Osmium isotope compositions of detrital Os-rich alloys from the Rhine River provide evidence for a global late Mesoproterozoic mantle depletion event

We report osmium isotopic compositions for 297 mantle-derived detrital Ru–Os–Ir alloy grains found in gold and platinum-group mineral bearing placers of the Rhine River. These alloys were likely formed as a result of high degree melting in the convective mantle and derived from residual Paleozoic mantle peridotites in the Alps of Central Europe that were accreted as part of a collage of Gondwana-derived ‘Armorican’ terranes before the Variscan Orogeny. The 187Os/188Os isotope ratios of the Os-rich alloys show a wide distribution, with two modes at 0.1244 and 0.1205. These two modes correspond to rhenium depletion ages, interpreted to correspond with episodes of high-degree mantle melting, at ∼0.5 and ∼1.1 Ga. The data confirm the ability of the oceanic mantle to preserve evidence of ancient melting events. Our new data, in combination with published data on Os-rich alloys from the Urals and Tasmania and with data for abyssal peridotites, indicate a geographically widespread record of a major global Late Mesoproterozoic (1.0–1.2 Ga) high-degree melting event in Paleozoic oceanic mantle rocks. This model age peak is essentially absent from the crustal record of Central-Western Europe, but does coincide with the apparent peak in global continental crust zircon ages at this time. Thus, high-degree mantle melting peaking in the 1.0–1.2 Ga interval may have affected a large part of Earth's mantle. This interval occurred during a period of relative super-continental stability, which may have been accompanied in the oceanic realm by rapid seafloor spreading and extensive subduction, and by unusually high activity of mantle plumes forming two active mantle superswells

Musculoskeletal complaints and disability in a group of young adults with major congenital upper limb differences in The Netherlands

Purpose: To determine prevalence of musculoskeletal complaints (MSCs) in adults with major congenital upper limb differences (CoULD) compared to able-bodied controls, and to examine associations of MSCs and disability with various biopsychosocial factors. Materials and methods: Questionnaire-based cross-sectional study assessing MSCs, disability (using the Disabilities of the Arm, Shoulder and Hand questionnaire (DASH)), general and mental health status, physical work demands, and upper extremity range of motion. Results: Seventy-one individuals with CoULD (participation rate: 41%) and 71 controls matched on age, gender, and education were included (49% female, mean age 28.9 years). Year prevalence of MSCs was significantly higher in the CoULD group (35%) than in the control group (18%). The CoULD group was less often employed and had lower scores on all measures of upper limb range of motion and hand grip. MSCs were associated with higher DASH scores and higher reported work demands. Disability was associated with female gender, more joints with limited range of motion, unemployment, and lower general and mental health. Factors associated with disability did not differ between groups.Conclusions: MSCs are a frequent problem in young adults with major CoULD. To prevent or reduce MSC and disability, clinicians and researchers should be aware of the associated factors. Implications for rehabilitation The year prevalence of musculoskeletal complaints (MSCs) in those with major congenital upper limb differences (CoULD) was approximately double to that of the control group, implying a potential relationship between CoULD and MSCs. Rehabilitation professionals should develop personalized strategies to manage work demands in those with CoULD, considering the association between MSCs and higher reported work demands. Recognizing the impact of a negatively perceived body image on mental health, clinicians should integrate psychological counseling into rehabilitation treatments to support mental well-being and improve overall quality of life in those with CoULD. Rehabilitation professionals should educate individuals with CoULD about the potential associations between upper limb work demands, MSCs, and disability.</p

Low sclerostin levels after long-term remission of acromegaly

Purpose Bone health is compromised in acromegaly resulting in vertebral fractures (VFs), regardless of biochemical remission. Sclerostin is a negative inhibitor of bone formation and is associated with increased fracture risk in the general population. Therefore, we compared sclerostin concentrations between well-controlled acromegaly patients and healthy controls, and assessed its relationship with bone mineral density (BMD), and VFs in acromegaly. Methods Seventy-nine patients (mean age 58.9 +/- 11.4 years, 49% women) with controlled acromegaly, and 91 healthy controls (mean age 51.1 +/- 16.9 years, 59% women) were included. Plasma sclerostin levels (pg/mL) in patients were measured with an ELISA assay, whereas in controls, serum levels were converted to plasma levels by multiplication with 3.6. In patients, VFs were radiographically assessed, and BMD was assessed using dual X-ray absorptiometry. Results Median sclerostin concentration in controlled acromegaly patients was significantly lower than in healthy controls (104.5 pg/mL (range 45.7-234.7 pg/mL) vs 140.0 pg/mL (range 44.8-401.6 pg/mL), p < 0.001). Plasma sclerostin levels were not related to age, current growth hormone (GH) or insulin-like factor-1 (IGF-1) levels, gonadal state, treatment modality, remission duration, or BMD, VF presence, severity or progression. Conclusion Patients with long-term controlled acromegaly have lower plasma sclerostin levels than healthy controls, as a reflection of decreased osteocyte activity. Further longitudinal studies are needed to establish the course of sclerostin during different phases of disease and its exact effects in acromegalic osteopathy.Diabetes mellitus: pathophysiological changes and therap

Can patients with Parkinson's disease use dry powder inhalers during off periods?

Because of its rapid onset of action, pulmonary administration of levodopa is an interesting alternative to oral administration for the rescue treatment of Parkinson's disease patients in an off period. We studied the ability of Parkinson's disease patients to operate a dry powder inhaler (DPI) correctly during an off period. We used an instrumented test inhaler with three different resistances to air flow to record flow curves and computed various inhalation parameters. We observed that all (13) patients were able to generate pressure drops > 2 kPa over the highest resistance and 10 out of 13 patients achieved at least 4 kPa. Inhaled volumes (all resistances) varied from 1.2 L to 3.5 L. Total inhalation time and the time to peak inspiratory flow rate both decreased with decreasing inhaler resistance. Twelve out of thirteen patients could hold their breath for at least five seconds after inhalation and nine could extend this time to ten seconds. The data from this study indicate that patients with Parkinson's disease will indeed be able to use a dry powder inhaler during an off period and they provide an adequate starting point for the development of a levodopa powder inhaler to treat this particular patient group

Randomized, placebo-controlled trial of low molecular weight heparin in active ulcerative colitis

Background: In several open and 1 controlled trial, unfractionated heparin was effective in the treatment of active ulcerative colitis (UC). Low molecular weight heparin (LMWH) had a similar effect in several open studies.Methods: We studied the efficacy, safety, and tolerability of LMWH in mild to moderately active UC in a randomized, double-blind, placebo-controlled trial. In all, 29 patients with a mild or moderate recurrence of UC during salicylate treatment were randomized to receive either reviparin 3,436 IU (n = 15) subcutaneously twice daily or placebo (n = 14). The study period was 8 weeks. Treatment was discontinued if there was no improvement at 4 weeks or at any disease progression. Primary outcome measure was clinical improvement at 8 weeks measured by the Colitis Activity Index (CAI) and the Clinical Symptoms Grading (CSG, based on the CAI). Endoscopic and histologic grading and quality of life as measured by the Inflammatory Bowel Disease Questionnaire (IBDQ) were secondary outcome measures. Patients were closely monitored for adverse events.Results: Twenty of 29 patients finished the 8-week treatment period (reviparin versus placebo: 11 versus 9; P = 0.70). There was no difference in CSG, CAI, endoscopic and histologic grading, or IBDQ. Treatment was well tolerated and no serious adverse events occurred.Conclusion: In this study, treatment with LMWH showed no significant clinical advantage compared to placebo in mild to moderately active UC.(Inflamm Bowel Dis 2007)

Leucocyte and platelet activation in cardiac surgery patients with and without lung injury: a prospective cohort study

OBJECTIONS: Development of acute lung injury after cardiac surgery is associated with an unfavourable outcome. Acute respiratory distress syndrome in general is, besides cytokine and interleukin activation, associated with activation of platelets, monocytes and neutrophils. In relation to pulmonary outcome after cardiac surgery, leucocyte and platelet activation is described in animal studies only. Therefore, we explored the perioperative time course of platelet and leucocyte activation in cardiac surgery and related these findings to acute lung injury assessed via PaO2/FiO(2) (P/F) ratio measurements. METHODS: A prospective cohort study was performed, including 80 cardiac surgery patients. At five time points, blood samples were directly assessed by flow cytometry. For time course analyses in low (200) P/F ratio groups, repeated measurement techniques with linear mixed models were used. RESULTS: Already before the start of the operation, platelet activatability (P = 0.003 for thrombin receptor-activator peptide and P = 0.017 for adenosine diphosphate) was higher, and the expression of neutrophil activation markers was lower (CD18/CD11; P = 0.001, CD62L; P = 0.013) in the low P/F group. After correction for these baseline differences, the peri- and postoperative thrombin receptor-activator peptide-induced thrombocyte activatability was decreased in the low P/F ratio group (P = 0.008), and a changed pattern of neutrophil activation markers was observed. CONCLUSIONS: Prior to surgery, an upregulated inflammatory state with higher platelet activatability and indications for higher neutrophil turnover were demonstrated in cardiac surgery patients who developed lung injury. It is difficult to distinguish whether these factors are mediators or are also aetiologically related to the development of lung injury after cardiac surgery. Further research is warranted.Thoracic Surger

On the Non-Existence of Optimal Solutions and the Occurrence of “Degeneracy” in the CANDECOMP/PARAFAC Model

The CANDECOMP/PARAFAC (CP) model decomposes a three-way array into a prespecified number of R factors and a residual array by minimizing the sum of squares of the latter. It is well known that an optimal solution for CP need not exist. We show that if an optimal CP solution does not exist, then any sequence of CP factors monotonically decreasing the CP criterion value to its infimum will exhibit the features of a so-called “degeneracy”. That is, the parameter matrices become nearly rank deficient and the Euclidean norm of some factors tends to infinity. We also show that the CP criterion function does attain its infimum if one of the parameter matrices is constrained to be column-wise orthonormal