Prototype Design for Grading Structures in Powder Bed Fusion Processes.

While targeted alignment in certain additive manufacturing (AM) methods such as material extrusion (MEX) and stereolithography (SLA) has been well documented in the research community, a method for targeted alignment of added fillers or fibrous materials in powder bed fusion (PBF) AM devices has yet to be successfully achieved. Similarly, incorporation of multimaterials does not work easily with any of the AM technologies. This study creates a prototype design that could be integrated into a PBF system to allow for multimaterial layer deposition and alignment of powders and powder blends. The rheological properties of polyamide powder and a range of polyamide composite blends (incorporating milled carbon fibre, graphite flakes, polytetrafluoroethylene, and glass microspheres) in different concentrations were studied, and together with the particle size distribution and particle morphology analysis were applied for the design of a prototype hopper for incorporation in the PBF system to create targeted multimaterial deposition. Different concept designs, multichambered and multi-hopper with hopper angles calculated specifically for the composite blend powders selected, were proposed. Initial deposition trials outside a PBF process were tested, and the deposited layers were measured.

Using an electronic health record alert to prompt blood-borne virus testing in primary care.

BACKGROUND: Late diagnosis of HIV, hepatitis B (HBV) and hepatitis C (HCV) remains relatively common in the UK and many people who present late have missed opportunities for testing in primary care. The objective was to assess the effectiveness and acceptance of a prototype application (BBV_TP1), embedded in a primary care electronic health record (EHR), to increase real-time blood-borne virus (BBV) testing. METHODS: This prospective cohort study assessed BBV_TP1 in 14 general practices in North East England, in comparison with 54 similar practices in 2019. Rates of HIV, hepatitis B virus (HBV) and hepatitis C virus (HCV) testing in practices were measured before and after the application was activated. Patient and clinician acceptance of the technology was assessed by surveys. RESULTS: In the 6 months following the intervention, HIV testing rates increased 555% and combined HBV/HCV testing rates increased 362%. No significant differences were observed for any BBV testing rates in the nonintervention practices over the same period. Monthly testing rates declined towards baseline after initial increases. Clinician's perceptions of the prompt system were positive, with average additional time required for BBV test discussion in consultations estimated at 2 min. The patient survey also showed high acceptance of the technology. CONCLUSION: This pilot study demonstrated that BBV_TP1 increased BBV testing rates in primary care via targeted screening, although testing rates subsequently fell whilst the application remained active. Such systems can potentially reduce late diagnoses, while having high acceptance by clinicians and patients. Larger studies with longer follow-up are needed to demonstrate efficacy and cost-effectiveness.

Snorkelling and breath-hold diving fatalities in New Zealand, 2007 to 2016.

INTRODUCTION: New Zealand's (NZ) long coastline offers a diverse underwater environment with abundant opportunities for harvesting seafood and for recreation. Fatalities from snorkelling/breath-hold diving have been reported from the 1960s through to 2006. Those from 2007 to 2016 are reported here. METHODS: The National Coronial Information System, the Australasian Diving Safety Foundation diving fatality database, and the Water Safety NZ "Drownbase" were searched and additional coronial data provided by the NZ Ministry of Justice. An anonymised database was created and analysed for multiple factors. A chain of events analysis was performed for each case. RESULTS: There were 38 snorkelling or breath-hold-related deaths in NZ, 33 men and five women. Twenty-nine were breath-hold divers involved in gathering seafood, and six 'surface snorkellers', predominantly sightseeing. Two-thirds were diving alone and/or were not being observed by anyone out of the water. Twenty-eight victims were classified as overweight or obese and 19/38 were Maori. Pre-existing health factors that may have or definitely contributed to the fatality were present in 30 cases. The most common of these were cardiac (18/38). Two divers had insulin-dependent diabetes mellitus, one each epilepsy and asthma whilst cannabis and/or alcohol were possible factors in seven deaths. Five (possibly six) deaths resulted from apnoeic hypoxia. CONCLUSIONS: Overall, death from snorkelling/breath-hold diving was an uncommon event (38 in 10 years). Poor judgement was a common feature. Middle-aged Maori men with pre-existing disease feature strongly. This suggests an on-going need for appropriate water safety education within and beyond the Maori community.

A Reasonable Officer: Examining the Relationships Among Stress, Training, and Performance in a Highly Realistic Lethal Force Scenario.

Under conditions of physiological stress, officers are sometimes required to make split-second life-or-death decisions, where deficits in performance can have tragic outcomes, including serious injury or death and strained police-community relations. The current study assessed the performance of 122 active-duty police officers during a realistic lethal force scenario to examine whether performance was affected by the officer's level of operational skills training, years of police service, and stress reactivity. Results demonstrated that the scenario produced elevated heart rates (i.e., 150 beats per minute), as well as perceptual and cognitive distortions, such as tunnel vision, commensurate with those observed in naturalistic use of force encounters. The average performance rating from the scenario was 59%, with 27% of participants making at least one lethal force error. Elevated stress reactivity was a predictor of poorer performance and increased lethal force errors. Level of training and years of police service had differential and complex effects on both performance and lethal force errors. Our results illustrate the need to critically reflect on police training practices and continue to make evidence-based improvements to training. The findings also highlight that while training may significantly improve outcomes, flawless performance is likely not probable, given the limits of human performance under stress. Implications for the objective reasonableness standard, which is used to assess the appropriateness of force in courts of law, are discussed.

Excited delirium syndrome (ExDS): Situational factors and risks to officer safety in non-fatal use of force encounters.

STUDY OBJECTIVE: Police use of force (UoF) encounters include individuals with Excited Delirium Syndrome (ExDS) with some frequency. Situational factors and risks to officer safety associated with these encounters have not been well studied. We examined the likelihood that subjects displaying various concomitant features of ExDS were under the influence of drugs and/or alcohol. We also examined the extent of subject violence, and the impact of this behaviour on the encounter (e.g., the odds of a struggle). Greater understanding of the prevalence of ExDS and the specific risk it represents to law enforcement officers and the subjects they encounter will guide appropriate policy and response strategies. METHODS: A prospective evaluation of a consecutive cohort of subjects involved in UoF encounters with police was conducted. Data were collected from January 2012 to December 2015. Consistent with previous research, the presence of six or more features was used to identify probable cases of ExDS. The odds that subjects in a state of probable ExDS were under the influence of drugs and/or alcohol was calculated and compared against subjects who exhibited less than three features of ExDS. In addition, the violent nature of subjects (e.g., the odds of a subject being in possession of a weapon) displaying various concomitant features of the syndrome was examined. The number of sudden and unexpected arrest-related death (ARDs) was documented. RESULTS: UoF occurred in 9006 of 10.9 million police-public interactions (0.08%). Of the UoF encounters, 156 (1.7%) subjects displayed six or more features of ExDS. With four recorded sudden and unexpected ARDs of violent and agitated subjects in our cohort, up to 6.3% of these subjects experiencing probable ExDS could be expected to be at risk of sudden death. Logistic regression analyses indicated that there were significantly higher odds that subjects exhibiting more features of ExDS (e.g., six or more) were under the influence of drugs. On the other hand, there were significantly lower odds that individuals exhibiting ExDS were under the influence of alcohol alone. In addition, those displaying a greater number of features demonstrated higher odds of engaging in assaultive behaviour, presenting a threat of grievous bodily harm or death, and being involved in a struggle that went to the ground with an officer. A slight increase in the presence of weapons was observed in encounters with probable ExDS. CONCLUSION: Our study provides important information to guide the development of policy and procedure in law enforcement. Police encounter a subject with ExDS 1 in every 58 UoF incidents (1.7%). Those individuals are at higher odds of being intoxicated with drugs according to officers' assessments and at risk of being further exerted during a struggle on the ground, both of which appear to play a major role in deaths associated to ExDS. There is a demonstrable increase in risk to officers and public safety from the violent behaviour displayed by subjects presenting a greater number of features of ExDS. Our data suggests that up to 6.3% of subjects in a state of ExDS could succumb to ARDs; however, we cannot comment on the prevalence of death for persons with ExDS who do not encounter police. Further research is needed to determine which force options optimize outcome for police and subjects. Additionally, research surrounding pathophysiology leading to death should focus on subjects with six or more features of ExDS. Ultimately, a better understanding in this area will contribute to improving the outcomes of these encounters for those suffering from ExDS and those tasked with assisting them.

Provisional report on diving-related fatalities in Australian waters in 2012.

INTRODUCTION: An individual case review of known diving-related deaths that occurred in Australia in 2012 was conducted. METHOD: The case studies were compiled using statements from witnesses and reports of the police and coroners. In each case, the particular circumstances of the accident and details from the post-mortem examination, where available, are provided. RESULTS: There were 26 reported fatalities (four less than the previous year). Only two of the victims were female (one snorkeller and one scuba diver). Fourteen deaths occurred while snorkelling and/or breath-hold diving, 11 while scuba diving and one diver died while using surface supplied breathing apparatus in a commercial pearl diving setting. Two breath-hold divers likely drowned as a result of apnoeic hypoxia. Cardiac-related issues were thought to have contributed to the deaths of at least three and possibly seven snorkellers and four scuba divers. CONCLUSIONS: Pre-existing medical conditions; poor organisation, planning and supervision; equipment-related problems; snorkelling or diving alone or with loose buddy oversight and apnoeic hypoxia were features in several deaths in this series.

Duloxetine for the Treatment of Patients with Suspected Sphincter of Oddi Dysfunction: A Pilot Study.

OBJECTIVE: To examine the tolerability and efficacy of duloxetine in patients with suspected sphincter of Oddi dysfunction (SOD). METHODS: An open-label, single-center, 12-week trial of duloxetine 60 mg once daily was conducted in 20 patients with suspected SOD. All patients were evaluated by expert pancreato-biliary specialists. The primary outcome measure was a Patient Global Impression of Change (PGIC) scale. Secondary measures included the pain burden, assessed by the Recurrent Abdominal Pain Intensity and Disability scale, the Short-Form Health Survey, and the Hospital Anxiety and Depression Scale. A positive clinical response was defined as a PGIC score of much or very much improved at 3 months and was estimated using a two-sided 90 % confidence interval. The primary outcome was analyzed using a one-sample binomial test at a significance level of 0.10. RESULTS: Of the 20 screened patients, 18 were enrolled; 14 completed at least one post-baseline evaluation; and 10 patients completed the third month endpoint visit. Patients missing the third month visit were considered non-responders for the primary outcome. Response rates were 90 % for study completers (n = 10; 90 % CI 74-100; p = 0.02) and 64 % for patients who completed at least one post-baseline evaluation (n = 14; 90 % CI 43-85; p = 0.42). Seven patients did not complete the study due to adverse events (mostly fatigue and nausea). CONCLUSIONS: Duloxetine showed an indication of efficacy in the treatment of pain in patients with suspected SOD, but adverse events limited its use. These preliminary, open-label results justify definitive placebo-controlled trials.

Distinguishing features of Excited Delirium Syndrome in non-fatal use of force encounters.

STUDY OBJECTIVE: The frequency with which the police encounter non-fatal cases of Excited Delirium Syndrome (ExDS) has not been well studied. To date only a single prospective, epidemiologic study has been completed to determine the prevalence of the features of ExDS in police use of force (UoF) encounters. We examined a cluster of previously published features associated with ExDS to establish if these features were consistently recognizable across policing populations, thus demonstrating reproducibility. We further sought to determine whether any feature or number of concomitant features were likely to have physiologic significance. These are important first steps in determining a case definition of ExDS in a law enforcement and medical setting. METHODS: A prospective evaluation of a consecutive cohort of subjects involved in UoF encounters with police was conducted. Data were collected through the UoF reporting database of a large Canadian law enforcement agency from January, 2012 to December, 2013. The ten core characteristics of ExDS that have been observed in past research were documented by officers and, consistent with previous research, the presence of six or more features was used to identify probable cases of ExDS and a state of medical emergency. RESULTS: UoF occurred in 4799 of 5.4 million police-public interactions (0.09%). Of the UoF encounters, 73 (1.5%) subjects displayed six or more features of ExDS. Upwards of 9.2% of these subjects could be expected to be at risk of sudden and unexpected arrest-related death (ARD). Features with the highest odds of being presented with a large number of concomitant features included "Does not Fatigue", "Superhuman Strength" and "Tactile Hyperthermia" (287, 137 and 93 times higher, respectively). Moreover, "Tactile Hyperthermia" demonstrated the highest odds of being presented in individuals with a large number of features as opposed to those with fewer (33 times higher). CONCLUSION: We demonstrate that there is the ability for law enforcement officers to consistently recognize and report features of ExDS that have been associated with ARD. The varying presence of features across the examined categories indicates that some features are more distinguishing than others, which may enable narrowing the scope of features that represent ExDS and understanding its pathophysiology. The current debate surrounding whether or not ExDS exists limits first responders and emergency physicians in their ability to increase awareness, improve training and interventions, and design appropriate policy and response protocols to reduce ARDs.

A computational model of invasive aspergillosis in the lung and the role of iron.

BACKGROUND: Invasive aspergillosis is a severe infection of immunocompromised hosts, caused by the inhalation of the spores of the ubiquitous environmental molds of the Aspergillus genus. The innate immune response in this infection entails a series of complex and inter-related interactions between multiple recruited and resident cell populations with each other and with the fungal cell; in particular, iron is critical for fungal growth. RESULTS: A computational model of invasive aspergillosis is presented here; the model can be used as a rational hypothesis-generating tool to investigate host responses to this infection. Using a combination of laboratory data and published literature, an in silico model of a section of lung tissue was generated that includes an alveolar duct, adjacent capillaries, and surrounding lung parenchyma. The three-dimensional agent-based model integrates temporal events in fungal cells, epithelial cells, monocytes, and neutrophils after inhalation of spores with cellular dynamics at the tissue level, comprising part of the innate immune response. Iron levels in the blood and tissue play a key role in the fungus' ability to grow, and the model includes iron recruitment and consumption by the different types of cells included. Parameter sensitivity analysis suggests the model is robust with respect to unvalidated parameters, and thus is a viable tool for an in silico investigation of invasive aspergillosis. CONCLUSIONS: Using laboratory data from a mouse model of invasive aspergillosis in the context of transient neutropenia as validation, the model predicted qualitatively similar time course changes in fungal burden, monocyte and neutrophil populations, and tissue iron levels. This model lays the groundwork for a multi-scale dynamic mathematical model of the immune response to Aspergillus species.

Antiretroviral treatment use, co-morbidities and clinical outcomes among Aboriginal participants in the Australian HIV Observational Database (AHOD).

BACKGROUND: There are few data regarding clinical care and outcomes of Indigenous Australians living with HIV and it is unknown if these differ from non-Indigenous HIV-positive Australians. METHODS: AHOD commenced enrolment in 1999 and is a prospective cohort of HIV-positive participants attending HIV outpatient services throughout Australia, of which 20 (74 %) sites report Indigenous status. Data were collected up until March 2013 and compared between Indigenous and non-Indigenous participants. Person-year methods were used to compare death rates, rates of loss to follow-up and rates of laboratory testing during follow-up between Indigenous and non-Indigenous participants. Factors associated with time to first combination antiretroviral therapy (cART) regimen change were assessed using Kaplan Meier and Cox Proportional hazards methods. RESULTS: Forty-two of 2197 (1.9 %) participants were Indigenous. Follow-up amongst Indigenous and non-Indigenous participants was 332 & 16270 person-years, respectively. HIV virological suppression was achieved in similar proportions of Indigenous and non-Indigenous participants 2 years after initiation of cART (81.0 % vs 76.5 %, p = 0.635). Indigenous status was not independently associated with shorter time to change from first- to second-line cART (aHR 0.95, 95 % CI 0.51-1.76, p = 0.957). Compared with non-Indigenous participants, Indigenous participants had significantly less frequent laboratory monitoring of CD4 count (rate:2.76 tests/year vs 2.97 tests/year, p = 0.025) and HIV viral load (rate:2.53 tests/year vs 2.93 tests/year, p < 0.001), while testing rates for lipids and blood glucose were almost half that of non-indigenous participants (rate:0.43/year vs 0.71 tests/year, p < 0.001). Loss to follow-up (23.8 % vs 29.8 %, p = 0.496) and death (2.4 % vs 7.1 %, p = 0.361) occurred in similar proportions of indigenous and non-Indigenous participants, respectively, although causes of death in both groups were mostly non-HIV-related. CONCLUSIONS: As far as we are aware, these are the first data comparing clinical outcomes between Indigenous and non-Indigenous HIV-positive Australians. The forty-two Indigenous participants represent over 10 % of all Indigenous Australians ever diagnosed with HIV. Although outcomes were not significantly different, Indigenous patients had lower rates of laboratory testing for HIV and lipid/glucose parameters. Given the elevated risk of cardiovascular disease in the general Indigenous community, the additional risk factor of HIV infection warrants further focus on modifiable risk factors to maximise life expectancy in this population.

Facilitators and barriers to implementation of a pragmatic clinical trial in Aboriginal health services.

OBJECTIVE: To identify facilitators and barriers to clinical trial implementation in Aboriginal health services. DESIGN: Indepth interview study with thematic analysis. SETTING: Six Aboriginal community-controlled health services and one government-run service involved in the Kanyini Guidelines Adherence with the Polypill (KGAP) study, a pragmatic randomised controlled trial that aimed to improve adherence to indicated drug treatments for people at high risk of cardiovascular disease. PARTICIPANTS: 32 health care providers and 21 Aboriginal and Torres Strait Islander patients. RESULTS: A fundamental enabler was that participants considered the research to be governed and endorsed by the local health service. That the research was perceived to address a health priority for communities was also highly motivating for both providers and patients. Enlisting the support of Aboriginal and Torres Strait Islander staff champions who were visible to the community as the main source of information about the trial was particularly important. The major implementation barrier for staff was balancing their service delivery roles with adherence to often highly demanding trial-related procedures. This was partially alleviated by the research team's provision of onsite support and attempts to make trial processes more streamlined. Although more intensive support was highly desired, there were usually insufficient resources to provide this. CONCLUSION: Despite strong community and health service support, major investments in time and resources are needed to ensure successful implementation and minimal disruption to already overstretched, routine services. Trial budgets will necessarily be inflated as a result. Funding agencies need to consider these additional resource demands when supporting trials of a similar nature.

Sexual behaviour, drug use and health service use by young Noongar people in Western Australia: a snapshot.

UNLABELLED: Background This study aimed to describe sexual health behaviour, alcohol and other drug use, and health service use among young Noongar people in the south-west of Western Australia. METHOD: A cross-sectional survey was undertaken among a sample of 244 Noongar people aged 16-30 years. RESULTS: The sample was more disadvantaged than the wider Noongar population. Sexual activity was initiated at a young age, 18% had two or more casual sex partners in the previous 12 months, with men more likely to have done so than women (23% vs 14%). Condoms were always or often carried by 57% of men and 37% of women, and 36% of men and 23% of women reported condom use at last sex with a casual partner. Lifetime sexually transmissible infection diagnosis was 14%. Forty percent currently smoked tobacco and 25% reported risky alcohol consumption on a weekly and 7% on an almost daily basis. Cannabis was used by 37%, 12% used drugs in addition to cannabis and 11% reported recently injecting drugs. In the previous 12 months, 66% had a health check and 31% were tested for HIV or sexually transmissible infections. Additionally, 25% sought advice or assistance for mental health or alcohol and other drug issues. DISCUSSION: Although some respondents engaged in risky sexual behaviour, alcohol and other drug use or both, most did not. Particularly encouraging was the engagement of respondents with the health care system, especially among those engaging in risky behaviours. The results confound negative stereotypes of Aboriginal people and demonstrate a level of resilience among respondents.

Human Hematopoietic Signal peptide-containing Secreted 1 (hHSS1) modulates genes and pathways in glioma: implications for the regulation of tumorigenicity and angiogenesis.

BACKGROUND: Human Hematopoietic Signal peptide-containing Secreted 1 (hHSS1) is a truly novel protein, defining a new class of secreted factors. We have previously reported that ectopic overexpression of hHSS1 has a negative modulatory effect on cell proliferation and tumorigenesis in glioblastoma model systems. Here we have used microarray analysis, screened glioblastoma samples in The Cancer Genome Atlas (TCGA), and studied the effects of hHSS1 on glioma-derived cells and endothelial cells to elucidate the molecular mechanisms underlying the anti-tumorigenic effects of hHSS1. METHODS: Gene expression profiling of human glioma U87 and A172 cells overexpressing hHSS1 was performed. Ingenuity® iReport™ and Ingenuity Pathway Analysis (IPA) were used to analyze the gene expression in the glioma cells. DNA content and cell cycle analysis were performed by FACS, while cell migration, cell invasion, and effects of hHSS1 on HUVEC tube formation were determined by transwell and matrigel assays. Correlation was made between hHSS1 expression and specific genes in glioblastoma samples in the TCGA database. RESULTS: We have clarified the signaling and metabolic pathways (i.e. role of BRCA1 in DNA damage response), networks (i.e. cell cycle) and biological processes (i.e. cell division process of chromosomes) that result from hHSS1effects upon glioblastoma growth. U87-overexpressing hHSS1 significantly decreased the number of cells in the G0/G1 cell cycle phase, and significantly increased cells in the S and G2/M phases (P < 0.05). U87-overexpressing hHSS1 significantly lost their ability to migrate (P < 0.001) and to invade (P < 0.01) through matrigel matrix. hHSS1-overexpression significantly decreased migration of A172 cells (P < 0.001), inhibited A172 tumor-induced migration and invasion of HUVECs (P < 0.001), and significantly inhibited U87 tumor-induced invasion of HUVECs (P < 0.001). Purified hHSS1 protein inhibited HUVEC tube formation. TCGA database revealed significant correlation between hHSS1 and BRCA2 (r = -0.224, P < 0.0005), ADAMTS1 (r = -0.132, P <0.01) and endostatin (r = 0.141, P < 0.005). CONCLUSIONS: hHSS1-overexpression modulates signaling pathways involved in tumorigenesis. hHSS1 inhibits glioma-induced cell cycle progression, cell migration, invasion and angiogenesis. Our data suggest that hHSS1 is a potential therapeutic for malignant glioblastoma possessing significant antitumor and anti-angiogenic activity.

Single low-dose rHuIL-12 safely triggers multilineage hematopoietic and immune-mediated effects.

BACKGROUND: Recombinant human interleukin 12 (rHuIL-12) regulates hematopoiesis and cell-mediated immunity. Based on these hematopoietic and immunomodulatory activities, a recombinant human IL-12 (rHuIL-12) is now under development to address the unmet need for a medical countermeasure against the hematopoietic syndrome of the acute radiation syndrome (HSARS) that occurs in individuals exposed to lethal radiation, and also to serve as adjuvant therapy that could provide dual hematopoietic and immunotherapeutic benefits in patients with cancer receiving chemotherapy. We sought to demonstrate in healthy subjects the safety of rHuIL-12 at single, low doses that are appropriate for use as a medical countermeasure for humans exposed to lethal radiation and as an immunomodulatory anti-cancer agent. METHODS: Two placebo-controlled, double-blinded studies assessed the safety, tolerability, pharmacokinetics and pharmacodynamics of rHuIL-12. The first-in-human (FIH) dose-escalation study randomized subjects to single subcutaneous injections of placebo or rHuIL-12 at 2, 5, 10, and 20 µg doses. Due to toxicity, dose was reduced to 15 µg and then to 12 µg. The phase 1b expansion study randomized subjects to the highest safe and well tolerated dose of 12 µg. RESULTS: Thirty-two subjects were enrolled in the FIH study: 4 active and 2 placebo at rHuIL-12 doses of 2, 5, 10, 12, and 15 µg; 1 active and 1 placebo at 20 µg. Sixty subjects were enrolled in the expansion study: 48 active and 12 placebo at 12 µg dose of rHuIL-12. In both studies, the most common adverse events (AEs) related to rHuIL-12 were headache, dizziness, and chills. No immunogenicity was observed. Elimination of rHuIL-12 was biphasic, suggesting significant distribution into extravascular spaces. rHuIL-12 triggered transient changes in neutrophils, platelets, reticulocytes, lymphocytes, natural killer cells, and CD34+ hematopoietic progenitor cells, and induced increases in interferon-γ and C-X-C motif chemokine 10. CONCLUSION: A single low dose of rHuIl-12 administered subcutaneously can elicit hematological and immune-mediated effects without undue toxicity. The safety and the potent multilineage hematopoietic/immunologic effects triggered by low-dose rHuIL-12 support the development of rHuIL-12 both as a radiation medical countermeasure and as adjuvant immunotherapy for cancer. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01742221.

Provisional report on diving-related fatalities in Australian waters 2008.

INTRODUCTION: An individual case review of diving-related deaths, reported as occurring in Australia in 2008, was conducted as part of the DAN Asia-Pacific dive fatality reporting project. METHOD: The case studies were compiled using reports from witnesses, the police and coroners. In each case, the particular circumstances of the accident and details from the post-mortem examination, where available, are provided. RESULTS: In total, there were 19 reported fatalities (the same as for 2007), 17 involving males. Twelve deaths occurred while snorkelling and/or breath-hold diving,and six while scuba diving. One diver died while using surface-supply breathing apparatus. Two breath-hold divers appear to have died as a result of apnoeic hypoxia, at least one case likely associated with hyperventilation. Two deaths resulted from trauma: one from impact with a boat and the other from an encounter with a great white shark. Cardiac-related issues were thought to have contributed to the deaths of five snorkellers and at least two, possibly three, scuba divers. CONCLUSIONS: Trauma from a marine creature, snorkelling or diving alone, apnoeic hypoxia and pre-existing medical conditions were once again features in several deaths in this series.

Provisional report on diving-related fatalities in Australian waters 2009.

INTRODUCTION: An individual case review of diving-related deaths reported as occurring in Australia in 2009 was conducted as part of the DAN Asia-Pacific Dive Fatality Reporting Project. METHOD: The case studies were compiled using reports from witnesses, the police and coroners. In each case, the particular circumstances of the accident and details from the post-mortem examination, where available, are provided. RESULTS: In total, there were 21 reported fatalities (two more than in 2008), including 18 males and three females. Twelve deaths occurred while snorkelling and/or breath-hold diving, eight while scuba diving and one while using surface-supply breathing apparatus. Apneic hypoxia continues to be a problem with breath-hold divers and appears to have caused the death of three victims in this series. Cardiac-related issues were thought to have been the disabling injury in the deaths of at least three snorkel divers and at least three scuba divers. One of the victims was a student who became separated from her instructor on an introductory scuba dive in poor visibility. CONCLUSIONS: Apneic hypoxia, pre-existing medical conditions, snorkelling or diving alone, separation and inadequate supervision were once again features in several deaths in this series.

Provisional report on diving-related fatalities in Australian waters 2006.

INTRODUCTION: An individual case review of diving-related deaths reported as occurring in Australia in 2006 was conducted as part of the Divers Alert Network Asia-Pacific (DAN AP) dive fatality reporting project. METHOD: The case studies were compiled using reports from witnesses, the police and coroners. In each case, the particular circumstances of the accident and details from the post-mortem examination, where available, are provided. RESULTS: In total, there were 16 reported fatalities (eight fewer than 2005), all involving males. Ten deaths occurred while snorkelling and/or breath-hold diving and six while scuba diving, one of which involved the use of a closed-circuit rebreather. One death resulted from an encounter with a stingray and two involved scuba divers diving alone after an extended absence from diving. Cardiac-related issues were thought likely to have contributed to the deaths of six snorkel divers and one scuba diver. CONCLUSIONS: Trauma from a marine creature, snorkelling or diving alone and pre-existing medical conditions once again featured in several deaths in this series.

Discovery of tetrahydroisoquinoline (THIQ) derivatives as potent and orally bioavailable LFA-1/ICAM-1 antagonists.

This letter describes the discovery of a novel series of tetrahydroisoquinoline (THIQ)-derived small molecules that potently inhibit both human T-cell migration and super-antigen induced T-cell activation through disruption of the binding of integrin LFA-1 to its receptor, ICAM-1. In addition to excellent in vitro potency, 6q shows good pharmacokinetic properties and its ethyl ester (6t) demonstrates good oral bioavailability in both mouse and rat. Either intravenous administration of 6q or oral administration of its ethyl ester (6t) produced a significant reduction of neutrophil migration in a thioglycollate-induced murine peritonitis model.