Causal etiology of the research of James M. Robins

This issue of Statistical Science draws its inspiration from the work of James M. Robins. Jon Wellner, the Editor at the time, asked the two of us to edit a special issue that would highlight the research topics studied by Robins and the breadth and depth of Robins' contributions. Between the two of us, we have collaborated closely with Jamie for nearly 40 years. We agreed to edit this issue because we recognized that we were among the few in a position to relate the trajectory of his research career to date.Fil: Richardson, Thomas S.. University of Washington; Estados UnidosFil: Rotnitzky, Andrea Gloria. Universidad Torcuato Di Tella. Departamento de Economía; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Allogromiid test construction

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Are neighbourhood food resources distributed inequitably by income and race in the USA? Epidemiological findings across the urban spectrum

ObjectiveMany recent policies focus on socioeconomic inequities in availability of healthy food stores and restaurants. Yet understanding of how socioeconomic inequities vary across neighbourhood racial composition and across the range from rural to urban settings is limited, largely due to lack of large, geographically and socio-demographically diverse study populations. Using a national sample, the authors examined differences in neighbourhood food resource availability according to neighbourhood-level poverty and racial/ethnic population in non-urban, low-density urban and high-density urban areas.DesignCross-sectional data from an observational cohort study representative of the US middle and high school-aged population in 1994 followed into young adulthood.ParticipantsUsing neighbourhood characteristics of participants in the National Longitudinal Study of Adolescent Health (Wave III, 2001–2002; n=13 995 young adults aged 18–28 years representing 7588 US block groups), the authors examined associations between neighbourhood poverty and race/ethnicity with neighbourhood food resource availability in urbanicity-stratified multivariable linear regression.Primary and secondary outcome measuresNeighbourhood availability of grocery/supermarkets, convenience stores and fast-food restaurants (measured as number of outlets per 100 km roadway).ResultsNeighbourhood race and income disparities were most pronounced in low-density urban areas, where high-poverty/high-minority areas had lower availability of grocery/supermarkets (β coefficient (β)=–1.91, 95% CI –2.73 to –1.09) and convenience stores (β=–2.38, 95% CI –3.62 to –1.14) and greater availability of fast-food restaurants (β=4.87, 95% CI 2.26 to 7.48) than low-poverty/low-minority areas. However, in high-density urban areas, high-poverty/low-minority neighbourhoods had comparatively greater availability of grocery/supermarkets (β=8.05, 95% CI 2.52 to 13.57), convenience stores (β=2.89, 95% CI 0.64 to 5.14) and fast-food restaurants (β=4.03, 95% CI 1.97 to 6.09), relative to low-poverty/low-minority areas.ConclusionsIn addition to targeting disproportionate fast-food availability in disadvantaged dense urban areas, our findings suggest that policies should also target disparities in grocery/supermarket and fast-food restaurant availability in low-density areas.Article summaryArticle focusUsing national data, we examined whether neighbourhood food resource availability exhibits joint race and socioeconomic inequities across levels of urbanicity.Key messagesSocio-demographic inequities in neighbourhood food resource availability were most pronounced in low-density urban (largely suburban) areas.In high-density urban areas, higher neighbourhood poverty was associated with greater availability of all food resources.Whereas policy has focused on dense urban settings, less urban areas might also benefit from policies addressing food access.Strengths and limitations of this studyWhile business records provide comparable data across the USA, these data may contain error and do not indicate availability of specific foods.National coverage enabled examination of the joint role of neighbourhood race and socioeconomic status across urban strata within a single study

Should a Sentinel Node Biopsy Be Performed in Patients with High-Risk Breast Cancer?

A negative sentinel lymph node (SLN) biopsy spares many breast cancer patients the complications associated with lymph node irradiation or additional surgery. However, patients at high risk for nodal involvement based on clinical characteristics may remain at unacceptably high risk of axillary disease even after a negative SLN biopsy result. A Bayesian nomogram was designed to combine the probability of axillary disease prior to nodal biopsy with customized test characteristics for an SLN biopsy and provides the probability of axillary disease despite a negative SLN biopsy. Users may individualize the sensitivity of an SLN biopsy based on factors known to modify the sensitivity of the procedure. This tool may be useful in identifying patients who should have expanded upfront exploration of the axilla or comprehensive axillary irradiation

Objectively measured physical activity of USA adults by sex, age, and racial/ethnic groups: a cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Accelerometers were incorporated in the 2003–2004 National Health and Nutritional Examination Survey (NHANES) study cycle for objective assessment of physical activity. This is the first time that objective physical activity data are available on a nationally representative sample of U.S. residents. The use of accelerometers allows researchers to measure total physical activity, including light intensity and unstructured activities, which may be a better predictor of health outcomes than structured activity alone. The aim of this study was to examine objectively determined physical activity levels by sex, age and racial/ethnic groups in a national sample of U.S. adults.</p> <p>Methods</p> <p>Data were obtained from the 2003–2004 NHANES, a cross-sectional study of a complex, multistage probability sample of the U.S. population. Physical activity was assessed with the Actigraph AM-7164 accelerometer for seven days following an examination. 2,688 U.S. adults with valid accelerometer data (i.e. at least four days with at least 10 hours of wear-time) were included in the analysis. Mean daily total physical activity counts, as well as counts accumulated in minutes of light, and moderate-vigorous intensity physical activity are presented by sex across age and racial/ethnic groups. Generalized linear modeling using the log link function was performed to compare physical activity in sex and racial/ethnic groups adjusting for age.</p> <p>Results</p> <p>Physical activity decreases with age for both men and women across all racial/ethnic groups with men being more active than women, with the exception of Hispanic women. Hispanic women are more active at middle age (40–59 years) compared to younger or older age and not significantly less active than men in middle or older age groups (i.e. age 40–59 or age 60 and older). Hispanic men accumulate more total and light intensity physical activity counts than their white and black counterparts for all age groups.</p> <p>Conclusion</p> <p>Physical activity levels measured objectively by accelerometer demonstrated that Hispanic men are, in general, more active than their white and black counterparts. This appears to be in contrast to self-reported physical activity previously reported in the literature and identifies the need to use objective measures in situations where the contribution of light intensity and/or unstructured physical activity cannot be assumed homogenous across the populations of interest.</p

Potent and Broad Inhibition of HIV-1 by a Peptide from the gp41 Heptad Repeat-2 Domain Conjugated to the CXCR4 Amino Terminus.

HIV-1 entry can be inhibited by soluble peptides from the gp41 heptad repeat-2 (HR2) domain that interfere with formation of the 6-helix bundle during fusion. Inhibition has also been seen when these peptides are conjugated to anchoring molecules and over-expressed on the cell surface. We hypothesized that potent anti-HIV activity could be achieved if a 34 amino acid peptide from HR2 (C34) were brought to the site of virus-cell interactions by conjugation to the amino termini of HIV-1 coreceptors CCR5 or CXCR4. C34-conjugated coreceptors were expressed on the surface of T cell lines and primary CD4 T cells, retained the ability to mediate chemotaxis in response to cognate chemokines, and were highly resistant to HIV-1 utilization for entry. Notably, C34-conjugated CCR5 and CXCR4 each exhibited potent and broad inhibition of HIV-1 isolates from diverse clades irrespective of tropism (i.e., each could inhibit R5, X4 and dual-tropic isolates). This inhibition was highly specific and dependent on positioning of the peptide, as HIV-1 infection was poorly inhibited when C34 was conjugated to the amino terminus of CD4. C34-conjugated coreceptors could also inhibit HIV-1 isolates that were resistant to the soluble HR2 peptide inhibitor, enfuvirtide. When introduced into primary cells, CD4 T cells expressing C34-conjugated coreceptors exhibited physiologic responses to T cell activation while inhibiting diverse HIV-1 isolates, and cells containing C34-conjugated CXCR4 expanded during HIV-1 infection in vitro and in a humanized mouse model. Notably, the C34-conjugated peptide exerted greater HIV-1 inhibition when conjugated to CXCR4 than to CCR5. Thus, antiviral effects of HR2 peptides can be specifically directed to the site of viral entry where they provide potent and broad inhibition of HIV-1. This approach to engineer HIV-1 resistance in functional CD4 T cells may provide a novel cell-based therapeutic for controlling HIV infection in humans

Instability of one-step replica-symmetry-broken phase in satisfiability problems

We reconsider the one-step replica-symmetry-breaking (1RSB) solutions of two random combinatorial problems: k-XORSAT and k-SAT. We present a general method for establishing the stability of these solutions with respect to further steps of replica-symmetry breaking. Our approach extends the ideas of [A.Montanari and F. Ricci-Tersenghi, Eur.Phys.J. B 33, 339 (2003)] to more general combinatorial problems. It turns out that 1RSB is always unstable at sufficiently small clauses density alpha or high energy. In particular, the recent 1RSB solution to 3-SAT is unstable at zero energy for alpha< alpha_m, with alpha_m\approx 4.153. On the other hand, the SAT-UNSAT phase transition seems to be correctly described within 1RSB.Comment: 26 pages, 7 eps figure

Results from a natural experiment: initial neighbourhood investments do not change objectively-assessed physical activity, psychological distress or perceptions of the neighbourhood

Abstract Background Few studies have assessed objectively measured physical activity (PA), active transportation, psychological distress and neighborhood perceptions among residents of a neighborhood before and after substantial improvements in its physical environment. Also, most research-to-date has employed study designs subject to neighborhood selection, which may introduce bias in reported findings. We built upon a previously enrolled cohort of households from two low-income predominantly African American Pittsburgh neighborhoods, matched on socio-demographic composition including race/ethnicity, income and education. One of the two neighborhoods received substantial neighborhood investments over the course of this study including, but not limited to public housing development and greenspace/landscaping. We implemented a natural experiment using matched intervention and control neighborhoods and conducted pre-post assessments among the cohort. Our comprehensive assessments included accelerometry-based PA, active transportation, psychological distress and perceptions of the neighborhood, with assessments conducted both prior to and following the neighborhood changes. In 2013, we collected data from 1003 neighborhood participants and in 2016, we re-interviewed 676 of those participants. We conducted an intent to treat analysis, with a difference-in-difference estimator using attrition weighting to account for nonresponse between 2013 and 2016. In addition, we derived an individual-level indicator of exposure to neighbourhood investment and estimated effect of exposure to investment on the same set of outcomes using covariate-adjusted models. Results We observed no statistically significant differences in activity, psychological distress, satisfaction with one’s neighborhood as a place to live or any of the other measures we observed prior to and after the neighborhood investments between the intervention and control neighborhoods or those exposed vs not exposed to investments. Conclusions Using this rigorous study design, we observed no significant changes in the intervention neighborhood above and beyond secular trends present in the control neighborhood. Although neighborhood investment may have other benefits, we failed to see improvement in PA, psychological distress or related outcomes in the low-income African American neighborhoods in our study. This may be an indication that improvements in the physical environment may not directly translate into improvements in residents’ physical activity or health outcomes without additional individual-level interventions. It is also possible that these investments were not dramatic enough to spur change within the three year period. Additional studies employing similar design with other cohorts in other settings are needed to confirm these results. Trial registration Trial Registration is not applicable since we did not prospectively assign individuals to a health-related intervention.https://deepblue.lib.umich.edu/bitstream/2027.42/148333/1/12966_2019_Article_793.pd

The mediating roles of workplace support and ethical work environment in associations between leadership and moral distress:a longitudinal study of Canadian health care workers during the COVID-19 pandemic

Introduction: The COVID-19 pandemic has resulted in heightened moral distress among health care workers (HCWs) worldwide. Past research has shown that effective leadership may mitigate potential for the development of moral distress. However, no research to date has considered the mechanisms by which leadership might have an influence on moral distress. We sought to evaluate longitudinally whether Canadian HCWs’ perceptions of workplace support and ethical work environment would mediate associations between leadership and moral distress.Methods: A total of 239 French- and English-speaking Canadian HCWs employed during the COVID-19 pandemic were recruited to participate in a longitudinal online survey. Participants completed measures of organizational and supervisory leadership at baseline and follow-up assessments of workplace support, perceptions of an ethical work environment, and moral distress.Results: Associations between both organizational and supervisory leadership and moral distress were fully mediated by workplace supports and perceptions of an ethical work environment.Discussion: To ensure HCW well-being and quality of care, it is important to ensure that HCWs are provided with adequate workplace supports, including manageable work hours, social support, and recognition for efforts, as well as an ethical workplace environment