The Ancillary Benefits from Climate Policy in the United States

This study investigates the benefits to human health that would occur in the United States (U.S.) due to reductions in local air pollutant emissions stemming from a federal policy to reduce greenhouse gas emissions (GHG). In order to measure the impacts of reduced emissions of local pollutants, this study considers a representative U.S. climate policy. Specifically, the climate policy modeled in this analysis is the Warner-Lieberman bill (S.2191) of 2008 and the paper considers the impacts of reduced emissions in the transport and electric power sectors. This analysis provides strong evidence that climate change policy in the U.S. will generate significant returns to society in excess of the benefits due to climate stabilization. The total health-related co-benefits associated with a representative climate policy over the years 2006 to 2030 range between $90 and$725 billion in present value terms depending on modeling assumptions. The majority of avoided damages are due to reduced emissions of SO2 from coal-fired power plants. Among the most important assumptions is whether remaining coal-fired generation capacity is permitted to “backslide” up to the Clean Air Interstate Rule (CAIR) cap on emissions. This analysis models two scenarios specifically related to this issue. Co-benefits increase from $90 billion, when the CAIR cap is met, to$256 billion if SO2 emissions are not permitted to exceed current emission rates. On a per ton basis, the co-benefit per ton of GHG emissions is projected to average between $2 and$14 ($2006). The per ton marginal abatement cost for the representative climate policy is estimated at$9 ($2006).

Effets du programme d’Apprentissage à l’utilisation du Transport en Commun (ATraCo) : une étude pré-expérimentale

Afin de maintenir ou d’augmenter leurs déplacements et leur intégration sociale, notamment pour pallier une cessation de la conduite automobile, l’apprentissage à l’utilisation du transport en commun peut s’avérer essentiel chez les aînés. Peu de programmes ayant cet objectif sont toutefois actuellement disponibles et ont été évalués. La présente étude visait à bonifier et à évaluer les effets d’un programme sur l’apprentissage à l’utilisation du transport en commun chez les aînés. Le Programme d’Apprentissage à l’utilisation du Transport en Commun (ATraCo) comprend une formation théorique (90 minutes) et pratique (accompagnement personnalisé pour 1 trajet à partir du domicile de la personne). Un devis pré-expérimental de type pré-test/post-test a permis d’évaluer le degré de confiance et d’aisance, les connaissances et la fréquence d’utilisation du transport en commun d’un échantillon de convenance de 16 aînés. Le degré de satisfaction des participants envers la formation a aussi été mesuré. Les résultats de cette étude démontrent, qu’à la suite du programme ATraCo, le degré de confiance et d’aisance (p = 0,001), et les connaissances (p = 0,001) des participants se sont améliorés. Les participants ont unanimement apprécié le cours théorique. Par ailleurs, plus du tiers des participants ont utilisé le transport en commun au moins une fois au cours des huit semaines suivant le programme. D’autres études sont nécessaires pour mieux comprendre et favoriser l’utilisation du transport en commun chez les aînés. Le programme ATraCo pourrait être adapté pour favoriser l’apprentissage de l’utilisation du transport en commun de différentes clientèles ayant des atteintes cognitives ou des troubles de santé mentale

Addressing the Supportive Transportation Challenges of Community-Residing Older Adults

The ability to get to where you want to go, when you want to go there is a key factor for aging-in-place in our communities. It is often taken for granted until that ability is compromised. The informal network of family and friends, if it exists, is not likely to be a sustainable transportation alternative for persons with cognitive impairment or for older adults with limitations that may not fit eligibility criteria for senior transportation services, where they exist. The purpose of this study was to investigate the potential of communities to address the specialized supportive mobility needs of community-residing older adults. A major conclusion to emerge from the research is the connection of mobility to healthcare

Molecular Epidemiology of Glanders, Pakistan

We collected epidemiologic and molecular data from Burkholderia mallei isolates from equines in Punjab, Pakistan from 1999 through 2007. We show that recent outbreaks are genetically distinct from available whole genome sequences and that these genotypes are persistent and ubiquitous in Punjab, probably due to human-mediated movement of equines

Predictors of left ventricular ejection fraction in high-risk percutaneous coronary interventions

Revascularization completeness after percutaneous coronary intervention (PCI) is associated with improved long-term outcomes. Mechanical circulatory support [intra-aortic balloon pump (IABP) or Impella] is used during high-risk PCI (HR-PCI) to enhance peri-procedural safety and achieve more complete revascularization. The relationship between revascularization completeness [post-PCI residual SYNTAX Score (rSS)] and left ventricular ejection fraction (LVEF) in HR-PCI has not been established. We investigated LVEF predictors at 90 days post-PCI with Impella or IABP support. Individual patient data (IPD) were analyzed from PROTECT II (NCT00562016) in the base case. IPD from PROTECT II and RESTORE-EF (NCT04648306) were naïvely pooled in the sensitivity analysis. Using complete cases only, linear regression was used to explore the predictors of LVEF at 90 days post-PCI. Models were refined using stepwise selection based on Akaike Information Criterion and included: treatment group (Impella, IABP), baseline characteristics [age, gender, race, New York Heart Association Functional Classification, LVEF, SYNTAX Score (SS)], and rSS. Impella treatment and higher baseline LVEF were significant predictors of LVEF improvement at 90 days post-PCI (p ≤ 0.05), and a lower rSS contributed to the model (p = 0.082). In the sensitivity analysis, Impella treatment, higher baseline LVEF, and lower rSS were significant predictors of LVEF improvement at 90 days (p ≤ 0.05), and SS pre-PCI contributed to the model (p = 0.070). Higher baseline LVEF, higher SS pre-PCI, lower rSS (i.e. completeness of revascularization), and Impella treatment were predictors of post-PCI LVEF improvement. The findings suggest potential mechanisms of Impella include improving the extent and quality of revascularization, and intraprocedural ventricular unloading

Casein Kinase 1 Underlies Temperature Compensation of Circadian Rhythms in Human Red Blood Cells

Temperature compensation and period determination by casein kinase 1 (CK1) are conserved features of eukaryotic circadian rhythms, whereas the clock gene transcription factors that facilitate daily gene expression rhythms differ between phylogenetic kingdoms. Human red blood cells (RBCs) exhibit temperature-compensated circadian rhythms, which, because RBCs lack nuclei, must occur in the absence of a circadian transcription-translation feedback loop. We tested whether period determination and temperature compensation are dependent on CKs in RBCs. As with nucleated cell types, broad-spectrum kinase inhibition with staurosporine lengthened the period of the RBC clock at 37°C, with more specific inhibition of CK1 and CK2 also eliciting robust changes in circadian period. Strikingly, inhibition of CK1 abolished temperature compensation and increased the Q10 for the period of oscillation in RBCs, similar to observations in nucleated cells. This indicates that CK1 activity is essential for circadian rhythms irrespective of the presence or absence of clock gene expression cycles

Lessons learned from the Alberta Border Testing Pilot Program

BackgroundDuring the Coronavirus disease (COVID-19) pandemic, countries implemented border control and quarantine measures to reduce transmission. The Alberta Border Testing Pilot Program (ABTPP) allowed international travellers entering Alberta to reduce their quarantine period following two negative COVID-19 tests. We evaluated participant experiences with the ABTPP and implementation.MethodWe used a parallel convergent mixed-methods design to explore participant experiences through electronic web-based questionnaires (n = 21,089; n = 13,839) and semi-structured telephone interviews (n = 30). We evaluated implementation through three staff focus groups (n = 11). We analysed questionnaires using descriptive statistics and analysed interviews using inductive and deductive thematic analysis. We deductively coded focus group data using the 2009 Consolidated Framework for Implementation Research (CFIR).ResultsQuestionnaires indicated minimal issues with registration forms (91.7%), symptom reports (95.5%), and COVID-19 testing (95.7%). Most respondents (95.1%) expressed willingness to participate in the ABTPP again. Interviews revealed three themes related to participant experience: program efficiency, clarity of information, and requisite effort. Focus groups identified key implementation facilitators including the single health information system, strong stakeholder partnerships, and good communication across partnerships. Barriers included program complexity, implementation timeline, and evolving external context.DiscussionParticipants reported high satisfaction with the ABTPP. Border testing programs should have high efficiency, require low effort, and use messaging that is clear and consistent. The effective implementation of border testing programs may be facilitated by strong leadership, adaptability, automated components, good communication, and simple technology. Learnings from participants and staff may help improve the implementation of border control programs for future pandemics or other emergencies.ConclusionsThe ABTTP was a novel border control measure during the COVID-19 pandemic. Our evaluation of both participant and staff experiences demonstrated high levels of traveller satisfaction and identified areas for improvement that can inform the development of future border control measures

Lysyl-tRNA synthetase as a drug target in malaria and cryptosporidiosis

Malaria and cryptosporidiosis, caused by apicomplexan parasites, remain major drivers of global child mortality. New drugs for the treatment of malaria and cryptosporidiosis, in particular, are of high priority; however, there are few chemically validated targets. The natural product cladosporin is active against blood- and liver-stage; Plasmodium falciparum; and; Cryptosporidium parvum; in cell-culture studies. Target deconvolution in; P. falciparum; has shown that cladosporin inhibits lysyl-tRNA synthetase (; Pf; KRS1). Here, we report the identification of a series of selective inhibitors of apicomplexan KRSs. Following a biochemical screen, a small-molecule hit was identified and then optimized by using a structure-based approach, supported by structures of both; Pf; KRS1 and; C. parvum; KRS (; Cp; KRS). In vivo proof of concept was established in an SCID mouse model of malaria, after oral administration (ED; 90; = 1.5 mg/kg, once a day for 4 d). Furthermore, we successfully identified an opportunity for pathogen hopping based on the structural homology between; Pf; KRS1 and; Cp; KRS. This series of compounds inhibit; Cp; KRS and; C. parvum; and; Cryptosporidium hominis; in culture, and our lead compound shows oral efficacy in two cryptosporidiosis mouse models. X-ray crystallography and molecular dynamics simulations have provided a model to rationalize the selectivity of our compounds for; Pf; KRS1 and; Cp; KRS vs. (human); Hs; KRS. Our work validates apicomplexan KRSs as promising targets for the development of drugs for malaria and cryptosporidiosis

Effect of Deutetrabenazine on Chorea Among Patients With Huntington Disease A Randomized Clinical Trial

Importance Deutetrabenazine is a novel molecule containing deuterium, which attenuates CYP2D6 metabolism and increases active metabolite half-lives and may therefore lead to stable systemic exposure while preserving key pharmacological activity. Objective To evaluate efficacy and safety of deutetrabenazine treatment to control chorea associated with Huntington disease. Design, Setting, and Participants Ninety ambulatory adults diagnosed with manifest Huntington disease and a baseline total maximal chorea score of 8 or higher (range, 0-28; lower score indicates less chorea) were enrolled from August 2013 to August 2014 and randomized to receive deutetrabenazine (n = 45) or placebo (n = 45) in a double-blind fashion at 34 Huntington Study Group sites. Interventions Deutetrabenazine or placebo was titrated to optimal dose level over 8 weeks and maintained for 4 weeks, followed by a 1-week washout. Main Outcomes and Measures Primary end point was the total maximal chorea score change from baseline (the average of values from the screening and day-0 visits) to maintenance therapy (the average of values from the week 9 and 12 visits) obtained by in-person visits. This study was designed to detect a 2.7-unit treatment difference in scores. The secondary end points, assessed hierarchically, were the proportion of patients who achieved treatment success on the Patient Global Impression of Change (PGIC) and on the Clinical Global Impression of Change (CGIC), the change in 36-Item Short Form– physical functioning subscale score (SF-36), and the change in the Berg Balance Test. Results Ninety patients with Huntington disease (mean age, 53.7 years; 40 women [44.4%]) were enrolled. In the deutetrabenazine group, the mean total maximal chorea scores improved from 12.1 (95% CI, 11.2-12.9) to 7.7 (95% CI, 6.5-8.9), whereas in the placebo group, scores improved from 13.2 (95% CI, 12.2-14.3) to 11.3 (95% CI, 10.0-12.5); the mean between-group difference was –2.5 units (95% CI, –3.7 to –1.3) (P < .001). Treatment success, as measured by the PGIC, occurred in 23 patients (51%) in the deutetrabenazine group vs 9 (20%) in the placebo group (P = .002). As measured by the CGIC, treatment success occurred in 19 patients (42%) in the deutetrabenazine group vs 6 (13%) in the placebo group (P = .002). In the deutetrabenazine group, the mean SF-36 physical functioning subscale scores decreased from 47.5 (95% CI, 44.3-50.8) to 47.4 (44.3-50.5), whereas in the placebo group, scores decreased from 43.2 (95% CI, 40.2-46.3) to 39.9 (95% CI, 36.2-43.6), for a treatment benefit of 4.3 (95% CI, 0.4 to 8.3) (P = .03). There was no difference between groups (mean difference of 1.0 unit; 95% CI, –0.3 to 2.3; P = .14), for improvement in the Berg Balance Test, which improved by 2.2 units (95% CI, 1.3-3.1) in the deutetrabenazine group and by 1.3 units (95% CI, 0.4-2.2) in the placebo group. Adverse event rates were similar for deutetrabenazine and placebo, including depression, anxiety, and akathisia. Conclusions and Relevance Among patients with chorea associated with Huntington disease, the use of deutetrabenazine compared with placebo resulted in improved motor signs at 12 weeks. Further research is needed to assess the clinical importance of the effect size and to determine longer-term efficacy and safety