Search

IntroductionBalance is achieved through interactions between the vestibular, somatosensory, and visual systems. There are several clinical tests to measure postural stability. However, most of them do not assess postural stability with head movements, which is the main function of the vestibular system, and those that do, require the use of sizeable, expensive equipment. Therefore, an applicable, easy-to-perform test that challenges the function of the visual, somatosensory and vestibular systems, using head movements, is needed. The Zur Balance Scale (ZBS) contains ten conditions, which are a combination of surfaces (floor or Styrofoam with subject standing on its width in Romberg position or its length in tandem position), stances (Romberg or tandem), tasks (no head movement with eyes open or closed and horizontal or vertical head movements with eyes open). The purpose of this study was to determine the validity, inter- and intra-examiner reliability, and normal performance values of the ZBS among individuals 29–70-years of age and to introduce the modified version: the mZBS, using kinetic measurements.MethodsHealthy participants ages 29–70 years were evaluated for inter- and intra-tester reliability (n = 65), kinetic measurements on a force plate, and validity compared to the modified clinical test of sensory interaction and balance (mCTSIB) (n = 44) and characterization of normal values (n = 251).ResultsZur Balance Scale head movements, duration of each condition (up to 10 s) and the total ZBS score agreed across examiners (ICC > 0.8). Normal ZBS scores were negatively correlated with age (r = −0.34; P < 0.0001). Older subjects (60–70 years) had a median score of 95.5 compared with younger subjects, where medians ranged from 97.6 to 98.9. Kinetic parameters showed positive correlations between ZBS and the mCTSIB scores, with the highest correlation between the five Romberg tasks (modified ZBS).ConclusionZur Balance Scale is a valid and reliable test. Its advantages include using head movements and the ability to detect minimal differences in postural control, even in healthy populations. Kinetic evaluation of the ZBS enables the use of a modified, shorter version of the ZBS (mZBS).

Abstract Integration is often considered the core challenge and the defining characteristic of inter- and trans-disciplinary (ITD) research. Given its importance, it is surprising that the current system of higher education does not provide permanent positions for integration experts; i.e., experts who lead, administer, manage, monitor, assess, accompany, and/or advise others on integration within ITD projects or programs. Based on empirical results of an ITD 2019 Conference Workshop entitled “Is there a new profession of integration experts on the rise?” held in Gothenburg, Sweden, and our own experience in leading and studying ITD integration, the present article sheds light on the overarching question, “What are integration experts?”, thus contributing to the emerging literature on integration and integration expertise. We use direct quotes from participants to substantiate workshop results and triangulate them with recent literature on ITD research as well as Science of Team Science (SciTS) and Science and Technology Studies (STS). We conclude our article by discussing possible unintended consequences of establishing academic careers for integration experts, and suggest four complementary ways to support them, while mitigating potentially negative consequences: (a) establishing an international Community of Practice (CoP) to foster peer-to-peer exchange among integration experts, create greater visibility, and develop ideas for transforming academic structures; (b) studying academic careers of integration experts to provide empirical evidence of “successful” examples and disclose different ways of establishing related academic positions; (c) funding respective positions and aligning metrics for ITD research to foster integration within ITD projects or programs; and (d) engaging in collaborative dialog with academic institutions and funding agencies to present empirical results and lessons learnt from (a) and (b) to support them in establishing and legitimating careers for integration experts. If academia is to be serious about addressing the most pressing environmental and societal problems of our time, it needs to integrate its integrators.

Abstract In this paper, we develop and apply the concept of ‘insight discovery’ as a key competence for transdisciplinary research and learning. To address complex societal and environmental problems facing the world today, a particular expertise that can identify new connections between diverse knowledge fields is needed in order to integrate diverse perspectives from a wide range of stakeholders and develop novel solutions. The capacity for “insight discovery” means becoming aware of personal mental representations of the world and being able to shape and integrate perspectives different from one’s own. Based on experiences and empirical observations within the scope of an educational programme for Masters students, PhD candidates and post-doctoral researchers, we suggest that insights are the outcome of a learning process influenced by the collective and environment in which they are conceived, rather than instant moments of individual brilliance. The process which we describe, named the insight discovery process (IDP), is made up of five aspects. Within a group setting, a person begins with an “original mental model”, experiences an “insight trigger”, processes new information within the “liminal space”, “formulates an insight” and eventually forms an “adapted mental model”. There is a potential for incorporating such process as a fundamental competence for transdisciplinary curricula in undergraduate and graduate programmes by cultivating specific practices and safe learning environments, focused on the enquiry, exchange and integration of diverse perspectives.

Background: Viral infection is associated with a significant rewire of the host metabolic pathways, presenting attractive metabolic targets for intervention. Methods: We chart the metabolic response of lung epithelial cells to SARS-CoV-2 infection in primary cultures and COVID-19 patient samples and perform in vitro metabolism-focused drug screen on primary lung epithelial cells infected with different strains of the virus. We perform observational analysis of Israeli patients hospitalized due to COVID-19 and comparative epidemiological analysis from cohorts in Italy and the Veteran’s Health Administration in the United States. In addition, we perform a prospective non-randomized interventional open-label study in which 15 patients hospitalized with severe COVID-19 were given 145 mg/day of nanocrystallized fenofibrate added to the standard of care. Results: SARS-CoV-2 infection produced transcriptional changes associated with increased glycolysis and lipid accumulation. Metabolism-focused drug screen showed that fenofibrate reversed lipid accumulation and blocked SARS-CoV-2 replication through a PPARα-dependent mechanism in both alpha and delta variants. Analysis of 3233 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 non-randomized interventional open-label study was carried out on 15 patients hospitalized with severe COVID-19. The patients were treated with 145 mg/day of nanocrystallized fenofibrate in addition to standard-of-care. Patients receiving fenofibrate demonstrated a rapid reduction in inflammation and a significantly faster recovery compared to patients admitted during the same period. Conclusions: Taken together, our data suggest that pharmacological modulation of PPARα should be strongly considered as a potential therapeutic approach for SARS-CoV-2 infection and emphasizes the need to complete the study of fenofibrate in large randomized controlled clinical trials. Funding: Funding was provided by European Research Council Consolidator Grants OCLD (project no. 681870) and generous gifts from the Nikoh Foundation and the Sam and Rina Frankel Foundation (YN). The interventional study was supported by Abbott (project FENOC0003). Clinical trial number: NCT04661930.

The wicked nature of sustainability challenges facing food systems demands intentional and synergistic actions at multiple scales and sectors. The Southern Cone of Latin America, with its historical legacy of “feeding the world,” presents interesting opportunities for generating insights into potential trajectories and processes for food system transformation. To foster such changes would require the development of collective understanding and agency to effectively realize purposeful and well-informed action toward desirable and sustainable food futures. This in turn demands the transdisciplinary engagement of academia, the private sector, government/policy-makers, community groups, and other institutions, as well as the broader society as food consumers. While the need for contextualized knowledge, priorities and definitions of what sustainable food systems change means is recognized, there is limited literature reporting these differences and critically reflecting on the role of knowledge brokers in knowledge co-production processes. The political nature of these issues requires arenas for dialogue and learning that are cross-sectoral and transcend knowledge generation. This paper presents a case study developed by SARAS Institute, a bridging organization based in Uruguay. This international community of practice co-designed a 3-year multi-stakeholder transdisciplinary process entitled “Knowledges on the Table.” We describe how the process was designed, structured, and facilitated around three phases, two analytical levels and through principles of knowledge co-production. The case study and its insights offer a model that could be useful to inform similar processes led by transdisciplinary communities of practice or bridging institutions in the early stages of transformative work. In itself, it also represents a unique approach to generate a language of collaboration, dialogue, and imagination informed by design skills and methods. While this is part of a longer-term process toward capitalizing on still-unfolding insights and coalitions, we hope that this example helps inspire similar initiatives to imagine, support, and realize contextualized sustainable food system transformations.

Glioblastoma multiforme (GBM) is at present an incurable disease with a 5-year survival rate of 5.5%, despite improvements in treatment modalities such as surgery, radiation therapy, chemotherapy [e.g., temozolomide (TMZ)], and targeted therapy [e.g., the antiangiogenic agent bevacizumab (BEV)]. Diffusing alpha-emitters radiation therapy (DaRT) is a new modality that employs radium-224-loaded seeds that disperse alpha-emitting atoms inside the tumor. This treatment was shown to be effective in mice bearing human-derived GBM tumors. Here, the effect of DaRT in combination with standard-of-care therapies such as TMZ or BEV was investigated. In a viability assay, the combination of alpha radiation with TMZ doubled the cytotoxic effect of each of the treatments alone in U87 cultured cells. A colony formation assay demonstrated that the surviving fraction of U87 cells treated by TMZ in combination with alpha irradiation was lower than was achieved by alpha- or x-ray irradiation as monotherapies, or by x-ray combined with TMZ. The treatment of U87-bearing mice with DaRT and TMZ delayed tumor development more than the monotherapies. Unlike other radiation types, alpha radiation did not increase VEGF secretion from U87 cells in culture. BEV treatment introduced several days after DaRT implantation improved tumor control, compared to BEV or DaRT as monotherapies. The combination was also shown to be superior when starting BEV administration prior to DaRT implantation in large tumors relative to the seed size. BEV induced a decrease in CD31 staining under DaRT treatment, increased the diffusive spread of 224Ra progeny atoms in the tumor tissue, and decreased their clearance from the tumor through the blood. Taken together, the combinations of DaRT with standard-of-care chemotherapy or antiangiogenic therapy are promising approaches, which may improve the treatment of GBM patients.

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.

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.

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

Abstract The spatial extent of ecological processes has consequences for the generation of ecosystem services related to them. However, management often fails to consider issues of scale when targeting ecological processes underpinning ecosystem services generation. Here, we present a framework for conceptualizing how the amount and spatial scale (here discussed in terms of extent) of management interventions alter interactions among multiple ecosystem services. First, we identify four types of responses of ecosystem service generation: linear, exponential, saturating, and sigmoid, and how these are related to the amount of management intervention at a particular spatial scale. Second, using examples from multiple ecosystem services in agricultural landscapes, we examine how the shape of these relationships can vary with the spatial scale at which the management interventions are implemented. Third, we examine the resulting scale‐dependent consequences for trade‐offs and synergies between ecosystem services as a consequence of interventions. Finally, to inform guidelines for management of multiple ecosystem services in real landscapes, we end with a discussion linking the theoretical relationships with how landscape configurations and placement of interventions can alter the scale at which synergies and trade‐offs among services occur.

OBJECTIVE:We investigated the impact of clown-care on pain in 45 children with cerebral palsy who underwent recurrent Botulinum-toxin injections (age 7.04± 4.68 years). Participants were randomized to receive either clown (n = 20) or standard (n = 25) -care. METHODS:Pain Visual-Analogue-Scale (range 1-5) was reported before and after procedures. Pain assessment was lower for children undergoing Botulinum-toxin injections with clown-care (2.89± 1.36) compared to standard-care (3.85± 1.39; p = 0.036) even though pain anticipated prior to procedures was similar (~3). FINDINGS:Children who underwent the first procedure with clown-care reported lower pain even after they crossed-over to the following procedure which was standard (p = 0.048). Carryover effect was more prominent in injection-naïve children (p = 0.019) and during multiple procedures (p = 0.009). Prior pain experience correlated with pain in subsequent procedures only when first experience was standard-care (p = 0.001). CONCLUSIONS:Clown-care alleviated pain sensation during Botulinum-toxin injections and initial clown-care experience reduced pain during subsequent injections even though clowns were not present. TRIAL REGISTRATION:clinicaltrials.gov ID # NCT01377883.

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.

Food lies at the heart of both health and sustainability challenges. We use a social-ecological framework to illustrate how major changes to the volume, nutrition and safety of food systems between 1961 and today impact health and sustainability. These changes have almost halved undernutrition while doubling the proportion who are overweight. They have also resulted in reduced resilience of the biosphere, pushing four out of six analysed planetary boundaries across the safe operating space of the biosphere. Our analysis further illustrates that consumers and producers have become more distant from one another, with substantial power consolidated within a small group of key actors. Solutions include a shift from a volume-focused production system to focus on quality, nutrition, resource use efficiency, and reduced antimicrobial use. To achieve this, we need to rewire food systems in ways that enhance transparency between producers and consumers, mobilize key actors to become biosphere stewards, and re-connect people to the biosphere.

In their article ‘Freshwater savings from marine protein consumption’ (2014 Environ. Res. Lett. http://dx.doi.org/10.1088/1748-9326/9/1/014005 9 http://dx.doi.org/10.1088/1748-9326/9/1/014005 ), Gephart and her colleagues analyzed how consumption of marine animal protein rather than terrestrial animal protein leads to reduced freshwater allocation. They concluded that future water savings from increased marine fish consumption would be possible. We find the approach interesting and, if they only considered marine capture fisheries, their analysis would be quite straightforward and show savings of freshwater. However, both capture fisheries and aquaculture are considered in the analysis, and the fact that marine aquaculture is assumed to have a zero freshwater usage, makes the analysis incomplete. Feed resources used in marine aquaculture contain agriculture compounds, which results in a freshwater footprint. To correct this shortcoming we complement the approach taken by Gephart and her colleagues by estimating the freshwater footprint (WF) for crops used for feeding marine aquaculture. We show that this is critically important when estimating the true freshwater footprint for marine aquaculture, and that it will be increasingly so in the future. We also further expand on aquaculture’s dependency on fish resources, as this was only briefly touched upon in the paper. We do so because changes in availability of fish resources will play an important role for feed development and thereby for the future freshwater footprint of marine aquaculture.

The benefits and risks of any particular GM crop depend on the interactions of its ecological functions and natural history with the agroecosystem and ecosystems within which it is embedded. These evolutionary and ecological factors must be considered when assessing GM crops. We argue that the assessment of GM crops should be broadened to include alternative agricultural practices, ecosystem management, and agricultural policy. Such an assessment would be facilitated by a clearer understanding of the indirect costs of agriculture and the ecological services that support it. The benefits of GM crops should be compared to those of other means of agricultural intensification such as organic farming, integrated pest management, and agricultural policy reform. A gradual and cautious approach to the use of GM crops that relies on a truly comprehensive risk assessment could allow people to reap substantial benefits from GM crops while mitigating their serious risks.

Abstract??This study assessed current practice and methods for improvement in the management of families with hereditary non-polyposis colorectal cancer (HNPCC). HNPCC families registered at five London Genetics Centres and a specialised Colorectal family cancer clinic (CFCC) were identified. Ascertainment of management and outcome details were obtained by scrutiny of patient records and by correspondence with General practitioners (GPs). Two hundred and three families with HNPCC were identified. 79.5% (403/507) of at-risk relatives ascertained were contacted by the genetics centres, and 80.2% (65/81) by the CFCC (P?=?1.0). 54.8% (211/385) of probands and relatives within genetics centres? catchment areas were advised to undertake a surveillance programme, compared with 82.1% (64/78) of those cared for by the CFCC (P<4.2*106). Adherence to surveillance guidelines was 76.6% (49/64) in individuals cared for by the only centre that undertook responsibility for surveillance follow-up (CFCC) and 41.7% (88/211) for the genetics centres, which did not assume responsibility (P<8.9???10?7) (using two sidedP-values forP(O???E|O???E)). 15.3% of GPs were unaware their patient had been recommended a surveillance programme, 65% did not know who was responsible for ensuring surveillance follow-up. A questionnaire to fifteen UK genetics centres demonstrated that the majority (86.7%) did not assume responsibility for surveillance follow-up. Since surveillance adherence is clearly better where centres assume responsibility for follow-up, it is recommended that regional or national registers of HNPCC families be developed and maintained to ensure effective management. [ABSTRACT FROM AUTHOR]