Host, environment, and anthropogenic factors drive landscape dynamics of an environmentally transmitted pathogen: Sarcoptic mange in the bare-nosed wombat.

Understanding the spatial dynamics and drivers of wildlife pathogens is constrained by sampling logistics, with implications for advancing the field of landscape epidemiology and targeted allocation of management resources. However, visually apparent wildlife diseases, when combined with remote-surveillance and distribution modelling technologies, present an opportunity to overcome this landscape-scale problem. Here, we investigated dynamics and drivers of landscape-scale wildlife disease, using clinical signs of sarcoptic mange (caused by Sarcoptes scabiei) in its bare-nosed wombat (BNW; Vombatus ursinus) host. We used 53,089 camera-trap observations from over 3261 locations across the 68,401 km2 area of Tasmania, Australia, combined with landscape data and ensemble species distribution modelling (SDM). We investigated: (1) landscape variables predicted to drive habitat suitability of the host; (2) host and landscape variables associated with clinical signs of disease in the host; and (3) predicted locations and environmental conditions at greatest risk of disease occurrence, including some Bass Strait islands where BNW translocations are proposed. We showed that the Tasmanian landscape, and ecosystems therein, are nearly ubiquitously suited to BNWs. Only high mean annual precipitation reduced habitat suitability for the host. In contrast, clinical signs of sarcoptic mange disease in BNWs were widespread, but heterogeneously distributed across the landscape. Mange (which is environmentally transmitted in BNWs) was most likely to be observed in areas of increased host habitat suitability, lower annual precipitation, near sources of freshwater and where topographic roughness was minimal (e.g. human modified landscapes, such as farmland and intensive land-use areas, shrub and grass lands). Thus, a confluence of host, environmental and anthropogenic variables appear to influence the risk of environmental transmission of S. scabiei. We identified that the Bass Strait Islands are highly suitable for BNWs and predicted a mix of high and low suitability for the pathogen. This study is the largest spatial assessment of sarcoptic mange in any host species, and advances understanding of the landscape epidemiology of environmentally transmitted S. scabiei. This research illustrates how host-pathogen co-suitability can be useful for allocating management resources in the landscape.

Financial toxicity: a potential side effect of prostate cancer treatment among Australian men.

The purpose of this study was to understand the extent, nature and variability of the current economic burden of prostate cancer among Australian men. An online cross-sectional survey was developed that combined pre-existing economic measures and new questions. With few exceptions, the online survey was viable and acceptable to participants. The main outcomes were self-reported out-of-pocket costs of prostate cancer diagnosis and treatment, changes in employment status and household finances. Men were recruited from prostate cancer support groups throughout Australia. Descriptive statistical analyses were undertaken. A total of 289 men responded to the survey during April and June 2013. Our study found that men recently diagnosed (within 16 months of the survey) (n = 65) reported spending a median AU$8000 (interquartile range AU$14 000) for their cancer treatment while 75% of men spent up to AU$17 000 (2012). Twenty per cent of all men found the cost of treating their prostate cancer caused them 'a great deal' of distress. The findings suggest a large variability in medical costs for prostate cancer treatment with 5% of men spending $250 or less in out-of-pocket expenses and some men facing very high costs. On average, respondents in paid employment at diagnosis stated that they had retired 4-5 years earlier than planned.

Men's help-seeking in the first year after diagnosis of localised prostate cancer.

This study describes sources of support utilised by men with localised prostate cancer in the first year after diagnosis and examines characteristics associated with help-seeking for men with unmet needs. A cross-sectional survey of 331 patients from a population-based sample who were in the first year after diagnosis (M = 9.6, SD = 1.9) was conducted to assess sources of support, unmet supportive care needs, domain-specific quality of life and psychological distress. Overall, 82% of men reported unmet supportive care needs. The top five needs were sexuality (58%); prostate cancer-specific (57%); psychological (47%); physical and daily living (41%); and health system and information (31%). Professional support was most often sought from doctors (51%). Across most domains, men who were older (Ps ≤ 0.03), less well educated (Ps ≤ 0.04) and more depressed (Ps ≤ 0.05) were less likely to seek help for unmet needs. Greater sexual help-seeking was related to better sexual function (P = 0.03), higher education (P ≤ 0.03) and less depression (P = 0.05). Unmet supportive care needs are highly prevalent after localised prostate cancer diagnosis with older age, lower education and higher depression apparent barriers to help-seeking. Interventions that link across medicine, nursing and community based peer support may be an accessible approach to meeting these needs. Clinical Trial Registry: Trial Registration: ACTRN12611000392965.

The global burden of major infectious complications following prostate biopsy.

We present a systematic review providing estimates of the overall and regional burden of infectious complications following prostate biopsy. A directly standardized prevalence estimate was used because it reflects the burden of disease more explicitly. Complications included sepsis, hospitalization, bacteraemia, bacteriuria, and acute urinary retention after biopsy. There were 165 articles, comprising 162 577 patients, included in the final analysis. Our findings demonstrate that transrectal biopsy was associated with a higher burden of hospitalization (1·1% vs. 0·9%) and sepsis (0·8% vs. 0·1%) compared to transperineal biopsy, while acute urinary retention was more prevalent after transperineal than transrectal biopsy (4·2% vs. 0·9%). The differences were statistically non-significant because of large heterogeneity across countries. We also demonstrate and discuss regional variations in complication rates, with Asian studies reporting higher rates of sepsis and hospitalization.

Iterative development and the scope for plasticity: contrasts among trait categories in an adaptive radiation.

Phenotypic plasticity can influence evolutionary change in a lineage, ranging from facilitation of population persistence in a novel environment to directing the patterns of evolutionary change. As the specific nature of plasticity can impact evolutionary consequences, it is essential to consider how plasticity is manifested if we are to understand the contribution of plasticity to phenotypic evolution. Most morphological traits are developmentally plastic, irreversible, and generally considered to be costly, at least when the resultant phenotype is mis-matched to the environment. At the other extreme, behavioral phenotypes are typically activational (modifiable on very short time scales), and not immediately costly as they are produced by constitutive neural networks. Although patterns of morphological and behavioral plasticity are often compared, patterns of plasticity of life history phenotypes are rarely considered. Here we review patterns of plasticity in these trait categories within and among populations, comprising the adaptive radiation of the threespine stickleback fish Gasterosteus aculeatus. We immediately found it necessary to consider the possibility of iterated development, the concept that behavioral and life history trajectories can be repeatedly reset on activational (usually behavior) or developmental (usually life history) time frames, offering fine tuning of the response to environmental context. Morphology in stickleback is primarily reset only in that developmental trajectories can be altered as environments change over the course of development. As anticipated, the boundaries between the trait categories are not clear and are likely to be linked by shared, underlying physiological and genetic systems.

Noise exposure of commercial divers in the Norwegian Sector of the North Sea.

It is well known that exposure to high noise levels can adversely affect human hearing. Legislation exists in Europe to control or restrict the level of noise to which employees may be exposed during the course of their work. While the noise levels to which a worker may be exposed is well defined in air, human sensitivity to noise is different in high-pressure and mixed-gas conditions. Relatively little research exists to define human hearing in these circumstances, and few measurements exist of the levels of noise to which divers working in these conditions are exposed. A study using specially designed equipment has been undertaken in Norwegian waters to sample the noise levels present during typical saturation dives undertaken by commercial divers working in the Norwegian oil and gas industry. The divers were working in heliox at depths of 30 msw and 120 msw. It found noise levels were generally dominated by self-noise: flow noise while breathing and communications. The noise levels, both when corrected for the difference in hearing sensitivity under pressure in mixed gas and uncorrected, would exceed legislated limits for noise exposure in a working day without the use of noisy tools.

Low immunogenicity in non-small cell lung cancer; do new developments and novel treatments have a role?

Approximately 1.6 million new cases of lung cancer are diagnosed annually (Jemal et al. CA: A Cancer Journal for Clinicians, 61, 69-90, 2011) and it remains the leading cause of cancer-related mortality worldwide. Despite decades of bench and clinical research to attempt to improve outcome for locally advanced, good performance status patients, the 5-year survival remains less than 15 % (Molina et al. 2008). Immune checkpoint inhibitor (ICH) therapies have shown a significant promise in preclinical and clinical trails to date in the treatment of non-small cell lung cancer (NSCLC). The idea of combining these systemic immune therapies with local ablative techniques is one that is gaining momentum. Electrochemotherapy (ECT) is a unique atraumatic local therapy that has had very promising objective response rates and a number of advantages including but not limited to its immunostimulatory effects. ECT in combination with ICHs offers a novel approach for dealing with this difficult disease process.

Endovascular repair of thoracoabdominal aortic aneurysm (TAAA): early experience.

BACKGROUND: Repair of thoracoabdominal aortic aneurysms (TAAA) represents a considerable technical challenge. Since its first description in 1955, open repair of TAAA has been considered the gold standard of repair. Despite improvements in surgical techniques, spinal cord protection and post-operative critical care support, patients who undergo open repair are faced with a mortality rate of 5-35 %. We report the first Irish experience of endovascular management of TAAAs. RESULTS: To date five patients have undergone endovascular repair; four had hybrid repair and one a fenestrated graft. The mean age of the patients was 66.8 ± 3.4 and the mean aneurysm diameter was 6.74 ± 0.6 cm. All patients were ASA III. Two-stage hybrid repair was associated with an increased risk of complications, prolonged intensive care unit and overall hospital stay. One patient died in the perioperative period due to rupture of their aneurysm between the two stages of their hybrid repair. CONCLUSION: The role of endovascular techniques in the treatment of TAAA continues to evolve. Hybrid and complete endovascular repairs do not replace conventional repair, but provide an alternative for high-risk patients who might otherwise be denied treatment.

Prevalence and predictors of cancer specific distress in men with a family history of prostate cancer.

OBJECTIVE: To examine prevalence and predictors of cancer-specific distress in undiagnosed men with and without a family history of prostate cancer, and to examine the contribution of perceptions of an affected relative's cancer experience on the distress of unaffected male relatives. METHODS: Men with a first degree relative with prostate cancer (n = 207) and men without a family history (n = 239) from Australia completed a Computer Assisted Telephone Interview. Participants completed the Prostate Cancer Anxiety Subscale of the Memorial Anxiety Scale for Prostate Cancer, measures of perceived risk, and socio-demographic information. Men with a family history provided details about their family history (number of relatives diagnosed with and dead from prostate cancer, relationship to affected relative, months since diagnosis) and reported their perceptions of their affected relative's prostate cancer experience including perceptions of threat related to the relative's diagnosis and perceived treatment phase and prognosis. RESULTS: Cancer-specific distress was low for all men and there was no significant difference in the distress experienced by men with and without a family history. Regression analyses showed that for all men, cancer-specific distress increased with urinary symptoms and decreased in those with higher education and in older participants. For men with a family history, having a relative who died from prostate cancer and perceiving greater threat from a relative's diagnosis was associated with greater cancer-specific distress. CONCLUSIONS: Interventions would benefit from examining appraisals of familial risk and examining prospective assessments of distress in the unaffected male relatives of men with prostate cancer over the course of the cancer trajectory.

ProsCan for Couples: a feasibility study for evaluating peer support within a controlled research design.

BACKGROUND: The present study assessed the feasibility of delivering peer support for couples coping with prostate cancer within a trial design. METHODS/DESIGN: Ten peer volunteers completed training in research protocols and delivering tele-based couples support to men with prostate cancer and their partners. Twenty couples received an eight session intervention and were assessed before surgery and 3 and 6 months subsequently for adjustment outcomes. A focus group investigated the peers' experiences. RESULTS: Peers were motivated by altruism, a belief in research, and reported personal growth. The research protocol at times conflicted with lay models of helping, and the focus on sexuality and couples was challenging. Distress decreased over time but more so for partners; unmet sexuality needs did not improve. CONCLUSION: Peer support appears promising as a model to support couples facing prostate cancer.

Intervening to improve psychological outcomes for men with prostate cancer.

BACKGROUND: Prostate cancer is the most common cancer in men in the Western world with well-described negative effects from treatments. However, outcomes are highly heterogeneous. A Phase 3 trial of a psycho-educational intervention was undertaken, aiming to reduce cancer-specific and decision-related distress and improve quality of life for men newly diagnosed with localised prostate cancer. METHODS: Seven hundred forty (81.7%) men were recruited after diagnosis and before treatment and randomised to a tele-based nurse-delivered five-session psycho-educational intervention (N = 372) or usual care (N = 368). Participants were assessed before treatment and 2, 6, 12 and 24 months post-treatment. Outcome measures included cancer-specific and decision-related distress, cognitive judgmental adjustment, subjective well-being, and domain-specific and health-related quality of life. Social support was assessed as a potential moderator. RESULTS: No unconditioned effects were found. Classification analyses on pre-randomisation measures distinguished three subgroups: younger, higher education and income men (N = 90); younger, lower education and income men (N = 106); and older men (N = 344). Younger, higher education and income men showed positive intervention effects for cancer-specific distress (p = 0.008) and mental health (p = 0.042). By contrast, for younger, lower education men, participation in the intervention was associated with decreases in cognitive judgmental adjustment over time (p = 0.006). CONCLUSIONS: Response to intervention and adjustment over time varied according to previous sexual functioning, age, educational level and income. How to best intervene with younger, low education, low income men with prostate cancer is a critical future research question.

Using MS-MLPA as an efficient screening tool for detecting 9p21 abnormalities in pediatric acute lymphoblastic leukemia.

BACKGROUND: Characterization of recurrent genetic lesions in childhood acute lymphoblastic leukemia (ALL) has enabled therapeutic stratification with improved outcomes. The tumor suppressor genes, CDKN2A and CDKN2B, encoding p16(INK4a) , p14(ARF) , and p15(INK4b) have been localized to 9p21. Abnormalities of 9p21 have been reported in 10-30% of childhood ALL using conventional cytogenetics and fluorescence in situ hybridization (FISH). The incidence of 9p21 using more sensitive techniques, such as methylation specific multiplex ligation-dependent probe amplification (MS-MLPA), remains uncertain, and thus also the prognostic significance. PROCEDURE: We investigated the incidence and prognostic importance of 9p21 abnormalities in pediatric ALL patients using MS-MLPA and compared these results to FISH. RESULTS: In total, MS-MLPA or FISH detected aberrations (both dosage and methylation abnormalities) at 9p21 in a remarkable 32/48 (67%) patients in contrast to a much lower rate of only 8% of patients identified to have deletions by standard G banding cytogenetics. MS-MLPA identified five deletions not found by FISH. Aberrant methylation at CDKN2B was found in 19 (46%) patients. 9p21 abnormalities were associated with National Cancer Institute (NCI) high-risk criteria (P = 0.04) and were present in all five patients with T-cell disease. Four pre-B-cell ALL patients relapsed, three of whom had prior 9p21 abnormalities. CONCLUSIONS: MS-MLPA had a higher detection rate for 9p21 abnormalities than previously reported for other techniques. Given the ease of processing, minimal equipment and low cost of MS-MLPA, our results suggest that previous reports may have underestimated the true frequency of 9p21 abnormalities and their potential impact upon ALL outcome.

Seven prostate cancer susceptibility loci identified by a multi-stage genome-wide association study.

Prostate cancer (PrCa) is the most frequently diagnosed male cancer in developed countries. We conducted a multi-stage genome-wide association study for PrCa and previously reported the results of the first two stages, which identified 16 PrCa susceptibility loci. We report here the results of stage 3, in which we evaluated 1,536 SNPs in 4,574 individuals with prostate cancer (cases) and 4,164 controls. We followed up ten new association signals through genotyping in 51,311 samples in 30 studies from the Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL) consortium. In addition to replicating previously reported loci, we identified seven new prostate cancer susceptibility loci on chromosomes 2p11, 3q23, 3q26, 5p12, 6p21, 12q13 and Xq12 (P = 4.0 × 10(-8) to P = 2.7 × 10(-24)). We also identified a SNP in TERT more strongly associated with PrCa than that previously reported. More than 40 PrCa susceptibility loci, explaining ∼25% of the familial risk in this disease, have now been identified.

Fluid balance, thermoregulation and sprint and passing skill performance in female soccer players.

Ten females performed 90 min of the Loughborough Intermittent Shuttle Test (LIST) on two occasions separated by 7 days. Water [3 mL/kg body mass (BM)] was provided every 15 min during exercise (FL); no fluid was given in the other trial (NF). Participants performed the Loughborough Soccer Passing Test (LSPT) before and every 15 min during the LIST. Core temperature (T(c) ) was measured throughout using ingestible temperature sensors. Heart rate (HR), blood lactate ([La(-) ]) and ratings of perceived exertion (RPE) were collected at regular intervals during exercise. Participants experienced greater BM loss in NF (2.2 ± 0.4%) than FL (1.0 ± 0.4%; P<0.001). Sprint performance deteriorated by 2.7% during exercise (P<0.001) but there was no difference between trials (P=0.294). No significant differences in LSPT performance were detected between trials (P=0.31). T(c) was higher during exercise in NF and was 38.6 ± 0.3 °C (NF) and 38.3 ± 0.3 °C (FL; P<0.01) after 90 min. HR (P<0.001), [La(-) ] (P<0.01) and RPE (P=0.009) were higher during exercise in NF. Ingesting water during a 90-min match simulation reduces the mild dehydration seen in female soccer players when no fluid is consumed. However, there was no effect of fluid ingestion on soccer passing skill or sprint performance.

The relationship of retinal vessel diameter to changes in diabetic nephropathy structural variables in patients with type 1 diabetes.

AIMS/HYPOTHESIS: We examined whether retinal vessel diameter in persons with type 1 diabetes mellitus is associated with changes in subclinical anatomical and functional indicators of diabetic nephropathy. METHODS: Persons with type 1 diabetes mellitus had gradable fundus photographs and renal biopsy data at baseline and 5-year follow-up (n = 234). Retinal arteriolar and venular diameters were measured at baseline and follow-up. Central retinal arteriole equivalent (CRAE) and central retinal venule equivalent (CRVE) were computed. Baseline and 5-year follow-up renal structural variables were assessed by masked electron microscopic morphometric analyses from percutaneous renal biopsy specimens. Variables assessed included: mesangial fractional volume, glomerular basement membrane width, mesangial matrix fractional volume and glomerular basement membrane width composite glomerulopathy index. RESULTS: While controlling for other covariates, baseline CRAE was positively associated with change in the glomerulopathy index over the 5-year period. Change in CRAE was inversely related to a change in mesangial matrix fractional volume and abnormal mesangial matrix fractional volume, while change in CRVE was directly related to change in the volume fraction of cortex that was interstitium [Vv((Int/cortex))] over the 5-year period. Baseline CRAE or CRVE or changes in these diameters were not related to changes in other anatomical or functional renal endpoints. CONCLUSIONS/INTERPRETATION: Independently of other factors, baseline CRAE correlated with changes in glomerulopathy index, a composite measure of extracellular matrix accumulation in the mesangium and glomerular basement membrane. A narrowing of the CRAE was related to mesangial matrix accumulation. Changes in CRVE were related to changes in Vv((Int/cortex),) a measure of interstitial expansion in persons with type 1 diabetes mellitus.

Genome wide high density SNP-based linkage analysis of childhood absence epilepsy identifies a susceptibility locus on chromosome 3p23-p14.

Childhood absence epilepsy (CAE) is an idiopathic generalised epilepsy (IGE) characterised by typical absence seizures manifested by transitory loss of awareness with 2.5-4 Hz spike-wave complexes on ictal EEG. A genetic component to the aetiology is well recognised but the mechanism of inheritance and the genes involved are yet to be fully established. A genome wide single nucleotide polymorphism (SNP)-based high density linkage scan was carried out using 41 nuclear pedigrees with at least two affected members. Multipoint parametric and non-parametric linkage analyses were performed using MERLIN 1.1.1 and a susceptibility locus was identified on chromosome 3p23-p14 (Z(mean)=3.9, p<0.0001; HLOD=3.3, alpha=0.7). The linked region harbours the functional candidate genes TRAK1 and CACNA2D2. Fine-mapping using a tagSNP approach demonstrated disease association with variants in TRAK1.

A review of prostate-specific antigen screening prevalence and risk perceptions for first-degree relatives of men with prostate cancer.

First-degree relatives of men with prostate cancer have a higher risk of being diagnosed with prostate cancer than men without a family history. The present review examines the prevalence and predictors of testing in first-degree relatives, perceptions of risk, prostate cancer knowledge and psychological consequences of screening. Medline, PsycInfo and Cinahl databases were searched for articles examining risk perceptions or screening practices of first-degree relatives of men with prostate cancer for the period of 1990 to August 2007. Eighteen studies were eligible for inclusion. First-degree relatives participated in prostate-specific antigen (PSA) testing more and perceived their risk of prostate cancer to be higher than men without a family history. Family history factors (e.g. being an unaffected son rather than an unaffected brother) were consistent predictors of PSA testing. Studies were characterized by sampling biases and a lack of longitudinal assessments. Prospective, longitudinal assessments with well-validated and comprehensive measures are needed to identify factors that cue the uptake of screening and from this develop an evidence base for decision support. Men with a family history may benefit from targeted communication about the risks and benefits of prostate cancer testing that responds to the implications of their heightened risk.