Association between diabetes, diabetes treatment and risk of developing endometrial cancer.

BackgroundA growing body of evidence suggests that diabetes is a risk factor for endometrial cancer incidence. However, most of these studies used case-control study designs and did not adjust for obesity, an established risk factor for endometrial cancer. In addition, few epidemiological studies have examined the association between diabetes treatment and endometrial cancer risk. The objective of this study was to assess the relationships among diabetes, diabetes treatment and endometrial cancer risk in postmenopausal women participating in the Women's Health Initiative (WHI).MethodsA total of 88 107 postmenopausal women aged 50-79 years who were free of cancer and had no hysterectomy at baseline were followed until date of endometrial cancer diagnosis, death, hysterectomy or loss to follow-up, whichever came first. Endometrial cancers were confirmed by central medical record and pathology report review. Multivariate Cox proportional hazards regression models were used to estimate hazard ratios (HRs) (95% confidence interval (CI)) for diagnosis of diabetes and metformin treatment as risk factors for endometrial cancer.ResultsOver a mean of 11 years of follow-up, 1241 endometrial cancers developed. In the primary analysis that focused on prevalent diabetes at enrolment, compared with women without diabetes, women with self-reported diabetes, and the subset of women with treated diabetes, had significantly higher risk of endometrial cancer without adjusting for BMI (HR=1.44, 95% CI: 1.13-1.85 for diabetes, HR=1.57, 95% CI: 1.19-2.07 for treated diabetes). However after adjusting for BMI, the associations between diabetes, diabetes treatment, diabetes duration and the risk of endometrial cancer became non-significant. Elevated risk was noted when considering combining diabetes diagnosed at baseline and during follow-up as time-dependent exposure (HR=1.31, 95% CI: 1.08-1.59) even after adjusting for BMI. No significant association was observed between metformin use and endometrial cancer risk.ConclusionsOur results suggest that the relationship observed in previous research between diabetes and endometrial cancer incidence may be largely confounded by body weight, although some modest independent elevated risk remains

Reliability in the Identification of Midbrain Dopamine Neurons

Brain regions typically contain intermixed subpopulations of neurons with different connectivity and neurotransmitters. This complicates identification of neuronal phenotypes in electrophysiological experiments without using direct detection of unique molecular markers. A prime example of this difficulty is the identification of dopamine (DA) neurons in the midbrain ventral tegmental area (VTA). Although immunocytochemistry (ICC) against tyrosine hydroxylase (TH) is widely used to identify DA neurons, a high false negative rate for TH ICC following ex vivo electrophysiology experiments was recently reported, calling into question the validity of comparing DA and non-DA VTA neurons based on post-hoc ICC. However, in whole cell recordings from randomly selected rat VTA neurons we have found that TH labeling is consistently detected in ∼55% of neurons even after long recording durations (range: 2.5–150 min). This is consistent with our prior anatomical finding that 55% of VTA neurons are TH(+). To directly estimate a false negative rate for our ICC method we recorded VTA neurons from mice in which EGFP production is driven by the TH promoter. All 12 EGFP(+) neurons recorded with a K-gluconate internal solution (as used in our rat recordings) were strongly labeled by TH ICC (recording duration 16.6±1.8 min). However, using recording electrodes with an internal solution with high Cl− concentration reduced the intensity of TH co-labeling, in some cases to background (recording duration 16.7±0.9 min; n = 10). Thus TH is a highly reliable molecular marker for DA neurons in VTA patch clamp recordings provided compatible microelectrode solutions are used

A facility for high resolution spectroscopy: Laboratory and ground based observations in support of upper atmospheric research

This research task consists of operating a facility for making spectroscopic observations in support of upper atmospheric research. The facility responds to the needs and interests of the visiting investigators. Therefore, the research objectives are not predetermined except in broad outline. The emphasis is on studies that take advantage of the particular strengths of the Fourier Transform Spectrometer on Kitt Peak: high spectral resolution combined with wide spectral range and low noise

Estimating Rooftop Suitability for PV: A Review of Methods, Patents, and Validation Techniques

A number of methods have been developed using remote sensing data to estimate rooftop area suitable for the installation of photovoltaics (PV) at various geospatial resolutions. This report reviews the literature and patents on methods for estimating rooftop-area appropriate for PV, including constant-value methods, manual selection methods, and GIS-based methods. This report also presents NREL's proposed method for estimating suitable rooftop area for PV using Light Detection and Ranging (LiDAR) data in conjunction with a GIS model to predict areas with appropriate slope, orientation, and sunlight. NREL's method is validated against solar installation data from New Jersey, Colorado, and California to compare modeled results to actual on-the-ground measurements

Quantitative Phosphoproteomic Analysis Reveals Unique cAMP signaling Pools Emanating from AC2 and AC6 in Human Airway Smooth Muscle Cells

Human airway smooth muscle (HASM) is the primary target of ßAR agonists used to control airway hypercontractility in asthma and chronic obstructive pulmonary disease (COPD). ßAR agonists induce the production of cAMP by adenylyl cyclases (ACs), activate PKA and cause bronchodilation. Several other G-protein coupled receptors (GPCR) expressed in human airway smooth muscle cells transduce extracellular signals through cAMP but these receptors elicit different cellular responses. Some G-protein coupled receptors couple to distinct adenylyl cyclases isoforms with different localization, partly explaining this compartmentation, but little is known about the downstream networks that result. We used quantitative phosphoproteomics to define the downstream signaling networks emanating from cAMP produced by two adenylyl cyclases isoforms with contrasting localization in uman airway smooth muscle. After a short stimulus of adenylyl cyclases activity using forskolin, phosphopeptides were analyzed by LC-MS/MS and differences between cells overexpressing AC2 (localized in non-raft membranes) or AC6 (localized in lipid raft membranes) were compared to control human airway smooth muscle. The degree of AC2 and AC6 overexpression was titrated to generate roughly equal forskolin-stimulated cAMP production. 14 Differentially phosphorylated proteins (DPPs) resulted from AC2 activity and 34 differentially phosphorylated proteins resulted from AC6 activity. Analysis of these hits with the STRING protein interaction tool showed that AC2 signaling is more associated with modifications in RNA/DNA binding proteins and microtubule/spindle body proteins while AC6 signaling is associated with proteins regulating autophagy, calcium-calmodulin (Ca2+/CaM) signaling, Rho GTPases and cytoskeletal regulation. One protein, OFD1, was regulated in opposite directions, with serine 899 phosphorylation increased in the AC6 condition 1.5-fold but decreased to 0.46-fold by AC2. In conclusion, quantitative phosphoproteomics is a powerful tool for deciphering the complex signaling networks resulting from discreet signaling events that occur in cAMP compartments. Our data show key differences in the cAMP pools generated from AC2 and AC6 activity and imply that distinct cellular responses are regulated by these two compartments

Photoionization Broadening of the 1S-2S Transition in a Beam of Atomic Hydrogen

We consider the excitation dynamics of the two-photon \sts transition in a beam of atomic hydrogen by 243 nm laser radiation. Specifically, we study the impact of ionization damping on the transition line shape, caused by the possibility of ionization of the 2S level by the same laser field. Using a Monte-Carlo simulation, we calculate the line shape of the \sts transition for the experimental geometry used in the two latest absolute frequency measurements (M. Niering {\it et al.}, PRL 84, 5496 (2000) and M. Fischer {\it et al.}, PRL 92, 230802 (2004)). The calculated line shift and line width are in excellent agreement with the experimentally observed values. From this comparison we can verify the values of the dynamic Stark shift coefficient for the \sts transition for the first time on a level of 15%. We show that the ionization modifies the velocity distribution of the metastable atoms, the line shape of the \sts transition, and has an influence on the derivation of its absolute frequency.Comment: 10 pages, 5 figure

'Sly grog' and 'homebrew': a qualitative examination of illicit alcohol and some of its impacts on Indigenous communities with alcohol restrictions in regional and remote Queensland (Australia)

Background: Indigenous communities in Queensland (Australia) have been subject to Alcohol Management Plans since 2002/03, with significant penalties for breaching restrictions. 'Sly grog' and 'homebrew' provide access to alcohol despite restrictions. This paper describes how this alcohol is made available and the risks and impacts involved. In affected towns and communities across a large area of rural and remote Queensland, interviews and focus groups documented experiences and views of 255 long-standing community members and service providers. Using an inductive framework, transcribed interviews were analysed to identify supply mechanisms, community and service provider responses and impacts experienced. Results: 'Homebrew' was reportedly manufactured in just a few localities, in locally-specific forms bringing locally-specific harms. However, 'sly grog' sourced from licensed premises located long distances from communities, is a widespread concern across the region. 'Sly grog' sellers circumvent retailers' takeaway liquor license conditions, stockpile alcohol outside restricted areas, send hoax messages to divert enforcement and take extraordinary risks to avoid apprehension. Police face significant challenges to enforce restrictions. On-selling of 'sly grog' appears more common in remote communities with total prohibition. Despite different motives for involvement in an illicit trade 'sly grog' consumers and sellers receive similar penalties. Conclusions: There is a need for: (a) a more sophisticated regional approach to managing takeaway alcohol sales from licensed suppliers, (b) targeted penalties for 'sly grog' sellers that reflect its significant community impact, (c) strategies to reduce the demand for alcohol and (d) research to assess the effects of these strategies in reducing harms.Michelle S. Fitts, Jan Robertson, Simon Towle, Chris M. Doran, Robyn McDermott, Adrian Miller, Stephen Margolis, Valmae Ypinazar and Alan R. Cloug