A mathematical and computational review of Hartree-Fock SCF methods in Quantum Chemistry

We present here a review of the fundamental topics of Hartree-Fock theory in Quantum Chemistry. From the molecular Hamiltonian, using and discussing the Born-Oppenheimer approximation, we arrive to the Hartree and Hartree-Fock equations for the electronic problem. Special emphasis is placed in the most relevant mathematical aspects of the theoretical derivation of the final equations, as well as in the results regarding the existence and uniqueness of their solutions. All Hartree-Fock versions with different spin restrictions are systematically extracted from the general case, thus providing a unifying framework. Then, the discretization of the one-electron orbitals space is reviewed and the Roothaan-Hall formalism introduced. This leads to a exposition of the basic underlying concepts related to the construction and selection of Gaussian basis sets, focusing in algorithmic efficiency issues. Finally, we close the review with a section in which the most relevant modern developments (specially those related to the design of linear-scaling methods) are commented and linked to the issues discussed. The whole work is intentionally introductory and rather self-contained, so that it may be useful for non experts that aim to use quantum chemical methods in interdisciplinary applications. Moreover, much material that is found scattered in the literature has been put together here to facilitate comprehension and to serve as a handy reference.Comment: 64 pages, 3 figures, tMPH2e.cls style file, doublesp, mathbbol and subeqn package

NFATc1 supports imiquimod-induced skin inflammation by suppressing IL-10 synthesis in B cells

Epicutaneous application of Aldara cream containing the TLR7 agonist imiquimod (IMQ) to mice induces skin inflammation that exhibits many aspects of psoriasis, an inflammatory human skin disease. Here we show that mice depleted of B cells or bearing interleukin (IL)-10-deficient B cells show a fulminant inflammation upon IMQ exposure, whereas ablation of NFATc1 in B cells results in a suppression of Aldara-induced inflammation. In vitro, IMQ induces the proliferation and IL-10 expression by B cells that is blocked by BCR signals inducing NFATc1. By binding to HDAC1, a transcriptional repressor, and to an intronic site of the Il10 gene, NFATc1 suppresses IL-10 expression that dampens the production of tumour necrosis factor-α and IL-17 by T cells. These data indicate a close link between NFATc1 and IL-10 expression in B cells and suggest NFATc1 and, in particular, its inducible short isoform, NFATc1/αA, as a potential target to treat human psoriasis

The Effectiveness of Pharmacological and Non-Pharmacological Interventions for Improving Glycaemic Control in Adults with Severe Mental Illness: A Systematic Review and Meta-Analysis

People with severe mental illness (SMI) have reduced life expectancy compared with the general population, which can be explained partly by their increased risk of diabetes. We conducted a meta-analysis to determine the clinical effectiveness of pharmacological and non-pharmacological interventions for improving glycaemic control in people with SMI (PROSPERO registration: CRD42015015558). A systematic literature search was performed on 30/10/2015 to identify randomised controlled trials (RCTs) in adults with SMI, with or without a diagnosis of diabetes that measured fasting blood glucose or glycated haemoglobin (HbA1c). Screening and data extraction were carried out independently by two reviewers. We used random effects meta-analysis to estimate effectiveness, and subgroup analysis and univariate meta-regression to explore heterogeneity. The Cochrane Collaboration’s tool was used to assess risk of bias. We found 54 eligible RCTs in 4,392 adults (40 pharmacological, 13 behavioural, one mixed intervention). Data for meta-analysis were available from 48 RCTs (n = 4052). Both pharmacological (mean difference (MD), -0.11mmol/L; 95% confidence interval (CI), [-0.19, -0.02], p = 0.02, n = 2536) and behavioural interventions (MD, -0.28mmol//L; 95% CI, [-0.43, -0.12], p<0.001, n = 956) were effective in lowering fasting glucose, but not HbA1c (pharmacological MD, -0.03%; 95% CI, [-0.12, 0.06], p = 0.52, n = 1515; behavioural MD, 0.18%; 95% CI, [-0.07, 0.42], p = 0.16, n = 140) compared with usual care or placebo. In subgroup analysis of pharmacological interventions, metformin and antipsychotic switching strategies improved HbA1c. Behavioural interventions of longer duration and those including repeated physical activity had greater effects on fasting glucose than those without these characteristics. Baseline levels of fasting glucose explained some of the heterogeneity in behavioural interventions but not in pharmacological interventions. Although the strength of the evidence is limited by inadequate trial design and reporting and significant heterogeneity, there is some evidence that behavioural interventions, antipsychotic switching, and metformin can lead to clinically important improvements in glycaemic measurements in adults with SMI

Revisiting the B-cell compartment in mouse and humans: more than one B-cell subset exists in the marginal zone and beyond.

International audienceABSTRACT: The immunological roles of B-cells are being revealed as increasingly complex by functions that are largely beyond their commitment to differentiate into plasma cells and produce antibodies, the key molecular protagonists of innate immunity, and also by their compartmentalisation, a more recently acknowledged property of this immune cell category. For decades, B-cells have been recognised by their expression of an immunoglobulin that serves the function of an antigen receptor, which mediates intracellular signalling assisted by companion molecules. As such, B-cells were considered simple in their functioning compared to the other major type of immune cell, the T-lymphocytes, which comprise conventional T-lymphocyte subsets with seminal roles in homeostasis and pathology, and non-conventional T-lymphocyte subsets for which increasing knowledge is accumulating. Since the discovery that the B-cell family included two distinct categories - the non-conventional, or extrafollicular, B1 cells, that have mainly been characterised in the mouse; and the conventional, or lymph node type, B2 cells - plus the detailed description of the main B-cell regulator, FcγRIIb, and the function of CD40+ antigen presenting cells as committed/memory B-cells, progress in B-cell physiology has been slower than in other areas of immunology. Cellular and molecular tools have enabled the revival of innate immunity by allowing almost all aspects of cellular immunology to be re-visited. As such, B-cells were found to express "Pathogen Recognition Receptors" such as TLRs, and use them in concert with B-cell signalling during innate and adaptive immunity. An era of B-cell phenotypic and functional analysis thus began that encompassed the study of B-cell microanatomy principally in the lymph nodes, spleen and mucosae. The novel discovery of the differential localisation of B-cells with distinct phenotypes and functions revealed the compartmentalisation of B-cells. This review thus aims to describe novel findings regarding the B-cell compartments found in the mouse as a model organism, and in human physiology and pathology. It must be emphasised that some differences are noticeable between the mouse and human systems, thus increasing the complexity of B-cell compartmentalisation. Special attention will be given to the (lymph node and spleen) marginal zones, which represent major crossroads for B-cell types and functions and a challenge for understanding better the role of B-cell specificities in innate and adaptive immunology

Protocol for the \u27Supporting Young Cancer Survivors who Smoke\u27 study (PRISM): Informing the development of a smoking cessation intervention for childhood, adolescent and young adult cancer survivors in England

\ua9 2024 Brown et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Background: Childhood, adolescent and young adult (CAYA) cancer survivors are vulnerable to adverse late-effects. For CAYA cancer survivors, tobacco smoking is the most important preventable cause of ill-health and early death. Yet, effective strategies to support smoking cessation in this group are lacking. The PRISM study aims to undertake multi-method formative research to explore the need for, and if appropriate, inform the future development of an evidence-based and theory-informed tobacco smoking cessation intervention for CAYA cancer survivors. Materials and methods PRISM involves three phases of: 1) an environmental scan using multiple strategies to identify and examine a) smoking cessation interventions for CAYA cancer survivors that are published in the international literature and b) current smoking cessation services in England that may be available to, or tailorable to, CAYA cancer survivors; 2) a qualitative study involving semi-structured interviews with CAYA cancer survivors (aged 16–29 years and who are current or recent ex-smokers and/or current vapers) to explore their views and experiences of smoking, smoking cessation and vaping; and 3) stakeholder workshops with survivors, healthcare professionals and other stakeholders to consider the potential for a smoking cessation intervention for CAYA cancer survivors and what such an intervention would need to target and change. Findings will be disseminated to patient groups, healthcare professionals and researchers, through conference presentations, journal papers, plain English summaries and social media. Discussion PRISM will explore current delivery of, perceived need for, and barriers and facilitators to, smoking cessation advice and support to CAYA cancer survivors from the perspective of both survivors and healthcare professionals. A key strength of PRISM is the user involvement throughout the study and the additional exploration of survivors’ views on vaping, a behaviour which often co-occurs with smoking. PRISM is the first step in the development of a person-centred, evidence- and theory-based smoking cessation intervention for CAYA cancer survivors who smoke, which if effective, will reduce morbidity and mortality in the CAYA cancer survivor population

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

Modifying effect of dual antiplatelet therapy on incidence of stent thrombosis according to implanted drug-eluting stent type

Aim To investigate the putative modifying effect of dual antiplatelet therapy (DAPT) use on the incidence of stent thrombosis at 3 years in patients randomized to Endeavor zotarolimus-eluting stent (E-ZES) or Cypher sirolimus-eluting stent (C-SES). Methods and results Of 8709 patients in PROTECT, 4357 were randomized to E-ZES and 4352 to C-SES. Aspirin was to be given indefinitely, and clopidogrel/ticlopidine for ≥3 months or up to 12 months after implantation. Main outcome measures were definite or probable stent thrombosis at 3 years. Multivariable Cox regression analysis was applied, with stent type, DAPT, and their interaction as the main outcome determinants. Dual antiplatelet therapy adherence remained the same in the E-ZES and C-SES groups (79.6% at 1 year, 32.8% at 2 years, and 21.6% at 3 years). We observed a statistically significant (P = 0.0052) heterogeneity in treatment effect of stent type in relation to DAPT. In the absence of DAPT, stent thrombosis was lower with E-ZES vs. C-SES (adjusted hazard ratio 0.38, 95% confidence interval 0.19, 0.75; P = 0.0056). In the presence of DAPT, no difference was found (1.18; 0.79, 1.77; P = 0.43). Conclusion A strong interaction was observed between drug-eluting stent type and DAPT use, most likely prompted by the vascular healing response induced by the implanted DES system. These results suggest that the incidence of stent thrombosis in DES trials should not be evaluated independently of DAPT use, and the optimal duration of DAPT will likely depend upon stent type (Clinicaltrials.gov number NCT00476957

Accounting for the mortality benefit of drug-eluting stents in percutaneous coronary intervention: a comparison of methods in a retrospective cohort study

<p>Abstract</p> <p>Background</p> <p>Drug-eluting stents (DES) reduce rates of restenosis compared with bare metal stents (BMS). A number of observational studies have also found lower rates of mortality and non-fatal myocardial infarction with DES compared with BMS, findings not observed in randomized clinical trials. In order to explore reasons for this discrepancy, we compared outcomes after percutaneous coronary intervention (PCI) with DES or BMS by multiple statistical methods.</p> <p>Methods</p> <p>We compared short-term rates of all-cause mortality and myocardial infarction for patients undergoing PCI with DES or BMS using propensity-score adjustment, propensity-score matching, and a stent-era comparison in a large, integrated health system between 1998 and 2007. For the propensity-score adjustment and stent era comparisons, we used multivariable logistic regression to assess the association of stent type with outcomes. We used McNemar's Chi-square test to compare outcomes for propensity-score matching.</p> <p>Results</p> <p>Between 1998 and 2007, 35,438 PCIs with stenting were performed among health plan members (53.9% DES and 46.1% BMS). After propensity-score adjustment, DES was associated with significantly lower rates of death at 30 days (OR 0.49, 95% CI 0.39 - 0.63, <it>P </it>< 0.001) and one year (OR 0.58, 95% CI 0.49 - 0.68, <it>P </it>< 0.001), and a lower rate of myocardial infarction at one year (OR 0.72, 95% CI 0.59 - 0.87, <it>P </it>< 0.001). Thirty day and one year mortality were also lower with DES after propensity-score matching. However, a stent era comparison, which eliminates potential confounding by indication, showed no difference in death or myocardial infarction for DES and BMS, similar to results from randomized trials.</p> <p>Conclusions</p> <p>Although propensity-score methods suggested a mortality benefit with DES, consistent with prior observational studies, a stent era comparison failed to support this conclusion. Unobserved factors influencing stent selection in observational studies likely account for the observed mortality benefit of DES not seen in randomized clinical trials.</p