Liraglutide and renal outcomes in type 2 diabetes

In a randomized, controlled trial that compared liraglutide, a glucagon-like peptide 1 analogue, with placebo in patients with type 2 diabetes and high cardiovascular risk who were receiving usual care, we found that liraglutide resulted in lower risks of the primary end point (nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes) and death. However, the long-term effects of liraglutide on renal outcomes in patients with type 2 diabetes are unknown

Mental Illness Sexual Stigma: Implications for Health and Recovery

The majority of people in psychiatric care worldwide are sexually active, and studies have revealed sharply elevated rates of HIV infection in that group compared with the general population. Recovery-oriented treatment does not routinely address sexuality. We examined the relationship between gender, severe mental illness diagnosis, and stigma experiences related to sexuality among people in psychiatric outpatient care. Method: Sexually active adults attending 8 public outpatient psychiatric clinics in Rio de Janeiro (N = 641) were interviewed for psychiatric diagnosis and stigma experiences. Stigma mechanisms well-established in the literature but not previously examined in relation to sexuality were measured with the Mental Illness Sex Stigma Questionnaire, a 27-item interview about stigma in sexual situations and activities. Results: Experiences of stigma were reported by a majority of participants for 48% of questionnaire items. Most people reported supportive attitudes toward their sexuality from providers and family members. Those with severe mental illness diagnoses showed greater stigma on individual discrimination and structural stigma mechanisms than did those with nonsevere mental illness diagnoses, whereas there was no difference on the social psychological processes (internalized stigma) mechanism. Regardless of diagnosis or gender, a majority of participants devalued themselves as sexual partners. Conclusions and Implications for Practice: Adults in psychiatric outpatient care frequently reported stigma experiences related to aspects of their sexual lives. From the perspectives of both HIV prevention and recovery from mental illness, examinations of the consequences of stigma in the sexual lives of people in psychiatric care and improving their measurement would have wide applicability

Summer CO2 evasion from streams and rivers in the Kolyma River basin, north-east Siberia

Inland water systems are generally supersaturated in carbon dioxide (CO2) and are increasingly recognized as playing an important role in the global carbon cycle. The Arctic may be particularly important in this respect, given the abundance of inland waters and carbon contained in Arctic soils; however, a lack of trace gas measurements from small streams in the Arctic currently limits this understanding.We investigated the spatial variability of CO2 evasion during the summer low-flow period from streams and rivers in the northern portion of the Kolyma River basin in north-eastern Siberia. To this end, partial pressure of carbon dioxide (pCO2) and gas exchange velocities (k) were measured at a diverse set of streams and rivers to calculate CO2 evasion fluxes. We combined these CO2 evasion estimates with satellite remote sensing and geographic information system techniques to calculate total areal CO2 emissions. Our results show that small streams are substantial sources of atmospheric CO2 owing to high pCO2 and k, despite being a small portion of total inland water surface area. In contrast, large rivers were generally near equilibrium with atmospheric CO2. Extrapolating our findings across the Panteleikha-Ambolikha sub-watersheds demonstrated that small streams play a major role in CO2 evasion, accounting for 86% of the total summer CO2 emissions from inland waters within these two sub-watersheds. Further expansion of these regional CO2 emission estimates across time and space will be critical to accurately quantify and understand the role of Arctic streams and rivers in the global carbon budget

A novel method of using accelerometry for upper limb FES control.

This paper reports on a novel approach to using a 3-axis accelerometer to capture body segment angle for upper limb functional electrical stimulation (FES) control. The approach calculates the angle between the accelerometer x -axis and the gravity vector, while avoiding poor sensitivity at certain angles and minimizing errors when true acceleration is relatively large in comparison to gravity. This approach was incorporated into a state-machine controller which is used for the real-time control of FES during up- per limb functional task performance. An experimental approach was used to validate the new method. Two participants with different upper limb impairments resulting from a stroke carried out four different FES-assisted tasks. Comparisons were made between angle calculated from arm-mounted accelerometer data using our algorithm and angle calculated from limb-mounted reflective marker data. After removal of coordinate misalignment error, mean error across tasks and subjects ranged between 1.4 and 2.9 °. The approach shows promise for use in the control of upper limb FES and other human movement applications where true acceleration is relatively small in comparison with gravity

Association between exercise frequency with renal and cardiovascular outcomes in diabetic and non-diabetic individuals at high cardiovascular risk

Background: Guidelines recommend physical activity to reduce cardiovascular (CV) events. The association between physical activity and progression of chronic kidney disease (CKD) with and without diabetes is unknown. We assessed the association of self-reported physical activity with renal and CV outcomes in high-risk patients aged≥55 years over a median follow-up of 56 months in post-hoc analysis of a previously randomized trial program. Methods: Analyses were done with Cox regression analysis, mixed models for repeated measures, ANOVA and χ2 - test. 31,312 patients, among them 19,664 with and 11,648 without diabetes were analyzed. Results: Physical activity was inversely associated with renal outcomes (doubling of creatinine, end-stage kidney disease (ESRD)) and CV outcomes (CV death, myocardial infarction, stroke, heart failure hospitalization). Moderate activity (at least 2 times/week to every day) was associated with lower risk of renal outcomes and lower incidence of new albuminuria (p<0.0001 for both) compared to lower exercise levels. Similar results were observed for those with and without diabetes without interaction for renal outcomes (p=0.097–0.27). Physical activity was associated with reduced eGFR decline with a moderate association between activity and diabetes status (p=0.05). Conclusions: Moderate physical activity was associated with improved kidney outcomes with a threshold at two sessions per week. The association of physical activity with renal outcomes did not meaningfully difer with or without diabetes but absolute beneft of activity was even greater in people with diabetes. Thus, risks were similar between those with diabetes undertaking high physical activity and those without diabetes but low physical activity. Clinical trial registration: http://clinicaltrials.gov.uniqueidentifer:NCT00153101

Validation of TOI-1221 b: A warm sub-Neptune exhibiting TTVs around a Sun-like star

We present a validation of the long-period ($91.68278^{+0.00032}_{-0.00041}$ days) transiting sub-Neptune planet TOI-1221 b (TIC 349095149.01) around a Sun-like (m$_{\rm V}$=10.5) star. This is one of the few known exoplanets with period >50 days, and belongs to the even smaller subset of which have bright enough hosts for detailed spectroscopic follow-up. We combine TESS light curves and ground-based time-series photometry from PEST (0.3~m) and LCOGT (1.0~m) to analyze the transit signals and rule out nearby stars as potential false positive sources. High-contrast imaging from SOAR and Gemini/Zorro rule out nearby stellar contaminants. Reconnaissance spectroscopy from CHIRON sets a planetary scale upper mass limit on the transiting object (1.1 and 3.5 M$_{\rm Jup}$ at 1$\sigma$ and 3$\sigma$, respectively) and shows no sign of a spectroscopic binary companion. We determine a planetary radius of $R_{\rm p} = 2.91^{+0.13}_{-0.12} R_{\oplus}$, placing it in the sub-Neptune regime. With a stellar insolation of $S = 6.06^{+0.85}_{-0.77}\ S_{\oplus}$, we calculate a moderate equilibrium temperature of $T_{\rm eq} =$ 440 K, assuming no albedo and perfect heat redistribution. We find a false positive probability from TRICERATOPS of FPP $= 0.0014 \pm 0.0003$ as well as other qualitative and quantitative evidence to support the statistical validation of TOI-1221 b. We find significant evidence (>$5\sigma$) of oscillatory transit timing variations, likely indicative of an additional non-transiting planet.Comment: 17 pages, 9 figures, 4 table

Telomere disruption results in non-random formation of de novo dicentric chromosomes involving acrocentric human chromosomes

Copyright: © 2010 Stimpson et al.Genome rearrangement often produces chromosomes with two centromeres (dicentrics) that are inherently unstable because of bridge formation and breakage during cell division. However, mammalian dicentrics, and particularly those in humans, can be quite stable, usually because one centromere is functionally silenced. Molecular mechanisms of centromere inactivation are poorly understood since there are few systems to experimentally create dicentric human chromosomes. Here, we describe a human cell culture model that enriches for de novo dicentrics. We demonstrate that transient disruption of human telomere structure non-randomly produces dicentric fusions involving acrocentric chromosomes. The induced dicentrics vary in structure near fusion breakpoints and like naturally-occurring dicentrics, exhibit various inter-centromeric distances. Many functional dicentrics persist for months after formation. Even those with distantly spaced centromeres remain functionally dicentric for 20 cell generations. Other dicentrics within the population reflect centromere inactivation. In some cases, centromere inactivation occurs by an apparently epigenetic mechanism. In other dicentrics, the size of the alpha-satellite DNA array associated with CENP-A is reduced compared to the same array before dicentric formation. Extrachromosomal fragments that contained CENP-A often appear in the same cells as dicentrics. Some of these fragments are derived from the same alpha-satellite DNA array as inactivated centromeres. Our results indicate that dicentric human chromosomes undergo alternative fates after formation. Many retain two active centromeres and are stable through multiple cell divisions. Others undergo centromere inactivation. This event occurs within a broad temporal window and can involve deletion of chromatin that marks the locus as a site for CENP-A maintenance/replenishment.This work was supported by the Tumorzentrum Heidelberg/Mannheim grant (D.10026941)and by March of Dimes Research Foundation grant #1-FY06-377 and NIH R01 GM069514

Planetary Candidates Observed by Kepler, III: Analysis of the First 16 Months of Data

New transiting planet candidates are identified in sixteen months (May 2009 - September 2010) of data from the Kepler spacecraft. Nearly five thousand periodic transit-like signals are vetted against astrophysical and instrumental false positives yielding 1,091 viable new planet candidates, bringing the total count up to over 2,300. Improved vetting metrics are employed, contributing to higher catalog reliability. Most notable is the noise-weighted robust averaging of multi-quarter photo-center offsets derived from difference image analysis which identifies likely background eclipsing binaries. Twenty-two months of photometry are used for the purpose of characterizing each of the new candidates. Ephemerides (transit epoch, T_0, and orbital period, P) are tabulated as well as the products of light curve modeling: reduced radius (Rp/R*), reduced semi-major axis (d/R*), and impact parameter (b). The largest fractional increases are seen for the smallest planet candidates (197% for candidates smaller than 2Re compared to 52% for candidates larger than 2Re) and those at longer orbital periods (123% for candidates outside of 50-day orbits versus 85% for candidates inside of 50-day orbits). The gains are larger than expected from increasing the observing window from thirteen months (Quarter 1-- Quarter 5) to sixteen months (Quarter 1 -- Quarter 6). This demonstrates the benefit of continued development of pipeline analysis software. The fraction of all host stars with multiple candidates has grown from 17% to 20%, and the paucity of short-period giant planets in multiple systems is still evident. The progression toward smaller planets at longer orbital periods with each new catalog release suggests that Earth-size planets in the Habitable Zone are forthcoming if, indeed, such planets are abundant.Comment: Submitted to ApJS. Machine-readable tables are available at http://kepler.nasa.gov, http://archive.stsci.edu/kepler/results.html, and the NASA Exoplanet Archiv

Breast ultrasound: recommendations for information to women and referring physicians by the European Society of Breast Imaging

Abstract This article summarises the information that should be provided to women and referring physicians about breast ultrasound (US). After explaining the physical principles, technical procedure and safety of US, information is given about its ability to make a correct diagnosis, depending on the setting in which it is applied. The following definite indications for breast US in female subjects are proposed: palpable lump; axillary adenopathy; first diagnostic approach for clinical abnormalities under 40 and in pregnant or lactating women; suspicious abnormalities at mammography or magnetic resonance imaging (MRI); suspicious nipple discharge; recent nipple inversion; skin retraction; breast inflammation; abnormalities in the area of the surgical scar after breast conserving surgery or mastectomy; abnormalities in the presence of breast implants; screening high-risk women, especially when MRI is not performed; loco-regional staging of a known breast cancer, when MRI is not performed; guidance for percutaneous interventions (needle biopsy, pre-surgical localisation, fluid collection drainage); monitoring patients with breast cancer receiving neo-adjuvant therapy, when MRI is not performed. Possible indications such as supplemental screening after mammography for women aged 40–74 with dense breasts are also listed. Moreover, inappropriate indications include screening for breast cancer as a stand-alone alternative to mammography. The structure and organisation of the breast US report and of classification systems such as the BI-RADS and consequent management recommendations are illustrated. Information about additional or new US technologies (colour-Doppler, elastography, and automated whole breast US) is also provided. Finally, five frequently asked questions are answered. Teaching Points • US is an established tool for suspected cancers at all ages and also the method of choice under 40. • For US-visible suspicious lesions, US-guided biopsy is preferred, even for palpable findings. • High-risk women can be screened with US, especially when MRI cannot be performed. • Supplemental US increases cancer detection but also false positives, biopsy rate and follow-up exams. • Breast US is inappropriate as a stand-alone screening method