Global forecasts in reservoir computers.

A reservoir computer is a machine learning model that can be used to predict the future state(s) of time-dependent processes, e.g., dynamical systems. In practice, data in the form of an input-signal are fed into the reservoir. The trained reservoir is then used to predict the future state of this signal. We develop a new method for not only predicting the future dynamics of the input-signal but also the future dynamics starting at an arbitrary initial condition of a system. The systems we consider are the Lorenz, Rossler, and Thomas systems restricted to their attractors. This method, which creates a global forecast, still uses only a single input-signal to train the reservoir but breaks the signal into many smaller windowed signals. We examine how well this windowed method is able to forecast the dynamics of a system starting at an arbitrary point on a system's attractor and compare this to the standard method without windows. We find that the standard method has almost no ability to forecast anything but the original input-signal while the windowed method can capture the dynamics starting at most points on an attractor with significant accuracy.

Whole systems approach to diet and healthy weight: a longitudinal process evaluation in East Scotland.

AIMS: Obesity contributes to morbidity and early mortality, affecting people of all ages and sociodemographic backgrounds. Despite attempts to address obesity, efforts to date have only had limited success. Adopting a whole systems approach (WSA) may potentially address obesity and emphasise complex inter-relating factors beyond individual choice. This study aimed to assess implementation of WSA to diet and healthy weight in two council areas of Scotland, longitudinally exploring enablers and barriers. One area followed a Leeds Beckett WSA model (LBM) of implementation, while the other used a hybrid model incorporating existing working systems. METHODS: To assess the process of implementing a WSA, interviews and focus groups were conducted after initiation and 1 year later. RESULTS: Main enablers included: belief in WSA effectiveness; positive relationships between key personnel; buy-in at community and national levels; funding availability; the working group responsible for coordinating the system development comprising individuals with diverse expertise; good communication; and existing governance structures. Barriers included: insufficient funding; high staff turnover; inadequate training in WSA methodology; engaging all relevant stakeholders and reverting to 'old ways' of non-WSA working. The LBM provided a framework for system setup and generating an action plan. CONCLUSION: This study provides the first independent longitudinal process evaluation of WSAs that have incorporated Leeds Beckett methodology, and offers insights into how a WSA can be implemented to address diet and healthy weight.

Associations between air pollutants and blood pressure in an ethnically diverse cohort of adolescents in London, England.

Longitudinal evidence on the association between air pollution and blood pressure (BP) in adolescence is scarce. We explored this association in an ethnically diverse cohort of schoolchildren. Sex-stratified, linear random-effects modelling was used to examine how modelled residential exposure to annual average nitrogen dioxide (NO2), particulate matter (PM2.5, PM10) and ozone (O3), measures in µg/m3, associated with blood pressure. Estimates were based on 3,284 adolescents; 80% from ethnic minority groups, recruited from 51 schools, and followed up from 11-13 to 14-16 years old. Ethnic minorities were exposed to higher modelled annual average concentrations of pollution at residential postcode level than their White UK peers. A two-pollutant model (NO2 & PM2.5), adjusted for ethnicity, age, anthropometry, and pubertal status, highlighted associations with systolic, but not diastolic BP. A µg/m3 increase in NO2 was associated with a 0.30 mmHg (95% CI 0.18 to 0.40) decrease in systolic BP for girls and 0.19 mmHg (95% CI 0.07 to 0.31) decrease in systolic BP for boys. In contrast, a 1 µg/m3 increase in PM2.5 was associated with 1.34 mmHg (95% CI 0.85 to 1.82) increase in systolic BP for girls and 0.57 mmHg (95% CI 0.04 to 1.03) increase in systolic BP for boys. Associations did not vary by ethnicity, body size or socio-economic advantage. Associations were robust to adjustments for noise levels and lung function at 11-13 years. In summary, higher ambient levels of NO2 were associated with lower and PM2.5 with higher systolic BP across adolescence, with stronger associations for girls.

Remote-refocusing light-sheet fluorescence microscopy enables 3D imaging of electromechanical coupling of hiPSC-derived and adult cardiomyocytes in co-culture.

Improving cardiac function through stem-cell regenerative therapy requires functional and structural integration of the transplanted cells with the host tissue. Visualizing the electromechanical interaction between native and graft cells necessitates 3D imaging with high spatio-temporal resolution and low photo-toxicity. A custom light-sheet fluorescence microscope was used for volumetric imaging of calcium dynamics in co-cultures of adult rat left ventricle cardiomyocytes and human induced pluripotent stem cell-derived cardiomyocytes. Aberration-free remote refocus of the detection plane synchronously to the scanning of the light sheet along the detection axis enabled fast dual-channel 3D imaging at subcellular resolution without mechanical sample disturbance at up to 8 Hz over a ∼300 µm × 40 µm × 50 µm volume. The two cell types were found to undergo electrically stimulated and spontaneous synchronized calcium transients and contraction. Electromechanical coupling improved with co-culture duration, with 50% of adult-CM coupled after 24 h of co-culture, compared to 19% after 4 h (p = 0.0305). Immobilization with para-nitroblebbistatin did not prevent calcium transient synchronization, with 35% and 36% adult-CM coupled in control and treated samples respectively (p = 0.91), indicating that electrical coupling can be maintained independently of mechanotransduction.

Adverse childhood experiences and adolescent drug use in the UK: The moderating role of socioeconomic position and ethnicity.

Rationale: There is a paucity of prospective UK studies exploring the role of Adverse Childhood Experiences (ACEs) on adolescent teenage drug use and even less is known about the complex interplay between ACEs and adolescent social, demographic, and economic characteristics. To address these gaps, we use rich longitudinal data from the nationally representative Millennium Cohort Study. Methods: Sex-stratified survey logistic regression modelling was applied using data from 9,476 adolescents and their parents to examine associations between ACEs between ages 3 and 14 years and drug use at ages 14 and 17 years. We a) explore the extent to which associations are robust to adjustment for ethnicity, family income, parental social class, and parental education, b) examine whether associations differ by these factors, and c) estimate the proportion of drug use at ages 14 and 17 years attributable to ACEs after controlling for these factors. Results: Half of MCS cohort members had been exposed to at least one ACE and approximately 1 in 11 were exposed to 3+ ACEs. Multivariable analyses suggest that ACEs were associated with a higher likelihood of drug use at age 14 than age 17, especially for girls. No evidence was found that either advantaged socio-economic position or ethnicity acted as a buffer against the negative effects of ACEs in relation to adolescent drug use. Finally, we found that prevention of exposure to sexual violence, bullying and violence within the household (if causal) is more important for girls' drug use at age 14 than age 17. Conclusions: ACEs are associated with adolescent drug use with potential consequences on wider aspects of young people's lives, regardless of their social, ethnic, or economic background, adding further urgency to the need to reduce the incidence of these negative experiences.

Parental education and youth suicidal behaviours: a systematic review and meta-analysis.

AIMS: Lower parental education has been linked to adverse youth mental health outcomes. However, the relationship between parental education and youth suicidal behaviours remains unclear. We explored the association between parental education and youth suicidal ideation and attempts, and examined whether sociocultural contexts moderate such associations. METHODS: We conducted a systematic review and meta-analysis with a systematic literature search in PubMed, PsycINFO, Medline and Embase from 1900 to December 2020 for studies with participants aged 0-18, and provided quantitative data on the association between parental education and youth suicidal ideation and attempts (death included). Only articles published in English in peer-reviewed journals were considered. Two authors independently assessed eligibility of the articles. One author extracted data [e.g. number of cases and non-cases in each parental education level, effect sizes in forms of odds ratios (ORs) or beta coefficients]. We then calculated pooled ORs using a random-effects model and used moderator analysis to investigate heterogeneity. RESULTS: We included a total of 59 articles (63 study samples, totalling 2 738 374 subjects) in the meta-analysis. Lower parental education was associated with youth suicidal attempts [OR = 1.12, 95% Confidence Interval (CI) = 1.04-1.21] but not with suicidal ideation (OR = 1.05, 95% CI = 0.98-1.12). Geographical region and country income level moderated the associations. Lower parental education was associated with an increased risk of youth suicidal attempts in Northern America (OR = 1.26, 95% CI = 1.10-1.45), but with a decreased risk in Eastern and South-Eastern Asia (OR = 0.72, 95% CI = 0.54-0.96). An association of lower parental education and increased risk of youth suicidal ideation was present in high- income countries (HICs) (OR = 1.14, 95% CI = 1.05-1.25), and absent in low- and middle-income countries (LMICs) (OR = 0.91, 95% CI = 0.77-1.08). CONCLUSIONS: The association between youth suicidal behaviours and parental education seems to differ across geographical and economical contexts, suggesting that cultural, psychosocial or biological factors may play a role in explaining this association. Although there was high heterogeneity in the studies reviewed, this evidence suggests that the role of familial sociodemographic characteristics in youth suicidality may not be universal. This highlights the need to consider cultural, as well as familial factors in the clinical assessment and management of youth's suicidal behaviours in our increasingly multicultural societies, as well as in developing prevention and intervention strategies for youth suicide.

Power on: The rapid transition of a large interdisciplinary behavioral health department to telemental health during the COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic necessitated a rapid transition to telemental health (TMH) for behavioral health services in the behavioral health department of a large integrated primary care organization. Although the COVID-19 pandemic was the initial trigger for rapid organizational change, systems were developed with a focus on longer term scalability and sustainability. METHODS: This paper discusses the process of organizational change within our healthcare delivery system using the Strengths, Opportunities, Aspirations, and Results (SOAR) framework. Within this framework a structured mixed methods survey of 38 clinicians representing 5 different disciplines was conducted. Internal and survey data were analyzed to evaluate and guide the iterative change process. RESULTS: The majority of BH clinicians reported that they were as or more effective with TMH. The transition to TMH in our organization resulted in increased access to care, with a 10.3% increase in BH visit completions. The transition to TMH may benefit clinician work-life balance, but requires resources to support clinical, technological, and communication/teamwork changes. IMPLICATIONS/CONCLUSIONS: TMH is a feasible treatment modality for integrated care settings. It is cost-effective and well-accepted by clinicians. The SOAR framework can be used to guide rapid organizational change and ongoing QI processes.

Air pollution and trajectories of adolescent conduct problems: the roles of ethnicity and racism; evidence from the DASH longitudinal study.

PURPOSE: No known UK empirical research has investigated prospective associations between ambient air pollutants and conduct problems in adolescence. Ethnic minority children are disproportionately exposed to structural factors that could moderate any observed relationships. This prospective study examined whether exposure to PM2.5 and NO2 concentrations is associated with conduct problems in adolescence, and whether racism or ethnicity moderate such associations. METHODS: Longitudinal associations between annual mean estimated PM2.5 and NO2 concentrations at the residential address and trajectories of conduct problems, and the potential influence of racism and ethnicity were examined school-based sample of 4775 participants (2002-2003 to 2005-2006) in London, using growth curve models. RESULTS: Overall, in the fully adjusted model, exposure to lower concentrations of PM2.5 and NO2 was associated with a decrease in conduct problems during adolescence, while exposure to higher concentrations was associated with a flattened trajectory of conduct symptoms. Racism amplified the effect of PM2.5 (ß = 0.05 (95% CI 0.01 to 0.10, p < 0.01)) on adolescent trajectories of conduct problems over time. At higher concentrations of PM2.5, there was a divergence of trajectories of adolescent conduct problems between ethnic minority groups, with White British and Black Caribbean adolescents experiencing an increase in conduct problems over time. CONCLUSION: These findings suggest that the intersections between air pollution, ethnicity, and racism are important influences on the development of conduct problems in adolescence.

Validation of a combined ELISA to detect IgG, IgA and IgM antibody responses to SARS-CoV-2 in mild or moderate non-hospitalised patients.

BACKGROUND: Frequently SARS-CoV-2 results in mild or moderate disease with potentially lower concentrations of antibodies compared to those that are hospitalised. Here, we validated an ELISA using SARS-CoV-2 trimeric spike glycoprotein, with targeted detection of IgG, IgA and IgM (IgGAM) using serum and dried blood spots (DBS) from adults with mild or moderate disease. METHODS: Targeting the SARS-CoV-2 trimeric spike, a combined anti-IgG, IgA and IgM serology ELISA assay was developed using 62 PCR-confirmed non-hospitalised, mild or moderate COVID-19 samples, ≥14 days post symptom onset and 624 COVID-19 negative samples. The assay was validated using 73 PCR-confirmed non-hospitalised, mild or moderate COVID-19 samples, ≥14 days post symptom onset and 359 COVID-19 negative serum samples with an additional 81 DBSs. The assay was further validated in 226 PCR-confirmed non-hospitalised, mild or moderate COVID-19 samples, ≥14 days post symptom onset and 426 COVID-19 negative clinical samples. RESULTS: A sensitivity and specificity of 98.6% (95% CI, 92.6-100.0), 98.3% (95% CI, 96.4-99.4), respectively, was observed following validation of the SARS-CoV-2 ELISA. No cross-reactivities with endemic coronaviruses or other human viruses were observed, and no change in results were recorded for interfering substances. The assay was stable at temperature extremes and components were stable for 15 days once opened. A matrix comparison showed DBS to correlate with serum results. Clinical validation of the assay reported a sensitivity of 94.7% (95% CI, 90.9-97.2%) and a specificity of 98.4% (95% CI, 96.6-99.3%). CONCLUSIONS: The human anti-IgGAM SARS-CoV-2 ELISA provides accurate and sensitive detection of SARS-CoV-2 antibodies in non-hospitalised adults with mild or moderate disease. The use of dried blood spots makes the assay accessible to the wider community.

The potential utility of abbreviated breast MRI (FAST MRI) as a tool for breast cancer screening: a systematic review and meta-analysis.

AIM: To synthesise evidence comparing abbreviated breast magnetic resonance imaging (abMRI) to full-protocol MRI (fpMRI) in breast cancer screening. MATERIALS AND METHODS: A systematic search was undertaken in multiple databases. Cohort studies without enrichment, presenting accuracy data of abMRI in screening, for any level of risk (population, moderate, high risk) were included. Level of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE). Meta-analyses (bivariate random effects model) were performed for abMRI, with fpMRI and histology from fpMRI-positive cases as reference standard, and with follow-up to symptomatic detection added to the fpMRI. The review also covers evidence comparing abMRI with mammographic techniques. RESULTS: The title and abstract review retrieved 23 articles. Five studies (six articles) were included (2,763 women, 3,251 screening rounds). GRADE assessment of the evidence was very low because the reference standard was interpreted with knowledge of the index test and biopsy was not obtained for all abMRI positives. The overall sensitivity for abMRI, with fpMRI (and histology for fpMRI positives) as reference standard, was 94.8% (95% confidence interval [CI] 85.5-98.2) and specificity as 94.6% (95% CI: 91.5-96.6). Three studies (1,450 women, 1,613 screening rounds) presented follow-up data, enabling comparison between abMRI and fpMRI. Sensitivities and specificities for abMRI did not differ significantly from those for fpMRI (p=0.83 and p=0.37, respectively). CONCLUSION: A very low level of evidence suggests abMRI could be accurate for breast cancer screening. Research is required, with follow-up to interval cancer, to determine the effect its use could have on clinical outcome.

A systematic review of the effect of dietary pulses on microbial populations inhabiting the human gut.

Pulses are dry leguminous crops consisting of beans, lentils, chickpeas, and peas. They are a broad category of food that are often aggregated when their contribution to healthy dietary patterns are disseminated. However, the different genera and varieties of pulses vary in composition and are consumed in different amounts, largely dictated by geographic region and ethnicity. Given the number of pulse-derived components, including fibre, that have the capacity to alter the composition of the gut microbiome, the objective of this study was to systematically review dietary pulses and pulse-derived ingredients as a broader food group, to determine their effect on gut microbiota in humans. Major scientific databases were used to conduct the search, which spanned from 1990 until February 2019. The search strategy identified 2,444 articles and five studies were included in this analysis. Two studies used whole pulses (chickpeas and pinto beans), one study used cooked navy bean powder, and the two remaining studies used pulse-derived fibre (lupin or yellow pea hulls). Although inconsistent, some studies demonstrated that whole pulses (pinto beans and chickpeas), cooked navy bean powder, and pulse-derived fibre (lupin kernel fibre), did impose changes to the microbiota that inhabit the human large intestine. However, there was considerable variability concerning the methodologies and endpoints used to decipher the observed effects on the abundance, diversity, and/or richness of specific microbiota or the microbiome. More extensive human studies that directly link the effects of specific types of pulses on the gastrointestinal microbial environment to health outcomes in the host are required.

Investigation of the safety and feasibility of AAV1/SERCA2a gene transfer in patients with chronic heart failure supported with a left ventricular assist device - the SERCA-LVAD TRIAL.

The SERCA-LVAD trial was a phase 2a trial assessing the safety and feasibility of delivering an adeno-associated vector 1 carrying the cardiac isoform of the sarcoplasmic reticulum calcium ATPase (AAV1/SERCA2a) to adult chronic heart failure patients implanted with a left ventricular assist device. The SERCA-LVAD trial was one of a program of AAV1/SERCA2a cardiac gene therapy trials including CUPID1, CUPID 2 and AGENT trials. Enroled subjects were randomised to receive a single intracoronary infusion of 1 × 1013 DNase-resistant AAV1/SERCA2a particles or a placebo solution in a double-blinded design, stratified by presence of neutralising antibodies to AAV. Elective endomyocardial biopsy was performed at 6 months unless the subject had undergone cardiac transplantation, with myocardial samples assessed for the presence of exogenous viral DNA from the treatment vector. Safety assessments including ELISPOT were serially performed. Although designed as a 24 subject trial, recruitment was stopped after five subjects had been randomised and received infusion due to the neutral result from the CUPID 2 trial. Here we describe the results from the 5 patients at 3 years follow up, which confirmed that viral DNA was delivered to the failing human heart in 2 patients receiving gene therapy with vector detectable at follow up endomyocardial biopsy or cardiac transplantation. Absolute levels of detectable transgene DNA were low, and no functional benefit was observed. There were no safety concerns in this small cohort. This trial identified some of the challenges of performing gene therapy trials in this LVAD patient cohort which may help guide future trial design.

Personalising screening of sight-threatening diabetic retinopathy - qualitative evidence to inform effective implementation.

BACKGROUND: Internationally, systematic screening for sight-threatening diabetic retinopathy (STDR) usually includes annual recall. Researchers and policy-makers support extending screening intervals, citing evidence from observational studies with low incidence rates. However, there is little research around the acceptability to people with diabetes (PWD) and health care professionals (HCP) about changing eye screening intervals. METHODS: We conducted a qualitative study to explore issues surrounding acceptability and the barriers and enablers for changing from annual screening, using in-depth, semistructured interviews analysed using the constant comparative method. PWD were recruited from general practices and HCP from eye screening networks and related specialties in North West England using purposive sampling. Interviews were conducted prior to the commencement of and during a randomised controlled trial (RCT) comparing fixed annual with variable (6, 12 or 24 month) interval risk-based screening. RESULTS: Thirty PWD and 21 HCP participants were interviewed prior to and 30 PWD during the parallel RCT. The data suggests that a move to variable screening intervals was generally acceptable in principle, though highlighted significant concerns and challenges to successful implementation. The current annual interval was recognised as unsustainable against a backdrop of increasing diabetes prevalence. There were important caveats attached to acceptability and a need for clear safeguards around: the safety and reliability of calculating screening intervals, capturing all PWD, referral into screening of PWD with diabetic changes regardless of planned interval. For PWD the 6-month interval was perceived positively as medical reassurance, and the 12-month seen as usual treatment. Concerns were expressed by many HCP and PWD that a 2-year interval was too lengthy and was risky for detecting STDR. There were also concerns about a negative effect upon PWD care and increasing non-attendance rates. Amongst PWD, there was considerable conflation and misunderstanding about different eye-related appointments within the health care system. CONCLUSIONS: Implementing variable-interval screening into clinical practice is generally acceptable to PWD and HCP with important caveats, and misconceptions must be addressed. Clear safeguards against increasing non-attendance, loss of diabetes control and alternative referral pathways are required. For risk calculation systems to be safe, reliable monitoring and clear communication is required.

Influence of pH on the activity of finafloxacin against extracellular and intracellular Burkholderia thailandensis, Yersinia pseudotuberculosis and Francisella philomiragia and on its cellular pharmacokinetics in THP-1 monocytes.

OBJECTIVES: Burkholderia pseudomallei, Yersinia pestis and Francisella tularensis are facultative intracellular bacteria causing life-threatening infections. We have (a) compared the activity of finafloxacin (a fluoroquinolone in development showing improved activity at acidic pH) with that of ciprofloxacin, levofloxacin and imipenem against the extracellular and intracellular (THP-1 monocytes) forms of infection by attenuated surrogates of these species (B. thailandensis, Y. pseudotuberculosis, F. philomiragia) and (b) assessed finafloxacin cellular pharmacokinetics (accumulation, distribution, efflux). METHODS: Bacteria in broth or in infected monocytes were exposed to antibiotics at pH 7.4 or 5.5 for 24 hr. Maximal relative efficacies (Emax) and static concentrations (Cs) were calculated using the Hill equation (concentration-response curves). Finafloxacin pharmacokinetics in cells at pH 7.4 or 5.5 was investigated using 14C-labelled drug. RESULTS: Extracellularly, all drugs sterilized the cultures, with finafloxacin being two to six times more potent at acidic pH. Intracellularly, Emax reached the limit of detection (4-5 log10 cfu decrease) for finafloxacin against all species, but only against B. thailandensis and F. philomiragia for ciprofloxacin and levofloxacin, while imipenem caused less than 2 log10 cfu decrease for all species. At acid pH, Cs shifted to two to five times lower values for finafloxacin and to one to four times higher values for the other drugs. Finafloxacin accumulated in THP-1 cells by approximately fivefold at pH 7.4 but up to 20-fold at pH 5.5, and distributed in the cytosol. CONCLUSIONS: Fluoroquinolones have proven to be effective in reducing the intracellular reservoirs of B. thailandensis, Y. pseudotuberculosis and F. philomiragia, with finafloxacin demonstrating an additional advantage in acidic environments.

La Crosse virus: a scoping review of the global evidence.

Urbanisation and climate change are altering the pattern of California serogroup viruses in North America. As La Crosse virus (LACV) is the most pathogenic of the California serogroup, it is important to identify changes in distribution, transmission and pathogenesis. A scoping review (ScR) was prioritised to summarise the global evidence on LACV. A comprehensive search strategy was used, identified references were screened for relevance and relevant articles were characterised. Each step was conducted by two independent reviewers using pre-tested forms. Analysis identified areas of research saturation and gaps. The ScR included 481 research articles that were mostly journal articles (78.2%) conducted in North America (90.9%) from 1969 to 2016. Most evidence focused on epidemiology (44.9%), virus characteristics (25.8%), transmission conditions (18.7%) and pathogenesis of LACV in hosts (18.3%). Fewer studies evaluated the accuracy of diagnostic tests (8.7%), the efficacy of treatments (3.5%), prevention and control strategies (3.1%), the economic burden of infection (0.6%) and social impact (0.2%) of LACV. None of the literature predicted the impact of climate change on LACV, nor were any cases reported in Canada. These findings are intended to guide research to close knowledge gaps and inform evidence-based decisions surrounding activities for the prevention and control of LACV.

Measurement of Typhi Vi antibodies can be used to assess adaptive immunity in patients with immunodeficiency.

Vaccine-specific antibody responses are essential in the diagnosis of antibody deficiencies. Responses to Pneumovax II are used to assess the response to polysaccharide antigens, but interpretation may be complicated. Typhim Vi® , a polysaccharide vaccine for Salmonella typhoid fever, may be an additional option for assessing humoral responses in patients suspected of having an immunodeficiency. Here we report a UK multi-centre study describing the analytical and clinical performance of a Typhi Vi immunoglobulin (Ig)G enzyme-linked immunosorbent assay (ELISA) calibrated to an affinity-purified Typhi Vi IgG preparation. Intra- and interassay imprecision was low and the assay was linear, between 7·4 and 574 U/ml (slope = 0·99-1·00; R2  > 0·99); 71% of blood donors had undetectable Typhi Vi IgG antibody concentrations. Of those with antibody concentrations  > 7·4 U/ml, the concentration range was 7·7-167 U/ml. In antibody-deficient patients receiving antibody replacement therapy the median Typhi Vi IgG antibody concentrations were  < 25 U/ml. In vaccinated normal healthy volunteers, the median concentration post-vaccination was 107 U/ml (range 31-542 U/ml). Eight of eight patients (100%) had post-vaccination concentration increases of at least threefold and six of eight (75%) of at least 10-fold. In an antibody-deficient population (n = 23), only 30% had post-vaccination concentration increases of at least threefold and 10% of at least 10-fold. The antibody responses to Pneumovax II and Typhim Vi® correlated. We conclude that IgG responses to Typhim Vi® vaccination can be measured using the VaccZyme Salmonella typhi Vi IgG ELISA, and that measurement of these antibodies maybe a useful additional test to accompany Pneumovax II responses for the assessment of antibody deficiencies.

The trajectory of positive psychological change in a head and neck cancer population.

A stressful event may be sufficient to challenge a strongly held set of assumptions about the world and the self. In some people this may lead to post-traumatic stress disorder (PTSD) and in others to positive psychological change (PPC), whereby a person's reactions to the challenge are beneficial. Little research has investigated PPC in people who have had head and neck cancer (HNC). The aim of this study was to identify demographic, clinical, and psychological factors associated with PPC over time. A cross-sequential study collected data over 5 years. Participants were sent the Silver Lining Questionnaire (SLQ; a measure of PPC), the University of Washington HNC quality of life measure, and the Medical Outcomes Short-Form 12 each year. Additional data were collected from clinical records. Analysis using linear mixed-effects modelling revealed that participants with lower stage tumours and those who only had a surgical intervention reported greater PPC over time. Multivariable modelling adjusting for psychosocial variables found that PPC had a quadratic relationship with time since diagnosis, increasing initially and levelling off after 18 months. These findings build on the minimal PPC research with people following HNC. In particular it demonstrates a model of trajectories for the development of PPC longitudinally over time.

Molecular pathways of oestrogen receptors and ß-adrenergic receptors in cardiac cells: Recognition of their similarities, interactions and therapeutic value.

Oestrogen receptors (ERs) and ß-adrenergic receptors (ßARs) play important roles in the cardiovascular system. Moreover, these receptors are expressed in cardiac myocytes and vascular tissues. Numerous experimental observations support the hypothesis that similarities and interactions exist between the signalling pathways of ERs (ERα, ERß and GPR30) and ßARs (ß1 AR, ß2 AR and ß3 AR). The recently discovered oestrogen receptor GPR30 shares structural features with the ßARs, and this forms the basis for the interactions and functional overlap. GPR30 possesses protein kinase A (PKA) phosphorylation sites and PDZ binding motifs and interacts with A-kinase anchoring protein 5 (AKAP5), all of which enable its interaction with the ßAR pathways. The interactions between ERs and ßARs occur downstream of the G-protein-coupled receptor, through the Gαs and Gαi proteins. This review presents an up-to-date description of ERs and ßARs and demonstrates functional synergism and interactions among these receptors in cardiac cells. We explore their signalling cascades and the mechanisms that orchestrate their interactions and propose new perspectives on the signalling patterns for the GPR30 based on its structural resemblance to the ßARs. In addition, we explore the relevance of these interactions to cell physiology, drugs (especially ß-blockers and calcium channel blockers) and cardioprotection. Furthermore, a receptor-independent mechanism for oestrogen and its influence on the expression of ßARs and calcium-handling proteins are discussed. Finally, we highlight promising therapeutic avenues that can be derived from the shared pathways, especially the phosphatidylinositol-3-OH kinase (PI3K/Akt) pathway.

The impact of treatment for head and neck cancer on positive psychological change within a year of completing treatment.

Head and neck cancer carries a high level of morbidity and mortality. So why could anyone find having such a disease a positive event? The adversity hypothesis of "what doesn't kill you makes you stronger" suggests that people can use adversity to develop as human beings. This positive psychological change has received little attention in relation to head and neck cancer. Responses to the Silver Lining Questionnaire, University of Washington Quality of Life Questionnaire, and Short-Form 12 were collected from a postal survey, 3 to 12 months after the completion of treatment for head and neck cancer. Fifty-two (63%) people returned the survey and were included in the analysis. Time since completion of therapy did not show any relationship with positive psychological change. Tumour stage and treatment regimen both had a relationship with positive change. Participants with lower stage tumours had higher levels of positive change than those with tumours of higher stages. Participants who had surgery alone reported more positive change than those who had surgery with radiotherapy. A social factor related to greater change was being married or living with a partner when compared to living alone. Further research would aid the identification of bio-psychosocial factors that influence the development of positive psychological change and inform the development of rehabilitation interventions.