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Species sensitivity to forest fragmentation varies latitudinally, peaking in the tropics. A prominent explanation for this pattern is that historical landscape disturbance at higher latitudes has removed fragmentation-sensitive species or promoted the evolution of more resilient survivors. However, it is unclear whether this so-called extinction filter is the dominant driver of geographic variation in fragmentation sensitivity, particularly because climatic factors may also cause latitudinal gradients in dispersal ability, a key trait mediating sensitivity to habitat fragmentation. Here we combine field survey data with a morphological proxy for avian dispersal ability (hand-wing index) to assess responses to forest fragmentation in 1,034 bird species worldwide. We find that fragmentation sensitivity is strongly predicted by dispersal limitation and that other factors—latitude, body mass and historical disturbance events—have relatively limited explanatory power after accounting for species differences in dispersal. We also show that variation in dispersal ability is only weakly predicted by historical disturbance and more strongly associated with intra-annual temperature fluctuations (seasonality). Our results suggest that climatic factors play a dominant role in driving global variation in the impacts of forest fragmentation, emphasizing the need for more nuanced environmental policies that take into account local context and associated species traits.

Climate change impacts are accelerating and there is an urgent need to address this global issue. Tackling climate change in an effective and socially just manner needs to involve mitigation strategies that address the underlying causes of climate change, but also adaptation strategies that help us prepare for current and future impacts. Historically, mitigation and adaptation strategies have been treated separately, but there is now growing awareness of important synergies between them. We highlight these synergies across six key areas where humans need to make transformative changes in order to reduce the impacts of climate change, including energy, pollutants, nature, food, population and the economy. In doing so, we show the enormous potential for civil society, government, world leaders and the private sector to take advantage of the fact that mitigation strategies can also provide adaptation opportunities to lessen humanity’s suffering as we navigate the uncertainties of the climate crisis.

The ecological co-dependency between plants and hummingbirds is a classic example of a mutualistic interaction: hummingbirds rely on floral nectar to fuel their rapid metabolisms, and more than 7000 plant species rely on hummingbirds for pollination. However, threats to hummingbirds are mounting, with 10% of 366 species considered globally threatened and 60% in decline. Despite the important ecological implications of these population declines, no recent review has examined plant–hummingbird interactions in the wider context of their evolution, ecology, and conservation. To provide this overview, we (i) assess the extent to which plants and hummingbirds have coevolved over millions of years, (ii) examine the mechanisms underlying plant–hummingbird interaction frequencies and hummingbird specialization, (iii) explore the factors driving the decline of hummingbird populations, and (iv) map out directions for future research and conservation. We find that, despite close associations between plants and hummingbirds, acquiring evidence for coevolution (versus one-sided adaptation) is difficult because data on fitness outcomes for both partners are required. Thus, linking plant–hummingbird interactions to plant reproduction is not only a major avenue for future coevolutionary work, but also for studies of interaction networks, which rarely incorporate pollinator effectiveness. Nevertheless, over the past decade, a growing body of literature on plant–hummingbird networks suggests that hummingbirds form relationships with plants primarily based on overlapping phenologies and trait-matching between bill length and flower length. On the other hand, species-level specialization appears to depend primarily on local community context, such as hummingbird abundance and nectar availability. Finally, although hummingbirds are commonly viewed as resilient opportunists that thrive in brushy habitats, we find that range size and forest dependency are key predictors of hummingbird extinction risk. A critical direction for future research is to examine how potential stressors – such as habitat loss and fragmentation, climate change, and introduction of non-native plants – may interact to affect hummingbirds and the plants they pollinate.

Purpose: While lesbian, gay, bisexual, transgender, and queer or questioning (LGBTQ) elders face a multitude of barriers to healthy aging, little is known about needs and concerns specific to transgender elders, except that they face many self-perceived challenges to healthy aging, which exist at the individual, community, and institutional levels. To further understand these needs, we explored the perspectives of transgender individuals aged 65 and older on health care, expectations of aging, concerns for the future, and advice for young transgender people. Methods: We performed 19 semistructured interviews with individuals who identify as transgender elders, 10 transgender women and 9 transgender men. Interviews were transcribed and coded by three investigators to generate salient themes via thematic analysis. Results: We identified 7 major themes that exemplify the concerns and experiences of this sample of the aging transgender community: fear of mistreatment in elder care, isolation and loneliness exacerbated by transgender identity, increased vulnerability to financial stressors, perceived lack of agency, health care system and provider inclusivity, giving back to one's community, and embracing self-truth as a path to fulfillment. Conclusion: While some of these concerns, such as fear of mistreatment, are common among elders, the concerns of transgender elders are heightened due to stigma compounded by being both transgender and elderly. Health care providers, nursing home staff, and social workers must be sensitized to these needs and fears to provide appropriate, affirming, and respectful care and support to transgender elders.

The loss of forest is a leading cause of species extinction, and reforestation is 1 of 2 established interventions for reversing this loss. However, the role of reforestation for biodiversity conservation remains debated, and lacking is an assessment of the potential contribution that reforestation could make to biodiversity conservation globally. We conducted a spatial analysis of overlap between 1,550 forest-obligate threatened species' ranges and land that could be reforested after accounting for socioeconomic and ecological constraints. Reforestation on at least 43% (∼369 million ha) of reforestable area was predicted to potentially benefit threatened vertebrates. This is approximately 15% of the total area where threatened vertebrates occur. The greatest opportunities for conserving threatened vertebrate species are in the tropics, particularly Brazil and Indonesia. Although reforestation is not a substitute for forest conservation, and most of the area containing threatened vertebrates remains forested, our results highlight the need for global conservation strategies to recognize the potentially significant contribution that reforestation could make to biodiversity conservation. If implemented, reforestation of ∼369 million ha would also contribute substantially to climate-change mitigation, offering a way to achieve multiple sustainability commitments at once. Countries must now work to overcome key barriers (e.g., unclear revenue streams, high transaction costs) to investment in reforestation.Reforestación Mundial y Conservación de la Biodiversidad Resumen La pérdida de los bosques es una de las causas principales de la extinción de especies y la reforestación es una de las dos intervenciones establecidas para revertir esta pérdida. Sin embargo, el papel de la reforestación en la conservación de la biodiversidad todavía se debate, además de que hay una falta de evaluación de la contribución potencial que podría dar la reforestación a la conservación mundial de la biodiversidad. Realizamos un análisis espacial del traslape de la distribución de 1,550 especies obligadas de bosque que se encuentran amenazadas y el suelo que podría utilizarse para reforestar después de considerar las restricciones socioeconómicas y ecológicas. El análisis predijo que la reforestación en al menos el 43% (∼ 369 millones de ha) del área que se puede reforestar beneficiará potencialmente a los vertebrados amenazados. Esto es aproximadamente el 15% del área total en donde están presentes los vertebrados amenazados. Las oportunidades más grandes para conservar a las especies amenazadas de vertebrados se encuentran en los trópicos, particularmente en Brasil y en Indonesia. Aunque la reforestación no es un sustituto para la conservación de los bosques, y aunque la mayoría del área que contiene vertebrados amenazados todavía tiene flora original, nuestros resultados resaltan la necesidad de tener estrategias mundiales de conservación para reconocer la contribución potencialmente significativa que podría dar la reforestación a la conservación de la biodiversidad. Si se implementa, la reforestación de ∼369 millones de ha también contribuiría significativamente a la mitigación del cambio climático, ofreciendo así una manera de cumplir varios compromisos de sustentabilidad a la vez. Los países ahora deben trabajar para sobreponerse a las barreras importantes (p. ej.: flujos inciertos de ingresos, costos elevados de las transacciones) que enfrentan las inversiones para la reforestación.森林丧失是物种灭绝的主要原因, 而造林则是已确立的扭转森林丧失的两种干预措施之一。然而, 造林对生物多样性保护的作用仍存在争议, 目前尚缺乏造林对全球生物多样性保护潜在贡献的评估。我们考虑了社会经济和生态制约因素, 对 1550 个森林特有濒危物种的分布范围内可以造林的土地进行了空间重叠分析。据预测, 在至少 43% (约 3.69 亿公顷) 的可造林土地上实施造林, 将有助于受威胁脊椎动物的保护, 大约占受威胁脊椎动物分布总面积的15%。保护濒危脊椎动物的最大机会在热带地区, 特别是巴西和印度尼西亚。虽然再造林不能代替森林保护, 而且受威胁脊椎动物大部分栖息地仍是森林, 但我们的结果强调了认识到造林对生物多样性保护潜在重要贡献的全球保护战略的必要性。如果实施造林计划, 约 3.69 亿公顷的再造林还将大大有助于缓解气候变化, 为同时实现多项可持续承诺提供了途径。各国现在应努力克服投资造林的主要障碍 (如不明确的收入来源、高昂的交易成本) 。【翻译: 胡怡思; 审校: 聂永刚】.

Mutations in the Von Hippel–Lindau (VHL) gene are the driving force in many forms of clear cell renal cell carcinoma (ccRCC) and promote hypoxia-inducible factor (HIF)-dependent tumor proliferation, metastasis and angiogenesis. Despite the progress that has already been made, ccRCC generally remain resistant to conventional therapies and ccRCC patients suffer from metastasis and acquired resistance, highlighting the need for novel therapeutic options. Cysteinyl leukotriene receptor 1 (CysLTR1) antagonists, like zafirlukast, are administered in bronchial asthma to control eicosanoid signaling. Intriguingly, long-term use of zafirlukast decreases cancer risk and leukotriene receptor antagonists inhibit tumor growth, but the mechanisms still remain unexplored. Therefore, we aim to understand the mechanisms of zafirlukast-mediated cell death in ccRCC cells. We show that zafirlukast induces VHL-dependent and TNFα-independent non-apoptotic and non-necroptotic cell death in ccRCC cells. Cell death triggered by zafirlukast could be rescued with antioxidants and the PARP-1 inhibitor Olaparib, and additionally relies on HIF-2α. Finally, MG-132-mediated proteasome inhibition sensitized VHL wild-type cells to zafirlukast-induced cell death and inhibition of HIF-2α rescued zafirlukast- and MG-132-triggered cell death. Together, these results highlight the importance of VHL, HIF and proteasomal degradation in zafirlukast-induced oxidative cell death with potentially novel therapeutic implications for ccRCC.

BackgroundTransgender people face numerous barriers to accessing care, particularly in rural settings. Transportation, travel time, a lack of providers offering transgender care, and discrimination all contribute to these barriers. The Gender Wellness Center was established to fill a gap in rural transgender care, and was subsequently awarded a Robert Wood Johnson Foundation grant to establish a Center of Excellence. This study examines the implementation of the Center of Excellence, a complex intervention, over the course of 18 months.MethodsThe Consolidated Framework for Implementation Research was used to develop baseline and follow-up surveys. These were distributed to members of the core implementation team at the Gender Wellness Center at the midpoint and conclusion of the Robert Wood Johnson Foundation grant. Responses were largely open-ended and analyzed qualitatively.ResultsResults are presented in terms of Consolidated Framework domains and constructs, as well as the relative outlook (positive or negative) of implementation. Overall, there were improvements over time, with more encouraging feedback and examples of success at follow-up. Though true, organizational culture and individual beliefs about the provision of transgender care challenged implementation of the Center of Excellence throughout the project.ConclusionsThis study highlights the importance of organizational culture on implementation efforts, as well as the need for complex, multi-faceted interventions to overcome such challenges in order to improve care for marginalized populations.Trial registrationNot applicable

Background: Transgender people face numerous barriers to accessing care, particularly in rural settings. Transportation, travel time, a lack of providers offering transgender care, and discrimination all contribute to these barriers. The Gender Wellness Center was established to fill a gap in rural transgender care, and was subsequently awarded a Robert Wood Johnson Foundation grant to establish a Center of Excellence. This study examines the implementation of the Center of Excellence, a complex intervention, over the course of 18 months. Methods: The Consolidated Framework for Implementation Research was used to develop baseline and follow-up surveys. These were distributed to members of the core implementation team at the Gender Wellness Center at the midpoint and conclusion of the Robert Wood Johnson Foundation grant. Responses were largely open-ended and analyzed qualitatively. Results: Results are presented in terms of Consolidated Framework domains and constructs, as well as the relative outlook (positive or negative) of implementation. Overall, there were improvements over time, with more encouraging feedback and examples of success at follow-up. Though true, organizational culture and individual beliefs about the provision of transgender care challenged implementation of the Center of Excellence throughout the project. Conclusions: This study highlights the importance of organizational culture on implementation efforts, as well as the need for complex, multi-faceted interventions to overcome such challenges in order to improve care for marginalized populations. Trial registration: Not applicable

Despite the growth of the research on lean and green manufacturing systems, consideration of how circular economy principles complement lean has been virtually absent from the literature due to a mismatch between research on lean green, which has focused on the internal manufacturing operations (product and process levels), and research on the circular economy, which takes a broader, more holistic view of environmental impact (the system level). Only a few researchers have considered the lean and the circular together. We argue that there is a need to understand the complementarities and conflicts between “lean” and “circularity”. By combining the system level with process and product levels, this paper highlights which potentials in a lean manufacturing context are identified from a circular perspective and how to realize them. In this paper, we present a critical case study conducted at a Swedish manufacturing firm/original equipment manufacturer within the heavy-duty and off-road (HDOR) industry. Our results show that the company is locked into a lean and linear production, where material waste is not seen as a resource. We present how the three levels interplay and argue that they be combined when trying to integrate circular measures into this context.

A long-standing debate concerns how functional responses are best described. Theory suggests that ratio dependence is consistent with many food web patterns left unexplained by the simplest prey-dependent models. However, for logistical reasons, ratio dependence and predator dependence more generally have seen infrequent empirical evaluation and then only so in specialist predators, which are rare in nature. Here we develop an approach to simultaneously estimate the prey-specific attack rates and predator-specific interference (facilitation) rates of predators interacting with arbitrary numbers of prey and predator species in the field. We apply the approach to surveys and experiments involving two intertidal whelks and their full suite of potential prey. Our study provides strong evidence for predator dependence that is poorly described by the ratio dependent model over manipulated and natural ranges of species abundances. It also indicates how, for generalist predators, even the qualitative nature of predator dependence can be prey-specific.

Pelvic organ prolapse (POP) can cause incomplete bladder emptying or hydronephrosis and renal failure. These are serious conditions, especially in elderly women, requiring resolution of POP. Pessary use is an alternative, but there are specific problems or patients may not want it. We therefore conducted a retrospective study on surgical treatment of elderly women with respect to the type of surgery and intra- and postoperative complications.From two urogynecologic centers, we reviewed treatment data between 2003 and 2013, including patients ≥80 years of age. From the hospital records, intra- and postoperative data were extracted.91 cases met the inclusion criteria. Mean age was 84.38 years (±3.05, max 92 years). Two patients (2.2%) were diagnosed with hydronephrosis and two with urosepsis/renal failure. The mean length of surgery was 81 min (±45 min, range 10-270), 94.5% of patients were under general anesthesia. Two bowel lesions occurred. The mean length of hospital stay was 8 days (range 1-22, n = 90). There were no perioperative mortalities. Six patients (6.6%) were admitted to intensive care unit.In the future, we will be facing a growing number of elderly women seeking care for POP. In our retrospective analysis, we were able to show that POP surgery could be performed safely. We therefore consider surgical treatment as a valuable alternative if pessary use is not an option.

Many terrestrial endotherm food webs constitute three trophic level cascades. Others have two trophic level dynamics (food limited herbivores; plants adapted to tackle intense herbivory) or one trophic level dynamic (herbivorous endotherms absent, thus plants compete for the few places where they can survive and grow). According to the Exploitation Ecosystems Hypothesis (EEH), these contrasting dynamics are consequences of differences in primary productivity. The productivity thresholds for changing food web dynamics were assumed to be global constants. We challenged this assumption and found that several model parameters are sensitive to the contrast between persistently warm and seasonally cold climates. In persistently warm environments, three trophic level dynamics can be expected to prevail almost everywhere, save the most extreme deserts. We revised EEH accordingly and tested it by compiling direct evidence of three and two trophic level dynamics and by studying the global distribution of felids. In seasonally cold environments, we found evidence for three trophic level dynamics only in productive ecosystems, while evidence for two trophic level dynamics appeared in ecosystems with low primary productivity. In persistently warm environments, we found evidence for three trophic level dynamics in all types of ecosystems. The distribution of felids corroborated these results. The empirical evidence thus indicates that two trophic level dynamics, as defined by EEH, are restricted to seasonally cold biomes with low primary productivity, such as the artic–alpine tundra and the temperate steppe. © 2020 The Authors. Ecography published by John Wiley & Sons Ltd on behalf of Nordic Society Oikos This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Vulnerability to habitat fragmentation Habitat fragmentation caused by human activities has consequences for the distribution and movement of organisms. Betts et al. present a global analysis of how exposure to habitat fragmentation affects the composition of ecological communities (see the Perspective by Hargreaves). In a dataset consisting of 4489 animal species, regions that historically experienced little disturbance tended to harbor a higher proportion of species vulnerable to fragmentation. Species in more frequently disturbed regions were more resilient. High-latitude areas historically experienced more disturbance and harbor more resilient species, which suggests that extinction has removed fragmentation-sensitive species. Thus, conservation efforts to limit fragmentation are particularly important in the tropics. Science , this issue p. 1236 ; see also p. 1196

© 2019 The Authors. Conservation Letters published by Wiley Periodicals, Inc. Many of the world's vertebrates have experienced large population and geographic range declines due to anthropogenic threats that put them at risk of extinction. The largest vertebrates, defined as megafauna, are especially vulnerable. We analyzed how human activities are impacting the conservation status of megafauna within six classes: mammals, ray-finned fish, cartilaginous fish, amphibians, birds, and reptiles. We identified a total of 362 extant megafauna species. We found that 70% of megafauna species with sufficient information are decreasing and 59% are threatened with extinction. Surprisingly, direct harvesting of megafauna for human consumption of meat or body parts is the largest individual threat to each of the classes examined, and a threat for 98% (159/162) of threatened species with threat data available. Therefore, minimizing the direct killing of the world's largest vertebrates is a priority conservation strategy that might save many of these iconic species and the functions and services they provide.

Background . Breast cancer patients often use complementary and alternative medicine, but few prospectively collected data on the topic are available specifically for postmenopausal breast cancer patients. A large prospective study was therefore conducted within a noninterventional study in order to identify the characteristics of patients interested in integrative medicine. Methods . The EvAluate-TM study is a prospective, multicenter noninterventional study in which treatment with the aromatase inhibitor letrozole was evaluated in postmenopausal women with hormone receptor–positive primary breast cancer. Between 2008 and 2009, 5045 postmenopausal patients were enrolled at 339 certified breast centers in Germany. As part of the data collection process, patients were asked at the baseline about their interest in and information needs relating to integrative medicine. Results . Of the 5045 patients recruited, 3411 responded to the questionnaire on integrative medicine and took part in the analysis, 1583 patients expressed an interest in integrative medicine, and 1828 patients declared no interest. Relevant predictors of interest in integrative medicine were age, body mass index, tumor size, previous chemotherapy, and use of concomitant medications for other medical conditions. Interest in integrative medicine declined highly significantly ( P < .001) with age (65 years, 38.0%). Patients in favor of integrative medicine were significantly less satisfied with the information received about individual treatments and antihormonal therapy. Patients with interest in integrative medicine were more often interested in rehabilitation and fitness, nutritional counseling, and additional support from self-help organizations. These women were mostly interested in receiving information about their disease and integrative medicine from a physician, rather than from other sources. Conclusions . This study shows that a considerable proportion of postmenopausal breast cancer patients are interested in integrative medicine. Information about integrative medicine should therefore be provided as part of patient care for this group. It was found that receiving concomitant medication for other medical conditions is one of the main predictors for women not being interested in integrative medicine. This group of patients may need special attention and individualized information about integrative medicine. Additionally, most patients were interested in obtaining the relevant information from their doctor.

Wolf & Ripple [1] is a global study that explored the potential for large carnivore reintroductions, identifying protected areas and other regions with low human footprint that warrant further investigation as possible locations for rewilding. In his comment, Miranda [2] raised a number of points related to Wolf & Ripple [1]. His primary points are that Wolf and Ripple (i) used terminology (carnivore, apex predator, and guild) incorrectly, (ii) selected an inappropriate group of species to study and (iii) listed some unsuitable sites for large carnivore reintroductions. However, each of these criticisms is fundamentally flawed and only acts to hinder conservation efforts. Miranda stated that the species selected by Wolf and Ripple ‘were neither necessarily apex predators nor carnivores, but a subset of the mammalian order Carnivora, […]'. However, Wolf and Ripple did not claim that the species being studied are apex predators. In fact, the term ‘apex predator' does not appear anywhere in the main text or supplement of Wolf and Ripple. The species selected included 25 large carnivore species with a body mass greater than or equal to 15 kg that have relatively accurate historic and current range maps. The scope and purpose of Wolf and Ripple was to identify potential reintroduction sites for large-bodied members of order Carnivora without regard for whether each individual species was an apex predator, which is in itself context dependent. For example, coyotes ( Canis latrans ) may be considered mesopredators when wolves are present, but apex predators when wolves are absent [3]. Had Wolf and Ripple focused on potential reintroductions of a different taxonomic order, such as Primates, would Miranda then critique that the paper did not focus enough on other groups of vertebrates? Miranda is incorrect in his claim that the species selected are …

Pincheira-Donoso and Hodgson (1) discuss vertebrate endangerment patterns in their response to our recent article (2). They reassessed our conclusion of a bimodal body size distribution of endangerment for all vertebrates but did so using only data on body mass for amphibians. In our study, we collectively analyzed patterns of endangerment across six classes of vertebrates. Contrasting patterns specific to amphibians with results that pertain to all vertebrates fails to compare like to like and as such is perhaps an exercise of unclear value. Pincheira-Donoso and Hodgson (1) suggest that our vertebrate model is inadequate because “increases in endangerment of smaller vertebrates are heavily biased by a single class (Amphibia) . . . ” We investigated this potential bias by refitting our vertebrate model without amphibians … [↵][1]1To whom correspondence should be addressed. Email: bill.ripple{at}oregonstate.edu. [1]: #xref-corresp-1-1

Earth's terrestrial large carnivores form a highly endangered group of species with unique conservation challenges. The majority of these species have experienced major geographical range contractions, which puts many of them at high risk of extinction or of becoming ecologically ineffective. As a result of these range contractions and the associated loss of intact predator guilds, the ecological effects of these species are now far less widespread and common, with inevitable consequences for ecosystem function. Rewilding—which includes reintroducing species into portions of their former ranges—is an important carnivore conservation tool and means for restoring top-down ecological regulation. We conducted a global analysis of potential reintroduction areas. We first considered protected areas where one or more large carnivore species have been extirpated, identifying a total of 130 protected areas that may be most suitable for carnivore reintroduction. These protected areas include sites in every major world region, and are most commonly found in Mongolia ( n = 13), Canada ( n = 11), Thailand ( n = 9), Namibia ( n = 6), Indonesia ( n = 6) and Australia ( n = 6). We considered the sizes of protected areas, their levels of protection, the extent of human impacts within and around the protected areas, and the status of prey species in the protected areas. Finally, we used the ‘last of the wild’ approach to identify contiguous low human footprint regions within the former ranges of each species, identifying an additional 150 areas which could be the focus of conservation efforts to create conditions conducive to reintroductions. These low footprint regions were most commonly found in the USA ( n = 14), Russia ( n = 14), Canada ( n = 10), China ( n = 9) and Mauritania ( n = 8). Together, our results show the global-scale potential for carnivore rewilding projects to both conserve these species and provide critical ecological and social benefits.

Kalinkat et al. (1) discuss the biodiversity crisis in their reply to our article “Extinction risk is most acute for the world’s largest and smallest vertebrates” (2). We agree with Kalinkat et al. (1) that small freshwater species tend to have elevated extinction risk, an issue that we highlight in our paper (2). Specifically, 41% (36 of 87) of freshwater vertebrate species with body masses ≤ 0.001 kg are listed as threatened compared with 29% (1,578 of 5,428) threatened for … [↵][1]1To whom correspondence should be addressed. Email: bill.ripple{at}oregonstate.edu. [1]: #xref-corresp-1-1

Extinction risk in vertebrates has been linked to large body size, but this putative relationship has only been explored for select taxa, with variable results. Using a newly assembled and taxonomically expansive database, we analyzed the relationships between extinction risk and body mass (27,647 species) and between extinction risk and range size (21,294 species) for vertebrates across six main classes. We found that the probability of being threatened was positively and significantly related to body mass for birds, cartilaginous fishes, and mammals. Bimodal relationships were evident for amphibians, reptiles, and bony fishes. Most importantly, a bimodal relationship was found across all vertebrates such that extinction risk changes around a body mass breakpoint of 0.035 kg, indicating that the lightest and heaviest vertebrates have elevated extinction risk. We also found range size to be an important predictor of the probability of being threatened, with strong negative relationships across nearly all taxa. A review of the drivers of extinction risk revealed that the heaviest vertebrates are most threatened by direct killing by humans. By contrast, the lightest vertebrates are most threatened by habitat loss and modification stemming especially from pollution, agricultural cropping, and logging. Our results offer insight into halting the ongoing wave of vertebrate extinctions by revealing the vulnerability of large and small taxa, and identifying size-specific threats. Moreover, they indicate that, without intervention, anthropogenic activities will soon precipitate a double truncation of the size distribution of the world's vertebrates, fundamentally reordering the structure of life on our planet.

Patients with HER2-positive early breast cancer (EBC) preferred subcutaneous (s.c.) trastuzumab, delivered via single-use injection device (SID), over the intravenous (i.v.) formulation (Cohort 1 of the PrefHer study: NCT01401166). Here, we report patient preference, healthcare professional satisfaction, and safety data pooled from Cohort 1 and also Cohort 2, where s.c. trastuzumab was delivered via hand-held syringe.Patients were randomized to receive four adjuvant cycles of 600 mg fixed-dose s.c. trastuzumab followed by four cycles of standard i.v. trastuzumab, or vice versa. The primary endpoint was overall preference proportions for s.c. or i.v., assessed by patient interviews in the evaluable ITT population.A total of 245 patients were randomized to receive s.c. followed by i.v. and 243 received i.v. followed by s.c. (evaluable ITT populations: 235 and 232 patients, respectively). s.c. was preferred by 415/467 [88.9%; 95% confidence interval (CI) 85.7-91.6; P0.0001; two-sided test against null hypothesis of 65% s.c. preference]; 45/467 preferred i.v. (9.6%; 95% CI 7-13); 7/467 indicated no preference (1.5%; 95% CI 1-3). Clinician-reported adverse events occurred in 292/479 (61.0%) and 245/478 (51.3%) patients during the pooled s.c. and i.v. periods, respectively (P0.05; 2 × 2 χ(2)); 16 patients (3.3%) in each period experienced grade 3 events; none were grade 4/5.PrefHer revealed compelling and consistent patient preferences for s.c. over i.v. trastuzumab, regardless of SID or hand-held syringe delivery. s.c. was well tolerated and safety was consistent with previous reports, including the HannaH study (NCT00950300). No new safety signals were identified compared with the known i.v. profile in EBC. PrefHer and HannaH confirm that s.c. trastuzumab is a validated and preferred option over i.v. for improving patients' care in HER2-positive breast cancer.NCT01401166.

[Extract] We agree in how they describe the need to get more scientists into policymaking positions (Dror), to create a new global environmental ethic (Skubala), and to recognize economic growth as a major driver of environmental impacts (Pacheco et al.). The letters raise questions about how science interacts with society and how evidence-based reasoning can play an important role in creating a healthy relationship between humans and the biosphere.

The IPCC's Special Report on Climate Change and Land addresses the closely coupled relationship between land use and climate change. The report notes the climate change mitigation potential of dietary shifts and afforestation. Here, we briefly discuss how decreases in ruminant meat consumption associated with dietary shifts have the potential to free up area for forests, allowing for greater CO2 sequestration and benefiting biodiversity, while simultaneously reducing anthropogenic CO2 emissions.

In our recent perspective article, we noted that most (approximately 60 percent) terrestrial large carnivore and large herbivore species are now threatened with extinction, and we offered a 13-point declaration designed to promote and guide actions to save these iconic mammalian megafauna (Ripple et al. 2016). Some may worry that a focus on saving megafauna might undermine efforts to conserve biodiversity more broadly. We believe that all dimensions of biodiversity are important and that efforts to conserve megafauna are not in themselves sufficient to halt the dispiriting trends of species and population losses in recent decades. From 1970 to 2012, a recent global analysis showed a 58 percent overall decline in vertebrate population abundance (WWF 2016). Bold and varied approaches are necessary to conserve what remains of Earth’s biodiversity, and our declaration in no way disputes the value of specific conservation initiatives targeting other taxa. Indeed, the evidence is clear that without massively scaling up conservation efforts for all species, we will fail to achieve internationally agreed-upon targets for biodiversity.