Chirality Dependence of the KK-Momentum Dark Excitons in Carbon Nanotubes

Using a collection of twelve semiconducting carbon nanotube samples, each highly enriched in a single chirality, we study the chirality dependence of the $K$-momentum dark singlet exciton using phonon sideband optical spectroscopy. Measurements of bright absorptive and emissive sidebands of this finite momentum exciton identify its energy as 20 - 38 meV above the bright singlet exciton, a separation that exhibits systematic dependencies on tube diameter, $2n+m$ family, and semiconducting type. We present calculations that explain how chiral angle dependence in this energy separation relates to the Coulomb exchange interaction, and elaborate the dominance of the $K_{A_1'}$ phonon sidebands over the zone-center phonon sidebands over a wide range of chiralities. The Kataura plot arising from these data is qualitatively well described by theory, but the energy separation between the sidebands shows a larger chiral dependence than predicted. This latter observation may indicate a larger dispersion for the associated phonon near the $K$ point than expected from finite distance force modeling.Comment: 24 pages, 12 figures, 1 table; slight title change, Figures 1 and 11 added, reference added, presentation improved throughout documen

Effect of Proton Pump Inhibitors on Risks of Upper and Lower Gastrointestinal Bleeding among Users of Low-Dose Aspirin: A Population-Based Observational Study

Estimates of the effect of proton pump inhibitors (PPIs) on risks of upper and lower gastrointestinal bleeding (UGIB and LGIB) among low-dose aspirin users in routine clinical practice are variable (UGIB) or lacking (LGIB). We aimed to establish these risks in the same observational study population. Using UK primary care data, we followed 199, 049 new users of low-dose aspirin (75-300 mg/day) and matched non-users at start of follow-up to identify incident UGIB/LGIB cases. In nested case-control analyses, adjusted odds ratios (ORs) were calculated for concomitant PPI use vs. past (discontinued) PPI use among current low-dose aspirin users. For UGIB (n = 987), ORs (95% CIs) were 0.69 (0.54-0.88) for >1 month PPI use and 2.65 (1.62-4.3) for 1 month PPI use and 1.12 (0.73-1.71) for 1 month) was associated with a significantly reduced UGIB risk. Neither short nor long-term PPI use affected LGIB risk

Financial Conflicts of Interest and Stance on Tobacco Harm Reduction: A Systematic Review

Background. Tobacco companies have actively promoted the substitution of cigarettes with purportedly safer tobacco products (e.g., smokeless tobacco, e-cigarettes) as tobacco harm reduction (THR). Given the tobacco, e-cigarette, and pharmaceutical industries’ substantial financial interests, we quantified industry influence on support for THR. Objectives. To analyze a comprehensive set of articles published in peer-reviewed journals assessing funding sources and support for or opposition to substitution of tobacco or nicotine products as harm reduction. Search Methods. We searched PubMed, Embase, Web of Science, and PsycINFO with a comprehensive search string including all articles, comments, and editorials published between January 1, 1992 and July 26, 2016. Selection Criteria. We included English-language publications published in peer-reviewed journals addressing THR in humans and excluded studies on modified cigarettes, on South Asian smokeless tobacco variants, on pregnant women, on animals, not mentioning a tobacco or nicotine product, on US Food and Drug Administration–approved nicotine replacement therapies, and on nicotine vaccines. Data Collection and Analysis. We double-coded all articles for article type; primary product type (e.g., snus, e-cigarettes); themes for and against THR; stance on THR; THR concepts; funding or affiliation with tobacco, e-cigarette, pharmaceutical industry, or multiple industries; and each author’s country. We fit exact logistic regression models with stance on THR as the outcome (pro- vs anti-THR) and source of funding or industry affiliation as the predictor taking into account sparse data. Additional models included article type as the outcome (nonempirical or empirical) and industry funding or affiliation as predictor, and stratified analyses for empirical and nonempirical studies with stance on THR as outcome an

Public health impact of low-dose aspirin on colorectal cancer, cardiovascular disease and safety in the UK – Results from micro-simulation model

Background: Low-dose aspirin therapy reduces the risk of cardiovascular disease and may have a positive effect on the prevention of colorectal cancer. We evaluated the population-level expected effect of regular low-dose aspirin use on cardiovascular disease (CVD), colorectal cancer (CRC), gastrointestinal bleeding, symptomatic peptic ulcers, and intracranial hemorrhage, using a microsimulation study design. Methods: We used individual-level state transition modeling to assess the impact of aspirin in populations aged 50–59 or 60–69 years old indicated for low-dose aspirin usage for primary or secondary CVD prevention. Model parameters were based on data from governmental agencies from the UK or recent publications. Results: In the 50–59 years cohort, a decrease in incidence rates (IRs per 100 000 person years) of non-fatal CVD (-203 and -794) and fatal CVD (-97 and-381) was reported in the primary and secondary CVD prevention setting, respectively. The IR reduction of CRC (-96 and -93) was similar for primary and secondary CVD prevention. The IR increase of non-fatal (116 and 119) and fatal safety events (6 and 6) was similar for primary and secondary CVD prevention. Similar results were obtained for the 60–69 years cohort. Conclusions: The decrease in fatal CVD and CRC events was larger than the increase in fatal safety events and this difference was more pronounced when low-dose aspirin was used for secondary compared to primary CVD prevention. These results provide a comprehensive image of the expected effect of regular low-dose aspirin therapy in a UK population indicated to use aspirin for CVD prevention. © 202

Risk-Reducing Breast and Gynecological Surgery for BRCA Mutation Carriers: A Narrative Review

This narrative review aims to clarify the role of breast and gynecological risk-reduction surgery in BRCA mutation carriers. We examine the indications, contraindications, complications, technical aspects, timing, economic impact, ethical issues, and prognostic benefits of the most common prophylactic surgical options from the perspectives of a breast surgeon and a gynecologist. A comprehensive literature review was conducted using the PubMed/Medline, Scopus, and EMBASE databases. The databases were explored from their inceptions to August 2022. Three independent reviewers screened the items and selected those most relevant to this review’s scope. BRCA1/2 mutation carriers are significantly more likely to develop breast, ovarian, and serous endometrial cancer. Because of the Angelina effect, there has been a significant increase in bilateral risk-reducing mastectomy (BRRM) since 2013. BRRM and risk-reducing salpingo-oophorectomy (RRSO) significantly reduce the risk of developing breast and ovarian cancer. RRSO has significant side effects, including an impact on fertility and early menopause (i.e., vasomotor symptoms, cardiovascular disease, osteoporosis, cognitive impairment, and sexual dysfunction). Hormonal therapy can help with these symptoms. Because of the lower risk of developing breast cancer in the residual mammary gland tissue after BRRM, estrogen-only treatments have an advantage over an estrogen/progesterone combined treatment. Risk-reducing hysterectomy allows for estrogen-only treatments and lowers the risk of endometrial cancer. Although prophylactic surgery reduces the cancer risk, it has disadvantages associated with early menopause. A multidisciplinary team must carefully inform the woman who chooses this path of the broad spectrum of implications, from cancer risk reduction to hormonal therapies

Do pilocarpine drops help dry mouth in palliative care patients: A protocol for an aggregated series of n-of-1 trials

Background: It is estimated that 39,000 Australians die from malignant disease yearly. Of these, 60% to 88% of advanced cancer patients suffer xerostomia, the subjective feeling of mouth dryness. Xerostomia has significant physical, social and psychological consequences which compromise function and quality of life. Pilocarpine is one treatment for xerostomia. Most studies have shown some variation in individual response to pilocarpine, in terms of dose used, and timing and extent of response.We will determine a population estimate of the efficacy of pilocarpine drops (6 mg) three times daily compared to placebo in relieving dry mouth in palliative care (PC) patients. A secondary aim is to assess individual patients' response to pilocarpine and provide reports detailing individual response to patients and their treating clinician. Methods/Design. Aggregated n-of-1 trials (3 cycle, double blind, placebo-controlled crossover trials using standardized measures of effect). Individual trials will identify which patients respond to the medication. To produce a population estimate of a treatment effect, the results of all cycles will be aggregated. Discussion. Managing dry mouth with treatment supported by the best possible evidence will improve functional status of patients, and improve quality of life for patients and carers. Using n-of-1 trials will accelerate the rate of accumulation of high-grade evidence to support clinical therapies used in PC. Trial registration. Australia and New Zealand Clinical Trial Registry Number: 12610000840088. © 2013 Nikles et al.; licensee BioMed Central Ltd

Metaproteomic evidence of changes in protein expression following a change in electrode potential in a robust biocathode microbiome

Microorganisms that respire electrodes may be exploited for biotechnology applications if key pathways for extracellular electron transfer (EET) can be identified and manipulated through bioengineering. To determine whether expression of proposed Biocathode-MCL EET proteins are changed by modulating electrode potential without disrupting the relative distribution of microbial constituents, metaproteomic and 16S rRNA gene expression analyses were performed after switching from an optimal to suboptimal potential based on an expected decrease in electrode respiration. Five hundred and seventy-nine unique proteins were identified across both potentials, the majority of which were assigned to three previously defined Biocathode-MCL metagenomic clusters: a Marinobacter sp., a member of the family Chromatiaceae, and a Labrenzia sp. Statistical analysis of spectral counts using the Fisher's exact test identified 16 proteins associated with the optimal potential, five of which are predicted electron transfer proteins. The majority of proteins associated with the suboptimal potential were involved in protein turnover/turnover, motility, and membrane transport. Unipept and 16S rRNA gene expression analyses indicated that the taxonomic profile of the microbiome did not change after 52 hours at the suboptimal potential. These findings show that protein expression is sensitive to the electrode potential without inducing shifts in community composition, a feature that may be exploited for engineering Biocathode-MCL

Complete analysis of the B-cell response to a protein antigen, from in vivo germinal centre formation to 3-D modelling of affinity maturation

Somatic hypermutation of immunoglobulin variable region genes occurs within germinal centres (GCs) and is the process responsible for affinity maturation of antibodies during an immune response. Previous studies have focused almost exclusively on the immune response to haptens, which may be unrepresentative of epitopes on protein antigens. In this study, we have exploited a model system that uses transgenic B and CD4<sup>+</sup> T cells specific for hen egg lysozyme (HEL) and a chicken ovalbumin peptide, respectively, to investigate a tightly synchronized immune response to protein antigens of widely differing affinities, thus allowing us to track many facets of the development of an antibody response at the antigen-specific B cell level in an integrated system <i>in</i> <i>vivo</i>. Somatic hypermutation of immunoglobulin variable genes was analysed in clones of transgenic B cells proliferating in individual GCs in response to HEL or the cross-reactive low-affinity antigen, duck egg lysozyme (DEL). Molecular modelling of the antibody–antigen interface demonstrates that recurring mutations in the antigen-binding site, selected in GCs, enhance interactions of the antibody with DEL. The effects of these mutations on affinity maturation are demonstrated by a shift of transgenic serum antibodies towards higher affinity for DEL in DEL-cOVA immunized mice. The results show that B cells with high affinity antigen receptors can revise their specificity by somatic hypermutation and antigen selection in response to a low-affinity, cross-reactive antigen. These observations shed further light on the nature of the immune response to pathogens and autoimmunity and demonstrate the utility of this novel model for studies of the mechanisms of somatic hypermutation