Genetic integrity of European wildcats: Variation across biomes mandates geographically tailored conservation strategies

Hybridisation between domestic and wild taxa can pose severe threats to wildlife conservation, and human-induced hybridisation, often linked to species' introductions and habitat degradation, may promote reproductive opportunities between species for which natural interbreeding would be highly unlikely. Using a biome-specific approach, we examine the effects of a suite of ecological drivers on the European wildcat's genetic integrity, while assessing the role played by protected areas in this process. We used genotype data from 1217 putative European wildcat samples from 13 European countries to assess the effects of landcover, disturbance and legal landscape protection on the European wildcat's genetic integrity across European biomes, through generalised linear models within a Bayesian framework. Overall, we found European wildcats to have genetic integrity levels above the wildcat-hybrid threshold (ca. 83%; threshold = 80%). However, Mediterranean and Temperate Insular biomes (i.e., Scotland) revealed lower levels, with 74% and 46% expected genetic integrity, respectively. We found that different drivers shape the level of genetic introgression across biomes, although forest integrity seems to be a common factor promoting European wildcat genetic integrity. Wildcat genetic integrity remains high, regardless of landscape legal protection, in biomes where populations appear to be healthy and show recent local range expansions. However, in biomes more susceptible to hybridisation, even protected areas show limited effectiveness in mitigating this threat. In the face of the detected patterns, we recommend that species conservation and management plans should be biome- and landscape-context-specific to ensure effective wildcat conservation, especially in the Mediterranean and Temperate Insular biomes.Thanks are due to FCT/MCTES for the financial support to cE3c (UIDB/00329/2020), through national funds, and the co-funding by the FEDER, within the PT2020 Partnership Agreement and Compete 2020. PM was supported by UID/BIA/50027/2021 with funding from FCT/MCTES through national funds. FDR was supported by a postdoctoral contract from the University of Málaga (I Plan Propio de Investigación y Transferencia, call 2020). This study was partly funded by research projects CGL2009-10741, funded by the Spanish Ministry of Science and Innovation and EU-FEDER, and OAPN 352/2011, funded by the Organismo Autónomo Parques Nacionales (Spain). Luxembourg sample collection has been co-funded by the Ministry of Environment, Climate and Sustainable Development of Luxembourg. We would like to thank the Bavarian Forest National Park Administration for the approval and support in collecting samples.Peer reviewe

Multilevel Societies in Primates and Other Mammals: Introduction to the Special Issue

# The Author(s) 2012. This article is published with open access at Springerlink.co

Response to Osimertinib in a Patient with Non-Small Cell Lung Cancer and Two Uncommon *EGFR* Mutations

In advanced non-small cell lung cancer (NSCLC), epidermal growth factor receptor (*EGFR*) mutations are one of the most frequent oncogenic drivers. They confer a favorable prognosis and strongly predict sensitivity to EGFR tyrosine kinase inhibitors (TKIs). Over the last decades, several *EGFR* genetic alterations, common and uncommon mutations, have been described in exons 18−21. Common mutations are exon 19 deletions (most frequently E746-A750) and exon 21 L858R substitution. Uncommon mutations include exon 18 G719X, exon 20 S768l, exon 21 L861Q and many other rare ones. This report describes the case of a 55-year-old woman with a newly diagnosed metastatic lung adenocarcinoma harboring two rare *EGFR* mutations and showing sustained response to osimertinib

Where Are We Now and Where Might We Be Headed in Understanding and Managing Brain Metastases in Colorectal Cancer Patients?

Compared to liver and lung metastases, brain metastases (BMs) from colorectal cancer (CRC) are rare and remain poorly investigated despite the anticipated rise in their incidence. CRC patients bearing BM have a dismal prognosis with a median survival of 3-6 months, significantly lower than that of patients with BM from other primary tumors, and of those with metastatic CRC manifesting extracranially. While liver and lung metastases from CRC have more codified treatment strategies, there is no consensus regarding the treatment of BM in CRC, and their management follows the approaches of BM from other solid tumors. Therapeutic strategies are driven by the number and localisation of the lesion, consisting in local treatments such as surgery, stereotactic radiosurgery, or whole-brain radiotherapy. Novel treatment modalities are slowly finding their way into this shy unconsented armatorium including immunotherapy, monoclonal antibodies, tyrosine kinase inhibitors, or a combination of those, among others.This article reviews the pioneering strategies aiming at understanding, diagnosing, and managing this disease, and discusses future directions, challenges, and potential innovations in each of these domains. • With the increasing survival in CRC, brain and other rare/late-onset metastases are rising. • Distal colon/rectal primary location, long-standing progressive lung metastases, and longer survival are risk factors for BM development in CRC. • Late diagnosis and lack of consensus treatment strategies make BM-CRC diagnosis very dismal. • Liquid biopsies using circulating tumor cells might offer excellent opportunities in the early diagnosis of BM-CRC and the search for therapeutic options. • Multi-modality treatment including surgical metastatic resection, postoperative SRS with/without WBRT, and chemotherapy is the best current treatment option. • Recent mid-sized clinical trials, case reports, and preclinical models show the potential of unconventional therapeutic approaches as monoclonal antibodies, targeted therapies, and immunotherapy. Graphical abstract

La biopsie liquide, une nouvelle opportunité pour l’oncologie personnalisée [Liquid biopsy, a new opportunity for personalized oncology]

Knowledge about cancer biology is extending and has meaningful repercussions on patients' care. Therefore, there is a growing need to assess tumor biology not only at diagnosis, but also throughout the course of management. Tumor tissue biopsies are particularly useful, but are not convenient for repetitive analyses because of the need for invasive procedures. Advances in biotechnology allow currently getting more and more information from liquid biopsies, based on small amounts of tumor material released for instance into the peripheral blood. Already used in the treatment of non-small cell lung cancers, these new techniques represent more generally an important step forward for personalized oncology

Passive acoustic monitoring as a law enforcement tool for Afrotropical rainforests

Hunting for wild meat is pervasive in Afrotropical forests and often the primary threat to large-bodied mammals even within protected areas, the effectiveness of which (at reducing hunting) is correlated with law enforcement efforts, especially anti-poaching patrols. However, although tropical protected areas are critically underfunded and law enforcement accounts for a substantial proportion of their budgets, few have mechanisms in place to evaluate and adaptively adjust anti-poaching strategies based on robust field evidence

Passive acoustic monitoring as a law enforcement tool for Afrotropical rainforests

Hunting for wild meat is pervasive in Afrotropical forests and often the primary threat to large-bodied mammals even within protected areas, the effectiveness of which (at reducing hunting) is correlated with law enforcement efforts, especially anti-poaching patrols. However, although tropical protected areas are critically underfunded and law enforcement accounts for a substantial proportion of their budgets, few have mechanisms in place to evaluate and adaptively adjust anti-poaching strategies based on robust field evidence

Neurological Adverse Events Associated with Immune Checkpoint Inhibitors: Diagnosis and Management.

Immune checkpoint inhibitors represent a major step forward in the field of oncologic immunotherapy these last years and have significantly increased survival of cancer patients in an ever-growing number of indications. These agents block specific immune checkpoint molecules (programmed cell death protein 1 and its ligand as well as cytotoxic T-lymphocyte-associated antigen 4) that normally downregulate the immune response. These new agents show a specific range of adverse effects induced by abnormal immunologic activation. Many different neurologic adverse events have been described, including encephalitis, myelopathy, aseptic meningitis, meningoradiculitis, Guillain-Barré-like syndrome, peripheral neuropathy (including mononeuropathy, mononeuritis multiplex, and polyneuropathy) as well as myasthenic syndrome. Immune checkpoint inhibitors have shown promising results in cancer but can possibly induce autoimmune disorders. Although rare, neurological adverse events require prompt recognition and treatment to avoid substantial morbidity

Contrasting effects of human settlement on the interaction among sympatric apex carnivores

In the face of a growing human footprint, understanding interactions among threatened large carnivores is fundamental to effectively mitigating anthropogenic threats and managing species. Using data from a large-scale camera trap survey, we investigated the effects of environmental and anthropogenic variables on the interspecific interaction of a carnivore guild comprising of tiger, leopard, and dhole in Bhutan. We demonstrate the complex effects of human settlement density on large carnivore interactions. Specifically, we demonstrate that leopard-dhole co-occupancy probability was higher in areas with higher human settlement density. The opposite was true for tiger-leopard co-occupancy probability, but it was positively affected by large prey (gaur) abundance. These findings suggest that multi carnivore communities across land-use gradients are spatially structured and mediated also by human presence and/or the availability of natural prey. Our findings show that space-use patterns are driven by a combination of the behavioural mechanism of each species and its interactions with competing species. The duality of the effect of settlement density on species interactions suggests that the benefits of exploiting anthropogenic environments are a trade42 off between ecological opportunity (food subsidies or easy prey) and the risk of escalating conflict with humans