Wake Forest University

Abstract Genetic variants that inactivate protein-coding genes are a powerful source of information about the phenotypic consequences of gene disruption: genes that are crucial for the function of an organism will be depleted of such variants in natural populations, whereas non-essential genes will tolerate their accumulation. However, predicted loss-of-function variants are enriched for annotation errors, and tend to be found at extremely low frequencies, so their analysis requires careful variant annotation and very large sample sizes 1 . Here we describe the aggregation of 125,748 exomes and 15,708 genomes from human sequencing studies into the Genome Aggregation Database (gnomAD). We identify 443,769 high-confidence predicted loss-of-function variants in this cohort after filtering for artefacts caused by sequencing and annotation errors. Using an improved model of human mutation rates, we classify human protein-coding genes along a spectrum that represents tolerance to inactivation, validate this classification using data from model organisms and engineered human cells, and show that it can be used to improve the power of gene discovery for both common and rare diseases.

BACKGROUND: Epidemiologic studies have shown a relationship between glycated hemoglobin levels and cardiovascular events in patients with type 2 diabetes. We investigated whether intensive therapy to target normal glycated hemoglobin levels would reduce cardiovascular events in patients with type 2 diabetes who had either established cardiovascular disease or additional cardiovascular risk factors. METHODS: In this randomized study, 10,251 patients (mean age, 62.2 years) with a median glycated hemoglobin level of 8.1% were assigned to receive intensive therapy (targeting a glycated hemoglobin level below 6.0%) or standard therapy (targeting a level from 7.0 to 7.9%). Of these patients, 38% were women, and 35% had had a previous cardiovascular event. The primary outcome was a composite of nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes. The finding of higher mortality in the intensive-therapy group led to a discontinuation of intensive therapy after a mean of 3.5 years of follow-up. RESULTS: At 1 year, stable median glycated hemoglobin levels of 6.4% and 7.5% were achieved in the intensive-therapy group and the standard-therapy group, respectively. During follow-up, the primary outcome occurred in 352 patients in the intensive-therapy group, as compared with 371 in the standard-therapy group (hazard ratio, 0.90; 95% confidence interval [CI], 0.78 to 1.04; P=0.16). At the same time, 257 patients in the intensive-therapy group died, as compared with 203 patients in the standard-therapy group (hazard ratio, 1.22; 95% CI, 1.01 to 1.46; P=0.04). Hypoglycemia requiring assistance and weight gain of more than 10 kg were more frequent in the intensive-therapy group (P<0.001). CONCLUSIONS: As compared with standard therapy, the use of intensive therapy to target normal glycated hemoglobin levels for 3.5 years increased mortality and did not significantly reduce major cardiovascular events. These findings identify a previously unrecognized harm of intensive glucose lowering in high-risk patients with type 2 diabetes. (ClinicalTrials.gov number, NCT00000620.)

Quantum EXPRESSO is an integrated suite of open-source computer codes for quantum simulations of materials using state-of-the-art electronic-structure techniques, based on density-functional theory, density-functional perturbation theory, and many-body perturbation theory, within the plane-wave pseudopotential and projector-augmented-wave approaches. Quantum EXPRESSO owes its popularity to the wide variety of properties and processes it allows to simulate, to its performance on an increasingly broad array of hardware architectures, and to a community of researchers that rely on its capabilities as a core open-source development platform to implement their ideas. In this paper we describe recent extensions and improvements, covering new methodologies and property calculators, improved parallelization, code modularization, and extended interoperability both within the distribution and with external software.

Identification of key factors associated with the risk of developing cardiovascular disease and quantification of this risk using multivariable prediction algorithms are among the major advances made in preventive cardiology and cardiovascular epidemiology in the 20th century. The ongoing discovery of new risk markers by scientists presents opportunities and challenges for statisticians and clinicians to evaluate these biomarkers and to develop new risk formulations that incorporate them. One of the key questions is how best to assess and quantify the improvement in risk prediction offered by these new models. Demonstration of a statistically significant association of a new biomarker with cardiovascular risk is not enough. Some researchers have advanced that the improvement in the area under the receiver-operating-characteristic curve (AUC) should be the main criterion, whereas others argue that better measures of performance of prediction models are needed. In this paper, we address this question by introducing two new measures, one based on integrated sensitivity and specificity and the other on reclassification tables. These new measures offer incremental information over the AUC. We discuss the properties of these new measures and contrast them with the AUC. We also develop simple asymptotic tests of significance. We illustrate the use of these measures with an example from the Framingham Heart Study. We propose that scientists consider these types of measures in addition to the AUC when assessing the performance of newer biomarkers.

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. For example, a key point that needs to be emphasized is thatthere is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure flux through the autophagy pathway (i.e., the completeprocess including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defined as increasedautophagy induction coupled with increased delivery to, and degradation within, lysosomes (inmost higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in manycases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as forreviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multipleassays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation, it is imperative to target by gene knockout or RNA interference more than one autophagyrelated protein. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways implying that not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular assays, we hope to encourage technical innovation in the field.

A model of distributor firm and manufacturer firm working partnerships is presented and is assessed empirically on a sample of distributor firms and a sample of manufacturer firms. A multiple-informant research method is employed. Support is found for a number of the hypothesized construct relations and, in both manufacturer firm and distributor firm models, for the respecification of cooperation as an antecedent rather than a consequence of trust. Some implications for marketing practice are discussed briefly.

In observational studies, investigators have no control over the treatment assignment. The treated and non-treated (that is, control) groups may have large differences on their observed covariates, and these differences can lead to biased estimates of treatment effects. Even traditional covariance analysis adjustments may be inadequate to eliminate this bias. The propensity score, defined as the conditional probability of being treated given the covariates, can be used to balance the covariates in the two groups, and therefore reduce this bias. In order to estimate the propensity score, one must model the distribution of the treatment indicator variable given the observed covariates. Once estimated the propensity score can be used to reduce bias through matching, stratification (subclassification), regression adjustment, or some combination of all three. In this tutorial we discuss the uses of propensity score methods for bias reduction, give references to the literature and illustrate the uses through applied examples.

Full list of authors: Price-Whelan, Adrian M.; Lim, Pey Lian; Earl, Nicholas; Starkman, Nathaniel; Bradley, Larry; Shupe, David L.; Patil, Aarya A.; Corrales, Lia; Brasseur, C. E.; Noethe, Maximilian; Donath, Axel; Tollerud, Erik; Morris, Brett M.; Ginsburg, Adam; Vaher, Eero; Weaver, Benjamin A.; Tocknell, James; Jamieson, William; van Kerkwijk, Marten H.; Robitaille, Thomas P.; Merry, Bruce; Bachetti, Matteo; Gunther, H. Moritz; Aldcroft, Thomas L.; Alvarado-Montes, Jaime A.; Archibald, Anne M.; Bodi, Attila; Bapat, Shreyas; Barentsen, Geert; Bazan, Juanjo; Biswas, Manish; Boquien, Mederic; Burke, D. J.; Cara, Daria; Cara, Mihai; Conroy, Kyle E.; Conseil, Simon; Craig, Matthew W.; Cross, Robert M.; Cruz, Kelle L.; D'Eugenio, Francesco; Dencheva, Nadia; Devillepoix, Hadrien A. R.; Dietrich, Jorg P.; Eigenbrot, Arthur Davis; Erben, Thomas; Ferreira, Leonardo; Foreman-Mackey, Daniel; Fox, Ryan; Freij, Nabil; Garg, Suyog; Geda, Robel; Glattly, Lauren; Gondhalekar, Yash; Gordon, Karl D.; Grant, David; Greenfield, Perry; Groener, Austen M.; Guest, Steve; Gurovich, Sebastian; Handberg, Rasmus; Hart, Akeem; Hatfield-Dodds, Zac; Homeier, Derek; Hosseinzadeh, Griffin; Jenness, Tim; Jones, Craig K.; Joseph, Prajwel; Kalmbach, J. Bryce; Karamehmetoglu, Emir; Kaluszynski, Mikolaj; Kelley, Michael S. P.; Kern, Nicholas; Kerzendorf, Wolfgang E.; Koch, Eric W.; Kulumani, Shankar; Lee, Antony; Ly, Chun; Ma, Zhiyuan; MacBride, Conor; Maljaars, Jakob M.; Muna, Demitri; Murphy, N. A.; Norman, Henrik; O'Steen, Richard; Oman, Kyle A.; Pacifici, Camilla; Pascual, Sergio; Pascual-Granado, J.; Patil, Rohit R.; Perren, Gabriel, I; Pickering, Timothy E.; Rastogi, Tanuj; Roulston, Benjamin R.; Ryan, Daniel F.; Rykoff, Eli S.; Sabater, Jose; Sakurikar, Parikshit; Salgado, Jesus; Sanghi, Aniket; Saunders, Nicholas; Savchenko, Volodymyr; Schwardt, Ludwig; Seifert-Eckert, Michael; Shih, Albert Y.; Jain, Anany Shrey; Shukla, Gyanendra; Sick, Jonathan; Simpson, Chris; Singanamalla, Sudheesh; Singer, Leo P.; Singhal, Jaladh; Sinha, Manodeep; Sipocz, Brigitta M.; Spitler, Lee R.; Stansby, David; Streicher, Ole; Sumak, Jani; Swinbank, John D.; Taranu, Dan S.; Tewary, Nikita; Tremblay, Grant R.; De Val-Borro, Miguel; Vasovic, Zlatan; Van Kooten, Samuel J.; Verma, Shresth; Cardoso, Jose Vinicius de Miranda; Williams, Peter K. G.; Wilson, Tom J.; Winkel, Benjamin; Wood-Vasey, W. M.; Xue, Rui; Yoachim, Peter; Zhang, Chen; Zonca, Andrea; Astropy Project Contributors; TARDIS Collaboration; Astropy Coordination Comm.--This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

BACKGROUND: The combined thickness of the intima and media of the carotid artery is associated with the prevalence of cardiovascular disease. We studied the associations between the thickness of the carotid-artery intima and media and the incidence of new myocardial infarction or stroke in persons without clinical cardiovascular disease. METHODS: Noninvasive measurements of the intima and media of the common and internal carotid artery were made with high-resolution ultrasonography in 5858 subjects 65 years of age or older. Cardiovascular events (new myocardial infarction or stroke) served as outcome variables in subjects without clinical cardiovascular disease (4476 subjects) over a median follow-up period of 6.2 years. RESULTS: The incidence of cardiovascular events correlated with measurements of carotid-artery intima-media thickness. The relative risk of myocardial infarction or stroke increased with intima-media thickness (P<0.001). The relative risk of myocardial infarction or stroke (adjusted for age and sex) for the quintile with the highest thickness as compared with the lowest quintile was 3.87 (95 percent confidence interval, 2.72 to 5.51). The association between cardiovascular events and intima-media thickness remained significant after adjustment for traditional risk factors, showing increasing risks for each quintile of combined intima-media thickness, from the second quintile (relative risk, 1.54; 95 percent confidence interval, 1.04 to 2.28), to the third (relative risk, 1.84; 95 percent confidence interval, 1.26 to 2.67), fourth (relative risk, 2.01; 95 percent confidence interval, 1.38 to 2.91), and fifth (relative risk, 3.15; 95 percent confidence interval, 2.19 to 4.52). The results of separate analyses of myocardial infarction and stroke paralleled those for the combined end point. CONCLUSIONS: Increases in the thickness of the intima and media of the carotid artery, as measured noninvasively by ultrasonography, are directly associated with an increased risk of myocardial infarction and stroke in older adults without a history of cardiovascular disease.

CONTEXT: Survival estimates help individualize goals of care for geriatric patients, but life tables fail to account for the great variability in survival. Physical performance measures, such as gait speed, might help account for variability, allowing clinicians to make more individualized estimates. OBJECTIVE: To evaluate the relationship between gait speed and survival. DESIGN, SETTING, AND PARTICIPANTS: Pooled analysis of 9 cohort studies (collected between 1986 and 2000), using individual data from 34,485 community-dwelling older adults aged 65 years or older with baseline gait speed data, followed up for 6 to 21 years. Participants were a mean (SD) age of 73.5 (5.9) years; 59.6%, women; and 79.8%, white; and had a mean (SD) gait speed of 0.92 (0.27) m/s. MAIN OUTCOME MEASURES: Survival rates and life expectancy. RESULTS: There were 17,528 deaths; the overall 5-year survival rate was 84.8% (confidence interval [CI], 79.6%-88.8%) and 10-year survival rate was 59.7% (95% CI, 46.5%-70.6%). Gait speed was associated with survival in all studies (pooled hazard ratio per 0.1 m/s, 0.88; 95% CI, 0.87-0.90; P < .001). Survival increased across the full range of gait speeds, with significant increments per 0.1 m/s. At age 75, predicted 10-year survival across the range of gait speeds ranged from 19% to 87% in men and from 35% to 91% in women. Predicted survival based on age, sex, and gait speed was as accurate as predicted based on age, sex, use of mobility aids, and self-reported function or as age, sex, chronic conditions, smoking history, blood pressure, body mass index, and hospitalization. CONCLUSION: In this pooled analysis of individual data from 9 selected cohorts, gait speed was associated with survival in older adults.

Severe or therapy-resistant asthma is increasingly recognised as a major unmet need. A Task Force, supported by the European Respiratory Society and American Thoracic Society, reviewed the definition and provided recommendations and guidelines on the evaluation and treatment of severe asthma in children and adults. A literature review was performed, followed by discussion by an expert committee according to the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach for development of specific clinical recommendations. When the diagnosis of asthma is confirmed and comorbidities addressed, severe asthma is defined as asthma that requires treatment with high dose inhaled corticosteroids plus a second controller and/or systemic corticosteroids to prevent it from becoming "uncontrolled" or that remains "uncontrolled" despite this therapy. Severe asthma is a heterogeneous condition consisting of phenotypes such as eosinophilic asthma. Specific recommendations on the use of sputum eosinophil count and exhaled nitric oxide to guide therapy, as well as treatment with anti-IgE antibody, methotrexate, macrolide antibiotics, antifungal agents and bronchial thermoplasty are provided. Coordinated research efforts for improved phenotyping will provide safe and effective biomarker-driven approaches to severe asthma therapy.

Quantum EXPRESSO is an integrated suite of open-source computer codes for quantum simulations of materials using state-of-the-art electronic-structure techniques, based on density-functional theory, density-functional perturbation theory, and many-body perturbation theory, within the plane-wave pseudopotential and projector-augmented-wave approaches. Quantum EXPRESSO owes its popularity to the wide variety of properties and processes it allows to simulate, to its performance on an increasingly broad array of hardware architectures, and to a community of researchers that rely on its capabilities as a core open-source development platform to implement their ideas. In this paper we describe recent extensions and improvements, covering new methodologies and property calculators, improved parallelization, code modularization, and extended interoperability both within the distribution and with external software.

Identifying reliable biomarkers of aging is a major goal in geroscience. While the first generation of epigenetic biomarkers of aging were developed using chronological age as a surrogate for biological age, we hypothesized that incorporation of composite clinical measures of phenotypic age that capture differences in lifespan and healthspan may identify novel CpGs and facilitate the development of a more powerful epigenetic biomarker of aging. Using an innovative two-step process, we develop a new epigenetic biomarker of aging, DNAm PhenoAge, that strongly outperforms previous measures in regards to predictions for a variety of aging outcomes, including all-cause mortality, cancers, healthspan, physical functioning, and Alzheimer's disease. While this biomarker was developed using data from whole blood, it correlates strongly with age in every tissue and cell tested. Based on an in-depth transcriptional analysis in sorted cells, we find that increased epigenetic, relative to chronological age, is associated with increased activation of pro-inflammatory and interferon pathways, and decreased activation of transcriptional/translational machinery, DNA damage response, and mitochondrial signatures. Overall, this single epigenetic biomarker of aging is able to capture risks for an array of diverse outcomes across multiple tissues and cells, and provide insight into important pathways in aging.

Abstract These updated guidelines replace the previous management guidelines published in 2001. The guidelines are intended for use by health care providers who care for patients who either have these infections or may be at risk for them.

Assessments of anterior cingulate cortex in experimental animals and humans have led to unifying theories of its structural organization and contributions to mammalian behaviour. The anterior cingulate cortex forms a large region around the rostrum of the corpus callosum that is termed the anterior executive region. This region has numerous projections into motor systems, however, since these projections originate from different parts of anterior cingulate cortex and because functional studies have shown that it does not have a uniform contribution to brain functions, the anterior executive region is further subdivided into 'affect' and 'cognition' components. The affect division includes areas 25, 33 and rostral area 24, and has extensive connections with the amygdala and periaqueductal grey, and parts of it project to autonomic brainstem motor nuclei. In addition to regulating autonomic and endocrine functions, it is involved in conditioned emotional learning, vocalizations associated with expressing internal states, assessments of motivational content and assigning emotional valence to internal and external stimuli, and maternal-infant interactions. The cognition division includes caudal areas 24' and 32', the cingulate motor areas in the cingulate sulcus and nociceptive cortex. The cingulate motor areas project to the spinal cord and red nucleus and have premotor functions, while the nociceptive area is engaged in both response selection and cognitively demanding information processing. The cingulate epilepsy syndrome provides important support of experimental animal and human functional imaging studies for the role of anterior cingulate cortex in movement, affect and social behaviours. Excessive cingulate activity in cases with seizures confirmed in anterior cingulate cortex with subdural electrode recordings, can impair consciousness, alter affective state and expression, and influence skeletomotor and autonomic activity. Interictally, patients with anterior cingulate cortex epilepsy often display psychopathic or sociopathic behaviours. In other clinical examples of elevated anterior cingulate cortex activity it may contribute to tics, obsessive-compulsive behaviours, and aberrent social behaviour. Conversely, reduced cingulate activity following infarcts or surgery can contribute to behavioural disorders including akinetic mutism, diminished self-awareness and depression, motor neglect and impaired motor initiation, reduced responses to pain, and aberrent social behaviour. The role of anterior cingulate cortex in pain responsiveness is suggested by cingulumotomy results and functional imaging studies during noxious somatic stimulation. The affect division of anterior cingulate cortex modulates autonomic activity and internal emotional responses, while the cognition division is engaged in response selection associated with skeletomotor activity and responses to noxious stimuli. Overall, anterior cingulate cortex appears to play a crucial role in initiation, motivation, and goal-directed behaviours.(ABSTRACT TRUNCATED AT 400 WORDS)

1. Skinfold thickness, body circumferences and body density were measured in samples of 308 and ninety-five adult men ranging in age from 18 to 61 years. 2. Using the sample of 308 men, multiple regression equations were calculated to estimate body density using either the quadratic or log form of the sum of skinfolds, in combination with age, waist and forearm circumference. 3. The multiple correlations for the equations exceeded 0.90 with standard errors of approximately +/-0.0073 g/ml. 4. The regression equations were cross validated on the second sample of ninety-five men. The correlations between predicted and laboratory-determined body density exceeded 0.90 with standard errors of approximately 0.0077 g/ml. 5. The regression equations were shown to be valid for adult men varying in age and fatness.

Impression management, the process by which people control the impressions others form of them, plays an important role in interpersonal behavior. This article presents a 2-component model within which the literature regarding impression management is reviewed. This model conceptualizes im-pression management as being composed of 2 discrete processes. The 1st involves impression moti-vation—the degree to which people are motivated to control how others see them. Impression moti-vation is conceptualized as a function of 3 factors: the goal-relevance of the impressions one creates, the value of desired outcomes, and the discrepancy between current and desired images. The 2nd component involves impression construction. Five factors appear to determine the kinds of impres-sions people try to construct: the self-concept, desired and undesired identity images, role con-straints, target&amp;apos;s values, and current social image. The 2-component model provides coherence to the literature in the area, addresses controversial issues, and supplies a framework for future research regarding impression management. People have an ongoing interest in how others perceive and evaluate them. Each year, Americans spend billions of dollars on diets, cosmetics, and plastic surgery—all intended to make

Osteoarthritis (OA) is the most common form of arthritis and a major cause of pain and disability in older adults (1). Often OA is referred to as degenerative joint disease “(DJD)”. This is a misnomer because OA is not simply a process of wear and tear but rather abnormal remodeling of joint tissues driven by a host of inflammatory mediators within the affected joint. The most common risk factors for OA include age, gender, prior joint injury, obesity, genetic predisposition, and mechanical factors, including malalignment and abnormal joint shape (2, 3). Despite the multifactorial nature of OA, the pathological changes seen in osteoarthritic joints have common features that affect the entire joint structure resulting in pain, deformity and loss of function. The pathologic changes seen in OA joints (Figures 1 and ​and2)2) include degradation of the articular cartilage, thickening of the subchondral bone, osteophyte formation, variable degrees of synovial inflammation, degeneration of ligaments and, in the knee, the menisci, and hypertrophy of the joint capsule. There can also be changes in periarticular muscles, nerves, bursa, and local fat pads that may contribute to OA or the symptoms of OA. The findings of pathological changes in all of the joint tissues are the impetus for considering OA as a disease of the joint as an organ resulting in “joint failure”. In this review, we will summarize the key features of OA in the various joint tissues affected and provide an overview of the basic mechanisms currently thought to contribute to the pathological changes seen in these tissues. Open in a separate window Figure 1 Sagittal inversion recovery (A–C) and coronal fast spin echo (D–F) images illustrating the magnetic resonance imaging findings of osteoarthritis. (A) reactive synovitis (thick white arrow), (B) subchondral cyst formation (white arrow), (C) bone marrow edema (thin white arrows), (D) partial thickness cartilage wear (thick black arrow), (E–F) full thickness cartilage wear (thin black arrows), subchondral sclerosis (arrowhead) and marginal osteophyte formation (double arrow). Image courtesy of Drs. Hollis Potter and Catherine Hayter, Hospital for Special Surgery, New York, NY

BACKGROUND: The loss of muscle mass is considered to be a major determinant of strength loss in aging. However, large-scale longitudinal studies examining the association between the loss of mass and strength in older adults are lacking. METHODS: Three-year changes in muscle mass and strength were determined in 1880 older adults in the Health, Aging and Body Composition Study. Knee extensor strength was measured by isokinetic dynamometry. Whole body and appendicular lean and fat mass were assessed by dual-energy x-ray absorptiometry and computed tomography. RESULTS: Both men and women lost strength, with men losing almost twice as much strength as women. Blacks lost about 28% more strength than did whites. Annualized rates of leg strength decline (3.4% in white men, 4.1% in black men, 2.6% in white women, and 3.0% in black women) were about three times greater than the rates of loss of leg lean mass ( approximately 1% per year). The loss of lean mass, as well as higher baseline strength, lower baseline leg lean mass, and older age, was independently associated with strength decline in both men and women. However, gain of lean mass was not accompanied by strength maintenance or gain (ss coefficients; men, -0.48 +/- 4.61, p =.92, women, -1.68 +/- 3.57, p =.64). CONCLUSIONS: Although the loss of muscle mass is associated with the decline in strength in older adults, this strength decline is much more rapid than the concomitant loss of muscle mass, suggesting a decline in muscle quality. Moreover, maintaining or gaining muscle mass does not prevent aging-associated declines in muscle strength.

The brain's default mode network consists of discrete, bilateral and symmetrical cortical areas, in the medial and lateral parietal, medial prefrontal, and medial and lateral temporal cortices of the human, nonhuman primate, cat, and rodent brains. Its ...Read More