Melt movement through the Icelandic crust.

We use both seismology and geobarometry to investigate the movement of melt through the volcanic crust of Iceland. We have captured melt in the act of moving within or through a series of sills ranging from the upper mantle to the shallow crust by the clusters of small earthquakes it produces as it forces its way upward. The melt is injected not just beneath the central volcanoes, but also at discrete locations along the rift zones and above the centre of the underlying mantle plume. We suggest that the high strain rates required to produce seismicity at depths of 10-25 km in a normally ductile part of the Icelandic crust are linked to the exsolution of carbon dioxide from the basaltic melts. The seismicity and geobarometry provide complementary information on the way that the melt moves through the crust, stalling and fractionating, and often freezing in one or more melt lenses on its way upwards: the seismicity shows what is happening instantaneously today, while the geobarometry gives constraints averaged over longer time scales on the depths of residence in the crust of melts prior to their eruption. This article is part of the Theo Murphy meeting issue 'Magma reservoir architecture and dynamics'

Metabolomics and Lipidomics Signatures of Insulin Resistance and Abdominal Fat Depots in People Living with Obesity

The liver, skeletal muscle, and adipose tissue are major insulin target tissues and key players in glucose homeostasis. We and others have described diverse insulin resistance (IR) phenotypes in people at risk of developing type 2 diabetes. It is postulated that identifying the IR phenotype in a patient may guide the treatment or the prevention strategy for better health outcomes in populations at risk. Here, we performed plasma metabolomics and lipidomics in a cohort of men and women living with obesity not complicated by diabetes (mean [SD] BMI 36.0 [4.5] kg/m2, n = 62) to identify plasma signatures of metabolites and lipids that align with phenotypes of IR (muscle, liver, or adipose tissue) and abdominal fat depots. We used 2-step hyperinsulinemic-euglycemic clamp with deuterated glucose, oral glucose tolerance test, dual-energy X-ray absorptiometry and abdominal magnetic resonance imaging to assess muscle-, liver- and adipose tissue- IR, beta cell function, body composition, abdominal fat distribution and liver fat, respectively. Spearman’s rank correlation analyses that passed the Benjamini–Hochberg statistical correction revealed that cytidine, gamma-aminobutyric acid, anandamide, and citrate corresponded uniquely with muscle IR, tryptophan, cAMP and phosphocholine corresponded uniquely with liver IR and phenylpyruvate and hydroxy-isocaproic acid corresponded uniquely with adipose tissue IR (p < 7.2 × 10−4). Plasma cholesteryl sulfate (p = 0.00029) and guanidinoacetic acid (p = 0.0001) differentiated between visceral and subcutaneous adiposity, while homogentisate correlated uniquely with liver fat (p = 0.00035). Our findings may help identify diverse insulin resistance and adiposity phenotypes and enable targeted treatments in people living with obesity

Clinical and molecular characterization of a novel PLIN1 frameshift mutation identified in patients with familial partial lipodystrophy.

Perilipin 1 is a lipid droplet coat protein predominantly expressed in adipocytes, where it inhibits basal and facilitates stimulated lipolysis. Loss-of-function mutations in the PLIN1 gene were recently reported in patients with a novel subtype of familial partial lipodystrophy, designated as FPLD4. We now report the identification and characterization of a novel heterozygous frameshift mutation affecting the carboxy-terminus (439fs) of perilipin 1 in two unrelated families. The mutation cosegregated with a similar phenotype including partial lipodystrophy, severe insulin resistance and type 2 diabetes, extreme hypertriglyceridemia, and nonalcoholic fatty liver disease in both families. Poor metabolic control despite maximal medical therapy prompted two patients to undergo bariatric surgery, with remarkably beneficial consequences. Functional studies indicated that expression levels of the mutant protein were lower than wild-type protein, and in stably transfected preadipocytes the mutant protein was associated with smaller lipid droplets. Interestingly, unlike the previously reported 398 and 404 frameshift mutants, this variant binds and stabilizes ABHD5 expression but still fails to inhibit basal lipolysis as effectively as wild-type perilipin 1. Collectively, these findings highlight the physiological need for exquisite regulation of neutral lipid storage within adipocyte lipid droplets, as well as the possible metabolic benefits of bariatric surgery in this serious disease.Wellcome TrustThis is the author accepted manuscript. The final version is available from the American Diabetes Association via http://dx.doi.org/10.2337/db14-010

Patterns of analgesic use, pain and self-efficacy: a cross-sectional study of patients attending a hospital rheumatology clinic

Background: Many people attending rheumatology clinics use analgesics and non-steroidal anti-inflammatories for persistent musculoskeletal pain. Guidelines for pain management recommend regular and pre-emptive use of analgesics to reduce the impact of pain. Clinical experience indicates that analgesics are often not used in this way. Studies exploring use of analgesics in arthritis have historically measured adherence to such medication. Here we examine patterns of analgesic use and their relationships to pain, self-efficacy and demographic factors. Methods: Consecutive patients were approached in a hospital rheumatology out-patient clinic. Pattern of analgesic use was assessed by response to statements such as 'I always take my tablets every day.' Pain and self-efficacy (SE) were measured using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and Arthritis Self-Efficacy Scale (ASES). Influence of factors on pain level and regularity of analgesic use were investigated using linear regression. Differences in pain between those agreeing and disagreeing with statements regarding analgesic use were assessed using t-tests. Results: 218 patients (85% of attendees) completed the study. Six (2.8%) patients reported no current pain, 26 (12.3%) slight, 100 (47.4%) moderate, 62 (29.4%) severe and 17 (8.1%) extreme pain. In multiple linear regression self efficacy and regularity of analgesic use were significant (p < 0.01) with lower self efficacy and more regular use of analgesics associated with more pain. Low SE was associated with greater pain: 40 (41.7%) people with low SE reported severe pain versus 22 (18.3%) people with high SE, p < 0.001. Patients in greater pain were significantly more likely to take analgesics regularly; 13 (77%) of those in extreme pain reported always taking their analgesics every day, versus 9 (35%) in slight pain. Many patients, including 46% of those in severe pain, adjusted analgesic use to current pain level. In simple linear regression, pain was the only variable significantly associated with regularity of analgesic use: higher levels of pain corresponded to more regular analgesic use (p = 0.003). Conclusion: Our study confirms that there is a strong inverse relationship between self-efficacy and pain severity. Analgesics are often used irregularly by people with arthritis, including some reporting severe pain

An interdisciplinary intervention for older Taiwanese patients after surgery for hip fracture improves health-related quality of life

Abstract Background The effects of intervention programs on health-related quality of life (HRQOL) of patients with hip fracture have not been well studied. We hypothesized that older patients with hip fracture who received our interdisciplinary intervention program would have better HRQOL than those who did not. Methods A randomized experimental design was used. Older patients with hip fracture (N = 162), 60 to 98 years old, from a medical center in northern Taiwan were randomly assigned to an experimental (n = 80) or control (n = 82) group. HRQOL was measured by the SF-36 Taiwan version at 1, 3, 6, and 12 months after discharge. Results The experimental group had significantly better overall outcomes in bodily pain (&#946; = 9.38, p = 0.002), vitality (&#946; = 9.40, p &lt; 0.001), mental health (&#946; = 8.16, p = 0.004), physical function (&#946; = 16.01, p &lt; 0.001), and role physical (&#946; = 22.66, p &lt; 0.001) than the control group at any time point during the first year after discharge. Physical-related health outcomes (physical functioning, role physical, and vitality) had larger treatment effects than emotional/mental- and social functioning-related health outcomes. Conclusions This interdisciplinary intervention program may improve health outcomes of elders with hip fracture. Our results may provide a reference for health care providers in countries using similar programs with Chinese/Taiwanese immigrant populations. Trial registration NCT01052636http://deepblue.lib.umich.edu/bitstream/2027.42/78259/1/1471-2474-11-225.xmlhttp://deepblue.lib.umich.edu/bitstream/2027.42/78259/2/1471-2474-11-225.pdfPeer Reviewe

A Method for Determining Skeletal Lengths from DXA Images

<p>Abstract</p> <p>Background</p> <p>Skeletal ratios and bone lengths are widely used in anthropology and forensic pathology and hip axis length is a useful predictor of fracture. The aim of this study was to show that skeletal ratios, such as length of femur to height, could be accurately measured from a DXA (dual energy X-ray absorptiometry) image.</p> <p>Methods</p> <p>90 normal Caucasian females, 18–80 years old, with whole body DXA data were used as subjects. Two methods, linear pixel count (LPC) and reticule and ruler (RET) were used to measure skeletal sizes on DXA images and compared with real clinical measures from 20 subjects and 20 x-rays of the femur and tibia taken in 2003.</p> <p>Results</p> <p>Although both methods were highly correlated, the LPC inter- and intra-observer error was lower at 1.6% compared to that of RET at 2.3%. Both methods correlated positively with real clinical measures, with LPC having a marginally stronger correlation coefficient (r²= 0.94; r²= 0.84; average r²= 0.89) than RET (r²= 0.86; r²= 0.84; average r²= 0.85) with X-rays and real measures respectively. Also, the time taken to use LPC was half that of RET at 5 minutes per scan.</p> <p>Conclusion</p> <p>Skeletal ratios can be accurately and precisely measured from DXA total body scan images. The LPC method is easy to use and relatively rapid. This new phenotype will be useful for osteoporosis research for individuals or large-scale epidemiological or genetic studies.</p

Management of subtrochanteric femur fractures with internal fixation and recombinant human bone morphogenetic protein-7 in a patient with osteopetrosis: a case report

<p>Abstract</p> <p>Introduction</p> <p>Osteopetrosis is a group of conditions characterized by defects in the osteoclastic function of the bone resulting in defective bone resorption. Clinically, the condition is characterized by a dense, sclerotic, deformed bone which, despite an increased density observable by radiography, often results in an increased propensity to fracture and delayed union.</p> <p>Case Presentation</p> <p>We report the case of a 27-year-old Asian man presenting with bilateral subtrochanteric femur fractures. He had a displaced right subtrochanteric femur fracture after a low-energy fall, which was treated surgically. The second fracture that our patient endured was diagnosed as a stress fracture ten weeks later when he complained of pain in the contralateral left thigh. By that time, the right-sided fracture exhibited no radiographic evidence of healing, and when the left-sided stress fracture was being treated surgically, bone grafting with recombinant human bone morphogenetic protein-7 was also performed on the right side.</p> <p>Conclusion</p> <p>While there are no data supporting the use of bone morphogenic proteins in the management of delayed healing in patients with osteopetrosis, no other reliable osteoinductive grafting options are available to treat this condition. Both fractures in our patient healed, but based on the serial radiographic assessment it is uncertain to what degree the recombinant human bone morphogenetic protein-7 may have contributed to the successful outcome. It may have also contributed to the formation of heterotopic bone around the fracture site. Further investigation of the effectiveness and indications of bone morphogenic protein use for the management of delayed fracture healing in patients with osteopetrosis is warranted.</p

Glucose-6-phosphate dehydrogenase contributes to the regulation of glucose uptake in skeletal muscle

The development of skeletal muscle insulin resistance is an early physiological defect, yet the intracellular mechanisms accounting for this metabolic defect remained unresolved. Here, we have examined the role of glucose-6-phosphate dehydrogenase (G6PDH) activity in the pathogenesis of insulin resistance in skeletal muscle. Methods Multiple mouse disease states exhibiting insulin resistance and glucose intolerance, as well as obese humans defined as insulin-sensitive, insulin-resistant, or pre-diabetic, were examined. Results We identified increased glucose-6-phosphate dehydrogenase (G6PDH) activity as a common intracellular adaptation that occurs in parallel with the induction of insulin resistance in skeletal muscle and is present across animal and human disease states with an underlying pathology of insulin resistance and glucose intolerance. We observed an inverse association between G6PDH activity and nitric oxide synthase (NOS) activity and show that increasing NOS activity via the skeletal muscle specific neuronal (n)NOS&mu; partially suppresses G6PDH activity in skeletal muscle cells. Furthermore, attenuation of G6PDH activity in skeletal muscle cells via (a) increased nNOS&mu;/NOS activity, (b) pharmacological G6PDH inhibition, or (c) genetic G6PDH inhibition increases insulin-independent glucose uptake. Conclusions We have identified a novel, previously unrecognized role for G6PDH in the regulation of skeletal muscle glucose metabolism. <br /

Multi-layer scintillation detector for the MOON double beta decay experiment: Scintillation photon responses studied by a prototype detector MOON-1

An ensemble of multi-layer scintillators is discussed as an option of the high-sensitivity detector Mo Observatory Of Neutrinos (MOON) for spectroscopic measurements of neutrino-less double beta decays. A prototype detector MOON-1, which consists of 6 layer plastic-scintillator plates, was built to study the sensitivity of the MOON-type detector. The scintillation photon collection and the energy resolution, which are key elements for the high-sensitivity experiments, are found to be 1835+/-30 photo-electrons for 976 keV electrons and sigma = 2.9+/-0.1% (dE/E = 6.8+/-0.3 % in FWHM) at the Qbb ~ 3 MeV region, respectively. The multi-layer plastic-scintillator structure with good energy resolution as well as good background suppression of beta-gamma rays is crucial for the MOON-type detector to achieve the inverted hierarchy neutrino mass sensitivity.Comment: 8 pages, 16 figures, submitted to Nucl.Instrum.Met