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Diffusing alpha-emitters Radiation Therapy (DaRT) releases alpha-emitting atoms into the tumor microenvironment. The treatment effectively ablates human and mice xenografts and shows 100% response rates in skin or head and neck squamous cell carcinoma patients. DaRT induces specific and systemic antitumor immune activation and synergizes with immune stimulation and modulation in mice. Here, the transcriptional profile activated by DaRT, and its potential to enhance responsiveness to immune checkpoint inhibition by programmed cell death protein 1 (PD-1) blockade were studied.Squamous cell carcinoma tumor- bearing BALB/C mice were treated with DaRT or inert seeds in combination with anti-PD-1 (aPD-1) or IgG control antibody. Sixteen days after seed insertion, tumors and spleens were subjected to immunophenotyping and immunohistochemical staining. Combination of DaRT and aPD-1 was tested for efficacy. Gene expression analysis was performed on mRNA extracted from tumors 7 days after DaRT or inert insertion using Nanostring PanCancer-IO-360 panel, and tumors and spleens were subjected to flow cytometry analysis.DaRT in combination with aPD-1 delayed tumor development, induced CD3 and CD8 lymphocytes infiltration more efficiently than either monotherapy. The combined treatment reduced splenic polymorphonuclear myeloid derived suppressor cells more than aPD-1 therapy or control. Granzyme B release in the tumor was increased only in the combinational treatment and was correlated with T-lymphocyte infiltration. Gene expression and gene set enrichment analysis of mRNA levels 7 days after DaRT insertion indicated that DaRT upregulated apoptosis, p53 signaling, G1/S-related arrest, interferon signaling and myeloid related transcription, while downregulating DNA repair, cell proliferation, and notch-related transcription. Flow cytometry showed that DaRT increased dendritic cells activation and led to changes in MDSCs distribution.DaRT promotes a "hot" tumor microenvironment and changes in immune suppression that lead to a potentiation of aPD-1 blockade induced effector T cell function and improved treatment efficacy. This study provides rationale for investigating DaRT and aPD-1 combination in patients with squamous cell carcinoma.

Theory of Change (ToC) has been promoted as a useful tool in sustainability research for visioning, planning, communication, monitoring, evaluation and learning. It involves a mapping of steps towards a desired long-term goal supplemented with continuous reflection on how and why change is expected to happen in a particular context. However, there is limited reported experience with the development and application of ToCs in inter- and transdisciplinary research contexts. While some previous publications have focused on ex-post application, there has been little discussion about the process of developing and using ToCs in strategic planning and monitoring in large inter- and transdisciplinary research programs. This article reports challenges and lessons learned from the experience of developing and using ToCs in the inter- and transdisciplinary research program Wings (Water and sanitation innovations for non-grid solutions). Challenges include (1) managing time constraints, (2) balancing between concrete and abstract discussions, (3) ensuring diversity in group composition, (4) fluctuating between reservations and appreciation, and (5) fulfilling both service and science roles while leading the ToC process. The experience highlights the importance of alternating formal and informal interaction formats throughout the process, ensuring heterogenous group formation, involving early career scientists, being responsive to emergent needs and making the added value of developing and using ToCs explicit and tangible for all participants. Although these lessons are mainly derived from developing ToCs within the interdisciplinary program team, they can support other programs in both their inter- and transdisciplinary research endeavors.

Background: Combined peripheral occipital and trigeminal neurostimulation is clinically proven to alleviate migraine symptoms, however, it was previously possible only via high-risk surgical procedures. Neuromodulation using currently available peripheral nerve stimulation devices stimulates only one nerve. The objective of this prospective, randomized, double-blind, sham-controlled trial was to evaluate the efficacy, safety and tolerability of a novel external concurrent occipital and trigeminal neurostimulation (eCOT-NS) device designed as a self-administered home treatment for migraine (Relivion® MG, Neurolief, Ltd; Netanya, Israel).Methods: Episodic and chronic migraine subjects (N=55) were randomized to receive active (n=27) or sham (n=28) treatment. Each subject received an eCOT-NS device and performed a 60 ±20-minute treatment at home within 45 minutes of migraine episode onset. The primary endpoint was the change in mean baseline pain intensity based on VAS pain scores 1 hour after treatment initiation, defined as relative (percent) change. Treatment outcomes assessed at 1, 2 and 24 hours post-treatment initiation were pain-reduction, and proportion of pain-free subjects and treatment responders, defined as ≥50% pain reduction. Categorical pain ratings (none, mild, moderate, and severe pain) were also analyzed.Results: Active stimulation was significantly more effective than sham stimulation for decreasing pain intensity at 1 hour (53% vs.10%), 2 hours (52% vs. 17%) and 24-hours (71% vs. 34%). Pain-free ratings were greater for the active treatment arm at 1 hour (29.2% vs. 16%), 2 hours (41.7% vs. 20%) and 24 hours (65.2% vs. 40%). Subjects with moderate or severe migraine baseline pain who were pain-free at 2 hours was significantly greater among subjects receiving active treatment (43% vs. 10.5%). The responder rate was significantly higher among the active treatment group at 1 hour (67% vs. 20%), 2 hours (66.7% vs. 32%,) and 24 hours (78.3% vs. 48%). Overall headache-relief was significantly higher in the active treatment group at 1 hour (67% vs. 26%) and 2 hours (76% vs. 31.6%). Mild adverse events, reported by a minority of subjects, resolved spontaneously. Conclusions: eCOT-NS provides superior clinically meaningful relief and freedom of migraine pain compared to sham, offering a highly effective and safe non-pharmacological treatment for acute migraine.Trial registration: ClinicalTrials.gov Identifier NCT03398668.

Viruses are efficient metabolic engineers that actively rewire host metabolic pathways to support their lifecycle, presenting attractive metabolic targets for intervention. Here we chart the metabolic response of lung epithelial cells to SARS-CoV-2 infection in primary cultures and COVID-19 patient samples. Bulk and single-cell analyses show that viral replication induces endoplasmic stress and lipid accumulation. Protein expression screen suggests a role for viral proteins in mediating this metabolic response even in the absence of replication. Metabolism-focused drug screen showed that fenofibrate reversed lipid accumulation and blocked SARS-CoV-2 replication. Analysis of 3,233 Israeli patients hospitalized due to COVID-19 supported in vitro findings. Patients taking fibrates showed significantly lower markers of immunoinflammation and faster recovery. Additional corroboration was received by comparative epidemiological analysis from cohorts in Europe and the United States. A subsequent prospective interventional open-label study was carried out in 15 patients hospitalized with severe COVID-19. The patients were treated with 145 mg/day of nanocrystallized fenofibrate (TriCor®) in addition to standard-of-care. Patients receiving fenofibrate demonstrated a rapid reduction in inflammation and a significantly faster recovery compared to control patients admitted during the same period and treated with the standard-of-care. Taken together, our data show that elevated lipid metabolism underlies critical aspects of COVID-19 pathogenesis, suggesting that pharmacological modulation of lipid metabolism should be strongly considered for the treatment of coronavirus infection.

Purpose: To compare an analog visual scale in grading anterior chamber cells (ACC) to a modified Standardization of Uveitis Nomenclature (SUN) ACC scale. Method: A graphical representation of anterior chamber cells as a reference and a test set was created and shown to two groups of experienced uveitis experts. Group 1 was given the analog scale in written format, while group two was given the reference images for comparison. Each test subject was asked to provide the best approximation for each grade. Results: Eleven graders participated in phase 1. Correct grading occurred in 87.4% of cases. Discrepancies were seen at all grades. Only 3 of 11 graders were able to achieve a perfect score. Seven graders participated in phase 2. Agreement was 95.2% with 4/7 graders achieving a perfect score. Discrepancies were seen at higher grades only. Conclusions: ACC grading is improved by a visual grading scale, and interobserver variability is reduced.

Several works have reported on the antiepileptic impact of cannabis-based preparations in patients with treatment-resistant epilepsy (TRE). However, current formulations suffer from low bioavailability and side effects. PTL-101, an oral formulation containing highly purified cannabidiol (CBD) embedded in seamless gelatin matrix beadlets was designed to enhance bioavailability and maintain a constant gastrointestinal transit time.This phase II, prospective study was open to pediatric patients with TRE on stable antiepileptic drugs' (AEDs) doses, who experienced ≥4 seizures within four weeks of enrolment and with a history of ≥4 AEDs failing to provide seizure control. Following a 4-week observation period, patients began a 2-week dose-titration phase (up to ≤25mg/kg or 450mg, the lower of the two), followed by a 10-week maintenance treatment period. Caregivers recorded seizure frequency, type, and severity and ranked their global impressions after 7 and 12weeks of treatment. Responders were those showing a ≥50% reduction from baseline monthly seizure frequency. Safety assessments monitored vital signs, adverse effects, physical and neurological exams, and laboratory tests.Sixteen patients (age: 9.1±3.4) enrolled in the study; 11 completed the full treatment program. The average maintenance dose was 13.6±4.2mg/kg. Patient adherence to treatment regimens was 96.3±9.9%. By the end of the treatment period, 81.9% and 73.4±24.6% (p0.05) reductions from baseline median seizure count and monthly seizure frequency, respectively, were recorded. Responders' rate was 56%; two patients became fully seizure-free. By study end, 8 (73%) caregivers reported an improved/very much improved condition, and 9 (82%) reported reduced/very much reduced seizure severity. Most commonly reported treatment-related adverse effects were sleep disturbance/insomnia, (4 (25.0%) patients), followed by somnolence, increased seizure frequency, and restlessness (3 patients each (18.8%)). None were serious or severe, and all resolved.PTL-101 was safe and tolerable for use and demonstrated a potent seizure-reducing effect among pediatric patients with TRE.

Intrathecal morphine provides excellent analgesia after cesarean delivery; however, respiratory events such as apnea, bradypnea, and hypoxemia have been reported. The primary study aim was to estimate the number of apneas per subject, termed "apnea alert events" (AAEs) defined by no breath for 30-120 seconds, using continuous capnography in women who underwent cesarean delivery.We performed a prospective, observational study with institutional review board approval of women who underwent cesarean delivery with spinal anesthesia containing 150-µg intrathecal morphine. A STOP-Bang obstructive sleep apnea assessment was administered to all women. Women were requested to use continuous capnography and pulse oximetry for 24 hours after cesarean delivery. Nasal sampling cannula measured end-tidal carbon dioxide (EtCO2) and respiratory rate (RR), and oxygen saturation (SpO2) as measured by pulse oximetry. Capnography data were defined as "valid" when EtCO210 mm Hg, RR5 breaths per minute (bpm), SpO270%, or during apnea (AAE) defined as "no breath" (EtCO2,5 mm Hg) for 30-120 seconds. Individual respiratory variable alerts were 10-second means of EtCO210 mm Hg, RR8 bpm, and SpO294%. Nurse observations of RR (hourly and blinded to capnography) are reported.We recruited 80 women, mean (standard deviation [SD]) 35 (5) years, 47% body mass index30 kg/m2/weight90 kg, and 11% with suspected obstructive sleep apnea (known or STOP-Bang score3). The duration of normal capnography and pulse oximetry data was mean (SD) (range) 8:28 (7:51) (0:00-22:32) and 15:08 (6:42) (1:31-23:07) hours:minutes, respectively; 6 women did not use the capnography. There were 198 AAEs, mean (SD) duration 57 (27) seconds experienced by 39/74 (53%) women, median (95% confidence interval for median) (range) 1 (0-1) (0-29) per subject. Observation of RR by nurses was ≥14 bpm at all time-points for all women, r = 0.05 between capnography and nurse RR (95% confidence interval, -0.04 to 0.14). There were no clinically relevant adverse events for any woman. Sixty-five women (82%) had complaints with the capnography device, including itchy nose, nausea, interference with nursing baby, and overall inconvenience.We report 198 AAEs detected by capnography among women who underwent cesarean delivery after receiving intrathecal morphine. These apneas were not confirmed by the intermittent hourly nursing observations. Absence of observer verification precludes distinction between real, albeit nonclinically significant alerts with capnography versus false apneas. Discomfort with the nasal sampling cannula and frequent alerts may impact capnography application after cesarean delivery. No clinically relevant adverse events occurred.

Background Posttraumatic stress disorder (PTSD) is both prevalent and debilitating. While deep transcranial magnetic stimulation (dTMS) has shown preliminary efficacy, exposure therapy remains the most efficacious, though limited, treatment in PTSD. The medial prefrontal cortex (mPFC) is implicated in extinction learning, suggesting that concurrent mPFC stimulation may enhance exposure therapy. In this randomized controlled multicenter trial, the efficacy and safety of mPFC dTMS combined with a brief exposure procedure were studied in patients with PTSD. Methods Immediately following exposure to their trauma narrative, 125 outpatients were randomly assigned to receive dTMS or sham. Twelve sessions were administered over 4 weeks, with a primary end point of change in 5-week Clinician-Administered PTSD Scale for DSM-5 score. This clinical study did not include biological markers. Results Clinician-Administered PTSD Scale for DSM-5 score improved significantly in both groups at 5 weeks, though the improvement was smaller in the dTMS group (16.32) compared with the sham group (20.52; p = .027). At 9 weeks, improvement continued in Clinician-Administered PTSD Scale for DSM-5 score in both groups but remained smaller in dTMS (19.0) versus sham (24.4; p = .024). Conclusions Both groups showed significant PTSD symptom improvement, possibly from the brief script-driven imagery exposure. While our design was unable to rule out placebo effects, the magnitude and durability of improvement suggest that repeated ultrabrief exposure therapy alone may be an effective treatment for PTSD, warranting additional study. The surprising and unexpected effect in the dTMS group also suggests that repeated mPFC stimulation with the H7 coil may interfere with trauma memory–mediated extinction. Our results provide new insight for dTMS approaches for possible future avenues to treat PTSD.

BackgroundThe National Lung Screening Trial (NLST) demonstrated that annual screening with low dose CT in high-risk population was associated with reduction in lung cancer mortality. Nonetheless, the leading cause of mortality in the study was from cardiovascular diseases.PurposeTo determine whether the used machine learning automatic algorithms assessing coronary calcium score (CCS), level of liver steatosis and emphysema percentage in the lungs are good predictors of cardiovascular disease (CVD) mortality and incidence when applied on low dose CT scans.Materials and methodsThree fully automated machine learning algorithms were used to assess CCS, level of liver steatosis and emphysema percentage in the lung. The algorithms were used on low-dose computed tomography scans acquired from 12,332 participants in NLST.ResultsIn a multivariate analysis, association between the three algorithm scores and CVD mortality have shown an OR of 1.72 (p = 0.003), 2.62 (p < 0.0001) for CCS scores of 101-400 and above 400 respectively, and an OR of 1.12 (p = 0.044) for level of liver steatosis. Similar results were shown for the incidence of CVD, OR of 1.96 (p < 0.0001), 4.94 (p < 0.0001) for CCS scores of 101-400 and above 400 respectively. Also, emphysema percentage demonstrated an OR of 0.89 (p < 0.0001). Similar results are shown for univariate analyses of the algorithms.ConclusionThe three automated machine learning algorithms could help physicians to assess the incidence and risk of CVD mortality in this specific population. Application of these algorithms to existing LDCT scans can provide valuable health care information and assist in future research.

Sudden disruptions, or shocks, to food production can adversely impact access to and trade of food commodities. Seafood is the most traded food commodity and is globally important to human nutrition. The seafood production and trade system is exposed to a variety of disruptions including fishery collapses, natural disasters, oil spills, policy changes, and aquaculture disease outbreaks, aquafeed resource access and price spikes. The patterns and trends of these shocks to fisheries and aquaculture are poorly characterized and this limits the ability to generalize or predict responses to political, economic, and environmental changes. We applied a statistical shock detection approach to historic fisheries and aquaculture data to identify shocks over the period 1976–2011. A complementary case study approach was used to identify possible key social and political dynamics related to these shocks. The lack of a trend in the frequency or magnitude of the identified shocks and the range of identified causes suggest shocks are a common feature of these systems which occur due to a variety, and often multiple and simultaneous, causes. Shocks occurred most frequently in the Caribbean and Central America, the Middle East and North Africa, and South America, while the largest magnitude shocks occurred in Asia, Europe, and Africa. Shocks also occurred more frequently in aquaculture systems than in capture systems, particularly in recent years. In response to shocks, countries tend to increase imports and experience decreases in supply. The specific combination of changes in trade and supply are context specific, which is highlighted through four case studies. Historical examples of shocks considered in this study can inform policy for responding to shocks and identify potential risks and opportunities to build resilience in the global food system.

Objective To compare the reported accuracy and sensitivity of the various modalities used to diagnose autism spectrum disorders (ASD) in efforts to help focus further biomarker research on the most promising methods for early diagnosis. Methods The Medline scientific literature database was searched to identify publications assessing potential clinical ASD biomarkers. Reports were categorized by the modality used to assess the putative markers, including protein, genetic, metabolic, or objective imaging methods. The reported sensitivity, specificity, area under the curve, and overall agreement were summarized and analyzed to determine weighted averages for each diagnostic modality. Heterogeneity was measured using the I2 test. Results Of the 71 papers included in this analysis, each belonging to one of five modalities, protein-based followed by metabolite-based markers provided the highest diagnostic accuracy, each with a pooled overall agreement of 83.3% and respective weighted area under the curve (AUC) of 89.5% and 88.3%. Sensitivity provided by protein markers was highest (85.5%), while metabolic (85.9%) and protein markers (84.7%) had the highest specificity. Other modalities showed degrees of sensitivity, specificity, and overall agreements in the range of 73%-80%. Conclusions Each modality provided for diagnostic accuracy and specificity similar or slightly higher than those reported for the gold-standard Autism Diagnostic Observation Schedule (ADOS) instrument. Further studies are required to identify the most predictive markers within each modality and to evaluate biological pathways or clustering with possible etiological relevance. Analyses will also be necessary to determine the potential of these novel biomarkers in diagnosing pediatric patients, thereby enabling early intervention.

Fil: Rocha, Juan C. Stockholm University. Stockholm Resilience Centre. Stockholm, Suecia. Fil: Baraibar, Matilda M. Stockholm University. Department of Economic History and International Relations. Stockholm, Suecia. Fil: Deutsch, Lisa. Stockholm University. Stockholm Resilience Centre. Stockholm, Suecia. Fil: Bremond, Ariane de. University of Bern. Centre for Development and Environment. Bern, Suiza. Fil: Oestreicher, Jordan S. Universidade de Brasília. Centro de Desenvolvimento Sustentável. Distrito Federal, Brasil. Fil: Rositano, Florencia. Universidad de Buenos Aires. Facultad de Agronomía. Departamento de Producción Vegetal. Cátedra de Cerealicultura. Buenos Aires, Argentina. Fil: Gelabert, Cecilia Corina. Universidad de Buenos Aires. Facultad de Agronomía. Departamento de Economía, Desarrollo y Planeamiento Agrícola. Cátedra de Sistemas Agroalimentarios. Buenos Aires, Argentina. Climate change, financial shocks, and fluctuations in international trade are some of the reasons why resilience is increasingly invoked in discussions about land-use policy. However, resilience assessments come with the challenge of operationalization, upscaling their conclusions while considering the context-specific nature of land-use dynamics and the common lack of long-term data. We revisit the approach of system archetypes for identifying resilience surrogates and apply it to land-use systems using seven case studies spread across Latin America. The approach relies on expert knowledge and literature-based characterizations of key processes and patterns of land-use change synthesized in a data template. These narrative accounts are then used to guide development of causal networks, from which potential surrogates for resilience are identified. This initial test of the method shows that deforestation, international trade, technological improvements, and conservation initiatives are key drivers of land-use change, and that rural migration, leasing and land pricing, conflicts in property rights, and international spillovers are common causal pathways that underlie land-use transitions. Our study demonstrates how archetypes can help to differentiate what is generic from context dependant. They help identify common causal pathways and leverage points across cases to further elucidate how policies work and where, as well as what policy lessons might transfer across heterogeneous settings. tbls., grafs., mapas

OBJECTIVE:Complex Regional Pain Syndrome (CRPS), a chronic pain condition, develops mainly after limb trauma and severely inhibits function. While early diagnosis is essential, factors for CRPS onset are elusive. Therefore, identifying those at risk is crucial. Sensory modulation dysfunction (SMD), affects the capacity to regulate responses to sensory input in a graded and adaptive manner and was found associated with hyperalgesia in otherwise healthy individuals, suggestive of altered pain processing. AIM:To test SMD as a potential risk factor for CRPS. METHODS:In this cross-sectional study, forty-four individuals with CRPS (29.9±11 years, 27 men) and 204 healthy controls (27.4±3.7 years, 105 men) completed the Sensory Responsiveness Questionnaire-Intensity Scale (SRQ-IS). A physician conducted the CRPS Severity Score (CSS), testing individuals with CRPS. RESULTS:Thirty-four percent of the individuals with CRPS and twelve percent of the healthy individuals were identified to have SMD (χ2 (1) = 11.95; p

Nearly 40% of seafood is traded internationally and an even bigger proportion is affected by international trade, yet scholarship on marine fisheries has focused on global trends in stocks and catches, or on dynamics of individual fisheries, with limited attention to the link between individual fisheries, global trade and distant consumers. This paper examines the usefulness of fish price as a feedback signal to consumers about the state of fisheries and marine ecosystems. We suggest that the current nature of fisheries systems and global markets prevent transmission of such price signals from source fisheries to consumers. We propose several mechanisms that combine to weaken price signals, and present one example – the North Sea cod – to show how these mechanisms can be tested. The lack of a reliable price feedback to consumers represents a challenge for sustainable fisheries governance. We therefore propose three complimentary approaches to address the missing feedback: (i) strengthening information flow through improved traceability and visibility of individual fishers to consumers, (ii) capitalizing on the changing seafood trade structures and (iii) bypassing and complementing market mechanisms by directly targeting citizens and political actors regarding marine environmental issues through publicity and information campaigns. These strategies each have limitations and thus need to be pursued together to address the challenge of sustainability in global marine fisheries.

Major depressive disorder (MDD) is a prevalent and disabling condition, and many patients do not respond to available treatments. Deep transcranial magnetic stimulation (dTMS) is a new technology allowing non-surgical stimulation of relatively deep brain areas. This is the first double-blind randomized controlled multicenter study evaluating the efficacy and safety of dTMS in MDD. We recruited 212 MDD outpatients, aged 22–68 years, who had either failed one to four antidepressant trials or not tolerated at least two antidepressant treatments during the current episode. They were randomly assigned to monotherapy with active or sham dTMS. Twenty sessions of dTMS (18 Hz over the prefrontal cortex) were applied during 4 weeks acutely, and then biweekly for 12 weeks. Primary and secondary efficacy endpoints were the change in the Hamilton Depression Rating Scale (HDRS-21) score and response/remission rates at week 5, respectively. dTMS induced a 6.39 point improvement in HDRS-21 scores, while a 3.28 point improvement was observed in the sham group (p+0.008), resulting in a 0.76 effect size. Response and remission rates were higher in the dTMS than in the sham group (response: 38.4 vs. 21.4%, p+0.013; remission: 32.6 vs. 14.6%, p+0.005). These differences between active and sham treatment were stable during the 12-week maintenance phase. dTMS was associated with few and minor side effects apart from one seizure in a patient where a protocol violation occurred. These results suggest that dTMS constitutes a novel intervention in MDD, which is efficacious and safe in patients not responding to antidepressant medications, and whose effect remains stable over 3 months of maintenance treatment.

The ‘Great Acceleration’ graphs, originally published in 2004 to show socio-economic and Earth System trends from 1750 to 2000, have now been updated to 2010. In the graphs of socio-economic trends, where the data permit, the activity of the wealthy (OECD) countries, those countries with emerging economies, and the rest of the world have now been differentiated. The dominant feature of the socio-economic trends is that the economic activity of the human enterprise continues to grow at a rapid rate. However, the differentiated graphs clearly show that strong equity issues are masked by considering global aggregates only. Most of the population growth since 1950 has been in the non-OECD world but the world’s economy (GDP), and hence consumption, is still strongly dominated by the OECD world. The Earth System indicators, in general, continued their long-term, post-industrial rise, although a few, such as atmospheric methane concentration and stratospheric ozone loss, showed a slowing or apparent stabilisation over the past decade. The post-1950 acceleration in the Earth System indicators remains clear. Only beyond the mid-20th century is there clear evidence for fundamental shifts in the state and functioning of the Earth System that are beyond the range of variability of the Holocene and driven by human activities. Thus, of all the candidates for a start date for the Anthropocene, the beginning of the Great Acceleration is by far the most convincing from an Earth System science perspective.

Freshwater use for food production is projected to increase substantially in the coming decades with population growth, changing demographics, and shifting diets. Ensuring joint food-water security has prompted efforts to quantify freshwater use for different food products and production methods. However, few analyses quantify freshwater use for seafood production, and those that do use inconsistent water accounting. This inhibits water use comparisons among seafood products or between seafood and agricultural/livestock products. This ‘seafood gap’ in the food-water nexus literature will become increasingly problematic as seafood consumption is growing globally and aquaculture is one of the fastest growing animal food sectors in the world. Therefore, the present study 1) reviews freshwater use concepts as they relate to seafood production; 2) provides three cases to highlight the particular water use concerns for aquaculture, and; 3) outlines future directions to integrate seafood into the broader food-water nexus discussion. By revisiting water use concepts through a focus on seafood production systems, we highlight the key water use processes that should be considered for seafood production and offer a fresh perspective on the analysis of freshwater use in food systems more broadly.

Livestock production is one of the fastest growing agricultural subsector globally. Expansion and intensification of animal production increase demand for natural resources. Sustainable intensification approaches are needed that limit pressure on often already scarce land and water resources. This paper quantifies water requirements in three Uruguayan beef production systems - extensive, mixed and intensive - and explores impacts on water-related ecosystem services. Mixed beef production systems were found to make most effective use of water. However, the shift from pastures in crop rotation towards continuous feed-crop cultivation decreases soil organic-matter contents, reducing soil water-holding capacity; this may result in lower agricultural yields and reduced resilience to droughts.

Cities are rapidly increasing in importance as a major factor shaping the Earth system, and therefore, must take corresponding responsibility. With currently over half the world's population, cities are supported by resources originating from primarily rural regions often located around the world far distant from the urban loci of use. The sustainability of a city can no longer be considered in isolation from the sustainability of human and natural resources it uses from proximal or distant regions, or the combined resource use and impacts of cities globally. The world's multiple and complex environmental and social challenges require interconnected solutions and coordinated governance approaches to planetary stewardship. We suggest that a key component of planetary stewardship is a global system of cities that develop sustainable processes and policies in concert with its non-urban areas. The potential for cities to cooperate as a system and with rural connectivity could increase their capacity to effect change and foster stewardship at the planetary scale and also increase their resource security. © Royal Swedish Academy of Sciences 2012.

Aims Assessing the quality of wall motion (WM) on echocardiograms remains a challenge. Previously, we validated an automated application used by experienced echocardiographers for WM classification based on longitudinal two-dimensional (2D) strain. The aim of this study was to show that the use of this automatic application was independent of the user's experience. Methods and results We compared the WM classifications obtained by the application when used by 12 highly experienced readers (Exp-R) vs. 11 inexperienced readers (InExp-R). Both classifications were compared with expert consensus classifications using the standard visual method. Digitized clips of cardiac cycles from three apical views in 105 patients were used for these analyses. Reproducibility of both groups was high (overall intra-class correlation coefficient: InExp-R = 0.89, Exp-R = 0.83); the lowest was noted for hypokinetic segments (InExp-R = 0.79, Exp-R = 0.72). InExp-R scores were concordant with Exp-R mode scores in 88.8% of segments; they were overestimated in 5.8% and underestimated in 3.2%. The sensitivity, specificity, and accuracy of InExp-R vs. Exp-R for classifying segments as normal/abnormal were identical (87, 85, and 86%, respectively). Conclusion Classification of WM from apical views with an automatic application based on longitudinal 2D strain by InExp-R vs. Exp-R was similar to visual classification by Exp-R. This application may be useful for inexperienced echocardiographers/technicians and may serve as an automated ‘second opinion’ for experienced echocardiographers.

Over the past century, the total material wealth of humanity has been enhanced. However, in the twenty-first century, we face scarcity in critical resources, the degradation of ecosystem services, and the erosion of the planet’s capability to absorb our wastes. Equity issues remain stubbornly difficult to solve. This situation is novel in its speed, its global scale and its threat to the resilience of the Earth System. The advent of the Anthropence, the time interval in which human activities now rival global geophysical processes, suggests that we need to fundamentally alter our relationship with the planet we inhabit. Many approaches could be adopted, ranging from geo-engineering solutions that purposefully manipulate parts of the Earth System to becoming active stewards of our own life support system. The Anthropocene is a reminder that the Holocene, during which complex human societies have developed, has been a stable, accommodating environment and is the only state of the Earth System that we know for sure can support contemporary society. The need to achieve effective planetary stewardship is urgent. As we go further into the Anthropocene, we risk driving the Earth System onto a trajectory toward more hostile states from which we cannot easily return.

Feeding aquaculture growth through globalization: exploitation of marine ecosystems for fishmeal

Patients with schizophrenia have deficits in some types of procedural learning. Several mechanisms contribute to this learning in healthy individuals, including statistical and sequence-learning. To find preserved and impaired learning mechanisms in schizophrenia, we studied the time course and characteristics of implicitly introduced sequence-learning (SRT task) in 15 schizophrenia patients (seven mild and eight severe) and nine healthy controls, in short sessions over multiple days (5–22). The data show speed gains of similar magnitude for all groups, but the groups differed in overall speed and in the characteristics of the learning. By analyzing the data according to its spatial-position and temporal-order components, we provide evidence for two types of learning that could differentiate the groups: while the learning of the slower, severe group was dominated by statistical learning, the control group moved from a fast learning phase of statistical-related performance to subsequence learning (chunking). Our findings oppose the naïve assumption that a similar gain of speed reflects a similar learning process; they indicate that the slower performance reflects the activation of a different motor plan than does the faster performance; and demonstrate that statistical learning and subsequence learning are two successive stages in implicit sequence learning, with chunks inferred from prior statistical computations. Our results indicate that statistical learning is intact in patients with schizophrenia, but is slower to develop in the severe patients. We suggest that this slow learning rate and the associated slow performance contribute to their deficit in developing sequence-specific learning by setting a temporal constraint on developing higher order associations.

Analysis of food consumption and agricultural production trends in Sweden has focused on domestic food production levels and yields, over looking human dependence on ecosystem support. We estimate ...

This paper develops a methodology for identifying that natural capital-called critical natural capital (CNC)-the maintenance of which is essential for environmental sustainability. By consideration of the characteristics of natural capital, of the environmental functions that these characteristics enable natural capital to perform and of the importance of these functions to humans and the biosphere, it shows how sustainability standards in respect of these environmental functions may be derived. The difference between the current situation and these standards is termed the sustainability gap. The methodology that emerges from bringing these ideas together into a single analytical framework enables policy makers to identify the extent of current unsustainability, the principal causes of it, the elements and processes of natural capital (the CNC) which need to be maintained or restored to close the sustainability gap and the costs of so doing. The framework should therefore be of use in identifying priorities and policies for moving towards environmental sustainability. (C) 2002 Published by Elsevier Science B.V.

Complex dynamic ecosystems are important natural capital assets. We investigate how Swedish national policy has approached these assets in its work on environmental indicators. In particular, we are interested in whether or not the indicators address ecosystem performance. We discuss our inventory of Swedish indicators in the context of ecosystem services, such as source and sink functions, and the capacity of ecosystems to sustain these functions for human well-being. We find that effective indicators have been developed to reflect energy and material flows within society and how human activities put pressure on the environment. The part of natural capital that concerns living systems is reflected in several of the Swedish indicators in a progressive fashion, but indicators that capture the dynamic capacity of ecosystems in sustaining the flow of source and sink functions need to be further developed. We provide examples of recent developments that have started to address such indicators in the context of ecosystem resilience and environmental change, and discuss directions for their further development. We stress the importance of monitoring ecosystem resilience and performance to avoid undesirable state shifts and building ecological knowledge and understanding of this capacity into environmental indicators and their associated management institutions.

Modern food production is a complex, globalized system in which what we eat and how it is produced are increasingly disconnected. This thesis examines some of the ways in which global trade has changed the mix of inputs to food and feed, and how this affects food security and our perceptions of sustainability. One useful indicator of the ecological impact of trade in food and feed products is the Appropriated Ecosystem Areas (ArEAs), which estimates the terrestrial and aquatic areas needed to produce all the inputs to particular products.The method is introduced in Paper I and used to calculate and track changes in imported subsidies to Swedish agriculture over the period 1962-1994. In 1994, Swedish consumers needed agricultural areas outside their national borders to satisfy more than a third of their food consumption needs. The method is then applied to Swedish meat production in Paper II to show that the term “Made in Sweden” is often a misnomer. In 1999, almost 80% of manufactured feed for Swedish pigs, cattle and chickens was dependent on imported inputs, mainly from Europe, Southeast Asia and South America. Paper III examines ecosystem subsidies to intensive aquaculture in two nations: shrimp production in Thailand and salmon production in Norway. In both countries, aquaculture was shown to rely increasingly on imported subsidies. The rapid expansion of aquaculture turned these countries from fishmeal net exporters to fishmeal net importers, increasingly using inputs from the Southeastern Pacific Ocean.As the examined agricultural and aquacultural production systems became globalized, levels of dependence on other nations’ ecosystems, the number of external supply sources, and the distance to these sources steadily increased. Dependence on other nations is not problematic, as long as we are able to acknowledge these links and sustainably manage resources both at home and abroad. However, ecosystem subsidies are seldom recognized or made explicit in national policy or economic accounts. Economic systems are generally not designed to receive feedbacks when the status of remote ecosystems changes, much less to respond in an ecologically sensitive manner. Papers IV and V discuss the problem of “masking” of the true environmental costs of production for trade. One of our conclusions is that, while the ArEAs approach is a useful tool for illuminating environmentally-based subsidies in the policy arena, it does not reflect all of the costs. Current agricultural and aquacultural production methods have generated substantial increases in production levels, but if policy continues to support the focus on yield and production increases alone, taking the work of ecosystems for granted, vulnerability can result. Thus, a challenge is to develop a set of complementary tools that can be used in economic accounting at national and international scales that address ecosystem support and performance.We conclude that future resilience in food production systems will require more explicit links between consumers and the work of supporting ecosystems, locally and in other regions of the world, and that food security planning will require active management of the capacity of all involved ecosystems to sustain food production.

We applied computer modeling as a consensus building tool as part of the development of the Patagonia Coastal Zone Management Plan (PCZMP). The objective was to build a ‘scoping model’ to assess some of the important ecological and economic interlinkages of the coastal zone of Patagonia. The main purposes were to build consensus, integrate across several parts of the system. and to educate stakeholders about other sectors, not to create a detailed research model. Nevertheless, the model provides some interesting preliminary conclusions. This model indicates that the total net present value (NPV) of the fisheries sector over a period of 40 years may be increased by 13% compared with current income, with a decrease in hake fishing levels by ≈50%. The natural capital on which the fishery sector depends would be used in a more sustainable way, both ecologically and economically. The model also simulates possible impacts of oil spills and dumping of tanker ballast water on the penguin population. which can have a significant negative impact on tourist industry incomes. The model implies that the importance of the tourist sector in Patagonia could in the future greatly exceed the value of the fishing industry (by 29%). The results argue for more emphasis on integrating the currently disparate components of coastal zone management.

In this chapter we take a complex systems approach to exploring the linkages among the phenomenon of urbanization, the changing value systems and world perspectives of urban dwellers, the sometimes distant connections to the food production systems that support cities, and the often invisible ecosystem services that support food production and in turn are affected by food production.