Anthropogenic environmental change is exposing animals to changes in a complex array of interacting stressors and is already having important effects on the distribution and abundance of species. ...However, despite extensive examination of the effects of stressors in isolation, knowledge of the effects of stressors in combination is limited. This lack of information makes predicting the responses of organisms to anthropogenic environmental change challenging. Here, we focus on the effects of temperature and hypoxia as interacting stressors in fishes. A review of the available evidence suggests that temperature and hypoxia act synergistically such that small shifts in one stressor could result in large effects on organismal performance when a fish is exposed to the 2 stressors in combination. Although these stressors pose substantial challenges for fish, there also is substantial intraspecific variation in tolerance to these stressors that could act as the raw material for the evolution of improved tolerance. However, the potential for adaptive change is, in part, dependent on the nature of the correlations among traits associated with tolerance. For example, negative genetic correlations (or trade-offs) between tolerances to temperature and hypoxia could limit the potential for adaptation to the combined stressors, while positive genetic correlations might be of benefit. The limited data currently available suggest that tolerances to hypoxia and to high-temperature may be positively correlated in some species of fish, suggesting the possibility for adaptive evolution in these traits in response to anthropogenic environmental change.
Focal brain damage after aneurysmal subarachnoid haemorrhage predominantly results from intracerebral haemorrhage, and early and delayed cerebral ischaemia. The prospective, observational, ...multicentre, cohort, diagnostic phase III trial, DISCHARGE-1, primarily investigated whether the peak total spreading depolarization-induced depression duration of a recording day during delayed neuromonitoring (delayed depression duration) indicates delayed ipsilateral infarction. Consecutive patients (n = 205) who required neurosurgery were enrolled in six university hospitals from September 2009 to April 2018. Subdural electrodes for electrocorticography were implanted. Participants were excluded on the basis of exclusion criteria, technical problems in data quality, missing neuroimages or patient withdrawal (n = 25). Evaluators were blinded to other measures. Longitudinal MRI, and CT studies if clinically indicated, revealed that 162/180 patients developed focal brain damage during the first 2 weeks. During 4.5 years of cumulative recording, 6777 spreading depolarizations occurred in 161/180 patients and 238 electrographic seizures in 14/180. Ten patients died early; 90/170 developed delayed infarction ipsilateral to the electrodes. Primary objective was to investigate whether a 60-min delayed depression duration cut-off in a 24-h window predicts delayed infarction with >0.60 sensitivity and >0.80 specificity, and to estimate a new cut-off. The 60-min cut-off was too short. Sensitivity was sufficient = 0.76 (95% confidence interval: 0.65-0.84), P = 0.0014 but specificity was 0.59 (0.47-0.70), i.e. <0.80 (P < 0.0001). Nevertheless, the area under the receiver operating characteristic (AUROC) curve of delayed depression duration was 0.76 (0.69-0.83, P < 0.0001) for delayed infarction and 0.88 (0.81-0.94, P < 0.0001) for delayed ischaemia (reversible delayed neurological deficit or infarction). In secondary analysis, a new 180-min cut-off indicated delayed infarction with a targeted 0.62 sensitivity and 0.83 specificity. In awake patients, the AUROC curve of delayed depression duration was 0.84 (0.70-0.97, P = 0.001) and the prespecified 60-min cut-off showed 0.71 sensitivity and 0.82 specificity for reversible neurological deficits. In multivariate analysis, delayed depression duration (β = 0.474, P < 0.001), delayed median Glasgow Coma Score (β = -0.201, P = 0.005) and peak transcranial Doppler (β = 0.169, P = 0.016) explained 35% of variance in delayed infarction. Another key finding was that spreading depolarization-variables were included in every multiple regression model of early, delayed and total brain damage, patient outcome and death, strongly suggesting that they are an independent biomarker of progressive brain injury. While the 60-min cut-off of cumulative depression in a 24-h window indicated reversible delayed neurological deficit, only a 180-min cut-off indicated new infarction with >0.60 sensitivity and >0.80 specificity. Although spontaneous resolution of the neurological deficit is still possible, we recommend initiating rescue treatment at the 60-min rather than the 180-min cut-off if progression of injury to infarction is to be prevented.
The Chesapeake Bay watershed is representative of governance challenges relating to agricultural nonpoint source pollution and, more generally, of sustainable resources governance in complex ...multi-actor settings. We assess information flows around Best Management Practices (BMPs) undertaken by dairy farmers in central Pennsylvania, a subregion of the watershed. We apply a mixed-method approach, combining Social Network Analysis, the analysis of BMP-messaging (i.e. information source, flow, and their influences), and qualitative content analysis of stakeholders' interviews. Key strategic actors were identified through network centrality measures such as degree of node, betweenness centrality, and clustering coefficient. The perceived influence/credibility (by farmers) of BMP-messages and their source, allowed for the identification of strategic entry points for BMP-messages diffusion. Finally, the inductive coding process of stakeholders' interviews revealed major hindrances and opportunities for BMPs adoption. We demonstrate how improved targeting of policy interventions for BMPs uptake may be achieved, by better distributing entry-points across stakeholders. Our results reveal governance gaps and opportunities, on which we draw to provide insights for better tailored policy interventions. We propose strategies to optimize the coverage of policy mixes and the dissemination of BMP-messages by building on network diversity and actors' complementarities, and by targeting intervention towards specific BMPs and actors. We suggest that (i) conservation incentives could target supply chain actors as conservation intermediaries; (ii) compliance-control of manure management planning could be conducted by accredited private certifiers; (iii) policy should focus on incentivizing inter-farmers interaction (e.g. farmers' mobility, training, knowledge-exchange, and engagement in multi-stakeholders collaboration) via financial or non-pecuniary compensation; (iv) collective incentives could help better coordinate conservation efforts at the landscape or (sub-)watershed scale; (v) all relevant stakeholders (including farmers) should be concerted and included in the discussion, proposition, co-design and decision process of policy, in order to take their respective interests and responsibilities into account.
Dysfunction of neuroplasticity due to N-methyl-d-aspartate (NMDA) receptor hypofunction may be a causal factor for memory and executive dysfunctioning in schizophrenia. Deregulation of NMDA ...transmission in the prefrontal cortex may also explain negative and positive symptoms. Clozapine augmentation with memantine targets altered NMDA receptor-mediated neurotransmission in schizophrenia and showed substantial beneficial effects on several symptom domains in a small proof-of-concept study. We evaluate effects of memantine add-on treatment to clozapine for memory and executive function, and negative and positive symptoms in schizophrenia.
Clozapine-treated patients with refractory schizophrenia were randomly assigned to 12 weeks of double-blind adjunctive treatment with memantine (n = 26) or placebo (n = 26). Crossover occurred after a 2-week placebo wash-out period. Primary endpoints were change from baseline to 12 weeks treatment and 14 weeks to 26 weeks treatment on memory and executive function using the Cambridge Neuropsychological Test Automated Battery (CANTAB), Positive and Negative Syndrome Scale (PANSS), and Clinical Global Impression Severity Scale (CGI-S). Side effects were assessed using the Liverpool University Neuroleptic Side-Effect Rating Scale.
When compared with placebo, memantine improved a composite memory score comprising verbal recognition memory and paired associates learning task scores on the CANTAB (effect size = 0.30) and PANSS negative subscale score (effect size = 0.29). Side effects were mild and transient.
In patients with clozapine-treated refractory schizophrenia, memantine addition significantly improved verbal and visual memory and negative symptoms without serious adverse effects. These results justify further investigations on long-term memantine augmentation to clozapine in treatment-resistant schizophrenia.
Lecture is prominent, but practices vary
A large body of evidence demonstrates that strategies that promote student interactions and cognitively engage students with content (
1
) lead to gains in ...learning and attitudinal outcomes for students in science, technology, engineering, and mathematics (STEM) courses (
1
,
2
). Many educational and governmental bodies have called for and supported adoption of these student-centered strategies throughout the undergraduate STEM curriculum. But to the extent that we have pictures of the STEM undergraduate instructional landscape, it has mostly been provided through self-report surveys of faculty members, within a particular STEM discipline e.g., (
3
–
6
). Such surveys are prone to reliability threats and can underestimate the complexity of classroom environments, and few are implemented nationally to provide valid and reliable data (
7
). Reflecting the limited state of these data, a report from the U.S. National Academies of Sciences, Engineering, and Medicine called for improved data collection to understand the use of evidence-based instructional practices (
8
). We report here a major step toward a characterization of STEM teaching practices in North American universities based on classroom observations from over 2000 classes taught by more than 500 STEM faculty members across 25 institutions.
•A growing number of workers are exposed to engineered nanomaterials.•Exposure to some engineered nanomaterials may cause health effects in workers.•There is a rich literature on biomarkers of ...exposure and effect from exposure to engineered nanomaterials.•Biomonitoring of workers may ultimately be of utility as tool for exposure assessment and risk management.•Further research is needed to validate biomarkers for biomonitoring nanomaterial workers.
As the number of nanomaterial workers increase there is need to consider whether biomonitoring of exposure should be used as a routine risk management tool. Currently, no biomonitoring of nanomaterials is mandated by authoritative or regulatory agencies. However, there is a growing knowledge base to support such biomonitoring, but further research is needed as are investigations of priorities for biomonitoring. That research should be focused on validation of biomarkers of exposure and effect. Some biomarkers of effect are generally nonspecific. These biomarkers need further interpretation before they should be used. Overall biomonitoring of nanomaterial workers may be important to supplement risk assessment and risk management efforts.
Nanotechnology is an emerging science involving manipulation of materials at the nanometer scale. There are several exciting prospects for the application of engineered nanomaterials in medicine. ...However, concerns over adverse and unanticipated effects on human health have also been raised. In fact, the same properties that make engineered nanomaterials attractive from a technological and biomedical perspective could also make these novel materials harmful to human health and the environment. Carbon nanotubes are cylinders of one or several coaxial graphite layer(s) with a diameter in the order of nanometers, and serve as an instructive example of the Janus-like properties of nanomaterials. Numerous in vitro and in vivo studies have shown that carbon nanotubes and/or associated contaminants or catalytic materials that arise during the production process may induce oxidative stress and prominent pulmonary inflammation. Recent studies also suggest some similarities between the pathogenic properties of multi-walled carbon nanotubes and those of asbestos fibers. On the other hand, carbon nanotubes can be readily functionalized and several studies on the use of carbon nanotubes as versatile excipients for drug delivery and imaging of disease processes have been reported, suggesting that carbon nanotubes may have a place in the armamentarium for treatment and monitoring of cancer, infection, and other disease conditions. Nanomedicine is an emerging field that holds great promise; however, close attention to safety issues is required to ensure that the opportunities that carbon nanotubes and other engineered nanoparticles offer can be translated into feasible and safe constructs for the treatment of human disease.
Food labeling is the major health policy strategy to counter rising obesity rates. Based on traditional economic theory, such strategies assume that detailed nutritional information will necessarily ...help individuals make better, healthier choices. However, in contrast to the well-known utility of labels in food marketing, evidence for the efficacy of nutritional labeling is mixed. Psychological and behavioral economic theories suggest that successful marketing strategies activate automatic decision biases and emotions, which involve implicit emotional brain systems. Accordingly, simple, intuitive food labels that engage these neural systems could represent a promising approach for promoting healthier choices. Here we used functional MRI to investigate this possibility. Healthy, mildly hungry subjects performed a food evaluation task and a food choice task. The main experimental manipulation was to pair identical foods with simple labels that emphasized either taste benefits or health-related food properties. We found that such labels biased food evaluations in the amygdala, a core emotional brain system. When labels biased the amygdala's evaluations towards health-related food properties, the strength of this bias predicted behavioral shifts towards healthier choices. At the time of decision-making, amygdala activity encoded key decision variables, potentially reflecting active amygdala participation in food choice. Our findings underscore the potential utility of food labeling in health policy and indicate a principal role for emotional brain systems when labels guide food choices.
► Simple, incidental labels bias food evaluations in the amygdala. ► Biased valuations in the amygdala predict healthier food choices. ► Coding of decision variables in the amygdala suggests involvement in choices. ► Food labels in marketing and health policy may act on emotional brain systems.
The commercialization of engineered nanomaterials (ENMs) began in the early 2000's. Since then the number of commercial products and the number of workers potentially exposed to ENMs is growing, as ...is the need to evaluate and manage the potential health risks. Occupational exposure limits (OELs) have been developed for some of the first generation of ENMs. These OELs have been based on risk assessments that progressed from qualitative to quantitative as nanotoxicology data became available. In this paper, that progression is characterized. It traces OEL development through the qualitative approach of general groups of ENMs based primarily on read-across with other materials to quantitative risk assessments for nanoscale particles including titanium dioxide, carbon nanotubes and nanofibers, silver nanoparticles, and cellulose nanocrystals. These represent prototypic approaches to risk assessment and OEL development for ENMs. Such substance-by-substance efforts are not practical given the insufficient data for many ENMs that are currently being used or potentially entering commerce. Consequently, categorical approaches are emerging to group and rank ENMs by hazard and potential health risk. The strengths and limitations of these approaches are described, and future derivations and research needs are discussed. Critical needs in moving forward with understanding the health effects of the numerous EMNs include more standardized and accessible quantitative data on the toxicity and physicochemical properties of ENMs.
•Reviews the progression of risk assessments used for engineered nanomaterials.•Includes examples for titanium dioxide, carbon nanotubes, nanosilver, nanocellulose.•Identifies approaches for categorical risk assessments.•Risk assessments is likely to shift to focus towards early biological events.
Soil is the most important natural resource for life on Earth after water. Given its fundamental role in sustaining the human population, both the availability and quality of soil must be managed ...sustainably and protected. To ensure sustainable management we need to understand the intrinsic functional capacity of different soils across Europe and how it changes over time. Soil monitoring is needed to support evidence-based policies to incentivise sustainable soil management. To this aim, we assessed which soil attributes can be used as potential indicators of five soil functions; (1) primary production, (2) water purification and regulation, (3) carbon sequestration and climate regulation, (4) soil biodiversity and habitat provisioning and (5) recycling of nutrients. We compared this list of attributes to existing national (regional) and EU-wide soil monitoring networks. The overall picture highlighted a clearly unbalanced dataset, in which predominantly chemical soil parameters were included, and soil biological and physical attributes were severely under represented. Methods applied across countries for indicators also varied. At a European scale, the LUCAS-soil survey was evaluated and again confirmed a lack of important soil biological parameters, such as C mineralisation rate, microbial biomass and earthworm community, and soil physical measures such as bulk density. In summary, no current national or European monitoring system exists which has the capacity to quantify the five soil functions and therefore evaluate multi-functional capacity of a soil and in many countries no data exists at all. This paper calls for the addition of soil biological and some physical parameters within the LUCAS-soil survey at European scale and for further development of national soil monitoring schemes.