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Low testosterone levels in males have been linked with increase in proinflammatory cytokines-a primary culprit in COVID-19 disease progression-and with adverse COVID-19 outcomes. To date, however, no published studies have assessed the effect of testosterone therapy on COVID-19 outcomes in older men.To examine whether testosterone therapy reduced disease progression in older men diagnosed with COVID-19.Nested within a national cohort of older (aged ≥50 years) male patients diagnosed with COVID-19 between January 1, 2020 and July 1, 2021 from the Optum electronic health record COVID-19 database, two matched case-control studies of COVID-19 outcomes were conducted. Cases-defined, respectively, as persons who (a) were hospitalized ≤30 days after COVID-19 diagnosis (n = 33,380), and (b) were admitted to the intensive care unit or received mechanical ventilation during their COVID-19 hospitalization (n = 10,273)-were matched 1:1 with controls based on demographic and clinical factors.Testosterone therapy was defined based on receipt of prescription at ≤60, ≤90, or ≤120 days before COVID-19 diagnosis.Adjusted odds ratios (ORs) for the risk of hospitalization within 30 days of COVID-19 diagnosis and intensive care unit admission/mechanical ventilation during COVID-19 hospitalization.The use of testosterone therapy was not associated with decreased odds of hospitalization (≤60 days: OR = 0.92, 95% confidence interval [CI] = 0.70-1.20; ≤90 days: OR = 0.87, 95% CI = 0.68-1.13; ≤120 days: OR = 0.97, 95% CI = 0.72-1.32) or intensive care unit admission/mechanical ventilation (≤60 days: OR = 0.67, 95% CI = 0.37-1.23; ≤90 days: OR = 0.63, 95% CI = 0.36-0.11; ≤120 days: OR = 0.58, 95% CI = 0.29-1.19).This study showed that testosterone therapy was not associated with decreased risks of COVID-19 adverse outcomes. These findings may provide clinically relevant information regarding testosterone treatment in older men with COVID-19 and other respiratory viral infections with similar pathogenesis.

Objectives Anecdotal evidence suggests that oropharyngeal squamous cell carcinoma (OPSCC) should be suspected in patients presenting with symptoms of peritonsillar abscess (PTA) or cellulitis (PTC). The aim of this study was to estimate the prevalence of OPSCC in patients presenting with symptoms of PTA/PTC. Method, Setting and Participants We retrospectively identified all adults with a coded diagnosis of PTA or PTC who presented between 2012-2016 inclusive, across six ENT units in ——–. Records were compared to that of the centralised regional head and neck cancer database. The clinical records of a subset of patients were reviewed for the purposes of data validation. Results A total of 1975 patients with PTA/PTC were identified. Three patients were subsequently diagnosed with OPSCC. None of the three actually had an objective underlying diagnosis of PTA/PTC on the same side. The prevalence of OPSCC in patients admitted with symptoms of PTA/PTC was 0.15%, or approximately 1:650 admissions. The records of 510 patients who presented over a one-year period (2016) were reviewed in even greater detail. There were 298 patients with PTA (59.4%), 151 with PTC (29.1%) and 61 had an alternative diagnosis (11.9%). High risk features (age ≥40, tonsillar asymmetry or tonsillar lesion) were present in 106 patients (24%). Urgent follow up was expedited for 77 patients (73%). Conclusion This study estimates the risk of OPSCC in patients with peritonsillar symptoms. The prevalence is low, even in a region with a relatively heavy disease burden. Clinicians should, however, retain a high level of suspicion in patients with persistent symptoms.

BACKGROUND The objective of this study was to describe bladder cancer outcomes as a function of race among patients with high-risk non-muscle-invasive bladder cancer (NMIBC) in an equal-access setting. METHODS A total of 412 patients with high-risk NMIBC who received bacille Calmette-Guerin (BCG) from January 1, 2010, to December 31, 2015, were assessed. The authors used the Kaplan-Meier method to estimate event-free survival and Cox regression to determine the association between race and recurrence, progression, disease-specific, and overall survival outcomes. RESULTS A total of 372 patients who had complete data were included in the analysis; 48 (13%) and 324 (87%) were Black and White, respectively. There was no difference in age, sex, smoking status, or Charlson Comorbidity Index by race. White patients had a higher socioeconomic status with a greater percentage of patients living above the poverty level in comparison with Black patients (median, 85% vs 77%; P < .001). A total of 360 patients (97%) received adequate induction BCG, and 145 patients (39%) received adequate maintenance BCG therapy. There was no significant difference in rates of adequate induction or maintenance BCG therapy according to race. There was no significant difference in recurrence (hazard ratio [HR], 1.53; 95% confidence interval [CI], 0.64-3.63), progression (HR, 0.77; 95% CI, 0.33-1.82), bladder cancer-specific survival (HR, 1.01; 95% CI, 0.30-3.46), or overall survival (HR, 0.97; 95% CI, 0.56-1.66) according to Black race versus White race. CONCLUSIONS In this small study from an equal-access setting, there was no difference in the receipt of BCG or any differences in bladder cancer outcomes according to race.

OBJECTIVE Older patients diagnosed with cancer are at increased risk of physical and emotional distress; however, prescription utilization patterns largely remain to be elucidated. Our objective was to comprehensively assess prescription patterns and predictors in older patients with bladder cancer. METHODS A total of 10,516 older patients diagnosed with clinical stage T1-T4a, N0, M0 bladder urothelial carcinoma from 1 January 2008 to 31 December 2012 from the Surveillance, Epidemiology, and End Results (SEER)-Medicare were analyzed. We used multivariable analysis to determine predictors associated with psychotropic prescription rates (one or more). Medication possession ratio (MPR) was used as an index to measure adherence in intervals of 3 months, 6 months, 1 year, and 2 years. Evaluation of psychotropic prescribing patterns and adherence across different drugs and demographic factors was done. RESULTS Of the 10,516 older patients, 5621 (53%) were prescribed psychotropic drugs following cancer diagnosis. Overall, 3972 (38%) patients had previous psychotropic prescriptions prior to cancer diagnosis, and these patients were much more likely to receive a post-cancer diagnosis prescription. Prescription rates for psychotropic medications were higher among patients with higher stage BC (p

BACKGROUND: Disparity in mental health care among cancer patients remains understudied. METHODS: We conducted a large, retrospective, single tertiary-care institution cohort study based on de-identified electronic health record data of 54,852 adult cancer patients without prior mental health diagnosis (MHD) diagnosed at the University of California, San Francisco between 1/2012 and 9/2019. The exposure of interest was early onset MHD with or without psychotropic medication (PM) within 12 months of cancer diagnosis and primary outcome was all-cause mortality. RESULTS: 8.2% of patients received a new MHD at a median of 197 days (interquartile-range [IQR] 61-553) after incident cancer diagnosis, 31.0% received a PM prescription, and 3.7% a MHRV. 62.6% of patients were non-Hispanic white (NHW), 10.8% Asian, 9.8% Hispanic, and 3.8% Black. Compared to NHWs, minority cancer patients had reduced adjusted odds of MHDs, PM prescriptions, and MHRVs, particularly for generalized anxiety (Asian: odds ratio [OR] 0.66, 95% confidence interval 0.55-0.78; Black: OR 0.60, 0.45-0.79; Hispanic: OR 0.72, 0.61-0.85) and selective-serotonin-reuptake-inhibitors (SSRI; Asian: OR 0.43, 0.37-0.50; Black: OR 0.51, 0.40-0.61; Hispanic: OR 0.79, 0.70-0.89). New early MHD with PM was associated with elevated all-cause mortality (12-24 months: hazard ratio [HR] 1.43, 1.25-1.64) that waned by 24-36 months (HR 1.18, 0.95-1.45). CONCLUSIONS AND RELEVANCE: New mental health diagnosis with psychotropic medication was a marker of early mortality among cancer patients. Minority cancer patients were less likely to receive documentation of mental health diagnoses or treatment, which may represent missed opportunities to identify and treat cancer related mental health conditions.

Aim: Regional diversity can increase owing to either the packing of species within regional niche space or the expansion of regional niche space. Yet, the primary factors dictating these dynamics remain poorly understood. Here, we assess the relative influence of current environmental conditions (net primary productivity, NPP) versus historic environmental stability over the Last Glacial Maximum on niche filling patterns of vertebrates (mammals, birds, amphibians and reptiles) in the Australian Wet Tropics (AWTs). Location: Australian Wet Tropics. Taxon: Vertebrates (mammals, birds, amphibians and reptiles). Methods: We measured patterns of niche filling (niche packing vs. niche expansion) as the standardized departure of observed functional diversity (FD) from its null expectation. We fitted spatial models for vertebrates, and for each constituent class (mammals, birds, amphibians and reptiles) separately, to evaluate the relative effects of NPP and environmental stability on species richness and niche filling patterns. Results: Historical environmental stability had a greater effect than NPP on species richness and niche filling patterns. However, the directionality of this effect depended on phylogenetic scale, with vertebrates exhibiting niche packing while each constituent class (except reptiles) exhibited niche expansion with increasing environmental stability. Main Conclusion: Intra-class competition presumably leads to niche differentiation and expansion, whereas the overlap of functional traits among species from different classes leads to niche packing. That environmental stability over millennia is associated with an expanding niche space across multiple vertebrate classes suggests that the accumulation of FD within communities requires long recovery times.

Objective To develop and validate a claims-based comorbidity score for patients undergoing major surgery, and compare its performance with established comorbidity scores. Data source Five percent Medicare data from 2007 to 2014. Study design Retrospective cohort study of patients aged ≥65 years undergoing six major operations (N = 99 250). Data collection One-year mortality was the primary outcome. Secondary outcomes were hospital mortality, 30-day mortality, 30-day readmission, and length of stay. The comorbidity score was developed in the derivation cohort (70 percent sample) using logistic regression model. The comorbidity score was calibrated and validated in the validation cohort (30 percent sample), and compared against the Charlson, Elixhauser, and Centers for Medicare and Medicaid Services Hierarchical Condition Categories (CMS-HCC) comorbidity scores using c-statistic, net reclassification improvement, and integrated discrimination improvement. Principal findings In the validation cohort, the surgery-specific comorbidity score was well calibrated and performed better than the Charlson, Elixhauser, and CMS-HCC comorbidity scores for all outcomes; the performance was comparable to the CMS-HCC for 30-day readmission. For example, the surgery-specific comorbidity score (c-statistic = 0.792; 95% CI, 0.785-0.799) had greater discrimination than the Charlson (c-statistic = 0.747; 95% CI, 0.739-0.755), Elixhauser (c-statistic = 0.747; 95% CI, 0.735-0.755), or CMS-HCC (c-statistic = 0.755; 95% CI, 0.747-0.763) scores in predicting 1-year mortality. The net reclassification improvement and integrated discrimination improvement were greater for surgery-specific comorbidity score compared to the Charlson, Elixhauser, and CMS-HCC scores. Conclusions Compared to commonly used comorbidity measures, a surgery-specific comorbidity score better predicted outcomes in the surgical population.

BACKGROUND Although skeletal-related events (SREs) are linked with a reduced quality of life and worse outcomes, to the authors' knowledge the factors that predict SREs are minimally understood. The objective of the current study was to identify predictors of SREs and all-cause mortality among men with metastatic castration-resistant prostate cancer (mCRPC). METHODS Data were collected on 837 men with bone mCRPC at 8 Veterans Affairs medical centers within the Shared Equal Access Regional Cancer Hospital (SEARCH) database from 2000 through 2017. Patients were followed to assess development of SREs (pathological fracture, radiotherapy to bone, spinal cord compression, or surgery to bone). Cox proportional hazards models were used to evaluate predictors of SREs and mortality. RESULTS Of the 837 men with bone mCRPC, 287 developed a SRE and 740 men died (median follow-up, 26 months). Bone pain was found to be the strongest predictor of SREs (hazard ratio [HR], 2.96; 95% CI, 2.25-3.89). A shorter time from CRPC to the development of metastasis (HR, 0.92; 95% CI, 0.85-0.99), shorter progression to CRPC (HR, 0.94; 95% CI, 0.91-0.98), and visceral metastasis at the time of diagnosis of bone metastasis (HR, 1.91; 95% CI, 1.18-3.09) were associated with an increased risk of SREs. Ten or more bone metastases (HR, 2.17; 95% CI, 1.72-2.74), undergoing radical prostatectomy (HR, 0.73; 95% CI, 0.61-0.89), shorter progression to CRPC (HR, 0.97; 95% CI, 0.94-0.99), older age (HR, 1.03; 95% CI, 1.02-1.04), higher prostate-specific antigen level at the time of diagnosis of metastasis (HR, 1.21; 95% CI, 1.14-1.28), bone pain (HR, 1.44; 95% CI, 1.23-1.70), and visceral metastasis (HR, 1.72; 95% CI, 1.23-2.39) were associated with an increased mortality risk. CONCLUSIONS Among men with bone mCRPC, bone pain was found to be the strongest predictor of SREs and the number of bone metastases was a strong predictor of mortality. If validated, these factors potentially may be used for risk stratification and for SRE prevention strategies.

The effects of anthropogenic climate change on biodiversity are well known for some high‐profile Australian marine systems, including coral bleaching and kelp forest devastation. Less well‐published are the impacts of climate change being observed in terrestrial ecosystems, although ecological models have predicted substantial changes are likely. Detecting and attributing terrestrial changes to anthropogenic factors is difficult due to the ecological importance of extreme conditions, the noisy nature of short‐term data collected with limited resources, and complexities introduced by biotic interactions. Here, we provide a suite of case studies that have considered possible impacts of anthropogenic climate change on Australian terrestrial systems. Our intention is to provide a diverse collection of stories illustrating how Australian flora and fauna are likely responding to direct and indirect effects of anthropogenic climate change. We aim to raise awareness rather than be comprehensive. We include case studies covering canopy dieback in forests, compositional shifts in vegetation, positive feedbacks between climate, vegetation and disturbance regimes, local extinctions in plants, size changes in birds, phenological shifts in reproduction and shifting biotic interactions that threaten communities and endangered species. Some of these changes are direct and clear cut, others are indirect and less clearly connected to climate change; however, all are important in providing insights into the future state of terrestrial ecosystems. We also highlight some of the management issues relevant to conserving terrestrial communities and ecosystems in the face of anthropogenic climate change.

To augment mammal conservation in the Eastern Himalayan region, we assessed the resident 255 terrestrial mammal species and identified the 50 most threatened species based on conservation status, endemism, range size, and evolutionary distinctiveness. By using the spatial analysis package letsR and the complementarity core-area method in the conservation planning software Zonation, we assessed the current efficacy of their protection and identified priority conservation areas by comparing protected areas (PAs), land cover, and global ecoregion 2017 maps at a 100 × 100 m spatial scale. The 50 species that were most threatened, geographically restricted, and evolutionarily distinct faced a greater extinction risk than globally nonthreatened and wide-ranging species and species with several close relatives. Small, medium-sized, and data-deficient species faced extinction from inadequate protection in PAs relative to wide-ranging charismatic species. There was a mismatch between current PA distribution and priority areas for conservation of the 50 most endangered species. To protect these species, the skewed regional PA distribution would require expansion. Where possible, new PAs and transboundary reserves in the 35 priority areas we identified should be established. There are adequate remaining natural areas in which to expand current Eastern Himalayan PAs. Consolidation and expansion of PAs in the EH requires strengthening national and regional transboundary collaboration, formulating comprehensive regional land-use plans, diversifying conservation funding, and enhancing information sharing through a consolidated regional database.

Objectives To describe a step-by-step guide for using the first transperineal targeted prostate biopsy platform available in the USA. Patients and methods A total of 32 men with elevated prostate-specific antigen (PSA) levels were diagnosed with a region of interest on multiparametric magnetic resonance imaging (mpMRI) between February 2017 and January 2018. The transperineal targeted prostate biopsy procedure was accomplished via a transperineal approach and used a stepper, combined with advanced mpMRI/transrectal ultrasound fusion software, to perform targeted prostate biopsy. The detection of overall and clinically significant prostate cancer (PCa) was assessed as well as the rate of complications. Results The median patient age was 68.0 years and the median PSA was 8.0 ng/mL. Two patients (6%) were active surveillance candidates and 16 (50%) had a prior negative prostate biopsy. The detection rates for overall and clinically significant PCa were 81% and 59%, respectively. The two candidates for active surveillance and eight of the patients with a prior negative prostate biopsy had clinically significant PCa confirmed on targeted biopsy. There were no peri-operative complications. Conclusion These results demonstrate the promising potential of the first transperineal targeted prostate biopsy platform in the USA as an alternative diagnostic method for PCa.

According to a prevailing hypothesis, lowland tropical organisms are unlikely to successfully cross mountain passes because they have neither acclimated nor adapted to the colder temperatures found at higher elevations. However, this expectation assumes that changes in temperature are uniform across space and fails to account for the presence of diverse microclimates created by structurally complex ecosystems, such as rainforests. We collected and analyzed temperature data from Afrotropical, Indomalayan, and Australasian tropical mountain ecosystems to determine the degree of overlap between lowland and upland “thermal regimes” in three selected microenvironments. The thermal regimes of upland and lowland forest canopies overlapped to a greater extent than the thermal regimes of upland and lowland soils or ground-level sites. Tree-dwelling animals may therefore be able to bypass temperature constraints imposed by geography by virtue of where they live, which could lead to broader distributions and greater resilience to climatic change and variability as compared with ground-dwelling species.

Background This study was designed to adapt the Elixhauser comorbidity index for 4 cancer-specific populations (breast, prostate, lung, and colorectal) and compare 3 versions of the Elixhauser comorbidity score (individual comorbidities, summary comorbidity score, and cancer-specific summary comorbidity score) with 3 versions of the Charlson comorbidity score for predicting 2-year survival with 4 types of cancer. Methods This cohort study used Texas Cancer Registry-linked Medicare data from 2005 to 2011 for older patients diagnosed with breast (n = 19,082), prostate (n = 23,044), lung (n = 26,047), or colorectal cancer (n = 16,693). For each cancer cohort, the data were split into training and validation cohorts. In the training cohort, competing risk regression was used to model the association of Elixhauser comorbidities with 2-year noncancer mortality, and cancer-specific weights were derived for each comorbidity. In the validation cohort, competing risk regression was used to compare 3 versions of the Elixhauser comorbidity score with 3 versions of the Charlson comorbidity score. Model performance was evaluated with c statistics. Results The 2-year noncancer mortality rates were 14.5% (lung cancer), 11.5% (colorectal cancer), 5.7% (breast cancer), and 4.1% (prostate cancer). Cancer-specific Elixhauser comorbidity scores (c = 0.773 for breast cancer, c = 0.772 for prostate cancer, c = 0.579 for lung cancer, and c = 0.680 for colorectal cancer) performed slightly better than cancer-specific Charlson comorbidity scores (ie, the National Cancer Institute combined index; c = 0.762 for breast cancer, c = 0.767 for prostate cancer, c = 0.578 for lung cancer, and c = 0.674 for colorectal cancer). Individual Elixhauser comorbidities performed best (c = 0.779 for breast cancer, c = 0.783 for prostate cancer, c = 0.587 for lung cancer, and c = 0.687 for colorectal cancer). Conclusions The cancer-specific Elixhauser comorbidity score performed as well as or slightly better than the cancer-specific Charlson comorbidity score in predicting 2-year survival. If the sample size permits, using individual Elixhauser comorbidities may be the best way to control for confounding in cancer outcomes research. Cancer 2018;124:2018-25. © 2018 American Cancer Society.

Aim: Species that respond favourably to environmental change tend to be mobile or dispersive. Living within trees has some benefits over life on the ground. Species that move vertically within forest canopies can take advantage of increased complexity and resource availability, which should correspond to increased resilience to environmental variability and change. Here we show that two modes of movement, arboreality and horizontal dispersal, across an entire bioregional vertebrate fauna in the rain forests of Australia are associated with measures of historical environmental stability. Location: Wet Tropics, Queensland, Australia. Time period: Historical (c. 20,000 years ago) and current (1990-2009). Major taxa studied: Mammal, bird, reptile, and frog species. Methods: We analysed vertebrate distribution for 195 species and trait data from 20 years of standardized sampling. We derived an arboreality index (i.e., the extent of vertical habitat used by each species) from a large database of field observations combined with expert opinion scores on arboreality. We compared community-wide trends in arboreality and their horizontal dispersal potential with historical climate since the Last Glacial Maximum (c. 20,000 years ago) and current climate over 20 years of the recent past (1990–2009). Results: Vertical (arboreality) and horizontal (dispersal) movement were positively correlated, and both were negatively correlated with environmental stability. We found that arboreal species dominate communities in historically unstable areas, and these areas have both low richness and low endemism. Further, we show that low- and high-altitude arboreal species experience similar thermal regimes, whereas low- and high-altitude ground-dwelling species experience little overlap in thermal regimes. Main conclusion: Higher variability and overlap in temperature among rain forest canopies suggests less geographical separation in tolerable conditions for arboreal taxa when compared with ground-dwelling taxa. Increased ecological plasticity in horizontal and vertical movement as well as exposure and pre-selection to high temperature variability appears to allow arboreal species to exploit climatically uncertain areas, a capacity that may serve them well in responding to future climate change.

Background Conflicting evidence remains in the association of testosterone therapy (TTh) with prostate cancer (PCa). This inconsistency maybe due, in part, to the small sample sizes from previous studies and an incomplete assessment of comorbidities, particularly diabetes. Objective We investigated the association of PCa with TTh (injection or gel) and different TTh doses and determined whether this association varies by the presence of diabetes at baseline in a large, nationally representative, commercially insured cohort. Design We conducted a retrospective cohort study of 189 491 men aged 40-60 years old in the IBM MarketScan® Commercial Database, which included 1424 PCa cases diagnosed from 2011 to 2014. TTh was defined using CPT codes from inpatient and outpatient, and NDC codes from pharmacy claims. Multivariable adjusted Cox proportional hazards models were used to compute hazard ratios for patients with incident PCa. Results We found a 33% reduced association of PCa after comparing the highest category (>12) of TTh injections with the lowest (1-2 injections) category (HR = 0.67, 95% CI: 0.54-0.82). Similar statistical significant inverse association for PCa was observed for men who received TTh topical gels (>330 vs 1- to 60-days supply). Among nondiabetics, we found significant inverse association between TTh (injection and gel) and PCa, but a weak interaction between TTh injections and diabetes (P = .05). Conclusion Overall, increased use of TTh is inversely associated with PCa and this remained significant only among nondiabetics. These findings warrant further investigation in large randomized placebo-controlled trials to infer any health benefit by TTh.

BACKGROUND The objective of this study was to compare the overall survival of patients who undergo radical prostatectomy or radiotherapy versus noncancer controls to discern whether there is a survival advantage according to prostate cancer treatment and the impact of selection bias on these results. METHODS A matched cohort study was performed using the Surveillance, Epidemiology, and End Results (SEER)-Medicare–linked database. In total, 34,473 patients ages 66 to 75 years were identified who were without significant comorbidity, were diagnosed with localized prostate cancer, and received treatment treated with surgery or radiotherapy between 2004 and 2011. These patients were matched to a noncancer control cohort. The rates of all-cause mortality that occurred within the study period were compared. Cox proportional hazards regression analysis was used to identify determinants associated with overall survival. RESULTS Of 34,473 patients who were included in the analysis, 21,740 (63%) received radiation therapy, and 12,733 (37%) underwent surgery. There was improved survival in patients who underwent surgery (hazard ratio, 0.35; 95% confidence interval, 0.32-0.38) and in those who received radiotherapy (hazard ratio, 0.72; 95% confidence interval, 0.68-0.75) compared with noncancer controls. Overall survival improved significantly in both treatment groups, with the greatest benefit observed among patients who underwent surgery (log rank P

Most terrestrial species on Earth are ectothermic and track temperature at small spatial scales, from sun flecks to cool shaded spots. Current assessments of thermal heterogeneity in complex environments are predominately characterized by ambient temperature. This omission of solar radiation may lead to inaccurate conclusions regarding thermoregulation and distribution of species. We use thermal cameras to gather data on temperature heterogeneity in structurally complex rain forest environments. Using thermographic photographs, we capture the multidimensionality of climate created by vegetation by collecting over 76,000 temperature samples within approximately 1 m2 quadrats. The method was tested against three standard methods that record air temperature to determine possible omissions in capturing thermal heterogeneity in four geographic locations—Colombia, Borneo, Madagascar, and Australia. Across all locations, there was greater thermal heterogeneity in surface temperature than captured from ambient temperature technologies. Spatial variability in surface temperature on 1 d was greater than temporal variability of ambient temperature across the entire month, with extreme deviation from ambient temperatures. Importantly, when compared to the lower bounds for optimal performance for five tropical Anolis species, this technology captured thermal regimes that support the thermoregulatory needs of these species, whereas ambient air temperature methods suggested that these species would be in thermal debt. Sampling surface temperature at high resolutions across space in combination with intensive sampling of ambient temperature and informed spatial modeling should improve our understanding of the distribution of ectothermic species living within thermally heterogeneous environments.

OBJECTIVE To compare the risk of hospitalisation and associated costs in patients after treatment for prostate cancer. PATIENTS AND METHODS We identified 29 571 patients aged 66-75 years without significant comorbidity from the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database who were diagnosed with localised prostate cancer between 2004 and 2009. We compared the rates of all-cause and treatment-related hospitalisation that occurred within 365 days of the initiation of definitive therapy. We used multivariable logistic regression analysis to identify determinants associated with hospitalisation. RESULTS Men who underwent radical prostatectomy (RP) rather than radiotherapy (RT) had lower odds of being hospitalised for any cause after therapy [odds ratio (OR) 0.80, 95% confidence interval (CI): 0.74-0.87]. Patients who underwent RP rather than RT had higher odds of being hospitalised for treatment-related complications (OR 1.15, 95% CI: 1.03-1.29). However, men who underwent external beam RT (EBRT)/intensity modulated RT (IMRT) (OR 0.84, 95% CI: 0.72-0.99) had a 16% lower odds of hospitalisation from treatment-related complications than patients undergoing RP. Using propensity score-weighted analyses there was no significant difference in the odds of hospitalisation from treatment-related complications for men who underwent RP vs RT (OR 1.06, 95% CI: 0.92-1.21). Patients hospitalised for treatment-related complications after RT were costlier than patients who underwent RP (Mean $18 381 vs $13 203, P < 0.001). CONCLUSIONS With the exception of men who underwent EBRT/IMRT, there was no statistically significant difference in the odds of hospitalisation from treatment-related complications. Costs from hospitalisation after treatment were significantly higher for men undergoing RT than RP. Our findings are relevant in the context of penalties linked to hospital readmissions and bundled payment models.

Summary Phytophthora agathidicida (PTA) causes a root rot and collar rot of New Zealand kauri (Agathis australis). This study developed techniques to visualize early infection of kauri by PTA in deliberately inoculated seedlings. Conventional light microscopy was carried out on cleared and stained roots using trypan blue to observe PTA structures. Additionally, scanning electron microscopy (SEM) was used to study the PTA root structures at a higher resolution. A fluorescent in situ hybridization assay (FISH) was developed using a PTA-specific probe to label PTA structures in planta. Infection progression in roots of 2-year-old kauri inoculated with PTA at 5, 10, 16 and 20 days post-inoculation (d.p.i.) was compared using these three approaches. Light microscopy identified no Phytophthora-like structures in the control treatments. In PTA-inoculated plants, lignitubers were produced 5 d.p.i. in cortical cells. Infection was localized after 5 days, but as the infection progressed (up to 20 d.p.i.), the ‘degree’ of root infection increased, as did the number of replicates in which structures were observed. SEM provided higher resolution images; again, no PTA structures were observed in the negative control material examined. The slide-based FISH-specificity assay successfully hybridized with PTA hyphae. Fluorescence was observed using 330–380 nm excitation and an emission filter at 420 nm (DAPI), with PTA nuclei fluorescing a bright greenish-yellow. Cross-reactivity was not observed when the assay was applied to six other non-target Phytophthora species. Successful hybridization reactions occurred between the primer and PTA structures in planta. Applying this FISH assay has allowed clear differentiation of the intracellular and intercellular structures of PTA. The technique can be applied to longer term studies or analysis of ex situ inoculation studies aiming to elucidate differential host-responses to the pathogen. Additionally, the technique could be applied to study the interactions with other fungal endophytes (e.g. mycorrhizal fungi), which could be assessed for biocontrol potential as part of the integrated management of the disease.

BACKGROUND Despite recent interest in the overdiagnosis and overtreatment of prostate cancer, the acceptance of expectant management for patients with indolent prostate cancer has remained slow. Moreover, the intensity of surveillance strategies remains to be elucidated. The objective of this study was to determine the population-based intensity of surveillance strategy among patients diagnosed with localized prostate cancer who undergo watchful waiting/active surveillance and those who receive active treatment. METHODS Linked Surveillance, Epidemiology, and End Results (SEER)-Medicare data were used to identify men diagnosed with prostate cancer from 2004 to 2007 who were followed until December 31, 2009. Bivariate and multivariate regression analyses were used to quantify the use of prostate-specific antigen tests, office visits, and second prostate biopsies within 2 years of diagnosis. RESULTS Compared with patients who were receiving active treatment, those who were undergoing watchful waiting/active surveillance were less likely to receive prostate-specific antigen testing and to attend office visits within the 2 years after diagnosis (P

Kernel machine (KM) models are a powerful tool for exploring associations between sets of genetic variants and complex traits. Although most KM methods use a single kernel function to assess the marginal effect of a variable set, KM analyses involving multiple kernels have become increasingly popular. Multikernel analysis allows researchers to study more complex problems, such as assessing gene-gene or gene-environment interactions, incorporating variance-component based methods for population substructure into rare-variant association testing, and assessing the conditional effects of a variable set adjusting for other variable sets. The KM framework is robust, powerful, and provides efficient dimension reduction for multifactor analyses, but requires the estimation of high dimensional nuisance parameters. Traditional estimation techniques, including regularization and the "expectation-maximization (EM)" algorithm, have a large computational cost and are not scalable to large sample sizes needed for rare variant analysis. Therefore, under the context of gene-environment interaction, we propose a computationally efficient and statistically rigorous "fastKM" algorithm for multikernel analysis that is based on a low-rank approximation to the nuisance effect kernel matrices. Our algorithm is applicable to various trait types (e.g., continuous, binary, and survival traits) and can be implemented using any existing single-kernel analysis software. Through extensive simulation studies, we show that our algorithm has similar performance to an EM-based KM approach for quantitative traits while running much faster. We also apply our method to the Vitamin Intervention for Stroke Prevention (VISP) clinical trial, examining gene-by-vitamin effects on recurrent stroke risk and gene-by-age effects on change in homocysteine level.

Understanding the spatial variability in plant litter processes is essential for accurate comprehension of biogeochemical cycles and ecosystem function. We assessed spatial patterns in litter processes from local to regional scales, at sites throughout the wet tropical rain forests of northern Australia. We aimed to determine the controls (e.g., climate, soil, plant community composition) on annual litter standing crop, annual litterfall rate and in situ leaf litter decomposability. The level of spatial variance in these components, and leaf litter N, P, Ca, lignin, α-cellulose and total phenolics, was determined from within the scale of subregion, to site (1 km transects) to local/plot (~30 m2). Overall, standing crop was modeled with litterfall and its chemical composition, in situ decomposability, soil Na, and topography (r2 = 0.69, 36 plots). Litterfall was most closely aligned with plant species richness and stem density (negative correlation); leaf decomposability with leaf-P and lignin, soil Na, and dry season moisture (r2 = 0.89, 40 plots). The predominant scale of variability in litterfall rates was local (plot), while litter standing crop and α-cellulose variability was more evenly distributed across spatial scales. Litter decomposability, N, P and phenolics were more aligned with subregional differences. Leaf litter C, lignin and Ca varied most at the site level, suggesting more local controls. We show that variability in litter quality and decomposability are more easily accounted for spatially than litterfall rates, which vary widely over short distances possibly in response to idiosyncratic patterns of disturbance.

Identifying refugia is a critical component of effective conservation of biodiversity under anthropogenic climate change. However, despite a surge in conceptual and practical interest, identifying refugia remains a significant challenge across diverse continental landscapes. We provide an overview of the key properties of refugia that promote species' persistence under climate change, including their capacity to (i) buffer species from climate change; (ii) sustain long-term population viability and evolutionary processes; (iii) minimize the potential for deleterious species interactions, provided that the refugia are (iv) available and accessible to species under threat. Further, we classify refugia in terms of the environmental and biotic stressors that they provide protection from (i.e. thermal, hydric, cyclonic, pyric and biotic refugia), but ideally refugia should provide protection from a multitude of stressors. Our systematic characterization of refugia facilitates the identification of refugia in the Australian landscape. Challenges remain, however, specifically with respect to how to assess the quality of refugia at the level of individual species and whole species assemblages. It is essential that these challenges are overcome before refugia can live up to their acclaim as useful targets for conservation and management in the context of climate change.

Newer methods of management and harvesting of sugarcane are being considered to improve soil and water conservation in Brazil. Our aim in this study was to evaluate soil C dynamics under sugarcane cultivation as influenced by the use of conservation management, using measurements from four different management systems and land use histories, i.e. conventional management with preharvest burning, no burning with residue retention and two systems without burning plus additional organic amendments. Field sites also differed in terms of soil texture. We compared field measurements of soil C stocks, 13C and microbial biomass with simulated results from the Century ecosystem model for each of the sites and management histories. We also did long-term simulations of the management treatments and sites to approximate steady-state SOC levels, to explore potential management-induced differences in SOC stocks and interactions with soil texture. The model accurately represented treatment and site differences for total SOC stocks, in which SOC stocks were strongly affected by both rates of organic matter input to soil and soil clay content. However, the model tended to underestimate the relative contribution of sugarcane-derived C to total SOC for sites with high residue and external organic matter amendments. Measured microbial biomass C across the sites was closely aligned with relative amounts of organic matter input but did not appear to be strongly affected by soil texture, whereas the model predicted that both texture and organic matter input rate would impact microbial biomass C. Long-term simulations of the conservation management alternatives suggested that SOC stocks could be maintained at or above levels in the original native Cerradao vegetation, whereas conventional practices using residue burning would result in a reduction of SOC to ca. 60% of native levels. Our results support the use of the CENTURY model as an aid to assess the impacts of different soil management practices on SOC stocks under sugarcane in Brazil.

Species may circumvent the impacts of climate warming if the habitats they use reduce ambient temperature. In this study, we identified which frog species from a tropical montane rain forest in the Philippines may be vulnerable to climate warming. To do so, we selected five anuran species that utilize four breeding habitats and identified the sensitivity and exposure of tadpoles and direct-developer eggs to heat by measuring their critical thermal maximums (CTmax) and the habitat-specific temperatures they experience. Our study species included two direct-developer frogs—one species that lays its eggs on exposed leaves, and another that lays its eggs in ferns—and three species that produce aquatic free-swimming tadpoles—two stream breeders, and one phytotelm (tree hole) breeder. We compared thermal tolerances derived from microclimates of breeding habitats with tolerances derived from macroclimate (i.e., non-buffered air temperature taken from the rain forest canopy). We also examined whether differences in CTmax existed across life-history stages (egg, metamorph/young-of-year, and adult) for the two direct-developer frog species. Habitats buffered ambient temperature and expanded thermal tolerances of all frog species. We found that direct-developers, however, are more vulnerable to increased temperatures than aquatic breeders—indicated by their high sensitivity to temperature, and exposure to high temperatures. Direct-developer eggs were more sensitive to warming than both metamorph and adult life-history stages. Thermally buffered microhabitats may represent the only protection against current and impending climate warming. Our data highlight the importance of considering sensitivity and exposure in unison when deciphering warming vulnerability of frogs.

Aim: Correlative species distribution models (SDMs) combined with spatial layers of climate and species' localities represent a frequently utilized and rapid method for generating spatial estimates of species distributions. However, an SDM is only as accurate as the inputs upon which it is based. Current best-practice climate layers commonly utilized in SDM (e.g. ANUCLIM) are frequently inaccurate and biased spatially. Here, we statistically downscale 30 years of existing spatial weather estimates against empirical weather data and spatial layers of topography and vegetation to produce highly accurate spatial layers of weather. We proceed to demonstrate the effect of inaccurately quantified spatial data on SDM outcomes. Location: The Australian Wet Tropics. Methods: We use Boosted Regression Trees (BRTs) to generate 30 years of spatial estimates of daily maximum and minimum temperature for the study region and aggregate the resultant weather layers into 'accuCLIM' climate summaries, comparable with those generated by current best-practice climate layers. We proceed to generate for seven species of rainforest skink comparable SDMs within species; one model based on ANUCLIM climate estimates and another based on accuCLIM climate estimates. Results: Boosted Regression Trees weather layers are more accurate with respect to empirically measured temperature, particularly for maximum temperature, when compared to current best-practice weather layers. ANUCLIM climate layers are least accurate in heavily forested upland regions, frequently over-predicting empirical mean maximum temperature by as much as 7°. Distributions of the focal species as predicted by accuCLIM were more fragmented and contained less core distributional area. Conclusion: Combined these results reveal a source of bias in climate-based SDMs and indicate a solution in the form of statistical downscaling. This technique will allow researchers to produce fine-grained, ground-truthed spatial estimates of weather based on existing estimates, which can be aggregated in novel ways, and applied to correlative or process-based modelling techniques.

What's known on the subject? and What does the study add? Statins have shown broad spectrum anti-cancer properties in laboratory studies. In epidemiological studies, use of statins has been associated with reduced risk of advanced prostate cancer. However, the effects of statins on prostate cancer disease progression following curative treatment have not been extensively studied, and previous studies reported conflicting results. This study found no clear association between overall statin use and risk of disease progression, as well as lack of a monotone dose–response relationship between the use of statins, whether it was use before or after prostatectomy, and prostate cancer disease progression. Objective To investigate whether use of HMG-CoA reductase inhibitors (‘statins’), which have shown broad spectrum anti-cancer properties in laboratory studies, is associated with a reduced risk of recurrence in patients with prostate cancer who undergo radical prostatectomy. Patients and Methods All men with incident prostate cancer diagnosed between 2004 and 2005 who subsequently underwent radical prostatectomy by the end of 2005 in the Kaiser Permanente Southern California (KPSC) health plan were identified using KPSC's cancer registry. Subjects were followed for up to 5 years after prostatectomy for (i) biochemical recurrence, defined as a single PSA measurement >0.2 ng/mL, and (ii) clinical disease progression, defined as diagnosis of metastatic disease or prostate-cancer-related death. Information on statin use, demographics, comorbidities, patho-clinical factors and outcomes were ascertained from KPSC's electronic medical records. The effects of statin use prior to and after prostatectomy were both examined using bivariate and multivariate Cox models, adjusting for known prognostic factors. For postoperative statin exposure, a time-dependent Cox model was used. Results A total of 1200 men were included; 37% had preoperative and 56% had postoperative statin use. Neither preoperative nor postoperative statin use was associated with biochemical recurrence (hazard ratio [HR] = 1.00 [0.72–1.39] and 1.05 [0.76–1.46], respectively) or clinical disease progression (HR = 0.63 [0.31–1.27] and 1.20 [0.63–2.30], respectively). No clear dose–response relationship was found for duration of use. Conclusions Statin use may not prevent prostate cancer progression following radical prostatectomy. These findings do not provide support for the pursuit of a prospective clinical trial of statin use as a secondary prevention among surgically treated patients with prostate cancer.

Currently, there is very limited ability to measure the temperature of the brain, but a direct technique for its estimation in vivo could improve the detection of patients at risk of temperature-related brain damage, help in the diagnosis of stroke and tumour, and provide useful information on the mechanisms of thermoregulation of the brain. In this article, new calibrations in vitro of MRS thermometry using temperature-stabilised reference phantoms are reported. The phantoms comprise two concentric glass spheres: the inner sphere contains the phantom material to be measured by MRS, and the outer sphere contains a substance with a known temperature stable to within 0.2 °C. The substances were freezing organic fixed-point compounds (diphenyl ether and ethylene carbonate, freezing at 26.3 and 35.8 °C, respectively) or temperature-controlled circulating water. The phantom temperature was continuously monitored with a fluoroptic probe calibrated at the National Physical Laboratory with traceability to the International Temperature Scale 1990 (ITS-90). The MRS temperature calibration was obtained by measuring the chemical shift of water relative to N-acetylaspartate (NAA) in a single voxel as a function of temperature using a 1.5-T Philips Intera scanner. Measurements were made for several phantom materials to assess the effect of tissue composition on the water-NAA chemical shift against temperature calibration. The phantom mixtures contained 25 mm of NAA buffered to pH 6.5 or 7.5 and several ionic salts or bovine serum albumin (BSA). Spectra were acquired from 25 to 45 °C. The correlation between frequency differences and phantom temperature was very linear with small residuals. However, the linear fitting parameters varied with ionic composition and BSA concentration. The 'apparent' temperature (calibrated using the water-NAA frequency differences) decreased by approximately 1 °C for every 100 mm increase in ionic concentration and increased proportionally to the concentration of BSA.

Aim: To measure the effects of including biotic interactions on climate-based species distribution models (SDMs) used to predict distribution shifts under climate change. We evaluated the performance of distribution models for an endangered marsupial, the northern bettong (Bettongia tropica), comparing models that used only climate variables with models that also took into account biotic interactions. Location: North-east Queensland, Australia. Methods: We developed separate climate-based distribution models for the northern bettong, its two main resources and a competitor species. We then constructed models for the northern bettong by including climate suitability estimates for the resources and competitor as additional predictor variables to make climate + resource and climate + resource + competition models. We projected these models onto seven future climate scenarios and compared predictions of northern bettong distribution made by these differently structured models, using a 'global' metric, the I similarity statistic, to measure overlap in distribution and a 'local' metric to identify where predictions differed significantly. Results: Inclusion of food resource biotic interactions improved model performance. Over moderate climate changes, up to 3.0 °C of warming, the climate-only model for the northern bettong gave similar predictions of distribution to the more complex models including interactions, with differences only at the margins of predicted distributions. For climate changes beyond 3.0 °C, model predictions diverged significantly. The interactive model predicted less contraction of distribution than the simpler climate-only model. Main conclusions: Distribution models that account for interactions with other species, in particular direct resources, improve model predictions in the present-day climate. For larger climate changes, shifts in distribution of interacting species cause predictions of interactive models to diverge from climate-only models. Incorporating interactions with other species in SDMs may be needed for long-term prediction of changes in distribution of species under climate change, particularly for specialized species strongly dependent on a small number of biotic interactions.

Montane tropical rainforests are critically important areas for global bird diversity, but are projected to be highly vulnerable to contemporary climate change. Upslope shifts of lowland species may partially offset declines in upland species but also result in a process of lowland biotic attrition. This latter process is contingent on the absence of species adapted to novel warm climates, and isolation from pools of potential colonizers. In the Australian Wet Tropics, species distribution modelling has forecast critical declines in suitable environmental area for upland endemic birds, raising the question of the future role of both natural and assisted dispersal in species survival, but information is lacking for important neighbouring rainforest regions. Here we use expanded geographic coverage of data to model the realized distributions of 120 bird species found in north-eastern Australian rainforest, including species from potential source locations in the north and recipient locations in the south. We reaffirm previous conclusions as to the high vulnerability of this fauna to global warming, and extend the list of species whose suitable environmental area is projected to decrease. However, we find that expansion of suitable area for some species currently restricted to northern rainforests has the potential to offset biotic attrition in lowland forest of the Australian Wet Tropics. By examining contrasting dispersal scenarios, we show that responses to climate change in this region may critically depend on dispersal limitation, as climate change shifts the suitable environmental envelopes of many species south into currently unsuitable habitats. For lowland and northern species, future change in vegetation connectivity across contemporary habitat barriers is likely to be an important mediator of climate change impacts. In contrast, upland species are projected to become increasingly isolated and restricted. Their survival is likely to be more dependent on the viability of assisted migration, and the emergence and persistence of suitable environments at recipient locations.

Alternative stable state theory has been applied to understanding the control by landscape fire activity of pyrophobic tropical rain forest and pyrophytic eucalypt savanna boundaries, which are often separated by tall eucalypt forests. We evaluate the microclimate of three vegetation types across an elevational gradient and their relative fire risk as measured by McArthur's Forest Fire Danger Index (FFDI). Microclimatic data were collected from rain forest, tall eucalypt forest and savanna sites on eight vegetation boundaries throughout the humid tropics in north Queensland over a 3-year period and were compared with data from a nearby meteorological station. There was a clear annual pattern in daily FFDI with highest values in the austral winter dry season and lowest values in the austral summer wet season. There was a strong association of the meteorological station FFDI values with those from the three vegetation types, albeit they were substantially lower. The rank order of FFDI values among the vegetation types decreased from savanna, tall eucalypt forest, then rain forest, a pattern that was consistent across each transect. Only very rarely would rain forest be flammable, despite being adjacent to highly flammable savannas. These results demonstrate the very strong effect of vegetation type on microclimate and fire risk, compared with the weak effect of elevation, consistent with a fire–vegetation feedback. This study is the first demonstration of how vegetation type influences microclimate and fire risk across a topographically complex tropical forest–savanna gradient.

Future climates have the potential to alter decomposition rates in tropical forest with implications for carbon emissions, nutrient cycling and retention of standing litter. However, our ability to predict impacts, particularly for seasonally wet forests in the old world, is limited by a paucity of data, a limited understanding of the relative importance of different aspects of climate and the extent to which decomposition rates are constrained by factors other than climate (e.g. soil, vegetation composition). We used the litterbag method to determine leaf litter decay rates at 18 sites distributed throughout the Australian wet tropics bioregion over a 14-month period. Specifically, we investigated regional controls on litter decay including climate, soil and litter chemical quality. We used both in situ litter collected from litterfall on site and a standardized control leaf litter substrate. The control litter removed the effect of litter chemical quality and the in situ study quantified decomposition specific to the site. Decomposition was generally slower than for other tropical rainforests globally except in our wet and nutrient-richer sites. This is most likely attributable to the higher latitude, often highly seasonal rainfall and very poor soils in our system. Decomposition rates were best explained by a combination of climate, soil and litter quality. For in situ litter (native to the site) this included: average leaf wetness in the dry season (LWDS; i.e. moisture condensation) and the initial P content of the leaves, or LWDS and initial C. For control litter (no litter quality effect) this included: rainfall seasonality (% dry season days with 0-mm rainfall), soil P and mean annual temperature. These results suggest that the impact of climate change on decomposition rates within Australian tropical rainforests will be critically dependent on the trajectory of dry season moisture inputs over the coming decades.

Background The advanced age and comorbidities often associated with bladder cancer patients creates a difficult scenario regarding further management. Robotic-assisted laparoscopic radical cystectomy (RALRC) has had favorable results as am inimally invasive treatment option. We studied perioperative outcomes of RALRC in octogenarians to discern if there is any added benefi ti n this patient population. Methods One hundred and sixty robotic cystectomies have been performed between October 2003 and June 2010. We identified 24 octogenarians who underwent RALRC and form the cohort of the study. Results Mean patient age was 84.7years and mean BMI was 24kg/m 2 . Most of the patients in the study had serious medical comorbidities, as 82.6% of them had an ASA classification ≥3 and 95.6% had Charlson scores ≥3. There was one open conversion and two patients had positive surgical margins. There were a total of 45 complications in the study, with 14 major complications observed in the 90-day period after surgery. There were five patients who had no complications, and two patients expired as a result of multiple organ failure. At 24months the overall, disease-free and disease-specific survivals were 51.1%, 64.3%, and 79%, respectively. The 90-day mortality rate was 8.7%. Conclusions Octogenarians undergoing RALRC have a significant risk of morbidity and mortality. The relationship between advanced age and oncologic outcomes or complications needs to be discerned further as it relates to the octogenarian. Further study is needed to delineate the safety and efficacy of this approach. Copyright © 2012 John Wiley & Sons, Ltd.

Study Type – Therapy (prospective cohort) Level of Evidence 2a What's known on the subject? and What does the study add? Despite the increased popularity of emerging therapies for localised prostate cancer, such as cryotherapy and brachytherapy, outcomes data remains sparse beyond single-centre comparative studies. The present study identified that although less costly, cryotherapy was associated with more urinary and ED complications and a greater need for salvage ADT. Conversely, cryotherapy was associated with fewer bowel complications. Patients and providers alike should consider these population-based outcomes when discussing therapeutic options for localised prostate cancer. OBJECTIVE • To compare prostate cryotherapy vs brachytherapy outcomes and costs, as despite the greater popularity of these emerging therapies for localised prostate cancer, outcomes data remains sparse beyond single-centre comparative studies. PATIENTS AND METHODS • Observational study of 10 928 men who underwent primary cryotherapy (943 patients) or brachytherapy (9985) with ≥2 years of follow-up using USA Surveillance, Epidemiology, and End Results (SEER-) Medicare linked data. • Weighted propensity score methods were used. RESULTS • Use of cryotherapy increased four-fold whereas brachytherapy utilization remained the same from 2001 to 2005 (P < 0.001). Men who underwent cryotherapy vs brachytherapy were older (P < 0.001), more likely to be Black (P < 0.001), less likely to live in areas of higher education (P < 0.001), less likely to live in areas with greater income (P < 0.001), and were more likely to live in urban vs rural areas (P= 0.007). • In propensity score-weighted analyses, cryotherapy was associated with more urinary (41.4% vs 22.2%, P < 0.001) and erectile dysfunction (ED) complications (34.7% vs 21.0%, P < 0.001) while brachytherapy was associated with more bowel complications (19.0% vs 12.1%, P < 0.001). • Cryotherapy was associated with greater use of salvage androgen deprivation therapy (ADT; 1.4 vs 0.5 per 100 person-years, P < 0.001), suggesting worse cancer control. • Finally costs were significantly greater for brachytherapy vs cryotherapy ($16 887 vs $12 629 USA dollars, P < 0.001). CONCLUSIONS • Although less costly, cryotherapy was associated with more urinary and ED complications and greater need for salvage ADT. • Conversely, cryotherapy was associated with fewer bowel complications. Patients and providers alike should consider these population-based outcomes when discussing therapeutic options for localised prostate cancer.

Limited survival benefit and excess treatment because of prostate-specific antigen (PSA) screening in randomized trials suggests a need for more restricted selection of prostate biopsy candidates by discerning risk of histologically aggressive versus indolent cancer before biopsy.Subjects undergoing first prostate biopsy enrolled in a multicenter, prospective cohort of the National Cancer Institute Early Detection Research Network (N = 635) were analyzed to develop a model for predicting histologically aggressive prostate cancers. The control arm of the Prostate Cancer Prevention Trial (N = 3833) was used to validate the generalization of the predictive model.The Early Detection Research Network cohort was comprised of men among whom 57% had no cancer, 14% had indolent cancer, and 29% had aggressive cancer. Age, body mass index, family history of prostate cancer, abnormal digital rectal examination (DRE), and PSA density (PSAD) were associated with aggressive cancer (all P.001). The Early Detection Research Network model outperformed PSA alone in predicting aggressive cancer (area under the curve [AUC] = 0.81 vs 0.71, P.01). Model validation in the Prostate Cancer Prevention Trial cohort accurately identified men at low (10%) risk of aggressive cancer for whom biopsy could be averted (AUC = 0.78; 95% confidence interval, 0.75-0.80). Under criteria from the Early Detection Research Network model, prostate biopsy can be restricted to men with PSAD0.1 ng/mL/cc or abnormal DRE. When PSAD is0.1 ng/mL/cc, family history or obesity can identify biopsy candidates.A predictive model incorporating age, family history, obesity, PSAD, and DRE elucidates criteria whereby ¼ of prostate biopsies can be averted while retaining high sensitivity in detecting aggressive prostate cancer.

Transgenic models of human disease can be used to understand pathology and to discover biomarkers of disease presence, progression and response to therapy. Here we report a study of longitudinal metabolic differences between TASTPM transgenic Alzheimer's disease (AD) mice and their wild type counterparts using (1)H magnetic resonance spectroscopy (MRS) to look for potential biomarkers for use in AD research and drug discovery. Chloroform methanol extractions were performed on the brains of mice aged between 3 and 18 months. (1)H MR spectra were recorded from the aqueous fractions. Absolute metabolite concentrations, determined from resonance integrals relative to an internal standard, were analysed by 2-way ANOVA (genotype x age). Significant effects of age alone were identified for creatine, glutamine and total choline-containing compounds. There was a marked increase in creatine in the oldest (15-18 mo) TASTPM mice. The increase in creatine was unexpected and may be caused by osmotic stress in older animals as plaque load increases. Care should be taken when using creatine as a reference metabolite during scans of these animals in vivo. A significant effect of genotype alone was identified for myo-inositol (MI), which was higher in TASTPM mice at all ages. Succinate, glycerophosphocholine and choline all showed significant effects of age and genotype. No significant effects were detected in N-acetylaspartate (NAA) levels. Increased MI could be a marker of gliosis or microglial activation in TASTPM mice, but the absence of an age dependence for MI levels means it may be a biomarker of disease, but not of disease progression. Decreased succinate is indicative of disrupted neuronal energy metabolism, an effect that has been seen in human AD.

Plant-litter chemical quality is an important driver of many ecosystem processes, however, what actually constitutes high- or low-quality litter (chemical potential for fast and slow decomposition, respectively) is often interpreted by the indices available. Here, near-infrared spectroscopy (NIRS) was used to explore leaf-litter chemical quality and the controls on decomposition in the tropical rainforest region of north Queensland Australia. Leaf-litter samples from litterfall collections and litterbag studies were used. NIRS was used to calibrate the chemical compositions of the material (N, P, C, Mg, Ca, acid detergent fiber, acid detergent lignin, α-cellulose, and total phenolics) from a smaller sample set covering the spectral range in the full set of samples. Calibrations were compared for both separate (local) and combined models, for litterbags, and litterfall. Coefficients of determination (r2) in the local models ranged from 0.88 (litterbag Mg) to 0.99 (litterfall N), with residual prediction deviation ratios > 3 for all constituents except Mg (≈ 2.5). Mass loss in the litterbags was strongly related to the NIR spectra, with model r2's of 0.75 (in situ leaves) and 0.76 (common control leaf). In situ decomposability was determined from modeling the initial NIR spectra prior to decomposition with litterbag exponential-decay rates (model r2 of 0.81, n = 85 initial samples). A best subset model including litter-quality, climate, and soil variables predicted decay better than the NIR decomposability model (r2 = 0.87). For litter quality alone the NIR model predicted decay rate better than all of the best predictive litter–chemical quality indices. The decomposability model was used to predict in situ decomposability in the litterfall samples. The chemical variables explaining NIR decomposability for litterfall were initial P, C, and phenolics (linear model r2 = 0.80, n = 2471). NIRS is a holistic technique that is just as, if not more accurate, than litter–chemical quality indices, when predicting decomposition and decomposability, shown here in a regional field study.

Aim: Fire is a major driver of ecosystem structure and process, and shifts in fire regimes are implicated in the decline of many species. Shifting fire regimes have been documented around the world, and fire frequency and extent is predicted to increase in many areas because of changes in both climate and land management. Here, we evaluate how predicted increases in fire frequency are likely to impact on species distributions. Location: The tropical savannas of northern Australia. Methods: We developed distribution models for 44 bird species using the modelling algorithm Maxent. Our models incorporated bird locality records and environmental variables including climate, total fire frequency and the subset of fire frequency occurring late in the dry season. We investigated the effect of increasing total fire frequency and increasing fire late in the dry season, on species distributions by projecting species model algorithms onto scenarios of incrementally increased total fire frequency. Results: The probability of presence for most species was higher when fire frequency late in the dry season was low. Species showed a mixed response to an overall increase in total fire frequency, with one-third predicted to increase in distribution. However, almost all species (98%) showed a decrease in predicted range with increased late-dry season fire, and species distribution area was generally negatively correlated with an increase in late-dry season fire. Main conclusions: Our study highlighted the array of responses of species to increasing fire frequency and suggested that increased fire frequency late in the dry season is detrimental to most savanna-restricted bird species. The understanding of individual species' preferences for particular fire frequencies is important for informed conservation planning.