A US State Index of Successful Aging: Differences Between States and Over Time.

Policy Points The focus of successful aging is on the social contexts that enable individuals to be productively engaged and secure, with an emphasis on equity. There is currently no index to measure progress towards this goal at the US state level. We developed an empirical index for the evaluation of US state adaptation to societal aging across five critical domains that support successful population aging: (1) productivity and engagement, (2) security, (3) equity, (4) cohesion, and (5) well-being. Our index shows substantial variability over time and is not overly influenced by the performance of an individual domain. This suggests that it can be used to monitor state progress over time toward the goal of supporting successful aging. Rather than a major national trend, there are large between-state differences and changes in our index over time. This suggests individual US state policies and programs, as well as local economic conditions, may have a substantial impact on adaptations to societal aging. CONTEXT: Although it is recognized that aspects of US state environments impact the likelihood that older adults age successfully, there is currently no reliable and comprehensive measure of contexts that best support successful aging at a state level. The current project adapts a multidimensional index previously used to assess adaptation to successful aging in developed countries and applies it to the 50 US states and the District of Columbia. METHODS: We obtained data from multiple sources for all 50 US states and the District of Columbia from 2003 to 2017 in order to measure five distinct domains that define successful population aging: (1) productivity and engagement, (2) security, (3) equity, (4) cohesion, and (5) well-being. We created a ranking of states for the year 2017 based on these domains, and also examined how individual US state rankings changed over time from 2003 to 2017. FINDINGS: The level of adaptation to successful aging varied substantially between states and over time. The highest-ranked states in 2017 were Vermont, Hawaii, Iowa, Colorado, and New Hampshire, and the lowest-ranked states were Louisiana, Arkansas, Kentucky, West Virginia, and Mississippi. Mississippi, South Carolina, Iowa, Arizona, and Delaware had the greatest improvement in their ranking over the period of 2003 to 2017. Our findings were generally robust to the weighting scheme used and were not overly influenced by any particular domain. CONCLUSIONS: The US State Index of Successful Aging can be used to monitor US state progress in promoting the well-being and health of aging populations. Factors driving the changes in the index remain to be elucidated.

Thermal ecology of Northern Water Snakes (Nerodia sipedon) in a northern wetland in central Michigan.

Semi-aquatic north-temperate reptiles experience challenging environmental conditions for thermoregulation on both seasonal and daily bases. We studied the thermal biology of north-temperate Northern Water Snakes (Nerodia sipedon) in central Michigan by remote radiotelemetry monitoring of snake body temperature (Tb) using surgically implanted thermally-sensitive radio-transmitters and by measuring operative temperatures (Te) across a range of microhabitats using biophysical models. Our goals included evaluation of thermoregulatory capabilities at a locality that we viewed to be a fine-grained thermal environment, seasonal variations in patterns of thermoregulation, and the effects of sex on thermoregulation. During summer, snakes showed diel Tb cycling apparently using the open Sphagnum mat for late morning warming and shuttling among different microhabitats until early evening when a monotonic decline in Tb ensued and continued through the early morning hours. Snakes attained Tb within their laboratory-determined preferred body temperature range (Tset = 28-33 °C) mostly during late afternoon and with average percentages of Tb values for individual snakes within Tset range when permitted by operative temperatures (Ex) between 68 and 70% of the time depending on method of measurement. Relatively high investment in thermoregulation when thermal conditions were poor occurred only during September but declined thereafter as snakes prepared to overwinter. We did not detect differences in thermoregulation among reproductive females, non-reproductive females, and males. Relative to a population of N. sipedon at a higher latitude in Ontario our snakes showed a relatively high Tset range and thermoregulated more effectively, particularly during the daylight hours. It remains unclear how much inter-population variation in thermoregulation is due to potential adaptations to latitude, to habitat differences, or variations in methodologies.

Multidimensional comparison of countries' adaptation to societal aging.

As long-term changes in life expectancy and fertility drive the emergence of aging societies across the globe, individual countries vary widely in the development of age-relevant policies and programs. While failure to adapt to the demographic transformation carries not only important financial risks but also social risks, most efforts to gauge countries' preparedness focus on economic indicators. Using data from the Organization for Economic Cooperation and Development (OECD) and other sources, we developed a multidimensional Aging Society Index that assesses the status of older populations across five specific domains, including productivity and engagement, well-being, equity, economic and physical security, and intergenerational cohesion. For 18 OECD countries, the results demonstrate substantial diversity in countries' progress in adapting to aging. For any given domain, there are wide differences across countries, and within most countries, there is substantial variation across domains. Overall, Norway and Sweden rank first in adaptation to aging, followed by the United States, The Netherlands, and Japan. Central and eastern European countries rank at the bottom, with huge untapped potential for successful aging. The United States ranks best in productivity and engagement, in the top half for cohesion, and in the middle in well-being, but it ranks third from the bottom in equity. Only well-being and security showed significant between-domain correlation (r = 0.59, P = 0.011), strengthening the case for a multidimensional index. Examination of heterogeneity within and across domains of the index can be used to assess the need for, and effectiveness of, various programs and policies and facilitate successful adaptation to the demographic transition.

Precision Medicine in Internal Medicine.

Medicine has long sought to match diagnostic and treatment approaches to the particular needs and risks of individual patients. The decreasing cost and increasing ease of genetic sequencing have propelled the rise of precision medicine. Precision medicine aims to use genetic and other information to provide care tailored to the individual patient, with the goal of improving clinical outcomes and minimizing unnecessary diagnostic and therapeutic interventions. Although developments in genetic sequencing have the potential to transform clinical care, there are important limitations, including uncertainty in the clinical interpretation of many genetic variants and concerns about privacy, discrimination, and cost. To help clinicians understand the basics of genetic sequencing and how to apply it in clinical practice, Annals of Internal Medicine is launching a new "Precision Medicine" series. This introduction provides a general overview of clinical sequencing, with a focus on germline variation. Subsequent articles will use a case-based format to provide concise summaries of specific clinical precision medicine scenarios that are relevant to the practice of internal medicine. These cases will highlight specific clinical indications; interpretation of genetic test results; and ethical, legal, cost, and privacy issues related to genetic testing. The goal is to provide practical information on the appropriate application and interpretation of genomics in routine clinical practice.

Diel and seasonal variations in the thermal biology of San Cristobal Lava Lizards (Microlophus bivittatus).

Thermal biology, and therefore energy acquisition and survival, of ectotherms can be affected by diel and seasonal patterns of environmental temperatures. Galápagos Lava Lizards live in seasonal environments that are characterized by a warm and wet period when reproductive activity is maximal, and cooler and drier period. With the use of radiotelemetric techniques to record lizard surface temperatures (Ts), we studied the thermal ecology of the San Cristóbal Lava Lizard (Microlophus bivittatus) during both the warm and cool seasons over two years. During the diel activity period and when operative temperatures exceeded Tset-min, at least on rock faces without canopy, 52% or less of the Ts observations fell within the laboratory-determined Tset range (36-40 °C). Therefore, lizards may have avoided very warm midday temperatures in shaded microhabitats and the lag times in changes in Ts values occurred as operative temperatures rose rapidly during late morning warming phase. Lizards effectively thermoregulated during a year with moderate warm season temperatures and during a cool season that was unseasonably warm. In contrast, lizards less effectively thermoregulated during the warmest and coolest years of the study. We did not detect intersexual differences in thermoregulation although males may thermoregulate less effectively than do females during the cool season although we were unable to detect significant differences using our nonparametric statistical techniques.

Use of Intensive Care Services for Medicare Beneficiaries Undergoing Major Surgical Procedures.

BACKGROUND: Use of intensive care after major surgical procedures and whether routinely admitting patients to intensive care units (ICUs) improve outcomes or increase costs is unknown. METHODS: The authors examined frequency of admission to an ICU during the hospital stay for Medicare beneficiaries undergoing selected major surgical procedures: elective endovascular abdominal aortic aneurysm (AAA) repair, cystectomy, pancreaticoduodenectomy, esophagectomy, and elective open AAA repair. The authors compared hospital mortality, length of stay, and Medicare payments for patients receiving each procedure in hospitals admitting patients to the ICU less than 50% of the time (low use), 50 to 89% (moderate use), and 90% or greater (high use), adjusting for patient and hospital factors. RESULTS: The cohort ranged from 7,878 patients in 162 hospitals for esophagectomies to 69,989 patients in 866 hospitals for endovascular AAA. Overall admission to ICU ranged from 35.6% (endovascular AAA) to 71.3% (open AAA). Admission to ICU across hospitals ranged from less than 5% to 100% of patients for each surgical procedure. There was no association between hospital use of intensive care and mortality for any of the five surgical procedures. There was a consistent association between high use of intensive care with longer length of hospital stay and higher Medicare payments only for endovascular AAA. CONCLUSIONS: There is little consensus regarding the need for intensive care for patients undergoing major surgical procedures and no relationship between a hospital's use of intensive care and hospital mortality. There is also no consistent relationship across surgical procedures between use of intensive care and either length of hospital stay or payments for care.

Thermal and substrate color-induced melanization in laboratory reared red-eared sliders (Trachemys scripta elegans).

Color and pigmentation patterns of the integument can facilitate crypsis, thermoregulation, and social signaling. According to the "thermal melanism hypothesis", cold environmental temperature should increase the quantity of melanin that is deposited in the integument thereby facilitating radiative warming. We studied the influences of water temperature (26°C or 31°C) and substrate color (black or white) on the degree of melanization in the red-eared slider, Trachemys scripta elegans, under laboratory conditions. Turtles reared on a black substrate, or in 26°C water, for 120 days were darker than those reared on a white substrate or in 31°C water. A potential tradeoff between the fitness benefits of crypsis and the benefits of radiative warming through melanism was detected because turtles reared in 26°C water and on a white substrate were darker than those reared on a white substrate and in 31°C water. Low temperatures limited metabolic processes because turtles reared in 26°C water grew more slowly than those reared in 31°C water. However, histological analyses revealed that melanization was a dynamic process in all treatments confirming that the degree of melanization in the cool water treatment was not influenced by the initial and relatively dark hatchling coloration in individuals that grew relatively slowly.

Daily and annual patterns of thermoregulation in painted turtles (Chrysemys picta marginata) living in a thermally variable marsh in Northern Michigan.

The capacity for an ectothermic reptile to thermoregulate has implications for many components of its life history. Over two years, we studied thermoregulation in a population of Midland painted turtles (Chrysemys picta marginata) in a shallow, thermally variable wetland during summer in Northern Michigan. Mean body temperature (Tb) of free-ranging turtles was greater in 2008 (25.8 °C) than in 2010 (19.7 °C). Laboratory determined thermoregulatory set point (Tset) ranged from 25 °C (Tset-min) to 31 °C (Tset-max) and was lower during the fall (17-26 °C). Deviations of Tb distributions from field measured operative temperatures (Te) and indices of thermoregulation indicated that C. picta marginata were capable of a limited degree of thermoregulation. Operative temperatures and thermal quality (de=|Tset-min-Te| and |Te-Tset-max|) cycled daily with maximal thermal quality occurring during late morning and late afternoon. The accuracy of thermoregulation (db=|Tset-min-Tb| and |Tb-Tset-max|) was maximal (db values were minimal) as Tb declined and traversed Tset during the late afternoon-early evening hours and was higher on cloudy days than on sunny days because relatively low Te values decreased the number of Tb values that were above Tset. Our index of thermal exploitation (Ex=frequency of Tb observations within Tset) was 36%, slightly lower than that reported for an Ontario population of C. picta marginata. Regression of db (thermal accuracy) on de (thermal quality) indicated that turtles invested more in thermoregulation when thermal quality was low and when water levels were high than when they were low. There were no intersexual differences in mean Tb throughout the year but females had relatively high laboratory determined Tb values in the fall, perhaps reflecting the importance of maintaining ovarian development prior to winter.

The Forgotten Middle: Worsening Health And Economic Trends Extend To Americans With Modest Resources Nearing Retirement.

In an aging US society, anticipating the challenges that future seniors will face is essential. This study analyzed the health and economic well-being of five cohorts of Americans in their mid-fifties between 1994 and 2018 using the Future Elderly Model, a dynamic microsimulation based on the Health and Retirement Study. We projected mortality, quality-adjusted life years, health expenditures, and income and benefits. We classified individuals by economic status and focused on the lower middle and upper middle of the economic distribution. Outcome disparities between people in these two groups widened substantially between the 1994 and 2018 cohorts. Quality-adjusted life expectancy increased (5 percent) for the upper-middle economic status group but stagnated for their lower-middle peers. We found that the combined value of the current stock (financial and housing wealth) and the present value of the expected flow of resources (income, health expenditures, and quality-adjusted life-years) after age sixty grew 13 percent for the upper-middle group between cohorts, whereas people in the lower-middle group in 2018 were left scarcely better off (3 percent growth) than their peers two decades earlier. The relatively neglected "forgotten middle" group of near-retirees in the lower-middle group may require stronger supports than are currently available to them.

Gender differences in countries' adaptation to societal ageing: an international cross-sectional comparison.

BACKGROUND: Gender differences in life expectancy and societal roles have implications for a country's capacity to support its older population. Specifically, the longevity risk associated with longer life expectancy of women, with greater risk of morbidity entails different needs between genders in older age. We aimed to quantify gender differences in the ageing experience of older people in Organization for Economic Cooperation and Development (OECD) countries as a first step in identifying policy gaps and differences in the allocation of resources and social support for older men and women. METHODS: We constructed a multidimensional Ageing Index to account for gender differences in societal ageing, using mostly gender-disaggregated latest available data between 2015 and 2019, for 18 OECD countries. Our Ageing Index is a weighted sum of scores for five domains, which consisted of various measures, that are important for societal ageing: wellbeing, productivity and engagement, equity, security, and cohesion. The construction of the domains and their relative weighting was determined by the Research Network on an Ageing Society, an interdisciplinary group of academics. We computed the overall index and domain scores (from 0 to 100) for each gender and compared these scores between genders and countries. FINDINGS: In every country, gender differences in key domains of societal ageing favour men. Countries in northern Europe (ie, Denmark, Sweden, Finland and Norway), the Netherlands, and Japan had high overall Index scores for both genders, whereas many eastern and southern European countries (eg, Hungary, Poland, and Slovenia) performed less well. Countries with the largest gender difference in Index scores include the Netherlands, Germany, and Italy, whereas Ireland, Spain, and Poland had the smallest difference. Gender differences were present for the domains of productivity and engagement, security, and cohesion. Gender differences favoured men for domain productivity and engagement (mean 10·2, 95% CI 7·8-12·6; p<0·0001), security (10·3, 7·8-12·7; p<0·0001), and cohesion (21·1, 13·9-28·1; p<0·0001). Although the domains of wellbeing and equity showed more mixed results, they nonetheless showed a slight advantage for men. INTERPRETATION: Our multidimensional index helps to identify specific gender differences along key domains of societal ageing in various OECD countries. Furthermore, the inter-country comparisons reveal those countries with more successful societal ageing, which could be instructive for policy makers. FUNDING: John A Hartford Foundation and the Singapore Ministry of Education.

Application of machine learning to large in vitro databases to identify drug-cancer cell interactions: azithromycin and KLK6 mutation status.

Recent advances in machine learning promise to yield novel insights by interrogation of large datasets ranging from gene expression and mutation data to CRISPR knockouts and drug screens. We combined existing and new algorithms with available experimental data to identify potentially clinically relevant relationships to provide a proof of principle for the promise of machine learning in oncological drug discovery. Specifically, we screened cell line data from the Cancer Dependency Map for the effects of azithromycin, which has been shown to kill cancer cells in vitro. Our findings demonstrate a strong relationship between Kallikrein Related Peptidase 6 (KLK6) mutation status and the ability of azithromycin to kill cancer cells in vitro. While the application of azithromycin showed no meaningful average effect in KLK6 wild-type cell lines, statistically significant enhancements of cell death are seen in multiple independent KLK6-mutated cancer cell lines. These findings suggest a potentially valuable clinical strategy in patients with KLK6-mutated malignancies.

Rethinking the urban physical environment for century-long lives: from age-friendly to longevity-ready cities.

In response to increasing life expectancies and urbanization, initiatives for age-friendly cities seek to facilitate active and healthy aging by strengthening supports and services for older people. While laudable, these efforts typically neglect early-life exposures that influence long-term well-being. With a focus on the urban physical environment, we argue that longevity-ready cities can accomplish more than initiatives focused solely on old age. We review features of cities that cumulatively influence healthy aging and longevity, discuss the need for proactive interventions in a changing climate, and highlight inequities in the ambient physical environment, especially those encountered at early ages, that powerfully contribute to disparities in later life stages. Compared with strategies aimed largely at accommodating older populations, longevity-ready cities would aim to reduce the sources of disadvantages across the life course and simultaneously improve the well-being of older people.