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Background: To meet the health care challenges and increasing population health demands of today and the future, the Missouri Center for Nursing developed the Culture of Health Initiative Project (CHIP). Method: Phase one surveys examined 33 nurse leaders' responses to the population health knowledge and training needs of nurses in their organizations. In phase two, 71 nurse leaders' and practicing nurses' responses from the Population Health Nursing Skills Survey provided insight into the education needs of Missouri nurses. Results: Findings identified a lack of available education and resources related to nursing, limited knowledge of concepts among nursing leaders, and a need for flexibility in the format and content to educate nurses in all types of nursing practice. Conclusion: Professional development practitioners must collaborate with nurses and nurse leaders, in all settings, to meet the learning needs necessary for Culture of Health competence. [ J Contin Educ Nurs . 2020;51(12):568–573.]

In Staphylococcus aureus, the two-component system SaeRS is responsible for regulating various virulence factors essential for the success of this pathogen. SaeRS can be stimulated by neutrophil-derived products but has also recently been shown to be inactivated by the presence of free fatty acids. A mechanism for how fatty acids negatively impacts SaeRS has not been described. We found that unsaturated fatty acids, as well as fatty acids not commonly found in Staphylococcal membranes, prevent the activation of SaeRS at a lower concentration than their saturated counterparts. These fatty acids can negatively impact SaeRS without altering the respiratory capacity of the bacterium. To uncover a potential mechanism for how fatty acids impact SaeRS function/activity, we utilized a naturally occurring point mutation found in S. aureus as well as chimeric SaeS proteins. Using these tools, we identified that the native transmembrane domains of SaeS dictate the transcriptional response to fatty acids in S. aureus. Our data support a model where free fatty acids alter the activity of the two-component system SaeRS directly through the sensor kinase SaeS and is dependent on the transmembrane domains of the protein.

SummaryBackgroundThe world is at the cusp of experiencing local/regional hot-spots and spikes of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes COVID-19 disease. We aimed to formulate an applicable epidemiological model to accurately predict and forecast the impact of local resurgence and outbreaks to guide the local healthcare demand and capacity, policy making, and public health decisions.MethodsThe model utilised the aggregated daily COVID-19 situation reports (including counts of daily admissions, discharges, and occupancy) from the local NHS hospitals and Covid-19 related weekly deaths in hospitals and other settings in Sussex (population 1-7M), Southeast England. These datasets corresponded to the first wave of COVID-19 infections from 24 March-15 June 2020. The counts of death registrations and regional population estimates were obtained from the Office of National Statistics. A novel epidemiological predictive and forecasting model was then derived based on the local/regional surveillance data. Through a rigorous inverse parameter inference approach, the model parameters were estimated by fitting the model to the data in an optimal sense and then subsequently validated to make predictions subject to 95% confidence.FindingsThe inferred parameters were physically reasonable and matched up to the widely used parameter values derived from the national datasets. Unlike other predictive models, which are restricted to a couple of days, our model can predict local hospital admissions, discharges (including deaths) and occupancy for the next 10, 20, and 30 days at the local level.InterpretationWe have demonstrated that by using local/regional data, our predictive and forecasting model can be utilised to guide the local healthcare demand and capacity, policy making, and public health decisions to mitigate the impact of COVID-19 on the local population. Understanding how future COVID-19 spikes/waves could possibly affect the regional populations empowers us to ensure the timely commissioning and organisation of services. Primary care and community services can be guided by the projected number of infectious and recovered patients and hospital admissions/discharges to project discharge pathways to bedded and community settings, thus allowing services to understand their likely load in future spikes/waves. The flexibility of timings in the model, in combination with other early warning systems, produces a timeframe for these services to prepare and isolate capacity for likely and potential demand within regional hospitals. The model also allows local authorities to plan potential mortuary capacity and understand the burden on crematoria and burial services. The model algorithms have been integrated into a web-based multi-institutional toolkit, which can be used by NHS hospitals, local authorities, and public health departments in other regions of the UK and elsewhere. The parameters, which are locally informed, form the basis of predicting and forecasting exercises accounting for different scenarios and impact of COVID-19 transmission.FundingThis study was supported by the Higher Education Innovation Fund through the University of Sussex (ECF, JVY, AMa). This work was partly supported by the Global Challenges Research Fund through the Engineering and Physical Sciences Research Council grant number EP/T00410X/1: UK-Africa Postgraduate Advanced Study Institute in Mathematical Sciences (AMa, ECF). ECF is supported by the Wellcome Trust grant number 204833/Z/16/Z.Research in contextEvidence before this studySince the beginning of the COVID-19 pandemic, healthcare managers and policy makers relied on epidemiological models based on national datasets to predict and mitigate the spread of the disease. The performance of these models has not always been validated against the available data, and they depend strongly on the values for the model parameters. Statistical models, e.g. those arising from time-series analysis, lack the temporal dynamics of the compartmentalised epidemiological model for the evolution of the disease and thus fail to capture the evolution far into the future with great accuracy. Compartmental models, on the other hand, capture the underlying dynamics of an infectious disease but typically use parameters estimated using datasets from other regions or countries, thus lacking the ability to capture local demographics and policy and therefore lack predicting local dynamics with accuracy.Added value of this studyAlthough our compartmental model follows standard SEIR-D model structure, the inference algorithm described and applied in this report is novel, along with the prediction technique used to validate the model. We checked bioRxiv, medRxiv, and arXiv up to the end of August 2020 using the terms “mathematical inference”, “COVID-19”, and “SIR” and found that there is a substantial use of Bayesian approaches to fit parameters but none that use the combination of statistical approaches with compartmental models, hence the originality of our work. We designed a compartmentalised epidemiological model that captures the basic dynamics of the COVID-19 pandemic and revolves around the data that are available at the local/regional level. We estimated all the parameters in the model using the local surveillance data, and in consequence, our parameters reflect the characteristics of the local population. Furthermore, we validated the predictive power of the model by using only a subset of the available data to fit the parameters. To the best of our knowledge, this is the first study which combines statistical approaches with a compartmental model and as such benefits greatly from the ability to predict and forecast much further into the future using the dynamical structure of the compartmental model with a relatively much higher accuracy than previously presented in the literature. This research sets the gold-standard benchmark by laying the framework for future adaptations to the model when more precise (and comprehensive) datasets are made available.Implications of all the available evidenceThe predictive power of our model outperforms previously available models for local forecasting of the impact of COVID-19. Using local models, rather than trying to use national models at a local scale, ensures that the model reflects the local demographics and provides reliable local-data-driven predictions to guide the local healthcare demand and capacity, policy making, and public health decisions to mitigate the impact of COVID-19 on the local population. Local authorities can use these results for the planning of local hospital demand as well as death management services by developing scenario-based analysis to which different values of the reproduction number R exiting a COVID-19 lockdown are assumed and results, such as maximum hospital occupancy, are compared to the first wave to establish a potential strain on resources. This can work as an early warning detection system to see what value of R that is currently followed, which in turn informs the relevant capacity and resources needed to mitigate the impact of COVID-19. The Web toolkit developed by us as a result of this study (https://alpha.halogen-health.org) demonstrates the predictive power of our model as well as its flexibility with the scenario-based analysis. Although our model is based on the data from Sussex, using similar variables/data from other regions in our model would derive respective COVID-19 model parameters, and thus enable similar scenario-based investigations to predict and forecast the impact of local resurgence to guide the local healthcare demand and capacity, policy making, and public health decisions.

Staphylococcus aureus is a leading cause of skin and soft tissue infections (SSTIs). While studies have examined how the immune system responds to S. aureus SSTIs, most are limited in scope to a single time point or outcome. To set a foundation for future studies, we conducted a S. aureus skin infection experiment using female C57BL/6J mice and USA300 S. aureus to examine the host-pathogen interface up to 15 days post-infection (d.p.i.). We measured lesion size, bacterial titers, local cytokine and chemokine levels, phenotyped responding leukocytes, and collected skin for histopathologic analysis and Gram staining. Lesions were largest at 1 d.p.i. with peak necrotic tissue area at 3 d.p.i. and were largely resolved by 15 d.p.i. IL-6, IL-4, CCL2, and IL-1β were highest during early infection, while IL-17A/F peaked 7 days post-infection. Neutrophils were abundant in the skin throughout the infection and were the primary immune cell present until 9 d.p.i. Histopathologic analysis demonstrated swift and extensive keratinocyte death and robust and persistent neutrophil infiltration. Gram staining revealed subdermal S. aureus colonization and, later, limited migration into upper skin layers. Most leukocyte subsets decreased within 8h after infection and returned during wound resolution coincident with declining bacterial titers. These (re)emerging leukocytes included CD4+ T cells, innate lymphoid cells, inflammatory monocytes, macrophages, and dendritic cells. Collectively, these data illustrate a dynamic immune response to S. aureus skin infections and provide a foundation for further studies characterizing the host-pathogen interface. This research was supported by funding from the National Institute of Allergy and Infectious Diseases (NIAID) award R01AI121073 as well as pilot project grants from K-INBRE (P20GM130418) and University of Kansas Chemical Biology of Infectious Disease COBRE grant P20GM113117 to JLB. We acknowledge the Kansas Intellectual and Developmental Disabilities Research Center Histology Core which is sponsored in part by the NIH/NICHD (U54 HD090216) and the Flow Cytometry Core Laboratory, which is sponsored, in part, by the NIH/NIGMS COBRE grant P30 GM103326 and the NIH/NCI Cancer Center grant P30 CA168524.

Objectives: To examine how Americans’ opinions of the relative seriousness of various health problems have changed over time and to quantify the public’s preferences for research prioritization. Methods: We conducted a survey that asked respondents to rate the seriousness of 80 health problems on a four-point Likert scale (“very serious problem,” “somewhat serious problem,” “not too serious of a problem,” or “not a problem at all”). Results were compared to past surveys from 2001 and 2013 that examined the same set of health problems (with the exception of COVID-19). The survey also included 15 MaxDiff questions that asked respondents to select the health problems they considered most and least important for research funding. Respondents were recruited from the KnowledgePanel, a nationally-representative sample of American households. Results: A total of 768 adults competed the survey between September 3 and 14, 2020. The health problems that Americans consider to be very serious generally align with the leading causes of death and noncommunicable diseases like heart disease (rated “very serious” by 55.3% of sample), diabetes (45.0%), and mental health (e.g., mental illness - 53.6%;depression - 50.7%);however, several social determinants of health (e.g., violence - 62.6%;racial discrimination - 52.9%) are also identified. COVID-19 was a perhaps unsurprising top priority (ranked 3rd at 62.4%), while cancer remains the highest (ranked first at 65.5%) and a persistent priority for research funding. Conclusions: Americans consider a diverse set of health problems to be very serious, with recognition of social determinants of health rising. Our findings offer guidance as to the disease areas in which innovations would bring the greatest value to patients and society and also offers affirmations of the relief brought by recent innovations.

Asthma affects 300 million people across all age-groups and ethnicities and is the most common chronic condition affecting children1, 2. In the UK, the health care costs associated with asthma are estimated at £1.1 billion, however this amount typically excludes some societal costs (e.g. absence from work to care for children)3. The total number of days missed from school in England in the 2017/18 academic year was 59.1 million of which 54.7% were due to illness4 although the reasons for those illness-related absences are unknown. Given the high proportion of children with asthma and the fact that school absences are associated with low levels of achievement6, the primary aim of this study was to measure the proportion of asthma-related absences in school children and describe the factors reported by parents that predispose their children to these school absences. The secondary aim was to explore parents’ and school staff views on extending an app currently used for reporting school absences to one that might also provide tailored interventions.

EPI-Net, Combacte-Magnet and EUCIC Group for SUSPIRE: F. Burkert, E. Carrara, M. von Cube, L. Drgona, K. Gilchrist, H. Goossens, S. Harbarth, D. Hequet, H. Jafri, G. Kahlmeter, S. Kuster, C. Luxemburger, M. McCarthy, M. Niks, A. Oualim, M. Poljak, O. Sandulescu, A. Schweiger, C. Vuong, I. Wiegand, A. Widmer, A. T. Witschi, G. Zanetti, W. Zingg., [Objectives] Surveillance is a key component of any control strategy for healthcare-associated infections (HAIs) and antimicrobial resistance (AMR), and public availability of methodologic aspects is crucial for the interpretation of the data. We sought to systematically review publicly available information for HAIs and/or AMR surveillance systems organized by public institutions or scientific societies in European countries., [Methods] A systematic review of scientific and grey literature following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines was performed. Information on HAIs and/or AMR surveillance systems published until 31 October 2016 were included., [Results] A total of 112 surveillance systems were detected; 56 from 20 countries were finally included. Most exclusions were due to lack of publicly available information. Regarding AMR, the most frequent indicator was the proportion of resistant isolates (27 of 34 providing information, 79.42%); only 18 (52.9%) included incidence rates; the data were only laboratory based in 33 (78.5%) of the 42 providing this information. Regarding HAIs in intensive care units, all 22 of the systems providing data included central line–associated bloodstream infections, and 19 (86.3%) included ventilator-associated pneumonia and catheter-associated urinary tract infections; incidence density was the most frequent indicator. Regarding surgical site infections, the most frequent procedures included were hip prosthesis, colon surgery and caesarean section (21/22, 95.5%)., [Conclusions] Publicly available information about the methods and indicators of the surveillance system is frequently lacking. Despite the efforts of European Centre for Disease Control and Prevention (ECDC) and other organizations, wide heterogeneity in procedures and indicators still exists., Funded by the Innovative Medicines Initiative (IMI), New Drugs for Bad Bugs (ND4BB) programme, European Union's Seventh Framework Programme (FP7/2007-2013) and EFPIA (European Federation of Pharmaceutical Industries and Association) companies' in-kind contribution (IMI 11th) under grant 115737, COMBACTE-MAGNET (Combatting bacterial resistance in Europe—Molecule against Gram negative infections). JRB and MDT receive funding for research from Ministerio de Economía y Competitividad, Instituto de Salud Carlos III, cofinanced by European Regional Development Fund (ERDF) ‘A way to achieve Europe,’ Spanish Network for the Research in Infectious Diseases (REIPI RD12/0015 and REIPI RD16/0016).

Background Subjective wellbeing (SW) is a construct that aims to explain people’s self-reported thoughts and feelings about various aspects of their life. The concept is now increasingly used by governments and policy makers as one of the key measures of societal progress, and to inform and direct social and public health policy. There is little information on the possible impact of low SW on mental health conditions. We examined data from a population-based cross-sectional survey to assess possible association between SW and major depression. Methods The study used data from the health and wellbeing survey (n=2035) conducted in Brighton and Hove in 2012. SW was determined according to the UK Office of National Statistics (ONS) validated measures/questions on life satisfaction, fulfilment, happiness and anxiety; and prevalence of major depression was determined by using the standard Short Form Survey Instrument (SF-36). Data were modeled using multiple logistic regression and the results are presented as adjusted odds ratio (OR) and corresponding 95% confidence interval (95% CI). Results In the multivariate analysis, all the four ONS validated measures of SW were significantly associated with the prevalence of major depression: low life satisfaction (OR=2.9, 95% CI: 2.1-3.9), unfulfillment (OR=2.4, 95% CI: 1.8-3.2), unhappiness (OR=1.7, 95% CI: 1.3-2.3), anxiety (OR=2.9, 95% CI: 2.3-3.6). Overall, individuals with low SW were about 2 times more likely to report prevalence of major depression. Conclusions This study shows that there is a strong association between low (self-reported) SW and prevalence of major depression. Further studies are needed to ascertain the impact of low SW on other mental health conditions. Considering that major depression is one of the leading causes of disability worldwide and a key contributor to the risk of suicide and ischemic heart disease, our findings highlight the importance and benefits of improving SW in individuals and populations. Key messages • Low (self-reported) subjective wellbeing is strongly associated with major depression. • Subjective wellbeing can be measured effectively to inform the development of social and public health policy to improve the health and wellbeing of individuals and populations.

Background The concept of wellbeing is now increasingly used as one of the key measures of societal progress, along with the traditional methods that are based on economic activity. Subjective wellbeing (SW) is a construct by which national wellbeing can be measured—this can inform development of health and social policy. The objective of this study was to determine the association between sociodemographic/personal factors and low subjective wellbeing. Methods Data from the health and wellbeing survey conducted in Brighton and Hove in 2012 (n=2035) were analysed. The survey included the Office of National Statistics (ONS) verified measure of SW, which consisted of four questions regarding life satisfaction, fulfilment, happiness and anxiety. Low SW was the outcome measure, the threshold of which was determined according to the Faculty of Public Health outcome framework. The survey also included a range of population measures, sixteen of which were chosen as explanatory variables. The analysis included descriptive statistics and multivariate logistic regression, using the SPSS statistical programme. Results are presented as adjusted odds ratio (OR) and corresponding 95% confidence interval (95% CI). Results In the multivariate analysis, poor general health (self-reported) was strongly associated with low SW: dissatisfaction with life (OR=3.9, 95% CI, 2.7-5.6), unfulfilled (3.4, 2.3-4.8), unhappiness (3.0, 2.1-4.2), anxiety (2.4, 1.7-3.3). Other factors significantly associated with low SW included: illness and disability, low social capital, lack of physical exercise, a history of self-harm, not owning a home, not being in a relationship and being middle aged. On the other hand, unemployment, deprivation and poor education were not associated with SW. Conclusion This study demonstrates that an individual’s SW is likely to be affected by a number of sociodemographic/personal factors. The limitations of this study include the extent of external validity, the lack of causality and potential selection and information bias. These findings are relevant to the design and delivery of policy aimed at improving the perception of wellbeing in individuals and the general population.

Background: Most chronic diseases are strongly associated with four modifiable behaviours: smoking, alcohol consumption, low fruit and vegetable consumption and physical inactivity. When established early in life, these lifestyle factors could persist in adulthood and predict the incidence of chronic diseases. Little is known about how these behaviours cluster together, and what factors are associated with their prevalence and clustering in individuals. The objective of this study was to ascertain the association between sociodemographic and personal factors and clustering of multiple health-risk behaviours in young people in the city of Brighton and Hove (population, 274,000) in Southeast England. Methods: Data from the Brighton and Hove Safe and Well at School Surveys (2011-2014) were analysed to examine the clustering of these behaviours in Year 10 and 11 pupils (n=10,099; aged 14-16 year). The results were weighted and studied in the context of sociodemographic/personal characteristics: gender, ethnicity, sexual orientation, deprivation, school year, feeling safe at school, enjoying school, been bullied at school, health problems, family problems, feeling happy, feeling anxious and feeling lonely. Results: The majority (97%) of pupils were engaged in either one or more unhealthy behaviours: about 58% were engaged in 1-2 and 39% were engaged in 3-4 unhealthy behaviours, respectively. Multiple regression analysis showed that a number of factors were significantly associated with the clustering of 3-4 health-risk behaviours in young people. These included: being in Year 11 (OR=2.0, 95% CI, 1.8-2.2), family problems (1.8, 1.6-2.0), being female (1.7, 1.5-1.9), not enjoying school (1.6, 1.4-1.8), and rarely/never feeling happy (1.3, 1.0-1.6). Conclusions: These findings highlight the need for modifications in community-based and in-school health and wellbeing programmes to decrease the prevalence and clustering of multiple health-risk behaviours in young people. Main messages: There is a need for effective programmes for young people to increase their awareness about health impacts of smoking and alcohol consumption, and beneficial effects of healthy diet and exercise. The study also highlights areas which require particular considerations while designing these programmes for young people.

This paper describes the development and operation of a rotating double effect absorption heat pump, which uses an aqueous lithium bromide solution as the absorbent and dry heat rejection. The design principles are outlined including the operation of the major components and the ways in which the integration of the processes has been achieved. The operation of the fluid management system is described. Experimental performance data are presented from laboratory testing for the machine operating as a chiller.

Background Most chronic diseases are strongly associated with four modifiable behaviours: smoking, alcohol consumption, low fruit and vegetable consumption and physical inactivity. Most of the research is directed into understanding how a single behaviour affects health; and relatively little is known about how these behaviours cluster together in the population, and how the prevalence of multiple lifestyle risk behaviours have changed over time. The objective of this study was to examine the clustering …

In a comparison of 27-year-old Pinus radiata D. Don on a nitrogen deficient coastal dune and growing with or without lupin plus fertiliser, mean wood density, earlywood density, and latewood density in individual annual growth rings were significantly lower in treated as compared to control stands. Latewood percentage showed a similar pattern of variation in relation to treatment and tree age when the ring was laid down. Wood density and latewood percentage increased radially from pith to bark, both increasing more rapidly in unfertilised compared to fertilised trees. Mean density, earlywood density, and latewood percentage were significantly related to tree nitrogen status, as reflected by foliar analysis undertaken in the year rings were laid down, and to ring age. Other foliar nutrients tested (P, K, Ca, Mg, B, Mn, Zn, Cu) did not appear to influence wood density when analysed in the presence of N. Wood density was high at this trial site by New Zealand standards, even in fertilised stands, which can be explained at least partly by the low foliar N levels at Woodhill Forest. These exceeded 1.2% only in stands younger than 5 years old. Thereafter, foliar N decreased to ≈1.2% in fertilised stands receiving 100 kg N/ha of fertiliser annually for 10 years, and 0.8% in unfertilised controls. Foliar N levels on recent sands typically fall in the range of 0.9–1.2% at Woodhill Forest, compared to 1.2–>1.5% in most other soil types in NZ. Effective rainfall at Woodhill also tends to be lower than other forest growing areas in New Zealand. At Woodhill, low rainfall during autumn/winter/spring was associated with high latewood percentage and, hence, high ring mean density, while low summer rainfall had the opposite effects.

This paper describes the development and operation of a rotating double effect absorption chiller, which uses an aqueous solution of mixed metal hydroxides as the absorbent. The design principles are outlined including the operation of the major components and the ways in which the integration of the processes has been achieved. The operation of the fluid management system is described. Experimental performance data are presented from laboratory testing for the machine operating as a chiller.

This paper reviews the past research, experimental techniques and scaling relationships used in the studies of oscillatory buoyant diffusion flames and reports an experimental investigation conducted to determine the pulsating characteristics of such flames. The experimental data were obtained by using three techniques, namely, pressure fluctuation measurements, thermal imaging and high-speed video photography. Present findings are compared with data sets reported in the literature and correlations for pulsation frequency suggested by previous studies are independently verified. Analysis of the experimental data on frequency of pulsations in different burners shows that for a fixed-diameter flame the pulsation frequency is almost independent of fuel flow rate. The equation f=1.68D-0.5 gives the best approximation for the relationship between pulsating frequency and diameter over a wide range of data. An alternative way of expressing the relationship between the key variables is St=0.52*(1/Fr)0.505. This proves to be a better way of expressing the relationship since it can include the effect of the fuel flow rate. Slight modifications to this expression allows prediction of flame oscillations under elevated/reduced gravity and isothermal buoyant plumes. This relationship and the observations of the present study confirm the hydrodynamic nature of flame puffing: interplay of buoyancy and fluid motion.

SUMMARY Twenty-one pathologists and technicians participated in a study evaluating the variation present in mitotic counts for prognostication of breast cancer. The participants counted the mitotic figures in 20 breast cancer samples from ten high power fields (mitotic activity index, MAI, giving the results in mitotic figures per 10 fields) and also made a correction for field size and area fraction o f the neoplastic epithelium to get the standardized mitotic index (volume fraction corrected mitotic index, or M/Vv index, giving the result in mitotic figures per square mm o f neoplastic epithelium). The difference in variation between the two methods was not big, but the standardized mitotic index (SMI) showed consistently smaller variation among all participants and different subgroups. Experienced pathologists had the highest variation in mitotic counts, and specially trained technicians, the lowest. The efficiency o f the mitotic counts in grading (the grading efficiency) was used to evaluate the mitotic counts. I n groups without special training for mitotic counts the mean grading efficiency was lower (experienced and training pathologists both on average had the potential to grade 88% o f the cases correctly) than in the group specially trained for the purpose (trained technicians had the potential to grade 9S% o f the cases correctly). Among the specially trained technicians, the grading efficiency was o f the same magnitude as the grading efficiency achieved in determining the S-Phase fraction of cells from paraffin embedded breast cancers by flow cytometry in different laboratories. The results suggest that special training is helpful in making mitotic counts more reproducible, and that in trained hands, the mitotic counts give results comparable to more sophisticated methods o f determining proli ferative activity in breast cancer.

The bisphosphonate drug APD (pamidronate, 3-amino-1-hydroxypropylidene-1,1-bisphosphonate) has been shown to bind to human plasma proteins. This was an unexpected observation since this hydrophilic, anionic drug is not typical of molecules that exhibit this characteristic. At a concentration of 5 micrograms/ml the extent of binding of APD to fresh human plasma in vitro was variable between subjects 30.2% +/- 8.5% (mean +/- S.D., n = 10). Binding was not influenced by the time or concentration of APD over the range 0.05-10.0 micrograms/ml. At 20 and 50 micrograms/ml some precipitation of APD occurred. Both calcium and iron play a role in the binding of APD to plasma proteins, addition of calcium to plasma increased the degree of binding of APD, whereas the calcium chelators EDTA and EGTA reduced the binding of APD. Similarly, addition of iron to plasma increased the binding and the inclusion of the iron chelator desferrioxamine diminished the binding of the drug. The effects of iron and desferrioxamine were less pronounced than those of calcium and EDTA, indicating that the majority of the binding involves calcium ions and a smaller contribution is made by ferric ions. The equilibrium dissociation constants (Kd) for APD binding to calcium and iron binding sites on plasma proteins were estimated to be 852 microM and 29 microM, respectively. Calcium binding sites were of high capacity but low affinity and the iron binding sites were of lower capacity and higher affinity. Electrophoresis of plasma proteins following incubation with [14C]APD revealed binding to the transferrin and globulin fractions. However, there was some dissociation of protein bound APD during the electrophoresis. The consequences of hypercalcaemia on the pharmacokinetics of APD are discussed.

Malignant testicular tumors are an important clinical problem, and ultrasound is the most frequently ordered imaging modality once a palpable scrotal mass is discovered. Numerous articles discussing the role of ultrasound in the evaluation of testicular pathology have confirmed the value of preoperative imaging. This article presents a review of imaging literature regarding testicular neoplasms, with an emphasis on correlation of gross and microscopic tumor pathology and imaging findings. Also included are sections on anatomy, epidemiology, histogenesis, and tumor markers.

To summarize the current literature on the association between biologic prognostic factors and therapeutic implications.To illustrate how these biologic factors are determined and how they can affect treatment, three patients' biologic profiles and their implications for the patients' choice of therapeutic approaches were analyzed. Immunohistochemical techniques combined with image analysis was used to evaluate estrogen receptors, progesterone receptors, proliferation index and erbB-2. Visual assessment was used to evaluate P glycoprotein (MDR1), EGFR and p53.Data from the literature stress the importance of biologic profiles for defining tumor behavior and patient management. The examples of patients' biologic factors illustrated the possible importance of these factors for helping to design treatment.Today the data on the association of patient response to chemotherapy and molecular markers are only starting to accumulate. A larger database is needed for a more precise estimation of response probability in order to help physicians decide between treatment options.

Background Although childhood overweight and obesity rates have been falling in England in recent years, they remain an important public health concern because of the association between adolescent obesity and increased ill health risks in adult life including an increased risk of mortality from all causes independent of adult weight. Early intervention is important since behaviours contributing to obesity, higher energy diet and increased sedentary behaviour, are also prevalent during early childhood. We have conducted an epidemiological analysis of routine data collected at birth to examine the factors associated with overweight and obesity in children aged 10-11 years. Methods Administrative records of children in aged 10-11 years, measured between September 2006 and July 2010, as part of the National Child Measurement Programme in a large area on the South East coast of England were examined. Of the 19,924 children in the study with a valid height and weight measurement, 29% were overweight/obese. Factors identified from the literature as potential predictors of childhood overweight or obesity were extracted, where recorded. These are age; birth weight; gender; maternal smoking; previous live births; multiple birth; mother’s age; and Index of Multiple Deprivation quintile. Results Factors independently associated with an increased risk of overweight or obesity included deprivation (OR 1.6 [95% CI 1.4, 1.9]) (children born in most deprived areas compared with least deprived), regular maternal smoking during pregnancy (1.3 [1.2, 1.4]) and high brith weight (1.5 [1.2, 1.9]). Low birth weight (0.8 [0.7, 0.9]), being female (0.8 [0.8, 0.9]) and maternal age Conclusion Factors associated with childhood overweight and obesity at age 10-11 were neighbourhood deprivation, regular maternal smoking during pregnancy and high birth weight. Potential protective factors include low birth weight and young maternal age. Early intervention in tackling inequalities and maternal smoking in pregnancy are important strategies to help reduce childhood overweight and obesity.

Retroperitoneal paragangliomas are uncommon neoplasms that arise from neural crest cells. Typical retroperitoneal sites of origin include adrenal medulla, organs of Zuckerkandl, and along sympathetic and parasympathetic nerves. We present a case of a woman diagnosed with retroperitoneal paraganglioma treated with debulking, intraoperative radiotherapy and external beam radiation therapy. She experienced a 7-year disease-free interval prior to symptomatic metastatic recurrence. Such remissions are consistent with the natural history for paragangliomas. The purpose of this report and literature review is to summarize the pertinent biologic and therapeutic options for these uncommon tumors.

Introduction The current UK spending cuts have brought into stark light the need for the Public Sector to do more with less. A lower cost but more engaged Public Sector is embodied in the political vision of a “Big Society” which seeks to build on individual and community resilience. Knowledge of what community resilience resources are available however, is incomplete. Methods This study presents the findings from a community resilience mapping exercise undertaken in the spring of 2011, using routine data in Brighton and Hove. The Well-being and Resilience Measure (WARM) Tool was used to map out the epidemiology of community resilience in eight domains: Education Health Material well-being Strong and stable families Local economy Public services Crime and antisocial behaviour Infrastructure and belonging Results A series of electoral ward maps with some time trends describes community resilience in these eight domains with reference to four population groups. Children and young people Working age adults Older people Natural community groups Conclusions We believe that this is the first time a Public Sector organisation (NHS Brighton and Hove) in England has comprehensively mapped local resilience using routine data. The approach is timely and the findings are key to understanding the public capacity to deliver the political vision of a ‘Big Society9 and to implement the 2010 Public Health White Paper “Healthy Lives, Healthy People”, which explicitly seeks to “give communities the tools to address their own, particular needs”.

The current trial was designed to assess whether the addition of prednisone or prednisone + tamoxifen would enhance the therapeutic effectiveness of 1 year of adjuvant CMF therapy. Premenopausal women with ipsilateral axillary node-positive breast carcinoma and known estrogen receptor (ER) status were randomized to receive 1 year of postoperative treatment with 12 28-day cycles of cyclophosphamide, methotrexate, 5-fluorouracil (CMF), CMF plus prednisone (CMFP), or CMFP plus tamoxifen (CMFPT). There were 553 analyzed cases with 188 receiving CMF, 183 CMFP, and 182 CMFPT. The overall time to relapse (TTR) and survival comparisons between the regimens are not statistically different at a median follow-up time of 7.7 years. The major subgroups currently with a suggestive TTR difference are greater than 3N+ (CMFPT greater than CMF, P = 0.07) and estrogen receptor-negative (ER-) greater than 3N+ (CMFPT greater than CMF, P = 0.03). Patients receiving CMFPT appeared to have a superior survival to CMF in the ER- greater than 3N+ cohort (P = 0.02). The following patient characteristics were associated with a significantly longer TTR: decreasing nodal involvement or tumor size, positive ER status, age greater than or equal to 40 years, and decreasing obesity. The favorable effects of decreasing nodal involvement, positive ER status, age 40 years or greater, and decreasing obesity carried over to survival. Development of amenorrhea was also significantly associated with improved survival (P = 0.001). Toxicity was increased by the addition of prednisone to CMF and by the addition of tamoxifen to CMFP. Overall relapse patterns were similar among the three regimens. The results of the current trial do not currently suggest an overall therapeutic benefit for adding prednisone or only 1 year of tamoxifen to CMF adjuvant treatment.

Selective Inductive Heating of Lymph Nodes R. GILCHRIST;RICHARD MEDAL;WILLIAM SHOREY;RUSSELL HANSELMAN;JOHN PARROTT;C. TAYLOR; Annals of Surgery

Metastatic Leydig cell carcinomas account for less than 0.2% of all testicular cancers, and may be associated with sex hormone production. Leydig cell carcinoma is relatively refractory to radiotherapy and chemotherapy, and median survival of patients with metastatic disease is less than 2 years. Presented are three cases of metastatic Leydig cell cancer, and a review of the literature pertaining to this rare tumor.

THE PRESENT report deals with a case of tracheoesophageal fistula resulting from a severe blow over the sternum. This condition is extremely rare, and in a search of the literature only 2 similar cases with recovery were found. One of these, like the present case, presented no evidence of accompanying fracture of the ribs, cartilages or sternum. Both of the other cases were apparently reported twice. The relative frequency of tracheoesophageal fistula based on etiology is furnished by Mangabeira-Albernaz, 1 who in 1933 studied 682 cases collected from the world literature. His classification of these fistulas is given in the table. REPORT OF A CASE History. —On March 30, 1947, a 29 year old man was brought to the hospital by the police about fifteen minutes after injury. The patient stated that while driving home after having had some drinks he fell asleep at the wheel and his car struck

GENERALLY it is conceded that a greater operative risk attends the patient with coronary disease than is faced by the person with a normal heart. The mortality rate in surgical patients with myocardial infarction has been variously reported 1 from 5.2 to 44.5%. The unrelenting progress of medical science reflected in the increased life span necessarily brings to the surgeon a greater number of elderly patients with degenerative cardiac changes. Among these patients are those with evidence of severe angina pectoris or myocardial infarction harboring coexistent disease requiring urgent surgery. Usually these patients have some painful or malignant process in which delays in surgical therapeusis are costly, inviting reduced survival rates or even denying significant prolongation of a pain-free existence. In essence, the earliest auspicious application of a definitive operation designed to obviate these undesirable elements is implied by the term "urgent surgery." In most instances the operation is of