Effectiveness of a fourth dose of mRNA COVID-19 vaccine against all-cause mortality in long-term care facility residents and in the oldest old: A nationwide, retrospective cohort study in Sweden.

Background - The effect of a fourth dose of COVID-19 vaccine on the risk of death in the oldest and frailest individuals is unknown. Methods - Two matched cohorts were formed using Swedish nationwide registers. In the first, residents of long-term care facilities (LTCFs) given a fourth dose of an mRNA vaccine from 1 January 2022 onwards were matched 1:1 on birth year and county of residence to residents given at least a third dose (N = 24,524). In the second, all individuals aged ≥80 years given a fourth dose were matched 1:1 to individuals given at least a third dose (N = 394,104). Cox regression models were used to estimate hazard ratios for all-cause mortality in fourth-dose recipients as compared with in third-dose recipients, with relative vaccine effectiveness (VE) estimated as 1 minus the hazard ratio. Findings - From 7 days after baseline and onwards, there were 1119 deaths in the LTCF cohort during a median follow-up of 77 days and a maximum follow-up of 126 days. During days 7 to 60, the VE of the fourth dose was 39% (95% CI, 29-48), which declined to 27% (95% CI, -2-48) during days 61 to 126. In the cohort of all individuals aged ≥80 years, there were 5753 deaths during a median follow-up of 73 days and a maximum follow-up of 143 days. During days 7 to 60, the VE of the fourth dose was 71% (95% CI, 69-72), which declined to 54% (95% CI, 48-60) during days 61 to 143. The VE of the fourth dose seemed stronger when it was compared to third-dose recipients where at least four months had passed since vaccination (P Interpretation - As compared with a third dose, a fourth dose of an mRNA COVID-19 vaccine, administered during the Omicron era, was associated with reduced risk of death from all causes in residents of LTCFs and in the oldest old during the first two months, after which the protection became slightly lower. These findings suggest that a fourth dose may prevent premature mortality in the oldest and frailest even after the emergence of the Omicron variant, although the timing of vaccination seems to be important with respect to the slight waning observed after two months

Digital exercise interventions for improving measures of central obesity: a systematic review

Objectives - We aimed to systematically review the potential benefits of digital exercise interventions for improving measures of central obesity including visceral adipose tissue (VAT) and anthropometric surrogates for VAT in overweight or centrally obese adults aged 18 or over. Methods - A systematic literature search was conducted in three databases up until March 2020 (PROSPERO registration nr CRD42019126764). Results - N = 5 studies including 438 participants (age 48–80) with body mass index ≥ 25 kg/m2 met the eligibility criteria and were included. The duration of the interventions ranged from 8 to 24 weeks. No study measured the primary outcome VAT, although in N = 4 studies, waist circumference (WC) decreased by between 1.3 and 5.6 cm in the intervention groups. Conclusions - This systematic review shows that there is no evidence for the effects of digital exercise on VAT, although digital exercise may decrease WC. These findings highlight the need for additional randomized controlled trials to confirm the findings with respect to WC, and to further investigate the effects of digital exercise on VAT. Together, this may have important implications for reducing the burden of physical inactivity and obesity

Daily Step Count and Incident Diabetes in Community-Dwelling 70-Year-Olds: A Prospective Cohort Study

Background: Older adults with diabetes take fewer steps per day than those without diabetes. The purpose of the present study was to investigate the association of daily step count with incident diabetes in community-dwelling 70-year-olds. Methods: This prospective cohort study included N = 3055 community-dwelling 70-year-olds (52% women) who participated in a health examination in Umeå, Sweden during 2012–2017, and who were free from diabetes at baseline. Daily step count was measured for 1 week using Actigraph GT3X+ accelerometers. Cases of diabetes were collected from the Swedish National Patient Register. The dose-response association was evaluated graphically using a flexible parametric model, and hazard ratios (HR) with 95% confidence intervals (CI) were calculated using Cox regressions. Results: During a mean follow-up of 2.6 years, diabetes was diagnosed in 81 participants. There was an inverse nonlinear dose-response association between daily step count and incident diabetes, with a steep decline in risk of diabetes from a higher daily step count until around 6000 steps/day. From there, the risk decreased at a slower rate until it leveled off at around 8000 steps/day. A threshold of 4500 steps/day was found to best distinguish participants with the lowest risk of diabetes, where those taking ≥ 4500 steps/day, had 59% lower risk of diabetes, compared to those taking fewer steps (HR, 0.41, 95% CI, 0.25–0.66). Adjusting for visceral adipose tissue (VAT) attenuated the association (HR, 0.64, 95% CI, 0.38–1.06), which was marginally altered after further adjusting for sedentary time, education and other cardiometabolic risk factors and diseases (HR, 0.58, 95% CI, 0.32–1.05). Conclusions: A higher daily step count is associated with lower risk of incident diabetes in community-dwelling 70-year-olds. The greatest benefits occur at the lower end of the activity range, and much earlier than 10,000 steps/day. With the limitation of being an observational study, these findings suggest that promoting even a modest increase in daily step count may help to reduce the risk of diabetes in older adults. Because VAT appears to partly mediate the association, lifestyle interventions targeting diabetes should apart from promoting physical activity also aim to prevent and reduce central obesity

Prospective Association of Daily Steps with Cardiovascular Disease: A Harmonized Meta-Analysis

Background: Taking fewer than the widely promoted “10 000 steps per day” has recently been associated with lower risk of all-cause mortality. The relationship of steps and cardiovascular disease (CVD) risk remains poorly described. A meta-analysis examining the dose–response relationship between steps per day and CVD can help inform clinical and public health guidelines. Methods: Eight prospective studies (20 152 adults [ie, ≥18 years of age]) were included with device-measured steps and participants followed for CVD events. Studies quantified steps per day and CVD events were defined as fatal and nonfatal coronary heart disease, stroke, and heart failure. Cox proportional hazards regression analyses were completed using study-specific quartiles and hazard ratios (HR) and 95% CI were meta-analyzed with inverse-variance–weighted random effects models. Results: The mean age of participants was 63.2±12.4 years and 52% were women. The mean follow-up was 6.2 years (123 209 person-years), with a total of 1523 CVD events (12.4 per 1000 participant-years) reported. There was a significant difference in the association of steps per day and CVD between older (ie, ≥60 years of age) and younger adults (ie, <60 years of age). For older adults, the HR for quartile 2 was 0.80 (95% CI, 0.69 to 0.93), 0.62 for quartile 3 (95% CI, 0.52 to 0.74), and 0.51 for quartile 4 (95% CI, 0.41 to 0.63) compared with the lowest quartile. For younger adults, the HR for quartile 2 was 0.79 (95% CI, 0.46 to 1.35), 0.90 for quartile 3 (95% CI, 0.64 to 1.25), and 0.95 for quartile 4 (95% CI, 0.61 to 1.48) compared with the lowest quartile. Restricted cubic splines demonstrated a nonlinear association whereby more steps were associated with decreased risk of CVD among older adults. Conclusions: For older adults, taking more daily steps was associated with a progressively decreased risk of CVD. Monitoring and promoting steps per day is a simple metric for clinician–patient communication and population health to reduce the risk of CVD

Daily steps and all-cause mortality: a meta-analysis of 15 international cohorts

Background Although 10000 steps per day is widely promoted to have health benefits, there is little evidence to support this recommendation. We aimed to determine the association between number of steps per day and stepping rate with all-cause mortality. Methods In this meta-analysis, we identified studies investigating the effect of daily step count on all-cause mortality in adults (aged ≥18 years), via a previously published systematic review and expert knowledge of the field. We asked participating study investigators to process their participant-level data following a standardised protocol. The primary outcome was all-cause mortality collected from death certificates and country registries. We analysed the dose– response association of steps per day and stepping rate with all-cause mortality. We did Cox proportional hazards regression analyses using study-specific quartiles of steps per day and calculated hazard ratios (HRs) with inversevariance weighted random effects models. Findings We identified 15 studies, of which seven were published and eight were unpublished, with study start dates between 1999 and 2018. The total sample included 47 471 adults, among whom there were 3013 deaths (10·1 per 1000 participant-years) over a median follow-up of 7·1 years ([IQR 4·3–9·9]; total sum of follow-up across studies was 297 837 person-years). Quartile median steps per day were 3553 for quartile 1, 5801 for quartile 2, 7842 for quartile 3, and 10 901 for quartile 4. Compared with the lowest quartile, the adjusted HR for all-cause mortality was 0·60 (95% CI 0·51–0·71) for quartile 2, 0·55 (0·49–0·62) for quartile 3, and 0·47 (0·39–0·57) for quartile 4. Restricted cubic splines showed progressively decreasing risk of mortality among adults aged 60 years and older with increasing number of steps per day until 6000–8000 steps per day and among adults younger than 60 years until 8000–10000 steps per day. Adjusting for number of steps per day, comparing quartile 1 with quartile 4, the association between higher stepping rates and mortality was attenuated but remained significant for a peak of 30 min (HR 0·67 [95% CI 0·56–0·83]) and a peak of 60 min (0·67 [0·50–0·90]), but not significant for time (min per day) spent walking at 40 steps per min or faster (1·12 [0·96–1·32]) and 100 steps per min or faster (0·86 [0·58–1·28]). Interpretation Taking more steps per day was associated with a progressively lower risk of all-cause mortality, up to a level that varied by age. The findings from this meta-analysis can be used to inform step guidelines for public health promotion of physical activity

Research and Design of a Routing Protocol in Large-Scale Wireless Sensor Networks

无线传感器网络，作为全球未来十大技术之一，集成了传感器技术、嵌入式计算技术、分布式信息处理和自组织网技术，可实时感知、采集、处理、传输网络分布区域内的各种信息数据，在军事国防、生物医疗、环境监测、抢险救灾、防恐反恐、危险区域远程控制等领域具有十分广阔的应用前景。 本文研究分析了无线传感器网络的已有路由协议，并针对大规模的无线传感器网络设计了一种树状路由协议，它根据节点地址信息来形成路由，从而简化了复杂繁冗的路由表查找和维护，节省了不必要的开销，提高了路由效率，实现了快速有效的数据传输。 为支持此路由协议本文提出了一种自适应动态地址分配算——ADAR（AdaptiveDynamicAddre...As one of the ten high technologies in the future, wireless sensor network, which is the integration of micro-sensors, embedded computing, modern network and Ad Hoc technologies, can apperceive, collect, process and transmit various information data within the region. It can be used in military defense, biomedical, environmental monitoring, disaster relief, counter-terrorism, remote control of haz...学位：工学硕士院系专业：信息科学与技术学院通信工程系_通信与信息系统学号：2332007115216

Fysisk aktivitet, visceralt fett och kardiovaskulär sjukdom hos äldre personer : samband och effekter

BACKGROUND: Cardiovascular disease (CVD) poses a substantial public health burden and is the leading cause of mortality in older adults. With the population aging rapidly, interventions aimed at improving modifiable risk factors for CVD, such as physical inactivity and visceral obesity, could play an important role in reducing its burden, provided they are proven effective. PURPOSE AND AIMS: The overall purpose of this thesis was to create a deeper understanding of the links between physical activity, visceral adipose tissue (VAT), and CVD in older adults, by studying it from both an observational and an interventional perspective. The specific aims were to investigate the associations of objectively measured physical activity and VAT with the risk of CVD and all-cause mortality, to investigate the effect of structured physical activity (exercise) on VAT, and to review the effects of exercise on CVD and all-cause mortality based on evidence from randomized controlled trials (RCTs). METHODS: This thesis comprised two prospective cohort studies, one RCT, and one narrative review of evidence from RCTs. The cohort studies included about 3,300 men and women aged 70 years with baseline data on physical activity and VAT mass, as obtained using accelerometry and dual-energy X-ray absorptiometry, respectively. Cases of stroke, myocardial infarction, and all-cause mortality during follow-up were collected from Swedish nationwide registers. The RCT included 77 men and women aged 70 years with visceral obesity who were randomly allocated to either 10 weeks of supervised vigorous-intensity exercise or to no exercise, with VAT mass measured before and after the intervention. In the review, evidence from published RCTs and meta-analyses of RCTs reporting on the effects of exercise on CVD (N=19,162) and all-cause mortality (N=37,443) in general older adults and in individuals with chronic conditions (such as obesity, type 2 diabetes, and preexisting CVD) were reviewed. MAIN FINDINGS: In the cohort studies, greater amounts of physical activity of any intensity, but especially that of moderate to vigorous intensity, were associated with lower risk of stroke, myocardial infarction, and all-cause mortality. Conversely, greater VAT mass was associated with higher risk of stroke or myocardial infarction. In the RCT, short-term vigorous-intensity exercise seemed to decrease VAT mass slightly, but the effect was not statistically significant. Finally, the review showed that there is currently no convincing evidence from RCTs that exercise effectively reduces the risk of CVD or all-cause mortality, which stands in sharp contrast to the strong associations typically reported in observational studies. The reasons for the conflicting findings are likely complex and multifactorial. In the RCTs, a lack of statistical power could partly explain why no effects have been detected in the general population of older adults, but it is unlikely to explain the null findings in clinical populations, as some of these trials, including meta-analyses of such trials, have been large. Other potential explanations could be a ceiling effect due to the inclusion of participants who were healthier and more physically active than the general population, or that an effect of exercise was masked by the use of effective medications such as antihypertensives and lipid-lowering agents. On the other hand, observational studies have likely overestimated the benefits of physical activity, because these studies are vulnerable to selection bias, reverse causation, and unmeasured confounding, such as from heritable influences. CONCLUSIONS AND IMPLICATIONS: Despite strong associations, the protective effect of physical activity as a single intervention against CVD and all-cause mortality in older adults is probably not as substantial as is commonly presumed. To uncover the true role of physical activity in preventing CVD, further high-quality trials would be valuable. However, because these trials are very difficult and resource demanding, they should be complemented by innovative observational studies that seek to strengthen causal inference through addressing sources of bias and confounding that are often incompletely accounted for in conventional observational studies. This could include a variety of methodologies, such as utilizing negative control outcomes, instrumental variables, sibling comparisons, and other genetically informed designs. As the aging population continues to grow, it becomes increasingly important to take these scientific steps in order to provide a more definitive answer to the question of the extent to which physical activity alone can reduce the risk of CVD

Fysisk aktivitet, visceralt fett och kardiovaskulär sjukdom hos äldre personer : samband och effekter

BACKGROUND: Cardiovascular disease (CVD) poses a substantial public health burden and is the leading cause of mortality in older adults. With the population aging rapidly, interventions aimed at improving modifiable risk factors for CVD, such as physical inactivity and visceral obesity, could play an important role in reducing its burden, provided they are proven effective. PURPOSE AND AIMS: The overall purpose of this thesis was to create a deeper understanding of the links between physical activity, visceral adipose tissue (VAT), and CVD in older adults, by studying it from both an observational and an interventional perspective. The specific aims were to investigate the associations of objectively measured physical activity and VAT with the risk of CVD and all-cause mortality, to investigate the effect of structured physical activity (exercise) on VAT, and to review the effects of exercise on CVD and all-cause mortality based on evidence from randomized controlled trials (RCTs). METHODS: This thesis comprised two prospective cohort studies, one RCT, and one narrative review of evidence from RCTs. The cohort studies included about 3,300 men and women aged 70 years with baseline data on physical activity and VAT mass, as obtained using accelerometry and dual-energy X-ray absorptiometry, respectively. Cases of stroke, myocardial infarction, and all-cause mortality during follow-up were collected from Swedish nationwide registers. The RCT included 77 men and women aged 70 years with visceral obesity who were randomly allocated to either 10 weeks of supervised vigorous-intensity exercise or to no exercise, with VAT mass measured before and after the intervention. In the review, evidence from published RCTs and meta-analyses of RCTs reporting on the effects of exercise on CVD (N=19,162) and all-cause mortality (N=37,443) in general older adults and in individuals with chronic conditions (such as obesity, type 2 diabetes, and preexisting CVD) were reviewed. MAIN FINDINGS: In the cohort studies, greater amounts of physical activity of any intensity, but especially that of moderate to vigorous intensity, were associated with lower risk of stroke, myocardial infarction, and all-cause mortality. Conversely, greater VAT mass was associated with higher risk of stroke or myocardial infarction. In the RCT, short-term vigorous-intensity exercise seemed to decrease VAT mass slightly, but the effect was not statistically significant. Finally, the review showed that there is currently no convincing evidence from RCTs that exercise effectively reduces the risk of CVD or all-cause mortality, which stands in sharp contrast to the strong associations typically reported in observational studies. The reasons for the conflicting findings are likely complex and multifactorial. In the RCTs, a lack of statistical power could partly explain why no effects have been detected in the general population of older adults, but it is unlikely to explain the null findings in clinical populations, as some of these trials, including meta-analyses of such trials, have been large. Other potential explanations could be a ceiling effect due to the inclusion of participants who were healthier and more physically active than the general population, or that an effect of exercise was masked by the use of effective medications such as antihypertensives and lipid-lowering agents. On the other hand, observational studies have likely overestimated the benefits of physical activity, because these studies are vulnerable to selection bias, reverse causation, and unmeasured confounding, such as from heritable influences. CONCLUSIONS AND IMPLICATIONS: Despite strong associations, the protective effect of physical activity as a single intervention against CVD and all-cause mortality in older adults is probably not as substantial as is commonly presumed. To uncover the true role of physical activity in preventing CVD, further high-quality trials would be valuable. However, because these trials are very difficult and resource demanding, they should be complemented by innovative observational studies that seek to strengthen causal inference through addressing sources of bias and confounding that are often incompletely accounted for in conventional observational studies. This could include a variety of methodologies, such as utilizing negative control outcomes, instrumental variables, sibling comparisons, and other genetically informed designs. As the aging population continues to grow, it becomes increasingly important to take these scientific steps in order to provide a more definitive answer to the question of the extent to which physical activity alone can reduce the risk of CVD

Does exercise prevent major non-communicable diseases and premature mortality? : A critical review based on results from randomized controlled trials

Observational studies show that physical activity is strongly associated with a reduced risk of premature mortality and major non-communicable diseases. We reviewed to which extent these associations have been confirmed in randomized controlled trials (RCTs) for the outcomes of mortality, cardiovascular disease (CVD), type 2 diabetes (T2D), and fracture. The results show that exercise does not reduce all-cause mortality and incident CVD in older adults or in people with chronic conditions, based on RCTs comprising ∼50,000 participants. The results also indicate a lack of effect on cardiovascular mortality in people with chronic conditions, based on RCTs comprising ∼11,000 participants. Furthermore, there is inconsistent evidence regarding the effect of exercise on fractures in older adults, based on RCTs comprising ∼40,000 participants. Finally, based on RCTs comprising ∼17,000 participants, exercise reduces T2D incidence in people with prediabetes when combined with dietary modification, although evidence for the individual effect of exercise is lacking. Identified shortcomings of the current evidence include risks of publication bias, lack of high-quality studies in certain high-risk populations, and inconstant evidence with respect to some outcomes. Thus, additional large trials would be of value, especially with fracture as the primary outcome. In conclusion, according to current RCT evidence, exercise can prevent T2D assuming it is combined with dietary intervention. However, the current evidence shows that exercise does not prevent premature mortality or CVD, with inconsistent evidence for fractures