Evolution of acquired resistance in a ROS1+ KRAS G12C+ NSCLC through the MAPK pathway.

Patients with metastatic NSCLC bearing a ROS1 gene fusion usually experience prolonged disease control with ROS1-targeting tyrosine kinase inhibitors (TKI), but significant clinical heterogeneity exists in part due to the presence of co-occurring genomic alterations. Here, we report on a patient with metastatic NSCLC with a concurrent ROS1 fusion and KRAS p.G12C mutation at diagnosis who experienced a short duration of disease control on entrectinib, a ROS1 TKI. At progression, the patient continued entrectinib and started sotorasib, a small molecule inhibitor of KRAS p.G12C. A patient-derived cell line generated at progression on entrectinib demonstrated improved TKI responsiveness when treated with entrectinib and sotorasib. Cell-line growth dependence on both ROS1 and KRAS p.G12C was further reflected in the distinct downstream signaling pathways activated by each driver. Clinical benefit was not observed with combined therapy of entrectinib and sotorasib possibly related to an evolving KRAS p.G12C amplification identified on repeated molecular testing. This case supports the need for broad molecular profiling in patients with metastatic NSCLC for potential therapeutic and prognostic information.

Drivers of future urban flood risk.

Managing urban flood risk is a key global challenge of the twenty-first century. Drivers of future UK flood risk were identified and assessed by the Flood Foresight project in 2002-2004 and 2008; envisaging flood risk during the 2050s and 2080s under a range of scenarios for climate change and socio-economic development. This paper qualitatively reassesses and updates these drivers, using empirical evidence and advances in flood risk science, technology and practice gained since 2008. Of the original drivers, five have strengthened, three have weakened and 14 remain within their 2008 uncertainty bands. Rainfall, as impacted by climate change, is the leading source driver of future urban flood risk. Intra-urban asset deterioration, leading to increases in a range of consequential flood risks, is the primary pathway driver. Social impacts (risk to life and health, and the intangible impacts of flooding on communities) and continued capital investment in buildings and contents (leading to greater losses when newer buildings of higher economic worth are inundated) have strengthened as receptor drivers of urban flood risk. Further, we propose two new drivers: loss of floodable urban spaces and indirect economic impacts, which we suggest may have significant impacts on future urban flood risk. This article is part of the theme issue 'Urban flood resilience'.

Developing the implicit association test to uncover hidden preferences for sustainable drainage systems.

Understanding public perceptions of Sustainable Drainage Systems (SuDS) is critical for addressing barriers to their implementation. Perceptions are typically evaluated using explicit measures (e.g. questionnaires) that are subject to biases and may not fully capture attitudes towards SuDS. A novel image-based application of the Implicit Association Test is developed to investigate unconscious perceptions of SuDS in public greenspace and combined with explicit tests to evaluate perceptions of greenspace with and without SuDS, focusing on a sample population in Newcastle-upon-Tyne. Greenspace with or without SuDS is perceived positively by the sample population. Overall, respondents implicitly and explicitly prefer greenspace without SuDS and perceive greenspace without SuDS as more attractive, tidier and safer. The wide distribution of scores for SuDS, nonetheless, suggests a range of opinions and illustrates the complex nature of preferences for the use of greenspace. That the strongly negative explicit scores were not reflected in the implicit tests may suggest that explicit attitudes towards tidiness and safety may not be deep-rooted and are subject to social bias. Combined explicit and implicit tests may help us to understand any disconnect between expressed positive attitudes to natural spaces and behaviours around them and inform SuDS design to increase public acceptance. This article is part of the theme issue 'Urban flood resilience'.

Using Infant Mortality Data to Improve Maternal and Child Health Programs: An Application of Statistical Process Control Techniques for Rare Events.

Introduction The infant mortality rate (IMR) in the United States remains higher than most developed countries. To understand this public health issue and support state public health departments in displaying and analyzing data in ways that support learning, states participating in the Collaborative Improvement and Innovation Network to Reduce Infant Mortality (IM CoIIN) created statistical process control (SPC) charts for rare events. Methods State vital records data on live births and infant deaths was used to create U, T and G charts for Kansas and Alaska, two states participating in the IM CoIIN who sought methods to more effectively analyze IMR for subsets of their populations with infrequent number of deaths. The IMR and the number of days and number of births between infant deaths was charted for Kansas Non-Hispanic black population and six Alaska regions for the time periods 2013-2016 and 2011-2016, respectively. Established empirical patterns indicated points of special cause variation. Results The T and G charts for Kansas and G charts for Alaska depict points outside the upper control limit. These points indicate special cause variation and an increased number of days and/or births between deaths at these time periods. Discussion T and G charts offer value in examining rare events, and indicate special causes not detectable by U charts or other more traditional analytic methods. When small numbers make traditional analysis challenging, SPC has potential in the MCH field to better understand potential drivers of improvements in rare outcomes, inform decision making and take interventions to scale.

Patient-centered care innovations by accountable care organizations: Lessons from leaders.

Although there is a widespread belief that ACOs must be patient-centered to be successful, evidence to guide them in achieving that goal has been lacking. This case report examines four ACO innovators in patient-centered care that together represent urban, suburban and rural populations with a broad range of economic, racial, ethnic and geographic diversity. Seven patient-centeredness strategies emerged: transform primary care practices into patient-centered medical homes; move upstream to address social and economic issues; use both high-tech and high-touch to identify and engage high-risk patients; practice a whole-person orientation; optimize patient-reported measures; treat patients like valued customers; and incorporate patient voices into governance and operations. Exemplars prioritized direct care interventions perceived as central to financial and clinical success, and organizational maturity played a role. Activities that decreased the traditional system's authority, such as incorporating patient voices, were less popular. Local practice factors were important, and a mixture of mission and margin energized front-line staff in implementing patient-centered care as "the right thing to do." Unresolved questions remain that are related to the impact of individual and multiple interventions and how successful interventions can be disseminated widely. In order for patient-centeredness innovations to enable transformation, providers, payers and policymakers alike must consciously adopt strategies that nurture it.

IS WORK-FAMILY CONFLICT A MULTILEVEL STRESSOR LINKING JOB CONDITIONS TO MENTAL HEALTH? EVIDENCE FROM THE WORK, FAMILY AND HEALTH NETWORK.

PURPOSE: Most research on the work conditions and family responsibilities associated with work-family conflict and other measures of mental health uses the individual employee as the unit of analysis. We argue that work conditions are both individual psychosocial assessments and objective characteristics of the proximal work environment, necessitating multilevel analyses of both individual- and team-level work conditions on mental health. METHODOLOGY/APPROACH: This study uses multilevel data on 748 high-tech professionals in 120 teams to investigate relationships between team- and individual-level job conditions, work-family conflict, and four mental health outcomes (job satisfaction, emotional exhaustion, perceived stress, and psychological distress). FINDINGS: We find that work-to-family conflict is socially patterned across teams, as are job satisfaction and emotional exhaustion. Team-level job conditions predict team-level outcomes, while individuals' perceptions of their job conditions are better predictors of individuals' work-to-family conflict and mental health. Work-to-family conflict operates as a partial mediator between job demands and mental health outcomes. PRACTICAL IMPLICATIONS: Our findings suggest that organizational leaders concerned about presenteeism, sickness absences, and productivity would do well to focus on changing job conditions in ways that reduce job demands and work-to-family conflict in order to promote employees' mental health. ORIGINALITY/VALUE OF THE CHAPTER: We show that both work-to-family conflict and job conditions can be fruitfully framed as team characteristics, shared appraisals held in common by team members. This challenges the framing of work-to-family conflict as a "private trouble" and provides support for work-to-family conflict as a structural mismatch grounded in the social and temporal organization of work.

Manager support for work-family issues and its impact on employee-reported pain in the extended care setting.

OBJECTIVE: Supervisor-level policies and the presence of a manager engaged in an employee's need to achieve work-family balance, or "supervisory support," may benefit employee health, including self-reported pain. METHODS: We conducted a census of employees at four selected extended care facilities in the Boston metropolitan region (n = 368). Supervisory support was assessed through interviews with managers and pain was reported by employees. RESULTS: Our multilevel logistic models indicate that employees with managers who report the lowest levels of support for work-family balance experience twice as much overall pain as employees with managers who report high levels of support. CONCLUSIONS: Low supervisory support for work-family balance is associated with an increased prevalence of employee-reported pain in extended care facilities. We recommend that manager-level policies and practices receive additional attention as a potential risk factor for poor health in this setting.

Depressive symptoms in extended-care employees: children, social support, and work-family conditions.

To examine the relation between having a child aged 18 years and under in the home and employee depressive symptoms, we analyzed cross-sectional data from four extended care facilities in Boston, MA (n = 376 employees). Results show that having a child is associated with slightly higher depressive symptoms. The strength of this relationship in our models is attenuated with the inclusion of social support at home (ß = 1.08 and ß = 0.85, with and without support, respectively) and may differ by gender. We recommend that future research examine the role of parenting and social support in predicting employee mental health.

A review of state regulations to promote physical activity and safety on playgrounds in child care centers and family child care homes.

BACKGROUND: As interventions increasingly emphasize early child care settings, it is necessary to understand the state regulatory context that provides guidelines for outdoor physical activity and safety and sets standards for child care environments. METHODS: Researchers reviewed regulations for child care facilities for 50 states, the District of Columbia and the Virgin Islands. We compared state regulations with national standards for 17 physical activity- and safety-related items for outdoor playground settings outlined in Caring for Our Children: National Health and Safety Performance Standards: Guidelines for Out-of-Home Child Care Programs (CFOC). State regulations were coded as fully, partially or not addressing the CFOC standard and state-level summary scores were calculated. RESULTS: On average, state regulations fully addressed one-third of 17 CFOC standards in regulations for centers (34%) and family child care homes (27%). Data suggest insufficient attention to outdoor play area proximity and size, equipment height, surfacing, and inspections. CONCLUSIONS: Considerable variation exists among state regulations related to physical activity promotion and injury prevention within outdoor play areas. Many states' regulations do not comply with published national health and safety standards. Enhancing regulations is one component of a policy approach to promoting safe, physically active child care settings.

Social ties in relation to health status of low-income Brazilian women.

BACKGROUND: Social support resources are thought to buffer stressful life events and have been associated with numerous health outcomes in industrialized countries. Because the nature of supportive relationships varies by culture and social class, we studied the relationship of informal social support and networks to self-rated health among low-income women in northeastern Brazil. METHODS: Participants included 595 randomly sampled mothers from nine low-income communities in Teresina, Piauí, Brazil. Data on sociodemographic variables, social support, quality of the partner relationship, and self-rated health were collected cross-sectionally in 2002. Using multivariable logistic regression, we modeled the association between different aspects of social support and self-rated health. RESULTS: Poor or fair health was reported by 47% of participants. Women with poor partner relationships had an increased likelihood of poor or fair health (OR 1.7, 95% CI 1.1-2.7), as did those with no material support for food or money (OR 1.6, 95% CI 1.2, 2.0) and no support to resolve a conflict (OR 1.5, 95% CI 1.1, 2.1). Likewise, women with the lowest scores of the Medical Outcomes Study (MOS) social support survey were more likely than other women to report poor or fair health (OR 1.5, 95% CI 1.0, 2.1). CONCLUSIONS: Poor quality of a partner relationship, lack of support to resolve a conflict, and lack of material support as well as such sociodemographic variables as low education, poor sanitation, and depressive symptomatology are associated with lower health status in a population of low-income women from northeastern Brazil.