If you don’t take it – it can’t work: the consequences of not being treated or nonadherence to osteoporosis therapy

Osteoporosis is a growing problem worldwide, linked to an increasingly aging population. Despite the availability of a wide variety of treatments for osteoporosis, a significant number of patients are either not being prescribed treatment or discontinue therapy as early as 6 months after initiation. The reasons for a lack of adherence are many but poor adherence increases the risk of fracture and, therefore, the disease burden to the patient and society. Results from large-scale, randomized clinical studies have shown that different osteoporosis treatments are efficacious in reducing the risk of fracture. Studies assessing the effects of discontinuing osteoporosis therapies show that some treatments appear to continue to protect patients from the risk of future fracture even when treatment is stopped. However, these trials involve patients who have been compliant with treatment for between 2 and 5 years, a situation not reflective of real-world clinical practice. In reality, patients who discontinue therapy within the first 6 months may never achieve the optimum protection from fracture regardless of which treatment they have been prescribed. Clinicians need to develop management strategies to enable patients to adhere to their treatment. This will ultimately result in better prevention of fracture and a lower burden of disease to society and patients

An Analysis of Fundamental Waffle Mode in Early AEOS Adaptive Optics Images

Adaptive optics (AO) systems have significantly improved astronomical imaging capabilities over the last decade, and are revolutionizing the kinds of science possible with 4-5m class ground-based telescopes. A thorough understanding of AO system performance at the telescope can enable new frontiers of science as observations push AO systems to their performance limits. We look at recent advances with wave front reconstruction (WFR) on the Advanced Electro-Optical System (AEOS) 3.6 m telescope to show how progress made in improving WFR can be measured directly in improved science images. We describe how a "waffle mode" wave front error (which is not sensed by a Fried geometry Shack-Hartmann wave front sensor) affects the AO point-spread function (PSF). We model details of AEOS AO to simulate a PSF which matches the actual AO PSF in the I-band, and show that while the older observed AEOS PSF contained several times more waffle error than expected, improved WFR techniques noticeably improve AEOS AO performance. We estimate the impact of these improved WFRs on H-band imaging at AEOS, chosen based on the optimization of the Lyot Project near-infrared coronagraph at this bandpass.Comment: 15 pages, 11 figures, 1 table; to appear in PASP, August 200

Differences in intracellular localisation of ANKH mutants that relate to mechanisms of calcium pyrophosphate deposition disease and craniometaphyseal dysplasia

ANKH mutations are associated with calcium pyrophosphate deposition disease and craniometaphyseal dysplasia. This study investigated the effects of these ANKH mutants on cellular localisation and associated biochemistry. We generated four ANKH overexpression-plasmids containing either calcium pyrophosphate deposition disease or craniometaphyseal dysplasia linked mutations: P5L, E490del and S375del, G389R. They were transfected into CH-8 articular chondrocytes and HEK293 cells. The ANKH mutants dynamic differential localisations were imaged and we investigated the interactions with the autophagy marker LC3. Extracellular inorganic pyrophosphate, mineralization, ENPP1 activity expression of ENPP1, TNAP and PIT-1 were measured. P5L delayed cell membrane localisation but once recruited into the membrane it increased extracellular inorganic pyrophosphate, mineralization, and ENPP1 activity. E490del remained mostly cytoplasmic, forming punctate co-localisations with LC3, increased mineralization, ENPP1 and ENPP1 activity with an initial but unsustained increase in TNAP and PIT-1. S375del trended to decrease extracellular inorganic pyrophosphate, increase mineralization. G389R delayed cell membrane localisation, trended to decrease extracellular inorganic pyrophosphate, increased mineralization and co-localised with LC3. Our results demonstrate a link between pathological localisation of ANKH mutants with different degrees in mineralization. Furthermore, mutant ANKH functions are related to synthesis of defective proteins, inorganic pyrophosphate transport, ENPP1 activity and expression of ENPP1, TNAP and PIT-1

Effect of increasing fruit and vegetable intake by dietary intervention on nutritional biomarkers and attitudes to dietary change : a randomised trial

This work was funded by The Scottish Government Rural and Environmental Science and Analytical Sciences Division (RESAS) and supported by the Rank Prize Funds.Peer reviewedPublisher PD

Electron scale structures and magnetic reconnection signatures in the turbulent magnetosheath

Collisionless space plasma turbulence can generate reconnecting thin current sheets as suggested by recent results of numerical magnetohydrodynamic simulations. The MMS mission provides the first serious opportunity to check if small ion-electron-scale reconnection, generated by turbulence, resembles the reconnection events frequently observed in the magnetotail or at the magnetopause. Here we investigate field and particle observations obtained by the MMS fleet in the turbulent terrestrial magnetosheath behind quasi-parallel bow shock geometry. We observe multiple small-scale current sheets during the event and present a detailed look of one of the detected structures. The emergence of thin current sheets can lead to electron scale structures where ions are demagnetized. Within the selected structure we see signatures of ion demagnetization, electron jets, electron heating and agyrotropy suggesting that MMS spacecraft observe reconnection at these scales

Design of the Subpopulations and Intermediate Outcome Measures in COPD (SPIROMICS) AIR Study.

IntroductionPopulation-based epidemiological evidence suggests that exposure to ambient air pollutants increases hospitalisations and mortality from chronic obstructive pulmonary disease (COPD), but less is known about the impact of exposure to air pollutants on patient-reported outcomes, morbidity and progression of COPD.Methods and analysisThe Subpopulations and Intermediate Outcome Measures in COPD (SPIROMICS) Air Pollution Study (SPIROMICS AIR) was initiated in 2013 to investigate the relation between individual-level estimates of short-term and long-term air pollution exposures, day-to-day symptom variability and disease progression in individuals with COPD. SPIROMICS AIR builds on a multicentre study of smokers with COPD, supplementing it with state-of-the-art air pollution exposure assessments of fine particulate matter, oxides of nitrogen, ozone, sulfur dioxide and black carbon. In the parent study, approximately 3000 smokers with and without airflow obstruction are being followed for up to 3 years for the identification of intermediate biomarkers which predict disease progression. Subcohorts undergo daily symptom monitoring using comprehensive daily diaries. The air monitoring and modelling methods employed in SPIROMICS AIR will provide estimates of individual exposure that incorporate residence-specific infiltration characteristics and participant-specific time-activity patterns. The overarching study aim is to understand the health effects of short-term and long-term exposures to air pollution on COPD morbidity, including exacerbation risk, patient-reported outcomes and disease progression.Ethics and disseminationThe institutional review boards of all the participating institutions approved the study protocols. The results of the trial will be presented at national and international meetings and published in peer-reviewed journals

Observations of whistler mode waves with nonlinear parallel electric fields near the dayside magnetic reconnection separatrix by the Magnetospheric Multiscale mission

We show observations from the Magnetospheric Multiscale (MMS) mission of whistler mode waves in the Earth's low-latitude boundary layer (LLBL) during a magnetic reconnection event. The waves propagated obliquely to the magnetic field toward the X line and were confined to the edge of a southward jet in the LLBL. Bipolar parallel electric fields interpreted as electrostatic solitary waves (ESW) are observed intermittently and appear to be in phase with the parallel component of the whistler oscillations. The polarity of the ESWs suggests that if they propagate with the waves, they are electron enhancements as opposed to electron holes. The reduced electron distribution shows a shoulder in the distribution for parallel velocities between 17,000 and 22,000 km/s, which persisted during the interval when ESWs were observed, and is near the phase velocity of the whistlers. This shoulder can drive Langmuir waves, which were observed in the high-frequency parallel electric field data

Purkinje cell loss in experimental autoimmune encephalomyelitis

Gray matter atrophy observed by brain MRI is an important correlate to clinical disability and disease duration in multiple sclerosis. The objective of this study was to link brain atrophy visualized by neuroimaging to its underlying neuropathology using the MS model, experimental autoimmune encephalomyelitis (EAE). Volumetric changes in brains of EAE mice, as well as matched healthy normal controls, were quantified by collecting post-mortem high-resolution T2-weighted magnetic resonance microscopy and actively stained magnetic resonance histology images. Anatomical delineations demonstrated a significant decrease in the volume of the whole cerebellum, cerebellar cortex, and molecular layer of the cerebellar cortex in EAE as compared to normal controls. The pro-apoptotic marker caspase-3 was detected in Purkinje cells and a significant decrease in Purkinje cell number was found in EAE. Cross modality and temporal correlations revealed a significant association between Purkinje cell loss on neuropathology and atrophy of the molecular layer of the cerebellar cortex by neuroimaging. These results demonstrate the power of using combined population atlasing and neuropathology approaches to discern novel insights underlying gray matter atrophy in animal models of neurodegenerative disease