Adjustable wind selectivity in shearwaters implies knowledge of the foraging landscape.

Understanding the movements of highly mobile animals is challenging because of the many factors they must consider in their decision-making. Many seabirds, for example, are adapted to use winds to travel long distances at low energetic cost but also potentially benefit from targeting specific foraging hotspots. To investigate how an animal makes foraging decisions, given the inevitable trade-off between these factors, we tracked over 600 foraging trips of breeding Manx shearwaters (Puffinus puffinus; N = 218 individuals) using GPS accelerometers.

Adjuvant Pembrolizumab versus Observation in Muscle-Invasive Urothelial Carcinoma.

Background: Muscle-invasive urothelial carcinoma is an aggressive disease with high rates of relapse. Whether pembrolizumab as adjuvant therapy would be effective in patients with high-risk muscle-invasive urothelial carcinoma after radical surgery is unknown.

Methods: In this phase 3 trial, we randomly assigned patients, in a 1:1 ratio, to receive pembrolizumab at a dose of 200 mg every 3 weeks for 1 year or to undergo observation.

Final Results From a Phase I Trial and Expansion Cohorts of Cabozantinib and Nivolumab Alone or With Ipilimumab for Advanced/Metastatic Genitourinary Tumors.

Purpose: Cabozantinib and nivolumab (CaboNivo) alone or with ipilimumab (CaboNivoIpi) have shown promising efficacy and safety in patients with metastatic urothelial carcinoma (mUC), metastatic renal cell carcinoma (mRCC), and rare genitourinary (GU) tumors in a dose-escalation phase I study. We report the final data analysis of the safety, overall response rate (ORR), progression-free survival (PFS), and overall survival (OS) of the phase I patients and seven expansion cohorts.

Methods: This is an investigator-initiated, multicenter, phase I trial.

Enzalutamide Monotherapy in the EMBARK Trial Should Be Practice-changing and Existing Data Suggest How to Mitigate Toxicity.

Data from the EMBARK trial demonstrate the potential of enzalutamide monotherapy as an effective treatment for biochemically recurrent prostate cancer (BCR) without the side effects of testosterone-lowering therapy. Unfortunately, concerns about gynecomastia and how to manage this treatment-related toxicity have diminished enthusiasm. Existing data may offer an alternative scheduling strategy for enzalutamide monotherapy in BCR.

[Kidney disease in antiphospholipid antibody syndrome].

Antiphospholipid syndrome (APS) is a rare autoimmune disease characterized by recurrent arterial and venous thromboembolic events. Renal complications occur in 3 % of patients. Renal artery stenosis is the most common, and APS-related nephropathy is the predominant microvascular complication.

Predicting the spatial expansion of an animal population with presence-only data.

Predictive models can improve the efficiency of wildlife management by guiding actions at the local, landscape and regional scales. In recent decades, a vast range of modelling techniques have been developed to predict species distributions and patterns of population spread. However, data limitations often constrain the precision and biological realism of models, which make them less useful for supporting decision-making.

Quantitative Analysis of Serial Positron Emission Tomography Imaging in Men with Metastatic Castration-resistant Prostate Cancer Treated with Enzalutamide.

Background: The emergence of positron emission tomography (PET) in prostate cancer is impacting clinical practice, but little is known about PET imaging as a tool to determine treatment failure in metastatic castration-resistant prostate cancer (mCRPC).

Objective: To evaluate PET imaging dynamics in mCRPC patients on enzalutamide with stable computed tomography (CT) and technetium-99m (Tc99) bone scans.

Design, Setting, And Participants: All patients were on treatment with enzalutamide for first-line mCRPC in a clinical trial at the National Cancer Institute (Bethesda, MD, USA).

Avelumab in Patients With Metastatic Colorectal Cancer.

Background: Metastatic colorectal cancer (mCRC) is incurable, and median overall survival is less than 2½ years. Although monoclonal antibodies that block PD-1/PD-L1 interactions are active in microsatellite unstable/mismatch repair deficient tumors, a growing dataset shows that most patients with microsatellite stable/mismatch repair proficient tumors will not benefit from the blockade of PD-1/PD-L1 interactions. Here we present results from patients with mCRC (n = 22) treated with the anti-PD-L1 monoclonal antibody avelumab.

Relugolix in Clinical Practice: The Best Route for All?

Androgen deprivation therapy (ADT) has been a mainstay of prostate cancer treatment for decades. Relugolix was FDA-approved in 2020 and is currently the only ADT option via an oral route. While the opportunity to use an oral medication for this indication has some advantages, a balanced discussion is required to understand in what clinical settings this agent truly has benefit over long-acting injectable formulations of ADT.

Development, initial validation, and application of a visual read method for [F]MK-6240 tau PET.

Background: The positron emission tomography (PET) radiotracer [F]MK-6240 exhibits high specificity for neurofibrillary tangles (NFTs) of tau protein in Alzheimer's disease (AD), high sensitivity to medial temporal and neocortical NFTs, and low within-brain background. Objectives were to develop and validate a reproducible, clinically relevant visual read method supporting [F]MK-6240 use to identify and stage AD subjects versus non-AD and controls.

Methods: Five expert readers used their own methods to assess 30 scans of mixed diagnosis (47% cognitively normal, 23% mild cognitive impairment, 20% AD, 10% traumatic brain injury) and provided input regarding regional and global positivity, features influencing assessment, confidence, practicality, and clinical relevance.

Finger-Floor Distance Is Not a Valid Parameter for the Assessment of Lumbar Mobility.

Low back pain (LBP) could be associated with a reduced lumbar mobility. For the evaluation of lumbar flexibility, parameters such as finger-floor distance (FFD) are historically established. However, the extent of the correlation of FFD to lumbar flexibility or other involved joint kinematics such as pelvic motion, as well as the influence of LBP, is not yet known.

Avelumab in Men With Metastatic Castration-Resistant Prostate Cancer, Enriched for Patients Treated Previously With a Therapeutic Cancer Vaccine.

Therapeutic cancer vaccines including sipuleucel- T , a prostatic acid phosphatase (PAP) targeted vaccine that improves survival in metastatic castration-resistant prostate cancer (mCRPC), can produce immune responses that translate to clinical benefit. The effects of sequential checkpoint inhibitors after therapeutic vaccine on immune responses are unknown. Avelumab is an anti-programmed death ligand-1 monoclonal antibody evaluated in patients with mCRPC in the JAVELIN solid tumor phase 1 trial expansion cohort, enriched for patients with a previous therapeutic prostate cancer-targeted vaccine.

A Phase I Single-Arm Study of Biweekly NHS-IL12 in Patients With Metastatic Solid Tumors.

Background: NHS-IL12 is a first-in-class, recombinant fusion protein composed of the human monoclonal antibody NHS76 (binds exposed DNA/histones at sites of intratumoral necrosis) fused to 2 IL-12 heterodimers. The maximum tolerated dose (MTD) and recommended phase II dose (RP2D) of NHS-IL12 monotherapy given subcutaneously (SC) every 4 weeks was previously reported. The study was expanded to include a high-exposure cohort with NHS-IL12 SC every 2 weeks (q2w).

Seasonal range fidelity of a megaherbivore in response to environmental change.

For large herbivores living in highly dynamic environments, maintaining range fidelity has the potential to facilitate the exploitation of predictable resources while minimising energy expenditure. We evaluate this expectation by examining how the seasonal range fidelity of African elephants (Loxodonta africana) in the Kruger National Park, South Africa is affected by spatiotemporal variation in environmental conditions (vegetation quality, temperature, rainfall, and fire). Eight-years of GPS collar data were used to analyse the similarity in seasonal utilisation distributions for thirteen family groups.

Phosphoproteomic Analysis Identifies TYRO3 as a Mediator of Sunitinib Resistance in Metastatic Thymomas.

Background: After initially responding to empiric radio-chemotherapy, most advanced thymomas (TH) and thymic carcinomas (TC) become refractory and require second-line therapy. The multi-target receptor tyrosine kinase (RTK) inhibitor, sunitinib, is one of the few options, especially in patients with thymic carcinomas, and has resulted in partial remissions and prolonged overall survival. However, sunitinib shows variable activity in thymomas, and not all patients benefit equally.

Early drug development in solid tumours: analysis of National Cancer Institute-sponsored phase 1 trials.

Background: The low expectation of clinical benefit from phase 1 cancer therapeutics trials might negatively affect patient and physician participation, study reimbursement, and slow the progress of oncology research. Advances in cancer drug development, meanwhile, might have favourably improved treatment responses; however, little comprehensive data exist describing the response and toxicity associated with phase 1 trials across solid tumours. The aim of the study is to evaluate the trend of toxicity and response in phase 1 trials for solid tumours over time.

Resilience of the primary health care system - German primary care practitioners' perspectives during the early COVID-19 pandemic.

Background: Primary care is a relevant pillar in managing not only individual, but also societal medical crises. The COVID-19 pandemic has demanded a rapid response from primary care with interventions in the health care system. The aim of this paper was to explore the responses of primary care practitioners (PCP) during the early COVID-19 pandemic and to analyze these with a view on the resilience of the primary health care system from the PCPs perspective.

The effects of population management on wild ungulates: A systematic map of evidence for UK species.

Introduction: Over recent decades, the abundance and geographic ranges of wild ungulate species have expanded in many parts of Europe, including the UK. Populations are managed to mitigate their ecological impacts using interventions, such as shooting, fencing and administering contraception. Predicting how target species will respond to interventions is critical for developing sustainable, effective and efficient management strategies.

A Single-arm Phase II Study Combining NLG207, a Nanoparticle Camptothecin, with Enzalutamide in Advanced Metastatic Castration-resistant Prostate Cancer Post-Enzalutamide.

Background: Despite the clinical efficacy of enzalutamide monotherapy in patients with advanced prostate cancer, therapeutic resistance and disease progression are inevitable. We proposed a study to evaluate NLG207, a nanoparticle-drug conjugate (NDC) of the potent topoisomerase I inhibitor camptothecin, in combination with enzalutamide, in patients with metastatic castration-resistant prostate cancer (mCRPC) following progression on enzalutamide.

Methods: This was a single-arm, optimal two-stage, phase II study to evaluate the efficacy of NLG207 in combination with enzalutamide in patients with mCRPC who received prior enzalutamide.

A Randomized Phase II Trial of mFOLFOX6 + Bevacizumab Alone or with AdCEA Vaccine + Avelumab Immunotherapy for Untreated Metastatic Colorectal Cancer.

Background: FOLFOX plus bevacizumab is a standard of care (SOC) for first-line treatment of microsatellite-stable metastatic colorectal cancer (MSS mCRC). This study randomized patients to SOC or SOC plus avelumab (anti-PD-L1) plus CEA-targeted vaccine.

Methods: Patients with untreated MSS mCRC enrolled to a lead-in arm assessing safety of SOC + immuno-oncology agents (IO).

Trends in Grade 5 Toxicity and Response in Phase I Trials in Hematologic Malignancy: 20-Year Experience From the Cancer Therapy Evaluation Program at the National Cancer Institute.

Purpose: Cancer drug development has largely shifted from cytotoxic chemotherapy to targeted treatment in the past two decades. Although previous studies have highlighted improvement in response rates in recent phase I trials, disease-focused reporting is limited.

Methods: We integrated patient-level data for patients with hematologic malignancies who participated in phase I trials sponsored by the National Cancer Institute Cancer Therapy Evaluation Program between January 2000 and May 2019 and estimated the trend of grade 5 toxicity and response by disease subtype over time.

Social Disruption Impairs Predatory Threat Assessment in African Elephants.

The transmission of reliable information between individuals is crucial for group-living animals. This is particularly the case for cognitively advanced mammals with overlapping generations that acquire detailed social and ecological knowledge over long lifetimes. Here, we directly compare the ecological knowledge of elephants from two populations, with radically different developmental histories, to test whether profound social disruption affects their ability to assess predatory threat.

Management of adverse events associated with cabozantinib plus nivolumab in renal cell carcinoma: A review.

Tyrosine kinase inhibitors have been successfully developed in combination with immune checkpoint inhibitors to treat advanced renal cell carcinoma (RCC), further advancing treatment. While safety profiles are generally manageable with combination regimens, overlapping adverse events (AEs) and immune-related AEs can make treatment more complex. The CheckMate 9ER study evaluated the tyrosine kinase inhibitor cabozantinib in combination with the anti-programmed cell death protein-1 antibody nivolumab in patients with previously untreated advanced RCC.