Observation of Periodic Orbits on Curved Two - dimensional Geometries

We measure elastomechanical spectra for a family of thin shells. We show that these spectra can be described by a "semiclassical" trace formula comprising periodic orbits on geodesics, with the periods of these orbits consistent with those extracted from experiment. The influence of periodic orbits on spectra in the case of two-dimensional curved geometries is thereby demonstrated, where the parameter corresponding to Planck's constant in quantum systems involves the wave number and the curvature radius. We use these findings to explain the marked clustering of levels when the shell is hemispherical

Anomalous Transport in Conical Granular Piles

Experiments on 2+1-dimensional piles of elongated particles are performed. Comparison with previous experiments in 1+1 dimensions shows that the addition of one extra dimension to the dynamics changes completely the avalanche properties, appearing a characteristic avalanche size. Nevertheless, the time single grains need to cross the whole pile varies smoothly between several orders of magnitude, from a few seconds to more than 100 hours. This behavior is described by a power-law distribution, signaling the existence of scale invariance in the transport process.Comment: Accepted in PR

Associations between functional polymorphisms in the NFκB signaling pathway and response to anti-TNF treatment in Danish patients with inflammatory bowel disease

Antitumor necrosis factor-α (TNF-α) is used for treatment of severe cases of inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis (UC). However, one-third of the patients do not respond to the treatment. Genetic markers may predict individual response to anti-TNF therapy. Using a candidate gene approach, 39 mainly functional single nucleotide polymorphisms (SNPs) in 26 genes regulating inflammation were assessed in 738 prior anti-TNF-naive Danish patients with IBD. The results were analyzed using logistic regression (crude and adjusted for age, gender and smoking status). Nineteen functional polymorphisms that alter the NFκB-mediated inflammatory response (TLR2 (rs3804099, rs11938228, rs1816702, rs4696480), TLR4 (rs5030728, rs1554973), TLR9 (rs187084, rs352139), LY96 (MD-2) (rs11465996), CD14 (rs2569190), MAP3K14 (NIK) (rs7222094)), TNF-α signaling (TNFA (TNF-α) (rs361525), TNFRSF1A (TNFR1) (rs4149570), TNFAIP3(A20) (rs6927172)) and other cytokines regulated by NFκB (IL1B (rs4848306), IL1RN (rs4251961), IL6 (rs10499563), IL17A (rs2275913), IFNG (rs2430561)) were associated with response to anti-TNF therapy among patients with CD, UC or both CD and UC (P⩽0.05). In conclusion, the results suggest that polymorphisms in genes involved in activating NFκB through the Toll-like receptor (TLR) pathways, genes regulating TNF-α signaling and cytokines regulated by NFκB are important predictors for the response to anti-TNF therapy among patients with IBD. Genetically strong TNF-mediated inflammatory response was associated with beneficial response. In addition, the cytokines IL-1β, IL-6 and IFN-γ may be potential targets for treating patients with IBD who do not respond to anti-TNF therapy. These findings should be examined in independent cohorts before these results are applied in a clinical setting.The Pharmacogenomics Journal advance online publication, 29 April 2014; doi:10.1038/tpj.2014.19.</p

Older people and preventive home visits

In 1996, national preventive efforts for the elderly were introduced in Denmark with a general offer of home visits by preventive staff.The focal point of the preventive home visits has been the functional decline and the corresponding early and coordinated follow-up activities. This has proved an extremely suitable instrument in activities aimed at maintaining elderly people's autonomy, independence, and functional ability, in allowing them to continue taking care of themselves

Stochastic Responses May Allow Genetically Diverse Cell Populations to Optimize Performance with Simpler Signaling Networks

Two theories have emerged for the role that stochasticity plays in biological responses: first, that it degrades biological responses, so the performance of biological signaling machinery could be improved by increasing molecular copy numbers of key proteins; second, that it enhances biological performance, by enabling diversification of population-level responses. Using T cell biology as an example, we demonstrate that these roles for stochastic responses are not sufficient to understand experimental observations of stochastic response in complex biological systems that utilize environmental and genetic diversity to make cooperative responses. We propose a new role for stochastic responses in biology: they enable populations to make complex responses with simpler biochemical signaling machinery than would be required in the absence of stochasticity. Thus, the evolution of stochastic responses may be linked to the evolvability of different signaling machineries.National Institutes of Health (U.S.). Pioneer Awar

For whom is a health-promoting intervention effective? Predictive factors for performing activities of daily living independently

BACKGROUND: Health-promoting interventions tailored to support older persons to remain in their homes, so-called "ageing in place" is important for supporting or improving their health. The health-promoting programme "Elderly Persons in the Risk Zone," (EPRZ) was set up for this purpose and has shown positive results for maintaining independence in activities of daily living for older persons 80 years and above at 1- and 2 year follow-ups. The aim of this study was to explore factors for maintaining independence in the EPRZ health-promoting programme.METHODS: Total of 459 participants in the original trial was included in the analysis; 345 in the programme arm and 114 in the control arm. Thirteen variables, including demographic, health, and programme-specific indicators, were chosen as predictors for independence of activities of daily living. Logistic regression was performed separately for participants in the health promotion programme and in the control arm.RESULTS: In the programme arm, being younger, living alone and self-rated lack of tiredness in performing mobility activities predicted a positive effect of independence in activities of daily living at 1-year follow-up (odds ratio [OR] 1.18, 1.73, 3.02) and 2-year, (OR 1.13, 2.01, 2.02). In the control arm, being less frail was the only predictor at 1-year follow up (OR 1.6 1.09, 2.4); no variables predicted the outcome at the 2-year follow-up.CONCLUSIONS: Older persons living alone - as a risk of ill health - should be especially recognized and offered an opportunity to participate in health-promoting programmes such as "Elderly Persons in the Risk Zone". Further, screening for subjective frailty could form an advantageous guiding principle to target the right population when deciding to whom health-promoting intervention should be offered.TRIAL REGISTRATION: The original clinical trial was registered at ClinicalTrials.gov. Identifier: NCT00877058 , April 6, 2009

Increased masticatory activity and quality of life in elderly persons with dementia-a longitudinal matched cluster randomized single-blind multicenter intervention study.

Background: Worldwide, millions of people are suffering from dementia and this number is rising. An index of quality of life (QoL) can describe the impact a disease or treatment has on a person's wellbeing. QoL comprises many variables, including physical health and function, and mental health and function. QoL is related to masticatory ability and physical activity. Animal studies show that disruption of mastication due to loss of teeth or a soft diet leads to memory loss and learning problems. Since these are common complaints in dementia, it is hypothesized that improvement of masticatory function and normalization of diet consistency can increase QoL in elderly persons suffering from dementia. Therefore, the goal of the present study is to examine whether an increase in masticatory activity, achieved by increased food consistency and enhancement of masticatory function through improved oral health care has a positive effect on QoL, including cognition, mood, activities of daily living (ADL), and circadian rhythm in elderly persons with dementia.Methods and design: The described study is a prospective longitudinal matched cluster randomized single-blind multicenter study. Participants are elderly persons living in the Netherlands, suffering from dementia and receiving psychogeriatric care. An intervention group will receive improved oral health care and a diet of increased consistency. A control group receives care as usual. Participants will be assessed four times; outcome variables besides QoL are cognition, mood, independence, rest-activity rhythm, blood pressure, and masticatory function.Discussion: This research protocol investigates the effect of an intervention executed by daily caregivers. The intervention will increase masticatory activity, which is achieved by three different actions, (providing oral health care, increasing food consistency, or a combination of both). There is a certain amount of variety in the nature of the interventions due to local differences in nursing homes. This might be a scientific weakness in the study design; however, a practical implementation of any findings will be subject to the same factors, making this study design clinically relevant.Trial registration: NTR1561. © 2013 Weijenberg et al.; licensee BioMed Central Ltd

Minimal gene regulatory circuits for a lysis-lysogeny choice in the presence of noise

Gene regulatory networks (GRNs) that make reliable decisions should have design features to cope with random fluctuations in the levels or activities of biological molecules. The phage GRN makes a lysis-lysogeny decision informed by the number of phages infecting the cell. To analyse the design of decision making GRNs, we generated random in silico GRNs comprised of two or three transcriptional regulators and selected those able to perform a -like decision in the presence of noise. Various two-protein networks analogous to the CI-Cro GRN worked in noise-less conditions but failed when noise was introduced. Adding a CII-like protein significantly improved robustness to noise. CII relieves the CI-like protein of its ‘decider’ function, allowing CI to be optimized as a decision ‘maintainer’. CII's lysogenic decider function was improved by its instability and rapid removal once the decision was taken, preventing its interference with maintenance. A more reliable decision also resulted from simulated co-transcription of the genes for CII and the Cro-like protein, which correlates fluctuations in these opposing decider functions and makes their ratio less noisy. Thus, the decision network contains design features for reducing and resisting noise.Mikkel Avlund, Sandeep Krishna, Szabolcs Semsey, Ian B. Dodd and Kim Sneppe

Handgrip performance in relation to self-perceived fatigue, physical functioning and circulating IL-6 in elderly persons without inflammation

BACKGROUND: Low grip strength is recognized as one of the characteristics of frailty, as are systemic inflammation and the sensation of fatigue. Contrary to maximal grip strength, the physical resistance of the muscles to fatigue is not often included in the clinical evaluation of elderly patients. The aim of this study was to investigate if the grip strength and the resistance of the handgrip muscles to fatigue are related to self-perceived fatigue, physical functioning and circulating IL-6 in independently living elderly persons. METHODS: Forty elderly subjects (15 female and 25 male, mean age 75 ± 5 years) were assessed for maximal grip strength, as well as for fatigue resistance and grip work (respectively time and work delivered until grip strength drops to 50% of its maximum during sustained contraction), self perceived fatigue (VAS-Fatigue, Mob-Tiredness scale and the energy & fatigue items of the WHOQOL-100), self rated physical functioning (domain of physical functioning on the MOS short-form) and circulating IL-6. Relationships between handgrip performance and the other outcome measures were assessed. RESULTS: In the male participants, fatigue resistance was negatively related to actual sensation of fatigue (VAS-F, p < .05) and positively to circulating IL-6 (p < .05). When corrected for body weight, the relations of fatigue resistance with self-perceived fatigue became stronger and also apparent in the female. Grip strength and grip work were significantly related with several items of self-perceived fatigue and with physical functioning. These relations became more visible by means of higher correlation coefficients when grip strength and grip work were corrected for body weight. CONCLUSION: Well functioning elderly subjects presenting less handmuscle fatigue resistance and weaker grip strength are more fatigued, experience more tiredness during daily activities and are more bothered by fatigue sensations. Body weight seems to play an important role in the relation of muscle performance to fatigue perception. Elderly patients complaining from fatigue should be physically assessed, both evaluating maximal grip strength and fatigue resistance, allowing the calculation of grip work, which integrates both parameters. Grip work might best reflect the functional capacity resulting from the development of a certain strength level in relation to the time it can be maintained

Genetic Demixing and Evolutionary Forces in the One-Dimensional Stepping Stone Model

We review and extend results for mutation, selection, genetic drift, and migration in a one-dimensional continuous population. The population is described by a continuous limit of the stepping stone model, which leads to the stochastic Fisher-Kolmogorov-Petrovsky-Piscounov equation with additional terms describing mutations. Although the stepping stone model was first proposed for population genetics, it is closely related to "voter models" of interest in nonequilibrium statistical mechanics. The stepping stone model can also be regarded as an approximation to the dynamics of a thin layer of actively growing pioneers at the frontier of a colony of microorganisms undergoing a range expansion on a Petri dish. We find that the population tends to segregate into monoallelic domains. This segregation slows down genetic drift and selection because these two evolutionary forces can only act at the boundaries between the domains; the effects of mutation, however, are not significantly affected by the segregation. Although fixation in the neutral well-mixed (or "zero dimensional") model occurs exponentially in time, it occurs only algebraically fast in the one-dimensional model. If selection is weak, selective sweeps occur exponentially fast in both well-mixed and one-dimensional populations, but the time constants are different. We also find an unusual sublinear increase in the variance of the spatially averaged allele frequency with time. Although we focus on two alleles or variants, q-allele Potts-like models of gene segregation are considered as well. We also investigate the effects of geometry at the frontier by considering growth of circular colonies. Our analytical results are checked with simulations, and could be tested against recent spatial experiments on range expansions off linear inoculations of Escherichia coli and Saccharomyces cerevisiae.Comment: 29 pages, 20 figures; Reviews of Modern Physics, Volume 82, April-June 201