Clinical Issues Surrounding Once-Daily Aminoglycoside Dosing in Children

Aminoglycoside antibiotics are first-line treatment for many infectious diseases in the pediatric population and are effective in adults. The traditional dosing interval in children is every 8–12 hours. Studies in adults reported equivalent efficacy and equal or less toxicity with once-daily regimens. Despite many studies in the adult population, this approach has yet to become standard practice in most pediatric hospitals. Reasons for lack of acceptance of this strategy in children include rapid aminoglycoside clearance, unknown duration of postantibiotic effect, safety concerns, and limited clinical and efficacy data

How willing are you to accept sexual requests from slightly unattractive to exceptionally attractive imagined requestors?

This is the post print version of the article. The official published version can be accessed from the link below.In their classic study of differences in mating strategies (Clark & Hatfield, 1989), men and women demonstrated a striking difference in interest in casual sex. The current study examined the role of requestor physical attractiveness (slightly unattractive, moderately attractive and exceptionally attractive) on men's and women's willingness to accept three different requests (go out, come to apartment, go to bed) in a questionnaire study. We tested two hypotheses, using a sample of 427 men and 443 women from three countries. Hypothesis 1 states that men, relative to women, will demonstrate a greater willingness to accept the “come to apartment” and “go to bed” requests but not the “go out” request for all three levels of requestor attractiveness. This hypothesis reflects Clark and Hatfield's (1989) main findings. Hypothesis 2 states that the physical attractiveness of a potential partner will have a greater effect on women's than on men's willingness to accept all three requests, and particularly for the explicit request for casual sex. The results partially supported Hypothesis 1 and fully supported Hypothesis 2. The discussion highlights limitations of the current research and presents directions for future research

Advancing climate change health adaptation through implementation science

To date, there are few examples of implementation science studies that help guide climate-related health adaptation. Implementation science is the study of methods to promote the adoption and integration of evidence-based tools, interventions, and policies into practice to improve population health. These studies can provide the needed empirical evidence to prioritise and inform implementation of health adaptation efforts. This Personal View discusses five case studies that deployed disease early warning systems around the world. These cases studies illustrate challenges to deploying early warning systems and guide recommendations for implementation science approaches to enhance future research. We propose theory-informed approaches to understand multilevel barriers, design strategies to overcome those barriers, and analyse the ability of those strategies to advance the uptake and scale-up of climate-related health interventions. These findings build upon previous theoretical work by grounding implementation science recommendations and guidance in the context of real-world practice, as detailed in the case studies.Peer ReviewedArticle signat per 14 autors/es: Gila Neta, PhD; William Pan, DrPH; Prof Kristie Ebi, PhD; Daniel F Buss, PhD; Trisha Castranio, BS; Prof Rachel Lowe, PhD; Sadie J Ryan, PhD; Anna M Stewart-Ibarra, PhD; Limb K Hapairai, PhD; Meena Sehgal, MPH; Prof Michael C Wimberly, PhD; Leslie Rollock, DrPH; Prof Maureen Lichtveld, MD; John Balbus, MD"Postprint (published version

Genome-scale analysis identifies paralog lethality as a vulnerability of chromosome 1p loss in cancer.

Functional redundancy shared by paralog genes may afford protection against genetic perturbations, but it can also result in genetic vulnerabilities due to mutual interdependency1-5. Here, we surveyed genome-scale short hairpin RNA and CRISPR screening data on hundreds of cancer cell lines and identified MAGOH and MAGOHB, core members of the splicing-dependent exon junction complex, as top-ranked paralog dependencies6-8. MAGOHB is the top gene dependency in cells with hemizygous MAGOH deletion, a pervasive genetic event that frequently occurs due to chromosome 1p loss. Inhibition of MAGOHB in a MAGOH-deleted context compromises viability by globally perturbing alternative splicing and RNA surveillance. Dependency on IPO13, an importin-β receptor that mediates nuclear import of the MAGOH/B-Y14 heterodimer9, is highly correlated with dependency on both MAGOH and MAGOHB. Both MAGOHB and IPO13 represent dependencies in murine xenografts with hemizygous MAGOH deletion. Our results identify MAGOH and MAGOHB as reciprocal paralog dependencies across cancer types and suggest a rationale for targeting the MAGOHB-IPO13 axis in cancers with chromosome 1p deletion

Therminator DNA Polymerase: Modified Nucleotides and Unnatural Substrates

A variant of 9°N DNA polymerase [Genbank ID (AAA88769.1)] with three mutations (D141A, E143A, A485L) and commercialized under the name “Therminator DNA polymerase” has the ability to incorporate a variety of modified nucleotide classes. This Review focuses on how Therminator DNA Polymerase has enabled new technologies in synthetic biology and DNA sequencing. In addition, we discuss mechanisms for increased modified nucleotide incorporation

Análisis sincrónico de la gobernanza universitaria: una mirada teórica a los años sesenta y setenta

Resumen Estudiar las perspectivas en el campo del gobierno de las universidades tiene cada día mayor preeminencia, especialmente si se toma en cuenta la incuestionable necesidad de avanzar hacía organizaciones más eficientes, conectadas con las expectativas que sobre ellas tiene la sociedad. Considerando este escenario, el trabajo se ha planteado como propósito central realizar un análisis de carácter sincrónico del concepto de gobernanza y la constitución de los gobiernos universitarios. Desde el punto de vista metodológico se utilizaron fuentes secundarias: una revisión de papers publicados esencialmente en revistas de habla inglesa. El estudio comprende las décadas del sesenta y el setenta. Se centra en las raíces del concepto de gobernanza universitaria, en la delineación de los actores que participan en sus gobiernos y en las relaciones de poder que fluyen entre ellos.Entre las principales conclusiones, se pueden destacar como el estamento académico desde el principio de las universidades ha ocupado el rol casi plenipotenciario en su respectivo gobierno, producto de esto, en el correr del desarrollo y mientras la complejidad organizacional se incrementaba, es que fue necesario incorporar nuevos actores a los sistemas de gestión; todo lo anterior, teniendo en cuenta que dos elementos han sido fundamentales para la sobrevivencia de este tipo de instituciones, la legitimidad otorgada por la sociedad y los principios de estrategias del ámbito de la gestión

An Analysis of the Employment Effects of the Washington High Technology Business and Occupation (B&O) Tax Credit: Technical Report

This paper estimates the effects of an R&D tax credit in the state of Washington on job creation. The research uses micro-data on the job creation and tax credits received by individual firms in the state of Washington from 2004 to 2009. We correct for the endogeneity of R&D tax credits received by individual firms by using instrumental variables based in part on national industry factor shares for R&D. We estimate that this tax credit created jobs, but at a high cost. The cost per job-year created is estimated to be between $40,000 and$50,000. The credit was so high cost in part because the credit was non-refundable. As a result, about one-quarter of the firms receiving credits were maxed out on credit eligibility, so that the credit provided no marginal incentive for additional R&D spending or job creation