The human X and Y chromosomes evolved from an ordinary pair of autosomes, but millions of years ago genetic decay ravaged the Y chromosome, and only three percent of its ancestral genes survived. We reconstructed the evolution of the Y chromosome across eight mammals to identify biases in gene content and the selective pressures that preserved the surviving ancestral genes. Our findings indicate that survival was non-random, and in two cases, convergent across placental and marsupial mammals. We conclude that the Y chromosome's gene content became specialized through selection to maintain the ancestral dosage of homologous X-Y gene pairs that function as broadly expressed regulators of transcription, translation and protein stability. We propose that beyond its roles in testis determination and spermatogenesis, the Y chromosome is essential for male viability, and plays unappreciated roles in Turner syndrome and in phenotypic differences between the sexes in health and disease.
Background falls and fall-related injuries are common in older adults, have negative effects on functional independence and quality of life and are associated with increased morbidity, mortality and health related costs. Current guidelines are inconsistent, with no up-to-date, globally applicable ones present. Objectives to create a set of evidence- and expert consensus-based falls prevention and management recommendations applicable to older adults for use by healthcare and other professionals that consider: (i) a person-centred approach that includes the perspectives of older adults with lived experience, caregivers and other stakeholders; (ii) gaps in previous guidelines; (iii) recent developments in e-health and (iv) implementation across locations with limited access to resources such as low- and middle-income countries. Methods a steering committee and a worldwide multidisciplinary group of experts and stakeholders, including older adults, were assembled. Geriatrics and gerontological societies were represented. Using a modified Delphi process, recommendations from 11 topic-specific working groups (WGs), 10 ad-hoc WGs and a WG dealing with the perspectives of older adults were reviewed and refined. The final recommendations were determined by voting. Recommendations all older adults should be advised on falls prevention and physical activity. Opportunistic case finding for falls risk is recommended for community-dwelling older adults. Those considered at high risk should be offered a comprehensive multifactorial falls risk assessment with a view to co-design and implement personalised multidomain interventions. Other recommendations cover details of assessment and intervention components and combinations, and recommendations for specific settings and populations. Conclusions the core set of recommendations provided will require flexible implementation strategies that consider both local context and resources.
Heritability, the proportion of phenotypic variance explained by genetic factors, can be estimated from pedigree data 1 , but such estimates are uninformative with respect to the underlying genetic architecture. Analyses of data from genome-wide association studies (GWAS) on unrelated individuals have shown that for human traits and disease, approximately one-third to two-thirds of heritability is captured by common SNPs 2-5 . It is not known whether the remaining heritability is due to the imperfect tagging of causal variants by common SNPs, in particular if the causal variants are rare, or other reasons such as overestimation of heritability from pedigree data. Here we show that pedigree heritability for height and body mass index (BMI) appears to be fully recovered from whole-genome sequence (WGS) data on 21,620 unrelated individuals of European ancestry. We assigned 47.1 million genetic variants to groups based upon their minor allele frequencies (MAF) and linkage disequilibrium (LD) with variants nearby, and estimated and partitioned variation accordingly. The estimated heritability was 0.79 (SE 0.09) for height and 0.40 (SE 0.09) for BMI, consistent with pedigree estimates. Low-MAF variants in low LD with neighbouring variants were enriched for heritability, to a greater extent for protein altering variants, consistent with negative selection thereon. Cumulatively variants in the MAF range of 0.0001 to 0.1 explained 0.54 (SE 0.05) and 0.51 (SE 0.11) of heritability for height and BMI, respectively. Our results imply that the still missing heritability of complex traits and disease is accounted for by rare variants, in particular those in regions of low LD.
BackgroundElective surgeries can be associated with significant harm to older adults. The present study aimed to identify the prognostic factors associated with the development of postoperative complications among older adults undergoing elective surgery.MethodsMedline, EMBASE, CINAHL, Cochrane Central Register of Controlled Trials, and AgeLine were searched for articles published between inception and April 21, 2016. Prospective studies reporting prognostic factors associated with postoperative complications (composite outcome of medical and surgical complications), functional decline, mortality, post-hospitalization discharge destination, and prolonged hospitalization among older adults undergoing elective surgery were included. Study characteristics and prognostic factors associated with the outcomes of interest were extracted independently by two reviewers. Random effects meta-analysis models were used to derive pooled effect estimates for prognostic factors and incidences of adverse outcomes.ResultsOf the 5692 titles and abstracts that were screened for inclusion, 44 studies (12,281 patients) reported on the following adverse postoperative outcomes: postoperative complications (n =28), postoperative mortality (n = 11), length of hospitalization (n = 21), functional decline (n = 6), and destination at discharge from hospital (n = 13). The pooled incidence of postoperative complications was 25.17% (95% confidence interval (CI) 18.03–33.98%, number needed to follow = 4). The geriatric syndromes of frailty (odds ratio (OR) 2.16, 95% CI 1.29–3.62) and cognitive impairment (OR 2.01, 95% CI 1.44–2.81) were associated with developing postoperative complications; however, there was no association with traditionally assessed prognostic factors such as age (OR 1.07, 95% CI 1.00–1.14) or American Society of Anesthesiologists status (OR 2.62, 95% CI 0.78–8.79). Besides frailty, other potentially modifiable prognostic factors, including depressive symptoms (OR 1.77, 95% CI 1.22–2.56) and smoking (OR 2.43, 95% CI 1.32–4.46), were also associated with developing postoperative complications.ConclusionGeriatric syndromes are important prognostic factors for postoperative complications. We identified potentially modifiable prognostic factors (e.g., frailty, depressive symptoms, and smoking) associated with developing postoperative complications that can be targeted preoperatively to optimize care.Electronic supplementary materialThe online version of this article (doi:10.1186/s12916-017-0986-2) contains supplementary material, which is available to authorized users.
BackgroundPostoperative delirium is a common preventable complication experienced by older adults undergoing elective surgery. In this systematic review and meta-analysis, we identified prognostic factors associated with the risk of postoperative delirium among older adults undergoing elective surgery.MethodsMedline, EMBASE, CINAHL, Cochrane Central Register of Controlled Trials, and AgeLine were searched for articles published between inception and April 21, 2016. A total of 5692 titles and abstracts were screened in duplicate for possible inclusion. Studies using any method for diagnosing delirium were eligible. Two reviewers independently completed all data extraction and quality assessments using the Cochrane Risk-of-Bias Tool for randomized controlled trials (RCTs) and the Newcastle-Ottawa Scale (NOS) for cohort studies. Random effects meta-analysis models were used to derive pooled effect estimates.ResultsForty-one studies (9384 patients) reported delirium-related prognostic factors. Among our included studies, the pooled incidence of postoperative delirium was 18.4% (95% confidence interval [CI] 14.3–23.3%, number needed to follow [NNF] = 6). Geriatric syndromes were important predictors of delirium, namely history of delirium (odds ratio [OR] 6.4, 95% CI 2.2–17.9), frailty (OR 4.1, 95% CI 1.4–11.7), cognitive impairment (OR 2.7, 95% CI 1.9–3.8), impairment in activities of daily living (ADLs; OR 2.1, 95% CI 1.6–2.6), and impairment in instrumental activities of daily living (IADLs; OR 1.9, 95% CI 1.3–2.8). Potentially modifiable prognostic factors such as psychotropic medication use (OR 2.3, 95% CI 1.4–3.6) and smoking status (OR 1.8 95% CI 1.3–2.4) were also identified. Caregiver support was associated with lower odds of postoperative delirium (OR 0.69, 95% CI 0.52–0.91).DiscussionThough caution must be used in interpreting meta-analyses of non-randomized studies due to the potential influence of unmeasured confounding, we identified potentially modifiable prognostic factors including frailty and psychotropic medication use that should be targeted to optimize care.Electronic supplementary materialThe online version of this article (10.1007/s11606-017-4204-x) contains supplementary material, which is available to authorized users.
IMPORTANCEWith the global population aging, falls and fall-related injuries are ubiquitous, and several clinical practice guidelines for falls prevention and management for individuals 60 years or older have been developed. A systematic evaluation of the recommendations and agreement level is lacking.OBJECTIVES To perform a systematic review of clinical practice guidelines for falls prevention and management for adults 60 years or older in all settings (eg, community, acute care, and nursing homes), evaluate agreement in recommendations, and identify potential gaps. EVIDENCE REVIEW A systematic review following Preferred Reporting Items for SystematicReviews and Meta-analyses statement methods for clinical practice guidelines on fall prevention and management for older adults was conducted (updated July 1, 2021) using MEDLINE, PubMed, PsycINFO, Embase, CINAHL, the Cochrane Library, PEDro, and Epistemonikos databases. Medical Subject Headings search terms were related to falls, clinical practice guidelines, management and prevention, and older adults, with no restrictions on date, language, or setting for inclusion. Three independent reviewers selected records for full-text examination if they followed evidence-and consensus-based processes and assessed the quality of the guidelines using Appraisal of Guidelines for Research & Evaluation II (AGREE-II) criteria. The strength of the recommendations was evaluated using Grades of Recommendation, Assessment, Development, and Evaluation scores, and agreement across topic areas was assessed using the Fleiss κ statistic. FINDINGSOf 11 414 records identified, 159 were fully reviewed and assessed for eligibility, and 15 were included. All 15 selected guidelines had high-quality AGREE-II total scores (mean [SD], 80.1% [5.6%]), although individual quality domain scores for clinical applicability (mean [SD], 63.4% [11.4%]) and stakeholder (clinicians, patients, or caregivers) involvement (mean [SD], 76.3% [9.0%]) were lower. A total of 198 recommendations covering 16 topic areas in 15 guidelines were identified after screening 4767 abstracts that proceeded to 159 full texts. Most (Ն11) guidelines strongly recommended performing risk stratification, assessment tests for gait and balance, fracture and osteoporosis management, multifactorial interventions, medication review, exercise promotion, environment modification, vision and footwear correction, referral to physiotherapy, and cardiovascular interventions. The strengths of the recommendations were inconsistent for vitamin D supplementation, addressing cognitive factors, and falls prevention education. Recommendations on use of hip protectors and digital technology or wearables were often missing. None of the examined guidelines included a patient or caregiver panel in their deliberations.
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