The weaker sex? Vulnerable men and women's resilience to socio-economic disadvantage.

Sex differences in mortality vary over time and place as a function of social, health, and medical circumstances. The magnitude of these variations, and their response to large socioeconomic changes, suggest that biological differences cannot fully account for sex differences in survival. Drawing on a wide swath of mortality data across countries and over time, we develop a set of empiric observations with which any theory about excess male mortality and its correlates will have to contend. We show that as societies develop, M/F survival first declines and then increases, a "sex difference in mortality transition" embedded within the demographic and epidemiologic transitions. After the onset of this transition, cross-sectional variation in excess male mortality exhibits a consistent pattern of greater female resilience to mortality under socio-economic adversity. The causal mechanisms underlying these associations merit further research.

Avulsión de la tuberosidad tibial: reporte de un caso y revisión de la literatura / Tibial tubercle avulsion: a case report and literature review

Resumen La fractura por avulsión de la tuberosidad tibial es una patología poco común. Es una lesión característica de la infancia, con afección directa a la fisis, que amerita un diagnóstico oportuno y un tratamiento óptimo a fin de evitar complicaciones en el crecimiento, la mayoría de ellas graves. La reducción abierta y fijación interna ha probado ser un tratamiento adecuado en la mayoría de este tipo de lesiones; sin embargo, el procedimiento quirúrgico es un riesgo agregado al daño de la lesión per se. Con un adecuado tratamiento y rehabilitación la lesión tiende a una evolución por lo general satisfactoria. Tomando en cuenta la baja incidencia de esta patología, en el siguiente artículo reportamos el caso de un paciente de 13 años con avulsión de tuberosidad tibial tipo III de Watson-Jones, el abordaje diagnóstico-terapéutico y el éxito obtenido a 2 años de seguimiento; asimismo, realizamos una revisión de la literatura.

Abstract Tibial tubercle avulsion is an uncommon disease, usually found during childhood, with direct physis affection, that needs an accurate diagnosis and an optimum treatment in order to avoid growth complications which could have disastrous consequences for the child. Open reduction and internal fixation has been reported as an adequate treatment in most of these injuries; nevertheless, surgery increases the risk upon the injury itself. With an appropriate treatment and rehabilitation this injury tends to have a satisfactory evolution. Considering the low incidence of this pathology, a case report of a 13-year-old boy with a Watson-Jones type III avulsion, a diagnostic-therapeutic approach and the successful evolution for a two-years follow up is described, as well as a literature review.

Major concepts of health care economics.

This article applies major economic concepts, such as supply, demand, monopoly, monopsony, adverse selection, and moral hazard, to central features of U.S. health care. These illustrations help explain some of the principal problems of health policy-high cost and the uninsured-and why solutions are difficult to obtain.

Restructuring medical education to meet current and future health care needs.

U.S. health care is changing, and it will continue to change across multiple dimensions: a different mix of patients; more ambulatory, chronic care and less acute, inpatient care; an older population; expanded insurance coverage; a team approach to care; rapid growth of subspecialty care; growing emphasis on cost-effective care; and rapid technological change. These changes demand a corresponding evolution in physician roles and training. However, despite innovation in content and teaching methods, there has been little alteration to the basic structure of medical education since the Flexner Report sparked widespread reform in 1910. Looking to the future, medical education might evolve to include preparation for a team approach to care via practical training for multispecialty collaborative practice and preparing physicians to be leaders of primary care teams that include nonphysician providers; shorter training for some physicians via flexible pathways and "fast tracks" at each phase of training; cost-effective care in clinical practice; increased training in geriatrics; and "on ramps" and "off ramps" along the physician career path for flexible training over a lifetime. Although the challenges facing the health care system are great, meeting changing health care needs must begin at the foundation, in medical education.

Development of a large scale asymmetric synthesis of the glucocorticoid agonist BI 653048 BS H3PO4.

The development of a large scale synthesis of the glucocorticoid agonist BI 653048 BS H3PO4 (1·H3PO4) is presented. A key trifluoromethyl ketone intermediate 22 containing an N-(4-methoxyphenyl)ethyl amide was prepared by an enolization/bromine-magnesium exchange/electrophile trapping reaction. A nonselective propargylation of trifluoromethyl ketone 22 gave the desired diastereomer in 32% yield and with dr = 98:2 from a 1:1 diastereomeric mixture after crystallization. Subsequently, an asymmetric propargylation was developed which provided the desired diastereomer in 4:1 diastereoselectivity and 75% yield with dr = 99:1 after crystallization. The azaindole moiety was efficiently installed by a one-pot cross coupling/indolization reaction. An efficient deprotection of the 4-methoxyphenethyl group was developed using H3PO4/anisole to produce the anisole solvate of the API in high yield and purity. The final form, a phosphoric acid cocrystal, was produced in high yield and purity and with consistent control of particle size.

Zinc catalyzed and mediated asymmetric propargylation of trifluoromethyl ketones with a propargyl boronate.

The development of zinc-mediated and -catalyzed asymmetric propargylations of trifluoromethyl ketones with a propargyl borolane and the N-isopropyl-l-proline ligand is presented. The methodology provided moderate to high stereoselectivity and was successfully applied on a multikilogram scale for the synthesis of the Glucocorticoid agonist BI 653048. A mechanism for the boron-zinc exchange with a propargyl borolane is proposed and supported by modeling at the density functional level of theory. A water acceleration effect on the zinc-catalyzed propargylation was discovered, which enabled a catalytic process to be achieved. Reaction progress analysis supports a predominately rate limiting exchange for the zinc-catalyzed propargylation. A catalytic amount of water is proposed to generate an intermediate that catalyzes the exchange, thereby facilitating the reaction with trifluoromethyl ketones.