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PURPOSE Tubo-ovarian cancer (TOC) is a sentinel cancer for BRCA1 and BRCA2 pathogenic variants (PVs). Identification of a PV in the first member of a family at increased genetic risk (the proband) provides opportunities for cancer prevention in other at-risk family members. Although Australian testing rates are now high, PVs in patients with TOC whose diagnosis predated revised testing guidelines might have been missed. We assessed the feasibility of detecting PVs in this population to enable genetic risk reduction in relatives. PATIENTS AND METHODS In this pilot study, deceased probands were ascertained from research cohort studies, identification by a relative, and gynecologic oncology clinics. DNA was extracted from archival tissue or stored blood for panel sequencing of 10 risk-associated genes. Testing of deceased probands ascertained through clinic records was performed with a consent waiver. RESULTS We identified 85 PVs in 84 of 787 (11%) probands. Familial contacts of 39 of 60 (65%) deceased probands with an identified recipient (60 of 84; 71%) have received a written notification of results, with follow-up verbal contact made in 85% (33 of 39). A minority of families (n = 4) were already aware of the PV. For many (29 of 33; 88%), the genetic result provided new information and referral to a genetic service was accepted in most cases (66%; 19 of 29). Those who declined referral (4 of 29) were all male next of kin whose family member had died more than 10 years before. CONCLUSION We overcame ethical and logistic challenges to demonstrate that retrospective genetic testing to identify PVs in previously untested deceased probands with TOC is feasible. Understanding reasons for a family member's decision to accept or decline a referral will be important for guiding future TRACEBACK projects.

The azygos venous system, which comprises the azygos, hemiazygos, and accessory hemiazygos veins, assists in blood drainage into the superior vena cava (SVC) from the thoracic cage and portions of the posterior mediastinum. Routine dissection of a fresh-frozen cadaveric specimen revealed a split azygos vein. The azygos vein branched off the inferior vena cava (IVC) at the level of the second lumbar vertebra as a single trunk and then split into two tributaries after forming a venous plexus. The right side of this system drained into the SVC and, inferiorly, the collective system drained into the IVC. Variant forms in the venous system, especially the vena cavae, are prone to dilation and tortuosity, leading to an increased likelihood of injury. Knowledge of the anatomical variations of the azygos vein is important for surgeons who use an anterior approach to the spine for diverse procedures.

Safety precautions for laboratory staff working with meningococci should primarily rely on laboratory procedures preventing exposure to aerosols containing viable meningococci. Despite this, vaccination is a key component of protection in the occupational setting. In the UK in 2009, there were no licensed vaccines for meningococcal capsular group B or conjugate vaccines for capsular groups A, C, W and Y. We therefore undertook a Phase II trial in laboratory workers to investigate the safety and immunogenicity of a four component group B vaccine (4CMenB) and a quadrivalent group A, C, W and Y conjugate vaccine (ACWY-CRM). Enrolment was open to staff aged 18-65 years at the Public Health Laboratory, Manchester who may have had a potential occupational exposure risk to meningococci. 4CMenB was administered at 0, 2 and 6 months in the non-dominant arm and ACWY-CRM concomitantly at 0 months in the dominant arm. Pre- and post-vaccination blood samples were taken and analysed by the serum bactericidal antibody (SBA) assay against A, C, W and Y strains and a panel of seven diverse group B strains. Diary cards were used to record any local and systemic reactions following each vaccination. In total, 38 staff were enrolled and received initial vaccinations with 31 completing the trial per protocol. Both vaccines were proven safe, with local reactogenicity being more commonly reported following 4CMenB than ACWY-CRM. High proportions of subjects had putative protective SBA titres pre-vaccination, with 61-84 and 61-87% protected against A, C, W and Y strains and diverse MenB strains, respectively. Post-vaccination, SBA titres increased with 95-100 and 90-100% of subjects with protective SBA titres against A, C, W and Y strains and diverse MenB strains, respectively. These data suggest that 4CMenB and ACWY-CRM are safe when administered concomitantly and have the potential to enhance protection for laboratory workers. www.clinicaltrials.gov identifier: NCT00962624.

BACKGROUND This study aimed to estimate, following invasive pneumococcal disease (IPD), the proportion of children with protective immunoglobulin G (IgG) concentrations against the infecting serotype compared with other vaccine serotypes, and to assess risk of recurrent IPD. METHODS Pneumococcal antibody concentrations were available for 413 children with vaccine-type IPD diagnosed during 2006-2013. We compared serotype-specific IgG concentrations against the infecting vs other vaccine serotypes, after adjusting for confounders such as age using multilevel analyses. RESULTS After IPD, a higher proportion of vaccine-naive children had IgG concentrations ≥0.35 µg/mL against their infecting serotype than other vaccine serotypes (51% vs 36%; P < .001). In contrast, among children immunized with pneumococcal conjugate vaccine (PCV) both before and after IPD, the proportion with IgG concentrations ≥0.35 µg/mL against the infecting serotype was lower compared with other vaccine serotypes (71% vs 98%; P < .001). These children also had lower IgG geometric mean concentrations (GMCs) against the infecting serotype (2.22 µg/mL) vs other vaccine serotypes (15.64 µg/mL) in multilevel models (IgG GMC ratio, 0.24; 95% confidence interval, .18-.32), although their IgG GMC was higher compared with vaccine-naive children. Vaccinated children with IgG concentrations

The gas-sensing properties of orthorhombic and spinel ferrites (LaFeO 3 , NiFe 2 O 4 and CoFe 2 O 4 ) prepared by self-propagating high-temperature synthesis (SHS) have been investigated. This is one of the first reports of using an SHS derived powder for gas sensing applications. The gas response of the materials was tested against a wide range of environmentally important gases (ethanol, ethane, ethene, ammonia, propane, and CO) at a range of different operating temperatures. Good gas response behavior was found with excellent selectivity toward ethanol, particularly in the case of the LaFeO 3 sensor.

The illicit manufacture of drugs in the 21st century presents a danger to first responders, bystanders and the environment, making its detection important. Electronic noses based on metal oxide semiconducting (MOS) sensors present a potential technology to create devices for such purposes. An array of four thick film MOS gas sensors was fabricated, based on zinc oxide inks. Production took place using a commercially available screen printer, a 3 × 3 mm alumina substrate containing interdigitated electrodes and a platinum heater track. ZnO inks were modified using zeolite β, zeolite Y and mordenite admixtures. The sensors were exposed to four gases commonly found in the clandestine laboratory environment; these were nitrogen dioxide, ethanol, acetone and ammonia. Zeolite modification was found to increase the sensitivity of the sensor, compared to unmodified ZnO sensors, all of which showed strong responses to low ppm concentrations of acetone, ammonia and ethanol and to ppb concentrations of nitrogen dioxide. Machine learning techniques were incorporated to test the selectivity of the sensors. A high level of accuracy was achieved in determining the class of gas observed.

Port security with a focus on drug trafficking prevention requires inexpensive and portable systems for on-site analysis of containers in order to minimise transit delays. The potential of metal oxide semiconductors for illicit drug detection is explored here. A six-sensor array consisting of WO3 and SnO2 inks was devised. Zeolites H-Y and H-ZSM-5 were incorporated to introduce variations in sensor response. Sensors were tested against acetone, ethanol and toluene as proxies for their use in illicit drug manufacture and against ammonia and nitrogen dioxide as first models of amino- and nitro-containing compounds, given their prevalence in the structural framework of drugs and precursor molecules. Sensor sensitivity and selectivity were greatly enhanced by inclusion of zeolite materials. Admixed sensing materials were found to be particularly sensitive to the gases. Support vector machines were applied to the dataset as classification tools that accurately classified the data according to gas type. The sensing array was successful in targeting and discerning between the tested drug markers. This could be key for illicit drug detection with electronic noses based on MOS technology in the future.

Summary The Alfred Emergency and Trauma Centre has been organising, establishing and staffing a medical centre at The Australian FORMULA 1™ Grand Prix since its inception to Melbourne in 1996. A team of specialist staff are selected to best facilitate care to the FORMULA 1™ staff, the drivers and to the team personnel that travel the circuit every year. From primary health care and health promotion, to medical review and critical care reception from track incidents, the team is equipped to resuscitate the critically ill and stabilise prior to transfer to the Alfred Hospital. The logistics and organisation required to stage a medical centre involves intense planning, knowledge and experience. This paper will discuss the Australian Grand Prix Medical Centre (AGPMC) requirements, overview the development of the on track medical team personnel and equipment and provide a snapshot of the types of presentations seen at the 2011 event.

Limited data are available on the kinetics of meningococcal serogroup C (MenC)-specific antibody responses following parenteral or nasal challenge in those who have received prior MenC vaccination (polysaccharide or conjugate). Young adults who had previously received either meningococcal A/C polysaccharide (MACP) or MenC conjugate (MCC) vaccine or naïve subjects were challenged with MACP via one of two routes, nasal or parenteral. Blood samples were taken prevaccination and on days 1 to 4 and day 10 postvaccination. MenC serum bactericidal antibody (SBA) and MenC-specific IgG were measured. Following parenteral challenge, MenC SBA and IgG responses were seen to occur between 4 and 7 days postchallenge. A lower proportion of subjects responded following nasal challenge, with naïve subjects showing little change in SBA geometric mean titer (GMT) and IgG geometric mean concentration (GMC) over the 10 days following challenge. Increases in SBA GMTs were seen between 4 and 7 days after nasal challenge in those who had received prior MCC and between 7 and 10 days in those who had received prior MACP, and the responses in the prior-MACP group were of lower magnitude than the responses of the prior-MCC group. The data presented here indicate that, following MCC vaccination, memory has been induced at the mucosal level, and these subjects were able to respond with increases in SBA levels. These results demonstrate that the speed of response (primary or secondary) to challenge with MenC polysaccharide via the nasal or parenteral route does not differ and support concerns that immunological memory alone is too slow to provide protection.

Objective: A low case incidence and variable skill level prompted the development of a credentialing programme and specific surgical training in resuscitative thoracotomy for emergency physicians at The Alfred, a Level 1 Adult Victorian Major Trauma Service. Methods: A review of the incidence of traumatic pericardial tamponade and the objectives of resuscitative thoracotomy were undertaken. Results: A training programme involving pre-reading of a 17 page teaching manual, a 40 min didactic lecture and a 2 h surgical skills station using anaesthetized pigs were developed. The specific indication for resuscitative thoracotomy for this programme is ultrasound demonstrated cardiac tamponade secondary to blunt or penetrating truncal trauma in a haemodynamically unstable patient with a systolic blood pressure of less than 70 mmHg despite pleural decompression and intravenous volume replacement. Cardiac electrical activity must be present. The primary aims of resuscitative thoracotomy taught are release of cardiac tamponade, control of haemorrhage and access for internal cardiac massage. Conclusion: Emergency physicians working in high-volume Trauma Centres are expected to diagnose cardiac tamponade and on occasion decompress the pericardium. Specific training in the procedure should be undertaken.

The primary objective of this paper is to assess the affect of data 'censoring' on asset pricing tests. This is achieved by modifying tests to incorporate a 'selectivity bias' correction factor in a Gibbons (Journal of Financial Economics, 10, pp. 3-27, 1982) multivariate framework. The sample comprises daily Australian stock returns for 524 companies over the five-year period 1995 to 1999. First, it is found that the use of a 'selectivity bias' correction factor is generally justified in stocks with a degree of censoring at about 50% or above. This represents approximately 52% of the sample. Second, despite the first finding no evidence is found supporting the need for such a correction in asset pricing tests - the degree of support for the CAPM is not materially affected.

Asymptomatic and persistent colonization of the upper respiratory tract by Neisseria meningitidis occurs despite elicitation of adaptive immune responses against surface antigens. A putative mechanism for facilitating host persistence of this bacterial commensal and pathogen is alterations in expression of surface antigens by simple sequence repeat (SSR)-mediated phase variation. We investigated how often phase variation occurs during persistent carriage by analyzing the SSRs of eight loci in multiple isolates from 21 carriers representative of 1 to 6 months carriage. Alterations in repeat number were detected by a GeneScan analysis and occurred at 0.06 mutations/gene/month of carriage. The expression states were determined by Western blotting and two genes, fetA and nadA , exhibited trends toward low expression states. A critical finding from our unique examination of combinatorial expression states, “phasotypes,” was for significant reductions in expression of multiple phase-variable surface proteins during persistent carriage of some strains. The immune responses in these carriers were examined by measuring variant-specific PorA IgG antibodies, capsular group Y IgG antibodies and serum bactericidal activity in concomitant serum samples. Persistent carriage was associated with high levels of specific IgG antibodies and serum bactericidal activity while recent strain acquisition correlated with a significant induction of antibodies. We conclude that phase-variable genes are driven into lower expression states during long-term persistent meningococcal carriage, in part due to continuous exposure to antibody-mediated selection, suggesting localized hypermutation has evolved to facilitate host persistence.

Summary Background The use of NBs as a mode of analgesia for #NOF in the ED is not common practice despite the reported clinical benefits of quicker onset of pain relief, decreased use of additional analgesia and decreased amounts of analgesia required when more than one mode of analgesia is prescribed. Aim This study aims to test the hypothesis that the implementation of educational and awareness strategies increases knowledge, and implementation of the evidence based use of nerve blocks NB's, as a mode of analgesia for elderly patients with a fractured neck of femur (#NOF) in the Emergency Department (ED). Methods A retrospective clinical audit of medical records using explicit chart review pre and post implementation. Results Implementation of educational and awareness strategies on pain management to clinical staff in the ED resulted in a significant increase in the administration of NBs, use of multimodal analgesia, and a reduction in average milligrams of morphine administrated to elderly patients with #NOF. Conclusions The number of older people with #NOF presenting to the ED in Australia is increasing and historically, pain management in this group of patients could be improved. This study demonstrated that an audit, intervention and re-audit design that focused on the implementation of educational and promotional strategies informed by evidence on current and best practice standards were successful in improving delivery of analgesia to elderly patients with #NOF in the ED.

The gas-sensing properties of spinel and orthorhombic ferrites (NiFe2O4, CoFe2O4 and LaFeO3 respectively) prepared by self-propagating high-temperature synthesis (SHS) are reported. This is one of the first reports of using an SHS derived powder for gas sensing applications. The gas response of the materials was investigated against a range of gases (ethanol, ammonia, propane, CO, ethane, ethene) at a variety of operating temperatures. Good gas response behavior was found with excellent selectivity towards ethanol.

A national seroprevalence study was performed to determine the prevalence of Haemophilus influenzae type b (Hib) antibodies in England and Wales in 2009, when Hib disease incidence was the lowest ever recorded. A total of 2,693 anonymised residual sera from routine diagnostic testing submitted by participating National Health Service hospital laboratories were tested for Hib anti-polyribosyl-ribitol phosphate (PRP) IgG antibodies using a fluorescent bead assay. Median anti-PRP IgG concentrations were highest in toddlers aged 1-4 years (2.65 µg/ml), followed by children aged 5-9 years (1.95 µg/ml). Antibody concentrations were significantly lower after this age, but were still significantly higher among 10-19 year-olds (0.54 µg/ml) compared with adults aged >20 years (0.16 µg/ml; p

This study aimed to estimate the immunity of the UK population to tetanus and diphtheria, including the potential impact of new glycoconjugatate vaccines, and the addition of diphtheria to the school leaver booster in 1994.Residual sera (n=2697) collected in England in 2009/10 were selected from 18 age groups and tested for tetanus and diphtheria antibody. Results were standardised by testing a panel of sera (n=150) to enable comparison with a previously (1996) published serosurvey. Data were then standardised to the UK population.In 2009, 83% of the UK population were protected (≥0.1 IU/mL) against tetanus compared to 76% in 1996 (p=0.079), and 75% had at least basic protection against diphtheria (≥0.01 IU/mL) in 2009 compared to 60% in 1996 (p0.001). Higher antibody levels were observed in those aged 1-3 years in 2009 compared to 1996 for both tetanus and diphtheria. Higher diphtheria immunity was observed in those aged 16-34 years in 2009 compared to 1996 (geometric mean concentration [GMC] 0.15 IU/mL vs. 0.03 IU/mL, p0.001). Age groups with the largest proportion of susceptible individuals to both tetanus and diphtheria in 2009 were1 year old (29% susceptible), 45-69 years (20% susceptible) and 70+ years (32% susceptible). Low immunity was observed in those aged 10-11 years (19% susceptible), between the scheduled preschool and school leaver booster administration.The current schedule appears to induce protective levels; increases in the proportions protected/GMCs were observed for the ages receiving vaccinations according to UK policy. Glycoconjugate vaccines appear to have increased immunity, in particular for diphtheria, in preschool age groups. Diphtheria immunity in teenagers and young adults has increased as a result of the addition of diphtheria to the school leaver booster. However, currently older adults remain susceptible, without any further opportunities for immunisations planned according to the present schedule.

A low case incidence and variable skill level prompted the development of a credentialing programme and specific surgical training in resuscitative thoracotomy for emergency physicians at The Alfred, a Level 1 Adult Victorian Major Trauma Service.A review of the incidence of traumatic pericardial tamponade and the objectives of resuscitative thoracotomy were undertaken.A training programme involving pre-reading of a 17 page teaching manual, a 40 min didactic lecture and a 2 h surgical skills station using anaesthetized pigs were developed. The specific indication for resuscitative thoracotomy for this programme is ultrasound demonstrated cardiac tamponade secondary to blunt or penetrating truncal trauma in a haemodynamically unstable patient with a systolic blood pressure of less than 70 mmHg despite pleural decompression and intravenous volume replacement. Cardiac electrical activity must be present. The primary aims of resuscitative thoracotomy taught are release of cardiac tamponade, control of haemorrhage and access for internal cardiac massage.Emergency physicians working in high-volume Trauma Centres are expected to diagnose cardiac tamponade and on occasion decompress the pericardium. Specific training in the procedure should be undertaken.

Background Although a combined Haemophilus influenzae type b (Hib)/meningococcal capsular group C (MenC) conjugate vaccine with a tetanus toxoid carrier protein (Hib/MenC-TT) is not licensed for use in those above 2 years of age due to lack of data on safety and efficacy, certain patient groups at high risk of MenC and/or Hib disease are recommended to receive it. Laboratory workers working with Hib and/or MenC cultures may be at a potentially increased risk of acquiring infectious diseases and vaccination is therefore an important safety consideration. We undertook a clinical trial to investigate the safety and immunogenicity of Hib/MenC-TT vaccine in this cohort. Methods A total of 33 subjects were recruited to the trial, all of whom were vaccinated. Serology was completed on samples taken at baseline and four weeks following vaccination to determine MenC specific IgG, MenC serum bactericidal antibody (SBA), anti-Hib polyribosylribitol phosphate (PRP) IgG and anti-tetanus toxoid IgG responses. Results At baseline, high proportions of subjects had protective antibody concentrations against MenC, Hib and tetanus due to previous vaccination and/or natural exposure. Vaccination induced > 3, 10 and 220 fold increases in geometric mean concentrations for MenC SBA, anti-tetanus toxoid IgG and anti-Hib PRP IgG, respectively. Following vaccination, 97% of subjects had putative protective SBA titres ≥ 8, 100% had short term protective anti-Hib PRP IgG concentrations ≥ 0.15 μg/mL and 97% had protective anti-tetanus toxoid concentrations ≥ 0.1 IU/mL. No safety concerns were reported with minor local reactions being reported by 21% of subjects. Conclusions Immunological responses determined in this trial are likely a combination of primary and secondary responses due to previous vaccination and natural exposure. Subjects were a representative cross-section of laboratory workers, enabling us to conclude that a single dose of Hib/MenC-TT was safe and immunogenic in healthy adults providing the evidence that this vaccine may be used for providing protection in an occupational setting.