A Polymorphism in a Gene Encoding Perilipin 4 Is Associated with Height but not with Bone Measures in Individuals from the Framingham Osteoporosis Study

There is increasing interest in identifying new pathways and candidate genes that confer susceptibility to osteoporosis. There is evidence that adipogenesis and osteogenesis may be related, including a common bone marrow progenitor cell for both adipocytes and osteoblasts. Perilipin 1 (PLIN1) and Perilipin 4 (PLIN4) are members of the PATS family of genes and are involved in lipolysis of intracellular lipid deposits. A previous study reported gender-specific associations between one polymorphism of PLIN1 and bone mineral density (BMD) in a Japanese population. We hypothesized that polymorphisms in PLIN1 and PLIN4 would be associated with bone measures in adult Caucasian participants of the Framingham Osteoporosis Study (FOS). We genotyped 1,206 male and 1,445 female participants of the FOS for four single-nucleotide polymorphism (SNPs) in PLIN1 and seven SNPs in PLIN4 and tested for associations with measures of BMD, bone ultrasound, hip geometry, and height. We found several gender-specific significant associations with the measured traits. The association of PLIN4 SNP rs8887, G>A with height in females trended toward significance after simulation testing (adjusted P = 0.07) and remained significant after simulation testing in the combined-sex model (adjusted P = 0.033). In a large study sample of men and women, we found a significant association between one SNP in PLIN4 and height but not with bone traits, suggesting that PATS family genes are not important in the regulation of bone. Identification of genes that influence human height may lead to a better understanding of the processes involved in growth and development

The fitness for the Ageing Brain Study II (FABS II): protocol for a randomized controlled clinical trial evaluating the effect of physical activity on cognitive function in patients with Alzheimer's disease

Background: Observational studies have documented a potential protective effect of physical exercise in older adults who are at risk for developing Alzheimer's disease. The Fitness for the Ageing Brain II (FABS II) study is a multicentre randomized controlled clinical trial (RCT) aiming to determine whether physical activity reduces the rate of cognitive decline among individuals with Alzheimer's disease. This paper describes the background, objectives of the study, and an overview of the protocol including design, organization and data collection methods

GBR 12909 administration as a mouse model of bipolar disorder mania: mimicking quantitative assessment of manic behavior

Mania is a core feature of bipolar disorder (BD) that traditionally is assessed using rating scales. Studies using a new human behavioral pattern monitor (BPM) recently demonstrated that manic BD patients exhibit a specific profile of behavior that differs from schizophrenia and is characterized by increased motor activity, increased specific exploration, and perseverative locomotor patterns as assessed by spatial d. It was hypothesized that disrupting dopaminergic homeostasis by inhibiting dopamine transporter (DAT) function would produce a BD mania-like phenotype in mice as assessed by the mouse BPM. We compared the spontaneous locomotor and exploratory behavior of C57BL/6J mice treated with the catecholamine transporter inhibitor amphetamine or the selective DAT inhibitor GBR 12909 in the mouse BPM. We also assessed the duration of the effect of GBR 12909 by testing mice in the BPM for 3 h and its potential strain dependency by testing 129/SvJ mice. Amphetamine produced hyperactivity and increased perseverative patterns of locomotion as reflected in reduced spatial d values but reduced exploratory activity in contrast to the increased exploration observed in BD patients. GBR 12909 increased activity and reduced spatial d in combination with increased exploratory behavior, irrespective of inbred strain. These effects persisted for at least 3 h. Thus, selectively inhibiting the DAT produced a long-lasting cross-strain behavioral profile in mice that was consistent with that observed in manic BD patients. These findings support the use of selective DAT inhibition in animal models of the impaired dopaminergic homeostasis putatively involved in the pathophysiology of BD mania

CONNECT for quality: protocol of a cluster randomized controlled trial to improve fall prevention in nursing homes

<p>Abstract</p> <p>Background</p> <p>Quality improvement (QI) programs focused on mastery of content by individual staff members are the current standard to improve resident outcomes in nursing homes. However, complexity science suggests that learning is a social process that occurs within the context of relationships and interactions among individuals. Thus, QI programs will not result in optimal changes in staff behavior unless the context for social learning is present. Accordingly, we developed CONNECT, an intervention to foster systematic use of management practices, which we propose will enhance effectiveness of a nursing home Falls QI program by strengthening the staff-to-staff interactions necessary for clinical problem-solving about complex problems such as falls. The study aims are to compare the impact of the CONNECT intervention, plus a falls reduction QI intervention (CONNECT + FALLS), to the falls reduction QI intervention alone (FALLS), on fall-related process measures, fall rates, and staff interaction measures.</p> <p>Methods/design</p> <p>Sixteen nursing homes will be randomized to one of two study arms, CONNECT + FALLS or FALLS alone. Subjects (staff and residents) are clustered within nursing homes because the intervention addresses social processes and thus must be delivered within the social context, rather than to individuals. Nursing homes randomized to CONNECT + FALLS will receive three months of CONNECT first, followed by three months of FALLS. Nursing homes randomized to FALLS alone receive three months of FALLs QI and are offered CONNECT after data collection is completed. Complexity science measures, which reflect staff perceptions of communication, safety climate, and care quality, will be collected from staff at baseline, three months after, and six months after baseline to evaluate immediate and sustained impacts. FALLS measures including quality indicators (process measures) and fall rates will be collected for the six months prior to baseline and the six months after the end of the intervention. Analysis will use a three-level mixed model.</p> <p>Discussion</p> <p>By focusing on improving local interactions, CONNECT is expected to maximize staff's ability to implement content learned in a falls QI program and integrate it into knowledge and action. Our previous pilot work shows that CONNECT is feasible, acceptable and appropriate.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT00636675">NCT00636675</a></p

Weak-coupling superconductivity in an anisotropic three-dimensional repulsive Hubbard model

We study a three-dimensional single-band repulsive Hubbard model at weak coupling. We establish the superconducting phase diagram in the parameter space of the chemical potential and the out-of-plane hopping strength. The model continuously connects the Hubbard model in two and three dimensions. We confirm previously established results in these limits, and identify a rich structure of competing order parameters in between. Specifically, we find five types of p- and d-wave orders. In several regions of the phase diagram, even when the Fermi surface is a corrugated cylinder, the ground state is a time-reversal-symmetry-breaking superconductor with nodes, i.e., a Weyl superconductor

Statistical mechanics of dimers on quasiperiodic Ammann-Beenker tilings

We study classical dimers on two-dimensional quasiperiodic Ammann-Beenker (AB) tilings. Using the discrete scale-symmetry of quasiperiodic tilings, we prove that each infinite tiling admits “perfect matchings”, where every vertex is touched by one dimer. We show the appearance of so-called monomer pseudomembranes. These are sets of edges, which collectively host exactly one dimer, which bound certain eightfold-symmetric regions of the tiling. Regions bounded by pseudomembranes are matched together in a way that resembles perfect matchings of the tiling itself. These structures emerge at all scales, suggesting the preservation of collective dimer fluctuations over long distances. We provide numerical evidence, via Monte Carlo simulations, of dimer correlations consistent with power laws over a hierarchy of different lengthscales. We also find evidence of rich monomer correlations, with monomers displaying a pattern of attraction and repulsion to different regions within pseudomembranes, along with signatures of deconfinement within certain annular regions of the tiling