Relative contributions of lean and fat mass to bone mineral density: Insight from Prader-Willi syndrome

© 2018 Viardot, Purtell, Nguyen and Campbell. Context: Low bone mineral density (BMD) is the most important risk factor for fragility fracture. Body weight is a simple screening predictor of difference in BMD between individuals. However, it is not clear which component of body weight, lean (LM), or fat mass (FM), is associated with BMD. People with the genetic disorder of Prader-Willi syndrome (PWS) uniquely have a reduced LM despite increased FM. Objective: We sought to define the individual impact of LM and FM on BMD by investigating subjects with and without PWS. Design, Setting and Participants: This cross-sectional study was conducted at the Clinical Research Facility of the Garvan Institute of Medical Research, with PWS and control participants recruited from a specialized PWS clinic and from the general public by advertisement, respectively. The study involved 11 adults with PWS, who were age- and sex-matched with 12 obese individuals (Obese group) and 10 lean individuals (Lean group). Main Outcome Measures: Whole body BMD was measured by dual-energy X-ray absorptiometry. Total body FM and LM were derived from the whole body scan. Differences in BMD between groups were assessed by the analysis of covariance model, taking into account the effects of LM and FM. Results: The PWS group had significantly shorter height than the lean and obese groups. As expected, there was no significant difference in FM between the Obese and PWS group, and no significant difference in LM between the Lean and PWS group. However, obese individuals had greater LM than lean individuals. BMD in lean individuals was significantly lower than in PWS individuals (1.13 g/cm2 vs. 1.21 g/cm2, p < 0.05) and obese individuals (1.13 g/cm2 vs. 1.25 g/cm2, p < 0.05). After adjusting for both LM and FM, there was no significant difference in BMD between groups, and the only significant predictor of BMD was LM. Conclusions: These data from the human genetic model Prader-Willi syndrome suggest that LM is a stronger determinant of BMD than fat mass

Hummingbird: An Energy-Efficient GPS Receiver for Small Satellites

Global positioning system (GPS) is the most widely adopted localization technique for satellites in low earth orbits (LEOs). To enable many state-of-the-art applications on satellites, the exact position of the satellites is necessary. With the increasing demand for small satellites, the need for a low-power GPS for satellites is also increasing. However, building low-power GPS receivers for small satellites poses significant challenges, mainly due to the high speeds (similar to 7.8 km/s) of satellites and low available energy. While duty cycling the receiver is a possible solution, the high relative Doppler shift among the GPS satellites and the small satellite contributes to an increase in Time to First Fix (TTFF), which negatively impacts energy consumption. Further, if the satellite tumbles, the GPS receiver may not be able to receive signals properly from the GPS satellites, thus leading to an even longer TTFF. In the worst case, the situation may result in no GPS fix due to disorientation of the receiver antenna. In this work, we elucidate the design of a low-cost, low-power GPS receiver for small satellites. We also propose an energy optimization algorithm to improve the TTFF. With the extensive evaluation of our GPS receiver on an operational nanosatellite, we show that up to 96.16% of energy savings can be achieved using our algorithm without significantly compromising (similar to 10 m) the positioning accuracy

Serum creatine kinase and lactate dehydrogenase activities in patients with thyroid disorders

Background and Objectives: There is the recognition of a pattern of elevations of serum enzymes in hyperthyroid and hypothyroid patients. The aims of this study were to determine the activities of serum creatine kinase (CK) and lactate deydrogenase (LDH) in thyroid disorders, and to evaluate the relationship between CK, LDH and FT4, and TSH levels.Materials and Methods: In this retrospective study, thyroid function tests, serum CK and LDH activities were obtained from the medical records of newly diagnosed hyperthyroid and hypothyroid patients attending the Endocrinology Clinic at the University Hospital of the West Indies from 2005- 2009.Results: Elevation of CK activity was found in 5 patients (28%, 5/18) with overt hypothyroidism and in 12 patients (24.0%, 12/50) with subclinical hypothyroidism. The mean CK activity in subclinical hypothyroid patients was 179.80 &plusmn; 125.68 U/L compared with 389.901 &plusmn; 381.20 U/L in overt hypothyroid patients. The elevation of LDH activity was found in 6 patients (33.3%, 6/18) with overt hypothyroidism and in 37 patients (74.0%, 37/50) with subclinical hypothyroidism. In the hypothyroid patients, a positive correlation was found between CK activity and TSH (r = 0.292, P = 0.015), and a negative correlation between CK activity and FT4 (r = - 0.325, P = 0.007); and between FT4 and TSH (r = - 0.371, P = 0.002).Conclusion: The significant elevation in serum CK and LDH activities indicates that these can be used as parameters for screening hypothyroid patients but not hyperthyroid patients

Diminished temperature and vegetation seasonality over northern high latitudes

Global temperature is increasing, especially over northern lands (>50° N), owing to positive feedbacks1. As this increase is most pronounced in winter, temperature seasonality (ST)—conventionally defined as the difference between summer and winter temperatures—is diminishing over time2, a phenomenon that is analogous to its equatorward decline at an annual scale. The initiation, termination and performance of vegetation photosynthetic activity are tied to threshold temperatures3. Trends in the timing of these thresholds and cumulative temperatures above them may alter vegetation productivity, or modify vegetation seasonality (SV), over time. The relationship between ST and SV is critically examined here with newly improved ground and satellite data sets. The observed diminishment of ST and SV is equivalent to 4° and 7° (5° and 6°) latitudinal shift equatorward during the past 30 years in the Arctic (boreal) region. Analysis of simulations from 17 state-of-the-art climate models4 indicates an additional STdiminishment equivalent to a 20° equatorward shift could occur this century. How SV will change in response to such large projected ST declines and the impact this will have on ecosystem services5 are not well understood. Hence the need for continued monitoring6 of northern lands as their seasonal temperature profiles evolve to resemble thosefurther south.Lopullinen vertaisarvioitu käsikirjoitu

A western diet increases serotonin availability in rat small intestine

Diet-induced obesity is associated with changes in gastrointestinal function and induction of a mild inflammatory state. Serotonin (5-HT) containing enterochromaffin (EC) cells within the intestine respond to nutrients and are altered by inflammation. Thus, our aim was to characterize the uptake and release of 5-HT from EC cells of the rat ileum in a physiologically relevant model of diet-induced obesity. In chow-fed (CF) and Western diet-fed (WD) rats electrochemical methods were used to measure compression evoked (peak) and steady state (SS) 5-HT levels with fluoxetine used to block the serotonin reuptake transporter (SERT). The levels ofmRNAfor tryptophan hydroxylase 1 (TPH1) and SERT were determined by quantitative PCR, while EC cell numbers were determined immunohistochemically. In WD rats, the levels of 5-HT were significantly increased (SS: 19.2±3.7 ±M; peak: 73.5±14.1 ±M) compared with CF rats (SS: 12.3±1.8 ±M; peak: 32.2±7.2 ±M), while SERTdependent uptake of 5-HT was reduced (peak WD: 108% of control versus peak CF: 212% control). In WD rats, there was a significant increase in TPH1 mRNA, a decrease in SERT mRNA and protein, and an increase in EC cells. In conclusion, our data show that foods typical of a Western diet are associated with an increased 5-HT availability in the rat ileum. Increased 5-HT availability is driven by the up-regulation of 5-HT synthesis genes, decreased re-uptake of 5-HT, and increased numbers and/or 5-HT content of EC cells which are likely to cause altered intestinal motility and sensation in vivo. Copyright © 2010 The Endocrine Society. All rights reserved

Balance and coordination after viewing stereoscopic 3D television.

Manufacturers and the media have raised the possibility that viewing stereoscopic 3D television (S3D TV) may cause temporary disruption to balance and visuomotor coordination. We looked for evidence of such effects in a laboratory-based study. Four hundred and thirty-three people aged 4-82 years old carried out tests of balance and coordination before and after viewing an 80 min movie in either conventional 2D or stereoscopic 3D, while wearing two triaxial accelerometers. Accelerometry produced little evidence of any change in body motion associated with S3D TV. We found no evidence that viewing the movie in S3D causes a detectable impairment in balance or in visuomotor coordination

Incidence of new foci of hepatocellular carcinoma after radiofrequency ablation: role of multidetector CT

Purpose. The authors sought to assess the incidence of new foci of hepatocellular carcinoma (HCC) using multidetector computed tomography (MDCT) in patients treated with radiofrequency ablation (RFA). Materials and methods. Two readers retrospectively reviewed by consensus the follow-up MDCT studies of 125 patients (88 men and 37 women; mean age 68 years) with 141 HCCs (size 1\u20135.2 cm; mean 2.2 cm) treated with RFA. MDCT follow-up was performed at 1 and 3 months and every 6\u201312 months thereafter. Reviewers assessed: (1) the presence of new HCC foci in the same liver segment or in a different segment; (2) complete or incomplete tumor ablation; (3) tumour progression. Results. A total of 113 new HCCs (size 0.7\u20134.8 cm; mean 1.7 cm) were detected in 69/125 (55.2%) patients (mean follow-up 30.38\ub119.14 months). Of these, 86 (76.1%) new HCCs were multiple (p<0.0001), and 92 (81.4%) occurred in a different segment from that of the treated HCC (p<0.0001). New HCCs were observed in the first 12 months, between 12 and 24 months and after 24 months in 31/69 (44.9%), 24/69 (34.8%) and 14/69 (20.3%) patients, respectively (p=0.175). Mean diseasefree interval was 16.1\ub116.31 (range 1\u201352) months. Complete tumour ablation was achieved in 132/141 (93.6%) treated HCCs, and tumour progression occurred in 29/141 (20.6%) cases. Conclusions. In patients with RFA-treated HCCs, MDCT follow-up revealed a high incidence of new HCCs, even after 1 year of follow-up. The new foci tended to be multiple and located in a liver segment different from that of the previously treated nodules

Robustness Analysis of DCE-MRI-Derived Radiomic Features in Breast Masses: Assessing Quantization Levels and Segmentation Agreement

Featured Application The use of highly robust radiomic features is fundamental to reduce intrinsic dependencies and to provide reliable predictive models. This work presents a study on breast tumor DCE-MRI considering the radiomic feature robustness against the quantization settings and segmentation methods. Machine learning models based on radiomic features allow us to obtain biomarkers that are capable of modeling the disease and that are able to support the clinical routine. Recent studies have shown that it is fundamental that the computed features are robust and reproducible. Although several initiatives to standardize the definition and extraction process of biomarkers are ongoing, there is a lack of comprehensive guidelines. Therefore, no standardized procedures are available for ROI selection, feature extraction, and processing, with the risk of undermining the effective use of radiomic models in clinical routine. In this study, we aim to assess the impact that the different segmentation methods and the quantization level (defined by means of the number of bins used in the feature-extraction phase) may have on the robustness of the radiomic features. In particular, the robustness of texture features extracted by PyRadiomics, and belonging to five categories-GLCM, GLRLM, GLSZM, GLDM, and NGTDM-was evaluated using the intra-class correlation coefficient (ICC) and mean differences between segmentation raters. In addition to the robustness of each single feature, an overall index for each feature category was quantified. The analysis showed that the level of quantization (i.e., the 'bincount' parameter) plays a key role in defining robust features: in fact, in our study focused on a dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) dataset of 111 breast masses, sets with cardinality varying between 34 and 43 robust features were obtained with 'binCount' values equal to 256 and 32, respectively. Moreover, both manual segmentation methods demonstrated good reliability and agreement, while automated segmentation achieved lower ICC values. Considering the dependence on the quantization level, taking into account only the intersection subset among all the values of 'binCount' could be the best selection strategy. Among radiomic feature categories, GLCM, GLRLM, and GLDM showed the best overall robustness with varying segmentation methods

Asymptomatic Clostridium difficile colonization in two Australian tertiary hospitals, 2012-2014: prospective, repeated cross-sectional study.

OBJECTIVES: To investigate the prevalence and risk factors for asymptomatic toxigenic (TCD) and nontoxigenic Clostridium difficile (NTCD) colonization in a broad cross section of the general hospital population over a 3-year period. METHODS: Patients without diarrhoea admitted to two Australian tertiary hospitals were randomly selected through six repeated cross-sectional surveys conducted between 2012 and 2014. Stool specimens were cultured under anaerobic conditions, and C. difficile isolates were tested for the presence of toxin genes and ribotyped. Patients were then grouped into noncolonized, TCD colonized or NTCD colonized for identifying risk factors using multinomial logistic regression models. RESULTS: A total of 1380 asymptomatic patients were enrolled; 76 patients (5.5%) were TCD colonized and 28 (2.0%) were NTCD colonized. There was a decreasing annual trend in TCD colonization, and asymptomatic colonization was more prevalent during the summer than winter months. TCD colonization was associated with gastro-oesophageal reflux disease (relative risk ratio (RRR) = 2.20; 95% confidence interval (CI) 1.17-4.14), higher number of admissions in the previous year (RRR = 1.24; 95% CI 1.10-1.39) and antimicrobial exposure during the current admission (RRR = 2.78; 95% CI 1.23-6.28). NTCD colonization was associated with chronic obstructive pulmonary disease (RRR = 3.88; 95% CI 1.66-9.07) and chronic kidney failure (RRR = 5.78; 95% CI 2.29-14.59). Forty-eight different ribotypes were identified, with 014/020 (n = 23), 018 (n = 10) and 056 (n = 6) being the most commonly isolated. CONCLUSIONS: Risk factors differ between patients with asymptomatic colonization by toxigenic and nontoxigenic strains. Given that morbidity is largely driven by toxigenic strains, this novel finding has important implications for disease control and prevention

MRAP deficiency impairs adrenal progenitor cell differentiation and gland zonation.

Melanocortin 2 receptor accessory protein (MRAP) is a single transmembrane domain accessory protein and a critical component of the hypothamo-pituitary-adrenal axis. MRAP is highly expressed in the adrenal gland and is essential for adrenocorticotropin hormone (ACTH) receptor expression and function. Human loss-of-function mutations in MRAP cause familial glucocorticoid (GC) deficiency (FGD) type 2 (FGD2), whereby the adrenal gland fails to respond to ACTH and to produce cortisol. In this study, we generated Mrap-null mice to study the function of MRAP in vivo. We found that the vast majority of Mrap-/- mice died at birth but could be rescued by administration of corticosterone to pregnant dams. Surviving Mrap-/- mice developed isolated GC deficiency with normal mineralocorticoid and catecholamine production, recapitulating FGD2. The adrenal glands of adult Mrap-/- mice were small, with grossly impaired adrenal capsular morphology and cortex zonation. Progenitor cell differentiation was significantly impaired, with dysregulation of WNT4/β-catenin and sonic hedgehog pathways. These data demonstrate the roles of MRAP in both steroidogenesis and the regulation of adrenal cortex zonation. This is the first mouse model of isolated GC deficiency and reveals the role of MRAP in adrenal progenitor cell regulation and cortex zonation.-Novoselova, T. V., Hussain, M., King, P. J., Guasti, L., Metherell, L. A., Charalambous, M., Clark, A. J. L., Chan, L. F. MRAP deficiency impairs adrenal progenitor cell differentiation and gland zonation