Treating frailty-a practical guide

Frailty is a common syndrome that is associated with vulnerability to poor health outcomes. Frail older people have increased risk of morbidity, institutionalization and death, resulting in burden to individuals, their families, health care services and society. Assessment and treatment of the frail individual provide many challenges to clinicians working with older people. Despite frailty being increasingly recognized in the literature, there is a paucity of direct evidence to guide interventions to reduce frailty. In this paper we review methods for identification of frailty in the clinical setting, propose a model for assessment of the frail older person and summarize the current best evidence for treating the frail older person. We provide an evidence-based framework that can be used to guide the diagnosis, assessment and treatment of frail older people

Supporting conditional mouse mutagenesis with a comprehensive cre characterization resource.

Full realization of the value of the loxP-flanked alleles generated by the International Knockout Mouse Consortium will require a large set of well-characterized cre-driver lines. However, many cre driver lines display excision activity beyond the intended tissue or cell type, and these data are frequently unavailable to the potential user. Here we describe a high-throughput pipeline to extend characterization of cre driver lines to document excision activity in a wide range of tissues at multiple time points and disseminate these data to the scientific community. Our results show that the majority of cre strains exhibit some degree of unreported recombinase activity. In addition, we observe frequent mosaicism, inconsistent activity and parent-of-origin effects. Together, these results highlight the importance of deep characterization of cre strains, and provide the scientific community with a critical resource for cre strain information

The ability of three different models of frailty to predict all-cause mortality: Results from the European Male Aging Study (EMAS)

Few studies have directly compared the ability of the most commonly used models of frailty to predict mortality among community-dwelling individuals. Here, we used a frailty index (FI), frailty phenotype (FP), and FRAIL scale (FS) to predict mortality in the EMAS. Participants were aged 40-79 years (n = 2929) at baseline and 6.6% (n = 193) died over a median 4.3 years of follow-up. The FI was generated from 39 deficits, including self-reported health, morbidities, functional performance and psychological assessments. The FP and FS consisted of five phenotypic criteria and both categorized individuals as robust when they had 0 criteria, prefrail as 1-2 criteria and frail as 3+ criteria. The mean FI increased linearly with age (r(2) = 0.21) and in Cox regression models adjusted for age, center, smoking and partner status the hazard ratio (HR) for death for each unit increase of the FI was 1.49. Men who were prefrail or frail by either the FP or FS definitions, had a significantly increased risk of death compared to their robust counterparts. Compared to robust men, those who were FP frail at baseline had a HR for death of 3.84, while those who were FS frail had a HR of 3.87. All three frailty models significantly predicted future mortality among community-dwelling, middle-aged and older European men after adjusting for potential confounders. Our data suggest that the choice of frailty model may not be of paramount importance when predicting future risk of death, enabling flexibility in the approach used. (C) 2013 Elsevier Ireland Ltd. All rights reserved

New directions in clinical trials for frontotemporal lobar degeneration: Methods and outcome measures.

IntroductionFrontotemporal lobar degeneration (FTLD) is the most common form of dementia for those under 60 years of age. Increasing numbers of therapeutics targeting FTLD syndromes are being developed.MethodsIn March 2018, the Association for Frontotemporal Degeneration convened the Frontotemporal Degeneration Study Group meeting in Washington, DC, to discuss advances in the clinical science of FTLD.ResultsChallenges exist for conducting clinical trials in FTLD. Two of the greatest challenges are (1) the heterogeneity of FTLD syndromes leading to difficulties in efficiently measuring treatment effects and (2) the rarity of FTLD disorders leading to recruitment challenges.DiscussionNew personalized endpoints that are clinically meaningful to individuals and their families should be developed. Personalized approaches to analyzing MRI data, development of new fluid biomarkers and wearable technologies will help to improve the power to detect treatment effects in FTLD clinical trials and enable new, clinical trial designs, possibly leveraged from the experience of oncology trials. A computational visualization and analysis platform that can support novel analyses of combined clinical, genetic, imaging, biomarker data with other novel modalities will be critical to the success of these endeavors

Spatio-Temporal Dynamics of Foraging Networks in the Grass-Cutting Ant Atta bisphaerica Forel, 1908 (Formicidae, Attini)

International audienceForaging networks are a key element for ant colonies because they facilitate the flow of resources from the environment to the nest and they allow the sharing of information among individuals. Here we report the results of an 8-month survey, extending from November 2009 to June 2010, of the foraging networks of four mature colonies of Atta bisphaerica, a species of grass-cutting ant which is considered as a pest in Brazil. We found that the distribution of foraging effort was strongly influenced by the landscape features around the nests, in particular by the permanently wet parts of the pasture in which the nests were located. The foraging networks consisted of underground tunnels which opened on average at 21.5m from the nests and of above-ground physical trails that reached on average 4.70m in length. The use of the foraging networks was highly dynamic, with few sections of the networks used for long periods of time. Three different phases, which could be linked to the seasonal change in the local rainfall regime, could be identified in the construction and use of the foraging networks. The first phase corresponded to the beginning of the rainy season and was characterized by a low foraging activity, as well as a low excavation and physical trail construction effort. The second phase, which began in February and extended up to the end of the humid season at the end of March, was characterized by an intense excavation and trail construction effort, resulting in an expansion of the foraging networks. Finally, in the third phase, which corresponded to the beginning of the dry season, the excavation and trail construction effort leveled off or decreased while foraging activity kept increasing. Our hypothesis is that ants could benefit from the underground tunnels and physical trails built during the humid season to maintain their foraging activity at a high level