Genetic characterization of the prion protein gene in camels (Camelus) with comments on the evolutionary history of prion disease in Cetartiodactyla.

Transmissible spongiform encephalopathies (TSEs) are a fatal neurogenerative disease that include Creutzfeldt-Jakob disease in humans, scrapie in sheep and goats, bovine spongiform encephalopathy (BSE), and several others as well as the recently described camel prion disease (CPD). CPD originally was documented in 3.1% of camels examined during an antemortem slaughterhouse inspection in the Ouargla region of Algeria. Of three individuals confirmed for CPD, two were sequenced for the exon 3 of the prion protein gene (PRNP) and were identical to sequences previously reported for Camelus dromedarius. Given that other TSEs, such as BSE, are known to be capable of cross-species transmission and that there is household consumption of meat and milk from Camelus, regulations to ensure camel and human health should be a One Health priority in exporting countries. Although the interspecies transmissibility of CPD currently is unknown, genotypic characterization of Camelus PRNP may be used for predictability of predisposition and potential susceptibility to CPD. Herein, eight breeds of dromedary camels from a previous genetic (mitochondrial DNA and microsatellites) and morphological study were genotyped for PRNP and compared to genotypes from CPD-positive Algerian camels. Sequence data from PRNP indicated that Ethiopian camels possessed 100% sequence identity to CPD-positive camels from Algeria. In addition, the camel PRNP genotype is unique compared to other members of the Orders Cetartiodactyla and Perissodactyla and provides an in-depth phylogenetic analysis of families within Cetartiodactyla and Perissodactyla that was used to infer the evolutionary history of the PRNP gene.

Going Wild in the City-Animal Feralization and Its Impacts on Biodiversity in Urban Environments.

Domestication describes a range of changes to wild species as they are increasingly brought under human selection and husbandry. Feralization is the process whereby a species leaves the human sphere and undergoes increasing natural selection in a wild context, which may or may not be geographically adjacent to where the originator wild species evolved prior to domestication. Distinguishing between domestic, feral, and wild species can be difficult, since some populations of so-called "wild species" are at least partly descended from domesticated "populations" (e.g., junglefowl, European wild sheep) and because transitions in both directions are gradual rather than abrupt. In urban settings, prior selection for coexistence with humans provides particular benefit for a domestic organism that undergoes feralization. One risk is that such taxa can become invasive not just at the site of release/escape but far away. As humanity becomes increasingly urban and pristine environments rapidly diminish, we believe that feralized populations also hold conservation value.

Challenges and solutions to biodiversity conservation in arid lands.

The strategic goals of the United Nations and the Aichi Targets for biodiversity conservation have not been met. Instead, biodiversity has continued to rapidly decrease, especially in developing countries. Setting a new global biodiversity framework requires clarifying future priorities and strategies to bridge challenges and provide representative solutions. Hyper-arid, arid, and semi-arid lands (herein, arid lands) form about one third of the Earth's terrestrial surface. Arid lands contain unique biological and cultural diversity, and biodiversity loss in arid lands can have a disproportionate impact on these ecosystems due to low redundancy and a high risk of trophic cascades. They contain unique biological and cultural diversity and host many endemic species, including wild relatives of key crop plants. Yet extensive agriculture, unsustainable use, and global climate change are causing an irrecoverable damage to arid lands, with far-reaching consequences to the species, ground-water resources, ecosystem productivity, and ultimately the communities' dependant on these systems. However, adequate research and effective policies to protect arid land biodiversity and sustainability are lacking because a large proportion of arid areas are in developing countries, and the unique diversity in these systems is frequently overlooked. Developing new priorities for global arid lands and mechanisms to prevent unsustainable development must become part of public discourse and form the basis for conservation efforts. The current situation demands the combined efforts of researchers, practitioners, policymakers, and local communities to adopt a socio-ecological approach for achieving sustainable development (SDGs) in arid lands. Applying these initiatives globally is imperative to conserve arid lands biodiversity and the critical ecological services they provide for future generations. This perspective provides a framework for conserving biodiversity in arid lands for all stakeholders that will have a tangible impact on sustainable development, nature, and human well-being.

Sequencing of Androgen-Deprivation Therapy With External-Beam Radiotherapy in Localized Prostate Cancer: A Phase III Randomized Controlled Trial.

PURPOSE: Dose-escalated radiotherapy (RT) with androgen-deprivation therapy (ADT) is a standard definitive treatment of localized prostate cancer (LPCa). The optimal sequencing of these therapies is unclear. Our phase III trial compared neoadjuvant versus concurrent initiation of ADT in combination with dose-escalated prostate RT (PRT). PATIENTS AND METHODS: Patients with newly diagnosed LPCa with Gleason score ≤ 7, clinical stage T1b to T3a, and prostate-specific antigen < 30 ng/mL were randomly allocated to neoadjuvant and concurrent ADT for 6 months starting 4 months before RT (neoadjuvant group) or concurrent and adjuvant ADT for 6 months starting simultaneously with RT (concurrent group). The primary end point was biochemical relapse-free survival (bRFS). Stratified log-rank test was used to compare bRFS and overall survival (OS). Incidence of grade ≥ 3 late RT-related toxicities was compared by log-rank test. RESULTS: Overall, 432 patients were randomly assigned to the neoadjuvant (n = 215) or concurrent group (n = 217). At 10 years, bRFS rates for the two groups were 80.5% and 87.4%, respectively. Ten-year OS rates were 76.4% and 73.7%, respectively. There was no significant difference in bRFS (P = .10) or OS (P = .70) between the two groups. Relative to the neoadjuvant group, the hazard ratio for the concurrent group was 0.66 (95% CI, 0.41 to 1.07) for bRFS and 0.94 (95% CI, 0.68 to 1.30) for OS. No significant difference was observed in the 3-year incidence of late RT-related grade ≥ 3 GI (2.5% v 3.9%) or genitourinary toxicity (2.9% v 2.9%). CONCLUSION: In our study, there was no statistically significant difference in bRFS between the two treatment groups. Similarly, no difference was seen in OS or late RT-related toxicities. On the basis of these results, both neoadjuvant and concurrent initiations of short-term ADT with dose-escalated PRT are reasonable standards of care for LPCa.

Dosimetric and radiobiological investigation of permanent implant prostate brachytherapy based on Monte Carlo calculations.

PURPOSE: Permanent implant prostate brachytherapy plays an important role in prostate cancer treatment, but dose evaluations typically follow the water-based TG-43 formalism, ignoring patient anatomy and interseed attenuation. The purpose of this study is to investigate advanced TG-186 model-based dose calculations via retrospective dosimetric and radiobiological analysis for a new patient cohort. METHODS AND MATERIALS: A cohort of 155 patients treated with permanent implant prostate brachytherapy from The Ottawa Hospital Cancer Centre is considered. Monte Carlo (MC) dose calculations are performed using tissue-based virtual patient models. Dose-volume histogram (DVH) metrics (target, organs at risk) are extracted from 3D dose distributions and compared with those from calculations under TG-43 assumptions (TG43). Equivalent uniform biologically effective dose and tumor control probability are calculated. RESULTS: For the target, D90 (V100) is 136.7 ± 20.6 Gy (85.8% ± 7.8%) for TG43 and 132.8 ± 20.1 Gy (84.1% ± 8.2%) for MC; D90 is 3.0% ± 1.1% lower for MC than TG43. For organs at risk, MC D1cc = 104.4 ± 27.4 Gy (TG43: 106.3 ± 28.3 Gy) for rectum and 80.8 ± 29.7 Gy (TG43: 78.4 ± 28.4 Gy) for bladder; D1cc = 185.9 ± 30.2 Gy (TG43: 191.1 ± 32.0 Gy) for urethra. Equivalent uniform biologically effective dose and tumor control probability are generally lower when evaluated using MC doses. The largest dosimetric and radiobiological discrepancies between TG43 and MC are for patients with intraprostatic calcifications, for whom there are low doses (cold spots) in the vicinity of calcifications within the target, identified with MC but not TG43. CONCLUSIONS: DVH metrics and radiobiological indices evaluated with TG43 are systematically inaccurate by upward of several percent compared with MC patient-specific models. Mean cohort DVH metrics and their MC:TG43 variances are sensitive to patient cohort and clinical practice, underlining the importance of further retrospective MC studies toward widespread clinical adoption of advanced model-based dose calculations.

On piecewise models and species-area patterns.

AIM: Area thresholds, at which the form of the species-area relationship (SAR) changes abruptly, have played an important role in the theoretical framework of conservation biogeography and biodiversity research. The application of piecewise regressions has been advocated as a rigorous statistical technique to identify such thresholds within SARs, but a large variety of piecewise models remains untested. We explore the prevalence and number of thresholds in SARs and examine whether the currently widely used method for detecting the small island effect (SIE) is robust. LOCATION: Global. TAXON: We consider all multicellular taxa based on the criteria of datasets selection. METHODS: We apply 15 regression models, including linear regression and piecewise regressions with two and three segments to 68 global island datasets that are sourced from the literature. RESULTS: The number of area thresholds in SARs varied among groups and correlated positively with area range of a studied system. Under the AIC or AICc criterion, three-segment piecewise models were more prevalent, whereas under the BIC criterion, two-segment piecewise models were more prevalent. From the results of Aegean Sea isopods, West Indies herpetofauna, and Australian Islands mammals, we found evidence that the traditional criteria for detection of SIEs are not robust. MAIN CONCLUSIONS: Our study demonstrates that (a) to detect an SIE, the comparison should use as many models as possible, including not only variants with and without a left-horizontal part, but also those with two and more segments; (b) naive use of the traditional two-segment piecewise regressions may cause poor estimations of both slope and breakpoint values; (c) the number of thresholds increases with the area range of a studied system; (d) conservation biologists and applied ecologists should determine the number of area thresholds when estimating the precise species-area patterns and making management strategies in fragmented landscapes.

The sprightly little sphaerodactyl: Systematics and biogeography of the Puerto Rican dwarf geckos Sphaerodactylus (Gekkota, Sphaerodactylidae).

Studies of the Caribbean herpetofauna (amphibians and reptiles) have made significant contributions to our knowledge of evolutionary patterns and processes. A prerequisite for these studies are accurate taxonomies and robust phylogenetic hypotheses. One notable Caribbean radiation lacking such data are dwarf geckos of the genus Sphaerodactylus. Systematics of the Puerto Rican Sphaerodactylus have been turbulent since the initial species descriptions and no molecular phylogenies exist that include complete or near-complete taxon sampling. Here, we combine a multi-locus molecular phylogeny with extensive morphological information to investigate the current diversity of Sphaerodactylus geckos from the Puerto Rican Bank, with a large number of species from Hispaniola as an outgroup. In particular, we focus our efforts on resolving the taxonomy of the Sphaerodactylus macrolepis Günther species complex. We find S. macrolepis sensu lato (currently two nominal species with nine subspecies) is made up of at least four diagnosable species within two clades: (1) the sister species Sphaerodactylus macrolepis sensu stricto from the Virgin Islands (including St. Croix) and Culebra, and S. parvus King from islands in the northern Lesser Antilles; and (2) all other Sphaerodactylus macrolepis subspecies from Puerto Rico, Vieques, and Culebra. We resurrect Sphaerodactylus grandisquamis Stejneger from synonymy to refer to all subspecies from Puerto Rico and elevate the subspecies Sphaerodactylus inigoi Thomas Schwartz for geckos from Vieques and western Culebra. The resulting phylogeny and revised taxonomy will be a useful tool for subsequent research into Sphaerodactylus conservation and evolution.

Morphometric and genetic variation in 8 breeds of Ethiopian camels (Camelus dromedarius).

Dromedary camels (Camelus dromedarius) are a domesticated and closely guarded economic staple of indigenous people located throughout Ethiopian territorial states. Seventeen morphometric variables were examined to determine intraspecific variation among 8 pastoralist-designated breeds of camels. Additionally, DNA sequences from mitochondrial cytochrome-b gene and genotyping of 6 nuclear microsatellite loci were examined to assess genetic diversity and phylogenetic relationship of Ethiopian camels. Examination of 525 individuals revealed significant morphometric differentiation in Afar as compared with the remaining 7 breeds. Analysis of cytochrome-b sequences failed to recover monophyletic groups associated with pastoralist-recognized breeds. Analysis of 6 microsatellite loci from 104 individuals depicted no resolution of distinct genetic lineages in accordance to geographical or designated breeds. Overall, separation of 2 ecotypes based on the morphometric data was supported; however, genetic analysis of cytochrome-b and microsatellite data failed to support any unique genetic lineage or statistically significant population structure.

Detecting the small island effect and nestedness of herpetofauna of the West Indies.

To detect the small island effect (SIE) and nestedness patterns of herpetofauna of the West Indies, we derived and updated data on the presence/absence of herpetofauna in this region from recently published reviews. We applied regression-based analyses, including linear regression and piecewise regressions with two and three segments, to detect the SIE and then used the Akaike's information criterion (AIC) as a criterion to select the best model. We used the NODF (a nestedness metric based on overlap and decreasing fill) to quantify nestedness and employed two null models to determine significance. Moreover, a random sampling effort was made to infer about the degree of nestedness at portions of the entire community. We found piecewise regression with three segments performed best, suggesting the species-area relationships possess three different patterns that resulted from two area thresholds: a first one, delimiting the SIE, and a second one, delimiting evolutionary processes. We also found that taxa with lower resource requirement, higher dispersal ability, and stronger adaptation to the environment generally displayed lower corresponding threshold values, indicating superior taxonomic groups could earlier end the SIE period and start in situ speciation as the increase of island size. Moreover, the traditional two-segment piecewise regression method may cause poor estimations for both slope and threshold value of the SIE. Therefore, we suggest previous SIE detection works that conducted by two-segment piecewise regression method, ignoring the possibility of three segments, need to be reanalyzed. Antinestedness occurred in the entire system, whereas high degree of nestedness could still occur in portions within the region. Nestedness may still be applicable to conservation planning at portions even if it is antinested at the regional scale. However, nestedness may not be applicable to conservation planning at the regional scale even if nestedness does exist among sampling islands from a portion.

The Three Rs of Animal Research: What they Mean for the Institutional Animal Care and Use Committee and Why.

The Institutional Animal Care and Use Committee (IACUC) is entrusted with assessing the ethics of proposed projects prior to approval of animal research. The role of the IACUC is detailed in legislation and binding rules, which are in turn inspired by the Three Rs: the principles of Replacement, Reduction, and Refinement. However, these principles are poorly defined. Although this provides the IACUC leeway in assessing a proposed project, it also affords little guidance. Our goal is to provide procedural and philosophical clarity to the IACUC without mandating a particular outcome. To do this, we analyze the underlying logic of the Three Rs and conclude that the Three Rs accord animals moral standing, though not necessarily "rights" in the philosophical sense. We suggest that the Rs are hierarchical, such that Replacement, which can totally eliminate harm, should be considered prior to Reduction, which decreases the number of animals harmed, with Refinement being considered last. We also identify the need for a hitherto implicit fourth R: Reject, which allows the IACUC to refuse permission for a project which does not promise sufficient benefit to offset the pain and distress likely to be caused by the proposed research.

Species-area relationships and additive partitioning of diversity of native and nonnative herpetofauna of the West Indies.

To evaluate the regional biogeographical patterns of West Indian native and nonnative herpetofauna, we derived and updated data on the presence/absence of all herpetofauna in this region from the recently published reviews. We divided the records into 24 taxonomic groups and classified each species as native or nonnative at each locality. For each taxonomic group and in aggregate, we then assessed the following: (1) multiple species-area relationship (SAR) models; (2) C- and Z-values, typically interpreted to represent insularity or dispersal ability; and (3) the average diversity of islands, among-island heterogeneity, γ-diversity, and the contribution of area effect toward explaining among-island heterogeneity using additive diversity partitioning approach. We found the following: (1) SARs were best modeled using the Cumulative Weibull and Lomolino relationships; (2) the Cumulative Weibull and Lomolino regressions displayed both convex and sigmoid curves; and (3) the Cumulative Weibull regressions were more conservative than Lomolino at displaying sigmoid curves within the range of island size studied. The Z-value of all herpetofauna was overestimated by Darlington (Zoogeography: The geographic distribution of animals, John Wiley, New York, 1957), and Z-values were ranked: (1) native > nonnative; (2) reptiles > amphibians; (3) snake > lizard > frog > turtle > crocodilian; and (4) increased from lower- to higher-level taxonomic groups. Additive diversity partitioning showed that area had a weaker effect on explaining the among-island heterogeneity for nonnative species than for native species. Our findings imply that the flexibility of Cumulative Weibull and Lomolino has been underappreciated in the literature. Z-value is an average of different slopes from different scales and could be artificially overestimated due to oversampling islands of intermediate to large size. Lower extinction rate, higher colonization, and more in situ speciation could contribute to high richness of native species on large islands, enlarging area effect on explaining the between-island heterogeneity for native species, whereas economic isolation on large islands could decrease the predicted richness, lowering the area effect for nonnative species. For most of the small islands less affected by human activities, extinction and dispersal limitation are the primary processes producing low species richness pattern, which decreases the overall average diversity with a large among-island heterogeneity corresponding to the high value of this region as a biodiversity hotspot.

Real-time measurement of urethral dose and position during permanent seed implantation for prostate brachytherapy.

PURPOSE: The in vivo dosimetry tool, RADPOS, has been modified to include a metal oxide-silicon semiconductor field effect transistor (MOSFET) array with an electromagnetic positioning sensor. This allows dose monitoring at five points rather than just at single dose point as in the other versions of the device. The detector has been used in a clinical trial, which is the first to measure both urethral dose and internal motion concurrently during permanent seed implantation for prostate brachytherapy using a single probe. METHODS AND MATERIALS: The RADPOS detector was secured inside a Foley catheter inside the patient's urethra. Spatial coordinates of the RADPOS detector were read every 0.5s, and the timing of events such as needle insertion was noted. The MOSFET readings were taken over two 10-min periods; once all seeds had been implanted both before and after the transrectal ultrasound (TRUS), the probe was removed. Measurements were completed for 16 patients. RESULTS: Maximum integral dose in the prostatic urethral ranged from 89 to 195Gy, and dose varied from -66% to 36% depending on the rectal probe position. The change in position of the RADPOS sensor owing to the removal of the TRUS probe ranged from 1.4 to 9.7mm. CONCLUSIONS: The modified RADPOS detector with MOSFET array is able to provide real-time dose information, which can be used to monitor dose rates while implantation is performed and to estimate the total integrated dose. Changes in position including those owing to the TRUS probe can be significant and should be quantified to evaluate the influence on dose distributions.

The ethics of wildlife research: a nine R theory.

The commonsense ethical constraints on laboratory animal research known as the three Rs are widely accepted, but no constraints tailored to research on animals in the wild are available. In this article, we begin to fill that gap. We sketch a set of commonsense ethical constraints on ecosystem research parallel to the constraints that govern laboratory animal research. Then we combine the animal and ecosystem constraints into a single theory to govern research on animals in the wild.

A phase 3 trial of whole brain radiation therapy and stereotactic radiosurgery alone versus WBRT and SRS with temozolomide or erlotinib for non-small cell lung cancer and 1 to 3 brain metastases: Radiation Therapy Oncology Group 0320.

BACKGROUND: A phase 3 Radiation Therapy Oncology Group (RTOG) study subset analysis demonstrated improved overall survival (OS) with the addition of stereotactic radiosurgery (SRS) to whole brain radiation therapy (WBRT) in non-small cell lung cancer (NSCLC) patients with 1 to 3 brain metastases. Because temozolomide (TMZ) and erlotinib (ETN) cross the blood-brain barrier and have documented activity in NSCLC, a phase 3 study was designed to test whether these drugs would improve the OS associated with WBRT + SRS. METHODS AND MATERIALS: NSCLC patients with 1 to 3 brain metastases were randomized to receive WBRT (2.5 Gy × 15 to 37.5 Gy) and SRS alone, versus WBRT + SRS + TMZ (75 mg/m(2)/day × 21 days) or ETN (150 mg/day). ETN (150 mg/day) or TMZ (150-200 mg/m(2)/day × 5 days/month) could be continued for as long as 6 months after WBRT + SRS. The primary endpoint was OS. RESULTS: After 126 patients were enrolled, the study closed because of accrual limitations. The median survival times (MST) for WBRT + SRS, WBRT + SRS + TMZ, and WBRT + SRS + ETN were qualitatively different (13.4, 6.3, and 6.1 months, respectively), although the differences were not statistically significant. Time to central nervous system progression and performance status at 6 months were better in the WBRT + SRS arm. Grade 3 to 5 toxicity was 11%, 41%, and 49% in arms 1, 2, and 3, respectively (P<.001). CONCLUSION: The addition of TMZ or ETN to WBRT + SRS in NSCLC patients with 1 to 3 brain metastases did not improve survival and possibly had a deleterious effect. Because the analysis is underpowered, these data suggest but do not prove that increased toxicity was the cause of inferior survival in the drug arms.

Clinical use of a novel in vivo 4D monitoring system for simultaneous patient motion and dose measurements.

PURPOSE: A new 4D in vivo dosimetry tool, RADPOS, has been used on lung cancer patients to evaluate the feasibility of using the detectors to characterize variations in patient breathing patterns as well as to monitor daily variations in dose. METHODS AND MATERIALS: The RADPOS system combines a MOSFET dosimeter with an electromagnetic positioning sensor for simultaneous measurement of real-time dose and spatial coordinates. Three RADPOS sensors were placed on patients' chest and abdomen during a 4DCT and daily treatments. A fourth detector was also placed on the couch as reference. Position data were collected in real-time and total dose was read at the end of each fraction. RESULTS: Significant deviations in surface motion have been found between the day of 4DCT and treatment fractions in 9 of 10 patients. Variations in daily dose ranged from 2.5 to 13.7 cGy (2.8-14.0%) and results agreed with treatment plan values for all but three points. CONCLUSIONS: Changes in breathing motion have been found that emphasize a need for continued position monitoring. RADPOS measurements can be used to monitor such variations as well as to measure surface dose without any disruption to the treatment schedule or discomfort to patients.

Surface water mitigates the anti-metamorphic effects of perchlorate in New Mexico spadefoot toads (Spea multiplicata) and African clawed frogs (Xenopus laevis).

Spea multiplicata (New Mexico spadefoot toad) larvae were exposed to 60, 110, and 1000 microg L(-1) perchlorate dissolved in natural surface water to determine risks associated with perchlorate exposure in desert-adapted anurans. Hind- and forelimb development and tail resorption were measured to identify effects of perchlorate exposure. No perchlorate-related effects on snout-vent length, hindlimb length, and proportion metamorphosed were observed in the highest treatment group (positive control; 1000 microg L(-1)) suggesting that either S.multiplicata are not sensitive to the effects of perchlorate at the concentrations tested or that unidentified constituents of natural surface water mitigated perchlorate toxicity. To identify whether surface water mitigated perchlorate toxicity, Xenopuslaevis were exposed to 20 and 60 microg L(-1) perchlorate in surface water and synthetic laboratory prepared water (i.e., FETAX media). X.laevis exposed to perchlorate dissolved in surface water exhibited no perchlorate-related anti-metamorphic effects, whereas X.laevis exposed to perchlorate in FETAX media experienced changes in percent metamorphosing (p<0.001), time to metamorphosis (p<0.001), snout-vent length (p<0.001), and hindlimb length (p<0.001) as compared to FETAX controls. These results suggest that natural surface water can mediate perchlorate effects at concentrations up to 60 microg L(-1) for X.laevis and greater than 1 mg L(-1) for S.multiplicata, potentially due to physicochemical properties of surface water. CAPSULE: This manuscript discusses the effects of perchlorate in natural surface water to S.multiplicata and X.laevis.

Forecasting the risk of brown tree snake dispersal from Guam: a mixed transport-establishment model.

The brown tree snake (Boiga irregularis) is a devastating invader that has ecologically and economically affected Guam and is poised to disperse further. Interdiction efforts are being conducted on Guam and some of the potential receiving sites, but no tools exist for evaluating the potential for snake incursion; thus, the amount of effort that should be invested in protecting particular sites is unknown. We devised a model that predicts the relative risk of establishment of the brown tree snake (BTS) at a given site. To calculate overall risk, we incorporated in the model information on the likelihood of an organism entering the transportation system, avoiding detection, surviving to arrive at another location, and establishing at the receiving end. On the basis of documented rates of snake arrival at receiving sites, the model produced realistic predictions of invasion risk. Model outputs can thus be used to prioritize interdiction efforts to focus on especially vulnerable receiving locations. We provide examples of the utility of the model in evaluating the impacts of changes in transportation parameters. Finally, the model can be used to evaluate the impacts that BTS establishment at an additional site and that creation of a new source of snakes would have. The use of qualitative inputs allows the model to be adapted by substituting data on other invasive species or transportation systems.

Twenty-four-month postradiation prostate biopsies are strongly predictive of 7-year disease-free survival: results from a Canadian randomized trial.

BACKGROUND: The objective of this study was to evaluate the predictive value of prostate biopsies that were obtained 24 months after the completion of radiotherapy (RT) with respect to disease-free survival (DFS) in a randomized trial that compared 3 months versus 8 months of neoadjuvant hormone therapy before conventional dose external RT. METHODS: From February 1995 to June 2001, 378 men were randomized to receive either 3 months or 8 months of combined flutamide and goserelin before they received 66 Gray of RT at 4 participating centers. By risk group, 26% of patients were categorized as low risk, 43% were categorized as intermediate risk, and 31% were categorized as high risk. The 2 treatment arms were balanced in terms of age, Gleason score, clinical tumor classification, risk group, and presenting prostate-specific antigen level. The median follow-up for the patients who remained alive was 6.6 years (range, 1.6-10.1 years). Of 361 evaluable patients, 290 patients remained alive. Post-RT prostate biopsies were performed between 24 and 30 months after the completion of RT in 3 of the 4 centers. Biopsies that had residual tumor with severe treatment effect were considered indeterminate, and biopsies that had minimal or no treatment effect were considered positive. RESULTS: The 5-year rate of actuarial freedom from any failure for the 3-month arm versus the 8-month arm was 72% versus 75% (P = .18). The DFS for patients who had negative and indeterminate biopsies was similar. Two-year post-treatment biopsy status was a strong predictor of 5-year DFS rate (82% and 83% for negative and indeterminate biopsies, respectively, vs 27% for positive biopsies; P < .0001). Multivariate analysis indicated that biopsy status (P < .0001) and Gleason score (P < .0001) were the strongest determinates of biochemical DFS. CONCLUSIONS: Two-year post-RT prostate biopsies were strongly predictive of subsequent DFS. Biopsies with severe treatment effect were considered negative.

Final report of multicenter Canadian Phase III randomized trial of 3 versus 8 months of neoadjuvant androgen deprivation therapy before conventional-dose radiotherapy for clinically localized prostate cancer.

PURPOSE: To evaluate the effect of 3 vs. 8 months of neoadjuvant hormonal therapy before conventional-dose radiotherapy (RT) on disease-free survival for localized prostate cancer. METHODS AND MATERIALS: Between February 1995 and June 2001, 378 men were randomized to either 3 or 8 months of flutamide and goserelin before 66 Gy RT at four participating centers. The median baseline prostate-specific antigen level was 9.7 ng/mL (range, 1.3-189). Of the 378 men, 26% had low-, 43% intermediate-, and 31% high-risk disease. The two arms were balanced in terms of age, Gleason score, clinical T category, risk group, and presenting prostate-specific antigen level. The median follow-up for living patients was 6.6 years (range, 1.6-10.1). Of the 378 patients, 361 were evaluable, and 290 were still living. RESULTS: The 5-year actuarial freedom from failure rate for the 3- vs. 8-month arms was 72% vs. 75%, respectively (p = 0.18). No difference was found in the failure types between the two arms. The median prostate-specific antigen level at the last follow-up visit for patients without treatment failure was 0.6 ng/mL in the 3-month arm vs. 0.50 ng/mL in the 8-month arm. The disease-free survival rate at 5 years was improved for the high-risk patients in the 8-month arm (71% vs. 42%, p = 0.01). CONCLUSION: A longer period of NHT before standard-dose RT did not alter the patterns of failure when combined with 66-Gy RT. High-risk patients in the 8-month arm had significant improvement in the 5-year disease-free survival rate.

Improving interactions between animal rights groups and conservation biologists.

Invasive species are often considered to be a major threat to biodiversity, leading conservation biologists to often recommend their complete eradication. Animal rights groups typically categorically oppose killing animals, and their opposition has brought eradication attempts of gray squirrels in northern Italy (Europe) and mute swans in Vermont to a halt. As a result native red squirrels may disappear from Europe and ecosystem-wide impacts are expected to be caused by the swan. In contrast, cooperation between managers and animal rights groups has resulted in a successful control program for feral pigs in Fort Worth, Texas (U.S.A.). The philosophical differences between animal rights and conservation biologists' views make cooperation seem unlikely, yet documented cases of cooperation have been beneficial for both groups. We recommend that managers dealing with invasive species should consult with social scientists and ethicists to gain a better understanding of the implications of some of their policy decisions. In addition, we recommend that animal rights groups do more to support alternatives to lethal control, which are often excluded by economic limitations. Prevention of arrival of invasive species via application of the precautionary principle may be an especially productive avenue for such collaboration because it fits the goals and values of both groups.