Abstract
Cognitive functioning in older age profoundly impacts quality of life and health. While most research on cognition in older age has focused on mean levels, intraindividual variability (IIV) ...around this may have risk factors and outcomes independent of the mean value. Investigating risk factors associated with IIV has typically involved deriving a summary statistic for each person from residual error around a fitted mean. However, this ignores uncertainty in the estimates, prohibits exploring associations with time-varying factors, and is biased by floor/ceiling effects. To address this, we propose a mixed-effects location scale beta-binomial model for estimating average probability and IIV in a word recall test in the English Longitudinal Study of Ageing. After adjusting for mean performance, an analysis of 9,873 individuals across 7 (mean = 3.4) waves (2002–2015) found IIV to be greater at older ages, with lower education, in females, with more difficulties in activities of daily living, in later birth cohorts, and when interviewers recorded issues potentially affecting test performance. Our study introduces a novel method for identifying groups with greater IIV in bounded discrete outcomes. Our findings have implications for daily functioning and care, and further work is needed to identify the impact for future health outcomes.
Many people experience unilateral degraded vision, usually owing to a developmental or age-related disorder. There are unresolved questions regarding the extent to which such unilateral visual ...deficits impact on sensorimotor performance; an important issue as sensorimotor limitations can constrain quality of life by restricting 'activities of daily living'. Examination of the relationship between visual deficit and sensorimotor performance is essential for determining the functional implications of ophthalmic conditions. This study attempts to explore the effect of unilaterally degraded vision on sensorimotor performance.
In Experiment 1 we simulated visual deficits in 30 participants using unilateral and bilateral Bangerter filters to explore whether motor performance was affected in water pouring, peg placing, and aiming tasks. Experiment 2 (n = 74) tested the hypothesis that kinematic measures are associated with visuomotor deficits by measuring the impact of small visual sensitivity decrements created by monocular viewing on sensorimotor interactions with targets presented on a planar surface in aiming, tracking and steering tasks.
In Experiment 1, the filters caused decreased task performance-confirming that unilateral (and bilateral) visual loss has functional implications. In Experiment 2, kinematic measures were affected by monocular viewing in two of three tasks requiring rapid online visual feedback (aiming and steering).
Unilateral visual loss has a measurable impact on sensorimotor performance. The benefits of binocular vision may be particularly important for some groups (e.g. older adults) where an inability to complete sensorimotor tasks may necessitate assisted living. There is an urgent need to develop rigorous kinematic approaches to the quantification of the functional impact of unilaterally degraded vision and of the benefits associated with treatments for unilateral ophthalmic conditions to enable informed decisions around treatment.
Background Life-Space Assessment captures community mobility and social participation and quantifies the distance, frequency, and independence obtained as an older adult moves through his or her ...environment. Reduced estimated glomerular filtration rate (eGFR) is associated with decline in activities of daily living among older adults, but less is known about the association of eGFR with restrictions in mobility. Study Design Prospective observational cohort study. Setting & Participants Community-dwelling Medicare beneficiaries from the University of Alabama at Birmingham Study of Aging who had serum creatinine measured during a baseline in-home study visit and completed at least one telephone follow-up (N = 390). Predictor eGFR ≥ 60, 45-59, and <45 mL/min/1.73 m2. Outcome Life-space mobility trajectory. Measurements Life-space mobility was evaluated by telephone every 6 months for up to 4.5 years using the previously validated Life-Space Assessment. Scores using this tool range from 0-120 (higher scores indicate greater mobility). Results Mean age of the 390 participants was 77.6 ± 5.8 (SD) years, 41% were African American, 50.5% were women; 30.0% had eGFR of 45-59 mL/min/1.73 m2 , and 20.2% had eGFR < 45 mL/min/1.73 m2 . Age-, race-, and sex-adjusted mean baseline life-space mobility scores were 64.8 (95% CI, 62.0-67.6), 63.8 (95% CI, 60.3-67.4), and 58.3 (95% CI, 53.8-62.7) among those with eGFR categories ≥ 60, 45-59, and <45 mL/min/1.73 m2 , respectively. Compared with those with eGFRs ≥ 60 mL/min/1.73 m2 , a more rapid decline in life-space mobility was found among those with eGFRs < 45 mL/min/1.73 m2 , though this did not reach statistical significance ( P = 0.06); a similar effect was not seen among those with eGFRs of 45-59 mL/min/1.73 m2 ( P = 0.3). Limitations Urinary albumin or longitudinal measures of eGFR were not available. Conclusions eGFR < 45 mL/min/1.73 m2 was associated with a trend toward a more rapid decline in life-space mobility among community-dwelling older adults. Findings should be confirmed in a larger population.
Purpose This report reveals the results of a multicenter, randomized, controlled study using transurethral prostate convective water vapor thermal energy to treat lower urinary tract symptoms ...associated with benign prostatic hyperplasia. Materials and Methods Men 50 years old or older with an International Prostate Symptom Score of 13 or greater, maximum flow rate of 15 ml per second or less and prostate size 30 to 80 cc were randomized 2:1 between thermal therapy with the Rezūm® System and control. Thermal water vapor was injected into the transition zone and median lobe as needed. The control procedure was rigid cystoscopy with simulated active treatment sounds. The primary end point compared International Prostate Symptom Score reduction at 3 months. Treatment subjects were followed for 12 months. Results There were 197 men randomized (active 136, control 61). Thermal therapy and control International Prostate Symptom Score was reduced by 11.2 ± 7.6 and 4.3 ± 6.9 respectively (p <0.0001). Treatment subject baseline International Prostate Symptom Score of 22 decreased at 2 weeks (18.6, p=0.0006) and by 50% or greater at 3, 6 and 12 months, p <0.0001. The peak flow rate increased by 6.2 ml per second at 3 months and was sustained throughout 12 months (p <0.0001). No de novo erectile dysfunction was reported. Adverse events were mild to moderate and resolved quickly. Conclusions Convective water vapor thermal therapy provides rapid and durable improvements in benign prostatic hyperplasia symptoms and preserves erectile and ejaculatory function. Treatment can be delivered in an office or hospital setting using oral pain medication and is applicable to all prostate zones including the median lobe.
Group 2 innate lymphoid cells (ILC2s) and type 2 helper T cells (Th2 cells) are the primary source of interleukin 5 (IL-5) and IL-13 during type 2 (allergic) inflammation in the lung. In Th2 cells, T ...cell receptor (TCR) signaling activates the transcription factors nuclear factor of activated T cells (NFAT), nuclear factor κB (NF-κB), and activator protein 1 (AP-1) to induce type 2 cytokines. ILC2s lack a TCR and respond instead to locally produced cytokines such as IL-33. Although IL-33 induces AP-1 and NF-κB, NFAT signaling has not been described in ILC2s. In this study, we report a nonredundant NFAT-dependent role for lipid-derived leukotrienes (LTs) in the activation of lung ILC2s. Using cytokine reporter and LT-deficient mice, we find that complete disruption of LT signaling markedly diminishes ILC2 activation and downstream responses during type 2 inflammation. Type 2 responses are equivalently attenuated in IL-33- and LT-deficient mice, and optimal ILC2 activation reflects potent synergy between these pathways. These findings expand our understanding of ILC2 regulation and may have important implications for the treatment of airways disease.
Melanism is widespread in different taxa and has been hypothesized to provide adaptive benefits in certain environments. Melanism is typically caused by mutations in one of two regulatory genes: the ...Melanocortin 1 Receptor (
) or the Agouti Signaling Protein (
). Melanism has repeatedly evolved among tree squirrels and their relatives (tribe Sciurini) in at least 12 different species based on our review of the literature. The causal mutations for melanism have been characterized in two species so far. This study examines Abert's Squirrel (
), which has a melanistic morph whose genetic basis has not yet been established. We sequenced the
and
genes for five wild-type and seven melanistic
individuals to search for melanism-associated mutations. A novel single base pair mutation in the
gene, unique to
, was found to be associated with melanism in the species, indicating that melanism in
evolved independently from other tree squirrels and thus represents an example of convergent evolution. The independent evolution of melanism in this species suggests that there is an adaptive advantage to the melanistic phenotype. The geographic range and habitat of
suggest possible benefits associated with thermoregulation, post-forest-fire camouflage, or other untested hypotheses.
The cut-off value of a P-LACT < 2.5 mmol/l used in our population yielded a sensitivity of 80% (corresponding to a low probability of major haemorrhage as the authors rightly mention), and hence was ...inadequate to be used in isolation. To identify patients with a high likelihood of major haemorrhage requiring in-hospital transfusion, a P-LACT of 6.0 mmol/l was used, as at this this point the predicted probability curve (Fig. 2 in our original article) starts to flatten: using a higher cut-off would not have yielded a higher specificity, whereas a lower cut-off would have dropped specificity whilst not yielding a much higher proportion of the population meeting the cut-off criteria (n = 13, 6.7% for a lactate of 6.0 mmol/l vs. n = 17, 8.7% for a lactate of 5.5 mmol/l). ...we acknowledge that transfusion requirement is not always a good surrogate to use for outcome, especially not when confounding by indication may be present: using lactate may result in transfusing more patients in the pre-hospital setting, which again may result in a lower threshold to continue transfusion in-hospital.
Purpose We report 2-year outcomes of a multicenter randomized controlled trial plus 1-year results of a crossover trial after treatment with convective radiofrequency water vapor thermal energy for ...lower urinary tract symptoms due to benign prostatic hyperplasia. Materials and Methods A total of 197 men at least 50 years old with I-PSS (International Prostate Symptom Score) 13 or greater, maximum flow rate 15 ml per second or less and prostate size 30 to 80 cc were randomized 2:1 to thermal therapy with the Rezūm® System or a control group. Rigid cystoscopy with simulated active treatment sounds served as the control procedure. After unblinding at 3 months control subjects could requalify for crossover study. Convectively delivered radiofrequency thermal energy was delivered into obstructive prostate tissue, including the median lobe as needed. The primary efficacy end point was a change in severity of symptom scores. Results Convective radiofrequency thermal therapy improved urinary symptoms significantly over controls at 3 months and provided a sustained 51% reduction from baseline at 24 months (p <0.0001). This produced a 5 and 8-point or greater score decrease in 84% and 74% of subjects, respectively, at 24 months. Crossover subject symptoms, flow rate and quality of life measures were markedly improved after thermal therapy compared to after the control procedure (p = 0.024 to <0.0001). No de novo erectile dysfunction was reported. Conclusions Convective radiofrequency water vapor thermal therapy is a minimally invasive office or outpatient procedure that provides early effective symptom relief that remains durable for 2 years and is applicable to the median lobe.
It has been suggested that moderate reductions in estimated GFR (eGFR) among older adults may not reflect chronic kidney disease (CKD).
We examined age-specific (<60, 60 to 69, 70 to 79, and ≥80 ...years) associations between eGFR level and six concurrent CKD complications among 30,528 participants from the National Health and Nutrition Examination Survey (NHANES) 1988 to 1994 and 1999 to 2006 (n = 8242 from NHANES 2003 to 2006 for hyperparathyroidism). Complications included anemia (hemoglobin <12 g/dl women, <13.5 g/dl men), acidosis (bicarbonate <22 mEq/L), hyperphosphatemia (phosphorus ≥4.5 mg/dl), hypoalbuminemia (albumin <3.5 mg/dl), hyperparathyroidism (intact parathyroid hormone ≥70 pg/ml), and hypertension (systolic/diastolic BP ≥140/90 mmHg or antihypertensive use).
Among participants ≥80 years old, compared with those with estimated GFR (eGFR) ≥60 ml/min per 1.73 m(2), the multivariable adjusted prevalence ratios (95% confidence interval) associated with eGFR levels of 45 to 59 and <45 ml/min per 1.73 m(2) were 1.39 (1.11 to1.73) and 2.06 (1.59 to 2.67) for anemia, 1.33 (0.89 to 1.98) and 2.47 (1.52 to 4.00) for acidosis, 1.11 (0.70 to 1.76) and 2.16 (1.36 to 3.42) for hyperphosphatemia, 2.04 (1.39 to 3.00) and 2.83 (1.76 to 4.53) for hyperparathyroidism and 1.09 (1.03 to 1.14), and 1.12 (1.05 to 1.19) for hypertension, respectively. Higher prevalence ratios for these complications at lower eGFR levels were also present at younger ages. Reduced eGFR was associated with hypoalbuminemia only for adults <70.
Reduced eGFR was associated with a higher prevalence of several concurrent CKD complications, regardless of age.
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