Effect of saxagliptin on renal outcomes in the SAVOR-TIMI 53 trial.

OBJECTIVE: Dipeptidyl peptidase 4 inhibitors may have a protective effect in diabetic nephropathy. RESEARCH DESIGN AND METHODS: We studied renal outcomes of 16,492 patients with type 2 diabetes, randomized to saxagliptin versus placebo and followed for a median of 2.1 years in the Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus Thrombolysis in Myocardial Infarction 53 trial. RESULTS: At baseline: 9,696 (58.8%) subjects had normoalbuminuria (albumin/creatinine ratio [ACR] 300 mg/g). Treatment with saxagliptin was associated with improvement in and/or less deterioration in ACR categories from baseline to end of trial (EOT) (P = 0.021, P 50 mL/min/BSA, -105 mg/g (P = 0.011) for 50 ≥ eGFR ≥ 30 mL/min/BSA, and -245.2 mg/g (P = 0.086) for eGFR 6.0 mg/dL, were similar as well. CONCLUSIONS: Treatment with saxagliptin improved ACR, even in the normoalbuminuric range, without affecting eGFR. The beneficial effect of saxagliptin on albuminuria could not be explained by its effect on glycemic control

Entangled-State Cycles of Atomic Collective-Spin States

We study quantum trajectories of collective atomic spin states of $N$ effective two-level atoms driven with laser and cavity fields. We show that interesting ``entangled-state cycles'' arise probabilistically when the (Raman) transition rates between the two atomic levels are set equal. For odd (even) $N$, there are $(N+1)/2$ ($N/2$) possible cycles. During each cycle the $N$-qubit state switches, with each cavity photon emission, between the states $(|N/2,m>\pm |N/2,-m>)/\sqrt{2}$, where $|N/2,m>$ is a Dicke state in a rotated collective basis. The quantum number $m$ ($>0$), which distinguishes the particular cycle, is determined by the photon counting record and varies randomly from one trajectory to the next. For even $N$ it is also possible, under the same conditions, to prepare probabilistically (but in steady state) the Dicke state $|N/2,0>$, i.e., an $N$-qubit state with $N/2$ excitations, which is of particular interest in the context of multipartite entanglement.Comment: 10 pages, 9 figure

Mitochondrial phylogeography and demographic history of the Vicuña: implications for conservation

The vicuña (Vicugna vicugna; Miller, 1924) is a conservation success story, having recovered from near extinction in the 1960s to current population levels estimated at 275 000. However, lack of information about its demographic history and genetic diversity has limited both our understanding of its recovery and the development of science-based conservation measures. To examine the evolution and recent demographic history of the vicuña across its current range and to assess its genetic variation and population structure, we sequenced mitochondrial DNA from the control region (CR) for 261 individuals from 29 populations across Peru, Chile and Argentina. Our results suggest that populations currently designated as Vicugna vicugna vicugna and Vicugna vicugna mensalis comprise separate mitochondrial lineages. The current population distribution appears to be the result of a recent demographic expansion associated with the last major glacial event of the Pleistocene in the northern (18 to 22°S) dry Andes 14–12 000 years ago and the establishment of an extremely arid belt known as the 'Dry Diagonal' to 29°S. Within the Dry Diagonal, small populations of V. v. vicugna appear to have survived showing the genetic signature of demographic isolation, whereas to the north V. v. mensalis populations underwent a rapid demographic expansion before recent anthropogenic impacts

Wavelet packets based denoising method for measurement domain repeat-time multipath filtering in GPS static high-precision positioning

Repeatable satellite orbits can be used for multipath mitigation in GPS-based deformation monitoring and other high-precision GPS applications that involve continuous observation with static antennas. Multipath signals at a static station repeat when the GPS constellation repeats given the same site environment. Repeat-time multipath filtering techniques need noise reduction methods to remove the white noise in carrier phase measurement residuals in order to retrieve the carrier phase multipath corrections for the next day. We propose a generic and robust three-level wavelet packets based denoising method for repeat-time-based carrier phase multipath filtering in relative positioning; the method does not need tuning to work with different data sets. The proposed denoising method is tested rigorously and compared with two other denoising methods. Three rooftop data sets collected at the University of Nottingham Ningbo China and two data sets collected at three Southern California Integrated GPS Network high-rate stations are used in the performance assessment. Test results of the wavelet packets denoising method are compared with the results of the resistor–capacitor (RC) low-pass filter and the single-level discrete wavelet transform (DWT) denoising method. Multipath mitigation efficiency in carrier phase measurement domain is shown by spectrum analysis of two selected satellites in two data sets. The positioning performance of the repeat-time-based multipath filtering techniques is assessed. The results show that the performance of the three noise reduction techniques is about 1–46 % improvement on positioning accuracy when compared with no multipath filtering. The statistical results show that the wavelet packets based denoising method is always better than the RC filter by 2–4 %, and better than the DWT method by 6–15 %. These results suggest that the proposed wavelet packets based denoising method is better than both the DWT method and the relatively simple RC low-pass filter for noise reduction in multipath filtering. However, the wavelet packets based denoising method is not significantly better than the RC filter

Phenotypic Signatures Arising from Unbalanced Bacterial Growth

Fluctuations in the growth rate of a bacterial culture during unbalanced growth are generally considered undesirable in quantitative studies of bacterial physiology. Under well-controlled experimental conditions, however, these fluctuations are not random but instead reflect the interplay between intra-cellular networks underlying bacterial growth and the growth environment. Therefore, these fluctuations could be considered quantitative phenotypes of the bacteria under a specific growth condition. Here, we present a method to identify “phenotypic signatures” by time-frequency analysis of unbalanced growth curves measured with high temporal resolution. The signatures are then applied to differentiate amongst different bacterial strains or the same strain under different growth conditions, and to identify the essential architecture of the gene network underlying the observed growth dynamics. Our method has implications for both basic understanding of bacterial physiology and for the classification of bacterial strains

Context Matters: The Illusive Simplicity of Macaque V1 Receptive Fields

Even in V1, where neurons have well characterized classical receptive fields (CRFs), it has been difficult to deduce which features of natural scenes stimuli they actually respond to. Forward models based upon CRF stimuli have had limited success in predicting the response of V1 neurons to natural scenes. As natural scenes exhibit complex spatial and temporal correlations, this could be due to surround effects that modulate the sensitivity of the CRF. Here, instead of attempting a forward model, we quantify the importance of the natural scenes surround for awake macaque monkeys by modeling it non-parametrically. We also quantify the influence of two forms of trial to trial variability. The first is related to the neuron’s own spike history. The second is related to ongoing mean field population activity reflected by the local field potential (LFP). We find that the surround produces strong temporal modulations in the firing rate that can be both suppressive and facilitative. Further, the LFP is found to induce a precise timing in spikes, which tend to be temporally localized on sharp LFP transients in the gamma frequency range. Using the pseudo R[superscript 2] as a measure of model fit, we find that during natural scene viewing the CRF dominates, accounting for 60% of the fit, but that taken collectively the surround, spike history and LFP are almost as important, accounting for 40%. However, overall only a small proportion of V1 spiking statistics could be explained (R[superscript 2]~5%), even when the full stimulus, spike history and LFP were taken into account. This suggests that under natural scene conditions, the dominant influence on V1 neurons is not the stimulus, nor the mean field dynamics of the LFP, but the complex, incoherent dynamics of the network in which neurons are embedded.National Institutes of Health (U.S.) (K25 NS052422-02)National Institutes of Health (U.S.) (DP1 ODOO3646

Effect of telehealth on glycaemic control: analysis of patients with type 2 diabetes in the Whole Systems Demonstrator cluster randomised trial

Background: The Whole Systems Demonstrator was a large, pragmatic, cluster randomised trial that compared telehealth with usual care among 3,230 patients with long-term conditions in three areas of England. Telehealth involved the regular transmission of physiological information such as blood glucose to health professionals working remotely. We examined whether telehealth led to changes in glycosylated haemoglobin (HbA1c) among the subset of patients with type 2 diabetes. Methods: The general practice electronic medical record was used as the source of information on HbA1c. Effects on HbA1c were assessed using a repeated measures model that included all HbA1c readings recorded during the 12-month trial period, and adjusted for differences in HbA1c readings recorded before recruitment. Secondary analysis averaged multiple HbA1c readings recorded for each individual during the trial period. Results: 513 of the 3,230 participants were identified as having type 2 diabetes and thus were included in the study. Telehealth was associated with lower HbA1c than usual care during the trial period (difference 0.21% or 2.3 mmol/mol, 95% CI, 0.04% to 0.38%, p = 0.013). Among the 457 patients in the secondary analysis, mean HbA1c showed little change for controls following recruitment, but fell for intervention patients from 8.38% to 8.15% (68 to 66 mmol/mol). A higher proportion of intervention patients than controls had HbA1c below the 7.5% (58 mmol/mol) threshold that was targeted by general practices (30.4% vs. 38.0%). This difference, however, did not quite reach statistical significance (adjusted odds ratio 1.63, 95% CI, 0.99 to 2.68, p = 0.053). Conclusions: Telehealth modestly improved glycaemic control in patients with type 2 diabetes over 12 months. The scale of the improvements is consistent with previous meta-analyses, but was relatively modest and seems unlikely to produce significant patient benefit

Behind the confession: Relating false confession, interrogative compliance, personality traits, and psychopathy

The present study further supports the established notion that personality traits contribute to the phenomenon of false confessions and compliance in an interrogative setting. Furthermore, the study provides an investigation into the more recent interest in the potential effect of psychopathic traits in this context. A sample of university students (N = 607) completed questionnaires measuring psychopathic traits, interrogative compliance, and the big five personality factors. Of these, only 4.9% (n=30) claimed to have falsely confessed to an academic or criminal offense, with no participant taking the blame for both types of offense. Across measures the big five personality traits were the strongest predictors of compliance. The five personality traits accounted for 17.9 % of the total variance in compliance, with neuroticism being the strongest predictor, followed by openness and agreeableness. Psychopathy accounted for 3.3% of variance, with the lifestyle facet being the only significant predictor. After controlling for the big five personality factors, psychopathy only accounted for a small percentage of interrogative compliance, indicating that interrogators should take into account a person’s personality traits during the interrogation.N/

Somatostatin and dopamine receptors as targets for medical treatment of Cushing's Syndrome

Somatostatin (SS) and dopamine (DA) receptors are widely expressed in neuroendocrine tumours that cause Cushing's Syndrome (CS). Increasing knowledge of specific subtype expression within these tumours and the ability to target these receptor subtypes with high-affinity compounds, has driven the search for new SS- or DA-based medical therapies for the various forms of CS. In Cushing's disease, corticotroph adenomas mainly express dopamine receptor subtype 2 (D2) and somatostatin receptor subtype 5 (sst5), whereas sst2is expressed at lower levels. Activation of these receptors can inhibit ACTH-release in primary cultured corticotroph adenomas and compounds that target either sst5(pasireotide, or SOM230) or D2(cabergoline) have shown significant efficacy in subsets of patients in recent clinical studies. Combination therapy, either by administration of both types of compounds separately or by treatment with novel somatostatin-dopamine chimeric molecules (e.g. BIM-23A760), appears to be a promising approach in this respect. In selected cases of Ectopic ACTH-producing Syndrome (EAS), the sst2-preferring compound octreotide is able to reduce cortisol levels effectively. A recent study showed that D2receptors are also significantly expressed in the majority of EAS and that cabergoline may decrease cortisol levels in subsets of these patients. In both normal adrenal tissue as well as in adrenal adenomas and carcinomas that cause CS, sst and DA receptor expression has been demonstrated. Although selected cases of adrenal CS may benefit from sst or DA-targeted treatment, its total contribution to the treatment of these patients is likely to be low as surgery is effective in most cases