456 research outputs found

    The Changing Demographic Profile of the United States

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    [Excerpt] The United States, the third most populous country globally, accounts for about 4.5% of the world’s population. The U.S. population—currently estimated at 308.7 million persons—has more than doubled since its 1950 level of 152.3 million. More than just being double in size, the population has become qualitatively different from what it was in 1950. As noted by the Population Reference Bureau, “The U.S. is getting bigger, older, and more diverse.” The objective of this report is to highlight some of the demographic changes that have already occurred since 1950 and to illustrate how these and future trends will reshape the nation in the decades to come (through 2050). The United States Is Getting Bigger. U.S. population growth is due to the trends over time in the interplay of increased births, decreased deaths, and increased net immigration. The United States Is Getting Older. Aside from the total size, one of the most important demographic characteristics of a population for public policy is its age and sex structure. This report illustrates how the United States has been in the midst of a profound demographic change: the rapid aging of its population, as reflected by an increasing proportion of persons aged 65 and older, and an increasing median age in the population. The United States Is Becoming More Racially and Ethnically Diverse, reflecting the major influence that immigration has had on both the size and the age structure of the U.S. population. This section considers the changing profile of the five major racial groups in the United States. In addition, trends in the changing ethnic composition of the Hispanic or Latino Origin population are discussed. Although this report will not specifically discuss policy options to address the changing demographic profile, it is important to recognize that the inexorable demographic momentum will have important implications for the economic and social forces that will shape future societal well-being. There is ample reason to believe that the United States will be able to cope with the current and projected demographic changes if policymakers accelerate efforts to address and adapt to the changing population profile as it relates to a number of essential domains, such as work, retirement, and pensions; private wealth and income security; the federal budget and intergenerational equity; health, healthcare, and health spending; and the health and well-being of the aging population. These topics, among others, are discussed briefly in the final section of this report. This report will be updated as needed

    PTK6 Regulates IGF-1-Induced Anchorage-Independent Survival

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    Background: Proteins that are required for anchorage-independent survival of tumor cells represent attractive targets for therapeutic intervention since this property is believed to be critical for survival of tumor cells displaced from their natural niches. Anchorage-independent survival is induced by growth factor receptor hyperactivation in many cell types. We aimed to identify molecules that critically regulate IGF-1-induced anchorage-independent survival. Methods and Results: We conducted a high-throughput siRNA screen and identified PTK6 as a critical component of IGF-1 receptor (IGF-1R)-induced anchorage-independent survival of mammary epithelial cells. PTK6 downregulation induces apoptosis of breast and ovarian cancer cells deprived of matrix attachment, whereas its overexpression enhances survival. Reverse-phase protein arrays and subsequent analyses revealed that PTK6 forms a complex with IGF-1R and the adaptor protein IRS-1, and modulates anchorage-independent survival by regulating IGF-1R expression and phosphorylation. PTK6 is highly expressed not only in the previously reported Her2+^+ breast cancer subtype, but also in high grade ER+^+, Luminal B tumors and high expression is associated with adverse outcomes. Conclusions: These findings highlight PTK6 as a critical regulator of anchorage-independent survival of breast and ovarian tumor cells via modulation of IGF-1 receptor signaling, thus supporting PTK6 as a potential therapeutic target for multiple tumor types. The combined genomic and proteomic approaches in this report provide an effective strategy for identifying oncogenes and their mechanism of action

    Standardizing data reporting in the research community to enhance the utility of open data for SARS-CoV-2 wastewater surveillance

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    SARS-CoV-2 RNA detection in wastewater is being rapidly developed and adopted as a public health monitoring tool worldwide. With wastewater surveillance programs being implemented across many different scales and by many different stakeholders, it is critical that data collected and shared are accompanied by an appropriate minimal amount of meta-information to enable meaningful interpretation and use of this new information source and intercomparison across datasets. While some databases are being developed for specific surveillance programs locally, regionally, nationally, and internationally, common globally-adopted data standards have not yet been established within the research community. Establishing such standards will require national and international consensus on what meta-information should accompany SARS-CoV-2 wastewater measurements. To establish a recommendation on minimum information to accompany reporting of SARS-CoV-2 occurrence in wastewater for the research community, the United States National Science Foundation (NSF) Research Coordination Network on Wastewater Surveillance for SARS-CoV-2 hosted a workshop in February 2021 with participants from academia, government agencies, private companies, wastewater utilities, public health laboratories, and research institutes. This report presents the primary two outcomes of the workshop: (i) a recommendation on the set of minimum meta-information that is needed to confidently interpret wastewater SARS-CoV-2 data, and (ii) insights from workshop discussions on how to improve standardization of data reporting

    Combating subclonal evolution of resistant cancer phenotypes

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    Metastatic breast cancer remains challenging to treat, and most patients ultimately progress on therapy. This acquired drug resistance is largely due to drug-refractory sub-populations (subclones) within heterogeneous tumors. Here, we track the genetic and phenotypic subclonal evolution of four breast cancers through years of treatment to better understand how breast cancers become drug-resistant. Recurrently appearing post-chemotherapy mutations are rare. However, bulk and single-cell RNA sequencing reveal acquisition of malignant phenotypes after treatment, including enhanced mesenchymal and growth factor signaling, which may promote drug resistance, and decreased antigen presentation and TNF-α signaling, which may enable immune system avoidance. Some of these phenotypes pre-exist in pre-treatment subclones that become dominant after chemotherapy, indicating selection for resistance phenotypes. Post-chemotherapy cancer cells are effectively treated with drugs targeting acquired phenotypes. These findings highlight cancer's ability to evolve phenotypically and suggest a phenotype-targeted treatment strategy that adapts to cancer as it evolves

    Early Life Child Micronutrient Status, Maternal Reasoning, and a Nurturing Household Environment have Persistent Influences on Child Cognitive Development at Age 5 years : Results from MAL-ED

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    Funding Information: The Etiology, Risk Factors and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development Project (MAL-ED) is carried out as a collaborative project supported by the Bill & Melinda Gates Foundation, the Foundation for the NIH, and the National Institutes of Health/Fogarty International Center. This work was also supported by the Fogarty International Center, National Institutes of Health (D43-TW009359 to ETR). Author disclosures: BJJM, SAR, LEC, LLP, JCS, BK, RR, RS, ES, LB, ZR, AM, RS, BN, SH, MR, RO, ETR, and LEM-K, no conflicts of interest. Supplemental Tables 1–5 and Supplemental Figures 1–3 are available from the “Supplementary data” link in the online posting of the article and from the same link in the online table of contents at https://academic.oup.com/jn/. Address correspondence to LEM-K (e-mail: [email protected]). Abbreviations used: HOME, Home Observation for Measurement of the Environment inventory; MAL-ED, The Etiology, Risk Factors, and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development Project; TfR, transferrin receptor; WPPSI, Wechsler Preschool Primary Scales of Intelligence.Peer reviewe

    Early life child micronutrient status, maternal reasoning, and a nurturing household environment have persistent influences on child cognitive development at age 5 years: Results from MAL-ED

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    Background: Child cognitive development is influenced by early-life insults and protective factors. To what extent these factors have a long-term legacy on child development and hence fulfillment of cognitive potential is unknown. Objective: The aim of this study was to examine the relation between early-life factors (birth to 2 y) and cognitive development at 5 y. Methods: Observational follow-up visits were made of children at 5 y, previously enrolled in the community-based MAL-ED longitudinal cohort. The burden of enteropathogens, prevalence of illness, complementary diet intake, micronutrient status, and household and maternal factors from birth to 2 y were extensively measured and their relation with the Wechsler Preschool Primary Scales of Intelligence at 5 y was examined through use of linear regression. Results: Cognitive T-scores from 813 of 1198 (68%) children were examined and 5 variables had significant associations in multivariable models: mean child plasma transferrin receptor concentration (ÎČ: −1.81, 95% CI: −2.75, −0.86), number of years of maternal education (ÎČ: 0.27, 95% CI: 0.08, 0.45), maternal cognitive reasoning score (ÎČ: 0.09, 95% CI: 0.03, 0.15), household assets score (ÎČ: 0.64, 95% CI: 0.24, 1.04), and HOME child cleanliness factor (ÎČ: 0.60, 95% CI: 0.05, 1.15). In multivariable models, the mean rate of enteropathogen detections, burden of illness, and complementary food intakes between birth and 2 y were not significantly related to 5-y cognition. Conclusions: A nurturing home context in terms of a healthy/clean environment and household wealth, provision of adequate micronutrients, maternal education, and cognitive reasoning have a strong and persistent influence on child cognitive development. Efforts addressing aspects of poverty around micronutrient status, nurturing caregiving, and enabling home environments are likely to have lasting positive impacts on child cognitive development.publishedVersio

    A three arm cluster randomised controlled trial to test the effectiveness and cost-effectiveness of the SMART work & life intervention for reducing daily sitting time in office workers : study protocol

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    Background:Office-based workers typically spend 70-85% of working hours, and a large proportion of leisure time, sitting. High levels of sitting have been linked to poor health. There is a need for fully powered randomised controlled trials (RCTs) with long-term follow-up to test the effectiveness of interventions to reduce sitting. This paper describes the methodology of a three-arm cluster RCT designed to determine the effectiveness and cost-effectiveness of the SMART Work & Life intervention, delivered with and without a height-adjustable desk, for reducing daily sitting. Methods/Design:A three-arm cluster RCT of 33 clusters (660 council workers) will be conducted in three areas in England (Leicester; Manchester; Liverpool). Office groups (clusters) will be randomised to the SMART Work & Life intervention delivered with (group 1) or without (group 2) a height-adjustable desk or a control group (group 3). SMART Work & Life includes organisational (e.g., management buy-in, provision/support for standing meetings), environmental (e.g., relocating waste bins, printers), and group/individual (education, action planning, goal setting, addressing barriers, coaching, self-monitoring, social support) level behaviour change strategies, with strategies driven by workplace champions. Baseline, 3, 12 and 24 month measures will be taken. Objectively measured daily sitting time (activPAL3). objectively measured sitting, standing, stepping, prolonged sitting and moderate-to-vigorous physical activity time and number of steps at work and daily; objectively measured sleep (wrist accelerometry). Adiposity, blood pressure, fasting glucose, glycated haemoglobin, cholesterol (total, HDL, LDL) and triglycerides will be assessed from capillary blood samples. Questionnaires will examine dietary intake, fatigue, musculoskeletal issues, job performance and satisfaction, work engagement, occupational and general fatigue, stress, presenteeism, anxiety and depression and sickness absence (organisational records). Quality of life and resources used (e.g. GP visits, outpatient attendances) will also be assessed. We will conduct a full process evaluation and cost-effectiveness analysis. Discussion:The results of this RCT will 1) help to understand how effective an important simple, yet relatively expensive environmental change is for reducing sitting, 2) provide evidence on changing behaviour across all waking hours, and 3) provide evidence for policy guidelines around population and workplace health and well-being. Trial registration: ISRCTN11618007 . Registered on 21 January 2018
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