The family Mustelidae is the largest among the order Carnivora. While we know a great deal about certain species, there is still a lack of information about many mustelids.
We first investigated the ...International Union for Conservation of Nature (IUCN) Red List species‐level assessments for each mustelid species. Then, we undertook a systematic review of the scientific literature with the aim of identifying the primary threats and subthreats reported, and which species are most studied. Threats are defined by the IUCN as “the proximate human activities or processes that have impacted, are impacting, or may impact the status of the taxon”.
We analysed 1003 published articles. For each article, we collected year of publication, geographical zone of each study, species studied, and the threats and subthreats identified.
The majority of species (62%) were classified as Least Concern on the IUCN Red List, but 31 out of 63 species were found to be declining globally and only two species were increasing. The species studied and location of studies were biased, with 72% of studies undertaken in North America or Europe and focussing on very few species. A high proportion of species distributed predominantly in the tropics were categorised as declining, and threats linked with hunting, fishing, and logging were identified as the most common for mustelids by the IUCN Red List and in the scientific literature. Differences in the proportion of threats affecting each subfamily were also reported.
The nature of threats varies in different parts of the world and between species. It is essential to undertake more research with a strong focus towards species in highly biodiverse regions. A greater understanding of threats such as wildlife pet trade, emerging diseases, and climate change must also be central to prevent declines.
The family Mustelidae is the largest among the order Carnivora. While we know a great deal about certain species, there is still a lack of information about many mustelids. Here, we investigated the International Union for Conservation of Nature (IUCN) Red List species‐level assessments for each mustelid species. Then, we undertook a systematic review of the scientific literature with the aim of identifying the primary threats and subthreats reported, and which species are most studied. We found that 31 out of 63 species were found to be declining globally and only two species were increasing. A high proportion of species distributed predominantly in the tropics were categorised as declining, and threats linked with hunting, fishing, and logging were identified as the most common for mustelids by the IUCN Red List and in the scientific literature. Most studies (72%) took place in North America or Europe and focused on very few species. It is therefore essential to undertake more research with a strong focus towards species in highly biodiverse regions. A greater understanding of threats such as wildlife pet trade, emerging diseases, and climate change must also be central to prevent declines.
To evaluate the impact of the QuinteT Recruitment Intervention (QRI) on recruitment in challenging randomized controlled trials (RCTs) that have applied the intervention. The QRI aims to understand ...recruitment difficulties and then implements “QRI actions” to address these as recruitment proceeds.
A mixed-methods study, comprising (1) before-and-after comparisons of recruitment rates and the numbers of patients approached and (2) qualitative case studies, including documentary analysis and interviews with RCT investigators.
Five UK-based publicly funded RCTs were included in the evaluation. All recruited to target. Randomized controlled trial 2 and RCT 5 both received up-front prerecruitment training before the intervention was applied. Randomized controlled trial 2 did not encounter recruitment issues and recruited above target from its outset. Recruitment difficulties, particularly communication issues, were identified and addressed through QRI actions in RCTs 1, 3, 4, and 5. Randomization rates significantly improved after QRI action in RCTs 1, 3, and 4. Quintet Recruitment Intervention actions addressed issues with approaching eligible patients in RCTs 3 and 5, which both saw significant increases in the number of patients approached. Trial investigators reported that the QRI had unearthed issues they had been unaware of and reportedly changed their practices after QRI action.
There is promising evidence to suggest that the QRI can support recruitment to difficult RCTs. This needs to be substantiated with future controlled evaluations.
Effective conservation management for species that function as metapopulations requires an understanding of population dynamics at the landscape scale. The water vole,
Arvicola amphibius
, is one ...such species. Water voles have recently undergone a significant decline in the UK, as a result of habitat loss and predation from the introduced American mink,
Neovison vison
. Large reed bed and grazing marsh sites can provide refuge habitats for water voles from mink predation, in which case populations within these sites could sustain metapopulations in the surrounding landscape where conditions are less favourable. We carried out a study using a stochastic patch occupancy model to determine the long term viability of water vole metapopulations in the wider landscape around a series of extensive reed bed and grazing marsh sites designated as National Key Sites for water voles. The results of our model simulations show that a large protected core site, or mainland, is essential in maintaining the long term viability of these systems. Our results also show how these metapopulations could be enhanced by increasing patch numbers through habitat creation and/or restoration and suggest what the minimum effective size of created or restored patches should be. The study shows how population modelling can provide insight into some effective practical ways of enhancing the viability of water vole metapopulations at the landscape scale. Furthermore it demonstrates that extensive wetlands are an appropriate focus for water vole conservation measures.
To explore how the concept of randomization is described by clinicians and understood by patients in randomized controlled trials (RCTs) and how it contributes to patient understanding and ...recruitment.
Qualitative analysis of 73 audio recordings of recruitment consultations from five, multicenter, UK-based RCTs with identified or anticipated recruitment difficulties.
One in 10 appointments did not include any mention of randomization. Most included a description of the method or process of allocation. Descriptions often made reference to gambling-related metaphors or similes, or referred to allocation by a computer. Where reference was made to a computer, some patients assumed that they would receive the treatment that was “best for them”. Descriptions of the rationale for randomization were rarely present and often only came about as a consequence of patients questioning the reason for a random allocation.
The methods and processes of randomization were usually described by recruiters, but often without clarity, which could lead to patient misunderstanding. The rationale for randomization was rarely mentioned. Recruiters should avoid problematic gambling metaphors and illusions of agency in their explanations and instead focus on clearer descriptions of the rationale and method of randomization to ensure patients are better informed about randomization and RCT participation.
•Practices commonly used to describe randomisation in RCT recruitment could confuse patients.•Patients found it difficult to comprehend gambling-related metaphors of randomisation.•Computer-agency descriptions led to patients believing they would receive the best treatment.
It is estimated that one million wild animals are killed on UK roads each year and these casualties are potentially a valuable source of data relating to the size and distribution of populations. ...Road kill surveys have the potential to form the basis of a nationwide mammal monitoring scheme with multi-species coverage and excellent area sampling. However it has been argued that road casualty counts cannot be used to monitor population change because variation in the number of road deaths is related more to variation in traffic flow than to population density. We used rabbit and hedgehog as study species to examine if there was a relationship between traffic flow and road kill counts. We found no correlation between changes in traffic flow and road counts of hedgehog or rabbit. We conclude that a decrease in road kill counts of these species is highly likely to represent a decrease in absolute abundance and would therefore be a good index with which to monitor population decline.
In a number of countries around the world, introduced American mink are acknowledged to have had a negative effect on a number of native species, many of which are of particular conservation concern. ...In the UK, there has been an observed correlation between the spread of mink and the decline of the, once common and widespread, water vole. Large wetlands, such as extensive reed bed, appear to mitigate the impact of mink predation on water voles and some bird species. The present study was carried out to test the hypothesis that the observed refuge effect of reed beds arises from the way mink forage in this type of wetland. The results suggest that the interior of reed bed offers a spatial refuge for water voles, and other species, from predation by mink, because more than 60% of mink foraging activity occurred within 10 m of a main (>10 m wide) channel. Where mink ventured within the reed bed itself, they associated closely with scrub. The implication is that easily navigable channels and areas of scrub probably compromise the refuge effect of reed beds. This can be used to inform management recommendations at these sites.
Abstract
Background: Multi-parameter tumour gene expression assays (MPAs) are widely used to estimate individual patient risk and to guide chemotherapy use in hormone-sensitive, HER2-negative early ...breast cancer. The TAILORx trial supports MPA use in a node-negative population. Evidence in node-positive breast cancer is limited. OPTIMA (Optimal Personalised Treatment of early breast cancer usIng Multi-parameter Analysis) (ISRCTN42400492) is a prospective international randomised controlled trial (RCT) designed to validate MPA’s as predictors of chemotherapy sensitivity in a largely node-positive breast cancer population.
Methods: OPTIMA is a partially blinded study with an adaptive two-stage design. The main eligibility criteria are women and men age 40 or older with resected ER-positive, HER2-negative invasive breast cancer and up to 9 involved axillary lymph nodes. Randomisation is to standard management (chemotherapy and endocrine therapy) or to MPA-directed treatment using the Prosigna (PAM50) test. Those with a Prosigna tumour Score (ROR_PT) >60 receive standard management whilst those with a low score (≤60) are treated with endocrine therapy alone. Endocrine therapy for pre-menopausal women includes ovarian suppression. Prosigna tests are currently performed only for participants randomised to MPA-directed treatment. More than 1 tumour may be tested if participants have multi-focal tumours with discordant features and/or are considered clinically significant. The co-primary outcomes are: (1) Invasive Disease Free Survival (IDFS) and (2) cost-effectiveness. Secondary outcomes include IDFS in patients with low-score tumours and quality of life. Recruitment of 4500 patients over 5 years will permit demonstration of 3% non-inferiority of test-directed treatment, assuming 5-year IDFS of 85% with standard management. An integrated qualitative recruitment study addresses challenges to consent and recruitment, building on experience from the feasibility study which found that a multidisciplinary approach is important for recruitment success.
Results: The OPTIMA main trial opened in January 2017. Overall recruitment as of 1 July 2019 was 1123 (1100 from UK, 13 from Norway); 91% had axillary node macro-metastases. Median time from consent to treatment allocation was 12 days (interquartile range 10-14 days). The withdrawal rate from trial treatment is 3%; 50% of these continue with follow up. Prosigna tests have been performed on 608 tumours for 549 participants; 59% were luminal A, 38% were luminal B and 3% non-luminal (6 patients with non-luminal tumours 1% overall were ineligible on receptor retesting). Of the 53 (10%) participants with >1 tumour tested, 3 (6%) had discordant scores only, 7 (13%) had discordant subtypes only and 8 (15%) had both discordant scores and subtypes. Two thirds of the MPA-directed arm participants have been allocated to endocrine therapy only. The test failure rate is <1%.
Conclusion: OPTIMA is one of two large scale prospective trials validating the use of test-guided chemotherapy decisions in node-positive early breast cancer. It is expected to have a global impact on breast cancer treatment.
Funding: OPTIMA is funded by the UK NIHR HTA Programme (10/34/501). Views expressed are those of the authors and not those of the HTA Programme, NIHR, NHS or the Department of Health.
Trial Inquiries: OPTIMA@warwick.ac.uk
Citation Format: Robert C Stein, Andrea Marshall, Andreas Makris, Luke Hughes-Davies, Iain R MacPherson, Carmel Conefrey, Leila Rooshenas, Sarah E Pinder, Abeer M Shaaban, Bjørn Naume, David A Cameron, Daniel W Rea, Helena M Earl, Christopher J Poole, Peter S Hall, Georgina Dotchin, Stuart A McIntosh, Victoria Harmer, Adrienne Morgan, Bethany Shinkins, Nigel Stallard, Christopher McCabe, Jenny L Donovan, John MS Bartlett, Janet A Dunn. OPTIMA: A prospective randomized trial to validate the clinical utility and cost-effectiveness of gene expression test-directed chemotherapy decisions in mostly node-positive early breast cancer abstract. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr OT3-17-01.
Conservation translocations are complex and challenging, but are frequently employed to tackle biodiversity decline. Large predator translocations can be particularly emotive and contentious, in part ...because they present actual or perceived risks to the safety and livelihoods of people. Understanding the social feasibility of conservation translocations is imperative, and provides opportunities to identify and address these risks.
In Britain, the Eurasian lynx Lynx lynx is the most frequently raised prospect for large carnivore reintroduction. We used Q‐Methodology to explore stakeholder perspectives on the prospect of lynx reintroduction to Scotland.
We identified five perspectives: Lynx for Change was supportive of lynx reintroduction, feeling that lynx could facilitate ecosystem restoration. Lynx for Economy was also supportive, anticipating economic benefits to local communities. No to Lynx was strongly opposed, perceiving that humans were fulfilling the roles of absent large carnivores. Scotland is not Ready supported the conversation but perceived prohibitive socio‐ecological barriers. We are not Convinced was not satisfied that an adequate case for biodiversity gain had been made, but was open to further exploration of the potential.
There were important areas of divergence among the perspectives over the potential impacts on sheep farming and the degree to which environments should be managed by people or encouraged to self‐regulate. There was a consensus on a lack of trust between stakeholder groups, which was primarily rooted in participants' experiences of previous wildlife reintroductions and the contemporary management of recovering predators. However, there was also consensus that, should lynx reintroduction continue to be explored, a participatory, cross‐sectoral approach could address these trust issues, help manage existing and emergent conflicts, and build knowledge collaboratively.
We provide a foundation for future dialogue between stakeholders over the prospective reintroduction of the lynx to Scotland and recommend a stakeholder‐focused participatory process as the next step. Our findings have wider relevance for wildlife reintroductions, species recovery and conservation conflicts elsewhere.
Read the free Plain Language Summary for this article on the Journal blog.
Read the free Plain Language Summary for this article on the Journal blog.
Introduction
Bamlanivimab and etesevimab (BAM + ETE) are monoclonal antibodies (mAbs) effective in reducing COVID-19-related hospitalizations and all-cause mortality in adult participants at ...increased risk for severe disease. We present pharmacokinetic (PK), efficacy, and safety results from pediatric participants (< 18 years of age) with COVID-19 who were treated with BAM + ETE.
Methods
In an addendum to the phase 2/3 BLAZE-1 clinical trial (NCT04427501), pediatric participants received open-label weight-based dosing (WBD,
n
= 94) based on exposure-matching to the authorized dose of BAM + ETE in adult participants. For efficacy and safety assessments, placebo (
n
= 14) and BAM + ETE (
n
= 20)-treated adolescent participants (> 12 to < 18 years of age) from the BLAZE-1 trial were included in the overall pediatric population (
N
= 128). All participants had mild to moderate COVID-19 upon enrollment and ≥ 1 risk factor for severe COVID-19. The primary objective was to characterize the PK of BAM and ETE in the WBD population.
Results
The median age of the participants was 11.2 years, 46.1% were female, 57.9% were Black/African American, and 19.7% were Hispanic/Latino. The area under the curve for BAM and ETE in the WBD population was similar to that previously observed in adults. There were no COVID-19-related hospitalizations or deaths. All adverse events (AE) except one were mild or moderate, with one participant reporting a serious AE.
Conclusion
WBD in pediatric participants achieved similar drug exposures compared to adult participants that received the authorized BAM + ETE dose. The pediatric efficacy and safety data were consistent with adults receiving mAbs for COVID-19.
Trial Registration Number
NCT04427501.
Reversing global declines in predator populations is a major conservation objective, though people frequently come into conflict over carnivore conservation. As part of a national recovery programme ...for the pine marten Martes martes, a protected mesocarnivore in the UK, we used Q‐methodology to understand the perspectives of residents living in an area in which a pine marten translocation project was planned.
In contrast to binary ‘for or against’ characterizations of debates surrounding such projects, we identified four perspectives with distinct priorities and concerns. A single perspective, ‘Concerned Manager’, opposed the translocation and marten recovery more generally, was apprehensive about impacts and favoured traditional predator management practices. Support was characterized by three perspectives: ‘Environmental Protectionist’, ‘Natural Resource Steward’ and ‘Cautious Pragmatist’. Two explicitly supported the translocation but differed in their priorities: Environmental Protectionist framed marten restoration as an ethical imperative, whereas Natural Resource Steward emphasized ecological and economic benefits. Cautious Pragmatist supported marten recovery, but expressed ambivalence about the translocation.
We identified areas of divergence between the four perspectives, particularly surrounding risks posed by martens and need for predator control. We identified two areas of consensus among the four perspectives: support for a biodiverse environment and translocations as a means of achieving this (though this was contingent on the species), and agreement there would be economic and ecological benefits if martens controlled non‐native grey squirrels Sciurus carolinensis.
We highlight that perspectives on this project were influenced by wider issues of wildlife management and conservation, particularly the impact and management of increasing populations of another mesocarnivore, the badger Meles meles. Negative experiences and perceptions of badgers were germane to the Concerned Manager perspective, and their fear that protected status would preclude marten population control. ‘Rewilding’ emerged as a divisive background issue, against which some participants evaluated the translocation.
In facilitating understanding of perspectives and establishing the contexts through which they were formed, we found that Q‐methodology enabled us, as a team comprising conservation practitioners and researchers, to engage meaningfully with affected residents. We recommend the tool as a useful step in assessing social feasibility of conservation translocations.
A free Plain Language Summary can be found within the Supporting Information of this article.
Crynodeb
Mae gwrthdroi dirywiad byd‐eang ym mhoblogaethau anifeiliaid ysglyfaethus yn un o nodau cadwraeth pennaf, er bod pobl yn aml yn dod i wrthdrawiad ynglŷn â gwarchodaeth anifeiliaid cigysol. Defnyddion ni Dull‐Q fel rhan o raglen genedlaethol ar gyfer adfer poblogaethau y bele'r coed Martes martes, anifail cigysol gwarchodedig ym Mhrydain, i ddeall safbwyntiau preswylwyr lleol mewn ardal lle cynlluniwyd prosiect trawsleoli belaod coed.
Mewn cyferbyniad â disgrifiadau deuaidd o ddadleuon ynghylch a phrosiectau o'r fath fel ‘o blaid neu yn erbyn’, darganfyddom pedwar safbwynt gwahanol gyda blaenoriaethau a phryderon gwahanol. Roedd un safbwynt (‘Rheolwr Pryderus’) yn gwrthwynebu trawsleoli ac yn gwrthwynebu adfer y bele'r coed yn gyffredinol, ac yn bryderus ynghylch ag effeithiau'r trawsleoliad, ac yn ffafrio arferion traddodiadol o reoli ysglyfaethwyr. Nodweddwyd cefnogaeth gan dri safbwynt: ‘Amddiffynnydd yr Amgylchedd’, ‘Stiward Adnoddau Naturiol’ a ‘Pragmatydd Pwyllog’. Fe wnaeth dau yn benodol cefnogi'r trawsleoliad ond roeddynt yn wahanol yn eu blaenoriaethau: Fe fframiodd Amddiffynnydd yr Amgylchedd adfer y bele'r coed fel rheidrwydd moesegol, tra pwysleisiodd Stiward Adnoddau Naturiol buddion ecolegol ac economaidd. Cefnogodd Pragmatydd Pwyllog adfer y bele, ond mynegodd ansicrwydd ynglŷn â'r trawsleoliad.
Darganfyddom gwahaniaethau rhwng y pedwar safbwynt, yn enwedig ynghylch â'r peryglon cysylltiedig â'r belaod a'r angen am reoli ysglyfaethwyr. Roedd dau faes o gonsensws ymhlith y pedwar safbwynt: cefnogaeth am amgylchedd bioamrywiol ac am drawsleoli fel ffordd i gyflawni hyn (ond roedd hyn yn dibynnu ar y rhywogaeth), a chytundeb y byddai manteision buddiol economaidd ac ecolegol pe bai belaod yn rheoli gwiwerod llwyd Sciurus carolinensis anfrodorol.
Rydym yn goleubwyntio bod materion ehangach cadwraeth a rheolaeth bywyd gwyllt wedi dylanwadu ar y safbwyntiau hyn, yn enwedig effaith a rheolaeth o boblogaethau cynyddol o anifail cigysol canolig arall, sef y mochyn daear Meles meles. O safbwynt y Rheolwr Pryderus, roedd profiadau a chanfyddiadau negyddol o foch daear yn dylanwadu ei safbwynt ar y belaod, a hefyd ar eu hofn y byddai statws gwarchodedig y bele yn atal rheoli'r boblogaeth. Mae'n amlwg bod ‘ail‐wylltio’ yn mater rhwygol yn y cefndir a roedd rhai cyfranogion yn mesur gwerth trawsleoliad yn ei erbyn.
Wrth hybu dealltwriaeth o'r safbwyntiau a sefydlu'r cysylltau lle cawsant eu ffurfio, fe welsom fod Dull‐Q yn ein galluogi ni, fel tîm sy'n cynnwys ymarferwyr cadwraeth ac ymchwilwyr, i ymgysylltu mewn ffordd ystyrlon gyda thrigolion a fyddai'n cael eu heffeithio. Rydym yn argymell y dull fel cam defnyddiol wrth asesu'r dichonoldeb cymdeithasol o brosiectau trawsleoli cadwraethol.
A free Plain Language Summary can be found within the Supporting Information of this article.
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