NT-proBNP by Itself Predicts Death and Cardiovascular Events in High-Risk Patients With Type 2 Diabetes Mellitus

BACKGROUND: NT-proBNP (N-terminal pro-B-type natriuretic peptide) improves the discriminatory ability of risk-prediction models in type 2 diabetes mellitus (T2DM) but is not yet used in clinical practice. We assessed the discriminatory strength of NT-proBNP by itself for death and cardiovascular events in high-risk patients with T2DM. METHODS AND RESULTS: Cox proportional hazards were used to create a base model formed by 20 variables. The discriminatory ability of the base model was compared with that of NT-proBNP alone and with NT-proBNP added, using C-statistics. We studied 5509 patients (with complete data) of 8561 patients with T2DM and cardiovascular and/or chronic kidney disease who were enrolled in the ALTITUDE (Aliskiren in Type 2 Diabetes Using Cardiorenal Endpoints) trial. During a median 2.6-year follow-up period, 469 patients died and 768 had a cardiovascular composite outcome (cardiovascular death, resuscitated cardiac arrest, nonfatal myocardial infarction, stroke, or heart failure hospitalization). NT-proBNP alone was as discriminatory as the base model for predicting death (C-statistic, 0.745 versus 0.744, P=0.95) and the cardiovascular composite outcome (C-statistic, 0.723 versus 0.731, P=0.37). When NT-proBNP was added, it increased the predictive ability of the base model for death (C-statistic, 0.779 versus 0.744, P<0.001) and for cardiovascular composite outcome (C-statistic, 0.763 versus 0.731, P<0.001). CONCLUSIONS: In high-risk patients with T2DM, NT-proBNP by itself demonstrated discriminatory ability similar to a multivariable model in predicting both death and cardiovascular events and should be considered for risk stratification. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00549757

Women, lipids, and atherosclerotic cardiovascular disease:a call to action from the European Atherosclerosis Society

Cardiovascular disease is the leading cause of death in women and men globally, with most due to atherosclerotic cardiovascular disease (ASCVD). Despite progress during the last 30 years, ASCVD mortality is now increasing, with the fastest relative increase in middle-aged women. Missed or delayed diagnosis and undertreatment do not fully explain this burden of disease. Sex-specific factors, such as hypertensive disorders of pregnancy, premature menopause (especially primary ovarian insufficiency), and polycystic ovary syndrome are also relevant, with good evidence that these are associated with greater cardiovascular risk. This position statement from the European Atherosclerosis Society focuses on these factors, as well as sex-specific effects on lipids, including lipoprotein(a), over the life course in women which impact ASCVD risk. Women are also disproportionately impacted (in relative terms) by diabetes, chronic kidney disease, and auto-immune inflammatory disease. All these effects are compounded by sociocultural components related to gender. This panel stresses the need to identify and treat modifiable cardiovascular risk factors earlier in women, especially for those at risk due to sex-specific conditions, to reduce the unacceptably high burden of ASCVD in women

Intrinsic gain modulation and adaptive neural coding

In many cases, the computation of a neural system can be reduced to a receptive field, or a set of linear filters, and a thresholding function, or gain curve, which determines the firing probability; this is known as a linear/nonlinear model. In some forms of sensory adaptation, these linear filters and gain curve adjust very rapidly to changes in the variance of a randomly varying driving input. An apparently similar but previously unrelated issue is the observation of gain control by background noise in cortical neurons: the slope of the firing rate vs current (f-I) curve changes with the variance of background random input. Here, we show a direct correspondence between these two observations by relating variance-dependent changes in the gain of f-I curves to characteristics of the changing empirical linear/nonlinear model obtained by sampling. In the case that the underlying system is fixed, we derive relationships relating the change of the gain with respect to both mean and variance with the receptive fields derived from reverse correlation on a white noise stimulus. Using two conductance-based model neurons that display distinct gain modulation properties through a simple change in parameters, we show that coding properties of both these models quantitatively satisfy the predicted relationships. Our results describe how both variance-dependent gain modulation and adaptive neural computation result from intrinsic nonlinearity.Comment: 24 pages, 4 figures, 1 supporting informatio

The Pathway to Detangle a Scrambled Gene

Programmed DNA elimination and reorganization frequently occur during cellular differentiation. Development of the somatic macronucleus in some ciliates presents an extreme case, involving excision of internal eliminated sequences (IESs) that interrupt coding DNA segments (macronuclear destined sequences, MDSs), as well as removal of transposon-like elements and extensive genome fragmentation, leading to 98% genome reduction in Stylonychia lemnae. Approximately 20-30% of the genes are estimated to be scrambled in the germline micronucleus, with coding segment order permuted and present in either orientation on micronuclear chromosomes. Massive genome rearrangements are therefore critical for development.To understand the process of DNA deletion and reorganization during macronuclear development, we examined the population of DNA molecules during assembly of different scrambled genes in two related organisms in a developmental time-course by PCR. The data suggest that removal of conventional IESs usually occurs first, accompanied by a surprising level of error at this step. The complex events of inversion and translocation seem to occur after repair and excision of all conventional IESs and via multiple pathways.This study reveals a temporal order of DNA rearrangements during the processing of a scrambled gene, with simpler events usually preceding more complex ones. The surprising observation of a hidden layer of errors, absent from the mature macronucleus but present during development, also underscores the need for repair or screening of incorrectly-assembled DNA molecules

‘Maintaining balance and harmony’: Javanese perceptions of health and cardiovascular disease

Community intervention programmes to reduce cardiovascular disease (CVD) risk factors within urban communities in developing countries are rare. One possible explanation is the difficulty of designing an intervention that corresponds to the local context and culture

Comparative indicators for cancer network management in England: Availability, characteristics and presentation

BACKGROUND: In 2000, the national cancer plan for England created 34 cancer networks, new organisational structures to coordinate services across populations varying between a half and three million people. We investigated the availability of data sets reflecting measures of structure, process and outcome that could be used to support network management. METHODS: We investigated the properties of national data sets relating to four common cancers - breast, colorectal, lung and prostate. We reviewed the availability and completeness of these data sets, identified leading items within each set and put them into tables of the 34 cancer networks. We also investigated methods of presentation. RESULTS: The Acute Hospitals Portfolio and the Cancer Standards Peer Review recorded structural characteristics at hospital and cancer service level. Process measures included Hospital Episode Statistics, recording admissions, and Hospital Waiting-List data. Patient outcome measures included the National Survey of Patient Satisfaction for cancer, and cancer survival, drawn from cancer registration. Data were drawn together to provide an exemplar indicator set a single network, and methods of graphical presentation were considered. CONCLUSION: While not as yet used together in practice, comparative indicators are available within the National Health Service in England for use in performance assessment by cancer networks

Shunting Inhibition Controls the Gain Modulation Mediated by Asynchronous Neurotransmitter Release in Early Development

The sensitivity of a neuron to its input can be modulated in several ways. Changes in the slope of the neuronal input-output curve depend on factors such as shunting inhibition, background noise, frequency-dependent synaptic excitation, and balanced excitation and inhibition. However, in early development GABAergic interneurons are excitatory and other mechanisms such as asynchronous transmitter release might contribute to regulating neuronal sensitivity. We modeled both phasic and asynchronous synaptic transmission in early development to study the impact of activity-dependent noise and short-term plasticity on the synaptic gain. Asynchronous release decreased or increased the gain depending on the membrane conductance. In the high shunt regime, excitatory input due to asynchronous release was divisive, whereas in the low shunt regime it had a nearly multiplicative effect on the firing rate. In addition, sensitivity to correlated inputs was influenced by shunting and asynchronous release in opposite ways. Thus, asynchronous release can regulate the information flow at synapses and its impact can be flexibly modulated by the membrane conductance

The response of a classical Hodgkin–Huxley neuron to an inhibitory input pulse

A population of uncoupled neurons can often be brought close to synchrony by a single strong inhibitory input pulse affecting all neurons equally. This mechanism is thought to underlie some brain rhythms, in particular gamma frequency (30–80 Hz) oscillations in the hippocampus and neocortex. Here we show that synchronization by an inhibitory input pulse often fails for populations of classical Hodgkin–Huxley neurons. Our reasoning suggests that in general, synchronization by inhibitory input pulses can fail when the transition of the target neurons from rest to spiking involves a Hopf bifurcation, especially when inhibition is shunting, not hyperpolarizing. Surprisingly, synchronization is more likely to fail when the inhibitory pulse is stronger or longer-lasting. These findings have potential implications for the question which neurons participate in brain rhythms, in particular in gamma oscillations

Galaxy And Mass Assembly (GAMA): galaxy close pairs, mergers and the future fate of stellar mass

We use a highly complete subset of the Galaxy And Mass Assembly II (GAMA-II) redshift sample to fully describe the stellar mass dependence of close pairs and mergers between 10(8) and 10(12)M(circle dot). Using the analytic form of this fit we investigate the total stellar mass accreting on to more massive galaxies across all mass ratios. Depending on how conservatively we select our robust merging systems, the fraction of mass merging on to more massive companions is 2.0-5.6 per cent. Using the GAMA-II data we see no significant evidence for a change in the close pair fraction between redshift z = 0.05 and 0.2. However, we find a systematically higher fraction of galaxies in similar mass close pairs compared to published results over a similar redshift baseline. Using a compendium of data and the function gamma(M) = A(1 + z)(m) to predict the major close pair fraction, we find fitting parameters of A = 0.021 +/- 0.001 and m = 1.53 +/- 0.08, which represents a higher low-redshift normalization and shallower power-law slope than recent literature values. We find that the relative importance of in situ star formation versus galaxy merging is inversely correlated, with star formation dominating the addition of stellar material below M* and merger accretion events dominating beyond M*. We find mergers have a measurable impact on the whole extent of the galaxy stellar mass function (GSMF), manifest as a deepening of the &#39;dip&#39; in the GSMF over the next similar to Gyr and an increase in M* by as much as 0.01-0.05 dex.</p

MIGHTEE: Are giant radio galaxies more common than we thought?

We report the discovery of two new giant radio galaxies (GRGs) using the MeerKAT International GHz Tiered Extragalactic Exploration (MIGHTEE) survey. Both GRGs were found within a ∼1 deg2 region inside the COSMOS field. They have redshifts of z = 0.1656 and z = 0.3363 and physical sizes of 2.4 Mpc and 2.0 Mpc, respectively. Only the cores of these GRGs were clearly visible in previous high resolution VLA observations, since the diffuse emission of the lobes was resolved out. However, the excellent sensitivity and uv coverage of the new MeerKAT telescope allowed this diffuse emission to be detected. The GRGs occupy an unpopulated region of radio power – size parameter space. Based on a recent estimate of the GRG number density, the probability of finding two or more GRGs with such large sizes at z < 0.4 in a ∼1 deg2 field is only 2.7 × 10−6, assuming Poisson statistics. This supports the hypothesis that the prevalence of GRGs has been significantly underestimated in the past due to limited sensitivity to low surface brightness emission. The two GRGs presented here may be the first of a new population to be revealed through surveys like MIGHTEE which provide exquisite sensitivity to diffuse, extended emission