Psychometrics of patient-reported bother from side effects of treatment single-items in industry-sponsored oncology trials.

BACKGROUND: Improvements in cancer treatment have increased the number of cancer survivors, but also increased the long-term and late effects from cancer therapy. Patient reported "side effect bother" could be used to measure the burden of treatment, and the risk for negative outcomes such as dose reduction, treatment delay or discontinuation. The current study addresses the psychometric properties of a single item, determines what represents a "meaningful change", and evaluates the correlation to safety endpoints and functioning. METHODS: Results from 5911 patients enrolled in 8 clinical trials representing 5 disease types in oncology and hematology who completed either the Functional Assessment of Cancer Therapy (FACT) GP5 item or a modified bother item (MBI) were assessed. RESULTS: Patients ranged in age from 18 to 93 years, with all cancer stages represented and approximately equal numbers of males and females. Test-retest reliability was acceptable, as were convergent and known groups validity. The GP5 and MBI effectively demonstrated sensitivity to change over time and established meaningful thresholds. CONCLUSIONS: The results indicate that these single-items are psychometrically sound, capable of distinguishing known groups, responsive to change and can identify meaningful change over time in terms of treatment-related symptoms. It extends the findings of recent scientific groups by providing analyses not included in prior studies, and further supports the FDA's recommendation to include a single item question in clinical trials.

The heritability of hemolysis in stored human red blood cells.

BACKGROUND: The transfusion of red blood cells (RBCs) with maximum therapeutic efficacy is a major goal in transfusion medicine. One of the criteria used in determining stored RBC quality is end-of-storage hemolysis. Between donors, a wide range of hemolysis is observed under identical storage conditions. Here, a potential mechanism for this wide range is investigated. We hypothesize that the magnitude of hemolysis is a heritable trait. Also, we investigated correlations between hemolysis and RBC metabolites; this will establish pathways influencing hemolysis as future targets for genetic analysis. STUDY DESIGN AND METHODS: Units of RBCs from identical and nonidentical twins were collected and stored under standard conditions for 56 days. Hemolysis, adenosine triphosphate (ATP), and total glutathione (tGSH) were measured throughout storage. Nontargeted metabolic analyses were performed on RBCs that had been stored for 28 days. Heritability was determined by comparing values between identical and nonidentical twins. RESULTS: Hemolysis was found to be heritable (mean > 45%) throughout the storage period. Potential correlations were observed between hemolysis and metabolites from the purine metabolism, lysolipid, and glycolysis pathways. These also exhibited heritability (>20%). No correlation was found with ATP or tGSH. CONCLUSION: The susceptibility of RBCs to lysis during storage is partly determined by inheritance. We have also uncovered several pathways that are candidate targets for future genomewide association studies. These findings will aid in the design of better storage solutions and the development of donor screening tools that minimize hemolysis during storage.

The heritability of metabolite concentrations in stored human red blood cells.

BACKGROUND: The degeneration of red blood cells (RBCs) during storage is a major issue in transfusion medicine. Family studies in the 1960s established the heritability of the RBC storage lesion based on poststorage adenosine triphosphate (ATP) concentrations. However, this critical discovery has not been further explored. In a classic twin study we confirmed the heritability of poststorage ATP concentrations and established the heritability of many other RBC metabolites. STUDY DESIGN AND METHODS: ATP concentrations and metabolomic profiles were analyzed in RBC samples from 18 twin pairs. On samples stored for 28 days, the heritability of poststorage ATP concentrations were 64 and 53% in CP2D- and AS-3-stored RBCs, respectively. RESULTS: Metabolomic analyses identified 87 metabolites with an estimated heritability of 20% or greater. Thirty-six metabolites were significantly correlated with ATP concentrations (p ≤ 0.05) and 16 correlated with borderline significance (0.05 ≤ p ≤ 0.10). Of the 52 metabolites that correlated significantly with ATP, 24 demonstrated 20% or more heritability. Pathways represented by heritable metabolites included glycolysis, membrane remodeling, redox homeostasis, and synthetic and degradation pathways. CONCLUSION: We conclude that many RBC metabolite concentrations are genetically influenced during storage. Future studies of key metabolic pathways and genetic modifiers of RBC storage could lead to major advances in RBC storage and transfusion therapy.

From good intentions to unexpected results - a cross-scale analysis of a fishery improvement project within the Indonesian blue swimming crab.

Private actors have become prominent players in the work to drive social and environmental sustainability transitions. In the fisheries sector, fishery improvement projects (FIPs) aim to address environmental challenges by leveraging the capacity of industry actors and using value chains to incentivize change. Despite globally rising FIP numbers, the incentive structures behind FIP establishment and the role of internal dynamics remain poorly understood. This paper uses institutional entrepreneurship as an analytical lens to examine the institutional change surrounding the management and trade of the Indonesian blue swimming crab and sheds light on how global market dynamics, local fishery dynamics, and value chain initiatives interact to affect the trajectory towards sustainability over time. We contribute to the institutional entrepreneurship framework by extending it with social-ecological dynamics, different actors' ability to realize or resist change, and outcomes of institutional change. These additions can improve its explanatory power in relation to sustainability initiatives in fisheries governance and beyond. Our cross-scale historical analysis of the value chain shows not only the entrepreneurship behind the FIP's establishment, and its institutional interventions, but also why these have been unsuccessful in improving the ecological sustainability of fishers' and traders' behavior. This provides valuable empirical grounding to a wider debate about industry leadership and private incentives for sustainability at large and helps disentangle under what conditions such initiatives are more (or less) likely to have intended effects. Supplementary Information: The online version contains supplementary material available at 10.1007/s40152-022-00285-y.

Whither the forest transition? Climate change, policy responses, and redistributed forests in the twenty-first century.

Forest transitions occur when net reforestation replaces net deforestation in places. Because forest transitions can increase biodiversity and augment carbon sequestration, they appeal to policymakers contending with the degrading effects of forest loss and climate change. What then can policymakers do to trigger forest transitions? The historical record over the last two centuries provides insights into the precipitating conditions. The early transitions often occurred passively, through the spontaneous regeneration of trees on abandoned agricultural lands. Later forest transitions occurred more frequently after large-scale crisis narratives emerged and spurred governments to take action, often by planting trees on degraded, sloped lands. To a greater degree than their predecessors, latecomer forest transitions exhibit centralized loci of power, leaders with clearly articulated goals, and rapid changes in forest cover. These historical shifts in forest transitions reflect our growing appreciation of their utility for countering droughts, floods, land degradation, and climate change.

Fishery Improvement Projects as a governance tool for fisheries sustainability: A global comparative analysis.

Fishery Improvement Projects (FIPs) are a form of private governance using seafood supply chains to reduce environmental impacts of fishing in some of the most challenged fisheries. Some FIPs are industry-led, others are championed by NGOs. They range across many different fishery types, in both high- and low-income settings. Their diversity is notable, and their proliferation remarkable. This rapid growth suggests FIPs are becoming a key feature of the fisheries governance landscape globally. Based on a global sample of 107 FIPs, we systematically examined their reported actions, the actors involved, and their achievements in terms of policy and practice outputs. The most common actions were dialogues with policy stakeholders, data collection, and educational efforts directed at fishers. Common policy outputs included development of management plans and/or a management body, and rules for limiting entry and increasing compliance. Practice related outputs were dominated by gear changes, and observer and traceability programs. Only crab and lobster FIPs engaged in sustained policy conversations as one of the most common actions. Shrimp and tuna fisheries report more engagement in testing and implementing changes to fishery practices. While supply chain actors are involved in all FIPs, retailers and 1st tier suppliers are relatively absent from FIP activities, and are primarily involved in rallying financial support or some policy engagement. Based on our analysis we discuss the opportunities and challenges FIPs will likely need to engage with to contribute to a global transition to more socially and environmentally sustainable fisheries. We outline key areas where further work is needed to understand how FIPs can improve their contribution to global fisheries governance in the future.

What does popular media have to tell us about the future of seafood?

We examined ∼300 newspaper and business-oriented articles published over a 10-year period to assess trends in how seafood "sustainability" is talked about. We mapped key concepts relating to seafood sustainability as the word was used. We asked if the reports provided evidence that perceptions of problems or solutions for sustainability in seafood have changed over time. What were emergent areas of interest, and what concepts relevant to sustainable fisheries and seafood were absent in the reports? The number of reports concerning sustainability that focused on the middle of the supply chain (e.g., primary processors and importers) increased over time; certification was cited as both part of sustainability problems and a solution. We observed very little change over time in the kinds of fishery and seafood problems reported in the media sampled; themes consistently focused on environmental aspects of fisheries (social wellbeing aspects did not appear in the sample as linked with the term "sustainability"); and very few media reports on sustainable seafood cited aquaculture as a solution. We discuss the gap between what many researchers may perceive as the state-of-the-art of ideas and communication in seafood sustainability, and what appeared empirically in media during the period under study.

Perpetuating the myth of the return of native forests.

Viña et al. imply that native forests account for China's marked increase in tree cover and that tree plantations play a minimal role. All 71 tweets linked to the article reinforce the idea that China's native forests are returning, whereas a review of their methodology indicates that it is not likely accurate. Referring news articles (n = 19) were dominated by terms associated with native forests, whereas tree plantations were rarely mentioned.

Plasma Metabolites and Risk of Radiation-induced Esophagitis: A Secondary Analysis from a Prospective Study.

AIM: Metabolic profiling was performed on plasma samples obtained prior to and during radiation therapy (RT) for locally advanced lung cancer to identify metabolites predictive of RT-induced esophagitis. PATIENTS AND METHODS: Patients received cisplatin/etoposide with RT as part of a prospective dose-escalation study (n=24). Plasma samples were collected at baseline, weeks 2 and 5 during RT, and 6 weeks post-RT. Metabolites were measured by ultrahigh-performance liquid chromatography-tandem mass spectroscopy at each time-point. Metabolite concentrations were compared between patients developing grade 0-1 and those with grade 2 or more esophagitis. RESULTS: At baseline, 23 metabolites differed significantly (p<0.05) between patients with grade 0-1 esophagitis and those with grade 2 or esophagitis. Sixty-seven metabolites were different at week 2. None reached statistical significance (q<0.05) after corrections for multiple comparisons. On random forest modeling, the predictive accuracy of the metabolite data was 33% at baseline and 50% at 2 weeks. CONCLUSION: No individual metabolite or group of metabolites was predictive of acute RT-induced esophagitis.

The consequences of landscape change on fishing strategies.

We show how land-use change can affect fisher-harvesting behavior. We test whether fisher harvesting behavior can be predicted by landscape change patterns at local (~200km) and regional (~1200km) levels. Our data suggest that fishers harvesting in areas near tree plantations reduced benthic-invertebrate harvests in favor of demersal and pelagic finfish that are usually located further offshore. Fishers' management areas, which were near tree plantations, had higher chlorophyll-a values, and contained shellfish with more endobionts. Technology (owning a boat) and experience (age, years fishing, and alternative livelihoods) explained little in fisher-harvesting behavior. The flagship Chilean fisheries management program and seafood companies sourcing from these areas will need to respond to these new challenges. Despite complexities in designing cross-scale, social-ecological studies, we can no longer ignore the interconnectedness of commodities in the biosphere.

The Role of Datasets on Scientific Influence within Conflict Research.

We inductively tested if a coherent field of inquiry in human conflict research emerged in an analysis of published research involving "conflict" in the Web of Science (WoS) over a 66-year period (1945-2011). We created a citation network that linked the 62,504 WoS records and their cited literature. We performed a critical path analysis (CPA), a specialized social network analysis on this citation network (~1.5 million works), to highlight the main contributions in conflict research and to test if research on conflict has in fact evolved to represent a coherent field of inquiry. Out of this vast dataset, 49 academic works were highlighted by the CPA suggesting a coherent field of inquiry; which means that researchers in the field acknowledge seminal contributions and share a common knowledge base. Other conflict concepts that were also analyzed-such as interpersonal conflict or conflict among pharmaceuticals, for example, did not form their own CP. A single path formed, meaning that there was a cohesive set of ideas that built upon previous research. This is in contrast to a main path analysis of conflict from 1957-1971 where ideas didn't persist in that multiple paths existed and died or emerged reflecting lack of scientific coherence (Carley, Hummon, and Harty, 1993). The critical path consisted of a number of key features: 1) Concepts that built throughout include the notion that resource availability drives conflict, which emerged in the 1960s-1990s and continued on until 2011. More recent intrastate studies that focused on inequalities emerged from interstate studies on the democracy of peace earlier on the path. 2) Recent research on the path focused on forecasting conflict, which depends on well-developed metrics and theories to model. 3) We used keyword analysis to independently show how the CP was topically linked (i.e., through democracy, modeling, resources, and geography). Publically available conflict datasets developed early on helped shape the operationalization of conflict. In fact, 94% of the works on the CP that analyzed data either relied on publically available datasets, or they generated a dataset and made it public. These datasets appear to be important in the development of conflict research, allowing for cross-case comparisons, and comparisons to previous works.

Metabolite Profiles of the Serum of Patients with Non-Small Cell Carcinoma.

INTRODUCTION: Alterations of serum metabolites may allow us to identify individuals with lung cancer and advance our understanding of the nature and treatment of their cancer. We aimed to identify serum metabolites that differentiate patients with lung cancer from at-risk controls. METHODS: Serum samples from patients with biopsy-confirmed untreated stage I through stage III non-small cell lung cancer and at-risk controls were divided into fractions for analysis by ultrahigh-performance liquid chromatography-tandem mass spectrometry and gas chromatography-mass spectrometry. Compounds were identified by comparison with library entries of purified standards. Differences in concentrations of single metabolites and metabolite ratios were identified. Prediction models were developed. RESULTS: Serum samples from 284 subjects was analyzed. The subjects' mean age was 67 and 48% were female. Ninety-four patients had lung cancer (50 had adenocarcinoma and 44 had squamous cell carcinoma), 44% had stage I disease, 17% had stage II disease, and 39% had stage III disease. The patients with cancer were slightly older than the controls (68.7 versus 66.2 years, p = 0.013). A total of 534 metabolites were identified in eight metabolite superpathways and 73 subpathways. The concentrations of 149 metabolites differed significantly (q values <0.05) between the cancer and control groups (70 were lower in the cancer group and 79 were higher), and 9723 metabolite ratios differed significantly (q values <0.001) between the cancer and control groups. The accuracies of the models (cancer and cancer subtypes versus control) trained on 70% of the subjects and tested on 30% (expressed as C-statistics) ranged from 0.748 to 0.858. CONCLUSIONS: Differences in the serum metabolite profile exist between patients with stage I through stage III non-small cell lung cancer and matched controls.