adherence, and adverse effects. Data analysis will follow ITT principles and primarily employ (generalized) linear mixed models. Discussion: This RCT will provide important insights into the effectiveness of an IMI integrating mindfulness to reduce cannabis use in frequent cannabis users. Trial registration: International Standard Randomized Controlled Trial Number Registry: ISRCTN14971662 ; date of registration: 09/09/2021. Keywords: Cannabis; Cognitive-behavioral therapy; Internet-based intervention; Mindfulness; Randomized controlled trial; Self-help

    RCC1-dependent activation of Ran accelerates cell cycle and DNA repair, inhibiting DNA damageā€“induced cell senescence

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    Ā© The Author(s), 2016. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Molecular Biology of the Cell 27 (2016): 1346-1357, doi:10.1091/mbc.E16-01-0025.The coordination of cell cycle progression with the repair of DNA damage supports the genomic integrity of dividing cells. The function of many factors involved in DNA damage response (DDR) and the cell cycle depends on their Ran GTPaseā€“regulated nuclearā€“cytoplasmic transport (NCT). The loading of Ran with GTP, which is mediated by RCC1, the guanine nucleotide exchange factor for Ran, is critical for NCT activity. However, the role of RCC1 or Ranā‹…GTP in promoting cell proliferation or DDR is not clear. We show that RCC1 overexpression in normal cells increased cellular Ranā‹…GTP levels and accelerated the cell cycle and DNA damage repair. As a result, normal cells overexpressing RCC1 evaded DNA damageā€“induced cell cycle arrest and senescence, mimicking colorectal carcinoma cells with high endogenous RCC1 levels. The RCC1-induced inhibition of senescence required Ran and exportin 1 and involved the activation of importin Ī²ā€“dependent nuclear import of 53BP1, a large NCT cargo. Our results indicate that changes in the activity of the Ranā‹…GTPā€“regulated NCT modulate the rate of the cell cycle and the efficiency of DNA repair. Through the essential role of RCC1 in regulation of cellular Ranā‹…GTP levels and NCT, RCC1 expression enables the proliferation of cells that sustain DNA damage.P.C., K.H., Y.P., J.-Q.C., M.A.H., S.K., and P.K. were supported by the Intramural Research Program of the Center for Cancer Research, NCI. D.O. and E.T. were supported by National Institutes of Health grant R01 GM071522

    Developing Theory to Guide Building Practitionersā€™ Capacity to Implement Evidence-Based Interventions

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    Public health and other community-based practitioners have access to a growing number of evidence-based interventions (EBIs), and yet EBIs continue to be underused. One reason for this underuse is that practitioners often lack the capacity (knowledge, skills, and motivation) to select, adapt, and implement EBIs. Training, technical assistance, and other capacity-building strategies can be effective at increasing EBI adoption and implementation. However, little is known about how to design capacity-building strategies or tailor them to differences in capacity required across varying EBIs and practice contexts. To address this need, we conducted a scoping study of frameworks and theories detailing variations in EBIs or practice contexts and how to tailor capacity-building to address those variations. Using an iterative process, we consolidated constructs and propositions across 24 frameworks and developed a beginning theory to describe salient variations in EBIs (complexity and uncertainty) and practice contexts (decision-making structure, general capacity to innovate, resource and values fit with EBI, and unity vs. polarization of stakeholder support). The theory also includes propositions for tailoring capacity-building strategies to address salient variations. To have wide-reaching and lasting impact, the dissemination of EBIs needs to be coupled with strategies that build practitionersā€™ capacity to adopt and implement a variety of EBIs across diverse practice contexts

    How are oxygen budgets influenced by dissolved iron and growth of oxygenic phototrophs in an iron-rich spring system? Initial results from the Espan Spring in FĆ¼rth, Germany

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    At present most knowledge on the impact of iron on 18Oā€‰/ā€‰16O ratios (i.e. Ī“18O) of dissolved oxygen (DO) under circum-neutral conditions stems from experiments carried out under controlled laboratory conditions. These showed that iron oxidation leads to an increase in Ī“18ODO values. Here we present the first study on effects of elevated Fe(II) concentrations on the Ī“18ODO in a natural, iron-rich, circum-neutral watercourse. Our results show that iron oxidation was the major factor for rising dissolved oxygen isotope compositions in the first 85ā€‰m of the system in the cold season (February) and for the first 15ā€‰m during the warm season (May). Further along the course of the stream, the Ī“18ODO decreased towards values known for atmospheric equilibration around +24.6ā€‰ā€° during both seasons. Possible drivers for these changes may be reduced iron oxidation, increased atmospheric exchange and DO production by oxygenic phototrophic algae mats. In the cold season, the Ī“18ODO values stabilized around atmospheric equilibrium, whereas in the warm season stronger influences by oxygenic photosynthesis caused values down to +21.8ā€‰ā€°. In the warm season from 145ā€‰m downstream of the spring, the Ī“18ODO increased again until it reached atmospheric equilibrium. This trend can be explained by respiratory consumption of DO combined with a relative decrease in photosynthetic activity and increasing atmospheric influences. Our study shows that dissolved Fe(II) can exert strong effects on the Ī“18ODO of a natural circum-neutral spring system even under constant supply of atmospheric O2. However, in the presence of active photosynthesis, with supply of O2 to the system, direct effects of Fe oxidation on the Ī“18ODO value become masked. Nonetheless, critical Fe(II) concentrations may indirectly control DO budgets by enhancing photosynthesis, particularly if cyanobacteria are involved

    The psychosocial outcomes of anoxic brain injury following cardiac arrest

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    Aim of the study: This exploratory study aimed to investigate the psychosocial outcomes for cardiac arrest survivors and explore if there is a greater impact on psychosocial outcome for individuals experiencing anoxic brain injury as a result of the cardiac arrest. Methods: Self-report measures were used to compare the quality of life, social functioning and symptoms of anxiety, depression and posttraumatic stress of individuals with and without anoxic brain injury. Secondary measures of subjective memory and executive difficulties were also used. Fifty-six participants (27 with anoxia, 29 without anoxia) took part in the study between six months and four years after experiencing cardiac arrest. Results: A MANOVA identified a significant difference between the two groups, with the anoxia group reporting more psychosocial difficulties. They reported more social functioning difficulties and more anxiety, depression and post-traumatic stress symptoms. There was, however, no significant difference in self-reported quality of life between the two groups. Conclusion: As the first known study to compare psychosocial outcomes for cardiac arrest survivors experiencing anoxic brain injury with those without anoxia, the current results suggest that cardiac arrest survivors with subsequent acquired brain injury experience more psychosocial difficulties. This could be due to a combination of neuropsychological, social and psychological factors

    Reduced Lentivirus Susceptibility in Sheep with TMEM154 Mutations

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    Visna/Maedi, or ovine progressive pneumonia (OPP) as it is known in the United States, is an incurable slow-acting disease of sheep caused by persistent lentivirus infection. This disease affects multiple tissues, including those of the respiratory and central nervous systems. Our aim was to identify ovine genetic risk factors for lentivirus infection. Sixty-nine matched pairs of infected cases and uninfected controls were identified among 736 naturally exposed sheep older than five years of age. These pairs were used in a genome-wide association study with 50,614 markers. A single SNP was identified in the ovine transmembrane protein (TMEM154) that exceeded genome-wide significance (unadjusted p-value 3Ɨ10āˆ’9). Sanger sequencing of the ovine TMEM154 coding region identified six missense and two frameshift deletion mutations in the predicted signal peptide and extracellular domain. Two TMEM154 haplotypes encoding glutamate (E) at position 35 were associated with infection while a third haplotype with lysine (K) at position 35 was not. Haplotypes encoding full-length E35 isoforms were analyzed together as genetic risk factors in a multi-breed, matched case-control design, with 61 pairs of 4-year-old ewes. The odds of infection for ewes with one copy of a full-length TMEM154 E35 allele were 28 times greater than the odds for those without (p-value<0.0001, 95% CI 5ā€“1,100). In a combined analysis of nine cohorts with 2,705 sheep from Nebraska, Idaho, and Iowa, the relative risk of infection was 2.85 times greater for sheep with a full-length TMEM154 E35 allele (p-value<0.0001, 95% CI 2.36ā€“3.43). Although rare, some sheep were homozygous for TMEM154 deletion mutations and remained uninfected despite a lifetime of significant exposure. Together, these findings indicate that TMEM154 may play a central role in ovine lentivirus infection and removing sheep with the most susceptible genotypes may help eradicate OPP and protect flocks from reinfection
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