Purpose:To assess image quality and image-guidance capabilities of a cone-beam CT based smallanimal image-guided irradiation unit ͑micro-IGRT͒. Methods: A micro-IGRT system has been developed in collaboration with the authors' laboratory as a means to study the radiobiological effects of conformal radiation dose distributions in small animals. The system, the X-Rad 225Cx, consists of a 225 kVp x-ray tube and a flat-panel amorphous silicon detector mounted on a rotational C-arm gantry and is capable of both fluoroscopic x-ray and cone-beam CT imaging, as well as image-guided placement of the radiation beams. Image quality ͑voxel noise, modulation transfer, CT number accuracy, and geometric accuracy characteristics͒ was assessed using water cylinder and micro-CT test phantoms. Image guidance was tested by analyzing the dose delivered to radiochromic films fixed to BB's through the endto-end process of imaging, targeting the center of the BB, and irradiation of the film/BB in order to compare the offset between the center of the field and the center of the BB. Image quality and geometric studies were repeated over a 5-7 month period to assess stability. Results: CT numbers reported were found to be linear ͑R 2 Ն 0.998͒ and the noise for images of homogeneous water phantom was 30 HU at imaging doses of approximately 1 cGy ͑to water͒. The presampled MTF at 50% and 10% reached 0.64 and 1.35 mm −1 , respectively. Targeting accuracy by means of film irradiations was shown to have a mean displacement error of ͓⌬x,⌬y,⌬z͔ = ͓−0.12, −0.05, −0.02͔ mm, with standard deviations of ͓0.02, 0.20, 0.17͔ mm. The system has proven to be stable over time, with both the image quality and image-guidance performance being reproducible for the duration of the studies. Conclusions:The micro-IGRT unit provides soft-tissue imaging of small-animal anatomy at acceptable imaging doses ͑Յ1 cGy͒. The geometric accuracy and targeting systems permit dose placement with submillimeter accuracy and precision. The system has proven itself to be stable over 2 yr of routine laboratory use ͑Ͼ1800 irradiations͒ and provides a platform for the exploration of targeted radiation effects in small-animal models.

Some humans age faster than others. Variation in biological aging can be measured in midlife, but the implications of this variation are poorly understood. We tested associations between midlife biological aging and indicators of future frailty risk in the Dunedin cohort of 1,037 infants born the same year and followed to age 45. Participants' 'Pace of Aging' was quantified by tracking declining function in 19 biomarkers indexing the cardiovascular, metabolic, renal, immune, dental and pulmonary systems across ages 26, 32, 38 and 45 years. At age 45 in 2019, participants with faster Pace of Aging had more cognitive difficulties, signs of advanced brain aging, diminished sensory-motor functions, older appearances and more pessimistic perceptions of aging. People who are aging more rapidly than same-age peers in midlife may prematurely need supports to sustain independence that are usually reserved for older adults. Chronological age does not adequately identify need for such supports.

Background. Paired exercise and cognitive training have the potential to enhance cognition by "priming" the brain and upregulating neurotrophins. Methods. Two-site randomized controlled trial. Fifty-two patients >6 months poststroke with concerns about cognitive impairment trained 50 to 70 minutes, 3× week for 10 weeks with 12-week follow-up. Participants were randomized to 1 of 2 physical interventions: Aerobic (>60% VO 2peak using <10% body weight-supported treadmill) or Activity (range of movement and functional tasks). Exercise was paired with 1 of 2 cognitive interventions (computerized dual working memory training [COG] or control computer games [Games]). The primary outcome for the 4 groups (Aerobic + COG, Aerobic + Games, Activity + COG, and Activity + Games) was fluid intelligence measured using Raven's Progressive Matrices Test administered at baseline, posttraining, and 3-month follow-up. Serum neurotrophins collected at one site (N = 30) included brain-derived neurotrophic factor (BDNF) at rest (BDNF resting) and after a graded exercise test (BDNF response) and insulin-like growth factor-1 at the same timepoints (IGF-1 rest , IGF-1 response). Results. At follow-up, fluid intelligence scores significantly improved compared to baseline in the Aerobic + COG and Activity + COG groups; however, only the Aerobic + COG group was significantly different (+47.8%) from control (Activity + Games −8.5%). Greater IGF-1 response at baseline predicted 40% of the variance in cognitive improvement. There was no effect of the interventions on BDNF resting or BDNF response ; nor was BDNF predictive of the outcome. Conclusions. Aerobic exercise combined with cognitive training improved fluid intelligence by almost 50% in patients >6 months poststroke. Participants with more robust improvements in cognition were able to upregulate higher levels of serum IGF-1 suggesting that this neurotrophin may be involved in behaviorally induced plasticity.

Background Virtual reality (VR) delivered through immersive headsets creates an opportunity to deliver interventions to improve physical, mental, and psychosocial health outcomes. VR app studies with older adults have primarily focused on rehabilitation and physical function including gait, balance, fall prevention, pain management, and cognition. Several systematic reviews have previously been conducted, but much of the extant literature is focused on rehabilitation or other institutional settings, and little is known about the effectiveness of VR apps using immersive headsets to target health outcomes among community-dwelling older adults. Objective The objective of this review was to evaluate the effectiveness of VR apps delivered using commercially available immersive headsets to improve physical, mental, or psychosocial health outcomes in community-dwelling older adults. Methods Peer-reviewed publications that included community-dwelling older adults aged ≥60 years residing in residential aged care settings and nursing homes were included. This systematic review was conducted in accordance with the Joanna Briggs Institute (JBI) methodology for systematic reviews of effectiveness evidence. The title of this review was registered with JBI, and the systematic review protocol was registered with the International Prospective Register of Systematic Reviews. Results In total, 7 studies that specifically included community-dwelling older adults were included in this review. VR apps using a head-mounted display led to improvements in a number of health outcomes, including pain management, posture, cognitive functioning specifically related to Alzheimer disease, and a decreased risk of falls. A total of 6 studies reported a statistically significant difference post VR intervention, and 1 study reported an improvement in cognitive function to reduce navigational errors. Only one study reported on the usability and acceptability of the interventions delivered through VR. While one study used a distraction mechanism for pain management, none of the studies used gaming technology to promote enjoyment. Conclusions Interventions to improve health outcomes through VR have demonstrated potential; however, the ability to synthesize findings by primary outcome for the older adult population is not possible. A number of factors, especially related to frailty, usability, and acceptability, also need to be explored before more substantial recommendations on the effectiveness of VR interventions for older adults can be made. Trial Registration PROSPERO CRD42019143504; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=143504

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