Underuse of coronary revascularization procedures in patients considered appropriate candidates for revascularization.

Background: Ratings by an expert panel of the appropriateness of treatments may offer better guidance for clinical practice than the variable decisions of individual clinicians, yet there have been no prospective studies of clinical outcomes. We compared the clinical outcomes of patients treated medically after angiography with those of patients who underwent revascularization, within groups defined by ratings of the degree of appropriateness of revascularization in varying clinical circumstances.Methods: This was a prospective study of consecutive patients undergoing coronary angiography at three London hospitals. Before patients were recruited, a nine-member expert panel rated the appropriateness of percutaneous transluminal coronary angioplasty (PTCA) and coronary-artery bypass grafting (CABG) on a nine-point scale (with 1 denoting highly inappropriate and 9 denoting highly appropriate) for specific clinical indications. These ratings were then applied to a population of patients with coronary artery disease. However, the patients were treated without regard to the ratings. A total of 2552 patients were followed for a median of 30 months after angiography.Results: Of 908 patients with indications for which PTCA was rated appropriate (score, 7 to 9), 34 percent were treated medically; these patients were more likely to have angina at follow-up than those who underwent PTCA (odds ratio, 1.97; 95 percent confidence interval, 1.29 to 3.00). Of 1353 patients with indications for which CABG was considered appropriate, 26 percent were treated medically; they were more likely than those who underwent CABG to die or have a nonfatal myocardial infarction - the composite primary outcome (hazard ratio, 4.08; 95 percent confidence interval, 2.82 to 5.93) - and to have angina (odds ratio, 3.03; 95 percent confidence interval, 2.08 to 4.42). Furthermore, there was a graded relation between rating and outcome over the entire scale of appropriateness (P for linear trend = 0.002).Conclusions: On the basis of the ratings of the expert panel, we identified substantial underuse of coronary revascularization among patients who were considered appropriate candidates for these procedures. Underuse was associated with adverse clinical outcomes. (N Engl J Med 2001;344:645-54.) Copyright (C) 2001 Massachusetts Medical Society

Dynamically-Coupled Oscillators -- Cooperative Behavior via Dynamical Interaction --

We propose a theoretical framework to study the cooperative behavior of dynamically coupled oscillators (DCOs) that possess dynamical interactions. Then, to understand synchronization phenomena in networks of interneurons which possess inhibitory interactions, we propose a DCO model with dynamics of interactions that tend to cause 180-degree phase lags. Employing an approach developed here, we demonstrate that although our model displays synchronization at high frequencies, it does not exhibit synchronization at low frequencies because this dynamical interaction does not cause a phase lag sufficiently large to cancel the effect of the inhibition. We interpret the disappearance of synchronization in our model with decreasing frequency as describing the breakdown of synchronization in the interneuron network of the CA1 area below the critical frequency of 20 Hz.Comment: 10 pages, 3 figure

Can explicit convection improve modelled dust in summertime West Africa?

Global and regional models have large systematic errors in their modelled dust fields over West Africa. It is well established that cold-pool outflows from moist convection (haboobs) can raise over 50% of the dust over parts of the Sahara and Sahel in summer, but parameterised moist convection tends to give a very poor representation of this in models. Here, we test the hypothesis that an explicit representation of convection in the Met Office Unified Model (UM) improves haboob winds and so may reduce errors in modelled dust fields. The results show that despite varying both grid spacing and the representation of convection there are only minor changes in dust aerosol optical depth (AOD) and dust mass loading fields between simulations. In all simulations there is an AOD deficit over the observed central Saharan dust maximum and a high bias in AOD along the west coast: both features are consistent with many climate (CMIP5) models. Cold-pool outflows are present in the explicit simulations and do raise dust. Consistent with this, there is an improved diurnal cycle in dust-generating winds with a seasonal peak in evening winds at locations with moist convection that is absent in simulations with parameterised convection. However, the explicit convection does not change the AOD field in the UM significantly for several reasons. Firstly, the increased windiness in the evening from haboobs is approximately balanced by a reduction in morning winds associated with the breakdown of the nocturnal low-level jet (LLJ). Secondly, although explicit convection increases the frequency of the strongest winds, they are still weaker than observed, especially close to the observed summertime Saharan dust maximum: this results from the fact that, although large mesoscale convective systems (and resultant cold pools) are generated, they have a lower frequency than observed and haboob winds are too weak. Finally, major impacts of the haboobs on winds occur over the Sahel, where, although dust uplift is known to occur in reality, uplift in the simulations is limited by a seasonally constant bare-soil fraction in the model, together with soil moisture and clay fractions which are too restrictive of dust emission in seasonally varying vegetated regions. For future studies, the results demonstrate (1) the improvements in behaviour produced by the explicit representation of convection, (2) the value of simultaneously evaluating both dust and winds and (3) the need to develop parameterisations of the land surface alongside those of dust-generating winds

Spatial Current Patterns, Dephasing and Current Imaging in Graphene Nanoribbons

Using the non-equilibrium Keldysh Green's function formalism, we investigate the local, non-equilibrium charge transport in graphene nanoribbons (GNRs). In particular, we demonstrate that the spatial current patterns associated with discrete transmission resonances sensitively depend on the GNRs' geometry, size, and aspect ratio, the location and number of leads, and the presence of dephasing. We identify a relation between the spatial form of the current patterns, and the number of degenerate energy states participating in the charge transport. Furthermore, we demonstrate a principle of superposition for the conductance and spatial current patterns in multiple-lead configurations. We demonstrate that scanning tunneling microscopy (STM) can be employed to image spatial current paths in GNR with atomic resolution, providing important insight into the form of local charge transport. Finally, we investigate the effects of dephasing on the spatial current patterns, and show that with decreasing dephasing time, the current patterns evolve smoothly from those of a ballistic quantum network to those of classical resistor network.Comment: 25 pages, 12 figure

Imaging and controlling electron transport inside a quantum ring

Traditionally, the understanding of quantum transport, coherent and ballistic1, relies on the measurement of macroscopic properties such as the conductance. While powerful when coupled to statistical theories, this approach cannot provide a detailed image of "how electrons behave down there". Ideally, understanding transport at the nanoscale would require tracking each electron inside the nano-device. Significant progress towards this goal was obtained by combining Scanning Probe Microscopy (SPM) with transport measurements2-7. Some studies even showed signatures of quantum transport in the surrounding of nanostructures4-6. Here, SPM is used to probe electron propagation inside an open quantum ring exhibiting the archetype of electron wave interference phenomena: the Aharonov-Bohm effect8. Conductance maps recorded while scanning the biased tip of a cryogenic atomic force microscope above the quantum ring show that the propagation of electrons, both coherent and ballistic, can be investigated in situ, and even be controlled by tuning the tip potential.Comment: 11 text pages + 3 figure

Four-month moxifloxacin-based regimens for drug-sensitive tuberculosis

Supported by the Global Alliance for TB Drug Development with support from the Bill and Melinda Gates Foundation, the European and Developing Countries Clinical Trials Partnership, U.S. Agency for International Development, U.K. Department for International Development, Directorate General for International Cooperation of the Netherlands, Irish Aid, Australia Department of Foreign Affairs and Trade, and National Institutes of Health, AIDS Clinical Trials Group and by grants from the National Institute of Allergy and Infectious Diseases (NIAID) (UM1AI068634, UM1 AI068636, and UM1AI106701) and by NIAID grants to the University of KwaZulu Natal, South Africa, AIDS Clinical Trials Group (ACTG) site 31422 (1U01AI069469); to the Perinatal HIV Research Unit, Chris Hani Baragwanath Hospital, South Africa, ACTG site 12301 (1U01AI069453); and to the Durban International Clinical Trials Unit, South Africa, ACTG site 11201 (1U01AI069426); Bayer Healthcare for the donation of moxifloxacin; and Sanofi for the donation of rifampin.Background: Early-phase and preclinical studies suggest that moxifloxacin-containing regimens could allow for effective 4-month treatment of uncomplicated, smear-positive pulmonary tuberculosis. Methods: We conducted a randomized, double-blind, placebo-controlled, phase 3 trial to test the noninferiority of two moxifloxacin-containing regimens as compared with a control regimen. One group of patients received isoniazid, rifampin, pyrazinamide, and ethambutol for 8 weeks, followed by 18 weeks of isoniazid and rifampin (control group). In the second group, we replaced ethambutol with moxifloxacin for 17 weeks, followed by 9 weeks of placebo (isoniazid group), and in the third group, we replaced isoniazid with moxifloxacin for 17 weeks, followed by 9 weeks of placebo (ethambutol group). The primary end point was treatment failure or relapse within 18 months after randomization. Results: Of the 1931 patients who underwent randomization, in the per-protocol analysis, a favorable outcome was reported in fewer patients in the isoniazid group (85%) and the ethambutol group (80%) than in the control group (92%), for a difference favoring the control group of 6.1 percentage points (97.5% confidence interval [CI], 1.7 to 10.5) versus the isoniazid group and 11.4 percentage points (97.5% CI, 6.7 to 16.1) versus the ethambutol group. Results were consistent in the modified intention-to-treat analysis and all sensitivity analyses. The hazard ratios for the time to culture negativity in both solid and liquid mediums for the isoniazid and ethambutol groups, as compared with the control group, ranged from 1.17 to 1.25, indicating a shorter duration, with the lower bounds of the 95% confidence intervals exceeding 1.00 in all cases. There was no significant difference in the incidence of grade 3 or 4 adverse events, with events reported in 127 patients (19%) in the isoniazid group, 111 (17%) in the ethambutol group, and 123 (19%) in the control group. Conclusions: The two moxifloxacin-containing regimens produced a more rapid initial decline in bacterial load, as compared with the control group. However, noninferiority for these regimens was not shown, which indicates that shortening treatment to 4 months was not effective in this setting. (Funded by the Global Alliance for TB Drug Development and others; REMoxTB ClinicalTrials.gov number, NCT00864383.)Publisher PDFPeer reviewe

COVID-19 pandemic impact on adolescent mental health: a reassessment accounting for development

Current prospective reports suggest a pandemic-related increase in adolescent mental health problems. We examine whether age-related change over 11-14 years accounts for this increase. Mothers and adolescents in a UK-based birth cohort (Wirral Child Health and Development Study; WCHADS; N = 737) reported on adolescent depression and behavioural problems pre-pandemic (December 2019-March 2020), mid-pandemic (June 2020-March 2021) and late pandemic (July 2021-March 2022). Analysis used repeated measures models for over-dispersed Poisson counts with an adolescent-specific intercept with age as a time-varying covariate. Maturational curves for girls, but not for boys, showed a significant increase in self-reported depression symptoms over ages 11-14 years. Behavioural problems decreased for both. After adjusting for age-related change, girls' depression increased by only 13% at mid-pandemic and returned to near pre-pandemic level at late pandemic (mid versus late - 12%), whereas boys' depression increased by 31% and remained elevated (mid versus late 1%). Age-adjusted behavioural problems increased for both (girls 40%, boys 41%) and worsened from mid- to late pandemic (girls 33%, boys 18%). Initial reports of a pandemic-related increase in depression in young adolescent girls could be explained by a natural maturational rise. In contrast, maturational decreases in boys' depression and both boys' and girls' behavioural problems may mask an effect of the pandemic

From multiple perspectives to shared understanding

The aim of this study was to explore how learners operating in a small group reach shared understanding as they work out joint research questions and build a theoretical framework and to identify the resources and tools they used in the process. The learners’ own interpretations of their group activities and learning were also taken into account. The data, consisting of group discussions and the documents produced by the group, were subjected to a qualitative content analysis. The group members employed a variety of resources and tools to exchange their individual perspectives and achieve shared understanding. Summaries of relevant literature laid a foundation for the group’s theoretical discussions. Reflective comparisons between their book knowledge and their personal experiences of online interaction and collaboration were frequent, suggesting that such juxtapositions may have enhanced their learning by intertwining the content to be mastered and the activities entailed by this particular content

Electron-beam propagation in a two-dimensional electron gas

A quantum mechanical model based on a Green's function approach has been used to calculate the transmission probability of electrons traversing a two-dimensional electron gas injected and detected via mode-selective quantum point contacts. Two-dimensional scattering potentials, back-scattering, and temperature effects were included in order to compare the calculated results with experimentally observed interference patterns. The results yield detailed information about the distribution, size, and the energetic height of the scattering potentials.Comment: 7 pages, 6 figure

Limited role of culture conversion for decision-making in individual patient care and for advancing novel regimens to confirmatory clinical trials

Supported by the European and Developing Country Clinical Trials Partnership (grant IP.2007.32011.011) and the Global Alliance for TB Drug Development, with support from the Bill & Melinda Gates Foundation, US Agency for International Development, UK Department for International Development, Directorate-General for International Cooperation of the Netherlands, Irish Aid and Australian Department of Foreign Affairs and Trade.Background Despite recent increased clinical trials activity, no regimen has proved able to replace the standard 6-month regimen for drug-sensitive tuberculosis. Understanding the relationship between microbiological markers measured during treatment and long-term clinical outcomes is critical to evaluate their usefulness for decision-making for both individual patient care and for advancing novel regimens into time-consuming and expensive pivotal phase III trials. Methods Using data from the randomized controlled phase III trial REMoxTB, we evaluated sputum-based markers of speed of clearance of bacilli: time to smear negative status; time to culture negative status on LJ or in MGIT; daily rate of change of log10(TTP) to day 56; and smear or culture results at weeks 6, 8 or 12; as individual- and trial-level surrogate endpoints for long-term clinical outcome. Results Time to culture negative status on LJ or in MGIT, time to smear negative status and daily rate of change in log10(TTP) were each independent predictors of clinical outcome, adjusted for treatment (p <0.001). However, discrimination between low and high risk patients, as measured by the c-statistic, was modest and not much higher than the reference model adjusted for BMI, history of smoking, HIV status, cavitation, gender and MGIT TTP. Conclusions Culture conversion during treatment for tuberculosis, however measured, has only a limited role in decision-making for advancing regimens into phase III trials or in predicting the outcome of treatment for individual patients. REMoxTB ClinicalTrials.gov number: NCT00864383.Publisher PDFPeer reviewe