Dispersal knowledge is essential for conservation management, and demand is growing. But are we accumulating dispersal knowledge at a pace that can meet the demand? To answer this question we tested ...for changes in dispersal data collection and use over time. Our systematic review of 655 conservation-related publications compared five topics: climate change, habitat restoration, population viability analysis, land planning (systematic conservation planning) and invasive species. We analysed temporal changes in the: (i) questions asked by dispersal-related research; (ii) methods used to study dispersal; (iii) the quality of dispersal data; (iv) extent that dispersal knowledge is lacking, and; (v) likely consequences of limited dispersal knowledge. Research questions have changed little over time; the same problems examined in the 1990s are still being addressed. The most common methods used to study dispersal were occupancy data, expert opinion and modelling, which often provided indirect, low quality information about dispersal. Although use of genetics for estimating dispersal has increased, new ecological and genetic methods for measuring dispersal are not yet widely adopted. Almost half of the papers identified knowledge gaps related to dispersal. Limited dispersal knowledge often made it impossible to discover ecological processes or compromised conservation outcomes. The quality of dispersal data used in climate change research has increased since the 1990s. In comparison, restoration ecology inadequately addresses large-scale process, whilst the gap between knowledge accumulation and growth in applications may be increasing in land planning. To overcome apparent stagnation in collection and use of dispersal knowledge, researchers need to: (i) improve the quality of available data using new approaches; (ii) understand the complementarities of different methods and; (iii) define the value of different kinds of dispersal information for supporting management decisions. Ambitious, multi-disciplinary research programs studying many species are critical for advancing dispersal research.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Older adults (aged ≥70 years) are at increased risk of severe disease and death if they develop COVID-19 and are therefore a priority for immunisation should an efficacious vaccine be developed. ...Immunogenicity of vaccines is often worse in older adults as a result of immunosenescence. We have reported the immunogenicity of a novel chimpanzee adenovirus-vectored vaccine, ChAdOx1 nCoV-19 (AZD1222), in young adults, and now describe the safety and immunogenicity of this vaccine in a wider range of participants, including adults aged 70 years and older.
In this report of the phase 2 component of a single-blind, randomised, controlled, phase 2/3 trial (COV002), healthy adults aged 18 years and older were enrolled at two UK clinical research facilities, in an age-escalation manner, into 18–55 years, 56–69 years, and 70 years and older immunogenicity subgroups. Participants were eligible if they did not have severe or uncontrolled medical comorbidities or a high frailty score (if aged ≥65 years). First, participants were recruited to a low-dose cohort, and within each age group, participants were randomly assigned to receive either intramuscular ChAdOx1 nCoV-19 (2·2 × 1010 virus particles) or a control vaccine, MenACWY, using block randomisation and stratified by age and dose group and study site, using the following ratios: in the 18–55 years group, 1:1 to either two doses of ChAdOx1 nCoV-19 or two doses of MenACWY; in the 56–69 years group, 3:1:3:1 to one dose of ChAdOx1 nCoV-19, one dose of MenACWY, two doses of ChAdOx1 nCoV-19, or two doses of MenACWY; and in the 70 years and older, 5:1:5:1 to one dose of ChAdOx1 nCoV-19, one dose of MenACWY, two doses of ChAdOx1 nCoV-19, or two doses of MenACWY. Prime-booster regimens were given 28 days apart. Participants were then recruited to the standard-dose cohort (3·5–6·5 × 1010 virus particles of ChAdOx1 nCoV-19) and the same randomisation procedures were followed, except the 18–55 years group was assigned in a 5:1 ratio to two doses of ChAdOx1 nCoV-19 or two doses of MenACWY. Participants and investigators, but not staff administering the vaccine, were masked to vaccine allocation. The specific objectives of this report were to assess the safety and humoral and cellular immunogenicity of a single-dose and two-dose schedule in adults older than 55 years. Humoral responses at baseline and after each vaccination until 1 year after the booster were assessed using an in-house standardised ELISA, a multiplex immunoassay, and a live severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) microneutralisation assay (MNA80). Cellular responses were assessed using an ex-vivo IFN-γ enzyme-linked immunospot assay. The coprimary outcomes of the trial were efficacy, as measured by the number of cases of symptomatic, virologically confirmed COVID-19, and safety, as measured by the occurrence of serious adverse events. Analyses were by group allocation in participants who received the vaccine. Here, we report the preliminary findings on safety, reactogenicity, and cellular and humoral immune responses. This study is ongoing and is registered with ClinicalTrials.gov, NCT04400838, and ISRCTN, 15281137.
Between May 30 and Aug 8, 2020, 560 participants were enrolled: 160 aged 18–55 years (100 assigned to ChAdOx1 nCoV-19, 60 assigned to MenACWY), 160 aged 56–69 years (120 assigned to ChAdOx1 nCoV-19: 40 assigned to MenACWY), and 240 aged 70 years and older (200 assigned to ChAdOx1 nCoV-19: 40 assigned to MenACWY). Seven participants did not receive the boost dose of their assigned two-dose regimen, one participant received the incorrect vaccine, and three were excluded from immunogenicity analyses due to incorrectly labelled samples. 280 (50%) of 552 analysable participants were female. Local and systemic reactions were more common in participants given ChAdOx1 nCoV-19 than in those given the control vaccine, and similar in nature to those previously reported (injection-site pain, feeling feverish, muscle ache, headache), but were less common in older adults (aged ≥56 years) than younger adults. In those receiving two standard doses of ChAdOx1 nCoV-19, after the prime vaccination local reactions were reported in 43 (88%) of 49 participants in the 18–55 years group, 22 (73%) of 30 in the 56–69 years group, and 30 (61%) of 49 in the 70 years and older group, and systemic reactions in 42 (86%) participants in the 18–55 years group, 23 (77%) in the 56–69 years group, and 32 (65%) in the 70 years and older group. As of Oct 26, 2020, 13 serious adverse events occurred during the study period, none of which were considered to be related to either study vaccine. In participants who received two doses of vaccine, median anti-spike SARS-CoV-2 IgG responses 28 days after the boost dose were similar across the three age cohorts (standard-dose groups: 18–55 years, 20 713 arbitrary units AU/mL IQR 13 898–33 550, n=39; 56–69 years, 16 170 AU/mL 10 233–40 353, n=26; and ≥70 years 17 561 AU/mL 9705–37 796, n=47; p=0·68). Neutralising antibody titres after a boost dose were similar across all age groups (median MNA80 at day 42 in the standard-dose groups: 18–55 years, 193 IQR 113–238, n=39; 56–69 years, 144 119–347, n=20; and ≥70 years, 161 73–323, n=47; p=0·40). By 14 days after the boost dose, 208 (>99%) of 209 boosted participants had neutralising antibody responses. T-cell responses peaked at day 14 after a single standard dose of ChAdOx1 nCoV-19 (18–55 years: median 1187 spot-forming cells SFCs per million peripheral blood mononuclear cells IQR 841–2428, n=24; 56–69 years: 797 SFCs 383–1817, n=29; and ≥70 years: 977 SFCs 458–1914, n=48).
ChAdOx1 nCoV-19 appears to be better tolerated in older adults than in younger adults and has similar immunogenicity across all age groups after a boost dose. Further assessment of the efficacy of this vaccine is warranted in all age groups and individuals with comorbidities.
UK Research and Innovation, National Institutes for Health Research (NIHR), Coalition for Epidemic Preparedness Innovations, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midlands NIHR Clinical Research Network, and AstraZeneca.
Extensive flooding occurred during the winter of 2013–14 in England. Previous studies have shown that flooding affects mental health. Using data from the 2013–14 Public Health England National Study ...of Flooding and Health, we compared the prevalence of symptoms of depression, anxiety, and post-traumatic stress disorder between participants displaced by flooding and those flooded, but not displaced, 1 year after flooding.
In this multivariable ordinal regression analysis, we collected data from a cross-sectional survey collected 1 year after the flooding event from flood-affected postcodes in five counties in England. The analysis was restricted to individuals whose homes were flooded (n=622) to analyse displacement due to flooding. The primary outcome measures were depression (measured by the PHQ-2 depression scale) and anxiety (measured by the two-item Generalised Anxiety Disorder GAD-2 anxiety scale), and post-traumatic stress disorder (measured by the Post-Traumatic Stress Disorder Checklist PCL-6 scale). We adjusted analyses for recorded potential confounders. We also analysed duration of displacement and amount of warning received.
People who were displaced from their homes were significantly more likely to have higher scores on each scale; odds ratio (OR) for depression 1·95 (95% CI 1·30–2·93), for anxiety 1·66 (1·12–2·46), and for post-traumatic stress disorder 1·70 (1·17–2·48) than people who were not displaced. The increased risk of depression was significant even after adjustment for severity of flooding. Scores for depression and post-traumatic stress disorder were higher in people who were displaced and reported receiving no warning than those who had received a warning more than 12 h in advance of flooding (p=0·04 for depression, p=0·01 for post-traumatic stress disorder), although the difference in anxiety scores was not significant.
Displacement after flooding was associated with higher reported symptoms of depression, anxiety, and post-traumatic stress disorder 1 year after flooding. The amount of warning received showed evidence of being protective against symptoms of the three mental illnesses studied, and the severity of flooding might be the reason for some, but not all, of the differences between the groups.
National Institute for Health Research Health Protection Research Units (HPRU) in Emergency Preparedness and Response at King's College London, Environmental Change and Health at the London School of Hygiene and Tropical Medicine, and Evaluation of Interventions at the University of Bristol, Public Health England.
Bathelt H., Munro A. K. and Spigel B. Challenges of transformation: innovation, re-bundling and traditional manufacturing in Canada's Technology Triangle, Regional Studies. This paper develops a ...perspective of regional re-bundling in overcoming economic crises. It does this by focusing on the effects of the recent global financial crisis on traditional manufacturing. It analyses the structure of innovation processes and their development over time in Canada's Technology Triangle - a region known for university-related spin-off processes and successful modernization. What is less well known is that this region has been strongly influenced by traditional manufacturing industries. It is shown that these industries have been well prepared to deal with the effects of the crisis due to ongoing innovation and diversification stimulated by prior economic crises.
Bathelt H., Munro A. K. and Spigel B. 转型的挑战：创新、再绑定以及加拿大技术三角中的传统制造业， 区域研究。本文提出了区域绑定视角来应对经济危机。文章通过集中于目前传统制造业全球金融危机效应，对此问题进行了考察。文章分析了创新过程的结构以及加拿大技术三角的发展。人们普遍认为加拿大技术三角的成功源自与大学相关的脱离过程以及现代化。但是对于该区域受传统制造业影响较大这一点较少研究关注。文章认为，这些产业足以应对由于持续的创新及前经济危机导致的多样化所引发的危机。
加拿大的技术三角 制造业 全球金融危机 再绑定 创新实践/策略
Bathelt H., Munro A. K. et Spigel B. Le défi de la transformation: l'innovation, le refusionnement et l'industrie manufacturière traditionnelle dans le triangle canadien de la technologie, Regional Studies. Cet article cherche à développer une idée du rôle du refusionnement quant à la résolution des crises économiques. On met l'accent sur les retombées de la dernière crise financière mondiale sur l'industrie manufacturière traditionnelle. On analyse la structure des processus en matière d'innovation et leur développement au fil du temps dans le triangle canadien de la technologie - une région bien connue pour les retombées universitaires et la modernisaion réussie. Ce qui est moins bien connu c'est la forte influence sur cette région des industries manufacturières traditionnelles. On démontre que ces industries ont été bien équipées pour faire face aux retombées de la crise en vertu de l'innovation en cours et de la diversification stimulée par les crises antérieures.
Triangle canadien de la technologie Secteur manufacturier Crise financière mondiale Refusionnement Pratiques et Stratégies en matière d'innovation
Bathelt H., Munro A. K. und Spigel B. Herausforderungen der Transformation: Innovation, Neubündelung und traditionelle Industrien in Canada's Technology Triangle, Regional Studies. Der Beitrag entwickelt eine Perspektive regionaler Neubündelungs (Re-bundling-) Prozesse zur Überwindung ökonomischer Krisen. Der Fokus der Studie liegt bei den Auswirkungen der globalen Finanzkrise Ende der 2000er Jahre auf traditionelle Industrien. Untersucht werden die Struktur von Innovationsprozessen und ihr Wandel am Beispiel von Canada's Technology Triangle - einer Region, die durch universitätsbezogene Spin-offs und ökonomische Modernisierungsprozesse bekannt geworden ist. Weniger bekannt ist dagegen, dass die Region ebenso durch traditionelle Industriesektoren geprägt ist. Die Ergebnisse der durchgeführten Unternehmensbefragungen zeigen, dass die betreffenden Industrien überraschend gut auf die Wirtschaftskrise vorbereitet waren und darauf reagieren konnten. Dies hing mit andauernden Innovationsprozessen und Diversifizierungsbemühungen zusammen, die durch vorhergehende Krisen ausgelöst wurden.
Canada's Technology Triangle Traditionelle Industrien Globale Finanzkrise Neubündelung (Re-bundling) Innovationspraktiken/-strategien
Bathelt H., Munro A. K. y Spigel B. Retos de transformación: procesos de innovación, recombinación y manufactura tradicional en el Triángulo Tecnológico canadiense, Regional Studies. En este artículo desarrollamos una perspectiva de recombinación regional en la superación de las crisis económicas. Para ello nos centramos en los efectos de la reciente crisis financiera mundial en la manufactura tradicional. Analizamos la estructura de los procesos de innovación y su desarrollo con el paso del tiempo en el Triángulo Tecnológico canadiense, una región conocida por los procesos spin-off universitarios y sus avances en modernización. Lo que es menos conocido es que esta región ha estado muy influenciada por las industrias manufactureras tradicionales. Demostramos que estas industrias han estado bien preparadas para tratar los efectos de la crisis debido a la continua innovación y diversificación estimuladas por las crisis económicas anteriores.
Triángulo Tecnológico canadiense Sector manufacturero Crisis financiera mundial Reconstrucción Prácticas/estrategias de innovación
•UCOE-containing cells show advantage in recombinant antibody expression.•Cell line generation involving the use of semi-solid cloning and ClonePix FL.•High throughput technology has a crucial role ...in clonal isolation.•Example of a clear, simple and streamlined path for biopharmaceutical development.
Therapeutic recombinant monoclonal antibodies (mAbs) are commonly produced by high-expressing, clonal, mammalian cells. Creation of these clones for manufacturing remains heavily reliant on stringent selection and gene amplification, which in turn can lead to genetic instability, variable expression, product heterogeneity and prolonged development timelines. Inclusion of cis-acting ubiquitous chromatin opening elements (UCOE™) in mammalian expression vectors has been shown to improve productivity and facilitate high-level gene expression irrespective of the chromosomal integration site without lengthy gene amplification protocols. In this study we have used high-throughput robotic clone selection in combination with UCOE™ containing expression vectors to develop a rapid, streamlined approach for early-stage cell line development and isolation of high-expressing clones for mAb production using Chinese hamster ovary (CHO) cells. Our results demonstrate that it is possible to go from transfection to stable clones in only 4 weeks, while achieving specific productivities exceeding 20pg/cell/day. Furthermore, we have used this approach to quickly screen several process-crucial parameters including IgG subtype, enhancer-promoter combination and UCOE™ length. The use of UCOE™-containing vectors in combination with automated robotic selection provides a rapid method for the selection of stable, high-expressing clones.
Diffuse large B-cell lymphoma (DLBCL) is a genetically heterogeneous cancer composed of at least 2 molecular subtypes that differ in gene expression and distribution of mutations. Recently, ...application of genome/exome sequencing and RNA-seq to DLBCL has revealed numerous genes that are recurrent targets of somatic point mutation in this disease. Here we provide a whole-genome-sequencing-based perspective of DLBCL mutational complexity by characterizing 40 de novo DLBCL cases and 13 DLBCL cell lines and combining these data with DNA copy number analysis and RNA-seq from an extended cohort of 96 cases. Our analysis identified widespread genomic rearrangements including evidence for chromothripsis as well as the presence of known and novel fusion transcripts. We uncovered new gene targets of recurrent somatic point mutations and genes that are targeted by focal somatic deletions in this disease. We highlight the recurrence of germinal center B-cell-restricted mutations affecting genes that encode the S1P receptor and 2 small GTPases (GNA13 and GNAI2) that together converge on regulation of B-cell homing. We further analyzed our data to approximate the relative temporal order in which some recurrent mutations were acquired and demonstrate that ongoing acquisition of mutations and intratumoral clonal heterogeneity are common features of DLBCL. This study further improves our understanding of the processes and pathways involved in lymphomagenesis, and some of the pathways mutated here may indicate new avenues for therapeutic intervention.
•Complete genome sequence analysis of 40 DLBCL tumors and 13 cell lines reveals novel somatic point mutations, rearrangements, and fusions.•Recurrence of mutations in genes involved in B-cell homing were identified in germinal center B-cell DLBCLs.
e17540 Background: Ovarian clear cell carcinoma (OCCC) is a rare subtype with distinct histologic and molecular features. The prognosis of advanced/recurrent OCCC treated with standard of care ...surgery and platinum-based chemotherapy remains poor due to inherent chemoresistance. Therefore, there is an urgent need to identify novel biological insights and personalized treatment approaches to improve outcomes. Methods: Participants were referred to the SMMART Program at the OHSU Knight Cancer Institute. Archival or fresh tissue was obtained from metastatic sites and processed through a multiomics platform that included immunohistochemistry (Ki67, HER2, CD4, CD8, PD-L1), fluorescent in-situ hybridization, targeted next-generation sequencing panel (225 genes), whole transcriptomic sequencing, chromosomal microarray, and multiplexed analysis of 67 key cancer proteins and phosphoproteins on the Nanostring GeoMx Digital Spatial Profiler. Results: 5 participants were enrolled with an average age of 62 years (range 52-72). Therapeutically relevant findings included detectable HER2 expression by IHC (2+, N=2; 3+, N=2), HER2 amplification by FISH (N=2), and high HER2 and phospho-HER2 protein expression compared to a breast cancer cohort (phospho-HER2 supports active HER2 signaling in the tumor cells). Additional findings include TMB <10 muts/Mb (N=5), microsatellite stable (N=5), Ki67 40-60% (N=4), mild to moderate CD4 and/or CD8 infiltration (N=4), PD-L1 >1% (N=3), low homologous recombination deficiency score (N=4), chromosomal losses including ATM, SMAD4, RB1, and TP53, and single nucleotide variations in ARID1A (N=4). Two participants with HER2 expression were treated with off-label trastuzumab deruxtecan for 6 or 7 cycles yielding significant clinical benefit. Participant A (HER2 = 3+, FISH negative) had an exceptional response while Participant B (HER2 = 2+, FISH amplified) had stable disease. The toxicity profile was consistent with literature. Conclusions: Our OCCC cohort revealed elevated HER2 expression with or without genomic amplification in 4/5 cases. Two participants experienced clinical benefit when treated with trastuzumab deruxtecan, supporting further exploration of HER2 antibody drug conjugates in this aggressive disease. More study is needed to determine the frequency of HER2 overexpression and amplification in OCCC, the importance of HER2 on OCCC pathophysiology, and the therapeutic benefit of targeting HER2 in this population.
Temperate grasslands and woodlands are the focus of extensive restoration efforts worldwide. Reintroduction of locally extinct soil-foraging and burrowing animals has been suggested as a means to ...restore soil function in these ecosystems. Yet little is known about the physical and chemical effects of digging on soil over time and how these effects differ between species of digging animal, vegetation types or ecosystems. We compared foraging pits of a native reintroduced marsupial, the eastern bettong (
) and that of the exotic European rabbit (
). We simulated pits of these animals and measured pit dimensions and soil chemical properties over a period of 2 years. We showed that bettong and rabbit pits differed in their morphology and longevity, and that pits had a strong moderating effect on soil surface temperatures. Over 75% of the simulated pits were still visible after 2 years, and bettong pits infilled faster than rabbit pits. Bettong pits reduced diurnal temperature range by up to 25 °C compared to the soil surface. We did not find any effects of digging on soil chemistry that were consistent across vegetation types, between bettong and rabbit pits, and with time since digging, which is contrary to studies conducted in arid biomes. Our findings show that animal foraging pits in temperate ecosystems cause physical alteration of the soil surface and microclimatic conditions rather than nutrient changes often observed in arid areas.
Phytophthora infestans is the most destructive pathogen of potato and a model organism for the oomycetes, a distinct lineage of fungus-like eukaryotes that are related to organisms such as brown ...algae and diatoms. As the agent of the Irish potato famine in the mid-nineteenth century, P. infestans has had a tremendous effect on human history, resulting in famine and population displacement. To this day, it affects world agriculture by causing the most destructive disease of potato, the fourth largest food crop and a critical alternative to the major cereal crops for feeding the world's population. Current annual worldwide potato crop losses due to late blight are conservatively estimated at $6.7 billion. Management of this devastating pathogen is challenged by its remarkable speed of adaptation to control strategies such as genetically resistant cultivars. Here we report the sequence of the P. infestans genome, which at approximately 240 megabases (Mb) is by far the largest and most complex genome sequenced so far in the chromalveolates. Its expansion results from a proliferation of repetitive DNA accounting for 74% of the genome. Comparison with two other Phytophthora genomes showed rapid turnover and extensive expansion of specific families of secreted disease effector proteins, including many genes that are induced during infection or are predicted to have activities that alter host physiology. These fast-evolving effector genes are localized to highly dynamic and expanded regions of the P. infestans genome. This probably plays a crucial part in the rapid adaptability of the pathogen to host plants and underpins its evolutionary potential.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract When fish stocks migrate across multiple exclusive economic zones (EEZs), they compel managers to examine management at both national and international levels. A strategic interaction ...emerges when the fishing activity of one country impacts fishing opportunities available for other countries sharing the stock. Left unaddressed, strategic interaction could lead to overexploitation and suboptimal payoffs. Here, we develop and apply a bioeconomic model to address the competitive fishing for silver pomfret in the Arabian/Persian Gulf—a highly commercial fish stock shared between Kuwait and Iran—and evaluate biological–economic trade-offs under competition, cooperation, and country-independent management using maximum sustainable yield (MSY) and fishing mortality that maintain MSY (Fmsy) policies. When cooperation involves an equal share of the overall Fmsy or a share based on the proportion of the stock available in each EEZ, countries are expected to cooperate given the substantially higher catch, biomass, and relative profits compared to other management regimes. However, other than these two arrangements, countries would favour different regimes. Besides providing policy insights to improve the perilous status of silver pomfret, our approach could be useful in exploring alternative fishing arrangements to sustainably harvest a transboundary fish stock while maximizing average yields.
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