Longitudinal relationships between fatigue and depression in cancer patients with depression and/or pain

OBJECTIVE: Fatigue is one of the most common and debilitating symptoms reported by cancer patients, yet relatively little is understood about its etiology. Recently, as researchers have begun to focus attention on cancer-related fatigue (CRF), depression has emerged as its strongest correlate. Few longitudinal studies, however, have examined directionality of the relationship between the two symptoms. Our aim was to evaluate the directionality of the association between depression and CRF. METHOD: The study used a single-group cohort design of longitudinal data (N = 329) from a randomized controlled trial of an intervention for pain and depression in a heterogeneous sample of cancer patients. Participants met criteria for clinically significant pain and/or depression. Our hypothesis that depression would predict change in fatigue over 3 months was tested using latent variable cross-lagged panel analysis. RESULTS: Depressive symptoms and fatigue were strongly correlated in the sample (baseline correlation of latent variables = 0.71). Although the model showed good fit to the data, χ(2) (66, N = 329) = 88.16, p = .04, SRMR = 0.030, RMSEA = 0.032, and CFI = 1.00, neither structural path linking depression and fatigue was significant, suggesting neither symptom preceded and predicted the other. CONCLUSIONS: Our findings did not support hypotheses regarding the directionality of the relationship between depressive symptoms and fatigue. The clinical implication is that depression-specific treatments may not be sufficient to treat CRF and that instead, interventions specifically targeting fatigue are needed

Quantification of habitat fragmentation reveals extinction risk in terrestrial mammals

Although habitat fragmentation is often assumed to be a primary driver of extinction, global patterns of fragmentation and its relationship to extinction risk have not been consistently quantified for any major animal taxon. We developed high-resolution habitat fragmentation models and used phylogenetic comparative methods to quantify the effects of habitat fragmentation on the world's terrestrial mammals, including 4,018 species across 26 taxonomic Orders. Results demonstrate that species with more fragmentation are at greater risk of extinction, even after accounting for the effects of key macroecological predictors, such as body size and geographic range size. Species with higher fragmentation had smaller ranges and a lower proportion of high-suitability habitat within their range, andmost high-suitability habitat occurred outside of protected areas, further elevating extinction risk. Our models provide a quantitative evaluation of extinction risk assessments for species, allow for identification of emerging threats in species not classified as threatened, and provide maps of global hotspots of fragmentation for the world's terrestrial mammals. Quantification of habitat fragmentation will help guide threat assessment and strategic priorities for global mammal conservation

Δ133p53α enhances metabolic and cellular fitness of TCR-engineered T cells and promotes superior antitumor immunity

Background Tumor microenvironment-associated T cell senescence is a key limiting factor for durable effective cancer immunotherapy. A few studies have demonstrated the critical role of the tumor suppressor TP53-derived p53 isoforms in cellular senescence process of non-immune cells. However, their role in lymphocytes, in particular tumor-antigen (TA) specific T cells remain largely unexplored.Methods Human T cells from peripheral blood were retrovirally engineered to coexpress a TA-specific T cell receptor and the Δ133p53α-isoform, and characterized for their cellular phenotype, metabolic profile and effector functions.Results Phenotypic analysis of Δ133p53α-modified T cells revealed a marked reduction of the T-cell inhibitory molecules (ie, CD160 and TIGIT), a lower frequency of senescent-like CD57+ and CD160+ CD8+ T cell populations, and an increased number of less differentiated CD28+ T cells. Consistently, we demonstrated changes in the cellular metabolic program toward a quiescent T cell state. On a functional level, Δ133p53α-expressing T cells acquired a long-term proliferative capacity, showed superior cytokine secretion and enhanced tumor-specific killing in vitro and in mouse tumor model. Finally, we demonstrated the capacity of Δ133p53α to restore the antitumor response of senescent T cells isolated from multiple myeloma patients.Conclusion This study uncovered a broad effect of Δ133p53α isoform in regulating T lymphocyte function. Enhancing fitness and effector functions of senescent T cells by modulation of p53 isoforms could be exploited for future translational research to improve cancer immunotherapy and immunosenescence-related diseases

Indefinite and Bidirectional Near Infrared Nanocrystal Photoswitching

Materials whose luminescence can be switched by optical stimulation drive technologies ranging from superresolution imaging1-4, nanophotonics5, and optical data storage6-8, to targeted pharmacology, optogenetics, and chemical reactivity9. These photoswitchable probes, including organic fluorophores and proteins, are prone to photodegradation, and often require phototoxic doses of ultraviolet (UV) or visible light. Colloidal inorganic nanoparticles have significant stability advantages over existing photoswitchable materials, but the ability to switch emission bidirectionally, particularly with NIR light, has not been reported with nanoparticles. Here, we present 2-way, near-infrared (NIR) photoswitching of avalanching nanoparticles (ANPs), showing full optical control of upconverted emission using phototriggers in the NIR-I and NIR-II spectral regions useful for subsurface imaging. Employing single-step photodarkening10-13 and photobrightening12,14-18, we demonstrate indefinite photoswitching of individual nanoparticles (>1000 cycles over 7 h) in ambient or aqueous conditions without measurable photodegradation. Critical steps of the photoswitching mechanism are elucidated by modeling and by measuring the photon avalanche properties of single ANPs in both bright and dark states. Unlimited, reversible photoswitching of ANPs enables indefinitely rewritable 2D and 3D multi-level optical patterning of ANPs, as well as optical nanoscopy with sub-{\AA} localization superresolution that allows us to distinguish individual ANPs within tightly packed clusters.Comment: 15 pages, 5 figure

Win-Win for Wind and Wildlife: A Vision to Facilitate Sustainable Development

Wind energy offers the potential to reduce carbon emissions while increasing energy independence and bolstering economic development. However, wind energy has a larger land footprint per Gigawatt (GW) than most other forms of energy production, making appropriate siting and mitigation particularly important. Species that require large unfragmented habitats and those known to avoid vertical structures are particularly at risk from wind development. Developing energy on disturbed lands rather than placing new developments within large and intact habitats would reduce cumulative impacts to wildlife. The U.S. Department of Energy estimates that it will take 241 GW of terrestrial based wind development on approximately 5 million hectares to reach 20% electricity production for the U.S. by 2030. We estimate there are ∼7,700 GW of potential wind energy available across the U.S., with ∼3,500 GW on disturbed lands. In addition, a disturbance-focused development strategy would avert the development of ∼2.3 million hectares of undisturbed lands while generating the same amount of energy as development based solely on maximizing wind potential. Wind subsidies targeted at favoring low-impact developments and creating avoidance and mitigation requirements that raise the costs for projects impacting sensitive lands could improve public value for both wind energy and biodiversity conservation

Promoting equity through inclusive learning, planning and implementing: lessons from Nigeria's mass drug administration programme for neglected tropical diseases

Background: An inclusive, localised approach to planning and implementing equitable mass drug administration was developed through participatory action research (PAR). This new approach aligns with principles of learning health systems (LHS). Tools were co-developed to support scaling up the new approach across two Nigerian states. Lessons are distilled here to enable learning for other programmes. Methods: Observations and reports by researchers (2019–2021) from 23 meetings and workshops, 8 in-depth interviews and 8 focus group discussions (FGDs) were used. Results: Nine key steps of best practice were identified to promote inclusive LHS for participatory planning and implementing: utilise participatory research methodologies to facilitate community engagement and tailor interventions; develop tools and governance structures to support learning, teamwork and sustainability; strengthen capacity for participation and collaboration with space for dialogue and shared learning; undertake participatory planning to develop action plans; advocate for implementation; monitor action plans; review and act on successes and challenges; apply community evaluation to understand challenges and enablers and disseminate policy and programme changes. Conclusions: PAR in disease programmes can support health systems to embed cyclical and iterative learning to sustainably address localised equity challenges. However, it takes time, resources and political commitment

Mapping Oil and Gas Development Potential in the US Intermountain West and Estimating Impacts to Species

Many studies have quantified the indirect effect of hydrocarbon-based economies on climate change and biodiversity, concluding that a significant proportion of species will be threatened with extinction. However, few studies have measured the direct effect of new energy production infrastructure on species persistence. in the western US and translate the build-out scenarios into estimated impacts on sage-grouse. We project that future oil and gas development will cause a 7–19 percent decline from 2007 sage-grouse lek population counts and impact 3.7 million ha of sagebrush shrublands and 1.1 million ha of grasslands in the study area.Maps of where oil and gas development is anticipated in the US Intermountain West can be used by decision-makers intent on minimizing impacts to sage-grouse. This analysis also provides a general framework for using predictive models and build-out scenarios to anticipate impacts to species. These predictive models and build-out scenarios allow tradeoffs to be considered between species conservation and energy development prior to implementation

Archaeological sites as Distributed Long-term Observing Networks of the Past (DONOP)

The authors would also like to acknowledge the support of the National Science Foundation, specifically the Arctic Social Sciences Program, and RANNIS (The Icelandic Center for Research).Archaeological records provide a unique source of direct data on long-term human-environment interactions and samples of ecosystems affected by differing degrees of human impact. Distributed long-term datasets from archaeological sites provide a significant contribution to establish local, regional, and continental-scale environmental baselines and can be used to understand the implications of human decision-making and its impacts on the environment and the resources it provides for human use. Deeper temporal environmental baselines are essential for resource and environmental managers to restore biodiversity and build resilience in depleted ecosystems. Human actions are likely to have impacts that reorganize ecosystem structures by reducing diversity through processes such as niche construction. This makes data from archaeological sites key assets for the management of contemporary and future climate change scenarios because they combine information about human behavior, environmental baselines, and biological systems. Sites of this kind collectively form Distributed Long-term Observing Networks of the Past (DONOP), allowing human behavior and environmental impacts to be assessed over space and time. Behavioral perspectives are gained from direct evidence of human actions in response to environmental opportunities and change. Baseline perspectives are gained from data on species, landforms, and ecology over timescales that long predate our typically recent datasets that only record systems already disturbed by people. And biological perspectives can provide essential data for modern managers wanting to understand and utilize past diversity (i.e., trophic and/or genetic) as a way of revealing, and potentially correcting, weaknesses in our contemporary wild and domestic animal populations.PostprintPeer reviewe

ECLAIRE: Effects of Climate Change on Air Pollution Impacts and Response Strategies for European Ecosystems. Project final report

The central goal of ECLAIRE is to assess how climate change will alter the extent to which air pollutants threaten terrestrial ecosystems. Particular attention has been given to nitrogen compounds, especially nitrogen oxides (NOx) and ammonia (NH3), as well as Biogenic Volatile Organic Compounds (BVOCs) in relation to tropospheric ozone (O3) formation, including their interactions with aerosol components. ECLAIRE has combined a broad program of field and laboratory experimentation and modelling of pollution fluxes and ecosystem impacts, advancing both mechanistic understanding and providing support to European policy makers. The central finding of ECLAIRE is that future climate change is expected to worsen the threat of air pollutants on Europe’s ecosystems. Firstly, climate warming is expected to increase the emissions of many trace gases, such as agricultural NH3, the soil component of NOx emissions and key BVOCs. Experimental data and numerical models show how these effects will tend to increase atmospheric N deposition in future. By contrast, the net effect on tropospheric O3 is less clear. This is because parallel increases in atmospheric CO2 concentrations will offset the temperature-driven increase for some BVOCs, such as isoprene. By contrast, there is currently insufficient evidence to be confident that CO2 will offset anticipated climate increases in monoterpene emissions. Secondly, climate warming is found to be likely to increase the vulnerability of ecosystems towards air pollutant exposure or atmospheric deposition. Such effects may occur as a consequence of combined perturbation, as well as through specific interactions, such as between drought, O3, N and aerosol exposure. These combined effects of climate change are expected to offset part of the benefit of current emissions control policies. Unless decisive mitigation actions are taken, it is anticipated that ongoing climate warming will increase agricultural and other biogenic emissions, posing a challenge for national emissions ceilings and air quality objectives related to nitrogen and ozone pollution. The O3 effects will be further worsened if progress is not made to curb increases in methane (CH4) emissions in the northern hemisphere. Other key findings of ECLAIRE are that: 1) N deposition and O3 have adverse synergistic effects. Exposure to ambient O3 concentrations was shown to reduce the Nitrogen Use Efficiency of plants, both decreasing agricultural production and posing an increased risk of other forms of nitrogen pollution, such as nitrate leaching (NO3-) and the greenhouse gas nitrous oxide (N2O); 2) within-canopy dynamics for volatile aerosol can increase dry deposition and shorten atmospheric lifetimes; 3) ambient aerosol levels reduce the ability of plants to conserve water under drought conditions; 4) low-resolution mapping studies tend to underestimate the extent of local critical loads exceedance; 5) new dose-response functions can be used to improve the assessment of costs, including estimation of the value of damage due to air pollution effects on ecosystems, 6) scenarios can be constructed that combine technical mitigation measures with dietary change options (reducing livestock products in food down to recommended levels for health criteria), with the balance between the two strategies being a matter for future societal discussion. ECLAIRE has supported the revision process for the National Emissions Ceilings Directive and will continue to deliver scientific underpinning into the future for the UNECE Convention on Long-range Transboundary Air Pollution