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Nell'ultimo decennio la ricerca sull'utilizzo terapeutico degli psichedelici ha subito un'impennata, soprattutto per quanto riguarda la loro poten- ziale applicazione nel trattamento dei disturbi psichiatrici. In questi studi è stata indagata la sicurezza e l'efficacia delle varie sostanze psichedeliche, come gli psichedelici classici (psilocibina, ayahuasca e LSD) la ketamina e l'MDMA. Gli studi si sono focalizzati nel trattamento di diversi disturbi psi- chiatrici come la depressione, le dipendenze da sostanza e la sindrome da stress post-traumatico (PTSD). Inoltre, grazie allo sviluppo delle tecniche di neuroimaging è possibile indagare come queste sostanze modulino i di- versi network cerebrali, e come esse sembrino effettuare i loro meccanismi terapeutici. In questo articolo, verranno descritti gli aspetti generali delle diverse sostanze psichedeliche, dalla classificazione ai diversi meccanismi farmacologici sottolineando le differenze tra psichedelici classici e non. Inol- tre, verranno analizzate le diverse componenti della psicoterapia assistita da psichedelici con particolare riguardo alle variabili del set e del setting. Infi- ne, verrà effettuata una revisione della letteratura riguardante gli studi più importanti dell'ultimo decennio sul tema del trattamento di ansia e depres- sione con psichedelici classici e ketamina, dipendenze da sostanze trattate con psichedelici classici e ketamina e trattamento della sindrome da stress post-traumatico con MDMA.

An emerging body of literature supports the role of individualized prognostic tools to guide the management of patients after trauma. The aim of this study was to develop advanced modeling tools from multidimensional data sources, including immunological analytes and clinical and administrative data, to predict outcomes in trauma patients.This was a prospective study of trauma patients at Level 1 centers from 2015 to 2019. Clinical, flow cytometry, and serum cytokine data were collected within 48 hours of admission. Sparse logistic regression models were developed, jointly selecting predictors and estimating the risk of ventilator-associated pneumonia, acute kidney injury, complicated disposition (death, rehabilitation, or nursing facility), and return to the operating room. Model parameters (regularization controlling model sparsity) and performance estimation were obtained via nested leave-one-out cross-validation.A total of 179 patients were included. The incidences of ventilator-associated pneumonia, acute kidney injury, complicated disposition, and return to the operating room were 17.7%, 28.8%, 22.5%, and 12.3%, respectively. Regarding extensive resource use, 30.7% of patients had prolonged intensive care unit stay, 73.2% had prolonged length of stay, and 23.5% had need for prolonged ventilatory support. The models were developed and cross-validated for ventilator-associated pneumonia, acute kidney injury, complicated dispositions, and return to the operating room, yielding predictive areas under the curve from 0.70 to 0.91. Each model derived its optimal predictive value by combining clinical, administrative, and immunological analyte data.Clinical, immunological, and administrative data can be combined to predict post-traumatic outcomes and resource use. Multidimensional machine learning modeling can identify trauma patients with complicated clinical trajectories and high resource needs.

Microdissection testicular sperm extraction (mTESE) has been proposed as a salvage treatment option for men with a previously failed classic TESE (cTESE), but data are scarce. We aimed to assess the outcome of and potential predictors of successful salvage mTESE in a cohort of men previously submitted to unfruitful cTESE. Data from 61 men who underwent mTESE after a failed cTESE between 01/2014 and 10/2020, at 6 tertiary-referral centres in Italy were analysed. All men were investigated with semen analyses, testicular ultrasound, hormonal and genetic blood testing. Pathological diagnosis from TESE was collected in every man. Descriptive statistics and logistic regression models were used to investigate potential predictors of positive sperm retrieval (SR+) after salvage mTESE. Baseline serum Follicle-Stimulating hormone (FSH) and total testosterone levels were 17.2 (8.6–30.1) mUI/mL and 4.7 (3.5-6.4) ng/mL, respectively. Sertoli-cell-only syndrome (SCOS), maturation arrest (MA) and hypospermatogenesis were found in 24 (39.3%), 21 (34.4%) and 16 (26.2%) men after cTESE, respectively. At mTESE, SR+ was found in 30 (49.2%) men. Patients with a diagnosis of hypospermatogenesis had a higher rate of SR+ (12/16 (75%)) compared to MA (12/21 (57.1%)) and SCOS (6/24 (25%)) patients at mTESE (p < 0.01). No clinical and laboratory differences were observed between SR+ and SR- patients at mTESE. There were no significant complications after mTESE. At multivariable logistic regression analysis, only hypospermatogenesis (OR 9.5; p < 0.01) was independently associated with SR+ at mTESE, after accounting for age and FSH. In conclusion, salvage mTESE in NOA men with previous negative cTESE was safe and promoted SR+ in almost 50%. A baseline pathology of hypospermatogenesis at cTESE emerged as the only independent predictor of positive outcomes at salvage mTESE.

In the wake of stagnant modal share of the European rail freight sector, this support study provides market information for the revision of the Guidelines on State aid for railway undertakings. It addresses four areas of interest: status of rail infrastructure; accessibility and costs pertaining to rolling stock; profitability and demand elasticity of rail freight ser- vices; and effectiveness of State support measures. A novel dataset of costs and revenues of rail freight across Europe, compiled using both publicly available data and input from extensive stakeholder consultation was built for that purpose. The findings are as follows. The inadequacy of intermodal terminals, congested rail networks, and costliness of private sidings all restrict the capacity of European rail infrastructure. Access to rolling stock is characterised by high costs and a lack of technical standardisation across Member States. We find that rail freight sectors in many countries are loss-making, with some segments being profitable. Efficient transshipment and transport of high freight volumes over long distances improves profitability of intermodal operations. The study shows that price sen- sitivity of rail freight services differs depending on the level of competition faced by road transport. The study also highlights to what extent higher thresholds for proportionate State aid and improved flexibility of schemes could be considered.

BACKGROUND Normative cognitive data can distinguish impairment from healthy cognitive function and pathological decline from normal ageing. Traditional methods for deriving normative data typically require extremely large samples of healthy participants, stratifying test variation by pre-specified age groups and key demographic features (age, sex, education). Linear regression approaches can provide normative data from more sparsely sampled datasets, but non-normal distributions of many cognitive test results may lead to violation of model assumptions, limiting generalisability OBJECTIVE The aims of the study are to describe a novel methodological approach for generating normative cognitive data and examine the sensitivity of this novel approach in comparison to other methods for deriving normative data. METHODS The current study proposes a novel Bayesian framework for normative data generation. Participants (n=728; 368 male and 360 female, age 18-75 years), completed the Cambridge Neuropsychological Test Automated Battery via the research crowdsourcing website Prolific.ac. Participants completed tests of visuospatial recognition memory (Spatial Working Memory test), visual episodic memory (Paired Associate Learning test) and sustained attention (Rapid Visual Information Processing test). Test outcomes were modelled as a function of age using Bayesian Generalised Linear Models, which were able to derive posterior distributions of the authentic data, drawing from a wide family of distributions. RESULTS Markov Chain Monte Carlo algorithms generated a large synthetic dataset from posterior distributions for each outcome measure, capturing normative distributions of cognition as a function of age, sex and education. Comparison with stratified and linear regression methods showed converging results, with the Bayesian approach producing similar age, sex and education trends in the data, and similar categorisation of individual performance levels. CONCLUSIONS This study documents a novel, reproducible and robust method for describing normative cognitive performance with ageing using a large dataset.

The Salinas del Bebedero occupies an isolated basin in the foreland of central Argentina at 33°S and was flooded repeatedly over past 25 ka. Isotopic evidence demonstrates that this flooding was due to overflow of the nearby Río Desaguadero with waters derived from the distant (≥300 km) central Andes between 28–34°S. Stratigraphic and shoreline evidence shows that floods occurred most frequently from 14.3 to 11.4 ka, followed by lesser events between 14.3 to 11.4 ka, and during the late Holocene from 2.6 to ca. 0.2 ka. Hydraulic modeling (2D HEC-RAS) shows that these floods could have originated from repeated subglacial drainage or sudden outbursts with a volume of >100 × 106m3and a peak discharge of >1,000 m3s-1each. The absence of flood deposits from 11 to 3 ka points to exceptionally dry and virtually ice-free conditions in the Andes between 28–34°S. The floods were probably caused by major rainfall or dammed-lake outbursts clustered largely during wet pluvial periods in the otherwise moisture-limited central Andes and Atacama Desert, such as when the Intertropical Convergence Zone was shifted southward. These include Central Andean pluvial events (CAPE) I (17–14.5 ka) and II (12.5–9 ka), and the Neoglacial/Formative archeological period 2500 ka to near-present.

A comparison of three different electromagnetic scattering models for land surface delay-Doppler maps (DDMs) obtained from global navigation satellite system reflectometry (GNSS-R) along a Cyclone Global Navigation Satellite System (CYGNSS) track in the San Luis Valley, Colorado, USA, is presented. The three models are the analytical Kirchhoff solutions (AKS), the Soil And VEgetation Reflection Simulator (SAVERS), and the improved geometrical optics with topography (IGOT). Common inputs to the three models were defined by using field samples of soil moisture and texture, soil surface roughness measurements, and a digital elevation model (DEM). The resulting peak reflectivity profiles of the models and the CYGNSS data all had a dynamic range of 10 dB along the selected track, mainly due to the influence of topography. The reflectivities obtained from all three models agreed with one another to within 2.4 dB along the full length of the track. The models also showed general agreement with the corresponding CYGNSS data, although the modeled profiles were higher and smoother. Additional characterization of fine-scale surface roughness is identified as an area for future work to improve model fidelity. An intercomparison of DDM structure for three selected acquisitions is also provided.

Experimental studies of microbial evolution have largely focused on monocultures of model organisms, but most microbes live in communities where interactions with other species may impact rates and modes of evolution. Using the cheese rind model microbial community, we determined how species interactions shape the evolution of the widespread food- and animal-associated bacteriumStaphylococcus xylosus. We evolvedS. xylosusfor 450 generations alone or in co-culture with one of three microbes: the yeastDebaryomyces hansenii, the bacteriumBrevibacterium aurantiacum, and the moldPenicillium solitum. We used the frequency of colony morphology mutants (pigment and colony texture phenotypes) and whole-genome sequencing of isolates to quantify phenotypic and genomic evolution after 15 weeks of the evolution. The yeastD. hanseniistrongly promoted diversification ofS. xylosus; by the end of the experiment, all populations co-cultured with the yeast were dominated by pigment and colony morphology mutant phenotypes. Populations ofS. xylosusgrown alone, withBrevibacterium, or withPenicilliumdid not evolve novel phenotypic diversity. Whole-genome sequencing of individual mutant isolates across all four treatments revealed numerous unique mutations in the operons for the SigB, Agr, and WalKR global regulators, but only in theD. hanseniitreatment. Phenotyping and RNA-seq experiments demonstrated that these mutations altered pigment and biofilm production, spreading, stress tolerance, and metabolism ofS. xylosus. Fitness experiments revealed trade-offs of these mutations across biotic environments caused by antagonistic pleiotropy, where beneficial mutations that evolved in the presence of the yeastDebaryomyceshad strong negative fitness effects in other biotic environments.IMPORTANCESubstantial phenotypic and genomic variation exists within microbial species, but the ecological factors that shape this strain diversity are poorly characterized. We demonstrate that the biotic context of a widespreadStaphylococcusspecies can impact the evolution of strain diversity. This work demonstrates the potential for microbes in food production environments to rapidly evolve to novel substrates and biotic environments. Our findings may also help understand how otherStaphylococcusspecies may evolve in multispecies microbiomes.

In health care, second victims are traumatized clinicians involved in unanticipated or untoward patient events. Programs that address second victim syndrome are sparse and its diagnosis often goes unrecognized. Consistently, literature has identified gaps in support resources, leading to compromised patient care and provider health. This project evaluates the need for second victim resources in trauma care providers at a tertiary public level 1 trauma hospital by electronically implementing a validated second victim survey over 5 weeks. Our results illustrate that second victim syndrome is prevalent among 57.1% of trauma care providers, of which 22.9% agree that second victim syndrome results in some form of undesirable work intentions.

Traumatic injuries to the mesenteric vessels are rare and often lethal. Visceral vessels, such as the superior mesenteric artery (SMA) and vein (SMV), supply blood to the small and large bowel by a rich system of collaterals. Because fewer than 100 such injuries have been described in the literature, they pose challenges in both diagnosis and management and can unfortunately result in high mortality rates. Prompt diagnosis, surgical intervention, and resuscitation can lead to improved outcomes. Here, we review the literature surrounding traumatic injuries of the SMA/SMV and discuss management strategies.

P-glycoprotein (P-gp) is a key component of the intestinal epithelium playing a pivotal role in removal of toxins and efflux of endocannabinoids to prevent excessive inflammation and sustain homeostasis. Recent studies revealed butyrate and secondary bile acids, produced by the intestinal microbiome, potentiate the induction of functional P-gp expression. We now aim to determine the molecular mechanism by which this functional microbiome output regulates P-gp. RNA sequencing of intestinal epithelial cells responding to butyrate and secondary bile acids in combination discovered a unique transcriptional program involving multiple pathways that converge on P-gp induction. Using shRNA knockdown and CRISPR/Cas9 knockout cell lines, as well as mouse models, we confirmed the RNA sequencing findings and discovered a role for intestinal HNF4α in P-gp regulation. These findings shed light on a sophisticated signaling network directed by intestinal microbial metabolites that orchestrate P-gp expression and highlight unappreciated connections between multiple pathways linked to colonic health.

The spatial distribution of phytoplankton is characterized by distinct fine-scale (1-100km) patchiness associated with mesoscale and sub-mesoscale ocean dynamics. While fine-scale patchiness in total phytoplankton biomass is often observed in satellite and in-situ data, fine-scale structuring of phytoplankton communities is still rarely documented, limiting our ability to accurately characterize ocean biodiversity. Here we show results from a high resolution study aimed at characterizing fine-scale variations in the community composition of picophytoplankton inhabiting the summertime surface waters of the Southeastern Mediterranean. Combining high resolution (30m) Landsat imagery and in-situ measurements along two transacts, we show that in the ultra-oligotrophic conditions characterizing this region picophytoplankton may be assembled in fine-scale patches that significantly differ in their community composition. The separated patches are also characterized by distinct signatures in the surface temperature and salinity space, providing observational evidence to the phytoplanktonic landscape being organized in segregated fine-scale assemblages that differ in their life history. Our results indicate that fine-scale variability patterns and the processes underlying their formation should be considered when investigating ecological and biogeochemical processes in oligotrophic waters, and demonstrate the potential of harnessing very high resolution satellite data (~10 m) for that purpose.

Stretch-growth has been defined as a process that extends axons via the application of mechanical forces. In the present article, we used a protocol based on magnetic nanoparticles (NPs) for labeling the entire axon tract of hippocampal neurons, and an external magnetic field gradient to generate a dragging force. We found that the application of forces below 10 pN induces growth at a rate of 0.66 ± 0.02 µm h(−1) pN(−1). Calcium imaging confirmed the strong increase in elongation rate, in comparison with the condition of tip-growth. Enhanced growth in stretched axons was also accompanied by endoplasmic reticulum (ER) accumulation and, accordingly, it was blocked by an inhibition of translation. Stretch-growth was also found to stimulate axonal branching, glutamatergic synaptic transmission, and neuronal excitability. Moreover, stretched axons showed increased microtubule (MT) density and MT assembly was key to sustaining stretch-growth, suggesting a possible role of tensile forces in MT translocation/assembly. Additionally, our data showed that stretched axons do not respond to BDNF signaling, suggesting interference between the two pathways. As these extremely low mechanical forces are physiologically relevant, stretch-growth could be an important endogenous mechanism of axon growth, with a potential for designing novel strategies for axonal regrowth. SIGNIFICANCE STATEMENT Axon growth involves motion, and motion is driven by forces. The growth cone (GC) itself can generate very low intracellular forces by inducing a drastic cytoskeleton remodeling, in response to signaling molecules. Here, we investigated the key role of intracellular force as an endogenous regulator of axon outgrowth, which it has been neglected for decades because of the lack of methodologies to investigate the topic. Our results indicate a critical role of force in promoting axon growth by facilitating microtubule (MT) polymerization.

Tritordeum results from the crossbreeding of a wild barley (Hordeum chilense) species with durum wheat (Triticum turgidum spp. turgidum). This hexaploid crop exhibits agronomic and rheological characteristics like soft wheat, resulting in an innovative raw material to produce baked goods. We applied a gel-based proteomic approach on refined flours to evaluate protein expression differences among two widespread tritordeum cultivars (Aucan and Bulel) taking as the reference semolina and flour derived from a durum and a soft wheat cvs, respectively. The products of in vitro digestion of model breads were analyzed to compare bio-accessibility of nutrients and mapping tritordeum bread resistant peptides. Significant differences among the protein profiles of the four flours were highlighted by electrophoresis. The amino acid bio-accessibility and the reducing sugars of tritordeum and wheat breads were comparable. Tritordeum cvs had about 15% higher alpha-amino nitrogen released at the end of the duodenal simulated digestion than soft wheat (p < 0.05). Bulel tritordeum flour, bread and digested bread had about 55% less R5-epitopes compared to the soft wheat. Differences in protein expression found between the two tritordeum cvs reflected in diverse digestion products and allergenic and celiacogenic potential of the duodenal peptides. Proteomic studies of a larger number of tritordeum cvs may be successful in selecting those with good agronomical performances and nutritional advantages.

Artificial intelligence (AI) applications and digital technologies (DTs) are increasingly present in the daily lives of citizens, in cities and in industries. These developments generate large amounts of data and enhance analytical capabilities that could benefit the industrial ecology (IE) community and sustainability research in general. With this communication, we would like to address some of the opportunities, challenges, and next steps that could be undertaken by the industrial ecology community in this realm. This article is an adapted summary of the discussion held by experts in industrial ecology, AI, and sustainability during the 2021 Industrial Ecology Day conference session titled "The Future of Artificial Intelligence in the Context of Industrial Ecology." In brief, building on previous studies and communications, we advise the industrial ecology community to: (1) create internal committees and working groups to monitor and coordinate AI applications within and outside the community; (2) promote and ensure transdisciplinary efforts; (3) determine optimal infrastructure and governance of AI for IE to minimize undesired effects; and (4) act on effective representation and on reduction of digital divides., Journal of Industrial Ecology, 26 (4), ISSN:1088-1980, ISSN:1530-9290

The pathophysiology of the inflammatory response after major trauma is complex, and the magnitude correlates with severity of tissue injury and outcomes. Study of infection-mediated immune pathways has demonstrated that cellular microRNAs may modulate the inflammatory response. The authors hypothesize that the expression of microRNAs would correlate to complicated recoveries in polytrauma patients (PtPs). METHODS: Polytrauma patients enrolled in the prospective observational Tissue and Data Acquisition Protocol with Injury Severity Score of >15 were selected for this study. Polytrauma patients were divided into complicated recoveries and uncomplicated recovery groups. Polytrauma patients' blood samples were obtained at the time of admission (T0). Established biomarkers of systemic inflammation, including cytokines and chemokines, were measured using multiplexed Luminex-based methods, and novel microRNAs were measured in plasma samples using multiplex RNA hybridization. RESULTS: Polytrauma patients (n = 180) had high Injury Severity Score (26 [20–34]) and complicated recovery rate of 33%. MicroRNAs were lower in PtPs at T0 compared with healthy controls, and bivariate analysis demonstrated that variations of microRNAs correlated with age, race, comorbidities, venous thromboembolism, pulmonary complications, complicated recovery, and mortality. Positive correlations were noted between microRNAs and interleukin 10, vascular endothelial growth factor, Acute Physiology and Chronic Health Evaluation, and Sequential Organ Failure Assessment scores. Multivariable Lasso regression analysis of predictors of complicated recovery based on microRNAs, cytokines, and chemokines revealed that miR-21-3p and monocyte chemoattractant protein-1 were predictive of complicated recovery with an area under the curve of 0.78. CONCLUSION: Systemic microRNAs were associated with poor outcomes in PtPs, and results are consistent with previously described trends in critically ill patients. These early biomarkers of inflammation might provide predictive utility in early complicated recovery diagnosis and prognosis. Because of their potential to regulate immune responses, microRNAs may provide therapeutic targets for immunomodulation. LEVEL OF EVIDENCE: Diagnostic Tests/Criteria; Level II.

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The implementation of preparedness strategies to prevent and mitigate the impact of global health threats poses several challenges. It should promptly identify cross-cutting drivers of pandemic threats, assess context-specific risks, engage multiple stakeholders, and translate complex data from multiple sources into accessible information for action. This requires a coordinated, multidisciplinary and multisectoral effort engaging systems that, most of the time, work in isolation. The One Health (OH) approach promotes the collaboration and communication among different disciplines and sectors, and could be applied across the preparedness phases at national and international level. We discuss here gaps and needs in preparedness strategies, which can benefit from the OH approach, and a set of actionable recommendations, as shared with the G20-2021 with a dedicated Policy Brief. The discussion adds to the current debate about OH operationalization and promotes a paradigm shift towards coordinated prevention and preparedness strategies for early assessment and management of global health threats.

This work presents an overview of the activity developed in the frame of a project funded by the European Space Agency (ESA). The research was focused on the study of the potential applications of GNSS Reflectometry (GNSS- R) over land, with an emphasis on soil moisture (SM) and biomass. A study about the sensitivity with respect to the freeze–thaw dynamics was considered as well. The work started with an analysis of the sensitivity of GNSS-R reflec- tivity collected by the TechDemoSat-1 (TDS-1) experimental satellite, although, to a limited extent, the Cyclone GNSS (CyGNSS) constellation was considered as well. The en - couraging sensitivity outcomes led to the development of retrieval algorithms: three different approaches for SM and one for biomass based on neural networks. A more theoretical investigation was carried out to better understand and predict the signal from a satellite platform which required the updating of two different models. To - pography effects and sensitivity to moisture and roughness of a rough soil were included as well as the effect of vegeta- tion cover. The project was carried out by a large team involving different research groups in Europe. It has led to main con- clusions and recommendations derived from a beneficial collaboration and fertilization of ideas. The primary ap - proaches and outcomes are summarized here, including comparisons to the recent literature. This study has been conducted in the framework of the ESA contract 4000120299/17/NL/AF/hh, “Potential of Spaceborne GNSS-R for Land Applications.” The TDS-1 data have been freely collected from the MERRBYS portal at merrbys.co.uk. The CyGNSS and SMAP data were downloaded from the NASA Earthdata portal at podaac.jpl.nasa.gov and nsidc.org/data/smap, respectively. The SMOS data are made available from the ESA through the smos-diss.eo.esa.int website. This work has also been partially supported by the project of the Ministerio de Ciencia, Innovación y Universidades and EU ERDF ref. RTI2018-099008-B-C21/AEI/10.13089/E01100011083, “Sensing with Pioneering Opportunistic Techniques,” and grant MDM-2016-0600 to the CommSensLab-UPC “María de Maeztu” Excellent Research Unit. We thank the ISMN for the availability of soil moisture data.

Asthma is a chronic respiratory disease in which airway inflammation is a key feature, even in the milder expressions of the disease. The conventional pharmacological approach to mild asthma has long relied on reliever therapy with as-needed short-acting beta-agonists (SABAs), while anti-inflammatory maintenance with inhaled corticosteroids (ICSs) has been reserved for patients with more persistent asthma. Poor adherence to maintenance treatment is an important issue in asthma management, and can partly explain suboptimal symptom control. Over-reliance on SABA bronchodilators for rapid symptom relief is common in real life and potentially leads to an increased risk of asthma morbidity and mortality. Combined anti-inflammatory and reliever medications in a single inhaler have the potential to overcome these limitations. Recent studies in patients with mild asthma have shown that anti-inflammatory reliever therapy with budesonide-formoterol, given on an as-needed basis, is superior to SABA in ensuring asthma control and non-inferior to budesonide maintenance therapy in preventing exacerbations. To address the implications of these important findings for the management of patients with asthma, Italian specialists convened at a series of meetings held during the second half of 2018 across Italy. This article presents their position on these topics and includes a review of the evidence supporting the use of anti-inflammatory reliever therapy in mild asthma and the implementation of this novel approach in clinical practice.

Highlights Japan's economy-wide eco-efficiency of materials and itsdecomposition analysisare conducted for the first time. More than 400 materials, 13 impact categories, and 4 life cycle stages were analyzed. Material groups with a larger share of value added andenvironmental impactto national total, except for pig iron andcrude steel, show lower eco-efficiency. Resource consumption, land use, and global warming are the main impact categories and foreign supply chains is the major impact stage. Circular economyand shift to renewable energy to raise eco-efficiency are proposed by material group, focusing on the trade perspective, economic and environmental contribution.

Neuroprotective drug delivery to the posterior segment of the eye represents a major challenge to counteract vision loss. This work focuses on the development of a polymer-based nanocarrier, specifically designed for targeting the posterior eye. Polyacrylamide nanoparticles (ANPs) were synthesised and characterised, and their high binding efficiency was exploited to gain both ocular targeting and neuroprotective capabilities, through conjugation with peanut agglutinin (ANP:PNA) and neurotrophin nerve growth factor (ANP:PNA:NGF). The neuroprotective activity of ANP:PNA:NGF was assessed in an oxidative stress-induced retinal degeneration model using the teleost zebrafish. Upon nanoformulation, NGF improved the visual function of zebrafish larvae after the intravitreal injection of hydrogen peroxide, accompanied by a reduction in the number of apoptotic cells in the retina. Additionally, ANP:PNA:NGF counteracted the impairment of visual behaviour in zebrafish larvae exposed to cigarette smoke extract (CSE). Collectively, these data suggest that our polymeric drug delivery system represents a promising strategy for implementing targeted treatment against retinal degeneration.

El presente trabajo pretende indagar en la búsqueda, clasificación y registro de aquellos objetos cotidianos a los que les atribuimos, de forma individual o colectiva, un carácter sobrenatural de suerte o protección. La recopilación y representación de estos elementos tiene como finalidad construir una serie de publicaciones, que funcionen a modo de fascículos de una enciclopedia, donde se los ordene y clasifique en función de sus características atribuidas como objetos de cuidado y objetos de la suerte. La producción final fue construida desde una perspectiva de reproducción en serie a partir de las posibilidades plásticas que permite el manejo de una rotativa offset a una tinta RAM 3 y consiste inicialmente en dos publicaciones impresas que alojan a estos objetos clasificados en las categorías ficcionales propuestas. Asimismo se realizaron dos registros audiovisuales para la muestra virtual de los Trabajos de Graduación donde se pretendió, en uno de ellos, dar cuenta del proceso de producción e impresión en serie de estas publicaciones y en el otro, mostrar las publicaciones terminadas., Facultad de Artes

TB Programs should promote the use of digital health platforms, like Electronic Medical Records (EMR) to collect patients' information, thus reducing data incompleteness and low accuracy and eventually improving patients' care. Nevertheless, the potential of digital health systems remains largely unexploited in low-resource settings. Angola is one of the 14 countries with a triple burden of TB, TB/HIV and MDR-TB (multidrug-resistant TB) and it is among the three countries, together with Congo and Liberia that have never completed a drug-resistance survey so far. The Sanatorium Hospital of Luanda and the Tuberculosis Dispensary of Luanda are the two reference health facilities in Luanda dealing with most of the TB cases, and they both rely entirely on paper-based data collection. The aim of this paper is to describe a three-stage process for the development of a TB EMR system in these two health facilities of Luanda and to share the lessons learned. The description is focused on the activities that took place from March 2019 to January 2020. Main lessons learned were identified in the importance of engaging all the stakeholders in the development process, in the mainstream of the “think digital” transition, in the promotion of a monitoring and evaluation (M&E) culture and in the planning of the system's sustainability. This approach may be replicated in similar contexts where the development of a TB EMR system is sought, and the lessons learned could assist and facilitate the programming of the interventions.

Background Post-traumatic acute kidney injury has occurred in every major military conflict since its initial description during World War II. To ensure the proper treatment of combat casualties, early detection is critical. This study therefore aimed to investigate combat-related post-traumatic acute kidney injury in recent military conflicts, used machine learning algorithms to identify clinical and biomarker variables associated with the development of post-traumatic acute kidney injury, and evaluated the effects of post-traumatic acute kidney injury on wound healing and nosocomial infection. Methods We conducted a retrospective clinical cohort review of 73 critically injured US military service members who sustained major combat-related extremity wounds and had collected injury characteristics, assayed serum and tissue biopsy samples for the expression of protein and messenger ribonucleic acid biomarkers. Bivariate analyses and random forest recursive feature elimination classification algorithms were used to identify associated injury characteristics and biomarker variables. Results The incidence of post-traumatic acute kidney injury was 20.5%. Of that, 86% recovered baseline renal function and only 2 (15%) of the acute kidney injury group required renal replacement therapy. Random forest recursive feature elimination algorithms were able to estimate post-traumatic acute kidney injury with the area under the curve of 0.93, sensitivity of 0.91, and specificity of 0.91. Post-traumatic acute kidney injury was associated with injury severity score, serum epidermal growth factor, and tissue activin A type receptor 1, matrix metallopeptidase 10, and X-C motif chemokine ligand 1 expression. Patients with post-traumatic acute kidney injury exhibited poor wound healing and increased incidence of nosocomial infections. Conclusion The occurrence of acute kidney injury in combat casualties may be estimated using injury characteristics and serum and tissue biomarkers. External validations of these models are necessary to generalize for all trauma patients.

Background The role of minimally invasive surgery in trauma has continued to evolve over the past 20 years. Diagnostic laparoscopy (DL) has become increasingly utilized for the diagnosis and management of both blunt and penetrating injuries. Objective While the safety and feasibility of laparoscopy has been established for penetrating thoracoabdominal trauma, it remains a controversial tool for other injury patterns due to the concern for complications and missed injuries. We sought to examine the role of laparoscopy for the initial management of traumatic injuries at our urban Level 1 trauma center. Methods All trauma patients who underwent DL for blunt or penetrating trauma between 2009 and 2018 were retrospectively reviewed. Demographic data, indications for DL, injuries identified, rate of conversion to open surgery, and outcomes were evaluated. Results A total of 316 patients were included in the cohort. The mean age was 34.9 years old (± 13.7), mean GCS 14 (± 3), and median ISS 10 (4–18). A total of 110/316 patients (35%) sustained blunt injury and 206/316 patients (65%) sustained penetrating injury. Indications for DL included evaluation for peritoneal violation (152/316, 48%), free fluid without evidence of solid organ injury (52/316, 16%), evaluation of bowel injury (42/316, 13%), and evaluation for diaphragmatic injury (35/316, 11%). Of all DLs, 178/316 (56%) were negative for injury requiring intervention, which was 58% of blunt cases and 55% of penetrating cases. There were no missed injuries noted. Average hospital length of stay was significantly shorter for patients that underwent DL vs conversion to open exploration (2.2 days vs. 4.5 days, p

In this study, the capability of Global Navigation Satellite System Reflectometry in evaluating forest biomass from space has been investigated by using data coming from the TechDemoSat-1 (TDS-1) mission of Surrey Satellite Technology Ltd. and from the Cyclone Satellite System (CyGNSS) mission of NASA. The analysis has been first conducted using TDS-1 data on a local scale, by selecting five test areas located in different parts of the Earth's surface. The areas were chosen as examples of various forest coverages, including equatorial and boreal forests. Then, the analysis has been extended by using CyGNSS to a global scale, including any type of forest coverage. The peak of the Delay Doppler Map calibrated to retrieve an “equivalent” reflectivity has been exploited for this investigation and its sensitivity to forest parameters has been evaluated by a direct comparison with vegetation optical depth (VOD) derived from the Soil Moisture Active Passive L-band radiometer, with a pantropical aboveground biomass (AGB) map and then with a tree height (H) global map derived from the Geoscience Laser Altimeter System installed on-board the ICEsat satellite. The sensitivity analysis confirmed the decreasing trend of the observed equivalent reflectivity for increasing biomass, with correlation coefficients 0.31 ≤ R ≤ 0.54 depending on the target parameter (VOD, AGB, or H) and on the considered dataset (local or global). These correlations were not sufficient to retrieve the target parameters by simple inversion of the direct relationships. The retrieval has been therefore based on Artificial Neural Networks making it possible to add other inputs (e.g., the incidence angle, the signal to noise ratio, and the lat/lon information in case of global maps) to the algorithm. Although not directly correlated to the biomass, these inputs helped in improving the retrieval accuracy. The algorithm was tested on both the selected areas and globally, showing a promising ability to retrieve the target parameter, either AGB or H, with correlation coefficients R ≃ 0.8.

A significant quantity of space-borne Global Navigation Satellite Systems-Reflectometry (GNSS-R) data over land was made available in the last decade, leading to an increasing interest in the assessment of the potentialities of this new remote sensing technique for land monitoring. In this frame, an electromagnetic simulator, such as the Soil And VEgetation Reflection Simulator (SAVERS), has the key role to support the understanding of the physical mechanism involved in the bistatic scattering and to identify the surface features mainly contributing to the observed signal. Originally developed for ground and airborne GNSS-R observations over homogeneous areas, in this study, SAVERS was upgraded to account for space-borne systems. The new version of SAVERS takes into account the inhomogeneity characterizing the large area observed from space altitudes, due to a variable surface elevation and land cover. Coherent and incoherent scattering and polarization rotation are computed taking into account the local slope and elevation of the surface. The simulator was validated against TechDemoSat-1 observations over a bare surface with a complex topography and over a forested surface with a gentle topography. The validation results show the capability of SAVERS to correctly estimate the effect of the topography, enhancing the understanding of the observations. Moreover, it was found that the sensitivity to soil moisture is independent of the topography (about 1.5 dB for a 10% variation of soil moisture). Whereas a saturation of the GNSS-R reflectivity over a variable topography is reached for lower values of biomass, earlier than in the flat case.

Our knowledge of de novo anti-HLA donor-specific antibodies (dnDSA) in liver transplantation continues to be defined. We hypothesized that differences of HLA-DR/DQ mismatches can improve precision in alloimmune risk categorization and be applied to tailor immunosuppression.A retrospective chart review of 244 pediatric patients consecutively transplanted at our center between 2003 and 2019 was performed to identify patients tested for dnDSA. Records were queried for: demographics, pre-transplant diagnosis, biopsy-proven T-cell-mediated rejection (TCMR), radiology proven biliary complications, tacrolimus trough levels, dnDSA characteristics, and HLA typing. The eplet mismatch analyses were performed using HLAMatchmakerThere were 99 dnDSA-negative patients and 73 dnDSA-positive patients (n = 70 against class II and n = 3 against class I and II). ROC analysis identified optimal cutoff of eplet mismatch load for dnDSA and defined risk groups for an alloimmune outcome. Kaplan-Meier curves and log-rank tests showed high eplet mismatch load was associated with shorter dnDSA-free survival (log-rank p = .001). Multivariable Cox regression models showed that tacrolimus coefficient of variation and tacrolimus mean levels were significantly associated with dnDSA-free survival (p .001 and p = .036). Fisher's exact test showed that dnDSA was associated with an increased likelihood of TCMR (OR 14.94; 95% CI 3.65 - 61.19; p .001). Patients without TCMR were more likely to have dnDSA to HLA-DQ7 and less likely to have dnDSA to HLA-DQ2 (p = .03, p = .080).Mismatched epitope load predicts dnDSA-free survival in pediatric liver transplant, while dnDSA specificity may determine alloimmune outcome.

This study investigated the impact of COVID-19 infection on hospitalized trauma patients.A retrospective review of hospitalized trauma patients at a level I trauma center was performed from March-December 2020. Data pertaining to patient demographics, presentation and hospital course was compared between COVID positive and negative trauma patients.There were 4,912 patients and 179 (3.64%) were COVID-19 positive. Demographics and clinical presentation did not differ significantly between those with and without concomitant COVID-19. However, COVID positive trauma patients had higher rates of acute kidney injury (p = 0.016), sepsis (p = 0.016), unplanned intubation (p = 0.002) and unplanned return to the ICU (p = 0.01). The COVID positive cohort also had longer hospital stays (p 0.01) with no significant difference in mortality.In the setting of an ongoing pandemic, awareness of the complications COVID positive trauma patients are predisposed to is important for providers.

This thesis comprises three different chapters in the broad field of education economics, each making its own contribution in different facets of the topic. The first chapter studies the overeducation wage penalty and how it evolves over time for individuals who are stuck in an overeducated job. Using a Propensity Score Matching estimator, and relying on the panel structure of the data to satisfy the Conditional Independence Assumption, I find that these individuals see their relative position worsen over time, as the penalty follows an increasing trend. In the second chapter we study the effect of Higher Education completion on the mental health of young individuals using the Next Steps dataset. In the absence of a Randomised Control Trial we use different econometric techniques and provide evidence that obtaining a Higher Education degree has a protective effect on the mental health of the respondants. The third and final chapter studies the Gender Pay Gap across the distribution for young recent university graduates using an Oaxaca-Blinder decomposition complemented with the Recentered Influence Function of Firpo et al. (2009). While finding that differences in fields of studies and related jobs can explain most of the gap until the median earners, I also find evidence of strong glass ceiling effects for women, who suffer a wage gap of around 25% at the top of the distribution.

Freshly isolated primary cardiomyocytes (CM) are indispensable for cardiac research. Experimental CM research is generally incompatible with life of the donor animal, while human heart samples are usually small and scarce. CM isolation from animal hearts, traditionally performed by coronary artery perfusion of enzymes, liberates millions of cells from the heart. However, due to progressive cell remodeling following isolation, freshly isolated primary CM need to be used within 4–8 h post-isolation for most functional assays, meaning that the majority of cells is essentially wasted. In addition, coronary perfusion-based isolation cannot easily be applied to human tissue biopsies, and it does not straightforwardly allow for assessment of regional differences in CM function within the same heart. Here, we provide a method of multi-day CM isolation from one animal heart, yielding calcium-tolerant ventricular and atrial CM. This is based on cell isolation from cardiac tissue slices following repeated (usually overnight) storage of the tissue under conditions that prolong CM viability beyond the day of organ excision by two additional days. The maintenance of cells in their near-native microenvironment slows the otherwise rapid structural and functional decline seen in isolated CM during attempts for prolonged storage or culture. Multi-day slice-based CM isolation increases the amount of useful information gained per animal heart, improving reproducibility and reducing the number of experimental animals required in basic cardiac research. It also opens the doors to novel experimental designs, including exploring same-heart regional differences.

BACKGROUND The timing of coverage of an open wound is based on heavily on clinical gestalt. DoD's Surgical Critical Care Initiative created a clinical decision support tool that predicts wound closure success using clinical and biomarker data. The military uses a regimented protocol consisting of serial washouts and debridements. While decisions around wound closure in civilian centers are subject to the same clinical parameters, preclosure wound management is, generally, much more variable. We hypothesized that the variability in management would affect local biomarker expression within these patients. METHODS We compared data from 116 wounds in 73 military patients (MP) to similar data from 88 wounds in 78 civilian patients (CP). We used Wilcoxon rank-sum tests to assess concentrations of 32 individual biomarkers taken from wound effluent. Along with differences in the debridement frequency, we focused on these local biomarkers in MP and CP at both the first washout and the washout performed just prior to attempted closure. RESULTS On average, CP waited longer from the time of injury to closure (21.9 days, vs. 11.6 days, p < 0.0001) but had a similar number of washouts (3.86 vs. 3.44, p = 0.52). When comparing the wound effluent between the two populations, they had marked biochemical differences both when comparing the results at the first washout and at the time of closure. However, in a subset of civilian patients whose average number of days between washouts was never more than 72 hours, these differences ceased to be significant for most variables. CONCLUSION There were significant differences in the baseline biochemical makeup of wounds in the CP and MP. These differences could be eliminated if both were treated under similar wound care paradigms. Variations in therapy affect not only outcomes but also the actual biochemical makeup of wounds. LEVEL OF EVIDENCE Therapeutic, level IV.