Mass accommodation coefficient measurements for HNO3, HCl and N2O5 on water, ice and aqueous sulfuric acid droplet surfaces

Preliminary results are reported of the direct measurement of accommodation coefficients for HNO3, N2O5 and HCl on water drops, aqueous sulfuric acid drops and ice particles. The heterogeneous chemistry of these species together with ClONO2 has been implicated in the ozone depletion observed in the Antarctic stratosphere during the spring in the last eight years. The most plausible chemical mechanism involves the removal of nitrogen oxide species via condensation on ice particles in polar stratospheric clouds resulting in a increase in the active chlorine species responsible for the ozone depletion. The observation of low NO2 and high ClO densities in the Antarctic stratosphere last summer appear to be consistent with such a mechanism

Pericyclic reactions of vinyl-heteroaromatics :multi-component domino and sequential processes

PhD ThesisSequential intermolecular Diels-Alder/intermolecular ene reactions of electron-rich vinyl-heteroaromatics have been investigated, as the basis for a new class of three component coupling reactions. This relatively unexplored reaction sequence provides access to the biologically important scaffolds 4,5,6,7-tetrahydro-1H-benzo[d]imidazole and 2,3,4,9-tetrahydro-1H-carbazole, with high atom economy and diastereocontrol of up to 5 new stereocentres, following a two-step reaction process involving three simple molecules (a diene, a dienophile and an enophile). 2-Vinylfuran (1), 2-vinylthiophene (2), N-protected-3-vinylindole (3) and N-protected-4-vinyl-1H-imidazoles (4 and 5) were found to react as dienes in Diels-Alder reactions under thermal conditions, without the need for Lewis acid catalysis. 4 and 5 were then subjected to a program of N-protecting group and dienophile optimisation, and the resulting Diels-Alder adducts were isolated in moderate to high yields (31-79 %) as single diastereoisomers, arising from exclusively endo-cycloaddition (Scheme 1). Scheme 1. Sequential Diels-Alder/Ene reactions. The cycloadducts arising from the Diels-Alder reaction of N-trityl-4-vinylimidazole and N-phenylmaleimide (NPM) were shown to undergo hitherto unreported, facile, sterically driven N→N trityl migrations. These migrations were a key step in several novel, highly diastereoselective domino reaction sequences (Diels−Alder, [1,3]-H shift, [1,3]-trityl migration and Diels−Alder, [1,3]-H shift, [1,3]-trityl migration, Michael reaction), leading to architecturally complex molecules. Heterocycle R 1 Furan CH2OTBS 2 Thiophene CH2OTBS 3 Indole H 4 Imidazole CH2OTBS 5 Imidazole H X: O, NPh Y: CH, N R1: Trt, DMTr, Bn, BnOMe, Ts, Ns, DMAS X1=Y1: C=C, C=O, C=N, N=N, N=O, O=O | Abstract Page | iii The cycloadducts arising from the Diels-Alder reaction of 1-benzyl-4-vinyl-1H-imidazole, (E)-1-benzyl-4-(3-((tert-butyldimethylsilyl)oxy)prop-1-en-1-yl)-1H-imidazole and N,N-dimethyl-3-vinyl-1H-indole-1-sulfonamide were obtained in high yields, and were then tested in ene reactions with a range of reactive enophiles (Scheme 1). The resulting ene adducts were successfully isolated in moderate to excellent yields (53-95%)

Patient experience of the acute post-surgical period following total laryngectomy during the COVID-19 era

BACKGROUND: Total laryngectomy (TL) results in permanent functional changes requiring rapid development of complex new skills. A significant portion of this learning happens in the acute post‐surgical stage. There is increasing interest in enhanced recovery after surgery (ERAS) protocols in TL; however, implementation has been difficult. COVID‐19 has placed significant pressures on acute services, requiring rapid service changes for TL patients. AIMS: To understand the acute patient experience of having a TL both before and during COVID‐19. METHODS & PROCEDURES: Semi‐structured interviews using a pre‐designed topic guide were conducted with 10 people who had undergone a TL within the last 2 years. Participants were recruited by their speech and language therapists using purposive sampling. Braun and Clarke's iterative approach to data collection and thematic analysis was used to generate key themes from the data. OUTCOMES & RESULTS: Thematic analysis identified four main themes: (1) pre‐operative information‐giving: ‘it was just words’; (2) decision‐making influences: ‘I just wanted them to get it all out and get it over with’; (3) coping with adjustment to the new normal: ‘this is part of me now’; and (4) the importance of relationship‐building: ‘when you've had something like this, you need some care and understanding’. CONCLUSIONS & IMPLICATIONS: The need for an individualized approach to TL intervention which incorporates medical and psycho‐social approaches from pre‐treatment to acute discharge is vital. ERAS models should be reviewed to shift beyond the medical model alone. Rapid service changes due to COVID‐19 did not contribute any major changes to the acute patient‐reported experience. WHAT THIS PAPER ADDS: WHAT IS ALREADY KNOWN ON THE SUBJECT: We know that ERAS protocols have the potential to improve patient outcomes following TL. However, the research does not consider anything other than the early oral feeding debate and it has therefore been difficult to implement ERAS protocols in current service models. COVID19 required head and neck cancer services to make quick changes to surgical pathways, with the potential that some ERAS protocols had been adopted inadvertently. In order to understand the impact of this, we need to understand the patient experience following TL both before and during COVID19. WHAT THIS PAPER ADDS TO EXISTING KNOWLEDGE: This paper used qualitative interviews to understand the acute patient experience following TL both during and before COVID19. Findings from these interviews highlighted that people were on the most part, well prepared for the functional changes they would experience after surgery. However, people felt there were gaps in service delivery at the pre‐treatment and early discharge home period. Overall, the gaps identified were from a more psycho‐social need suggesting that future ERAS models of care should consider both medical and psycho‐social principles to enhance patient experience and outcome. WHAT ARE THE POTENTIAL OR ACTUAL CLINICAL IMPLICATIONS OF THIS WORK? Pre‐treatment services provided to people who have a TL could be reviewed to help maximize long‐term adjustment to life. Areas which could be reviewed include the method and mode of information delivery. Further work needs to be done in partnership with community services to improve the immediate discharge home experience

Securing safer care staff : a model for the assessment, selection and training of staff to work in residential care

The recruitment of staff into residential child care presents an ongoing challenge for organisations. Methods of recruitment in the past have been criticised in a range of government reports. Skinner (1992) and others have highlighted the need for better preparation and training of residential workers. At a national level, the Care Standards and the establishment of registration for residential staff have prompted a re-examination of selection and training practices

Shigella sonnei infection of zebrafish reveals that O-antigen mediates neutrophil tolerance and dysentery incidence.

Funder: Lister Institute of Preventive Medicine; funder-id: http://dx.doi.org/10.13039/501100001255Shigella flexneri is historically regarded as the primary agent of bacillary dysentery, yet the closely-related Shigella sonnei is replacing S. flexneri, especially in developing countries. The underlying reasons for this dramatic shift are mostly unknown. Using a zebrafish (Danio rerio) model of Shigella infection, we discover that S. sonnei is more virulent than S. flexneri in vivo. Whole animal dual-RNAseq and testing of bacterial mutants suggest that S. sonnei virulence depends on its O-antigen oligosaccharide (which is unique among Shigella species). We show in vivo using zebrafish and ex vivo using human neutrophils that S. sonnei O-antigen can mediate neutrophil tolerance. Consistent with this, we demonstrate that O-antigen enables S. sonnei to resist phagolysosome acidification and promotes neutrophil cell death. Chemical inhibition or promotion of phagolysosome maturation respectively decreases and increases neutrophil control of S. sonnei and zebrafish survival. Strikingly, larvae primed with a sublethal dose of S. sonnei are protected against a secondary lethal dose of S. sonnei in an O-antigen-dependent manner, indicating that exposure to O-antigen can train the innate immune system against S. sonnei. Collectively, these findings reveal O-antigen as an important therapeutic target against bacillary dysentery, and may explain the rapidly increasing S. sonnei burden in developing countries

Cancer-Related Fatigue in Head and Neck Cancer Survivors: Longitudinal Findings from the Head and Neck 5000 Prospective Clinical Cohort.

Cancer-related fatigue (CRF) is a common side-effect of cancer and its treatments. For head and neck cancer (HNC), CRF may exacerbate the symptom burden and poor quality-of-life. Using data from the Head and Neck 5000 prospective clinical cohort, we investigated clinically important CRF over a year post-diagnosis, assessing temporal trends, CRF by HNC site and treatment received, and subgroups at higher risk of CRF. Recruitment was undertaken in 2011-2014. Socio-demographic and clinical data, and patient-reported CRF (EORTC QLQ-C30 fatigue subscale score ≥39 of a possible 100) were collected at baseline (pre-treatment) and 4- and 12- months post-baseline. Mixed-effects logistic multivariable regression was used to investigate time trends, compare cancer sites and treatment groups, and identify associations between clinical, socio-demographic and lifestyle variables and CRF. At baseline, 27.8% of 2847 patients scored in the range for clinically important CRF. This was 44.7% at 4 months and 29.6% at 12 months. In the multivariable model, after adjusting for time-point, the odds of having CRF over 12 months were significantly increased in females and current smokers; those with stage 3/4 disease, comorbidities and multimodal treatment; and those who had depression at baseline. The high prevalence of clinically important CRF indicates the need for additional interventions and supports for affected HNC patients. These findings also identified patient subgroups towards whom such interventions could be targeted

Effect of a Web-Based Behavior Change Program on Weight Loss and Cardiovascular Risk Factors in Overweight and Obese Adults at High Risk of Developing Cardiovascular Disease: Randomized Controlled Trial.

Web-based programs are a potential medium for supporting weight loss because of their accessibility and wide reach. Research is warranted to determine the shorter- and longer-term effects of these programs in relation to weight loss and other health outcomes

Increasing long-acting reversible contraceptives: the Australian Contraceptive ChOice pRoject (ACCORd) cluster randomized trial

BACKGROUND: Long-active reversible contraceptives reduce unintended pregnancy and abortions, but uptake is low. Interventions to increase uptake in family medicine settings are untested. OBJECTIVE: The Australian Contraceptive ChOice pRoject, which was adapted from the successful US Contraceptive CHOICE study, aimed to evaluate whether a complex intervention in family medicine practices resulted in increased long-active reversible contraceptive uptake. STUDY DESIGN: This cluster randomized controlled trial was set in family practices in metropolitan Melbourne, Australia. From April 2016 to January 2017, we recruited 57 family physicians by mail invitation. Each family physician aimed to recruit at least 14 female patients. Eligible family physicians worked ≥3 sessions per week in computerized practices. Eligible women were English-speaking, sexually active, not pregnant, not planning a pregnancy in the next year, 16-45 years old, and interested in discussing contraception or in starting a new, reversible method. With the use of a randomization sequence with permuted blocks that were stratified by whether the family physician performed long-active reversible contraceptive insertion or not, family physicians were assigned randomly to a complex intervention that involved training to provide structured effectiveness-based contraceptive counselling and access to rapid referral to long-active reversible contraceptive insertion clinics. The 6-hour, online educational intervention was based on the US Contraceptive CHOICE Project and adapted for the Australian context. The control family physicians received neither the educational intervention nor access to the long-active reversible contraceptive rapid referral clinics and conducted their usual contraception counselling. We used the chi-square test, which was adjusted for clustering and stratification by whether the family physician inserted long-active reversible contraceptives, and binary regression models with generalized estimating equations and robust standard errors to compare, between the intervention and control groups, the proportions of women who had a long-active reversible contraceptive inserted. The primary outcome was the proportion of women with long-active reversible contraceptives that were inserted at 4 weeks. Secondary outcomes included women’s choice of contraceptive method, quality of life, and long-active reversible contraceptive use at 6 and 12 months. Analyses were performed according to intention-to-treat. RESULTS: A total of 25 intervention and 32 control family physicians recruited 307 and 433 women, respectively (N=740). Within 4 weeks, 19.3% of women in the intervention group and 12.9% of women in the control group had long-active reversible contraceptive inserted (relative risk, 2.0; 95% confidence interval, 1.1-3.9; P=.033). By 6 months, this number had risen to 44.4% and 29.3%, respectively (relative risk, 1.6; 95% confidence interval, 1.2-2.17; P=.001); by 12 months, it had risen to 46.6% and 32.8%, respectively (relative risk, 1.5; 95% confidence interval, 1.2-2.0; P=.0015). The levonorgestrel intrauterine system was the most commonly chosen long-active reversible contraceptive by women in the intervention group at all time points. Differences between intervention and control groups in mean quality-of-life scores across all domains at 6 and 12 months were small. CONCLUSION: A complex intervention combination of family physician training on contraceptive effectiveness counselling and rapid access to long-active reversible contraceptive insertion clinics resulted in greater long-active reversible contraceptive uptake and has the potential to reduce unintended pregnancies