Ejecta from the DART-produced active asteroid Dimorphos.

Some active asteroids have been proposed to be formed as a result of impact events1. Because active asteroids are generally discovered by chance only after their tails have fully formed, the process of how impact ejecta evolve into a tail has, to our knowledge, not been directly observed. The Double Asteroid Redirection Test (DART) mission of NASA2, in addition to having successfully changed the orbital period of Dimorphos3, demonstrated the activation process of an asteroid resulting from an impact under precisely known conditions. Here we report the observations of the DART impact ejecta with the Hubble Space Telescope from impact time T + 15 min to T + 18.5 days at spatial resolutions of around 2.1 km per pixel. Our observations reveal the complex evolution of the ejecta, which are first dominated by the gravitational interaction between the Didymos binary system and the ejected dust and subsequently by solar radiation pressure. The lowest-speed ejecta dispersed through a sustained tail that had a consistent morphology with previously observed asteroid tails thought to be produced by an impact4,5. The evolution of the ejecta after the controlled impact experiment of DART thus provides a framework for understanding the fundamental mechanisms that act on asteroids disrupted by a natural impact1,6.

Successful kinetic impact into an asteroid for planetary defence.

Although no known asteroid poses a threat to Earth for at least the next century, the catalogue of near-Earth asteroids is incomplete for objects whose impacts would produce regional devastation1,2. Several approaches have been proposed to potentially prevent an asteroid impact with Earth by deflecting or disrupting an asteroid1-3. A test of kinetic impact technology was identified as the highest-priority space mission related to asteroid mitigation1. NASA's Double Asteroid Redirection Test (DART) mission is a full-scale test of kinetic impact technology. The mission's target asteroid was Dimorphos, the secondary member of the S-type binary near-Earth asteroid (65803) Didymos. This binary asteroid system was chosen to enable ground-based telescopes to quantify the asteroid deflection caused by the impact of the DART spacecraft4. Although past missions have utilized impactors to investigate the properties of small bodies5,6, those earlier missions were not intended to deflect their targets and did not achieve measurable deflections. Here we report the DART spacecraft's autonomous kinetic impact into Dimorphos and reconstruct the impact event, including the timeline leading to impact, the location and nature of the DART impact site, and the size and shape of Dimorphos. The successful impact of the DART spacecraft with Dimorphos and the resulting change in the orbit of Dimorphos7 demonstrates that kinetic impactor technology is a viable technique to potentially defend Earth if necessary.

Momentum transfer from the DART mission kinetic impact on asteroid Dimorphos.

The NASA Double Asteroid Redirection Test (DART) mission performed a kinetic impact on asteroid Dimorphos, the satellite of the binary asteroid (65803) Didymos, at 23:14 UTC on 26 September 2022 as a planetary defence test1. DART was the first hypervelocity impact experiment on an asteroid at size and velocity scales relevant to planetary defence, intended to validate kinetic impact as a means of asteroid deflection. Here we report a determination of the momentum transferred to an asteroid by kinetic impact. On the basis of the change in the binary orbit period2, we find an instantaneous reduction in Dimorphos's along-track orbital velocity component of 2.70 ± 0.10 mm s-1, indicating enhanced momentum transfer due to recoil from ejecta streams produced by the impact3,4. For a Dimorphos bulk density range of 1,500 to 3,300 kg m-3, we find that the expected value of the momentum enhancement factor, ß, ranges between 2.2 and 4.9, depending on the mass of Dimorphos. If Dimorphos and Didymos are assumed to have equal densities of 2,400 kg m-3, [Formula: see text]. These ß values indicate that substantially more momentum was transferred to Dimorphos from the escaping impact ejecta than was incident with DART. Therefore, the DART kinetic impact was highly effective in deflecting the asteroid Dimorphos.

Bennu's near-Earth lifetime of 1.75 million years inferred from craters on its boulders.

An asteroid's history is determined in large part by its strength against collisions with other objects1,2 (impact strength). Laboratory experiments on centimetre-scale meteorites3 have been extrapolated and buttressed with numerical simulations to derive the impact strength at the asteroid scale4,5. In situ evidence of impacts on boulders on airless planetary bodies has come from Apollo lunar samples6 and images of the asteroid (25143) Itokawa7. It has not yet been possible, however, to assess directly the impact strength, and thus the absolute surface age, of the boulders that constitute the building blocks of a rubble-pile asteroid. Here we report an analysis of the size and depth of craters observed on boulders on the asteroid (101955) Bennu. We show that the impact strength of metre-sized boulders is 0.44 to 1.7 megapascals, which is low compared to that of solid terrestrial materials. We infer that Bennu's metre-sized boulders record its history of impact by millimetre- to centimetre-scale objects in near-Earth space. We conclude that this population of near-Earth impactors has a size frequency distribution similar to that of metre-scale bolides and originates from the asteroidal population. Our results indicate that Bennu has been dynamically decoupled from the main asteroid belt for 1.75 ± 0.75 million years.

High-resolution shape models of Phobos and Deimos from stereophotoclinometry.

We created high-resolution shape models of Phobos and Deimos using stereophotoclinometry and united images from Viking Orbiter, Phobos 2, Mars Global Surveyor, Mars Express, and Mars Reconnaissance Orbiter into a single coregistered collection. The best-fit ellipsoid to the Phobos model has radii of (12.95 ± 0.04) km × (11.30 ± 0.04) km × (9.16 ± 0.03) km, with an average radius of (11.08 ± 0.04) km. The best-fit ellipsoid to the Deimos model has radii of (8.04 ± 0.08) km × (5.89 ± 0.06) km × (5.11 ± 0.05) km with an average radius of (6.27 ± 0.07) km. The new shape models offer substantial improvements in resolution over existing shape models, while remaining globally consistent with them. The Phobos model resolves grooves, craters, and other surface features ~ 100 m in size across the entire surface. The Deimos model is the first to resolve geological surface features. These models, associated data products, and a searchable, coregistered collection of images across six spacecraft are publicly available in the Small Body Mapping Tool, and will be archived with the NASA Planetary Data System. These products enable an array of future studies to advance the understanding of Phobos and Deimos, facilitate coregistration of other past and future datasets, and set the stage for planning and operating future missions to the moons, including the upcoming Martian Moons eXploration (MMX) mission. Supplementary Information: The online version contains supplementary material available at 10.1186/s40623-023-01814-7.

COVID-19 in patients with lung cancer.

BACKGROUND: Patients with lung cancers may have disproportionately severe coronavirus disease 2019 (COVID-19) outcomes. Understanding the patient-specific and cancer-specific features that impact the severity of COVID-19 may inform optimal cancer care during this pandemic. PATIENTS AND METHODS: We examined consecutive patients with lung cancer and confirmed diagnosis of COVID-19 (n = 102) at a single center from 12 March 2020 to 6 May 2020. Thresholds of severity were defined a priori as hospitalization, intensive care unit/intubation/do not intubate ([ICU/intubation/DNI] a composite metric of severe disease), or death. Recovery was defined as >14 days from COVID-19 test and >3 days since symptom resolution. Human leukocyte antigen (HLA) alleles were inferred from MSK-IMPACT (n = 46) and compared with controls with lung cancer and no known non-COVID-19 (n = 5166). RESULTS: COVID-19 was severe in patients with lung cancer (62% hospitalized, 25% died). Although severe, COVID-19 accounted for a minority of overall lung cancer deaths during the pandemic (11% overall). Determinants of COVID-19 severity were largely patient-specific features, including smoking status and chronic obstructive pulmonary disease [odds ratio for severe COVID-19 2.9, 95% confidence interval 1.07-9.44 comparing the median (23.5 pack-years) to never-smoker and 3.87, 95% confidence interval 1.35-9.68, respectively]. Cancer-specific features, including prior thoracic surgery/radiation and recent systemic therapies did not impact severity. Human leukocyte antigen supertypes were generally similar in mild or severe cases of COVID-19 compared with non-COVID-19 controls. Most patients recovered from COVID-19, including 25% patients initially requiring intubation. Among hospitalized patients, hydroxychloroquine did not improve COVID-19 outcomes. CONCLUSION: COVID-19 is associated with high burden of severity in patients with lung cancer. Patient-specific features, rather than cancer-specific features or treatments, are the greatest determinants of severity.

Changes in spinal bone density, back muscle size, and visceral adipose tissue and their interaction following a multi-component exercise program in older men: secondary analysis of an 18-month randomized controlled trial.

In middle-aged and older men, an 18-month multi-component exercise program improved spinal trabecular BMD, paraspinal, and psoas muscle cross-sectional area (CSA) but not visceral adipose tissue (VAT). However, changes in both muscle and VAT CSA were associated with changes in spinal BMD, independent of the exercise intervention. INTRODUCTION: In older men, we previously reported that a multi-component exercise program improved lumbar spine (LS) trabecular volumetric BMD (Tb.vBMD) compared with no exercise. This study aimed to investigate the following: (1) the effect of the exercise program on paraspinal and psoas (back) muscle CSA and VAT, and 2) if any exercise-related changes in muscle CSA and/or VAT were associated with changes in spinal BMD. METHODS: Men (n = 180) aged 50-79 years were randomized to an exercise or no-exercise group. Exercise involved high-intensity progressive resistance training (60-85% max) with weight-bearing impact exercise (3 days/week) for 18 months. Quantitative computed tomography was used to assess L1-L3 Tb.vBMD, paraspinal, and psoas muscle CSA and VAT. RESULTS: Exercise resulted in a 2.6% ((95% CI, 1.1, 4.1), P < 0.01) net gain in back muscle CSA, but no effect on VAT (-1.6% (95% CI, -7.3, 4.2)) relative to no exercise. Robust regression indicated that percentage changes in Tb.vBMD were positively associated with changes (expressed as z-scores) in back muscle CSA in both the exercise (beta (ß)-coefficient = 1.9, 95% CI 0.5, 3.2, P = 0.007) and no-exercise (ß = 2.6, 95% CI, 1.1, 4.1, P = 0.001) group, and negatively with the changes in VAT (ß = -2.0, 95% CI -3.3, -0.7, P = 0.003) in the exercise only group. There were no group differences in the slopes for the muscle-bone or VAT-bone relationships. Regression analysis (pooled data) revealed that back muscle CSA and VAT were independent predictors of the change in Tb.vBMD, explaining 14% of the variance. CONCLUSION: A multi-component exercise program in middle-aged and older men improved spinal BMD and back muscle size but not visceral fat. However, changes in back muscle size and VAT were associated with the changes in spinal BMD, independent of exercise. TRIAL REGISTRATION: ACTRN 12617001224314, 22/08/2017 retrospectively registered.

Utility of four sarcopenia criteria for the prediction of falls-related hospitalization in older Australian women.

Numerous sarcopenia definitions are not associated with increased falls-related hospitalization risk over 5 years to 9.5 years in older community-dwelling Australian women. Measures of muscle strength and physical function, but not appendicular lean mass (measured by dual-energy X-ray absorptiometry) may help discriminate the risk of falls-related hospitalization. INTRODUCTION: The aim of this prospective, population-based cohort study of 903 Caucasian-Australian women (mean age 79.9 ± 2.6 years) was to compare the clinical utility of four sarcopenia definitions for the prediction of falls-related hospitalization over 9.5 years. METHODS: The four definitions were the United States Foundation for the National Institutes of Health (FNIH), the European Working Group on Sarcopenia in Older People (EWGSOP), and modified FNIH (AUS-POPF) and EWGSOP (AUS-POPE) definitions using Australian population-specific cut points (< 2 SD below the mean of young healthy Australian women). Components of sarcopenia including muscle strength, physical function, and appendicular lean mass (ALM) were quantified using hand grip strength, timed-up-and-go (TUG), and dual-energy X-ray absorptiometry (DXA), respectively. Incident 9.5-year falls-related hospitalization were captured by linked data. RESULTS: Baseline prevalence of sarcopenia according to FNIH (9.4%), EWGSOP (24.1%), AUS-POPF (12.0%), and AUS-POPE (10.7%) differed substantially. Sarcopenia did not increase the relative hazard ratio (HR) for falls-related hospitalization before or after adjustment for age (aHR): FNIH aHR 1.00 95%CI (0.69-1.47), EWGSOP aHR 1.20 95%CI (0.93-1.54), AUS-POPF aHR 0.96 95%CI (0.68-1.35), and AUS-POPE aHR 1.33 95%CI (0.94-1.88). When examining individual components of sarcopenia, only muscle strength and physical function but not ALM (adjusted for height2 or BMI) were associated with falls-related hospitalization. CONCLUSION: Current definitions of sarcopenia were not associated with falls-related hospitalization risk in this cohort of community-dwelling older Australian women. Finally, measures of muscle strength and physical function, but not ALM (measured by DXA) may help discriminate the risk of falls-related hospitalization.

Development and content validity of the Lupus Foundation of America rapid evaluation of activity in lupus (LFA-REAL™): a patient-reported outcome measure for lupus disease activity.

BACKGROUND/PURPOSE: The LFA REAL™ is a measurement system for evaluating lupus disease activity from both clinician and patient perspectives. Patients' viewpoints are captured using a patient-reported outcome (PRO) questionnaire. A series of visual analog scales are designed to rate disease severity and progress over the past 4 weeks. Brief instructions guide the patient to distinguish between active, potentially reversible symptoms and chronic pain or discomfort that are more likely due to damage. Beyond its simplicity and efficiency, the PRO can provide versatile assessments from a global, organ-based, and symptom-specific level. This paper describes the patient-centered approach used to evaluate the content validity of the LFA-REAL PRO. METHODS: The PRO was developed in accordance with FDA guidance. A two-phase qualitative study was performed with 25 lupus patients, 10 who participated in concept elicitation (Phase 1) and 15 in cognitive debriefing interviews (Phase 2). Qualitative data were analyzed using ATLAS.ti software v7.5. Upon completion of the interviews, participants completed the draft PRO and additional measures to characterize the sample. RESULTS: The mean age of participants was 45.6 and 88% were female, as expected in a lupus population. The mean SF-36 physical component score was 29.8 and the mean mental component score was 46.4. Phase 1 elicited symptom saturation and mapping of the draft PRO. Fatigue was reported by 100% of patients, highlighting its importance as a measurable domain. Additionally, 100% of patients spontaneously mentioned arthritis, which may be more important to this group than previously estimated, substantiating the approach of this PRO to break down components of arthritis into joint pain, stiffness, and swelling. Shortness of breath and fever were reported more frequently than expected. Phase 2 data demonstrated that participants found the instrument easy to use and offered recommendations to improve clarity, leading to adjustments in wording and formatting. CONCLUSIONS: Results suggest that the LFA-REAL PRO has content validity and, with some modifications suggested by participants, is ready for quantitative validation, including tests of reliability, validity, responsiveness to change, and performance relative to other PROs used in lupus trials. After validation, the LFA-REAL system is intended for use in clinical practice and research.

The effect of exercise on bone mineral density in adult cancer survivors: a systematic review and meta-analysis.

PURPOSE: Certain cancer treatments are associated with bone loss and increased fracture risk. Weight-bearing impact exercise, resistance training or the combination, are recommended to preserve or improve bone mineral density (BMD) inhealthy older adults, but their efficacy in cancer survivors is less well understood. The aim of this systematic review with meta-analysis of randomised control trials (RCT) was to review the evidence regarding the role of exercise to counteract cancer treatment-induced bone loss. METHODS: Four databases were searched systematically with 12 RCTs of at least 6-month duration investigating the effects of exercise on BMD compared to a control group in adult cancer survivors identified. RESULTS: Meta-analysis was completed using available data from six studies enrolling 814 participants, with lumbar spine, femoral neck and/or total hip BMD as the primary outcome measures. Overall, there was no significant benefit of exercise compared to controls on BMD at the lumbar spine (0.0071 g/cm , 95% CI -0.0002 to 0.0145, p = 0.057), femoral neck (0.0044 g/cm , 95% CI -0.0005 to 0.0093, p = 0.077), or total hip (0.0024 g/cm , 95% CI -0.0038 to 0.0086, p = 0.443). Subgroup analysis revealed a positive effect on lumbar spine BMD in three studies implementing a combined resistance and impact exercise intervention (0.015 g/cm , 95% CI 0.003 to 0.028, p = 0.019). CONCLUSIONS: From the evidence available, exercise may not be sufficient to improve bone health in cancer survivors, but given the heterogeneity in the participant characteristics and several exercise programs which may not have been designed to specifically optimise bone health, these findings should be interpreted with caution.

Association of sitting time and breaks in sitting with muscle mass, strength, function, and inflammation in community-dwelling older adults.

The mechanisms through which excessive sitting time impacts health are important to understand. This study found that each hour of sitting per day was not associated with physical function, although associations with poor body composition were observed. Reducing sitting time for improved weight management in older adults needs further exploration. INTRODUCTION: To examine the association of sitting time and breaks in sitting time with muscle mass, strength, function, and inflammation in older Australians. METHODS: Data from the thigh-worn activPAL3™ monitor (7-day continuous wear) was used to derive time spent sitting (hours) and total number of sit-stand transitions per day. Body composition (dual energy X-ray absorptiometry), lower-body muscle strength, function (timed up-and-go [TUG], 4-m gait speed, four square step test, 30-second sit-to-stand), and serum inflammatory markers (interleukin-[IL-6], IL-8, IL-10, tumor necrosis factor-alpha [TNF-α], and adiponectin) were measured. Multiple regression analyses, adjusted for age, sex, ethnicity, education, employment status, marital status, number of prescription medications, smoking status, vitamin D, and stepping time, were used to assess the associations. RESULTS: Data from 123 community-dwelling older adults (aged 65-84 years, 63% female) were used. Total daily sitting time was associated with lower percentage lean mass (ß [95%CI], - 1.70% [- 2.30, - 1.10]) and higher total body fat mass (2.92 kg [1.94, 3.30]). More frequent breaks in sitting time were associated with a 45% reduced risk of having pre-sarcopenia (OR = 0.55; 95% CI 0.34, 0.91; model 1), defined as appendicular lean mass divided by BMI. No significant associations were observed for sitting time or breaks in sitting with measures of muscle strength, function, or inflammation. CONCLUSION: In older community-dwelling adults, greater sitting time was associated with a lower percentage lean mass, while more frequent breaks in sitting time were associated with lower odds of having pre-sarcopenia. This suggests that reducing sedentary time and introducing frequent breaks in sedentary time may be beneficial for improving body composition in healthy older adults.

The caregiver burden in lupus: findings from UNVEIL, a national online lupus survey in the United States.

OBJECTIVES: Lupus imposes a substantial burden on patients; however, little is known about its impact on those caring for patients with the disease. In this study, we examined the impact 'caring for patients with lupus' has on caregivers from their own perspective. METHODS: UNVEIL was a one-time online national cross-sectional survey developed in partnership with the Lupus Foundation of America and fielded targeting the US Lupus Foundation of America constituents in 2014. Eligible caregivers were adults who self-identified as unpaid caregivers of patients with lupus. Eligible caregivers had to complete a series of sociodemographic questions as well as a series of well established outcome measures, such as the Short Form 12v2 Health Survey, the Work Productivity and Activity Index, the Caregiver Burden Inventory, and the Perceived Benefits of Caregiving Scale. RESULTS: A total of 253 caregivers completed the survey. The majority of caregivers (90.1%) were aged 60 years or younger, more than half (54.2%) were men, and more than half (59.7%) identified themselves as either a spouse or a partner to the patient with lupus they were caring for. Overall health-related quality of life was close to the norm mean of the general US population. Caregivers who were employed missed an average of 12.8% of paid work time due to caregiving responsibilities and reported a 33.5% reduction in on-the-job effectiveness. Nearly half of the caregivers surveyed (49.4%) indicated that their caregiving responsibilities impacted their ability to socialize with friends, and almost all caregivers (97.6%) reported experiencing increased anxiety and stress in relation to their caregiving role. CONCLUSIONS: Caregiving for patients with lupus has a substantial impact on the work productivity and the social and emotional functioning of caregivers. Healthcare professionals and policymakers should continually assess the impact of healthcare decisions on the well-being of those caring for patients with lupus.

Exercise and nutritional approaches to prevent frail bones, falls and fractures: an update.

Osteoporosis (low bone strength) and sarcopenia (low muscle mass, strength and/or impaired function) often co-exist (hence the term 'sarco-osteoporosis') and have similar health consequences with regard to disability, falls, frailty and fractures. Exercise and adequate nutrition, particularly with regard to vitamin D, calcium and protein, are key lifestyle approaches that can simultaneously optimize bone, muscle and functional outcomes in older people, if they are individually tailored and appropriately prescribed in terms of the type and dose. Not all forms of exercise are equally effective for optimizing musculoskeletal health. Regular walking alone has little or no effect on bone or muscle. Traditional progressive resistance training (PRT) is effective for improving muscle mass, size and strength, but it has mixed effects on muscle function and falls which may be due to the common prescription of slow and controlled movement patterns. At present, targeted multi-modal programs incorporating traditional and high-velocity PRT, weight-bearing impact exercises and challenging balance/mobility activities appear to be most effective for optimizing musculoskeletal health and function. Reducing and breaking up sitting time may also help attenuate muscle loss. There is also evidence to support an interaction between exercise and various nutritional factors, particularly protein and some multi-nutrient supplements, on muscle and bone health in the elderly. This review summary provides an overview of the latest evidence with regard to the optimal type and dose of exercise and the role of various nutritional factors for preventing bone and muscle loss and improving functional capacity in older people.

Feasibility of a multi-modal exercise program on cognition in older adults with Type 2 diabetes - a pilot randomised controlled trial.

BACKGROUND: Type 2 Diabetes (T2D) is associated with increased risk of dementia. We aimed to determine the feasibility of a randomised controlled trial (RCT) examining the efficacy of exercise on cognition and brain structure in people with T2D. METHODS: A 6-month pilot parallel RCT of a progressive aerobic- and resistance-training program versus a gentle movement control group in people with T2D aged 50-75 years (n = 50) at the University of Tasmania, Australia. Assessors were blinded to group allocation. Brain volume (total, white matter, hippocampus), cortical thickness and white matter microstructure (fractional anisotrophy and mean diffusivity) were measured using magnetic resonance imaging, and cognition using a battery of neuropsychological tests. Study design was assessed by any changes (during the pilot or recommended) to the protocol, recruitment by numbers screened and time to enrol 50 participants; randomisation by similarity of characteristics in groups at baseline, adherence by exercise class attendance; safety by number and description of adverse events and retention by numbers withdrawn. RESULTS: The mean age of participants was 66.2 (SD 4.9) years and 48% were women. There were no changes to the design during the study. A total of 114 people were screened for eligibility, with 50 participants with T2D enrolled over 8 months. Forty-seven participants (94%) completed the study (23 of 24 controls; 24 of 26 in the intervention group). Baseline characteristics were reasonably balanced between groups. Exercise class attendance was 79% for the intervention and 75% for the control group. There were 6 serious adverse events assessed as not or unlikely to be due to the intervention. Effect sizes for each outcome variable are provided. CONCLUSION: This study supports the feasibility of a large scale RCT to test the benefits of multi-modal exercise to prevent cognitive decline in people with T2D. Design changes to the future trial are provided. TRIAL REGISTRATION: ANZCTR 12614000222640 ; Registered 3/3/2014; First participant enrolled 26/6/2014, study screening commenced 1/9/2014; Australian and New Zealand Clinical Trial Registry.

Liver Allograft Provides Immunoprotection for the Cardiac Allograft in Combined Heart-Liver Transplantation.

When transplanted simultaneously, the liver allograft has been thought to have an immunoprotective role on other organs; however, detailed analyses in simultaneous heart-liver transplantation (SHLT) have not been done to date. We analyzed patient outcomes and incidence of immune-mediated injury in 22 consecutive SHLT versus 223 isolated heart transplantation (IHT) recipients between January 2004 and December 2013, by reviewing 3912 protocol- and indication-specific cardiac allograft biopsy specimens. Overall survival was similar (86.4%, 86.4%, and 69.1% for SHLT and 93.3%, 84.7%, and 70.0% for IHT at 1, 5, and 10 years; p = 0.83). Despite similar immunosuppression, the incidence of T cell-mediated rejection (TCMR) was lower in SHLT (31.8%) than in IHT (84.8%) (p < 0.0001). Although more SHLT patients had preexisting donor-specific HLA antibody (22.7% versus 8.1%; p = 0.04), the incidence of antibody-mediated rejection was not different in SHLT compared with IHT (4.5% versus 14.8%, p = 0.33). While the left ventricular ejection fraction was comparable in both groups at 5 years, the incidence and severity of cardiac allograft vasculopathy were reduced in the SHLT recipients (42.9% versus 66.8%, p = 0.03). Simultaneously transplanted liver allograft was associated with reduced risk of TCMR (odds ratio [OR] 0.003, 95% confidence interval [CI] 0-0.02; p < 0.0001), antibody-mediated rejection (OR 0.04, 95% CI 0-0.46; p = 0.004), and cardiac allograft vasculopathy (OR 0.26, 95% CI 0.07-0.84; p = 0.02), after adjusting for other risk factors. These data suggest that the incidence of alloimmune injury in the heart allograft is reduced in SHLT recipients.

Cytokine profiling of docetaxel-resistant castration-resistant prostate cancer.

BACKGROUND: Docetaxel improves symptoms and survival in metastatic castration-resistant prostate cancer (CRPC). However, ∼50% of patients are chemoresistant. This study examined whether changes in cytokine levels predict for docetaxel resistance in vitro and in a clinical cohort. METHODS: PC3 cells or their docetaxel-resistant subline (PC3Rx) were co-cultured with U937 monocytes, with and without docetaxel treatment, and cytokine levels were measured. The circulating levels of 28 cytokines were measured pre-/post cycle 1 of docetaxel from 55 men with CRPC, and compared with prostate-specific antigen (PSA) response. RESULTS: PC3Rx-U937 co-culture expressed more cytokines, chiefly markers of alternative macrophage differentiation, compared with PC3-U937 co-culture. Docetaxel treatment enhanced cytokine production by PC3Rx-U937 co-culture, while reducing cytokine levels in PC3-U937. In patients, changes in the levels of seven circulating cytokines (macrophage inhibitory cytokine 1 (MIC1), interleukin (IL)-1ra, IL-1ß, IL-4, IL-6, IL-12 and IFNγ) after cycle 1 of docetaxel were associated with progressive disease (all P<0.05). The combination of changes in MIC1, IL-4 and IL-6 most strongly predicted PSA response (P=0.002). CONCLUSIONS: In vitro studies suggest docetaxel resistance is mediated, at least in part, by cytokines induced by the interaction between the docetaxel-resistant tumour cells and macrophages. Early changes in circulating cytokine levels were associated with docetaxel resistance in CRPC patients. When considered together, these data suggest a significant role for the inflammatory response and macrophages in the development of docetaxel resistance in CRPC.

Association between serum concentration of 25-hydroxyvitamin D and the risk of hip arthroplasty for osteoarthritis: result from a prospective cohort study.

OBJECTIVES: There is ongoing debate regarding the optimal serum concentrations of 25-hydroxy-vitamin D for musculoskeletal health, including osteoarthritis (OA). The aim of this prospective cohort study was to determine whether serum 25-hydroxy-vitamin D concentrations were associated with the risk of hip arthroplasty for OA. DESIGN: This study examined 9135 participants from the Australian Diabetes, Obesity and Lifestyle Study who had serum 25-hydroxy-vitamin D measured in 1999-2000 and were aged ≥40 years at the commencement of arthroplasty data collection. The incidence of hip arthroplasty for OA during 2002-2011 was determined by linking cohort records to the Australian Orthopaedic Association National Joint Replacement Registry. RESULTS: Over an average 9.1 (standard deviation (SD) 2.7) years of follow-up, 201 hip arthroplasties for OA were identified (males n = 90; females n = 111). In males, a one-standard-deviation increase in 25-hydroxy-vitamin D was associated with a 25% increased incidence (HR 1.25, 95% CI 1.02-1.56), with a dose response relationship evident by quartiles of 25-hydroxy-vitamin D concentration (P for trend 0.04). These results were independent of age, body mass index (BMI), ethnicity, smoking status, physical activity, season of blood collection, latitude, hypertension and diabetes, area level disadvantage or after excluding those with extreme low 25-hydroxy-vitamin D concentrations. No significant association was observed in women (HR 1.10, 95% CI 0.87, 1.39). CONCLUSIONS: Increasing serum 25-hydroxy-vitamin D concentrations were associated with an increased risk of hip arthroplasty for OA in males, while no significant association was observed in females. The mechanism for the association warrants further investigation.

Associations between sedentary behaviour and body composition, muscle function and sarcopenia in community-dwelling older adults.

SUMMARY: While previous studies have reported detrimental associations of sedentary behaviours with cardiometabolic disorders and mortality, in this study, we report that higher levels of sitting time were associated with a greater risk of sarcopenia, with increased television (TV) viewing negatively associated with lean mass, independent of physical activity. INTRODUCTION: Sedentary behaviour has been linked to cardiometabolic disorders and mortality, but little is known about its effects on musculoskeletal health and function. This study investigated the relationship between total sitting and TV viewing time on sarcopenia and its determinants (muscle mass, strength and function) in older adults. METHODS: This cross-sectional study included 162 community-dwelling men and women aged 60 to 86 years who had complete assessment of total body and regional lean mass (LM) and fat mass (dual-energy X-ray absorptiometry (DXA)), lower limb muscle strength, power and functional performance. Sarcopenia was defined as the lowest sex-specific quartile for relative appendicular LM plus muscle strength and/or gait speed. Total sitting and TV viewing time were self-reported using a validated questionnaire. A sitting fragmentation ratio, as an index of breaks in sitting time, was calculated as the number of sitting bouts divided by total sitting time. RESULTS: Greater overall sitting time was associated with an increased risk of sarcopenia; for each 1-h increment, the risk increased by 33% [odds ratio 1.33 (95% confidence interval (CI) 1.05, 1.68)], independent of physical activity and other lifestyle and confounding factors. TV viewing time was associated with lower total body and leg LM after adjusting for various confounders and fat mass. There were no associations between total sitting or TV viewing time or the fragmentation ratio with any other measure. CONCLUSION: Higher levels of sedentary behaviour in older adults were associated with reduced muscle mass and an increased risk of sarcopenia in community-dwelling older adults, independent of physical activity.

Effects of vitamin D supplementation on neuroplasticity in older adults: a double-blinded, placebo-controlled randomised trial.

UNLABELLED: Vitamin D can improve muscle function and reduce falls, but whether it can strengthen neural connections within the brain and nervous system is not known. This 10-week randomised controlled trial indicates that treatment with 2,000 IU/day vitamin D3 does not significantly alter neuroplasticity relative to placebo in older adults. INTRODUCTION: The purpose of this study was to examine the effects of vitamin D supplementation on neuroplasticity, serum brain-derived neurotrophic factor (BDNF) and muscle strength and function in older adults. METHODS: This was a 10-week double-blinded, placebo-controlled randomised trial in which 26 older adults with 25-hydroxyvitamin D [25OHD] concentrations 25-60 nmol/L were randomised to 2,000 IU/day vitamin D3 or matched placebo. Single- and paired-pulse transcranial magnetic stimulation applied over the motor cortex was used to assess changes in motor-evoked potentials (MEPs) and short-interval intracortical inhibition (SICI), as measures of corticospinal excitability and inhibition respectively, by recording electromyography (EMG) responses to stimulation from the wrist extensors. Changes in muscle strength, stair climbing power, gait (timed-up-and-go), dynamic balance (four square step test), serum 25(OH)D and BDNF concentrations were also measured. RESULTS: After 10 weeks, mean 25(OH)D levels increased from 46 to 81 nmol/L in the vitamin D group with no change in the placebo group. The vitamin D group experienced a significant 8-11% increase in muscle strength and a reduction in cortical excitability (MEP amplitude) and SICI relative to baseline (all P < 0.05), but these changes were not significantly different from placebo. There was no effect of vitamin D on muscle power, function or BDNF. CONCLUSIONS: Daily supplementation with 2,000 IU vitamin D3 for 10 weeks had no significant effect on neuroplasticity compared to placebo, but the finding that vitamin D treatment alone was associated with a decrease in corticospinal excitability and intracortical inhibition warrants further investigation as this suggests that it may improve the efficacy of neural transmission within the corticospinal pathway.

Circulating microRNAs are associated with docetaxel chemotherapy outcome in castration-resistant prostate cancer.

BACKGROUND: Docetaxel is the first-line chemotherapy for castration-resistant prostate cancer (CRPC). However, response rates are ∼50% and determined quite late in the treatment schedule, thus non-responders are subjected to unnecessary toxicity. The potential of circulating microRNAs as early biomarkers of docetaxel response in CRPC patients was investigated in this study. METHODS: Global microRNA profiling was performed on docetaxel-resistant and sensitive cell lines to identify candidate circulating microRNA biomarkers. Custom Taqman Array MicroRNA cards were used to measure the levels of 46 candidate microRNAs in plasma/serum samples, collected before and after docetaxel treatment, from 97 CRPC patients. RESULTS: Fourteen microRNAs were associated with serum prostate-specific antigen (PSA) response or overall survival, according to Mann-Whitney U or log-rank tests. Non-responders to docetaxel and patients with shorter survival generally had high pre-docetaxel levels of miR-200 family members or decreased/unchanged post-docetaxel levels of miR-17 family members. Multivariate Cox regression with bootstrapping validation showed that pre-docetaxel miR-200b levels, post-docetaxel change in miR-20a levels, pre-docetaxel haemoglobin levels and visceral metastasis were independent predictors of overall survival when modelled together. CONCLUSIONS: Our study suggests that circulating microRNAs are potential early predictors of docetaxel chemotherapy outcome, and warrant further investigation in clinical trials.