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Ionising radiation (IR) is a cause of lipid peroxidation, and epidemiological data have revealed a correlation between exposure to IR and the development of eye lens cataracts. Cataracts remain the leading cause of blindness around the world. The plasma membranes of lens fibre cells are one of the most cholesterolrich membranes in the human body, forming lipid rafts and contributing to the biophysical properties of lens fibre plasma membrane. Liquid chromatography followed by mass spectrometry was used to analyse bovine eye lens lipid membrane fractions after exposure to 5 and 50 Gy and eye lenses taken from wholebody 2 Gy-irradiated mice. Although cholesterol levels do not change significantly, IR dose-dependant formation of the oxysterols 7β-hydroxycholesterol, 7-ketocholesterol and 5, 6-epoxycholesterol in bovine lens nucleus membrane extracts was observed. Whole-body X-ray exposure (2 Gy) of 12-week old mice resulted in an increase in 7β-hydroxycholesterol and 7-ketocholesterol in their eye lenses. Their increase regressed over 24 h in the living lens cortex after IR exposure. This study also demonstrated that the IR-induced fold increase in oxysterols was greater in the mouse lens cortex than the nucleus. Further work is required to elucidate the mechanistic link(s) between oxysterols and IR-induced cataract, but these data evidence for the first time that IR exposure of mice results in oxysterol formation in their eye lenses.

Plasmodium parasites are the causative agents of malaria, a disease with wide public health repercussions. Increasing drug resistance and the absence of a vaccine make finding new chemotherapeutic strategies imperative. Components of the ubiquitin and ubiquitin-like pathways have garnered increased attention as novel targets given their necessity to parasite survival. Understanding how these pathways are regulated in Plasmodium and identifying differences to the host is paramount to selectively interfering with parasites. Here, we focus on Nedd8 modification in Plasmodium falciparum, given its central role to cell division and DNA repair, processes critical to Plasmodium parasites given their unusual cell cycle and requirement for refined repair mechanisms. By applying a functional chemical approach, we show that deNeddylation is controlled by a different set of enzymes in the parasite versus the human host. We elucidate the molecular determinants of the unusual dual ubiquitin/Nedd8 recognition by the essential PfUCH37 enzyme and, through parasite transgenics and drug assays, determine that only its ubiquitin activity is critical to parasite survival. Our experiments reveal interesting evolutionary differences in how neddylation is controlled in higher versus lower eukaryotes, and highlight the Nedd8 pathway as worthy of further exploration for therapeutic targeting in antimalarial drug design.

Advanced Lipoxidation End-products (ALEs) are modified proteins that can act as pathogenic factors in several chronic diseases. Several molecular mechanisms have so far been considered to explain the damaging action of ALEs and among these a pathway involving the receptor for advanced glycation end products (RAGE) should be considered. The aim of the present work is to understand if ALEs formed from lipid peroxidation derived reactive carbonyl species (RCS) are able to act as RAGE binders and also to gain a deeper insight into the molecular mechanisms involved in the protein-protein engagement. ALEs were produced in vitro, by incubating human serum albumin (HSA) with 4-hydroxy-trans− 2-nonenal (HNE), acrolein (ACR) and malondialdehyde (MDA). The identification of ALEs was performed by MS. ALEs were then subjected to the VC1 Pull-Down assay (VC1 is the ligand binding domain of RAGE) and the enrichment factor (the difference between the relative abundance in the enriched sample minus the amount in the untreated one) as an index of affinity, was determined. Computation studies were then carried out to explain the factors governing the affinity of the adducted moieties and the site of interaction on adducted HSA for VC1-binding. The in silico analyses revealed the key role played by those adducts which strongly reduce the basicity of the modified residues and thus occur at their neutral state at physiological conditions (e.g. the MDA adducts, dihydropyridine-Lysine (DHPK) and N-2-pyrimidyl-ornithine (NPO), and acrolein derivatives, N-(3-formyl-3,4-dehydro-piperidinyl) lysine, FDPK). These neutral adducts become unable to stabilize ion-pairs with the surrounding negative residues which thus can contact the RAGE positive residues.In conclusion, ALEs derived from lipid peroxidation-RCS are binders of RAGE and this affinity depends on the effect of the adduct moiety to reduce the basicity of the target amino acid and on the acid moieties surrounding the aminoacidic target. Keywords: Advanced lipoxidation end products (ALEs), Human serum albumin (HSA), RAGE, Pull-down assay, VC1 domain, Reactive Carbonyl Species (RCS), 4-hydroxy-trans− 2-nonenal (HNE), Acrolein (ACR) and malondialdehyde (MDA)

The aim of the study is to compare the qualitative and semi-quantitative profile of the polyphenol fraction purified from the leaf (BLPF) and fruit (BFPF) of bergamot (Citrus bergamia), and to evaluate their antioxidant and anti-inflammatory activity. The analytical qualitative profile was carried out by LC-ESI/MS using three different approaches: targeted (searching analytes already reported in bergamot extract), semi-targeted (a selective search of 3-hydroxy-3-methylglutarate [HMG] derivatives involved in the cholesterol reducing activity of BPF) and untargeted. A total number of 108 compounds were identified by using the three approaches, 100 of which are present in both the extracts thus demonstrating a good qualitative overlapping of polyphenols between the two extracts. The antioxidant activity was higher for BLPF in respect to BFPF but when normalized in respect to the polyphenol content they were almost overlapping. Both the extracts were found to dose dependently inhibit cell inflammation stimulated with IL-1α. In conclusion, the comparison of the qualitative and quantitative profile of polyphenols as well as of the antioxidant and anti-inflammatory activity of bergamot leaf and fruit well indicates that leaf is a valid source of bergamot polyphenol extraction and an even richer source of polyphenol in respect to the fruit.

Trichinella spiralis is a muscle-specific parasitic worm that is uniquely intracellular. T. spiralis reprograms terminally differentiated skeletal muscle cells causing them to de-differentiate and re-enter the cell cycle, a process that cannot occur naturally in mammalian skeletal muscle cells, but one that holds great therapeutic potential. Although the host ubiquitin pathway is a common target for viruses and bacteria during infection, its role in parasite pathogenesis has been largely overlooked. Here we demonstrate that the secreted proteins of T. spiralis contain E2 Ub-conjugating and E3 Ub-ligase activity. The E2 activity is attributed to TsUBE2L3, a novel and conserved T. spiralis enzyme located in the secretory organ of the parasite during the muscle stages of infection. TsUBE2L3 cannot function with any T.spiralis secreted E3, but specifically binds to a panel of human RING E3 ligases, including the RBR E3 ARIH2 with which it interacts with a higher affinity than the mammalian ortholog UbcH7/UBE2L3. Expression of TsUBE2L3 in skeletal muscle cells causes a global downregulation in protein ubiquitination, most predominantly affecting motor, sarcomeric and extracellular matrix proteins, thus mediating their stabilization with regards to proteasomal degradation. This effect is not observed in the presence of the mammalian ortholog, suggesting functional divergence in the evolution of the parasite protein. These findings demonstrate the first example of host-parasite interactions via a parasite-derived Ub conjugating enzyme; an E2 that demonstrates a novel muscle protein stabilization function.

The spotted lanternfly, Lycorma delicatula, native to parts of East Asia and the Indomalayan region, is a polyphagous herbivore poised to become a major global agricultural pest. Since its establishment in the US in 2014, L. delicatula continues to expand its range, and its invasion into California is highly anticipated. Proactive work evaluating Anastatus orientalis, an egg parasitoid of L. delicatula in its native range, as a potential biological agent determined this parasitoid is too polyphagous for release in the US, and no other suitable egg parasitoids have been identified. Consequently, the potential of native North American egg parasitoids to provide biotic resistance to the L. delicatula invasion is being assessed. In a quarantine laboratory study, Anastatus reduvii, an egg parasitoid native to and widespread in North America, including California, parasitized 79% of L. delicatula egg masses with an average egg parasitism rate of 31%. Egg masses exposed to A. reduvii exhibited significantly reduced L. delicatula hatch rates (33%) compared to unexposed control egg masses (90%). These observed rates are comparable to that of A. orientalis attacking L. delicatula egg masses. Rearing A. reduvii from eggs of five different host species did not significantly affect parasitism or L. delicatula mortality, although parasitism was substantially higher compared to previous work using A. reduvii reared exclusively on Pentatomidae eggs. Mass-rearing of A. reduvii is highly feasible and continued investigations into the suitability of this egg parasitoid as a biological control agent for L. delicatula in the US are recommended.

Abstract The Greenland Ice Sheet is losing mass at increasing rates. Substantial amounts of this mass loss occur by ice discharge which is influenced by ocean thermal forcing. The ice sheet is surrounded by thousands of peripheral, dynamically decoupled glaciers. The mass loss from these glaciers is disproportionately high considering their negligible share in Greenland’ overall ice mass. We study the relevance of ocean thermal forcing for ice discharge evolution in the context of this contrasting behaviour. Our estimate of ice discharge from the peripheral tidewater glaciers yields a rather stable Greenland-wide mean of 5.40 ± 3.54 Gt a−1 over 2000–2021. The evolutions of ice discharge and ocean thermal forcing are heterogeneous around Greenland. We observe a significant sector-wide increase of ice discharge in the East and a significant sector-wide decrease in the Northeast. Ocean thermal forcing shows significant increases along the northern/eastern coast, while otherwise unchanged conditions or decreases prevail. For East Greenland, this implies a clear influence of ocean thermal forcing on ice discharge. Similarly, we find clear influences at peripheral tidewater glaciers with thick termini that are similar to ice sheet outlet glaciers. At the peripheral glaciers in Northeast Greenland ice discharge evolution opposes ocean thermal forcing for unknown reasons.

Incomplete species inventories for Antarctica represent a key challenge for comprehensive ecological research and conservation in the region. Additionally, data required to understand population dynamics, rates of evolution, spatial ranges, functional traits, physiological tolerances and species interactions, all of which are fundamental to disentangle the different functional elements of Antarctic biodiversity, are mostly missing. However, much of the fauna, flora and microbiota in the emerged ice-free land of the continent have an uncertain presence and/or unresolved status, with entire biodiversity compendia of prokaryotic groups (e.g. bacteria) being missing. All the available biodiversity information requires consolidation, cross-validation, re-assessment and steady systematic inclusion in order to create a robust catalogue of biodiversity for the continent.We compiled, completed and revised eukaryotic species inventories present in terrestrial and freshwater ecosystems in Antarctica in a new living database: terrANTALife (version 1.0). The database includes the first integration in a compendium for many groups of eukaryotic microorganisms. We also introduce a first catalogue of amplicon sequence variants (ASVs) of prokaryotic biodiversity. Available compendia and literature to date were searched for Antarctic terrestrial and freshwater species, integrated, taxonomically harmonised and curated by experts to create comprehensive checklists of Antarctic organisms. The final inventories comprises 470 animal species (including vertebrates, free-living invertebrates and parasites), 306 plants (including all Viridiplantae: embryophytes and green algae), 997 fungal species and 434 protists (sensu lato). We also provide a first account for many groups of microorganisms, including non-lichenised fungi and multiple groups of eukaryotic unicellular species (Stramenophila, Alveolata and Rhizaria (SAR), Chromists and Amoeba), jointly referred to as "protists". In addition, we identify 1753 bacterial (obtained from 348117 ASVs) and 34 archaeal genera (from 1848 ASVs), as well as, at least, 14 virus families. We formulate a basic tree of life in Antarctica with the main lineages listed in the region and their “known-accepted-species” numbers.

Abstract Background Large introductory lecture courses are frequently post-secondary students’ first formal interaction with science, technology, engineering, and mathematics (STEM) disciplines. Grade outcomes in these courses are often disparate across student populations, which, in turn, has implications for student retention. This study positions such disparities as a manifestation of systemic inequities along the dimensions of sex, race/ethnicity, income, and first-generation status and investigates the extent to which they are similar across peer institutions. Results We examined grade outcomes in a selected set of early STEM courses across six large, public, research-intensive universities in the United States over ten years. In this sample of more than 200,000 STEM course enrollments, we find that course grade benefits increase significantly with the number of systemic advantages students possess at all six institutions. The observed trends in academic outcomes versus advantage are strikingly similar across universities despite the fact that we did not control for differences in grading practices, contexts, and instructor and student populations. The findings are concerning given that these courses are often students’ first post-secondary STEM experiences. Conclusions STEM course grades are typically lower than those in other disciplines; students taking them often pay grade penalties. The systemic advantages some student groups experience are correlated with significant reductions in these grade penalties at all six institutions. The consistency of these findings across institutions and courses supports the claim that inequities in STEM education are a systemic problem, driven by factors that go beyond specific courses or individual institutions. Our work provides a basis for the exploration of contexts where inequities are exacerbated or reduced and can be used to advocate for structural change within STEM education. To cultivate more equitable learning environments, we must reckon with how pervasive structural barriers in STEM courses negatively shape the experiences of marginalized students.

Abstract Aims The present analysis from the multicentre prospective Altshock‐2 registry aims to better define clinical features, in‐hospital course, and management of cardiogenic shock complicating acutely decompensated heart failure (ADHF‐CS) as compared with that complicating acute myocardial infarction (AMI‐CS). Methods and results All patients with AMI‐CS or ADHF‐CS enrolled in the Altshock‐2 registry between March 2020 and February 2022 were selected. The primary objective was the characterization of ADHF‐CS patients as compared with AMI‐CS. In‐hospital length of stay and mortality were secondary endpoints. One‐hundred‐ninety of the 238 CS patients enrolled in the aforementioned period were considered for the present analysis: 101 AMI‐CS (80% ST‐elevated myocardial infarction and 20% non‐ST‐elevated myocardial infarction) and 89 ADHF‐CS. As compared with AMI‐CS, ADHF‐CS patients were younger [63 (IQR 59–76) vs. 67 (IQR 54–73) years, P = 0.01], but presented with higher creatinine [1.6 (IQR 1.0–2.6) vs. 1.2 (IQR 1.0–1.4) mg/dL, P

Abstract Background Electroencephalography (EEG)-based brain-computer interfaces (BCIs) allow to modulate the sensorimotor rhythms and are emerging technologies for promoting post-stroke motor function recovery. The Promotoer study aims to assess the short and long-term efficacy of the Promotoer system, an EEG-based BCI assisting motor imagery (MI) practice, in enhancing post-stroke functional hand motor recovery. This paper details the statistical analysis plan of the Promotoer study. Methods The Promotoer study is a randomized, controlled, assessor-blinded, single-centre, superiority trial, with two parallel groups and a 1:1 allocation ratio. Subacute stroke patients are randomized to EEG-based BCI-assisted MI training or to MI training alone (i.e. no BCI). An internal pilot study for sample size re-assessment is planned. The primary outcome is the effectiveness of the Upper Extremity Fugl-Meyer Assessment (UE-FMA) score. Secondary outcomes include clinical, functional, and user experience scores assessed at the end of intervention and at follow-up. Neurophysiological assessments are also planned. Effectiveness formulas have been specified, and intention-to-treat and per-protocol populations have been defined. Statistical methods for comparisons of groups and for development of a predictive score of significant improvement are described. Explorative subgroup analyses and methodology to handle missing data are considered. Discussion The Promotoer study will provide robust evidence for the short/long-term efficacy of the Promotoer system in subacute stroke patients undergoing a rehabilitation program. Moreover, the development of a predictive score of response will allow transferring of the Promotoer system to optimal clinical practice. By carefully describing the statistical principles and procedures, the statistical analysis plan provides transparency in the analysis of data. Trial registration ClinicalTrials.gov NCT04353297 . Registered on April 15, 2020.

Introduction: Kelvin-Helmholtz (KH) and tearing mode (TM) instabilities are one of the most important mechanisms of solar wind energy, momentum and plasma transport within the magnetosphere.Methods: To investigate the conditions under which KHTM instabilities occur in the Earth environment it is fundamental to combine simultaneous multipoint in situ measurements and MHD simulations. We analyzed data from the THEMIS and Cluster spacecraft considering two Space Weather (SWE) events starting with an M2.0 flare event (hereafter Case-1) that occurred on 21 June 2015 and the most-intensive flare (X9.3) of solar cycle 24 that occurred on 6 September 2017 (hereafter Case-2).Results: Our analysis utilized a 2D MHD model for incompressible and viscous flow. The results from Case-1 indicate the presence of KH and TM instabilities, suggesting existence of observed low-amplitude oscillations at the nose of the magnetopause. However, the MHD simulations for Case-2 did not show any evidence of KH vortices, but did reveal the presence of “magnetic island” structures during a low-shear condition. The reconnection rate derived from the observations is compared with the computed one in the presence of developed instabilities inside the Earth’s magnetopause.

Calculation of the calving loss of tidewater glaciers depends on accurate bedrock information. In regional to global-scale projections of future tidewater glacier evolution this dependence is problematic. Bedrock topographies are often unknown and can only be modelled from surface properties. Existing approaches, however, mostly underestimate the ice thickness towards the calving fronts of marine-terminating glaciers. This implies a compromised performance of global-scale projection models which often employ functions of water depth at the calving fronts of tidewater glaciers. Here, we present a sensitivity study that analyses the impact of five different bedrock datasets on projected mass losses from the tidewater glacier Hansbreen in southern Svalbard. Our modelling study calculates the glacier's response to artificial mass-balance forcing. We show that bedrock inaccuracies may lead to a substantially deviating retreat behaviour. The common underestimation of frontal ice thickness/water depth in the modelled bedrock datasets induces an underestimation of sea level-relevant mass losses over the first several decades of modelling. The duration of this period is reduced when assuming warmer climates. Our results thus underline the importance of accurate bedrock topography data for the reliability of glacier evolution projections and for the accuracy of the temporal trajectories of related sea level-relevant mass losses.

Digital twin technology is an emerging technology within the built environment. Yet, there are many unexplored opportunities to utilize digital twins for facilitating the transformation toward a climate-neutral building stock while also meeting the expectations from the building occupants. This article presents a case study of a digital twin, developed for an existing commercial building stock of campus areas in Sweden. The overarching purpose of the digital twin is to support both building occupants and building operators. This two-fold human-centric approach represents a novel approach for building digital twins. The digital twin is based on 3D scanning, and together with geospatial data, a real-like navigational indoor environment is created. Three innovative features are presented: the building analysis module, the digital twin mobile application, and the building operations module. The results show that the digital twin improves the building occupant’s experience by supporting navigation and providing access to the room booking system via this dedicated interface. Building management is also benefited by the digital twin through easier access to building data aggregated into one platform and a state-of-the-art analysis tool for optimizing the use of indoor space. The digital twin holds future potential to achieve operational excellence by incorporating feedback mechanisms and utilizing artificial intelligence to enable intelligent fault detection and prevention.

The disability, mortality and costs due to ionizing radiation (IR)-induced osteoporotic bone fractures are substantial and no effective therapy exists. Ionizing radiation increases cellular oxidative damage, causing an imbalance in bone turnover that is primarily driven via heightened activity of the bone-resorbing osteoclast. We demonstrate that rats exposed to sublethal levels of IR develop fragile, osteoporotic bone. At reactive surface sites, cerium ions have the ability to easily undergo redox cycling: drastically adjusting their electronic configurations and versatile catalytic activities. These properties make cerium oxide nanomaterials fascinating. We show that an engineered artificial nanozyme composed of cerium oxide, and designed to possess a higher fraction of trivalent (Ce3+) surface sites, mitigates the IR-induced loss in bone area, bone architecture, and strength. These investigations also demonstrate that our nanozyme furnishes several mechanistic avenues of protection and selectively targets highly damaging reactive oxygen species, protecting the rats against IR-induced DNA damage, cellular senescence, and elevated osteoclastic activity in vitro and in vivo. Further, we reveal that our nanozyme is a previously unreported key regulator of osteoclast formation derived from macrophages while also directly targeting bone progenitor cells, favoring new bone formation despite its exposure to harmful levels of IR in vitro. These findings open a new approach for the specific prevention of IR-induced bone loss using synthesis-mediated designer multifunctional nanomaterials.

Background and purpose: Antibiotic-loaded bone cement (ALBC) and systemic antibiotic prophylaxis (SAP) have been used to reduce periprosthetic joint infection (PJI) rates. We investigated the use of ALBC and SAP in primary total knee arthroplasty (TKA). Patients and methods: This observational study is based on 2,971,357 primary TKAs reported in 2010–2020 to national/regional joint arthroplasty registries in Australia, Denmark, Finland, Germany, Italy, the Netherlands, New Zealand, Norway, Romania, South Africa, Sweden, Switzerland, the UK, and the USA. Aggregate-level data on trends and types of bone cement, antibiotic agents, and doses and duration of SAP used was extracted from participating registries. Results: ALBC was used in 77% of the TKAs with variation ranging from 100% in Norway to 31% in the USA. Palacos R+G was the most common (62%) ALBC type used. The primary antibiotic used in ALBC was gentamicin (94%). Use of ALBC in combination with SAP was common practice (77%). Cefazolin was the most common (32%) SAP agent. The doses and duration of SAP used varied from one single preoperative dosage as standard practice in Bolzano, Italy (98%) to 1-day 4 doses in Norway (83% of the 40,709 TKAs reported to the Norwegian arthroplasty register). Conclusion: The proportion of ALBC usage in primary TKA varies internationally, with gentamicin being the most common antibiotic. ALBC in combination with SAP was common practice, with cefazolin the most common SAP agent. The type of ALBC and type, dose, and duration of SAP varied among participating countries.

Abstract Rice (Oryza sativa L.) is an excellent source of starch, which is composed of amylopectin and amylose. Resistant starch (RS) is a starch product that is not easily digestible and absorbed in the stomach or small intestine and instead is passed on directly to the large intestine. Cereals high in RS may be beneficial to improve human health and reduce the risk of diet‐related chronic diseases. It has been reported through chemical mutagenesis and RNA interference studies that starch branching enzymes (SBEs) play a major role in contributing to higher levels of RS in cereal crops. In this study, we used multiplex clustered regularly interspaced short palindromic repeat (CRISPR)–CRISPR associated protein 9 (Cas9) genome editing to simultaneously target all four SBE genes in rice using the endogenous transfer RNA (tRNA)‐processing system for expressing the single‐guide RNAs (sgRNAs) targeting these genes. The CRISPR–Cas9 vector construct with four SBE gene sgRNAs was transformed into the U.S. rice cultivar Presidio using Agrobacterium‐mediated transformation. Knockout mutations were identified at all four SBE genes across eight transgene‐positive T0 plants. Transgene‐free T1 lines with different combinations of disrupted SBE genes were identified, with several SBE‐edited lines showing significantly increased RS content up to 15% higher than the wild‐type (WT) cultivar Presidio. Although further efforts are needed to fix all of the mutant alleles as homozygous, our study demonstrated the potential of multiplex genome editing to develop high‐RS lines.

Energy-intense activities and the unpredictable and complex behavior of building occupants lead to an increase in building energy demand. It is, therefore, crucial to study underlying factors for building energy demand related to the users. Higher educational buildings are relevant to study for several reasons: they host the future workforce and citizens, they are predicted to increase in numbers, and they represent a building type less studied. Furthermore, green-rated buildings equipped with smart building systems also represent a research gap that is relevant to address since such a building design involves IoT-functionalities and digital features for the building occupants to interact with. There is also a conceivable risk that if the users know that the building is green-rated and technologically advanced, this may alter their perception of the building operation and thus their behavior. To study the relationship between building occupants and such green and smart educational structure, a survey was conducted in a Swedish higher educational building; as a result, 300 responses were collected and analyzed. The responses revealed that the building occupants act with energy awareness, and they are conscious about energy-saving behaviors. One building feature in particular was studied: the Digital Room Panels (DRPs). The DRP allows the building occupants to modify the indoor temperature and is, therefore, essential for thermal comfort. One key finding from the survey revealed that 70% of the building occupants did not know how the DRPs operate. This study argues that this result can be explained with a lack of communication and user friendliness. Inadequate interactions with building systems could also result in opportunities for energy saving might not be realized. The findings of this case study led to valuable recommendations and suggestions for future research endeavors.

We calibrate the calving parameterisation implemented in the Open Global Glacier Model via two methods (velocity constraint and surface mass balance (SMB) constraint) and assess the impact of accounting for frontal ablation on the ice volume estimate of Greenland tidewater peripheral glaciers (PGs). We estimate an average regional frontal ablation flux of 7.38±3.45 Gta−1 after calibrating the model with two different satellite velocity products, and of 0.69±0.49 Gta−1 if the model is constrained using frontal ablation fluxes derived from independent modelled SMB averaged over an equilibrium reference period (1961–90). This second method makes the assumption that most PGs during that time have an equilibrium between mass gain via SMB and mass loss via frontal ablation. This assumption serves as a basis to assess the order of magnitude of dynamic mass loss of glaciers when compared to the SMB imbalance. The differences between results from both methods indicate how strong the dynamic imbalance might have been for PGs during that reference period. Including frontal ablation increases the estimated regional ice volume of PGs, from 14.47 to 14.64±0.12 mm sea level equivalent when using the SMB method and to 15.84±0.32 mm sea level equivalent when using the velocity method.

Abstract Background Meloidae (blister beetles) are known to synthetize cantharidin (CA), a toxic and defensive terpene mainly stored in male accessory glands (MAG) and emitted outward through reflex-bleeding. Recent progresses in understanding CA biosynthesis and production organ(s) in Meloidae have been made, but the way in which self-protection is achieved from the hazardous accumulation and release of CA in blister beetles has been experimentally neglected. To provide hints on this pending question, a comparative de novo assembly transcriptomic approach was performed by targeting two tissues where CA is largely accumulated and regularly circulates in Meloidae: the male reproductive tract (MRT) and the haemolymph. Differential gene expression profiles in these tissues were examined in two blister beetle species, Lydus trimaculatus (Fabricius, 1775) (tribe Lyttini) and Mylabris variabilis (Pallas, 1781) (tribe Mylabrini). Upregulated transcripts were compared between the two species to identify conserved genes possibly involved in CA detoxification and transport. Results Based on our results, we hypothesize that, to avoid auto-intoxication, ABC, MFS or other solute transporters might sequester purported glycosylated CA precursors into MAG, and lipocalins could bind CA and mitigate its reactivity when released into the haemolymph during the autohaemorrhaging response. We also found an over-representation in haemolymph of protein-domains related to coagulation and integument repairing mechanisms that likely reflects the need to limit fluid loss during reflex-bleeding. Conclusions The de novo assembled transcriptomes of L. trimaculatus and M. variabilis here provided represent valuable genetic resources to further explore the mechanisms employed to cope with toxicity of CA in blister beetle tissues. These, if revealed, might help conceiving safe and effective drug-delivery approaches to enhance the use of CA in medicine.

Highlights The New Urban Science leverages digital tools and techniques to develop new knowledge that can inform urban development processes. Interdisciplinary and transdisciplinary approaches are critical to expanding and enhancing digital modes of urban scientific knowledge production. An expansive approach to the New Urban Science can be used to develop urban transformative capacity by fostering communities of learning to leverage the commonalities and differences between and within cities.

Background: SARS-COV-2, in most cases, only generates a mild acute respiratory disease. However, patients with severe disease show an exaggerated response of the immune system, creating a pro-inflammatory state, which could cause abnormalities in the coagulation system that increases mortality. Latin American countries, specially those with limited resources, have few studies about clinical features, coagulation and inflammatory biomarkers that could be useful at admission to assess poor outcomes. Objective: The objective of this study is to describe the clinical features, coagulation, and inflammatory biomarkers, and identify risk factors at admission that are associated poor outcomes in Honduran population. Methods: A cohort study was conducted. 210 patients were included, which 105 died during hospitalization due to COVID-19 and 105 were discharged alive, between September 2020 and January 2021. Clinical and laboratorial data was retrospectively collected. Results: 57,6% of the population were male. The median age was 58 years. The median time between symptom onset and hospital admission was 6 days. D-dimer median was higher in the dead group compared with the alive group. Poor prognosis factors in the Cox multivariable model were male gender, age, symptom's duration, obesity and an elevated d dimer at admission. Conclusion: In low-middle income countries, the assessment of these clinical and laboratory tools, especially in those with risk factors for prothrombotic states, could help clinicians to correctly stratify disease prognosis, establish a baseline to evaluate further evolution, and also predict outcomes, thus improving patient management.

Background Alcohol use disorder (AUD) is a chronic, relapsing brain disorder that accounts for 5% of deaths annually, and there is an urgent need to develop new targets for therapeutic intervention. The glucagon-like peptide-1 (GLP-1) receptor agonist exenatide reduces alcohol consumption in rodents and nonhuman primates, but its efficacy in patients with AUD is unknown.Methods In a randomized, double-blinded, placebo-controlled clinical trial, treatment-seeking AUD patients were assigned to receive exenatide (2 mg subcutaneously) or placebo once weekly for 26 weeks, in addition to standard cognitive-behavioral therapy. The primary outcome was reduction in number of heavy drinking days. A subgroup also completed functional MRI (fMRI) and single-photon emission CT (SPECT) brain scans.Results A total of 127 patients were enrolled. Our data revealed that although exenatide did not significantly reduce the number of heavy drinking days compared with placebo, it significantly attenuated fMRI alcohol cue reactivity in the ventral striatum and septal area, which are crucial brain areas for drug reward and addiction. In addition, dopamine transporter availability was lower in the exenatide group compared with the placebo group. Exploratory analyses revealed that exenatide significantly reduced heavy drinking days and total alcohol intake in a subgroup of obese patients (BMI > 30 kg/m2). Adverse events were mainly gastrointestinal.Conclusion This randomized controlled trial on the effects of a GLP-1 receptor agonist in AUD patients provides new important knowledge on the effects of GLP-1 receptor agonists as a novel treatment target in addiction.Trial registration EudraCT: 2016-003343-11. ClinicalTrials.gov (NCT03232112).Funding Novavi Foundation; Research Foundation, Mental Health Services, Capital Region of Denmark; Research Foundation, Capital Region of Denmark; Ivan Nielsen Foundation; A.P. Moeller Foundation; Augustinus Foundation; Woerzner Foundation; Grosserer L.F. Foghts Foundation; Hartmann Foundation; Aase and Ejnar Danielsen Foundation; P.A. Messerschmidt and Wife Foundation; and Lundbeck Foundation.

In the light of global climate change and the current energy crisis, it is crucial to target sustainable energy use in all sectors. Buildings still remain one of the most energy-demanding sectors. Campus buildings and higher educational buildings are important to target due to their high and increasing energy demand. This building segment also represents a research gap, as mostly office or domestic buildings have been studied previously. In the quest for thermal comfort, a key stakeholder in building energy demand is the building occupant. It is therefore crucial to promote energy-aware behaviors. The building systems are another key factor to consider. As conventional building systems are replaced with smart building systems, the entire scenario is redrawn for how building occupants interact with the building and its systems. This study argues that behavior is evolving with the smartness of building systems. By means of a semi-systematic literature review, this study presents key findings from peer-reviewed research that deal with building occupant behavior, building systems and energy use in campus buildings. The literature review was an iterative process based on six predefined research questions. Two key results are presented: a graph of reported energy-saving potentials and a conceptual framework to evaluate building occupants impact on building energy use. Furthermore, based on the identified research gaps in the selected literature, areas for future research are proposed.

Rhizosphere microbial communities exert critical roles in plant health, nutrient cycling, and soil fertility. Despite the essential functions conferred by microbes, the source and acquisition of the rhizosphere are not entirely clear. Therefore, we investigated microbial community diversity and potential source using the only two native Antarctic plants, Deschampsia antarctica (Da) and Colobanthus quitensis (Cq), as models. We interrogated rhizosphere and bulk soil microbiomes at six locations in the Byers Peninsula, Livingston Island, Antarctica, both individual plant species and their association (Da.Cq). Our results show that host plant species influenced the richness and diversity of bacterial communities in the rhizosphere. Here, the Da rhizosphere showed the lowest richness and diversity of bacteria compared to Cq and Da.Cq rhizospheres. In contrast, for rhizosphere fungal communities, plant species only influenced diversity, whereas the rhizosphere of Da exhibited higher fungal diversity than the Cq rhizosphere. Also, we found that environmental geographic pressures (i.e., sampling site, latitude, and altitude) and, to a lesser extent, biotic factors (i.e., plant species) determined the species turnover between microbial communities. Moreover, our analysis shows that the sources of the bacterial communities in the rhizosphere were local soils that contributed to homogenizing the community composition of the different plant species growing in the same sampling site. In contrast, the sources of rhizosphere fungi were local (for Da and Da.Cq) and distant soils (for Cq). Here, the host plant species have a specific effect in acquiring fungal communities to the rhizosphere. However, the contribution of unknown sources to the fungal rhizosphere (especially in Da and Da.Cq) indicates the existence of relevant stochastic processes in acquiring these microbes. Our study shows that rhizosphere microbial communities differ in their composition and diversity. These differences are explained mainly by the microbial composition of the soils that harbor them, acting together with plant species-specific effects. Both plant species acquire bacteria from local soils to form part of their rhizosphere. Seemingly, the acquisition process is more complex for fungi. We identified a significant contribution from unknown fungal sources due to stochastic processes and known sources from soils across the Byers Peninsula.

Selection protocols such as SELEX, where molecules are selected over multiple rounds for their ability to bind to a target of interest, are popular methods for obtaining binders for diagnostic and therapeutic purposes. We show that Restricted Boltzmann Machines (RBMs), an unsupervised two-layer neural network architecture, can successfully be trained on sequence ensembles from single rounds of SELEX experiments for thrombin aptamers. RBMs assign scores to sequences that can be directly related to their fitnesses estimated through experimental enrichment ratios. Hence, RBMs trained from sequence data at a given round can be used to predict the effects of selection at later rounds. Moreover, the parameters of the trained RBMs are interpretable and identify functional features contributing most to sequence fitness. To exploit the generative capabilities of RBMs, we introduce two different training protocols: one taking into account sequence counts, capable of identifying the few best binders, and another based on unique sequences only, generating more diverse binders. We then use RBMs model to generate novel aptamers with putative disruptive mutations or good binding properties, and validate the generated sequences with gel shift assay experiments. Finally, we compare the RBM's performance with different supervised learning approaches that include random forests and several deep neural network architectures.

Abstract Background Stroke is a leading cause of long-term disability. Cost-effective post-stroke rehabilitation programs for upper limb are critically needed. Brain-Computer Interfaces (BCIs) which enable the modulation of Electroencephalography (EEG) sensorimotor rhythms are promising tools to promote post-stroke recovery of upper limb motor function. The “Promotoer” study intends to boost the application of the EEG-based BCIs in clinical practice providing evidence for a short/long-term efficacy in enhancing post-stroke hand functional motor recovery and quantifiable indices of the participants response to a BCI-based intervention. To these aims, a longitudinal study will be performed in which subacute stroke participants will undergo a hand motor imagery (MI) training assisted by the Promotoer system, an EEG-based BCI system fully compliant with rehabilitation requirements. Methods This longitudinal 2-arm randomized controlled superiority trial will include 48 first ever, unilateral, subacute stroke participants, randomly assigned to 2 intervention groups: the BCI-assisted hand MI training and a hand MI training not supported by BCI. Both interventions are delivered (3 weekly session; 6 weeks) as add-on regimen to standard intensive rehabilitation. A multidimensional assessment will be performed at: randomization/pre-intervention, 48 h post-intervention, and at 1, 3 and 6 month/s after end of intervention. Primary outcome measure is the Fugl-Meyer Assessment (FMA, upper extremity) at 48 h post-intervention. Secondary outcome measures include: the upper extremity FMA at follow-up, the Modified Ashworth Scale, the Numeric Rating Scale for pain, the Action Research Arm Test, the National Institute of Health Stroke Scale, the Manual Muscle Test, all collected at the different timepoints as well as neurophysiological and neuroimaging measures. Discussion We expect the BCI-based rewarding of hand MI practice to promote long-lasting retention of the early induced improvement in hand motor outcome and also, this clinical improvement to be sustained by a long-lasting neuroplasticity changes harnessed by the BCI-based intervention. Furthermore, the longitudinal multidimensional assessment will address the selection of those stroke participants who best benefit of a BCI-assisted therapy, consistently advancing the transfer of BCIs to a best clinical practice. Trial registration Name of registry: BCI-assisted MI Intervention in Subacute Stroke (Promotoer). Trial registration number: NCT04353297 ; registration date on the ClinicalTrial.gov platform: April, 15/2020.

Drug–Drug Interactions (DDIs) produce essential and valuable insights for healthcare professionals, since they provide data on the impact of concurrent administration of medications to patients during therapy. In that sense, some relevant works, related to the DDIExtraction2013 Challenge, are available in the current technical literature. This study aims to improve previous results, using two models, where a Gaussian noise layer is added to achieve better DDI relationship extraction. (1) A Piecewise Convolutional Neural Network (PW-CNN) model is used to capture relationships among pharmacological entities described in biomedical databases. Additionally, the model incorporates multichannel words to enrich a person’s vocabulary and reduce unfamiliar words. (2) The model uses the pre-trained BERT language model to classify relationships, while also integrating data from the target entities. After identifying the target entities, the model transfers the relevant information through the pre-trained architecture and integrates the encoded data for both entities. The results of the experiment show an improved performance, with respect to previous models.

Cerium dioxide CeO _2 (ceria) is an important material in catalysis and energy applications. The intrinsic Frenkel and Schottky defects can impact a wide range of material properties including the oxygen storage capacity, the redox cycle, and the ionic and thermal transport. Here, we study the impact of Frenkel and Schottky defects on the structural dynamics and thermal properties of ceria using density functional theory. The phonon contributions to the free energy are found to reduce the defect formation free energies at elevated temperature. The phonon dispersions of defective CeO _2 show significant broadening of the main branches compared to stoichiometric ceria. Phonon modes associated with the defects are identifiable in the infrared spectra through characteristic shoulders on the main features of the stoichiometric fluorite structure. Finally, the presence of Frenkel and Schottky defects are also found to reduce the thermal conductivity by up to 88% compared to stoichiometric CeO _2 .

Phytopatogenic fungi cause severe economic losses worldwide. Rhizoctonia solani Kühn is a pathogenic fungi affecting several crops, controlled mainly by agrochemicals. Biological control has arisen as another option for managing this pathogen. In this study, we evaluated the biocontroller potential of five orchid mycorrhizal fungi (OMF) isolated from terrestrial Chilean orchids on R. solani. We compared the biocontroller effect of these OMFs with that of Trichoderma harzianum Rifai in an in vitro dual culture experiment. We found that R. solani can be controlled in vitro by OMF isolated from native orchids. The OMF isolated from Chloraea virescens and C. lamellata showed the best biocontroller results, which were similar, or even higher, than with T. harzianum. Thus, OMFs could become a relevant alternative for the integral control of R. solani, contributing to the reduction in the use of agrochemicals in crops.

Abstract Background Add-on robot-mediated therapy has proven to be more effective than conventional therapy alone in post-stroke gait rehabilitation. Such robot-mediated interventions routinely use also visual biofeedback tools. A better understanding of biofeedback content effects when used for robotic locomotor training may improve the rehabilitation process and outcomes. Methods This randomized cross-over pilot trial aimed to address the possible impact of different biofeedback contents on patients’ performance and experience during Lokomat training, by comparing a novel biofeedback based on online biological electromyographic information (EMGb) versus the commercial joint torque biofeedback (Rb) in sub-acute non ambulatory patients. 12 patients were randomized into two treatment groups, A and B, based on two different biofeedback training. For both groups, study protocol consisted of 12 Lokomat sessions, 6 for each biofeedback condition, 40 min each, 3 sessions per week of frequency. All patients performed Lokomat trainings as an add-on therapy to the conventional one that was the same for both groups and consisted of 40 min per day, 5 days per week. The primary outcome was the Modified Ashworth Spasticity Scale, and secondary outcomes included clinical, neurological, mechanical, and personal experience variables collected before and after each biofeedback training. Results Lokomat training significantly improved gait/daily living activity independence and trunk control, nevertheless, different effects due to biofeedback content were remarked. EMGb was more effective to reduce spasticity and improve muscle force at the ankle, knee and hip joints. Robot data suggest that Rb induces more adaptation to robotic movements than EMGb. Furthermore, Rb was perceived less demanding than EMGb, even though patient motivation was higher for EMGb. Robot was perceived to be effective, easy to use, reliable and safe: acceptability was rated as very high by all patients. Conclusions Specific effects can be related to biofeedback content: when muscular-based information is used, a more direct effect on lower limb spasticity and muscle activity is evidenced. In a similar manner, when biofeedback treatment is based on joint torque data, a higher patient compliance effect in terms of force exerted is achieved. Subjects who underwent EMGb seemed to be more motivated than those treated with Rb.

The presence of cubic PuH2 and PuH3, the products of hydrogen corrosion of Pu, during long-term storage is of concern because of the materials’ pyrophoricity and ability to catalyse the oxidation reaction of Pu to form PuO2. Here, we modelled cubic PuH2 and PuH3 using Density Functional Theory (DFT) and assessed the performance of the PBEsol+U+SOC (0 ≤ U ≤ 7 eV) including van der Waals dispersion using the Grimme D3 method and the hybrid HSE06sol+SOC. We investigated the structural, magnetic and electronic properties of the cubic hydride phases. We considered spin–orbit coupling (SOC) and non-collinear magnetism to study ferromagnetic (FM), longitudinal and transverse antiferromagnetic (AFM) orders aligned in the , and directions. The hybrid DFT confirmed that FM orders in the and directions were the most stable for cubic PuH2 and PuH3, respectively. For the standard DFT, the most stable magnetic order is dependent on the value of U used, with transitions in the magnetic order at higher U values (U > 5 eV) seen for both PuH2 and PuH3.

Background: Crutches are the most common walking aids prescribed to improve mobility in subjects with central nervous system (CNS) lesions. To increase adherence to the appropriate level of crutch usage, providing load-related auditory feedback (aFB) may be a useful approach. We sensorized forearm crutches and developed a custom software to provide aFB information to both user and physical therapist (PhT).Aim: Evaluate aFB effects on load control during gait by a self-controlled case series trial.Methods: A single experimental session was conducted enrolling 12 CNS lesioned participants. Load on crutch was recorded during 10 Meter Walk Test performed with and without aFB. In both cases, crutch load data, and gait speed were recorded. Usability and satisfaction questionnaires were administered to participants and PhTs involved.Results: Reliable data were obtained from eight participants. Results showed that compared to the no FB condition, aFB yielded a significant reduction in the mean load on the crutches during gait (p = 0.001). The FB did not influence gait speed or fatigue (p > 0.05). The experience questionnaire data indicated a positive experience regarding the use of aFB from both participants' and PhTs' perspectives.Conclusion: aFB significantly improves compliance with crutch use and does not affect gait speed or fatigue by improving the load placed on crutches. The FB is perceived by users as helpful, safe, and easy to learn, and does not interfere with attention or concentration while walking. Furthermore, the PhTs consider the system to be useful, easy to learn and reliable.

Digitalization offers new, unprecedented possibilities to increase the energy efficiency and improve the indoor conditions in buildings in a cost-efficient way. Smart buildings are seen by many stakeholders as the way forward. Smart buildings feature advanced monitoring and control systems that allow a better control of the buildings’ indoor spaces, but it is becoming evident that the massive amount of data produced in smart buildings is rarely used. This work presents a long-term evaluation of a smart building testbed for one year; the building features state-of-the-art monitoring capability and local energy generation (PV). The analysis shows room for improving energy efficiency and indoor comfort due to non-optimal control settings; for instance, average indoor temperatures in all winter months were above 24 °C. The analysis of electricity and domestic hot water use has shown a relevant spread in average use, with single users consuming approximately four times more than the average users. The combination of CO2 and temperature sensor was sufficient to pinpoint the anomalous operation of windows in wintertime, which has an impact on energy use for space heating. Although the quantification of the impact of users on the overall energy performance of the building was beyond the scope of this paper, this study showcases that modern commercial monitoring systems for buildings have the potential to identify anomalies. The evidence collected in the paper suggests that this data could be used to promote energy-efficient behaviors among building occupants and shows that cost-effective actions could be carried out if data generated by the monitoring and control systems were used more extensively.

Objective: The aim of the present observational study is to report on the data from a large sample of inpatients, clinical staff and other workers at an Italian neurorehabilitation hospital dealing with SARS-CoV-2 infections, in order to analyze how it might have affected the management and the effectiveness of neurorehabilitation.Methods: The data on infection monitoring, obtained by 2,192 swabs, were reported and compared among 253 patients, 722 clinical professionals and 232 other hospital workers. The number of admissions and neurorehabilitation sessions performed in the period from March-May 2020 was compared with those of the same period in 2019.Results: Four patients and three clinical professionals were positive for COVID-19 infection. Six out of these seven people were from the same ward. Several measures were taken to handle the infection, putting in place many restrictions, with a significant reduction in new admissions to the hospital (p < 0.001). However, neither the amount of neurorehabilitation for inpatients (p = 0.681) nor the effectiveness of treatments (p = 0.464) were reduced when compared to the data from 2019.Conclusions: Our data show that the number of infections was contained in our hospital, probably thanks to the protocols adopted for reducing contagion and the environmental features of our wards. This allowed inpatients to continue to safely spend more than 3 hours per day in neurorehabilitation, effectively improving their independence in the activities of daily living.

Affinity maturation is a complex dynamical process allowing the immune system to generate antibodies capable of recognizing antigens. We introduce a model for the evolution of the distribution of affinities across the antibody population in germinal centers. The model is amenable to detailed mathematical analysis and gives insight on the mechanisms through which antigen availability controls the rate of maturation and the expansion of the antibody population. It is also capable, upon maximum-likelihood inference of the parameters, to reproduce accurately the distributions of affinities of IgG-secreting cells we measure in mice immunized against Tetanus Toxoid under largely varying conditions (antigen dosage, delay between injections). Both model and experiments show that the average population affinity depends non-monotonically on the antigen dosage. We show that combining quantitative modeling and statistical inference is a concrete way to investigate biological processes underlying affinity maturation (such as selection permissiveness), hardly accessible through measurements.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV2), the cause of the current pandemic coronavirus disease 2019 (COVID-19), primarily targets the respiratory system. Some patients also experience neurological signs and symptoms ranging from anosmia, ageusia, headache, nausea, and vomiting to confusion, encephalitis, and stroke. Approximately 36% of those with severe COVID-19 experience neurological complications. The virus may enter the central nervous system through the olfactory nerve in the nasal cavity and damage neurons in the brainstem nuclei involved in the regulation of respiration. Patients with cerebellar ataxia (CA) are particularly vulnerable to severe outcome if they contract COVID-19 because of the complexity of their disease, the presence of comorbidities, and their use of immunosuppressive therapies. Most CA patients burdened by progressive neurologic deficits have substantially impaired mobility and other essential functions, for which they rely heavily on ambulatory services, including rehabilitation and psychosocial care. Cessation of these interventions because of isolation restrictions places the CA patient population at risk of further deterioration. This international panel of ataxia experts provides recommendations for neurologists caring for patients with CA, emphasizing a pro-active approach designed to maintain their autonomy and well-being: continue long-term medications, promote rehabilitation efforts, utilize the technology of virtual visits for regular contact with healthcare providers, and pay attention to emotional and psychosocial health. Neurologists should play an active role in decision-making in those CA cases requiring escalation to intensive care and resuscitation. Multi-disciplinary collaboration between care teams is always important, and never more so than in the context of the current pandemic.

Plant traits such as phenological development, growth rate, stress tolerance and seeds production may play an important role in the process of acclimatisation to new environments for introduced plants. Experiments that distinguish phenotypic plasticity from ecotypic differentiation would allow an understanding of the role of plant traits in the invasion process. We quantified the variation in phenological and overall performance traits associated with the invasion process for three herbaceous species native to Spain and invasive to Chile (Trifolium glomeratum, Hypochaeris glabra and Leontodon saxatilis). We grew plants from native and exotic populations along rainfall gradients in outdoor common gardens, located in the native and the introduced ranges and measured plant survival, phenology (days to flowering), biomass and seed output. Days to flowering was positively correlated with precipitation of the origin population for T. glomeratum and the native populations of H. glabra, but this pattern was not adaptive, as it was not associated with an increase in performance traits of these species. Phenology may instead reflect ecotypic differentiation to the environmental conditions of the original populations. Comparison between ranges (i.e. performance in both common gardens) was only possible for L. saxatilis. This species showed little variation in phenology and both native and exotic populations had higher fitness in the introduced range. This suggests that plasticity enhances invasiveness through increased propagule pressure in the novel environment. Our findings highlight the utility of common garden experiments in examining patterns of phenological and performance traits that relate to species invasiveness.

Abstract Growing evidence indicates that perceptual-motor codes may be associated with and influenced by actual bodily states. Following a spinal cord injury (SCI), for example, individuals exhibit reduced visual sensitivity to biological motion. However, a dearth of direct evidence exists about whether profound alterations in sensorimotor traffic between the body and brain influence audio-motor representations. We tested 20 wheelchair-bound individuals with lower skeletal-level SCI who were unable to feel and move their lower limbs, but have retained upper limb function. In a two-choice, matching-to-sample auditory discrimination task, the participants were asked to determine which of two action sounds matched a sample action sound presented previously. We tested aural discrimination ability using sounds that arose from wheelchair, upper limb, lower limb, and animal actions. Our results indicate that an inability to move the lower limbs did not lead to impairment in the discrimination of lower limb-related action sounds in SCI patients. Importantly, patients with SCI discriminated wheelchair sounds more quickly than individuals with comparable auditory experience (i.e. physical therapists) and inexperienced, able-bodied subjects. Audio-motor associations appear to be modified and enhanced to incorporate external salient tools that now represent extensions of their body schemas.

Insanity defense is sometimes invoked in criminal cases, and its demonstration is usually based on a multifactorial contribution of behavioural, clinical, and neurological elements. Neuroradiological evidence of structural alterations in cerebral areas that involve decision-making and moral reasoning is often accepted as a useful tool in these evaluations. On the other hand, the genetic predisposition to anti-social behavior is still controversial. In this paper, we describe two cases of violent crimes committed by young carriers of genetic variants associated with personality disorder; both the defendants claimed to be insane at the time of the crime. We discuss these cases and review the scientific literature regarding the relationship between legal incapacity/predisposition to criminal behavior and genetic mutations. In conclusion, despite some genetic variants being able to influence several cognitive processes (like moral judgement and impulse control), there is currently no evidence that carriers of these mutations are, per se, incapable of intentionally committing crimes.

Colobanthus quitensis (Kunt) is one of the two vascular plant species present in Antarctica and develops under severe environmental conditions, being found in both pristine and human-threatened environments. We determined the Cd, Cr, Cu, Mn, Ni, Pb, and Zn levels in C. quitensis roots, leaves, and soils of origin using flame atomic absorption spectroscopy. In January 2017, we collected samples from four geographical zones on the longitudinal gradient along which C. quitensis is distributed, starting from Punta Arenas (PAR) at the extreme south of mainland Chile and moving southwards to the Antarctic territory from King George Island (KGI) to Hannah Point Peninsula (PHA) and finally Lagotellerie Island (LAT). We used certified reference material to validate the plant tissues and soil samples we collected. The highest concentrations of metals that we measured in the soils and in the C. quitensis roots and leaves were in samples we collected at the KGI station, the zone with the greatest human activity. The lowest concentrations we measured were at the LAT station, an island with little human intervention and scarce fauna. The mean concentrations of metals in the roots and leaves of C. quitensis followed a similar order at all sampling locations: Mn > Zn > Cu > Ni > Pb > Cr > Cd. In contrast, in soil, they followed the following order: Mn > Zn > Cu > Cr > Pb > Ni > Cd. The concentration levels obtained for the different metals in the soil and plants tissue samples in this region of Antarctica indicated that the area was non-polluted. However, the metallic trace element (MTE) concentrations may be at an early stage of contamination, as described in other areas of the Antarctic, being a new threat to this continent.

The revolutionary armed forces of Cuba (FAR) are undoubtedly a key agent for the political future of the island, with this fact as a starting point, this article presents an analysis from a theoretical and analytical framework of the military instrument, to foresee the FAR of Cuba as an actor and the role it may play in possible future scenarios. Military power; armed forces; Cuba; expansion of the institutional role

Los Andes de Chile es un gradiente geográfico latitudinal con una marcada variación de sus condiciones climáticas. A lo largo de sus laderas se distribuyen la siempreverde Nothofagus dombeyi y la decidua Nothofagus pumilio, las cuales difieren en sus hábitos foliares, extensión de sus rangos y límites de distribución latitudinal. La ecología vegetal propone que las condiciones climáticas desfavorables son factores limitantes en la distribución de las especies arbóreas, y que las respuestas de los rasgos funcionales hidráulicos permiten entender los mecanismos a los que subyace la distribución actual de estas. Hipotetizamos que ambas especies tendrán bajos valores promedio de la conductividad hidráulica específica de hoja (KL) y del xilema (KS) en poblaciones cercanas a sus límites de distribución comparado con poblaciones centrales, ya que las primeras tienen predominantemente condiciones climáticas desfavorables. Cuantificamos in situ la KL y KS, en poblaciones cercanas a los límites septentrionales y meridionales como una población central para N. dombeyi y N. pumilio a lo largo de los Andes de Chile. Los resultados muestran que ambas especies el KL y KS tuvieron valores promedios más bajos en sus sitios septentrionales y meridionales comparados con sus sitios centrales. Además, el desempeño hidráulico de los individuos de N. pumilio del sitio central fue mayor que N. dombeyi. Concluimos que una menor conductividad hidráulica asociada a los límites de distribución para ambas especies estudiadas, implica una menor probabilidad de verse afectadas por el embolismo, independiente de su hábito foliar, mostrando una convergencia funcional hidráulica frente a menor disponibilidad de agua o frío.

Patients with acute myocardial infarction (AMI) are at increased risk of recurrent ischemic events after hospital discharge, despite optimal medical therapy. Current practice guidelines strongly encourage the early assessment of the residual ischemic risk in post-AMI patients, in order to identify those who may benefit from a prolonged dual antiplatelet therapy. To this end, some scoring systems have been proposed. However, most scores were developed for patients with stable coronary artery disease undergoing percutaneous coronary intervention. Moreover, nearly all failed to be implemented in everyday clinical practice, probably because of the perceived complexity due to the large number of incorporated variables. Therefore, the identification of the ideal AMI patient who can benefit from a prolonged (beyond 1 year after the index event) dual antiplatelet therapy remains to be clarified, especially when the bleeding risk associated with such therapy is considered. In this review, we summarize the current evidence on the prolonged use of dual antiplatelet therapy after AMI, with a special focus on recent advances regarding the identification of high-risk patients who may derive a favorable net clinical benefit from such a therapeutic strategy.