Computational Modelling of Patella Femoral Kinematics During Gait Cycle and Experimental Validation

The effect of loading and boundary conditions on patellar mechanics is significant due to the complications arising in patella femoral joints during total knee replacements. To understand the patellar mechanics with respect to loading and motion, a computational model representing the patella femoral joint was developed and validated against experimental results. The computational model was created in IDEAS NX and simulated in MSC ADAMS/VIEW software. The results obtained in the form of internal external rotations and anterior posterior displacements for a new and experimentally simulated specimen for patella femoral joint under standard gait condition were compared with experimental measurements performed on the Leeds ProSim knee simulator. A good overall agreement between the computational prediction and the experimental data was obtained for patella femoral kinematics. Good agreement between the model and the past studies was observed when the ligament load was removed and the medial lateral displacement was constrained. The model is sensitive to ±5 % change in kinematics, frictional, force and stiffness coefficients and insensitive to time step

Risk factors for incident falls in older men and women:The English longitudinal study of ageing

Background: falls are a major cause of disability and death in older people, particularly women. Cross-sectional surveys suggest that some risk factors associated with a history of falls may be sex-specific, but whether risk factors for incident falls differ between the sexes is unclear. We investigated whether risk factors for incident falls differ between men and women.Methods: participants were 3298 people aged ≥60 who took part in the Waves 4-6 surveys of the English Longitudinal Study of Ageing. At Wave 4, they provided information about sociodemographic, lifestyle, behavioural and medical factors and had their physical and cognitive function assessed. Data on incident falls during the four-year follow-up period was collected from them at Waves 5 and 6. Poisson regression with robust variance estimation was used to derive relative risks (RR) for the association between baseline characteristics and incident falls.Results: in multivariable-adjusted models that also controlled for history of falls, older age was the only factor associated with increased risk of incident falls in both sexes. Some factors were only predictive of falls in one sex, namely more depressive symptoms (RR (95% CI) 1.03 (1.01,1.06)), incontinence (1.12 (1.00,1.24)) and never having married in women (1.26 (1.03,1.53)), and greater comorbidity (1.04 (1.00,1.08)), higher levels of pain (1.10 (1.04,1.17) and poorer balance, as indicated by inability to attempt a full-tandem stand, (1.23 (1.04,1.47)) in men. Of these, only the relationships between pain, balance and comorbidity and falls risk differed significantly by sex.Conclusions: there were some differences between the sexes in risk factors for incident falls. Our observation that associations between pain, balance and comorbidity and incident falls risk varied by sex needs further investigation in other cohorts. <br/

β-hairpin-mediated formation of structurally distinct multimers of neurotoxic prion peptides

Protein misfolding disorders are associated with conformational changes in specific proteins, leading to the formation of potentially neurotoxic amyloid fibrils. During pathogenesis of prion disease, the prion protein misfolds into β-sheet rich, protease-resistant isoforms. A key, hydrophobic domain within the prion protein, comprising residues 109–122, recapitulates many properties of the full protein, such as helix-to-sheet structural transition, formation of fibrils and cytotoxicity of the misfolded isoform. Using all-atom, molecular simulations, it is demonstrated that the monomeric 109–122 peptide has a preference for α-helical conformations, but that this peptide can also form β-hairpin structures resulting from turns around specific glycine residues of the peptide. Altering a single amino acid within the 109–122 peptide (A117V, associated with familial prion disease) increases the prevalence of β-hairpin formation and these observations are replicated in a longer peptide, comprising residues 106–126. Multi-molecule simulations of aggregation yield different assemblies of peptide molecules composed of conformationally-distinct monomer units. Small molecular assemblies, consistent with oligomers, comprise peptide monomers in a β-hairpin-like conformation and in many simulations appear to exist only transiently. Conversely, larger assemblies are comprised of extended peptides in predominately antiparallel β-sheets and are stable relative to the length of the simulations. These larger assemblies are consistent with amyloid fibrils, show cross-β structure and can form through elongation of monomer units within pre-existing oligomers. In some simulations, assemblies containing both β-hairpin and linear peptides are evident. Thus, in this work oligomers are on pathway to fibril formation and a preference for β-hairpin structure should enhance oligomer formation whilst inhibiting maturation into fibrils. These simulations provide an important new atomic-level model for the formation of oligomers and fibrils of the prion protein and suggest that stabilization of β-hairpin structure may enhance cellular toxicity by altering the balance between oligomeric and fibrillar protein assemblies

Varieties of living things: Life at the intersection of lineage and metabolism

publication-status: Publishedtypes: Articl

Modified bathroom scale and balance assessment: a comparison with clinical tests

Frailty and detection of fall risk are major issues in preventive gerontology. A simple tool frequently used in daily life, a bathroom scale (balance quality tester: BQT), was modified to obtain information on the balance of 84 outpatients consulting at a geriatric clinic. The results computed from the BQT were compared to the values of three geriatric tests that are widely used either to detect a fall risk or frailty (timed get up and go: TUG; 10 m walking speed: WS; walking time: WT; one-leg stand: OS). The BQT calculates four parameters that are then scored and weighted, thus creating an overall indicator of balance quality. Raw data, partial scores and the global score were compared with the results of the three geriatric tests. The WT values had the highest correlation with BQT raw data (r = 0.55), while TUG (r = 0.53) and WS (r = 0.56) had the highest correlation with BQT partial scores. ROC curves for OS cut-off values (4 and 5 s) were produced, with the best results obtained for a 5 s cut-off, both with the partial scores combined using Fisher's combination (specificity 85 %: 0.48), and with the empirical score (specificity 85 %: 8). A BQT empirical score of less than seven can detect fall risk in a community dwelling population

Cognitive frailty: rational and definition from an (I.A.N.A./I.A.G.G.) international consensus group.

The frailty syndrome has recently attracted attention of the scientific community and public health organizations as precursor and contributor of age-related conditions (particularly disability) in older persons. in parallel, dementia and cognitive disorders also represent major healthcare and social priorities. although physical frailty and cognitive impairment have shown to be related in epidemiological studies, their pathophysiological mechanisms have been usually studied separately. an international Consensus Group on “Cognitive Frailty” was organized by the international academy on nutrition and aging (i.a.n.a) and the international association of Gerontology and Geriatrics (i.a.G.G) on april 16th, 2013 in toulouse (France). the present report describes the results of the Consensus Group and provides the first definition of a “Cognitive Frailty” condition in older adults. specific aim of this approach was to facilitate the design of future personalized preventive interventions in older persons. Finally, the Group discussed the use of multidomain interventions focused on the physical, nutritional, cognitive and psychological domains for improving the well-being and quality of life in the elderly. the consensus panel proposed the identification of the so-called “cognitive frailty” as an heterogeneous clinical manifestation characterized by the simultaneous presence of both physical frailty and cognitive impairment. in particular, the key factors defining such a condition include: 1) presence of physical frailty and cognitive impairment (Cdr=0.5); and 2) exclusion of concurrent ad dementia or other dementias. under different circumstances, cognitive frailty may represent a precursor of neurodegenerative processes. a potential for reversibility may also characterize this entity. a psychological component of the condition is evident and concurs at increasing the vulnerability of the individual to stressors

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

Interventions to prevent disability in frail community-dwelling elderly: a systematic review

<p>Abstract</p> <p>Background</p> <p>There is an interest for intervention studies aiming at the prevention of disability in community-dwelling physically frail older persons, though an overview on their content, methodological quality and effectiveness is lacking.</p> <p>Methods</p> <p>A search for clinical trials involved databases PubMed, CINAHL and Cochrane Central Register of Controlled Trials and manually hand searching. Trials that included community-dwelling frail older persons based on physical frailty indicators and used disability measures for outcome evaluation were included. The selection of papers and data-extraction was performed by two independent reviewers. Out of 4602 titles, 10 papers remained that met the inclusion criteria. Of these, 9 were of sufficient methodological quality and concerned 2 nutritional interventions and 8 physical exercise interventions.</p> <p>Results</p> <p>No evidence was found for the effect of nutritional interventions on disability measures. The physical exercise interventions involved 2 single-component programs focusing on lower extremity strength and 6 multi-component programs addressing a variety of physical parameters. Out of 8 physical exercise interventions, three reported positive outcomes for disability. There was no evidence for the effect of single lower extremity strength training on disability. Differences between the multi-component interventions in e.g. individualization, duration, intensity and setting hamper the interpretation of the elements that consistently produced successful outcomes.</p> <p>Conclusion</p> <p>There is an indication that relatively long-lasting and high-intensive multicomponent exercise programs have a positive effect on ADL and IADL disability for community-living moderate physically frail older persons. Future research into disability prevention in physical frail older persons could be directed to more individualized and comprehensive programs.</p

A standard procedure for creating a frailty index

<p>Abstract</p> <p>Background</p> <p>Frailty can be measured in relation to the accumulation of deficits using a frailty index. A frailty index can be developed from most ageing databases. Our objective is to systematically describe a standard procedure for constructing a frailty index.</p> <p>Methods</p> <p>This is a secondary analysis of the Yale Precipitating Events Project cohort study, based in New Haven CT. Non-disabled people aged 70 years or older (n = 754) were enrolled and re-contacted every 18 months. The database includes variables on function, cognition, co-morbidity, health attitudes and practices and physical performance measures. Data came from the baseline cohort and those available at the first 18-month follow-up assessment.</p> <p>Results</p> <p>Procedures for selecting health variables as candidate deficits were applied to yield 40 deficits. Recoding procedures were applied for categorical, ordinal and interval variables such that they could be mapped to the interval 0–1, where 0 = absence of a deficit, and 1= full expression of the deficit. These individual deficit scores were combined in an index, where 0= no deficit present, and 1= all 40 deficits present. The values of the index were well fit by a gamma distribution. Between the baseline and follow-up cohorts, the age-related slope of deficit accumulation increased from 0.020 (95% confidence interval, 0.014–0.026) to 0.026 (0.020–0.032). The 99% limit to deficit accumulation was 0.6 in the baseline cohort and 0.7 in the follow-up cohort. Multivariate Cox analysis showed the frailty index, age and sex to be significant predictors of mortality.</p> <p>Conclusion</p> <p>A systematic process for creating a frailty index, which relates deficit accumulation to the individual risk of death, showed reproducible properties in the Yale Precipitating Events Project cohort study. This method of quantifying frailty can aid our understanding of frailty-related health characteristics in older adults.</p

Elderly persons in the risk zone. Design of a multidimensional, health-promoting, randomised three-armed controlled trial for "prefrail" people of 80+ years living at home

Background The very old (80+) are often described as a "frail" group that is particularly exposed to diseases and functional disability. They are at great risk of losing the ability to manage their activities of daily living independently. A health-promoting intervention programme might prevent or delay dependence in activities of daily life and the development of functional decline. Studies have shown that those who benefit most from a health-promoting and disease-preventive programme are persons with no, or discrete, activity restrictions. The three-armed study "Elderly in the risk zone" is designed to evaluate if multi-dimensional and multi-professional educational senior meetings are more effective than preventive home visits, and if it is possible to prevent or delay deterioration if an intervention is made when the persons are not so frail. In this paper the study design, the intervention and the outcome measures as well as the baseline characteristics of the study participants are presented. Methods/Design The study is a randomised three-armed single-blind controlled trial with follow-ups 3 months, 1 and 2 years. The study group should comprise a representative sample of pre-frail 80-year old persons still living at home in two municipalities of Gothenburg. To allow for drop-outs, it was estimated that a total of about 450 persons would need to be included in the study. The participants should live in their ordinary housing and not be dependent on the municipal home help service or care. Further, they should be independent of help from another person in activities of daily living and be cognitively intact, having a score of 25 or higher as assessed with the Mini Mental State Examination (MMSE). Discussion We believe that the design of the study, the randomisation procedure, outcome measurements and the study protocol meetings should ensure the quality of the study. Furthermore, the multi-dimensionality of the intervention, the involvement of both the professionals and the senior citizens in the planning of the intervention should have the potential to effectively target the heterogeneous needs of the elderly. Trial registration ClinicalTrials.gov, NCT0087705