Are bisphosphonates effective in the treatment of osteoarthritis pain? A meta-analysis and systematic review.

Osteoarthritis (OA) is the most common form of arthritis worldwide. Pain and reduced function are the main symptoms in this prevalent disease. There are currently no treatments for OA that modify disease progression; therefore analgesic drugs and joint replacement for larger joints are the standard of care. In light of several recent studies reporting the use of bisphosphonates for OA treatment, our work aimed to evaluate published literature to assess the effectiveness of bisphosphonates in OA treatment

Reaction rates and transport in neutron stars

Understanding signals from neutron stars requires knowledge about the transport inside the star. We review the transport properties and the underlying reaction rates of dense hadronic and quark matter in the crust and the core of neutron stars and point out open problems and future directions.Comment: 74 pages; commissioned for the book "Physics and Astrophysics of Neutron Stars", NewCompStar COST Action MP1304; version 3: minor changes, references updated, overview graphic added in the introduction, improvements in Sec IV.A.

Evolution of Skull and Mandible Shape in Cats (Carnivora: Felidae)

The felid family consists of two major subgroups, the sabretoothed and the feline cats, to which all extant species belong, and are the most anatomically derived of all carnivores for predation on large prey with a precision killing bite. There has been much controversy and uncertainty about why the skulls and mandibles of sabretoothed and feline cats evolved to become so anatomically divergent, but previous models have focused on single characters and no unifying hypothesis of evolutionary shape changes has been formulated. Here I show that the shape of the skull and mandible in derived sabrecats occupy entirely different positions within overall morphospace from feline cats, and that the evolution of skull and mandible shape has followed very different paths in the two subgroups. When normalised for body-size differences, evolution of bite forces differ markedly in the two groups, and are much lower in derived sabrecats, and they show a significant relationship with size and cranial shape, whereas no such relationship is present in feline cats. Evolution of skull and mandible shape in modern cats has been governed by the need for uniform powerful biting irrespective of body size, whereas in sabrecats, shape evolution was governed by selective pressures for efficient predation with hypertrophied upper canines at high gape angles, and bite forces were secondary and became progressively weaker during sabrecat evolution. The current study emphasises combinations of new techniques for morphological shape analysis and biomechanical studies to formulate evolutionary hypotheses for difficult groups

Jaguar Densities across Human-Dominated Landscapes in Colombia: The Contribution of Unprotected Areas to Long Term Conservation

Large carnivores such as jaguars (Panthera onca) are species of conservation concern because they are suffering population declines and are keystone species in their ecosystems. Their large area requirements imply that unprotected and ever-increasing agricultural regions can be important habitats as they allow connectivity and dispersal among core protected areas. Yet information on jaguar densities across unprotected landscapes it is still scarce and crucially needed to assist management and range-wide conservation strategies. Our study provides the first jaguar density estimates of Colombia in agricultural regions which included cattle ranching, the main land use in the country, and oil palm cultivation, an increasing land use across the Neotropics. We used camera trapping across two agricultural landscapes located in the Magdalena River valley and in the Colombian llanos (47–53 stations respectively; >2000 trap nights at both sites) and classic and spatially explicit capture-recapture models with the sex of individuals as a covariate. Density estimates were 2.52±0.46–3.15±1.08 adults/100 km2 in the Magdalena valley, whereas 1.12±0.13–2.19±0.99 adults/100 km2 in the Colombian llanos, depending on analysis used. We suggest that jaguars are able to live across unprotected human-use areas and co-exist with agricultural landscapes including oil-palm plantations if natural areas and riparian habitats persist in the landscape and hunting of both jaguar and prey is limited. In the face of an expanding agriculture across the tropics we recommend land-use planning, adequate incentives, regulations, and good agricultural practices for range-wide jaguar connectivity and survival

[Plasma 2020 Decadal] The essential role of multi-point measurements in turbulence investigations: the solar wind beyond single scale and beyond the Taylor Hypothesis

This paper briefly reviews a number of fundamental measurements that need to be made in order to characterize turbulence in space plasmas such as the solar wind. It has long been known that many of these quantities require simultaneous multipoint measurements to attain a proper characterization that would reveal the fundamental physics of plasma turbulence. The solar wind is an ideal plasma for such an investigation, and it now appears to be technologically feasible to carry out such an investigation, following the pioneering Cluster and MMS missions. Quantities that need to be measured using multipoint measurements include the two-point, two-time second correlation function of velocity, magnetic field and density, and higher order statistical objects such as third and fourth order structure functions. Some details of these requirements are given here, with a eye towards achieving closure on fundamental questions regarding the cascade rate, spectral anisotropy, characteristic coherent structures, intermittency, and dissipation mechanisms that describe plasma turbuelence, as well as its variability with plasma parameters in the solar wind. The motivation for this discussion is the current planning for a proposed Helioswarm mission that would be designed to make these measurements,leading to breakthrough understanding of the physics of space and astrophysical turbulence

Eukaryotic Evolutionary Transitions Are Associated with Extreme Codon Bias in Functionally-Related Proteins

Codon bias in the genome of an organism influences its phenome by changing the speed and efficiency of mRNA translation and hence protein abundance. We hypothesized that differences in codon bias, either between-species differences in orthologous genes, or within-species differences between genes, may play an evolutionary role. To explore this hypothesis, we compared the genome-wide codon bias in six species that occupy vital positions in the Eukaryotic Tree of Life. We acquired the entire protein coding sequences for these organisms, computed the codon bias for all genes in each organism and explored the output for relationships between codon bias and protein function, both within- and between-lineages. We discovered five notable coordinated patterns, with extreme codon bias most pronounced in traits considered highly characteristic of a given lineage. Firstly, the Homo sapiens genome had stronger codon bias for DNA-binding transcription factors than the Saccharomyces cerevisiae genome, whereas the opposite was true for ribosomal proteins – perhaps underscoring transcriptional regulation in the origin of complexity. Secondly, both mammalian species examined possessed extreme codon bias in genes relating to hair – a tissue unique to mammals. Thirdly, Arabidopsis thaliana showed extreme codon bias in genes implicated in cell wall formation and chloroplast function – which are unique to plants. Fourthly, Gallus gallus possessed strong codon bias in a subset of genes encoding mitochondrial proteins – perhaps reflecting the enhanced bioenergetic efficiency in birds that co-evolved with flight. And lastly, the G. gallus genome had extreme codon bias for the Ciliary Neurotrophic Factor – which may help to explain their spontaneous recovery from deafness. We propose that extreme codon bias in groups of genes that encode functionally related proteins has a pathway-level energetic explanation

Effect of eplerenone on parathyroid hormone levels in patients with primary hyperparathyroidism: a randomized, double-blind, placebo-controlled trial

<p>Abstract</p> <p>Background</p> <p>Increasing evidence suggests the bidirectional interplay between parathyroid hormone and aldosterone as an important mechanism behind the increased risk of cardiovascular damage and bone disease observed in primary hyperparathyroidism. Our primary object is to assess the efficacy of the mineralocorticoid receptor-blocker eplerenone to reduce parathyroid hormone secretion in patients with parathyroid hormone excess.</p> <p>Methods/design</p> <p>Overall, 110 adult male and female patients with primary hyperparathyroidism will be randomly assigned to eplerenone (25 mg once daily for 4 weeks and 4 weeks with 50 mg once daily after dose titration] or placebo, over eight weeks. Each participant will undergo detailed clinical assessment, including anthropometric evaluation, 24-h ambulatory arterial blood pressure monitoring, echocardiography, kidney function and detailed laboratory determination of biomarkers of bone metabolism and cardiovascular disease.</p> <p>The study comprises the following exploratory endpoints: mean change from baseline to week eight in (1) parathyroid hormone(1–84) as the primary endpoint and (2) 24-h systolic and diastolic ambulatory blood pressure levels, NT-pro-BNP, biomarkers of bone metabolism, 24-h urinary protein/albumin excretion and echocardiographic parameters reflecting systolic and diastolic function as well as cardiac dimensions, as secondary endpoints.</p> <p>Discussion</p> <p>In view of the reciprocal interaction between aldosterone and parathyroid hormone and the potentially ensuing target organ damage, the EPATH trial is designed to determine whether eplerenone, compared to placebo, will effectively impact on parathyroid hormone secretion and improve cardiovascular, renal and bone health in patients with primary hyperparathyroidism.</p> <p>Trial registration</p> <p>ISRCTN33941607</p