The clinical landscape of cell-free DNA alterations in 1671 patients with advanced biliary tract cancer.

BACKGROUND: Targeted therapies have transformed clinical management of advanced biliary tract cancer (BTC). Cell-free DNA (cfDNA) analysis is an attractive approach for cancer genomic profiling that overcomes many limitations of traditional tissue-based analysis. We examined cfDNA as a tool to inform clinical management of patients with advanced BTC and generate novel insights into BTC tumor biology. PATIENTS AND METHODS: We analyzed next-generation sequencing data of 2068 cfDNA samples from 1671 patients with advanced BTC generated with Guardant360. We carried out clinical annotation on a multi-institutional subset (n = 225) to assess intra-patient cfDNA-tumor concordance and the association of cfDNA variant allele fraction (VAF) with clinical outcomes. RESULTS: Genetic alterations were detected in cfDNA in 84% of patients, with targetable alterations detected in 44% of patients. Fibroblast growth factor receptor 2 (FGFR2) fusions, isocitrate dehydrogenase 1 (IDH1) mutations, and BRAF V600E were clonal in the majority of cases, affirming these targetable alterations as early driver events in BTC. Concordance between cfDNA and tissue for mutation detection was high for IDH1 mutations (87%) and BRAF V600E (100%), and low for FGFR2 fusions (18%). cfDNA analysis uncovered novel putative mechanisms of resistance to targeted therapies, including mutation of the cysteine residue (FGFR2 C492F) to which covalent FGFR inhibitors bind. High pre-treatment cfDNA VAF was associated with poor prognosis and shorter response to chemotherapy and targeted therapy. Finally, we report the frequency of promising targets in advanced BTC currently under investigation in other advanced solid tumors, including KRAS G12C (1.0%), KRAS G12D (5.1%), PIK3CA mutations (6.8%), and ERBB2 amplifications (4.9%). CONCLUSIONS: These findings from the largest and most comprehensive study to date of cfDNA from patients with advanced BTC highlight the utility of cfDNA analysis in current management of this disease. Characterization of oncogenic drivers and mechanisms of therapeutic resistance in this study will inform drug development efforts to reduce mortality for patients with BTC.

A novel founder MSH2 deletion in Ethiopian Jews is mainly associated with early-onset colorectal cancer.

Lynch syndrome is an inherited cancer predisposition syndrome caused by germline defects in any of the mismatch repair (MMR) genes. Diagnosis of carriers makes precision prevention, early detection, and tailored treatment possible. Herein we report a novel founder deletion of 18,758 bp, mediated by Alu repeats on both sides, detected in Ethiopian Jews. The deletion, which encompasses exon 9-10 of the MSH2 coding sequence, is associated mainly with early-onset MSH2/MSH6-deficient colorectal cancer (CRC) and liposarcoma. Testing of 35 members of 5 seemingly unrelated families of Ethiopian origin yielded 10/21 (48%) carriers, of whom 9 had CRC. Age at first tumor diagnosis ranged from 16 to 89 years. Carriers from the oldest generations were diagnosed after age 45 years (mean 57), and carriers from the younger generation were diagnosed before age 45 years (mean 30). Awareness of this founder deletion is important to improve patient diagnosis, institute surveillance from an early age, and refer patients for genetic counseling addressing the risk of bi-allelic constitutional MMR deficiency syndrome.

Spatial behaviour of sheep during the neonatal period: Preliminary study on the influence of shelter.

Effective shelter has been demonstrated to reduce neonatal lamb mortality rates during periods of inclement weather. Periods of high wind speed and rainfall have been shown to influence shelter usage; however, it is not yet known how ewe factors such as breed, age and body condition score influence shelter-seeking behaviour. This study, conducted on a working upland farm in the UK, examined impact of artificial shelter on the biological and climatic factors that influence peri-parturient ewe behaviour. Pregnant ewes (n = 147) were randomly allocated between two adjacent fields which were selected for their similarity in size, topography, pasture management, orientation to the prevailing wind and available natural shelter. In one field, three additional artificial shelters were installed to increase the available shelter for ewes, this field was designated the Test field; no additional artificial shelter was provided in the second field which was used as the Control field. Individual ewes were observed every 2 h between 0800 and 1600 for 14 continuous days to monitor their location relative to shelter. Ewe breed (Aberfield and Highlander), age (2-8 years) and body condition score were considered as explanatory variables to explain flock and individual variance in shelter-seeking behaviour and the prevalence of issues which required the intervention of the shepherd, termed 'shepherding problems'. Any ewe observed with dystocia, a dead or poor vigour lamb or who exhibited mismothering behaviour was recorded as a shepherding problem. The prevalence of these shepherding problems which necessitate human intervention represents arguably the most critical limiting factor for the successful management of commercial sheep flocks in outdoor lambing systems. Overall, ewes in the Test field with access to additional artificial shelter experienced fewer shepherding problems than those in the Control field (P < 0.05). A significant breed effect was also observed, with Highlander ewes more likely to seek shelter than Aberfield ewes (P < 0.001), and experiencing significantly fewer shepherding interventions (P < 0.05). These findings demonstrate the substantial and significant benefits to animal welfare and productivity that can be achieved through the provision of shelter in commercial, upland, outdoor lambing systems in the UK.

Comparing the accuracy of lay diagnosis of childhood malaria and pneumonia with that of the revised IMCI guidelines in Nigeria.

BACKGROUND: Improving caregivers' recognition of childhood malaria and pneumonia is crucial to early treatment and improving outcomes. The objective of this study was to assess the accuracy and reliability of caregivers' recognition of malaria and pneumonia (lay diagnosis) as compared to the revised IMCI guidelines. METHODS: A cross-sectional study design was used to recruit 903 children aged 2-59 months who were assessed for malaria and pneumonia by health workers at five primary healthcare centres in Benin City, Nigeria. Accuracy of lay diagnosis as compared to the revised IMCI guidelines was assessed using sensitivity, specificity, positive and negative predictive values and area under the receiver operating characteristic curve (AUROC) values. RESULTS: The accuracy of caregivers' ability to recognise malaria (AUROC: 0.60; 95% CI: 0.57-0.64) and pneumonia (AUROC: 0.54; 95% CI: 0.50-0.58) was, respectively, moderate and poor as compared to the IMCI guidelines. Caregivers were better able to identify children without than those with malaria and pneumonia. Agreement between caregivers and the IMCI guidelines for malaria and pneumonia diagnosis was poor (k = 0.14, 95% CI: 0.09-0.19; P = 0.0001). CONCLUSION: Caregivers' ability to recognise these childhood diseases as compared to the IMCI guidelines was poor overall, which was partly due to the approach used to ascertain lay diagnosis.

Learning to implement Smart Healthy Age-Friendly Environments.

To develop trainings on the implementation of smart healthy age-friendly environments for people who aim to support, for example, their parents, their neighbours or local community, there are precautionary measures that have to be taken into account: the role of the facilitator (volunteer or self-employed), the level of skills, the needs of the end-users, training content and methodologies together with the sustainability of the learning. This article examines these aspects, based on desk research and expert interviews in the Smart Healthy Age-Friendly Environments (SHAFE) fields.

International comparison of civilian violent deaths: a public health approach to reduce gun-related deaths in US youth.

OBJECTIVES: The political controversy surrounding firearm fatalities in US youths (aged 15-24 years) continues. This study examines whether a public health approach could reduce gun-related deaths in the US. METHODS: Based on the latest World Health Organization (WHO) data, current (2015) numbers and rates per million of US civilian violent deaths (CVDs) (including transport deaths, suicides and homicides) for both the general population and youths (aged 15-24 years) are examined. US CVD results are considered in a wider context by comparing the results with those of seven other major Western countries (MWCs). To demonstrate the effectiveness of a public health policy, transport deaths between 1979 and 2015 are analysed, which corresponds to a time period when government interventions based on technical improvements and behaviour change were implemented to improve road safety. The statistical significance of the comparison between road fatalities and suicide rates between 1979 and 2015 is determined by the chi-squared test. RESULTS: In 2015, the total number of US CVDs was 101,456, consisting of 44,193 suicides and 17,588 homicides (of which 30,891 were likely to be gun-related deaths). Youth deaths totalled 17,432; 5491 suicides and 4732 homicides, including approximately 5112 gun-related deaths. US CVDs are substantially higher than the other MWCs for both the general population and youths. In 1979, US transport deaths were 57,577, which decreased to 39,675 in 2015. Every country's public health approach to reduce road deaths, when compared with suicides, was highly statistically significant. CONCLUSIONS: Government interventions have reduced transport deaths; thus, new policies may also reduce gun-related violence. The evidence points towards a public health approach, such as that used to reduce road deaths, which could help reduce US firearm-related deaths to levels comparable with other MWCs.

Smart monitoring and control system test apparatus.

In underground metal/nonmetal mines, repeated localized short-term exposure to high levels of airborne contaminants can become a serious health issue. Currently, there are no common mechanisms to control or mitigate these short-term high exposures to contaminants. To improve miners' health and safety, the U.S. National Institute for Occupational Safety and Health's Spokane Mining Research Division (SMRD) is developing a smart monitoring and control (SMAC) system for the real-time monitoring of mine air quality, with integrated countermeasures to reduce high concentrations of airborne contaminants in localized sections of mines. To develop and test a SMAC system capable of being implemented in an underground mine, SMRD researchers built a test apparatus incorporating a fan, louver, ducting and sensors combined with atmospheric monitoring and control software. This system will institute effective countermeasures to reduce contaminant levels, improving miner safety and health.

Controlled population-based comparative study of USA and international adult [55-74] neurological deaths 1989-2014.

OBJECTIVES: A population-based controlled study to determine whether adult (55-74 years) neurological disease deaths are continuing to rise and are there significant differences between America and the twenty developed countries 1989-91 and 2012-14. METHOD: Total Neurological Deaths (TND) rates contrasted against control Cancer and Circulatory Disease Deaths (CDD) extrapolated from WHO data. Confidence intervals compare USA and the other countries over the period. The Over-75's TND and population increases are examined as a context for the 55-74 outcomes. RESULTS: Male neurological deaths rose >10% in eleven countries, the other countries average rose 20% the USA 43% over the period. Female neurological deaths rose >10% in ten counties, averaging 14%, the USA up 68%. USA male and female neurological deaths increased significantly more than twelve and seventeen countries, respectively. USA over-75s population increased by 49%, other countries 56%. Other countries TND up 187% the USA rose fourfold. Male and female cancer and CDD fell in every country averaging 26% and 21%, respectively, and 64% and 67% for CDD. Male neurological rates rose significantly more than Cancer and CCD in every country; Female neurological deaths rose significantly more than cancer in 17 countries and every country for CDD. There was no significant correlation between increases in neurological deaths and decreases in control mortalities. CONCLUSIONS: There are substantial increases in neurological deaths in most countries, significantly so in America. Rises in the 55-74 and over-75's rates are not primarily due to demographic changes and are a matter of concern warranting further investigation.

The cost-effectiveness of patient-controlled analgesia vs. standard care in patients presenting to the Emergency Department in pain, who are subsequently admitted to hospital.

The clinical effectiveness of patient-controlled analgesia has been demonstrated in a variety of settings. However, patient-controlled analgesia is rarely utilised in the Emergency Department. The aim of this study was to compare the cost-effectiveness of patient-controlled analgesia vs. standard care in participants admitted to hospital from the Emergency Department with pain due to traumatic injury or non-traumatic abdominal pain. Pain scores were measured hourly for 12 h using a visual analogue scale. Cost-effectiveness was measured as the additional cost per hour in moderate to severe pain avoided by using patient-controlled analgesia rather than standard care (the incremental cost-effectiveness ratio). Sampling variation was estimated using bootstrap methods and the effects of parameter uncertainty explored in a sensitivity analysis. The cost per hour in moderate or severe pain averted was estimated as £24.77 (€29.05, US$30.80) (bootstrap estimated 95%CI £8.72 to £89.17) for participants suffering pain from traumatic injuries and £15.17 (€17.79, US$18.86) (bootstrap estimate 95%CI £9.03 to £46.00) for participants with non-traumatic abdominal pain. Overall costs were higher with patient-controlled analgesia than standard care in both groups: pain from traumatic injuries incurred an additional £18.58 (€21.79 US$23.10) (95%CI £15.81 to £21.35) per 12 h; and non-traumatic abdominal pain an additional £20.18 (€23.67 US$25.09) (95%CI £19.45 to £20.84) per 12 h.

The portrayal of infant feeding in British women's magazines: a qualitative and quantitative content analysis.

Background: Exclusive breastfeeding is the best start an infant can receive. However, in many high-income countries breastfeeding rates are low and this may be a reflection of social norms which in turn may be influenced by the media. This study therefore explored the portrayal of infant feeding in women's general interest magazines. Methods: The five top selling women's weekly magazines in Britain and Ireland for 2013 over a 4-month period were included. A quantitative and qualitative content analysis was conducted for both written and visual content. Results: In 58 magazines, there were 90 references to infant feeding with an average of 1.5 (range: 0-5) per magazine. Breastfeeding and formula feeding references were present in equal number and both were predominantly portrayed positively. There was only 1 visual representation of breast feeding compared with 11 of bottle feeding. Potential drivers for breastfeeding included its role in post-pregnancy weight loss and celebrity endorsement while family routine, the role of males in the house and concerns about adverse health effects were identified as barriers to breastfeeding. Conclusion: An improvement in visual representations of breast feeding and factual information in women's weekly magazines may be helpful in re-defining social norms regarding infant feeding. Keywords: food and nutrition, health promotion, public health.

Circulating microRNAs and sudden cardiac arrest outcomes.

AIM: MicroRNAs (miRNAs) have regulatory functions in organs critical in resuscitation from sudden cardiac arrest due to ventricular fibrillation (VF-SCA); therefore, circulating miRNAs may be markers of VF-SCA outcome. METHODS: We measured candidate miRNAs (N=45) in plasma using qRT-PCR among participants of a population-based VF-SCA study. Participants were randomly selected cases who died in the field (DF, n=15), died in hospital (DH, n=15), or survived to discharge (DC, n=15), and, age-, sex-, and race-matched controls (n=15). MiRNA levels were compared using ANOVA, t-tests, and fold-changes. RESULTS: Mean age of groups ranged from 66.9 to 69.7. Most participants were male (53-67%) and white (67%). Comparing cases to controls, plasma levels of 17 miRNAs expressed in heart, brain, liver, and other tissues (including miR-29c, -34a, -122, -145, -200a, -210, -499-5p, and -663b) were higher and three non-specific miRNAs lower (miR-221, -330-3p, and -9-5p). Among DH or DC compared with DF cases, levels of two miRNAs (liver-specific miR-122 and non-specific miR-205) were higher and two heart-specific miRNAs (miR-208b and -499-5p) lower. Among DC vs. DF cases, levels of three miRNAs (miR-122, and non-specific miR-200a and -205) were higher and four heart-specific miRNAs (miR-133a, -133b, -208b, and -499-5p) lower. Among DC vs. DH cases, levels of two non-specific miRNAs (miR-135a and -9-3p) were lower. CONCLUSIONS: Circulating miRNAs expressed in heart, brain, and other tissues differ between VF-SCA cases and controls and are related to resuscitation outcomes. Measurement of miRNAs may clarify mechanisms underlying resuscitation, improve prognostication, and guide development of therapies. Results require replication.

TSH overcomes Braf(V600E)-induced senescence to promote tumor progression via downregulation of p53 expression in papillary thyroid cancer.

The BRAF(V600E) mutation is found in approximately 40% of papillary thyroid cancers (PTC). Mice with thyroid-specific expression of Braf(V600E) (TPO-Braf(V600E)) develop PTC rapidly with high levels of serum thyroid-stimulating hormone (TSH). It is unclear to what extent the elevated TSH contributes to tumor progression. To investigate the progression of Braf(V600E)-induced PTC (BVE-PTC) under normal TSH, we transplanted BVE-PTC tumors subcutaneously into nude and TPO-Braf(WT) mice. Regression of the transplanted tumors was observed in both nude and TPO-Braf(WT) mice. They were surrounded by heavy lymphocyte infiltration and oncogene-induced senescence (OIS) was demonstrated by strong ß-gal staining and absence of Ki-67 expression. In contrast, BVE-PTC transplants continued to grow when transplanted into TPO-Braf(V600E) mice. The expression of Trp53 was increased in tumor transplants undergoing OIS. Trp53 inactivation reversed OIS and enabled tumor transplants to grow in nude mice with characteristic cell morphology of anaplastic thyroid cancer (ATC). PTC-to-ATC transformation was also observed in primary BVE-PTC tumors. ATC cells derived from Trp53 knockout tumors had increased PI3K/AKT signaling and became resistant to Braf(V600E) inhibitor PLX4720, which could be overcome by combined treatment of PI3K inhibitor LY294002 and PLX4720. In conclusion, BVE-PTC progression could be contained via p53-dependent OIS and TSH is a major disruptor of this balance. Simultaneous targeting of both MAPK and PI3K/AKT pathways offer a better therapeutic outcome against ATC. The current study reinforces the importance of rigorous control of serum TSH in PTC patients.

Characterization of novel markers of senescence and their prognostic potential in cancer.

Cellular senescence is a terminal differentiation state that has been proposed to have a role in both tumour suppression and ageing. This view is supported by the fact that accumulation of senescent cells can be observed in response to oncogenic stress as well as a result of normal organismal ageing. Thus, identifying senescent cells in in vivo and in vitro has an important diagnostic and therapeutic potential. The molecular pathways involved in triggering and/or maintaining the senescent phenotype are not fully understood. As a consequence, the markers currently utilized to detect senescent cells are limited and lack specificity. In order to address this issue, we screened for plasma membrane-associated proteins that are preferentially expressed in senescent cells. We identified 107 proteins that could be potential markers of senescence and validated 10 of them (DEP1, NTAL, EBP50, STX4, VAMP3, ARMX3, B2MG, LANCL1, VPS26A and PLD3). We demonstrated that a combination of these proteins can be used to specifically recognize senescent cells in culture and in tissue samples and we developed a straightforward fluorescence-activated cell sorting-based detection approach using two of them (DEP1 and B2MG). Of note, we found that expression of several of these markers correlated with increased survival in different tumours, especially in breast cancer. Thus, our results could facilitate the study of senescence, define potential new effectors and modulators of this cellular mechanism and provide potential diagnostic and prognostic tools to be used clinically.

Study protocol for a double blind, randomised, placebo-controlled trial of continuous subpectoral local anaesthetic infusion for pain and shoulder function following mastectomy: SUB-pectoral Local anaesthetic Infusion following MastEctomy (SUBLIME) study.

INTRODUCTION: Over 16 000 mastectomies are performed in England and Wales annually. Acute postoperative pain and nausea are common. The most frequently occurring long-term complications are chronic pain (up to 50%) and reduced shoulder function (reported at 35%). Regional techniques that improve acute postoperative pain relief may reduce the incidence of these complications. This study assesses the effectiveness of a 24-hour continuous local anaesthetic in the subpectoral plane in improving postoperative pain and quality of life in patients undergoing mastectomy. METHODS AND ANALYSIS: This is a randomised, double blind, placebo-controlled, two-centre, parallel group trial in women undergoing mastectomy with or without axillary involvement. One hundred and sixty participants will be randomised in a 1:1 ratio to receive either 0.25% levobupivacaine or 0.9% saline by subpectoral infusion postoperatively for 24 h. All participants will be provided with an intravenous morphine patient-controlled analgesia (PCA) system. Participants will be followed-up for 24 h in hospital and at approximately 14 days and 6 months postoperatively. Joint primary outcome measures are total morphine consumption and total pain score (captured via patient-recorded visual analogue scale (VAS) 4 hourly) during the first 24 h postoperatively. Primary statistical analysis of total pain is based on the area under the curve of pain versus time graph. Secondary outcomes include PCA attempts in first 24 h; VAS pain scores and shoulder function by goniometry at 24 h, 14 days (approximately) and 6 months; Verbal Rating Scale pain scores in first 24 h; Brief Pain Inventory and Oxford Shoulder Score at 6 months; duration of hospital stay; incidence of postoperative nausea and vomiting; cost-effectiveness. ETHICS AND DISSEMINATION: The study is approved by the South West England Research Ethics Committee (12/SW/0149). RESULTS: will be published in a peer-reviewed journal and presented at local, national and international scientific meetings. TRIAL REGISTRATION: ISRCTN46621916. EudraCT 2011-005775-16.

Investigation of induced recirculation during planned ventilation system maintenance.

The Office of Mine Safety and Health Research (OMSHR) investigated ways to increase mine airflow to underground metal/nonmetal (M/NM) mine working areas to improve miners' health and safety. One of those areas is controlled recirculation. Because the quantity of mine air often cannot be increased, reusing part of the ventilating air can be an effective alternative, if implemented properly, until the capacity of the present system is improved. The additional airflow can be used to provide effective dilution of contaminants and higher flow velocities in the underground mine environment. Most applications of controlled recirculation involve taking a portion of the return air and passing it back into the intake to increase the air volume delivered to the desired work areas. OMSHR investigated a Nevada gold mine where shaft rehabilitation was in progress and one of the two main fans was shut down to allow reduced air velocity for safe shaft work. Underground booster fan operating pressures were kept constant to maintain airflow to work areas, inducing controlled recirculation in one work zone. Investigation into system behavior and the effects of recirculation on the working area during times of reduced primary ventilation system airflow would provide additional information on implementation of controlled recirculation into the system and how these events affect M/NM ventilation systems. The National Institute for Occupational Safety and Health monitored the ventilation district when both main fans were operating and another scenario with one of the units turned off for maintenance. Airflow and contaminants were measured to determine the exposure effects of induced recirculation on miner health. Surveys showed that 19% controlled recirculation created no change in the overall district airflow distribution and a small reduction in district fresh air intake. Total dust levels increased only modestly and respirable dust levels were also low. Diesel particulate matter (DPM) levels showed a high increase in district intake mass flow, but minor increases in exposure levels related to the recirculation percentage. Utilization of DPM mass flow rates allows input into ventilation modeling programs to better understand and plan for ventilation changes and district recirculation effects on miners' health.

Changing patterns of neurological mortality in the 10 major developed countries--1979-2010.

OBJECTIVES: To examine whether there is a continued increase in neurological deaths in the major developed countries over the period 1979-2010. STUDY DESIGN: Analyzes changing patterns of neurological deaths and Total Mortality of people aged 55-74 years by sex. METHODS: Baseline WHO 3-year average mortality for 1979-81 were compared with changes in 2008-10, for Total Mortality and the neurological categories Nervous Disease, and Alzheimer & other Dementias deaths in rates per million. To control for different diagnostic practice, the focus is upon Total Neurological Deaths in relation to Total Mortality and Odds ratios are calculated. UK Motor Neuron Disease, Parkinson's disease and variant CJD are explored as possible constituent categories of Nervous Disease for other countries. RESULTS: Total Mortality fell substantially in every country, conversely, Nervous Disease and Alzheimer's rose in seven and six countries respectively. Total Neurological Deaths for males and females increased significantly in Australia, Canada, England & Wales, Italy, the Netherlands and especially the USA. Unlike motor neurone disease, variant CJD' deaths in England and Wales did not contribute substantially to the overall neurological increases found. Odds ratios indicated that neurological deaths differentially increased significantly in every country compared to Total Mortality. CONCLUSIONS: These results pose a major public health problem, as the epigenetic contribution to these changes, rather than longevity, have serious implications indicating earlier onset of neurological morbidity pressurizing families, health and social care services, with resource implications especially for Australia, Canada, Italy, Netherlands, Spain, the UK and the USA.

Case study of controlled recirculation at a Wyoming trona mine.

Controlled recirculation has been used in the metal/nonmetal mining industry for energy savings when heating and cooling air, in undersea mining and for increasing airflow to mining areas. For safe and effective use of controlled district recirculation, adequate airflow to dilute contaminants must exist prior to implementation, ventilation circuit parameters must be accurately quantified, ventilation network modeling must be up to date, emergency planning scenarios must be performed and effective monitoring and control systems must be installed and used. Safety and health issues that must be considered and may be improved through the use of controlled district recirculation include blasting fumes, dust, diesel emissions, radon and contaminants from mine fires. Controlled recirculation methods are expected to become more widely used as mines reach greater working depths, requiring that these health and safety issues be well understood. The U.S. National Institute for Occupational Safety and Health (NIOSH) conducted two controlled recirculation tests over three days at a Wyoming trona mine, utilizing an inline booster fan to improve airflow to a remote and difficult-to-ventilate development section. Test results were used to determine the effect that recirculation had on air qualities and quantities measured in that section and in other adjacent areas. Pre-test conditions, including ventilation quantities and pressures, were modeled using VnetPC. During each test, ventilation quantities and pressures were measured, as well as levels of total dust. Sulfur hexafluoride (SF 6 ) tracer gas was used to simulate a mine contaminant to monitor recirculation wave cycles. Results showed good correlation between the model results and measured values for airflows, pressure differentials, tracer gas arrival times, mine gasses and dust levels.

Investigation of zoonotic infections among Auckland Zoo staff: 1991-2010.

Investigation was undertaken to assess the occurrence of zoonotic infection among staff at Auckland Zoological Park, New Zealand, in 1991, 2002 and 2010. Serial cross-sectional health surveys in 1991, 2002 and 2010 comprising a health questionnaire, and serological, immunological and microbiological analysis for a range of potential zoonotic infections were performed. Laboratory results for zoo animals were also reviewed for 2004-2010 to assess the occurrence of potential zoonotic infections. Veterinary clinic, animal handler, grounds, maintenance and administrative staff participated in the surveys, with 49, 42 and 46 participants in the 1991, 2002 and 2010 surveys, respectively (29% of total zoo staff in 2010). A small number of staff reported work-related infections, including erysipelas (1), giardiasis (1) and campylobacteriosis (1). The seroprevalence of antibodies to hepatitis A virus and Toxoplasma gondii closely reflected those in the Auckland community. No carriage of hepatitis B virus (HBV) was detected, and most of those with anti-HBV antibodies had been vaccinated. Few staff had serological evidence of past leptospiral infection. Three veterinary clinic staff had raised Chlamydophila psittaci antibodies, all < 1 : 160 indicating past exposure. Two staff (in 1991) had asymptomatic carriage of Giardia lamblia and one person (in 2010) had a dermatophyte infection. After 1991, positive tests indicating exposure to Mycobacterium tuberculosis were < 10%, comparable to the general New Zealand population. Zoo animals had infections with potential zoonotic agents, including G. lamblia, Salmonella spp., Campylobacter spp. and T. gondii, although the occurrence was low. Zoonotic agents pose an occupational risk to zoo workers. While there was evidence of some zoonotic transmission at Auckland Zoo, this was uncommon and risks appear to be adequately managed under current policies and procedures. Nevertheless, ongoing assessment of risk factors is needed as environmental, human and animal disease and management factors change. Policies and procedures should be reviewed periodically in conjunction with disease monitoring results for both animals and staff to minimise zoonotic transmission.

Comparing cancer mortality and GDP health expenditure in England and Wales with other major developed countries from 1979 to 2006.

BACKGROUND: Cancer and gross-domestic-product on health expenditure (GDPHE) are critical issues for major developed countries (MDC). Each country's economic input, GDPHE 1980-2005 is contrasted with clinical outputs, cancer mortality rates (CMRs), to compare their efficiency and effectiveness in reducing CMR. METHODS: World Health Organization's CMR data for baseline years (1979-1981) are compared with 2004-2006 by sex and age. The χ(2)-tests are used to determine differences between MDC. Efficiency is analysed by calculating a ratio of average GDPHE to reduced CMR over the period. RESULTS: Inputs: All the countries GDPHE grew substantially. For the United Kingdom this reached 9.3%, which is below the MDC average (10%). Outputs: CMR fell substantially (>20%) in six of the ten countries. The male average (15-74 years) CMR in England and Wales had been third highest but by 2004-2006 was sixth, a 31% reduction, which was significantly greater than seven other countries. Initially England and Wales female average CMR was the highest of all countries and is now the second highest. There were significantly greater reductions for the 55-64 and 65-74 years old than in seven and four countries, respectively. GDPHE reduced CMR ratios--the average GDPHE:reduced CMR ratio of England and Wales was 1:120, greater than all MDC and double that in four countries. CONCLUSION: Comparing GDPHE input with CMR output showed that relatively the NHS achieved more with proportionately less than other MDC.