The Lawyer's Mind: Why a Twenty-First Century Legal Practice Will Not Thrive Using Nineteenth Century Thinking (With Thanks to George Lakoff)

Published in cooperation with the American Bar Association Section of Dispute Resolutio

The FANCM:p.Arg658* truncating variant is associated with risk of triple-negative breast cancer

Abstract: Breast cancer is a common disease partially caused by genetic risk factors. Germline pathogenic variants in DNA repair genes BRCA1, BRCA2, PALB2, ATM, and CHEK2 are associated with breast cancer risk. FANCM, which encodes for a DNA translocase, has been proposed as a breast cancer predisposition gene, with greater effects for the ER-negative and triple-negative breast cancer (TNBC) subtypes. We tested the three recurrent protein-truncating variants FANCM:p.Arg658*, p.Gln1701*, and p.Arg1931* for association with breast cancer risk in 67,112 cases, 53,766 controls, and 26,662 carriers of pathogenic variants of BRCA1 or BRCA2. These three variants were also studied functionally by measuring survival and chromosome fragility in FANCM−/− patient-derived immortalized fibroblasts treated with diepoxybutane or olaparib. We observed that FANCM:p.Arg658* was associated with increased risk of ER-negative disease and TNBC (OR = 2.44, P = 0.034 and OR = 3.79; P = 0.009, respectively). In a country-restricted analysis, we confirmed the associations detected for FANCM:p.Arg658* and found that also FANCM:p.Arg1931* was associated with ER-negative breast cancer risk (OR = 1.96; P = 0.006). The functional results indicated that all three variants were deleterious affecting cell survival and chromosome stability with FANCM:p.Arg658* causing more severe phenotypes. In conclusion, we confirmed that the two rare FANCM deleterious variants p.Arg658* and p.Arg1931* are risk factors for ER-negative and TNBC subtypes. Overall our data suggest that the effect of truncating variants on breast cancer risk may depend on their position in the gene. Cell sensitivity to olaparib exposure, identifies a possible therapeutic option to treat FANCM-associated tumors

Global, regional, and national disease burden estimates of acute lower respiratory infections due to respiratory syncytial virus in young children in 2015:a systematic review and modelling study

Background: We have previously estimated that respiratory syncytial virus (RSV) was associated with 22% of all episodes of (severe) acute lower respiratory infection (ALRI) resulting in 55 000 to 199 000 deaths in children younger than 5 years in 2005. In the past 5 years, major research activity on RSV has yielded substantial new data from developing countries. With a considerably expanded dataset from a large international collaboration, we aimed to estimate the global incidence, hospital admission rate, and mortality from RSV-ALRI episodes in young children in 2015. Methods: We estimated the incidence and hospital admission rate of RSV-associated ALRI (RSV-ALRI) in children younger than 5 years stratified by age and World Bank income regions from a systematic review of studies published between Jan 1, 1995, and Dec 31, 2016, and unpublished data from 76 high quality population-based studies. We estimated the RSV-ALRI incidence for 132 developing countries using a risk factor-based model and 2015 population estimates. We estimated the in-hospital RSV-ALRI mortality by combining in-hospital case fatality ratios with hospital admission estimates from hospital-based (published and unpublished) studies. We also estimated overall RSV-ALRI mortality by identifying studies reporting monthly data for ALRI mortality in the community and RSV activity. Findings: We estimated that globally in 2015, 33·1 million (uncertainty range [UR] 21·6–50·3) episodes of RSV-ALRI, resulted in about 3·2 million (2·7–3·8) hospital admissions, and 59 600 (48 000–74 500) in-hospital deaths in children younger than 5 years. In children younger than 6 months, 1·4 million (UR 1·2–1·7) hospital admissions, and 27 300 (UR 20 700–36 200) in-hospital deaths were due to RSV-ALRI. We also estimated that the overall RSV-ALRI mortality could be as high as 118 200 (UR 94 600–149 400). Incidence and mortality varied substantially from year to year in any given population. Interpretation: Globally, RSV is a common cause of childhood ALRI and a major cause of hospital admissions in young children, resulting in a substantial burden on health-care services. About 45% of hospital admissions and in-hospital deaths due to RSV-ALRI occur in children younger than 6 months. An effective maternal RSV vaccine or monoclonal antibody could have a substantial effect on disease burden in this age group

Minorities, Mediation, and Method: The View from One Court-Connected Mediation Program

This Article addresses cross-cultural dynamics in small claims court mediations in Oklahoma City (1 million population). Through the study of about 300 cases, the author concludes that (1) minority status may not matter as much as gender, (2) neither gender nor minority status may matter as much as socio-economic class, and (3) well-constructed and constantly monitored mediator training and supervision may make for fairer small claims cases where mediation is seen as adjunct to judge\u27s role. The author urges reconsideration of critical race theory critiques of mediation and ultimately concludes that just mediation proceedings require addressing individuals\u27 lack of knowledge

Privatization of Rural Public Hospitals: Implications for Access and Indigent Care

Public hospitals have long functioned as the primary source of acute care services in rural communities. Yet, just as the farm crisis and population shifts of the 1980s eroded the economic base of rural America, these same factors-coupled with changes in health care financing-have eroded the stability of rural hospitals. Many have closed or converted to subacute services. Other hospitals, facing the threat of future insolvency, inability to upgrade technology, loss of patient revenue base, or legal obstacles in forming cooperative networks with other providers, have opted to surrender their cumbersome governmental status to become leaner, private players in the new competitive health care market. Privatizations soared to quick popularity in the 1980s and covered a wide range of public functions. Whether health care services, electrical utilities, or garbage collection, the privatization movement asked whether these particular duties must be performed by government, and if not, it demanded that government divest itself of that role, ceding its role to the private sector. Theoretically, the private sector would be able to operate more efficiently, less burdened by regulation and politics. In health care, perhaps more so than in other areas, the issue of the proper governmental role in providing or financing health care services has generated significant passion and anguish. Especially in many rural areas, a majority of elderly and less affluent residents rely on the public hospital to provide care. There is, in their eyes, no other alternative within a reasonable travel distance. Furthermore, the public hospital may well be the last remaining major employer in the community. While taxpayers may wish to reduce the burden of supporting the public hospital, they understandably recoil at the prospect of reductions in force with the inherent implications of lost wages and reduced consumer spending. Because the timely provision of medical care is literally a matter of life and death, and because the public hospital may be the last economic anchor in a rural town, privatizations of rural public hospitals can be especially complex in form, function, and financing. Of particular concern is-or should be-whether the mode of privatization can effectively realize the ultimate governmental duty to provide access to care for the indigent. This Article presents and discusses in detail various corporate models for restructuring public hospitals, as they have developed in recent years. The Article analyzes each model in terms of its ability to achieve the usual goals of management flexibility, plus the stated inquiry of this symposium: assuring continued access and supporting indigent care