Links between energy budgets, somatic condition, and life history reveal heterogeneous energy management tactics in a group-living mesocarnivore.

BACKGROUND: Optimal management of voluntary energy expenditure is crucial to the survival and reproductive success of wild animals. Nevertheless, a growing appreciation of inter-individual variation in the internal state driving movement suggests that individuals may follow different, yet equally optimal tactics under the same environmental conditions. However, few studies in wild populations have investigated the occurrence and demographic context of different contemporaneous energetic expenditure tactics. Here, we explore this neglected aspect of energy budgeting in order to determine the effect of life-history traits such as age and reproductive status on the co-occurrence of different energy-budgeting tactics in wild populations. METHODS: We investigated inter-individual heterogeneity in energy expenditure within a wild population of European badgers (Meles meles) by quantifying individual overall dynamic body acceleration (ODBA, from tri-axial accelerometry collars) and total daily energy expenditure (DEE, from doubly-labelled water) during 6-9 day deployments and dosing periods over six different seasons (spring, summer, and autumn) in 2018-2019. We obtained ODBA values for 41 deployments (24 unique badgers) and DEE measurements for 41 dosings (22 unique badgers). We then evaluated correlations between these energetic metrics and computed individual ratios of ODBA/DEE as a proxy for the proportion of total energy spent on activity. We measured the impact of alternative ODBA/DEE ratios on body condition, and use survival models constructed using 29 years of demographic data from the same population to situate body-condition changes in the context of age and reproductive status. RESULTS: Both ODBA and DEE were highly variable between individuals and exhibited season-specific relationships with individual body condition and life-history factors. DEE scaled allometrically with body weight, but only in summer and autumn; post-reproductive female badgers were lighter than other badgers during the spring but expended on average 350 kJ/day more than predicted from allometric scaling. Older badgers expended significantly less energy on movement during the summer than did younger adults. The ratio of ODBA to DEE (OD) provides a measure of proportional investment into movement. This ratio correlated more significantly with next-season body condition than either energetic metric did independently. However, the majority of individuals with high OD ratios were either younger badgers or reproductive females, for which lower body condition typically presented less of a mortality risk in previous analyses of this population. CONCLUSIONS: Within a single population under the same environmental conditions, we found wide inter-individual variation in both mechanical and total energy expenditure. The adoption of different tactics aligns with relationships between life-history parameters and mortality risk previously studied within the population. Crucially, younger badgers and reproductive females appeared able to tolerate energy expenditure tactics that depleted their body condition more than other badgers. These findings provide a mechanism by which differences in individual energetic context set by life history can maintain heterogeneity in wild populations, providing a wide range of potential energetic tactics under changing environmental conditions.

RANO 2.0: Update to the Response Assessment in Neuro-Oncology Criteria for High- and Low-Grade Gliomas in Adults.

PURPOSE: The Response Assessment in Neuro-Oncology (RANO) criteria for high-grade gliomas (RANO-HGG) and low-grade gliomas (RANO-LGG) were developed to improve reliability of response assessment in glioma trials. Over time, some limitations of these criteria were identified, and challenges emerged regarding integrating features of the modified RANO (mRANO) or the immunotherapy RANO (iRANO) criteria. METHODS: Informed by data from studies evaluating the different criteria, updates to the RANO criteria are proposed (RANO 2.0). RESULTS: We recommend a standard set of criteria for both high- and low-grade gliomas, to be used for all trials regardless of the treatment modalities being evaluated. In the newly diagnosed setting, the postradiotherapy magnetic resonance imaging (MRI), rather than the postsurgical MRI, will be used as the baseline for comparison with subsequent scans. Since the incidence of pseudoprogression is high in the 12 weeks after radiotherapy, continuation of treatment and confirmation of progression during this period with a repeat MRI, or histopathologic evidence of unequivocal recurrent tumor, are required to define tumor progression. However, confirmation scans are not mandatory after this period nor for the evaluation of treatment for recurrent tumors. For treatments with a high likelihood of pseudoprogression, mandatory confirmation of progression with a repeat MRI is highly recommended. The primary measurement remains the maximum cross-sectional area of tumor (two-dimensional) but volumetric measurements are an option. For IDH wild-type glioblastoma, the nonenhancing disease will no longer be evaluated except when assessing response to antiangiogenic agents. In IDH-mutated tumors with a significant nonenhancing component, clinical trials may require evaluating both the enhancing and nonenhancing tumor components for response assessment. CONCLUSION: The revised RANO 2.0 criteria refine response assessment in gliomas.

The challenge of unprecedented floods and droughts in risk management.

Risk management has reduced vulnerability to floods and droughts globally1,2, yet their impacts are still increasing3. An improved understanding of the causes of changing impacts is therefore needed, but has been hampered by a lack of empirical data4,5. On the basis of a global dataset of 45 pairs of events that occurred within the same area, we show that risk management generally reduces the impacts of floods and droughts but faces difficulties in reducing the impacts of unprecedented events of a magnitude not previously experienced. If the second event was much more hazardous than the first, its impact was almost always higher. This is because management was not designed to deal with such extreme events: for example, they exceeded the design levels of levees and reservoirs. In two success stories, the impact of the second, more hazardous, event was lower, as a result of improved risk management governance and high investment in integrated management. The observed difficulty of managing unprecedented events is alarming, given that more extreme hydrological events are projected owing to climate change3.

China's online parrot trade: Generation length and body mass determine sales volume via price.

The wildlife trade threatens global biodiversity and animal welfare, where parrots are among the taxa most frequently traded, supplying exotic pets and captive breeders worldwide. Using phylogenetic path analysis, we examine how biological factors interact with price to influence online protected parrot trade volumes in China, using transactions recorded for 46 species (n = 5862 individuals). Trade was greatest in smaller, faster breeding species that commanded a lower price. This price effect followed the economic law of demand, with Relatively Inelastic Demand (-0.758), outweighing indicators of 'quality' such as body coloration, and conservation status. We identify two areas of concern: those larger, slower-breeding, rarer species, even though sold at lower numbers, may be at conservation risk if harvested from the wild. In contrast, the sheer numbers (over 90% of the individuals were under median generation length, body mass and/or price) and ready availability of smaller and more common species comprises a substantial overall animal welfare issue, given that the capture, importation, or captive breeding of many parrot species in China is illegal and thus unregulated. Our investigation highlights the importance of properly understanding the internal relations among drivers of wildlife trade to inform appropriate management.

Understanding decision making in a food-caching predator using hidden Markov models.

BACKGROUND: Tackling behavioural questions often requires identifying points in space and time where animals make decisions and linking these to environmental variables. State-space modeling is useful for analysing movement trajectories, particularly with hidden Markov models (HMM). Yet importantly, the ontogeny of underlying (unobservable) behavioural states revealed by the HMMs has rarely been verified in the field. METHODS: Using hidden Markov models of individual movement from animal location, biotelemetry, and environmental data, we explored multistate behaviour and the effect of associated intrinsic and extrinsic drivers across life stages. We also decomposed the activity budgets of different movement states at two general and caching phases. The latter - defined as the period following a kill which likely involves the caching of uneaten prey - was subsequently confirmed by field inspections. We applied this method to GPS relocation data of a caching predator, Persian leopard Panthera pardus saxicolor in northeastern Iran. RESULTS: Multistate modeling provided strong evidence for an effect of life stage on the behavioural states and their associated time budget. Although environmental covariates (ambient temperature and diel period) and ecological outcomes (predation) affected behavioural states in non-resident leopards, the response in resident leopards was not clear, except that temporal patterns were consistent with a crepuscular and nocturnal movement pattern. Resident leopards adopt an energetically more costly mobile behaviour for most of their time while non-residents shift their behavioural states from high energetic expenditure states to energetically less costly encamped behaviour for most of their time, which is likely to be a risk avoidance strategy against conspecifics or humans. CONCLUSIONS: This study demonstrates that plasticity in predator behaviour depending on life stage may tackle a trade-off between successful predation and avoiding the risks associated with conspecifics, human presence and maintaining home range. Range residency in territorial predators is energetically demanding and can outweigh the predator's response to intrinsic and extrinsic variables such as thermoregulation or foraging needs. Our approach provides an insight into spatial behavior and decision making of leopards, and other large felids in rugged landscapes through the application of the HMMs in movement ecology.

Optimal frequency of scans for patients on cancer therapies: A population kinetics assessment.

BACKGROUND: Optimal frequency of follow-up scans for patients receiving systemic therapies is poorly defined. Progression-free survival (PFS) generally follows first-order kinetics. We used exponential decay nonlinear regression analysis to calculate half-lives for 887 published PFS curves. METHOD: We used the Excel formula x = EXP(-tn *0.693/t1/2 ) to calculate proportion of residual patients remaining progression-free at different times, where tn is the interval in weeks between scans (eg, 6 weeks), * indicates multiplication, 0.693 is the natural logarithm of 2, and t1/2 is the PFS half-life in weeks. RESULTS: Proportion of residual patients predicted to remain progression-free at each subsequent scan varied with scan intervals and regimen PFS half-life. For example, with a 4-month half-life (17.3 weeks) and scans every 6 weeks, 21% of patients would progress by the first scan, 21% of the remaining patients would progress by the second scan at 12 weeks, etc With 2, 6- and 12-month half-lives (for example), the proportion of remaining patients progressing at each subsequent scan if repeated every 3 weeks would be 21%, 8% and 4%, respectively, while with scans every 12 weeks it would be 62%, 27% and 15%, respectively. Furthermore, optimal scan frequency can be calculated for populations comprised of distinct rapidly and slowly progressing subpopulations, as well as with convex curves arising from treatment breaks, where optimal scan frequency may differ during therapy administration vs during more rapid progression after therapy interruption. CONCLUSIONS: A population kinetics approach permits a regimen- and tumor-specific determination of optimal scan frequency for patients on systemic therapies.

Personalized perioperative medicine: a scoping review of personalized assessment and communication of risk before surgery.

BACKGROUND: Personalized medicine aims to improve outcomes through application of therapy directed by individualized risk profiles. Whether personalized risk assessment is routinely applied in practice is unclear; the impact of personalized preoperative risk prediction and communication on outcomes has not been synthesized. Our objective was to perform a scoping review to examine the extent, range, and nature of studies where personalized risk was evaluated preoperatively and communicated to the patient and/or healthcare professional. METHODS: A systematic search was developed, peer-reviewed, and applied to Embase, Medline, CINAHL, and Cochrane databases to identify studies of individuals having or considering surgery, where a process to assess personalized risk was applied and where these estimates were communicated to a patient and/or healthcare professional. All stages of the review were completed in duplicate. We narratively synthesized and described identified themes. RESULTS: We identified 796 studies; 24 underwent full-text review. Seven studies were included; one communicated personalized risk to patients, four to a healthcare professional, and two to both. Cardiac (n = 2) and orthopedic surgery (n = 2) were the most common surgical specialties. Four studies used electronic risk calculators, and three used paper-based tools. Personalized preoperative risk assessment and communication may improve accuracy of information provided to patients, improve consent processes, and influence length of stay. Methodologic weaknesses in study design were common. CONCLUSIONS: Personalized preoperative risk assessment and communication may improve patient and system outcomes. This evidence is limited, however, by weaknesses in study design. Appropriately powered, low risk of bias evaluation of personalized risk communication before surgery is needed.

"I just want to be treated like a normal person": Oral health care experiences of transgender adolescents and young adults.

BACKGROUND: Transgender and gender nonconforming (TGNC) people continue to experience health care disparities despite increasing visibility and acceptance. As far as is known, no information exists regarding their experiences with oral health care providers. In this study, the authors intended to understand how TGNC adolescents and young adults interface with their oral health care providers. METHODS: A total of 36 participants, including patients 14 through 24 years of age and their caregivers, were recruited from the Transgender Health Clinic at the Cincinnati Children's Hospital, Cincinnati, Ohio. Interviews were conducted using a semistructured interview guide. All interviews were transcribed verbatim, coded, and analyzed for major themes using grounded theory methodology. RESULTS: Overall, participants reported positive experiences with their oral health care providers. Those with negative experiences reported that the problems were corrected rapidly. Some participants reported issues processing insurance. Several indicated that stress and anxiety related to gender identity could be reduced via use of certain strategies. CONCLUSIONS: TGNC adolescents and young adults have minimal difficulty receiving oral health care. Oral health care providers can make minor modifications to intake forms and office design to improve patient experience and reduce stress and anxiety related to gender identity in the health care setting. PRACTICAL IMPLICATIONS: Although TGNC adolescents and young adults may not need oral health care specific to their identity, taking steps to provide a safe and comfortable treatment setting can improve patient experience for this vulnerable population.

Conservation geopolitics.

We reviewed recent work concerning the impact of geopolitics on wildlife conservation (and vice versa) and identified future priorities in conservation geopolitics research. Geopolitics is understood as both an analytical focus on geopolitical practices (especially concerning the behavior) of countries with respect to territory and national security and a set of theories developed to explain and predict those behaviors. We developed a typology of core geopolitical practices of relevance to conservation: territorial practices of colonization and the management of migrations and borders, and security practices relating to military, economic, and environmental security. We identified research that considers how these practices affect conservation situations and outcomes, noting the recent emergence of conceptual developments such as "environmental geopolitics" and "geopolitical ecology" that draw on multiple fields within the social sciences to theorize the links between geopolitics and environmental management. We defined a "geopolitical perspective" as a focus on geopolitical practices combined with an explicit engagement with geopolitical theory and identified conservation situations where this perspective could contribute to analytical clarity. We suggest the most pressing questions in conservation research to which the geopolitical perspective might contribute are how political and economic differences between countries affect biodiversity outcomes, how geopolitical practices to address those differences facilitate or frustrate conservation efforts, how national borders and human and wildlife movements can be better managed for the benefit of both, and how the most effective conservation strategies can be best selected to suit existing (and future) geopolitical realities.

Geopolítica de la Conservación Resumen Revisamos el trabajo reciente relativo al impacto que tiene la geopolítica sobre la conservación de la vida silvestre (y viceversa) e identificamos prioridades futuras para la investigación de la geopolítica de la conservación. Se define a la geopolítica como un enfoque analítico en las prácticas geopolíticas (especialmente en relación con el comportamiento) de los países con respecto al territorio y a la seguridad nacional y como un conjunto de teorías desarrolladas para explicar y predecir aquellos comportamientos. Desarrollamos una tipología de prácticas nucleares de geopolítica relevantes para la conservación: prácticas territoriales de colonización y el manejo de migraciones y de las fronteras, y prácticas de seguridad relacionadas con la seguridad militar, económica y ambiental. Identificamos las investigaciones que consideran cómo estas prácticas afectan a las situaciones de conservación y sus resultados, tomando en cuenta el surgimiento reciente de desarrollos conceptuales como los de "geopolítica ambiental" y "ecología geopolítica" que parten de múltiples campos de estudio situados dentro de las ciencias sociales para teorizar las conexiones entre la geopolítica y el manejo ambiental. Definimos una perspectiva geopolítica como el enfoque en las prácticas geopolíticas combinada con una participación explícita de la teoría geopolítica e identificamos situaciones de conservación en donde esta perspectiva podría contribuir a la claridad analítica. Sugerimos que las preguntas más urgentes para la investigación en la conservación para las cuales la perspectiva geopolítica podría contribuir son cómo las diferencias políticas y económicas entre los países afectan a los resultados de la biodiversidad, cómo las prácticas geopolíticas abordan esas diferencias facilita o frustra los esfuerzos de conservación, cómo las fronteras nacionales y los movimientos humanos y faunísticos pueden manejarse de mejor manera para el beneficio de ambos, y cómo las estrategias de conservación más efectivas pueden seleccionarse de mejor forma para acoplarse a las realidades geopolíticas existentes (y futuras).

Corticosteroid use endpoints in neuro-oncology: Response Assessment in Neuro-Oncology Working Group.

Background: Corticosteroids are the mainstay of treatment for peritumor edema but are often associated with significant side effects. Therapies that can reduce corticosteroid use would potentially be of significant benefit to patients. However, currently there are no standardized endpoints evaluating corticosteroid use in neuro-oncology clinical trials. Methods: The Response Assessment in Neuro-Oncology (RANO) Working Group has developed consensus recommendations for endpoints evaluating corticosteroid use in clinical trials in both adults and children with brain tumors. Results: Responders are defined as patients with a 50% reduction in total daily corticosteroid dose compared with baseline or reduction of the total daily dose to ≤2 mg of dexamethasone (or equivalent dose of other corticosteroid); baseline dose must be at least 4 mg of dexamethasone daily (or equivalent dose of other corticosteroids) for at least one week. Patients must have stable or improved Neurologic Assessment in Neuro-Oncology (NANO) score or Karnofsky performance status score or Eastern Cooperative Oncology Group (ECOG) (Lansky score for children age <16 y), and an improved score on a relevant clinical outcome assessment tool. These criteria must be sustained for at least 4 weeks after baseline assessment to be considered a response, and are confirmed 4 weeks after that (ie, 8 wk after baseline assessment) to be considered a sustained response. Conclusions: This RANO proposal for corticosteroid use endpoints in neuro-oncology clinical trials may need to be refined and will require prospective validation in clinical studies.

Clinical trial design for systemic agents in patients with brain metastases from solid tumours: a guideline by the Response Assessment in Neuro-Oncology Brain Metastases working group.

Patients with active CNS disease are often excluded from clinical trials, and data regarding the CNS efficacy of systemic agents are usually obtained late in the drug development process or not at all. In this guideline from the Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) working group, we provide detailed recommendations on when patients with brain metastases from solid tumours should be included or excluded in clinical trials of systemic agents. We also discuss the limitations of retrospective studies in determining the CNS efficacy of systemic drugs. Inclusion of patients with brain metastases early on in the clinical development of a drug or a regimen is needed to generate appropriate CNS efficacy or non-efficacy signals. We consider how to optimally incorporate or exclude such patients in systemic therapy trials depending on the likelihood of CNS activity of the agent by considering three scenarios: drugs that are considered very unlikely to have CNS antitumour activity or efficacy; drugs that are considered very likely to have CNS activity or efficacy; and drugs with minimal baseline information on CNS activity or efficacy. We also address trial design issues unique to patients with brain metastases, including the selection of appropriate CNS endpoints in systemic therapy trials.

Clinical trial design for local therapies for brain metastases: a guideline by the Response Assessment in Neuro-Oncology Brain Metastases working group.

The goals of therapeutic and biomarker development form the foundation of clinical trial design, and change considerably from early-phase to late-phase trials. From these goals, decisions on specific clinical trial design elements, such as endpoint selection and statistical approaches, are formed. Whereas early-phase trials might focus on finding a therapeutic signal to make decisions on further development, late-phase trials focus on the confirmation of therapeutic impact by considering clinically meaningful endpoints. In this guideline from the Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) working group, we highlight issues related to, and provide recommendations for, the design of clinical trials on local therapies for CNS metastases from solid tumours. We discuss endpoint selection criteria, the analysis appropriate for early-phase and late-phase trials, the association between tumour-specific and clinically meaningful endpoints, and possible issues related to the estimation of local control in the context of competing risks. In light of these discussions, we make specific recommendations on the clinical trial design of local therapies for brain metastases.

Response Assessment in Neuro-Oncology Clinical Trials.

Development of novel therapies for CNS tumors requires reliable assessment of response and progression. This requirement has been particularly challenging in neuro-oncology for which contrast enhancement serves as an imperfect surrogate for tumor volume and is influenced by agents that affect vascular permeability, such as antiangiogenic therapies. In addition, most tumors have a nonenhancing component that can be difficult to accurately quantify. To improve the response assessment in neuro-oncology and to standardize the criteria that are used for different CNS tumors, the Response Assessment in Neuro-Oncology (RANO) working group was established. This multidisciplinary international working group consists of neuro-oncologists, medical oncologists, neuroradiologists, neurosurgeons, radiation oncologists, neuropsychologists, and experts in clinical outcomes assessments, working in collaboration with government and industry to enhance the interpretation of clinical trials. The RANO working group was originally created to update response criteria for high- and low-grade gliomas and to address such issues as pseudoresponse and nonenhancing tumor progression from antiangiogenic therapies, and pseudoprogression from radiochemotherapy. RANO has expanded to include working groups that are focused on other tumors, including brain metastases, leptomeningeal metastases, spine tumors, pediatric brain tumors, and meningiomas, as well as other clinical trial end points, such as clinical outcomes assessments, seizures, corticosteroid use, and positron emission tomography imaging. In an effort to standardize the measurement of neurologic function for clinical assessment, the Neurologic Assessment in Neuro-Oncology scale was drafted. Born out of a workshop conducted by the Jumpstarting Brain Tumor Drug Development Coalition and the US Food and Drug Administration, a standardized brain tumor imaging protocol now exists to reduce variability and improve reliability. Efforts by RANO have been widely accepted and are increasingly being used in neuro-oncology trials, although additional refinements will be needed.

Use of minimal residual disease assessment in the treatment of chronic lymphocytic leukemia.

Progress in chronic lymphocytic leukemia (CLL) therapies has extended greatly the length and depth of remission, with the goal of treatment advancing towards a cure for some patients. Accordingly, clinical endpoints must evolve to capture these outcomes, and to provide faster access to novel therapies. Minimal residual disease (MRD) is an important endpoint representing more accurately the depth of remission than complete response (CR), and is highly prognostic of progression-free survival (PFS) and overall survival (OS). MRD could be considered a key outcome of clinical trials and, as a surrogate for PFS, could identify the most cost-effective and durable treatment sequencing. MRD testing could also determine which patients would benefit from additional therapy and, accordingly, ascertain when therapy should be stopped earlier, to reduce toxicity and increase treatment-free intervals. Our article discusses possible uses of MRD in the modern era of CLL, including its definition, measurement, and value as a surrogate endpoint in clinical trials, and its potential roles in clinical practice.

The Neurologic Assessment in Neuro-Oncology (NANO) scale: a tool to assess neurologic function for integration into the Response Assessment in Neuro-Oncology (RANO) criteria.

Background: The Macdonald criteria and the Response Assessment in Neuro-Oncology (RANO) criteria define radiologic parameters to classify therapeutic outcome among patients with malignant glioma and specify that clinical status must be incorporated and prioritized for overall assessment. But neither provides specific parameters to do so. We hypothesized that a standardized metric to measure neurologic function will permit more effective overall response assessment in neuro-oncology. Methods: An international group of physicians including neurologists, medical oncologists, radiation oncologists, and neurosurgeons with expertise in neuro-oncology drafted the Neurologic Assessment in Neuro-Oncology (NANO) scale as an objective and quantifiable metric of neurologic function evaluable during a routine office examination. The scale was subsequently tested in a multicenter study to determine its overall reliability, inter-observer variability, and feasibility. Results: The NANO scale is a quantifiable evaluation of 9 relevant neurologic domains based on direct observation and testing conducted during routine office visits. The score defines overall response criteria. A prospective, multinational study noted a >90% inter-observer agreement rate with kappa statistic ranging from 0.35 to 0.83 (fair to almost perfect agreement), and a median assessment time of 4 minutes (interquartile range, 3-5). Conclusion: The NANO scale provides an objective clinician-reported outcome of neurologic function with high inter-observer agreement. It is designed to combine with radiographic assessment to provide an overall assessment of outcome for neuro-oncology patients in clinical trials and in daily practice. Furthermore, it complements existing patient-reported outcomes and cognition testing to combine for a global clinical outcome assessment of well-being among brain tumor patients.

Daily energy expenditure in the face of predation: hedgehog energetics in rural landscapes.

Failure to balance daily energy expenditure (DEE) with energy intake can have an impact on survival and reproduction, and therefore on the persistence of populations. Here we study the DEE of the European hedgehog (Erinaceus europaeus), which is declining in the UK. We hypothesise that there is a gradient of suitable habitat for hedgehogs in rural areas, which is a result of fewer food resources, a higher risk from predation by badgers (Meles meles) and colder ambient temperatures, as distance to the nearest building increases. We used the doubly labelled water method to obtain 44 measurements of DEE from hedgehogs on four predominately arable sites, to determine the energetic costs associated with proximity to buildings, on sites with and without badgers. The mean±s.e.m. DEE was 508.9±34.8 kJ day-1 DEE increased the further a hedgehog was from buildings during the study, possibly as they ranged larger distances on arable land, supporting the hypothesis that hedgehogs select villages owing to the lower energy demands in comparison to arable farmland. Hedgehogs had an approximately 30% lower DEE on sites with badgers. We speculate that on badger-occupied sites, hedgehogs may restrict movement and foraging in response to a threat from predation and thus have reduced DEE. Therefore, hedgehogs may also seek refuge in villages where the perceived threat of predation is lower and foraging is unrestricted. In a broader context, we demonstrate that individual differences in DEE can aid in understanding habitat selection in a patchily distributed species.

Predicting Hotspots of Human-Elephant Conflict to Inform Mitigation Strategies in Xishuangbanna, Southwest China.

Research on the spatial patterns of human-wildlife conflict is fundamental to understanding the mechanisms underlying it and to identifying opportunities for mitigation. In the state of Xishuangbanna, containing China's largest tropical forest, an imbalance between nature conservation and economic development has led to increasing conflicts between humans and Asian elephants (Elephas maximus), as both elephant numbers and conversion of habitable land to rubber plantations have increased over the last several decades. We analyzed government data on the compensation costs of elephant-caused damage in Xishuangbanna between 2008 and 2012 to understand the spatial and temporal patterns of conflict, in terms of their occurrence, frequency and distribution. More than 18,261 incidents were reported, including episodes involving damage to rubber trees (n = 10,999), damage to crops such as paddy, upland rice, corn, bananas and sugarcane (n = 11,020), property loss (n = 689) and attacks on humans (n = 19). The conflict data reconfirmed the presence of elephants in areas which have lacked records since the late 1990s. Zero Altered Negative Binomial models revealed that the risk of damage to crops and plantations increased with proximity to protected areas, increasing distance from roads, and lower settlement density. The patterns were constant across seasons and types of crop damaged. Damage to rubber trees was essentially incidental as elephants searched for crops to eat. A predictive map of risks revealed hotspots of conflict within and around protected areas, the last refuges for elephants in the region, and along habitat corridors connecting them. Additionally, we analyzed how mitigation efforts can best diminish the risk of conflict while minimizing financial costs and adverse biological impacts. Our analytical approach can be adopted, adjusted and expanded to other areas with historical records of human-wildlife conflict.

Response assessment criteria for brain metastases: proposal from the RANO group.

CNS metastases are the most common cause of malignant brain tumours in adults. Historically, patients with brain metastases have been excluded from most clinical trials, but their inclusion is now becoming more common. The medical literature is difficult to interpret because of substantial variation in the response and progression criteria used across clinical trials. The Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) working group is an international, multidisciplinary effort to develop standard response and progression criteria for use in clinical trials of treatment for brain metastases. Previous efforts have focused on aspects of trial design, such as patient population, variations in existing response and progression criteria, and challenges when incorporating neurological, neuro-cognitive, and quality-of-life endpoints into trials of patients with brain metastases. Here, we present our recommendations for standard response and progression criteria for the assessment of brain metastases in clinical trials. The proposed criteria will hopefully facilitate the development of novel approaches to this difficult problem by providing more uniformity in the assessment of CNS metastases across trials.

Gemcitabine/dexamethasone/cisplatin vs cytarabine/dexamethasone/cisplatin for relapsed or refractory aggressive-histology lymphoma: cost-utility analysis of NCIC CTG LY.12.

BACKGROUND: The NCIC CTG LY.12 study showed that gemcitabine, dexamethasone, and cisplatin (GDP) were noninferior to dexamethasone, cytarabine, and cisplatin (DHAP) in patients with relapsed or refractory aggressive histology lymphoma prior to autologous stem cell transplantation. We conducted an economic evaluation from the perspective of the Canadian public healthcare system based on trial data. METHODS: The primary outcome was an incremental cost utility analysis comparing costs and benefits associated with GDP vs DHAP. Resource utilization data were collected from 519 Canadian patients in the trial. Costs were presented in 2012 Canadian dollars and disaggregated to highlight the major cost drivers of care. Benefit was measured as quality-adjusted life-years (QALYs) based on utilities translated from prospectively collected quality-of-life data. All statistical tests were two-sided. RESULTS: The mean overall costs of treatment per patient in the GDP and DHAP arms were $19 961 (95% confidence interval (CI) = $17 286 to $24 565) and $34 425 (95% CI = $31 901 to $39 520), respectively, with an incremental difference in direct medical costs of $14 464 per patient in favor of GDP (P < .001). The predominant cost driver for both treatment arms was related to hospitalizations. The mean discounted quality-adjusted overall survival with GDP was 0.161 QALYs and 0.152 QALYs for DHAP (difference = 0.01 QALYs, P = .146). In probabilistic sensitivity analysis, GDP was associated with both cost savings and improved quality-adjusted outcomes compared with DHAP in 92.6% of cost-pair simulations. CONCLUSIONS: GDP was associated with both lower costs and similar quality-adjusted outcomes compared with DHAP in patients with relapsed or refractory lymphoma. Considering both costs and outcomes, GDP was the dominant therapy.

Priorities for global felid conservation.

Conservation resources are limited, necessitating prioritization of species and locations for action. Most prioritization approaches are based solely on biologically relevant characteristics of taxa or areas and ignore geopolitical realities. Doing so risks a poor return on conservation investment due to nonbiological factors, such as economic or political instability. We considered felids, a taxon which attracts intense conservation attention, to demonstrate a new approach that incorporates both intrinsic species traits and geopolitical characteristics of countries. We developed conservation priority scores for wild felids based on their International Union for Conservation of Nature status, body mass, habitat, range within protected area, evolutionary distinctiveness, and conservation umbrella potential. We used published data on governance, economics and welfare, human population pressures, and conservation policy to assign conservation-likelihood scores to 142 felid-hosting countries. We identified 71 countries as high priorities (above median) for felid conservation. These countries collectively encompassed all 36 felid species and supported an average of 96% of each species' range. Of these countries, 60.6% had below-average conservation-likelihood scores, which indicated these countries are relatively risky conservation investments. Governance was the most common factor limiting conservation likelihood. It was the major contributor to below-median likelihood scores for 62.5% of the 32 felid species occurring in lower-likelihood countries. Governance was followed by economics for which scores were below median for 25% of these species. An average of 58% of species' ranges occurred in 43 higher-priority lower-likelihood countries. Human population pressure was second to governance as a limiting factor when accounting for percentage of species' ranges in each country. As conservation likelihood decreases, it will be increasingly important to identify relevant geopolitical limitations and tailor conservation strategies accordingly. Our analysis provides an objective framework for biodiversity conservation action planning. Our results highlight not only which species most urgently require conservation action and which countries should be prioritized for such action, but also the diverse constraints which must be overcome to maximize long-term success.