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Objectives: To develop an online treatment decision aid (OTDA) to assist patients with low-risk prostate cancer (LRPC) and their partners in making treatment decisions. Patients and methods: Navigate, an OTDA for LRPC, was rigorously co-designed by patients with a confirmed diagnosis or at risk of LRPC and their partners, clinicians, researchers and website designers/developers. A theoretical model guided the development process. A mixed methods approach was used incorporating (1) evidence for essential design elements for OTDAs; (2) evidence for treatment options for LRPC; (3) an iterative co-design process involving stakeholder workshops and prototype review; and (4) expert rating using the International Patient Decision Aid Standards (IPDAS). Three co-design workshops with potential users (n = 12) and research and web-design team members (n = 10) were conducted. Results from each workshop informed OTDA modifications to the OTDA for testing in the subsequent workshop. Clinician (n = 6) and consumer (n = 9) feedback on usability and content on the penultimate version was collected. Results: The initial workshops identified key content and design features that were incorporated into the draft OTDA, re-workshopped and incorporated into the penultimate OTDA. Expert feedback on usability and content was also incorporated into the final OTDA. The final OTDA was deemed comprehensive, clear and appropriate and met all IPDAS criteria. Conclusion: Navigate is an interactive and acceptable OTDA for Australian men with LRPC designed by men for men using a co-design methodology. The effectiveness of Navigate in assisting patient decision-making is currently being assessed in a randomised controlled trial with patients with LRPC and their partners.

The coronavirus disease 2019 (COVID-19) pandemic resulted in severe interruptions to clinical research worldwide. This global public health crisis required investigators and researchers to rapidly develop and implement new strategies and solutions to mitigate its negative impact on the progress of clinical trials. In this paper, we describe the challenges, strategies, and lessons learned regarding the continuation of a supportive oncology clinical trial during the pandemic. We hope to provide insight into the implementation of clinical trials during a public health emergency to be better prepared for future instances. Trial registration: ClinicalTrials.gov, a service of the US National Institute of Health (NCT03030859). Registered on 22 January 2017.

© 2021, The Author(s). Following publication of the original article [1], we were notified of a typo in the spelling of the 10th author name, originally spelt as “Cavdon” instead of “Cavedon” (i.e., missing “e”). The original article has been corrected.

© 2021, The Author(s). Background: Active surveillance (AS) is the disease management option of choice for low-risk prostate cancer. Despite this, men with low-risk prostate cancer (LRPC) find management decisions distressing and confusing. We developed Navigate, an online decision aid to help men and their partners make management decisions consistent with their values. The aims are to evaluate the impact of Navigate on uptake of AS; decision-making preparedness; decisional conflict, regret and satisfaction; quality of illness communication; and prostate cancer-specific quality of life and anxiety. In addition, the healthcare cost impact, cost-effectiveness and patterns of use of Navigate will be assessed. This paper describes the study protocol. Methods: Three hundred four men and their partners are randomly assigned one-to-one to Navigate or to the control arm. Randomisation is electronically generated and stratified by site. Navigate is an online decision aid that presents up-to-date, unbiased information on LRPC tailored to Australian men and their partners including each management option and potential side-effects, and an interactive values clarification exercise. Participants in the control arm will be directed to the website of Australia’s peak national body for prostate cancer. Eligible patients will be men within 3 months of being diagnosed with LRPC, aged 18 years or older, and who are yet to make a treatment decision, who are deemed eligible for AS by their treating clinician and who have Internet access and sufficient English to participate. The primary outcome is self-reported uptake of AS as the first-line management option. Secondary outcomes include self-reported preparedness for decision-making; decisional conflict, regret and satisfaction; quality of illness communication; and prostate cancer-specific quality of life. Uptake of AS 1 month after consent will be determined through patient self-report. Men and their partners will complete study outc

Background: Active surveillance (AS) is the disease management option of choice for low-risk prostate cancer. Despite this, men with low-risk prostate cancer (LRPC) find management decisions distressing and confusing. We developed Navigate, an online decision aid to help men and their partners make management decisions consistent with their values. The aims are to evaluate the impact of Navigate on uptake of AS; decision-making preparedness; decisional conflict, regret and satisfaction; quality of illness communication; and prostate cancer-specific quality of life and anxiety. In addition, the healthcare cost impact, cost-effectiveness and patterns of use of Navigate will be assessed. This paper describes the study protocol. Methods: Three hundred four men and their partners are randomly assigned one-to-one to Navigate or to the control arm. Randomisation is electronically generated and stratified by site. Navigate is an online decision aid that presents up-to-date, unbiased information on LRPC tailored to Australian men and their partners including each management option and potential side-effects, and an interactive values clarification exercise. Participants in the control arm will be directed to the website of Australia’s peak national body for prostate cancer. Eligible patients will be men within 3 months of being diagnosed with LRPC, aged 18 years or older, and who are yet to make a treatment decision, who are deemed eligible for AS by their treating clinician and who have Internet access and sufficient English to participate. The primary outcome is self-reported uptake of AS as the first-line management option. Secondary outcomes include self-reported preparedness for decision-making; decisional conflict, regret and satisfaction; quality of illness communication; and prostate cancer-specific quality of life. Uptake of AS 1 month after consent will be determined through patient self-report. Men and their partners will complete study outcome measures before

Abstract Background Active surveillance (AS) is the disease management option of choice for low-risk prostate cancer. Despite this, men with low-risk prostate cancer (LRPC) find management decisions distressing and confusing. We developed Navigate, an online decision aid to help men and their partners make management decisions consistent with their values. The aims are to evaluate the impact of Navigate on uptake of AS; decision-making preparedness; decisional conflict, regret and satisfaction; quality of illness communication; and prostate cancer-specific quality of life and anxiety. In addition, the healthcare cost impact, cost-effectiveness and patterns of use of Navigate will be assessed. This paper describes the study protocol. Methods Three hundred four men and their partners are randomly assigned one-to-one to Navigate or to the control arm. Randomisation is electronically generated and stratified by site. Navigate is an online decision aid that presents up-to-date, unbiased information on LRPC tailored to Australian men and their partners including each management option and potential side-effects, and an interactive values clarification exercise. Participants in the control arm will be directed to the website of Australia’s peak national body for prostate cancer. Eligible patients will be men within 3 months of being diagnosed with LRPC, aged 18 years or older, and who are yet to make a treatment decision, who are deemed eligible for AS by their treating clinician and who have Internet access and sufficient English to participate. The primary outcome is self-reported uptake of AS as the first-line management option. Secondary outcomes include self-reported preparedness for decision-making; decisional con

© 2021, The Author(s). Following publication of the original article [1], we were notified of a typo in the spelling of the 10th author name, originally spelt as “Cavdon” instead of “Cavedon” (i.e., missing “e”). The original article has been corrected.

© 2021, The Author(s). Background: Active surveillance (AS) is the disease management option of choice for low-risk prostate cancer. Despite this, men with low-risk prostate cancer (LRPC) find management decisions distressing and confusing. We developed Navigate, an online decision aid to help men and their partners make management decisions consistent with their values. The aims are to evaluate the impact of Navigate on uptake of AS; decision-making preparedness; decisional conflict, regret and satisfaction; quality of illness communication; and prostate cancer-specific quality of life and anxiety. In addition, the healthcare cost impact, cost-effectiveness and patterns of use of Navigate will be assessed. This paper describes the study protocol. Methods: Three hundred four men and their partners are randomly assigned one-to-one to Navigate or to the control arm. Randomisation is electronically generated and stratified by site. Navigate is an online decision aid that presents up-to-date, unbiased information on LRPC tailored to Australian men and their partners including each management option and potential side-effects, and an interactive values clarification exercise. Participants in the control arm will be directed to the website of Australia’s peak national body for prostate cancer. Eligible patients will be men within 3 months of being diagnosed with LRPC, aged 18 years or older, and who are yet to make a treatment decision, who are deemed eligible for AS by their treating clinician and who have Internet access and sufficient English to participate. The primary outcome is self-reported uptake of AS as the first-line management option. Secondary outcomes include self-reported preparedness for decision-making; decisional conflict, regret and satisfaction; quality of illness communication; and prostate cancer-specific quality of life. Uptake of AS 1 month after consent will be determined through patient self-report. Men and their partners will complete study outc

Kidney transplant recipients may be at a high risk of developing critical coronavirus disease 2019 (COVID-19) illness due to chronic immunosuppression and comorbidities. We identified hospitalized adult kidney transplant recipients at 12 transplant centers in the United States, Italy, and Spain who tested positive for COVID-19. Clinical presentation, laboratory values, immunosuppression, and treatment strategies were reviewed, and predictors of poor clinical outcomes were determined through multivariable analyses. Among 9845 kidney transplant recipients across centers, 144 were hospitalized due to COVID-19 during the 9-week study period. Of the 144 patients, 66% were male with a mean age of 60 (±12) years, and 40% were Hispanic and 25% were African American. Prevalent comorbidities included hypertension (95%), diabetes (52%), obesity (49%), and heart (28%) and lung (19%) disease. Therapeutic management included antimetabolite withdrawal (68%), calcineurin inhibitor withdrawal (23%), hydroxychloroquine (71%), antibiotics (74%), tocilizumab (13%), and antivirals (14%). During a median follow-up period of 52 days (IQR: 16-66 days), acute kidney injury occurred in 52% cases, with respiratory failure requiring intubation in 29%, and the mortality rate was 32%. The 46 patients who died were older, had lower lymphocyte counts and estimated glomerular filtration rate levels, and had higher serum lactate dehydrogenase, procalcitonin, and interleukin-6 levels. In sum, hospitalized kidney transplant recipients with COVID-19 have higher rates of acute kidney injury and mortality.

IntroductionMuch of the higher risk for end-stage kidney disease (ESKD) in African American individuals relates to ancestry-specific variation in the apolipoprotein L1 gene (APOL1). Relative to kidneys from European American deceased-donors, kidneys from African American deceased-donors have shorter allograft survival and African American living-kidney donors more often develop ESKD. The National Institutes of Health (NIH)-sponsored APOL1 Long-term Kidney Transplantation Outcomes Network (APOLLO) is prospectively assessing kidney allograft survival from donors with recent African ancestry based on donor and recipient APOL1 genotypes.MethodsAPOLLO will evaluate outcomes from 2614 deceased kidney donor-recipient pairs, as well as additional living-kidney donor-recipient pairs and unpaired deceased-donor kidneys.ResultsThe United Network for Organ Sharing (UNOS), Association of Organ Procurement Organizations, American Society of Transplantation, American Society for Histocompatibility and Immunogenetics, and nearly all U.S. kidney transplant programs, organ procurement organizations (OPOs), and histocompatibility laboratories are participating in this observational study. APOLLO employs a central institutional review board (cIRB) and maintains voluntary partnerships with OPOs and histocompatibility laboratories. A Community Advisory Council composed of African American individuals with a personal or family history of kidney disease has advised the NIH Project Office and Steering Committee since inception. UNOS is providing data for outcome analyses.ConclusionThis article describes unique aspects of the protocol, design, and performance of APOLLO. Results will guide use of APOL1 genotypic data to improve the assessment of quality in deceased-donor kidneys and could increase numbers of transplanted kidneys, reduce rates of discard, and improve the safety of living-kidney donation.

Kidney transplant recipients may be at a high risk of developing critical coronavirus disease 2019 (COVID-19) illness due to chronic immunosuppression and comorbidities. We identified hospitalized adult kidney transplant recipients at 12 transplant centers in the United States, Italy, and Spain who tested positive for COVID-19. Clinical presentation, laboratory values, immunosuppression, and treatment strategies were reviewed, and predictors of poor clinical outcomes were determined through multivariable analyses. Among 9845 kidney transplant recipients across centers, 144 were hospitalized due to COVID-19 during the 9-week study period. Of the 144 patients, 66% were male with a mean age of 60 (±12) years, and 40% were Hispanic and 25% were African American. Prevalent comorbidities included hypertension (95%), diabetes (52%), obesity (49%), and heart (28%) and lung (19%) disease. Therapeutic management included antimetabolite withdrawal (68%), calcineurin inhibitor withdrawal (23%), hydroxychloroquine (71%), antibiotics (74%), tocilizumab (13%), and antivirals (14%). During a median follow-up period of 52 days (IQR: 16-66 days), acute kidney injury occurred in 52% cases, with respiratory failure requiring intubation in 29%, and the mortality rate was 32%. The 46 patients who died were older, had lower lymphocyte counts and estimated glomerular filtration rate levels, and had higher serum lactate dehydrogenase, procalcitonin, and interleukin-6 levels. In sum, hospitalized kidney transplant recipients with COVID-19 have higher rates of acute kidney injury and mortality.

IntroductionMuch of the higher risk for end-stage kidney disease (ESKD) in African American individuals relates to ancestry-specific variation in the apolipoprotein L1 gene (APOL1). Relative to kidneys from European American deceased-donors, kidneys from African American deceased-donors have shorter allograft survival and African American living-kidney donors more often develop ESKD. The National Institutes of Health (NIH)-sponsored APOL1 Long-term Kidney Transplantation Outcomes Network (APOLLO) is prospectively assessing kidney allograft survival from donors with recent African ancestry based on donor and recipient APOL1 genotypes.MethodsAPOLLO will evaluate outcomes from 2614 deceased kidney donor-recipient pairs, as well as additional living-kidney donor-recipient pairs and unpaired deceased-donor kidneys.ResultsThe United Network for Organ Sharing (UNOS), Association of Organ Procurement Organizations, American Society of Transplantation, American Society for Histocompatibility and Immunogenetics, and nearly all U.S. kidney transplant programs, organ procurement organizations (OPOs), and histocompatibility laboratories are participating in this observational study. APOLLO employs a central institutional review board (cIRB) and maintains voluntary partnerships with OPOs and histocompatibility laboratories. A Community Advisory Council composed of African American individuals with a personal or family history of kidney disease has advised the NIH Project Office and Steering Committee since inception. UNOS is providing data for outcome analyses.ConclusionThis article describes unique aspects of the protocol, design, and performance of APOLLO. Results will guide use of APOL1 genotypic data to improve the assessment of quality in deceased-donor kidneys and could increase numbers of transplanted kidneys, reduce rates of discard, and improve the safety of living-kidney donation.

Kidney transplant recipients may be at a high risk of developing critical coronavirus disease 2019 (COVID-19) illness due to chronic immunosuppression and comorbidities. We identified hospitalized adult kidney transplant recipients at 12 transplant centers in the United States, Italy, and Spain who tested positive for COVID-19. Clinical presentation, laboratory values, immunosuppression, and treatment strategies were reviewed, and predictors of poor clinical outcomes were determined through multivariable analyses. Among 9845 kidney transplant recipients across centers, 144 were hospitalized due to COVID-19 during the 9-week study period. Of the 144 patients, 66% were male with a mean age of 60 (±12) years, and 40% were Hispanic and 25% were African American. Prevalent comorbidities included hypertension (95%), diabetes (52%), obesity (49%), and heart (28%) and lung (19%) disease. Therapeutic management included antimetabolite withdrawal (68%), calcineurin inhibitor withdrawal (23%), hydroxychloroquine (71%), antibiotics (74%), tocilizumab (13%), and antivirals (14%). During a median follow-up period of 52 days (IQR: 16-66 days), acute kidney injury occurred in 52% cases, with respiratory failure requiring intubation in 29%, and the mortality rate was 32%. The 46 patients who died were older, had lower lymphocyte counts and estimated glomerular filtration rate levels, and had higher serum lactate dehydrogenase, procalcitonin, and interleukin-6 levels. In sum, hospitalized kidney transplant recipients with COVID-19 have higher rates of acute kidney injury and mortality.

Background In contrast to studies showing gradual adaptation of melatonin (MT) rhythms to an advanced photoperiod in humans and rodents, we previously demonstrated that equine MT rhythms complete a 6-h light/dark (LD) phase advance on the first post-shift day. This suggested the possibility that melatonin secretion in the horse may be more strongly light-driven as opposed to endogenously rhythmic and light entrained. The present study investigates whether equine melatonin is endogenously rhythmic in extended darkness (DD). Methods Six healthy, young mares were maintained in a lightproof barn under an LD cycle that mimicked the ambient natural photoperiod outside. Blood samples were collected at 2-h intervals for 48 consecutive h: 24-h in LD, followed by 24-h in extended dark (DD). Serum was harvested and stored at -20°C until melatonin and cortisol were measured by commercial RIA kits. Results Two-way repeated measures ANOVA (n = 6/time point) revealed a significant circadian time (CT) x lighting condition interaction (p < .0001) for melatonin with levels non-rhythmic and consistently high during DD (CT 0-24). In contrast, cortisol displayed significant clock-time variation throughout LD and DD (p = .0009) with no CT x light treatment interaction (p = .4018). Cosinor analysis confirmed a significant 24-h temporal variation for melatonin in LD (p = .0002) that was absent in DD (p = .51), while there was an apparent circadian component in cortisol, which approached significance in LD (p = .076), and was highly significant in DD (p = .0059). Conclusions The present finding of no 24 h oscillation in melatonin in DD is the first evidence indicating that melatonin is not gated by a self-sustained circadian process in the horse. Melatonin is therefore not a suitable marker of circadian phase in this species. In conjunction with recent similar findings in reindeer, it appears that biosynthesis of melatonin in the pineal glands of some ungulates is strongly drive

Background In contrast to studies showing gradual adaptation of melatonin (MT) rhythms to an advanced photoperiod in humans and rodents, we previously demonstrated that equine MT rhythms complete a 6-h light/dark (LD) phase advance on the first post-shift day. This suggested the possibility that melatonin secretion in the horse may be more strongly light-driven as opposed to endogenously rhythmic and light entrained. The present study investigates whether equine melatonin is endogenously rhythmic in extended darkness (DD). Methods Six healthy, young mares were maintained in a lightproof barn under an LD cycle that mimicked the ambient natural photoperiod outside. Blood samples were collected at 2-h intervals for 48 consecutive h: 24-h in LD, followed by 24-h in extended dark (DD). Serum was harvested and stored at -20°C until melatonin and cortisol were measured by commercial RIA kits. Results Two-way repeated measures ANOVA (n = 6/time point) revealed a significant circadian time (CT) x lighting condition interaction (p < .0001) for melatonin with levels non-rhythmic and consistently high during DD (CT 0-24). In contrast, cortisol displayed significant clock-time variation throughout LD and DD (p = .0009) with no CT x light treatment interaction (p = .4018). Cosinor analysis confirmed a significant 24-h temporal variation for melatonin in LD (p = .0002) that was absent in DD (p = .51), while there was an apparent circadian component in cortisol, which approached significance in LD (p = .076), and was highly significant in DD (p = .0059). Conclusions The present finding of no 24 h oscillation in melatonin in DD is the first evidence indicating that melatonin is not gated by a self-sustained circadian process in the horse. Melatonin is therefore not a suitable marker of circadian phase in this species. In conjunction with recent similar findings in reindeer, it appears that biosynthesis of melatonin in the pineal glands of some ungulates is strongly drive

BACKGROUND: In the general population, excessive sedentary behaviour is associated with increased all-cause mortality. Few studies have examined this relationship in people with cardiovascular disease (CVD). Using a sample of people with CVD who were excluded from an analysis of the Australian Diabetes, Obesity and Lifestyle (AusDiab) study, we examined the relationship between sedentary behaviour and 13-year all-cause mortality. METHODS: In the original AusDiab study, television viewing time was used as a marker of sedentary behaviour in 609 adults (≥45 years of age) with CVD. During 6,291 person-years of follow-up (median follow-up 13 years), there were 294 deaths (48% of sample). Using the time scale of attained age, the Cox proportional hazards model predicting all-cause mortality adjusted for sex, self-rated general health, leisure-time physical activity, smoking status, education, household income, body mass index, lipid levels, blood pressure, and diabetes mellitus was used. RESULTS: Compared with a TV viewing time of <2hours per day, the fully adjusted hazard ratios for all-cause mortality were 1.18 (95% CI, 0.88 to 1.57) for ≥2 to <4hours per day and 1.52 (95% CI, 1.09 to 2.13) for >4hours per day. CONCLUSIONS: Sedentary behaviour was associated with increased risk of all-cause mortality in people with CVD, independent of physical activity and other confounders. In addition to the promotion of regular physical activity, cardiac rehabilitation efforts which also focus on reducing sedentary behaviour may be beneficial.

IntroductionAfatinib is an ErbB family receptor inhibitor with efficacy in head and neck squamous cell carcinoma (HNSCC). A phase I trial was conducted to determine the maximally tolerated dose (MTD) of afatinib in combination with carboplatin and paclitaxel as induction chemotherapy (IC).Material and methodsPatients with newly diagnosed, locally advanced HPV-negative or HPV-positive HNSCC with a significant smoking history were enrolled. Afatinib alone was given daily for two weeks as lead-in and subsequently given with carboplatin AUC 6mg/mlmin and paclitaxel 175mg/m(2) every 21days as IC. Afatinib was started at a dose of 20mg daily and dose escalated using a modified Fibonacci design. After completion of IC, afatinib was discontinued and patients received concurrent cisplatin 40mg/m(2) weekly and standard radiation. Toxicity was assessed using CTCAE version 4.0.ResultsSeven of nine patients completed afatinib lead-in and IC. Five patients had partial response and two patients had stable disease after IC. Dose level 1 (afatinib 20mg) was well tolerated with one grade 3 (ALT elevation) and one grade 4 (neutropenia) toxicities. However, dose level 2 (afatinib 30mg) was not well tolerated with nine grade 3 (pneumonia, abdominal pain, diarrhea, pancytopenia, and UTI), two grade 4 (sepsis) and one grade 5 (death) toxicities.ConclusionsThe MTD of afatinib given with carboplatin AUC 6mg/mlmin and paclitaxel 175mg/m(2) is 20mg daily. Combination of afatinib at doses higher than 20mg with carboplatin and paclitaxel should be administered with caution due to the toxicities.

BACKGROUND: Much attention has been given to identifying and supporting the minority of patients who develop severe clinical depression after a cardiac event. However, relatively little has been given to supporting the many patients who experience transient but significant emotional disturbance that we term the 'cardiac blues'. OBJECTIVE: The aim of this study was to investigate patients' preferences regarding information provision about cardiac blues. METHODS: One hundred and sixty consecutive cardiac patients admitted to two Victorian hospitals in Australia were interviewed three times over six months. They were asked about emotional issues, including information provision preferences. RESULTS: Four out of five (81%) patients would like to have received information about the cardiac blues, but only a minority received this information. CONCLUSION: Most patients want to know about cardiac blues. The development and evaluation of resources for health professionals and patients to support recovery through cardiac blues appears warranted.

BACKGROUND: In addition to HLA genetic incompatibility, non-HLA difference between donor and recipients of transplantation leading to allograft rejection are now becoming evident. We aimed to create a unique genome-wide platform to facilitate genomic research studies in transplant-related studies. We designed a genome-wide genotyping tool based on the most recent human genomic reference datasets, and included customization for known and potentially relevant metabolic and pharmacological loci relevant to transplantation. METHODS: We describe here the design and implementation of a customized genome-wide genotyping array, the 'TxArray', comprising approximately 782,000 markers with tailored content for deeper capture of variants across HLA, KIR, pharmacogenomic, and metabolic loci important in transplantation. To test concordance and genotyping quality, we genotyped 85 HapMap samples on the array, including eight trios. RESULTS: We show low Mendelian error rates and high concordance rates for HapMap samples (average parent-parent-child heritability of 0.997, and concordance of 0.996). We performed genotype imputation across autosomal regions, masking directly genotyped SNPs to assess imputation accuracy and report an accuracy of >0.962 for directly genotyped SNPs. We demonstrate much higher capture of the natural killer cell immunoglobulin-like receptor (KIR) region versus comparable platforms. Overall, we show that the genotyping quality and coverage of the TxArray is very high when compared to reference samples and to other genome-wide genotyping platforms. CONCLUSIONS: We have designed a comprehensive genome-wide genotyping tool which enables accurate association testing and imputation of ungenotyped SNPs, facilitating powerful and cost-effective large-scale genotyping of transplant-related studies.

Cancer-related fatigue is defined as a distressing, persistent, subjective sense of physical, emotional, and/or cognitive tiredness or exhaustion related to cancer or cancer treatment that is not proportional to recent activity and interferes with usual functioning. It is one of the most common side effects in patients with cancer. Fatigue has been shown to be a consequence of active treatment, but it may also persist into posttreatment periods. Furthermore, difficulties in end-of-life care can be compounded by fatigue. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Cancer-Related Fatigue provide guidance on screening for fatigue and recommendations for interventions based on the stage of treatment. Interventions may include education and counseling, general strategies for the management of fatigue, and specific nonpharmacologic and pharmacologic interventions. Fatigue is a frequently underreported complication in patients with cancer and, when reported, is responsible for reduced quality of life. Therefore, routine screening to identify fatigue is an important component in improving the quality of life for patients living with cancer.

BACKGROUND: In addition to HLA genetic incompatibility, non-HLA difference between donor and recipients of transplantation leading to allograft rejection are now becoming evident. We aimed to create a unique genome-wide platform to facilitate genomic research studies in transplant-related studies. We designed a genome-wide genotyping tool based on the most recent human genomic reference datasets, and included customization for known and potentially relevant metabolic and pharmacological loci relevant to transplantation. METHODS: We describe here the design and implementation of a customized genome-wide genotyping array, the 'TxArray', comprising approximately 782,000 markers with tailored content for deeper capture of variants across HLA, KIR, pharmacogenomic, and metabolic loci important in transplantation. To test concordance and genotyping quality, we genotyped 85 HapMap samples on the array, including eight trios. RESULTS: We show low Mendelian error rates and high concordance rates for HapMap samples (average parent-parent-child heritability of 0.997, and concordance of 0.996). We performed genotype imputation across autosomal regions, masking directly genotyped SNPs to assess imputation accuracy and report an accuracy of >0.962 for directly genotyped SNPs. We demonstrate much higher capture of the natural killer cell immunoglobulin-like receptor (KIR) region versus comparable platforms. Overall, we show that the genotyping quality and coverage of the TxArray is very high when compared to reference samples and to other genome-wide genotyping platforms. CONCLUSIONS: We have designed a comprehensive genome-wide genotyping tool which enables accurate association testing and imputation of ungenotyped SNPs, facilitating powerful and cost-effective large-scale genotyping of transplant-related studies.

Background: In addition to HLA genetic incompatibility, non-HLA difference between donor and recipients of transplantation leading to allograft rejection are now becoming evident. We aimed to create a unique genome-wide platform to facilitate genomic research studies in transplant-related studies. We designed a genome-wide genotyping tool based on the most recent human genomic reference datasets, and included customization for known and potentially relevant metabolic and pharmacological loci relevant to transplantation. Methods: We describe here the design and implementation of a customized genome-wide genotyping array, the 'TxArray', comprising approximately 782,000 markers with tailored content for deeper capture of variants across HLA, KIR, pharmacogenomic, and metabolic loci important in transplantation. To test concordance and genotyping quality, we genotyped 85 HapMap samples on the array, including eight trios. Results: We show low Mendelian error rates and high concordance rates for HapMap samples (average parent-parent-child heritability of 0.997, and concordance of 0.996). We performed genotype imputation across autosomal regions, masking directly genotyped SNPs to assess imputation accuracy and report an accuracy of >0.962 for directly genotyped SNPs. We demonstrate much higher capture of the natural killer cell immunoglobulin-like receptor (KIR) region versus comparable platforms. Overall, we show that the genotyping quality and coverage of the TxArray is very high when compared to reference samples and to other genome-wide genotyping platforms. Conclusions: We have designed a comprehensive genome-wide genotyping tool which enables accurate association testing and imputation of ungenotyped SNPs, facilitating powerful and cost-effective large-scale genotyping of transplant-related studies.

Background: In addition to HLA genetic incompatibility, non-HLA difference between donor and recipients of transplantation leading to allograft rejection are now becoming evident. We aimed to create a unique genome-wide platform to facilitate genomic research studies in transplant-related studies. We designed a genome-wide genotyping tool based on the most recent human genomic reference datasets, and included customization for known and potentially relevant metabolic and pharmacological loci relevant to transplantation. Methods: We describe here the design and implementation of a customized genome-wide genotyping array, the 'TxArray', comprising approximately 782,000 markers with tailored content for deeper capture of variants across HLA, KIR, pharmacogenomic, and metabolic loci important in transplantation. To test concordance and genotyping quality, we genotyped 85 HapMap samples on the array, including eight trios. Results: We show low Mendelian error rates and high concordance rates for HapMap samples (average parent-parent-child heritability of 0.997, and concordance of 0.996). We performed genotype imputation across autosomal regions, masking directly genotyped SNPs to assess imputation accuracy and report an accuracy of >0.962 for directly genotyped SNPs. We demonstrate much higher capture of the natural killer cell immunoglobulin-like receptor (KIR) region versus comparable platforms. Overall, we show that the genotyping quality and coverage of the TxArray is very high when compared to reference samples and to other genome-wide genotyping platforms. Conclusions: We have designed a comprehensive genome-wide genotyping tool which enables accurate association testing and imputation of ungenotyped SNPs, facilitating powerful and cost-effective large-scale genotyping of transplant-related studies.

Objective To investigate whether attendance at cardiac rehabilitation (CR) independently predicts all-cause mortality over 14 years and whether there is a dose–response relationship between the proportion of CR sessions attended and long-term mortality. Design Retrospective cohort study. Setting CR programmes in Victoria, Australia Patients The sample comprised 544 men and women eligible for CR following myocardial infarction, coronary artery bypass surgery or percutaneous interventions. Participants were tracked 4 months after hospital discharge to ascertain CR attendance status. Main outcome measures All-cause mortality at 14 years ascertained through linkage to the Australian National Death Index. Results In total, 281 (52%) men and women attended at least one CR session. There were few significant differences between non-attenders and attenders. After adjustment for age, sex, diagnosis, employment, diabetes and family history, the mortality risk for non-attenders was 58% greater than for attenders (HR=1.58, 95% CI 1.16 to 2.15). Participants who attended <25% of sessions had a mortality risk more than twice that of participants attending ≥75% of sessions (OR=2.57, 95% CI 1.04 to 6.38). This association was attenuated after adjusting for current smoking (OR=2.06, 95% CI 0.80 to 5.29). Conclusions This study provides further evidence for the long-term benefits of CR in a contemporary, heterogeneous population. While a dose–response relationship may exist between the number of sessions attended and long-term mortality, this relationship does not occur independently of smoking differences. CR practitioners should encourage smokers to attend CR and provide support for smoking cessation.

BackgroundEpidermal growth factor receptor inhibitors (EGFRI) produce various dermatologic side effects in the majority of patients, and guidelines are crucial for the prevention and treatment of these untoward events. The purpose of this panel was to develop evidence-based recommendations for EGFRI-associated dermatologic toxicities.MethodsA multinational, interdisciplinary panel of experts in supportive care in cancer reviewed pertinent studies using established criteria in order to develop first-generation recommendations for EGFRI-associated dermatologic toxicities.ResultsProphylactic and reactive recommendations for papulopustular (acneiform) rash, hair changes, radiation dermatitis, pruritus, mucositis, xerosis/fissures, and paronychia are presented, as well as general dermatologic recommendations when possible.ConclusionPrevention and management of EGFRI-related dermatologic toxicities is critical to maintain patients' health-related quality of life and dose intensity of antineoplastic regimens. More rigorous investigation of these toxicities is warranted to improve preventive and treatment strategies.

BackgroundEpidermal growth factor receptor inhibitors (EGFRI) produce various dermatologic side effects in the majority of patients, and guidelines are crucial for the prevention and treatment of these untoward events. The purpose of this panel was to develop evidence-based recommendations for EGFRI-associated dermatologic toxicities.MethodsA multinational, interdisciplinary panel of experts in supportive care in cancer reviewed pertinent studies using established criteria in order to develop first-generation recommendations for EGFRI-associated dermatologic toxicities.ResultsProphylactic and reactive recommendations for papulopustular (acneiform) rash, hair changes, radiation dermatitis, pruritus, mucositis, xerosis/fissures, and paronychia are presented, as well as general dermatologic recommendations when possible.ConclusionPrevention and management of EGFRI-related dermatologic toxicities is critical to maintain patients' health-related quality of life and dose intensity of antineoplastic regimens. More rigorous investigation of these toxicities is warranted to improve preventive and treatment strategies.

Following 10 years in operation, the European Monetary Union (EMU) has been shaken by the global financial crisis and some peripheral states have experienced significant economic shock. The pitfalls of currency unions have been well documented in the literature of International Political Economy (IPE), so the situation that these states find themselves in cannot come as a surprise to any member country. Without highly synchronised economies, some states will suffer significantly in the event of an exogenous shock. This begs the question why a country would make an "irrational" choice to join the monetary union to begin with. The predominant IPE theories on how the EMU was formed are explained using rational choice with material interests as the focus for interstate bargaining. By arguing that they really have no choice to begin with, rational choice theory renders small states impotent. Unsatisfied with this reductionist answer, this body of work explores the participation of one of the states currently in trouble by introducing a constructivist theory of economic identity politics. Exploring the historical record of Ireland in the period of 1978 and 1992, this work reveals that Ireland in fact had choices, and the "irrational" choices it made were significantly influenced by Irish identity politics. However Ireland's "irrational" motivation can only be understood by including economic identity politics into the analysis. It will reveal that the supranational institutions of the European Union can serve as economic instruments to further nationalist goals. In the process the institution can become embedded in the nation such a country like Ireland is now a hybrid - highly European monetarily while it still remains distinctively Irish. As small states now make up the majority of the European Union this thesis adds to our understanding of small state participation in its most ambitious institution thus far.

Following 10 years in operation, the European Monetary Union (EMU) has been shaken by the global financial crisis and some peripheral states have experienced significant economic shock. The pitfalls of currency unions have been well documented in the literature of International Political Economy (IPE), so the situation that these states find themselves in cannot come as a surprise to any member country. Without highly synchronised economies, some states will suffer significantly in the event of an exogenous shock. This begs the question why a country would make an "irrational" choice to join the monetary union to begin with. The predominant IPE theories on how the EMU was formed are explained using rational choice with material interests as the focus for interstate bargaining. By arguing that they really have no choice to begin with, rational choice theory renders small states impotent. Unsatisfied with this reductionist answer, this body of work explores the participation of one of the states currently in trouble by introducing a constructivist theory of economic identity politics. Exploring the historical record of Ireland in the period of 1978 and 1992, this work reveals that Ireland in fact had choices, and the "irrational" choices it made were significantly influenced by Irish identity politics. However Ireland's "irrational" motivation can only be understood by including economic identity politics into the analysis. It will reveal that the supranational institutions of the European Union can serve as economic instruments to further nationalist goals. In the process the institution can become embedded in the nation such a country like Ireland is now a hybrid - highly European monetarily while it still remains distinctively Irish. As small states now make up the majority of the European Union this thesis adds to our understanding of small state participation in its most ambitious institution thus far.

Following 10 years in operation, the European Monetary Union (EMU) has been shaken by the global financial crisis and some peripheral states have experienced significant economic shock. The pitfalls of currency unions have been well documented in the literature of International Political Economy (IPE), so the situation that these states find themselves in cannot come as a surprise to any member country. Without highly synchronised economies, some states will suffer significantly in the event of an exogenous shock. This begs the question why a country would make an "irrational" choice to join the monetary union to begin with. The predominant IPE theories on how the EMU was formed are explained using rational choice with material interests as the focus for interstate bargaining. By arguing that they really have no choice to begin with, rational choice theory renders small states impotent. Unsatisfied with this reductionist answer, this body of work explores the participation of one of the states currently in trouble by introducing a constructivist theory of economic identity politics. Exploring the historical record of Ireland in the period of 1978 and 1992, this work reveals that Ireland in fact had choices, and the "irrational" choices it made were significantly influenced by Irish identity politics. However Ireland's "irrational" motivation can only be understood by including economic identity politics into the analysis. It will reveal that the supranational institutions of the European Union can serve as economic instruments to further nationalist goals. In the process the institution can become embedded in the nation such a country like Ireland is now a hybrid - highly European monetarily while it still remains distinctively Irish. As small states now make up the majority of the European Union this thesis adds to our understanding of small state participation in its most ambitious institution thus far.

Following 10 years in operation, the European Monetary Union (EMU) has been shaken by the global financial crisis and some peripheral states have experienced significant economic shock. The pitfalls of currency unions have been well documented in the literature of International Political Economy (IPE), so the situation that these states find themselves in cannot come as a surprise to any member country. Without highly synchronised economies, some states will suffer significantly in the event of an exogenous shock. This begs the question why a country would make an "irrational" choice to join the monetary union to begin with. The predominant IPE theories on how the EMU was formed are explained using rational choice with material interests as the focus for interstate bargaining. By arguing that they really have no choice to begin with, rational choice theory renders small states impotent. Unsatisfied with this reductionist answer, this body of work explores the participation of one of the states currently in trouble by introducing a constructivist theory of economic identity politics. Exploring the historical record of Ireland in the period of 1978 and 1992, this work reveals that Ireland in fact had choices, and the "irrational" choices it made were significantly influenced by Irish identity politics. However Ireland's "irrational" motivation can only be understood by including economic identity politics into the analysis. It will reveal that the supranational institutions of the European Union can serve as economic instruments to further nationalist goals. In the process the institution can become embedded in the nation such a country like Ireland is now a hybrid - highly European monetarily while it still remains distinctively Irish. As small states now make up the majority of the European Union this thesis adds to our understanding of small state participation in its most ambitious institution thus far.

Following 10 years in operation, the European Monetary Union (EMU) has been shaken by the global financial crisis and some peripheral states have experienced significant economic shock. The pitfalls of currency unions have been well documented in the literature of International Political Economy (IPE), so the situation that these states find themselves in cannot come as a surprise to any member country. Without highly synchronised economies, some states will suffer significantly in the event of an exogenous shock. This begs the question why a country would make an "irrational" choice to join the monetary union to begin with. The predominant IPE theories on how the EMU was formed are explained using rational choice with material interests as the focus for interstate bargaining. By arguing that they really have no choice to begin with, rational choice theory renders small states impotent. Unsatisfied with this reductionist answer, this body of work explores the participation of one of the states currently in trouble by introducing a constructivist theory of economic identity politics. Exploring the historical record of Ireland in the period of 1978 and 1992, this work reveals that Ireland in fact had choices, and the "irrational" choices it made were significantly influenced by Irish identity politics. However Ireland's "irrational" motivation can only be understood by including economic identity politics into the analysis. It will reveal that the supranational institutions of the European Union can serve as economic instruments to further nationalist goals. In the process the institution can become embedded in the nation such a country like Ireland is now a hybrid - highly European monetarily while it still remains distinctively Irish. As small states now make up the majority of the European Union this thesis adds to our understanding of small state participation in its most ambitious institution thus far.

Military aviator helmet communications systems are designed to enhance speech intelligibility (SI) in background noise and reduce exposure to harmful levels of noise. Some aviators, over the course of their aviation career, develop noise-induced hearing loss that may affect their ability to perform required tasks. New technology can improve SI in noise for aviators with normal hearing as well as those with hearing loss. SI in noise scores were obtained from 40 rotary-wing aviators (20 with normal hearing and 20 with hearing-loss waivers). There were three communications systems evaluated: a standard SPH-4B, an SPH-4B aviator helmet modified with communications earplug (CEP), and an SPH-4B modified with active noise reduction (ANR). Subjects' SI was better in noise with newer technologies than with the standard issue aviator helmet. A significant number of aviators on waivers for hearing loss performed within the range of their normal hearing counterparts when wearing the newer technology. The rank order of perceived speech clarity was 1) CEP, 2) ANR, and 3) unmodified SPH-4B. To insure optimum SI in noise for rotary-wing aviators, consideration should be given to retrofitting existing aviator helmets with new technology, and incorporating such advances in communication systems of the future. Review of standards for determining fitness to fly is needed., Published in Aviation, Space, and Environmental Medicine, v75 n2 p132-137, Feb 2004.

A Cockpit Airbag System (CABS) is being developed for the UH-60A/L Black Hawk Helicopter. The U.S. Army Aeromedical Research Laboratory conducted tests to determine the risks to crewmembers and passengers associated with exposure to high impulse noise levels expected during an inadvertent system deployment. A series of 21 airbag deployment tests were conducted in a static UH-60A helicopter. Peak sound pressure levels ranged from 134 dB to 161 dB. Levels at pilot, copilot, and gunner stations exceeded 140 dB during all 21 deployments. Levels in the passenger compartment exceeded 140 dB during 9 of the 21 deployments. Army policy requires the aircrew in the UH-60 helicopter to wear helmets that provide hearing protection or a combination of helmet and earplugs. Passengers are required to wear protective earplugs or muffs or a combination of muffs and earplugs. This level of hearing protection also meets the requirements for protection against high impulse noise levels created by the deployment of airbags. Therefore, if the required hearing protective devices are worn, the potential of inadvertent deployment of the CABS in the UH-60 helicopter poses no additional risk to the hearing of crew and passengers.

Aviators assigned to OH-58D helicopter operational units participated in an expanded field assessment of the communications earplug (CEP). Characteristics of the CEP have been determined through laboratory and field testing over the past several years. Results of the laboratory studies showed that aviators were protected and provided with speech communications capability. The CEP is a low-cost and simple approach that is readily available for immediate fielding. During FY 98, Project Manager-Aircrew Integrated Systems (PM-ACIS) purchased enough CEPs to outfit all aviators currently assigned to OH-58D operational units. The objective of the purchase was to form a large sample of users for evaluating the effectiveness of the current CEP configuration in solving the problems associated with hearing protection and communication in the OH-58D helicopter. The acceptability of the CEP was assessed by comparison with the helmet systems currently used in the OH-58D helicopter. Comments and responses provided by the volunteers show that the CEP, with some modifications, is a substantial improvement over current systems. With improved cockpit communications, flying becomes less fatiguing and stressful. The CEP performs well during daily missions and is considered a viable solution to the problem of inadequate speech clarity and understanding in the Kiowa Warrior helicopter. Over 90 percent of the participants rated the CEP as having greater overall operational value than the aviator helmet as it is currently used. Aviators view the CEP as a viable solution to the communications problem and feel it should be fielded to all aviation units. Part 1 of this study presents the principal findings in summary form. Part II contains the data-set necessary to allow close inspection of individual subject responses., ADA371213

Aviators assigned to OH-58D helicopter operational units participated in an expanded field assessment of the communications earplug (CEP). Characteristics of the CEP have been determined through laboratory and field testing over the past several years. Results of the laboratory studies showed that aviators were protected and provided with speech communications capability. The CEP is a low-cost and simple approach that is readily available for immediate fielding. During FY 98, Project Manager-Aircrew Integrated Systems (PM-ACIS) purchased enough CEPs to outfit all aviators currently assigned to OH-58D operational units. The objective of the purchase was to form a large sample of users for evaluating the effectiveness of the current CEP configuration in solving the problems associated with hearing protection and communication in the OH-58D helicopter. The acceptability of the CEP was assessed by comparison with the helmet systems currently used in the OH-58D helicopter. Comments and responses provided by the volunteers show that the CEP, with some modifications, is a substantial improvement over current systems. With improved cockpit communications, flying becomes less fatiguing and stressful. The CEP performs well during daily missions and is considered a viable solution to the problem of inadequate speech clarity and understanding in the Kiowa Warrior helicopter. Over 90 percent of the participants rated the CEP as having greater overall operational value than the aviator helmet as it is currently used. Aviators view the CEP as a viable solution to the communications problem and feel it should be fielded to all aviation units. Part 1 of this study presents the principal findings in summary form. Part II contains the data-set necessary to allow close inspection of individual subject responses., ADA371212

Most personal protective equipment in current military aviation was designed with male aircrew in mind. To ensure that female aviator performance is not hampered by improperly fitted or sized equipment, the U.S. Navy (USN) established the Aircrew Modified Equipment Leading to Increased Accommodation (AMELIA) program. In this Phase I study, a novel questionnaire was distributed to a variety of USN and U.S. Marine Corps (USMC) aviation installations around the world to assess the effect of female hairstyles on flight helmet performance and safety. One hundred and one completed questionnaires were returned to the U.S. Army Aeromedical Research Laboratory (USAARL) resulting in a response rate of 21-40%.

Most personal protective equipment in current military aviation was designed with male aircrew in mind. To ensure that female aviator performance is not hampered by improperly fitted or sized equipment, the U.S. Navy (USN) established the Aircrew Modified Equipment Leading to Increased Accommodation (AMELIA) program. In this Phase I study, a novel questionnaire was distributed to a variety of USN and U.S. Marine Corps (USMC) aviation installations around the world to assess the effect of female hairstyles on flight helmet performance and safety. One hundred and one completed questionnaires were returned to the U.S. Army Aeromedical Research Laboratory (USARRL) resulting in a response rate of 21-40%.

Communications and hearing protection are usually necessary for personnel involved in Army operations. Aircraft and ground vehicles produce noise levels in excess of the limits defined in current hearing conservation standards. Hearing protection and communications elements of most helmets constitute a significant portion of the weight of standard helmets. Further, performance of most helmets is marginal with respect to speech intelligibility and hearing protection. Some noise environments require that earplugs be worn in combination with the helmet protector in order to achieve adequate protection. The communications earplug (CEP) consists of a high quality earphone coupled with an earplug protector. Results of laboratory and field tests have demonstrated the effectiveness of this device. Speech intelligibility of the CEP in high noise environments is as good or better than any other available communications/protector. Improvements in sound attenuation when worn in combination with the earcup allow for maximum time within any Army noise environment. The CEP is comfortable over a period of several hours and, in its current configuration, is considered highly acceptable by seasoned Army aviators and crewmembers. The CEP demonstrates significant improvements in speech intelligibility for the hearing impaired as well as normal hearing individuals. The weight of the system is less than 15 grams.