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This study aims to identify sustainable countries within the European Union in terms of renewable energy. The objective is to support renewable alternatives and enhance sustainability in the renewable sector among the top economic countries. The study reviews key drivers of sustainable development, establishes criteria for each dimension, and selects up-to-date indicators. The fuzzy analytical hierarchy process and expert judgments are employed to rank the countries, ensuring unbiased results, and reducing uncertainty. The findings indicate that Sweden, Belgium, Ireland, France, Germany, Spain, the Netherlands, Poland, and Italy exhibit their positions from the most advanced to the lower sustainable countries, respectively. Energy and environmental indicators play a primary role as the most influential drivers. Economic factors contribute as tertiary drivers, while social and institutional indicators have a relatively minor influence. Notably, Sweden, Belgium, and Ireland, despite being among the last three in terms of economic ranking, emerge as the most sustainable countries in renewable energy, surpassing stronger economies such as France, Germany, and Spain. On the other hand, the Netherlands, Poland, and Italy, as middle economy countries, rank lower in terms of sustainability. These results provide insights for harnessing renewable energy in high-growth economies and offer valuable policy advice for implementation.

Renewable Energy Sources (RES) are widely used worldwide due to their positive effect on the environment, being sustainable, low cost, and controllable. The power generated from RESs must be configured to interface and perfectly synchronize with the grid by using Power Electronics Converters (PEC). A Phase-Locked Loop (PLL) is one of the most popular synchronization techniques used due to its speed and robustness. A growing issue that results in oscillations in the estimated fundamental grid phase, frequency, and voltage amplitude is the DC-offset in the input of the PLL. This study was developed to eliminate the DC-offset in the single-phase grid synchronization using Delay Signal Cancellation (DSC) and a fixed-length Transfer Delay (TD)-based PLL. Then, the small-signal model, stability analysis, and selection of controller gains were discussed. The proposed PLL was simulated using MATLAB/Simulink. Moreover, to evaluate the proposed method, several scenarios were developed in order to compare it with other powerful PLLs in terms of performance indicators such as settling time, frequency, and phase error. As a result, the proposed PLL has the fastest dynamic response, completely rejects the DC-offset effect, and fully synchronizes with the electrical grid.

Conventional tissue sampling can lead to misdiagnoses and repeated biopsies. Additionally, tissue processed for histopathology suffers from poor nucleic acid quality and/or quantity for downstream molecular profiling. Targeted micro-sampling of tissue can ensure accurate diagnosis and molecular profiling in the presence of spatial heterogeneity, especially in tumors, and facilitate acquisition of fresh tissue for molecular analysis. In this study, we explored the feasibility of performing 1–2 mm precision biopsies guided by high-resolution reflectance confocal microscopy (RCM) and optical coherence tomography (OCT), and reflective metallic grids for accurate spatial targeting. Accurate sampling was confirmed with either histopathology or molecular profiling through next generation sequencing (NGS) in 9 skin cancers in 7 patients. Imaging-guided 1–2 mm biopsies enabled spatial targeting for in vivo diagnosis, feature correlation and depth assessment, which were confirmed with histopathology. In vivo 1-mm targeted biopsies achieved adequate quantity and high quality of DNA for next-generation sequencing. Subsequent mutational profiling was confirmed on 1 melanoma in situ and 2 invasive melanomas, using a 505-gene mutational panel called Memorial Sloan Kettering-Integrated mutational profiling of actionable cancer targets (MSK-IMPACT). Differential mutational landscapes, in terms of number and types of mutations, were found between invasive and in situ melanomas in a single patient. Our findings demonstrate feasibility of accurate sampling of regions of interest for downstream histopathological diagnoses and molecular pathology in both in vivo and ex vivo settings with broad diagnostic, therapeutic and research potential in cutaneous diseases accessible by RCM-OCT imaging.

The Human Disease Ontology (DO) (www.disease-ontology.org) database, has significantly expanded the disease content and enhanced our userbase and website since the DO’s 2018 Nucleic Acids Research DATABASE issue paper. Conservatively, based on available resource statistics, terms from the DO have been annotated to over 1.5 million biomedical data elements and citations, a 10× increase in the past 5 years. The DO, funded as a NHGRI Genomic Resource, plays a key role in disease knowledge organization, representation, and standardization, serving as a reference framework for multiscale biomedical data integration and analysis across thousands of clinical, biomedical and computational research projects and genomic resources around the world. This update reports on the addition of 1,793 new disease terms, a 14% increase of textual definitions and the integration of 22 137 new SubClassOf axioms defining disease to disease connections representing the DO’s complex disease classification. The DO’s updated website provides multifaceted etiology searching, enhanced documentation and educational resources., Graphical Abstract Graphical AbstractThe Human Disease Ontology (DO) integrates disease features and etiological factors to describe disease complexity. The DO is extensively cited and integrated into highly cited databases.

Cornual gestation is one of the most hazardous types of ectopic gestation. It carries a significant challenge and a greater maternal mortality risk than ampullary ectopic pregnancy. The diagnosis and treatment are challenging and frequently constitute a medical emergency. Traditionally, the treatment of cornual pregnancy has been hysterectomy or cornual resection at laparotomy. However endoscopic approach is a viable option and consists of conservative techniques such as laparoscopic cornual resection, laparoscopic cornuostomy, laparoscopic salpingectomy or hysteroscopic removal of interstitial ectopic tissue. Case presentation: We report a case of a 28-year-old multipara who had an unruptured left cornual ectopic gestation with moderate pelvic adhesions and concomitant partial intestinal obstruction. She was managed via laparoscopic adhesiolysis and left total salpingectomy. Conclusions: Cornual pregnancy occurs rarely, there is a need for early and prompt diagnosis to prevent potentially fatal complications.

Despite progress in the development of standards for describing and exchanging scientific information, the lack of easy-to-use standards for mapping between different representations of the same or similar objects in different databases poses a major impediment to data integration and interoperability. Mappings often lack the metadata needed to be correctly interpreted and applied. For example, are two terms equivalent or merely related? Are they narrow or broad matches? Are they associated in some other way? Such relationships between the mapped terms are often not documented, leading to incorrect assumptions and making them hard to use in scenarios that require a high degree of precision (such as diagnostics or risk prediction). Also, the lack of descriptions of how mappings were done makes it hard to combine and reconcile mappings, particularly curated and automated ones. The Simple Standard for Sharing Ontological Mappings (SSSOM) addresses these problems by: 1. Introducing a machine-readable and extensible vocabulary to describe metadata that makes imprecision, inaccuracy and incompleteness in mappings explicit. 2. Defining an easy to use table-based format that can be integrated into existing data science pipelines without the need to parse or query ontologies, and that integrates seamlessly with Linked Data standards. 3. Implementing open and community-driven collaborative workflows designed to evolve the standard continuously to address changing requirements and mapping practices. 4. Providing reference tools and software libraries for working with the standard. In this paper, we present the SSSOM standard, describe several use cases, and survey some existing work on standardizing the exchange of mappings, with the goal of making mappings Findable, Accessible, Interoperable, and Reusable (FAIR). The SSSOM specification is at http://w3id.org/sssom/spec., Comment: Corresponding author: Christopher J. Mungall

Animals have been known to be the main study subjects when investigating the epidemiology of zoonotic Gram-positive Clostridium difficile and Clostridium perfringens. This cross-sectional study was aimed at determining the occurrence of C. difficile and C. perfringens in pigs as well as the associated risk factors within Zaria and environs, in Kaduna State of Nigeria. A pre-sampling survey led to the selection of Shika, Samaru and Ungwan Mangu in the pig farming communities of Zaria and environs in Kaduna North as the study sites. Rectal swabs from 132 pigs were obtained and anaerobically cultured in fluid thioglycolate and further grown on reinforced clostridia agar. The colonies obtained were sub-cultured in Clostridium difficile moxalactam norfloxacin agar and reinforced clostridia agar containing egg yolk tellurite. C. difficile was not detected. However, C. perfringens was detected at a prevalence of 16.7 % (22/132). Isolates were tested for their susceptibility to 13 antimicrobials. Only 1 isolate (4.55 %) demonstrated susceptibility to vancomycin, gentamicin, chloramphenicol and erythromycin. Of the bivariate analyses of the risk factors studied, only the type of piggery and pig management were statistically significant (P < 0.05) for C. perfringens. Therefore, it should be recognized that there is a need for pig farmers to be enlightened about this pathogen and its prevention through good management practices and hygiene.

Plant response to climate depends on a species’ adaptive potential. To address this, we used reciprocal gardens to detect genetic and environmental plasticity effects on phenotypic variation and combined with genetic analyses. Four reciprocal garden sites were planted with three regional ecotypes of Andropogon gerardii, a dominant Great Plains prairie grass, using dry, mesic, and wet ecotypes originating from western KS to Illinois that span 500–1,200 mm rainfall/year. We aimed to answer: (a) What is the relative role of genetic constraints and phenotypic plasticity in controlling phenotypes? (b) When planted in the homesite, is there a trait syndrome for each ecotype? (c) How are genotypes and phenotypes structured by climate? and (d) What are implications of these results for response to climate change and use of ecotypes for restoration? Surprisingly, we did not detect consistent local adaptation. Rather, we detected co‐gradient variation primarily for most vegetative responses. All ecotypes were stunted in western KS. Eastward, the wet ecotype was increasingly robust relative to other ecotypes. In contrast, fitness showed evidence for local adaptation in wet and dry ecotypes with wet and mesic ecotypes producing little seed in western KS. Earlier flowering time in the dry ecotype suggests adaptation to end of season drought. Considering ecotype traits in homesite, the dry ecotype was characterized by reduced canopy area and diameter, short plants, and low vegetative biomass and putatively adapted to water limitation. The wet ecotype was robust, tall with high biomass, and wide leaves putatively adapted for the highly competitive, light‐limited Eastern Great Plains. Ecotype differentiation was supported by random forest classification and PCA. We detected genetic differentiation and outlier genes associated with primarily precipitation. We identified candidate gene GA1 for which allele frequency associated with plant height. Sourcing of climate adapted ecotypes should be considered for restoration.

Building reconstruction projects are mainly motivated by social factors, without a deep evaluation of the Best Available Techniques. The main aim of this work is to analyze the advantages of defining sustainable retrofitted buildings, previously building the edifice, by using methodologies towards sustainable systems. A real re-constructed building is considered as a case study. Three scenarios are investigated to analyze its sustainability, including the waste ruins of the old building (Scenario 1), the current re-constructed building (Scenario 2), and a hypothetical sustainable retrofitted building (Scenario 3). Firstly, the current energy consumption is studied including heating flow through walls (thermal bridges and condensation risk) as well as operational costs. Secondly, a new scenario is proposed adding passive solutions to this existing building, to improve its energy efficiency; also, energy consumption and costs of the refurbishment are analyzed. Results show that Scenario 1 leads to a bad image of a city involving the environment and social fields. Scenario 2 entails expensive operational costs. On the other hand, Scenario 3 results in approximately 90% of cost savings in heating energy demand, which would be traduced on high economic savings. Taken into account not only economic factors but environmental and social ones, it can be concluded that it is more sustainable and profitable constructing an efficient building from the beginning by using waste ruins and simulation software despite refurbishing a re-built edifice.

Buildings are one of the systems that more energy consumed in the European Union. The study of the thermal envelope is interesting in order to reduce the energy losses. For that, a mathematical model able to predict the system response to external temperature variations is developed. With the mathematical model, different thermal envelope elements of a building based on the lag and the cushioning of the resultant wave can be characterized. In addition, it is important to analyse where the insulation is placed, because when the insulation is outside and the thermal mass is inside, the system produces a response with smooth temperature variations than when the insulation is inside. Therefore, placing the outside insulation generates more steady indoor temperatures, increasing the thermal comfort inside the building. To complete the mathematical model that allows predicting the temperature inside a building taking into account the solar inputs and the thermal inertia of the building. This study will help to establish the optimum design parameters in order to build sustainable and comfortable buildings. Furthermore, it will take one step forward in the construction of nearly Zero-Energy Buildings.

Background: While harmaline has been used as a pharmacological model of essential tremor (ET) in rodents and pigs, less is known about the effects of this pharmacological treatment in awake-behaving non-human primates. In this study, we investigated the time-course, amplitude, frequency, and consistency of harmaline tremor in primates. Methods: Three rhesus macaques were administered doses of harmaline ranging from 2–12 mg/kg (i.m.), and tremorous movements were quantified with accelerometers. One subject was also trained to perform a self-paced cued reaching task, with task engagement assessed under harmaline doses ranging from 2–8 mg/kg (i.m.). Results: Whole-body tremors manifested within 30 minutes of threshold-dose administration, and peak oscillatory frequency ranged between 10–14 Hz. However, large differences in tremor intensity and intermittency were observed across individual subjects under similar dosing levels. Additionally, engagement with the reaching task was dependent on harmaline dose, with performance mostly unaffected at 2 mg/kg and with little task-engagement at 8 mg/kg. Discussion: We provide a detailed assessment of factors that may underlie the heterogeneous responses to harmaline, and lay out important caveats towards the applicability of the behaving harmaline-tremoring non-human primate as a preclinical model for ET. Highlights The harmaline-primate is revisited for its potential as a preclinical model of tremor. Spontaneous tremor was heterogenous in amplitude across subjects despite similar harmaline doses, action tremors were not consistently observed, and performance on a behavioral task degraded with higher dosages.

Castration is a common management procedure employed in North American cattle production and is known to cause a pain response. The present study was designed to investigate the effect of unmitigated surgical castration on the electroencephalography (EEG) responses and plasma substance P (SP) concentrations in calves of different ages under the same experimental conditions. Thirty male Holstein calves in three age categories [&lt, 6 weeks (6W), 3 months (3M), 6 months (6M), 10 calves per age group] were used in the study. Calves were subjected to a simulated castration session (SHAM) followed 24 h later by surgical castration (CAST) without analgesia. An EEG analysis was performed before the procedure (i.e., baseline), at treatment, and 0–5, 5–10, and 10–20 min post-treatment for both SHAM and CAST, respectively. Blood samples were collected immediately prior to both treatments (time 0) and again at 1, 2, 4, 8, and 12 h after both treatments. The EEG results showed a three-way interaction between treatment, age, and time for delta and beta absolute power, beta relative power, total power, and median frequency (p = 0.004, p = 0.04, p = 0.04, p = 0.03, and p = 0.008, respectively). Following CAST, EEG total power decreased, and median frequency increased relative to SHAM in 6W and 3M calves only following treatment. For 6W and 3M calves, delta and beta absolute power increased at CAST and at later time points relative to SHAM. Marginal evidence for two-way interactions was noted between time and treatment and between age and treatment on the concentration of SP (p = 0.068 and p = 0.066, respectively). Substance P concentrations decreased in CAST treatment compared to SHAM at the later times (8 h: p = 0.007, 12 h: p = 0.048), 6W calves showed lower SP concentration at CAST relative to SHAM (p = 0.017). These findings indicate variation in EEG responses and in SP concentrations following unmitigated surgical castration in calves and that these responses may be age specific. These EEG findings have implications for supporting the perception of the pain associated with surgical castration in young calves and emphasize the urgency of pain mitigation strategies during routine husbandry practices such as castration, as typically implemented in North American cattle management.

Objective: Pancreatic β-cell dysfunction is described to be present at the diagnosis of type 2 diabetes mellitus (T2DM) and progressively deteriorated with disease duration. However, its progression is variable and potentially influenced by several factors. The Magnesium (Mg) deficiency mediates insulin resistance but reports regarding its role in pancreatic β-cell dysfunction are scarce and conflicting. The aim of this study was to evaluate Mg deficiency effect on pancreatic β-cell function in T2DM patients at a specialist hospital in north eastern Nigeria. Materials and Methods: Study subjects were categorized in to two groups according to plasma Mg levels; 34 subjects with hypomagnesemia and 45 subjects with normal magnesium levels. Fasting blood samples were analyzed for Mg, glucose and insulin. Pancreatic β-cell function was estimated as HOMA-β. Results: Degree of pancreatic β-cell function, as measured by HOMA-β, was significantly lower among T2DM subjects with hypomagnesemia compared to the subjects with normal magnesium levels (38.1± 5.5 vs. 41.2± 6.2, Pvalue< 0.05). Lower plasma Mg was associated with decreased pancreatic β-cell function among the study subjects independent of age, BMI and duration of diabetes. Conclusion: We concluded that among subjects with T2DM in this study, Mg deficiency might be linked with worsening of pancreatic β-cell function.

The use of synthetic herbicides poses a serious threat to environment, health and food safety. The development of safe and effective bioherbicides for selective control of weeds is thus the primary concern in crop production around the world. Efforts are being made to investigate the use of a safe, ecofriendly and highly selective herbicides from biological origin. Coumarin and its derivatives are natural compounds renowned for their phytotoxic potential.Mellein, a dihydroisocoumarin designated as (R)-8-hydroxy-3-methylisochroman-1-one was isolated as an active metabolite from the broth of a new strain (this strain is one of the best among phytopathogenic strains collected) of Lasiodiplodia pseudotheobromae. The structural characterization of the compound was achieved by using combined spectroscopic analysis i.e. 1D and 2D NMR and LC–MS. The host range study was carried-out against plants from Cucurbitaceae, Solanaceae and Leguminosae, Poaceae and Valerianaceae families, the isolated phytotoxic metabolite from Lasiodiplodia pseudotheobromae at a concentration 10 µg/µl showed selective inhibition at 56%–66% against the latter two families only when inoculated.Hence, purified compound from Lasiodiplodia pseudotheobromae is recommended for large scale production of bioherbicides for the management of weeds in conventional farming to improve yield and enhance food security. Keywords: Bioherbicides, Lasiodiplodia pseudotheobromae, (R)-8-Hydroxy-3-methylisochroman-1-one and weed

Background and objective Experimental models suggest the use of different therapy protocols in rheumatoid arthritis (RA) as modulators on periodontal condition. This study evaluated the effects of conventional drug treatment and anti-TNF therapy in patients with RA on microbiological and periodontal condition, establishing the association of markers of periodontal infection with indexes of rheumatic activity. Materials and methods One hundred seventy nine individuals with RA were evaluated (62 with anti-TNF-. and 115 with only DMARDs). The periodontal evaluation included plaque and gingival indexes, bleeding on probing (BOP), clinical attachment loss (CAL), pocket depth (PD) and subgingival plaque samples for microbiological analysis. Rheumatologic evaluations included a clinical examination, rheumatoid factor (RF), antibodies against cyclic-citrullinated peptides (ACPAs), and activity markers (DAS28-ERS), high sensitive C-reactive protein (hs-CRP), erythrocyte sedimentation rate (ESR). Results Anti-TNF-alpha therapy influenced periodontal microbiota with a higher frequency of T. denticola (p=0.01). Methotrexate combined with leflunomide exhibited a higher extension of CAL (p=0.005), and anti-TNF-alpha therapy with methotrexate was associated with a lower extension of CAL (p=0.05). The use of corticosteroids exerted a protective effect on the number of teeth (p=0.027). The type of DMARD affected P. gingivalis, T. forsythia and E. nodatum presence. Elevated ACPAs titers were associated with the presence of red complex periodontal pathogens (p=0.025). Bleeding on probing was associated with elevated CPR levels (p=0.05), and ESR was associated with a greater PD (p=0.044) and presence of red complex (p=0.030). Conclusion Different pharmacological treatments for RA affect the clinical condition and subgingival microbiota.

Medical practitioners record the condition status of a patient through qualitative and quantitative observations. The measurement of vital signs and molecular parameters in the clinics gives a complementary description of abnormal phenotypes associated with the progression of a disease. The Clinical Measurement Ontology (CMO) is used to standardize annotations of these measurable traits. However, researchers have no way to describe how these quantitative traits relate to phenotype concepts in a machine-readable manner. Using the WHO clinical case report form standard for the COVID-19 pandemic, we modeled quantitative traits and developed OWL axioms to formally relate clinical measurement terms with anatomical, biomolecular entities and phenotypes annotated with the Uber-anatomy ontology (Uberon), Chemical Entities of Biological Interest (ChEBI) and the Phenotype and Trait Ontology (PATO) biomedical ontologies. The formal description of these relations allows interoperability between clinical and biological descriptions, and facilitates automated reasoning for analysis of patterns over quantitative and qualitative biomedical observations.

Background Two RCTs found no survival benefit for completion lymphadenectomy after positive sentinel lymph node biopsy compared with observation with ultrasound in patients with melanoma. Recurrence patterns and regional control are not well described for patients undergoing observation alone. Methods All patients with a positive sentinel node biopsy who did not have immediate completion lymphadenectomy were identified from a single-institution database (1995–2018). First recurrences were classified as node only, local and in-transit (LCIT) only, LCIT and nodal, or systemic. Regional control and factors associated with recurrence survival were analysed. Results Median follow-up was 33 months. Of 370 patients, 158 (42·7 per cent) had a recurrence. The sites of first recurrence were node only (13·2 per cent), LCIT only (11·9 per cent), LCIT and nodal (3·5 per cent), and systemic (13·8 per cent). The 3-year postrecurrence melanoma-specific survival rate was 73 (95 per cent c.i. 54 to 86) per cent for patients with node-only first recurrence, and 51 (31 to 68) per cent for those with initial systemic recurrence. In multivariable analysis, ulceration in the primary lesion (hazard ratio (HR) 2·53, 95 per cent c.i. 1·27 to 5·04), disease-free interval 12 months or less (HR 2·38, 1·28 to 4·35), and systemic (HR 2·57, 1·16 to 5·65) or LCIT and nodal (HR 2·94, 1·11 to 7·79) first recurrence were associated significantly with decreased postrecurrence survival. Maintenance of regional control required therapeutic lymphadenectomy in 13·0 per cent of patients during follow-up. Conclusion Observation after a positive sentinel lymph node biopsy is associated with good regional control, permits assessment of the time to and pattern of recurrence, and spares lymphadenectomy-related morbidity in patients with melanoma.

En la actualidad en las empresas agropecuarias e realizan constantes modificaciones tratando de mejorar la eficiencia de utilización de los recursos y estabilizar los resultados económicos. Por ello, es que la búsqueda de alternativas de diversificación son permanentes en el sector agropecuario. Este trabajo analiza la incidencia que tiene la incorporación de una actividad no tradicional como es la cría y engorde de ciervo colorado sobre los resultados económico en empresas de distinto potencial agroecológico y evalúa la sensibilidad que tiene esta actividad a los cambios de precio de sus productos. Además produce una herramienta electrónica que contenga un programa de simulación para analizar sistemas mixtos de producción agropecuaria y sirva para ser utilizada en la administración agropecuaria. Se utiliza un modelo de simulación formado por tres establecimientos ubicados en distintos ambientes en cuanto a potencial de producción agrícola-ganadero. La superficie de los establecimientos es d 500 ha. cada uno. La inclusión de la actividad cría y terminación de ciervo colorado mejora los resultados económicos de las empresas, porque alimenta lo ingresos sin afectar significativamente los costos de producción una vez que se haya estabilizado el sistema. Los mayores impactos de la incorporación de la actividad se producen en ambientes marginales para la agricultura. pero también aumenta el riesgo ante variaciones del precio de los productos. En cambio, en ambientes de buen potencial, este impacto depende tanto de los precios de los productos de esta actividad como de los precios de los productos de actividades tradicionales que son competitivos en estos ambientes. La incorporación de la nueva actividad no altera la eficiencia de los planteos existentes, pero por la gran demanda de capital necesario para la adquisición de animales e infraestructura que tiene esta actividad, hasta que no se estabilice dentro del establecimiento puede comprometer los resultados económicos de la empresa. Director: Ing. Agr.. Héctor D' Adam, Cátedra Administración Agropecuaria; e Ing. Agr. Gustavo Fernández e Ing. Agr. Aníbal Pordormingo, Cátedra: Zootecnia Especial I.

Launaea taraxacifolia (Willd) is a perennial herb, commonly known as wild lettuce, assumed the position of wild and underutilized. It is common in Asia, North America, Europe and North Africa. Various parts of L. taraxacifolia have ethnomedicinal importance as they are employed against various ailments and diseases in humans and its traditionally use in ruminant animals. Arguments on its family is presented in this study, so far only five compounds were identified i.e. caffeic acid (1), chlorogenic acid (2), ellagic acid (3), quercetin (4) and kaempferol (5), from this neglected vegetable and an extensive range of pharmacological effects such as antioxidant, antidiabetic and hypolipidemic, antibacterial, antimalarial, anticancer effects and drug-herb interaction of this medicinal plant with recombinant human enzymes i.e. CYP1A2, CYP2C9 and CYP3A4 was stated in this review. This study was carried out with a reason to highlight its importance and discusses its ethnomedicinal, phytochemical, pharmacological, toxicological and states its relevance beyond conventional nutritional gains. Furthermore, this review reiterates the needs to isolate constituents and carry out clinical studies to justify the scientific efficacy accrues to this medicinal plant from traditional uses and give it the due recognition as therapeutic supplement.

This paper presents the design of a Linear Matrix Inequality (LMI) based state feedback controller for position tracking, hook and payload oscillations of a double pendulum crane. In this work, a linearised model of the crane was firstly obtained. The idea of formulating the stability condition in the form of LMIs using the linearised model was proposed. Using this approach, the stabilisation conditions constraints the closed-loop poles of the system to be in an LMI region to guarantee the system stability and gives satisfied transient performance. Based on the stabilization conditions formulated, an LMI based state feedback tracking controller for trolley position tracking and swing angles control of the double pendulum crane is proposed. Mostly, two or more controllers were used for the control of double pendulum crane to control the trolley, hook and payload. However, in this work a single LMI based controller is used to achieve similar performance. This reduces the number of controllers which minimises cost, complexity and size of the control system. The performance of the proposed controller is investigated via simulations. The simulation result shows the proposed controller is able to track the trolley position relatively fast with minimum hook and payload swing angles hence, reduce the main problem of a double pendulum crane. From the performance comparison of the results, the proposed method has improved in terms of reducing the trolley position percentage overshoot, hook oscillation and payload oscillation with 72%, 52% and 65% respectively.

Deep brain stimulation (DBS) therapy is a potent tool for treating a range of brain disorders. High frequency stimulation (HFS) patterns used in DBS therapy are known to modulate neuronal spike rates and patterns in the stimulated nucleus; however, the spatial distribution of these modulated responses are not well understood. Computational models suggest that HFS modulates a volume of tissue spatially concentrated around the active electrode. Here, we tested this theory by investigating modulation of spike rates and patterns in non-human primate motor thalamus while stimulating the cerebellar-receiving area of motor thalamus, the primary DBS target for treating Essential Tremor. HFS inhibited spike activity in the majority of recorded cells, but increasing stimulation amplitude also shifted the response to a greater degree of spike pattern modulation. Modulated responses in both categories exhibited a sparse and long-range spatial distribution within motor thalamus, suggesting that stimulation preferentially affects afferent and efferent axonal processes traversing near the active electrode and that the resulting modulated volume strongly depends on the local connectome of these axonal processes. Such findings have important implications for current clinical efforts building predictive computational models of DBS therapy, developing directional DBS lead technology, and formulating closed-loop DBS strategies.

Introduction: Patients (pts) with hematological malignancies (HMs) are at increased risk for severe COVID19 infection and death (Grivas, 2021). Currently, vaccination represents the most effective prevention approach. HM pts have been shown to have lower immune responses to COVID19 vaccine, particularly those with lymphoid malignancies (LMs) (Herishanu, 2021; Thakkar 2021; Tzarfari 2021). We conducted an observational cohort study at Moffitt Cancer Center (MCC) to evaluate the immune response following one and two doses of the mRNA1273 (Moderna) vaccine in cancer pts. Here we report the results for pts with LMs and assessed associated factors. Methods: MCC pts who presented for the first mRNA-1273 vaccine dose from 1/12/2021-1/25/2021 and who provided consent were enrolled. Blood samples were collected prior to the 1 st and 2 nd doses (Days 1 and 29) and ~28 days after the 2 nd dose (Day 57). The IgG response against the SARS-CoV-2 spike (S) protein was measured using a two-step ELISA adapted from the Krammer (Icahn School of Medicine at Mount Sinai) protocol. The total 103 LM pts who received both vaccine doses and had samples at all time points were included in analyses. The 214 pts with solid tumors (ST) were included as comparison. Associations of seroconversion (SV) rates with pt characteristics were evaluated using the Fisher exact test or Chi-square test as appropriate. Associations of antibody (Ab) titers with pt characteristics were examined using Kruskal Wallis test. Factors independently associated with SV rates were evaluated using multivariable logistic regression. All analyses were performed using SAS 9.4 and R studio. Results: Baseline characteristics, cancer treatments and SV rates by these factors are listed in Tables 1 and 2. 55 pts had B-cell non-Hodgkin lymphoma (B-NHL), 23 had chronic lymphocytic leukemia (CLL), 15 had T- or NK-cell lymphoma (T/NK lymphoma) and 10 had Hodgkin lymphoma (HL). SV rates were significantly lower for LM pts compared to ST pts (49.5% vs 86.9% after the 1st dose and 68.9% vs 98.1% after the 2 nd dose, respectively, p12 months ago and 6 pts were in remission and have not received any cancer treatment after CAR-T. Pts with CLL and B-NHL but not on CD20 mAb/BTKi/PI3Ki/venetoclax or post CAR-T had much higher SV rates (31.3-60.5% after dose 1 and 79.0-81.3% after dose 2, Table 3). Other factors associated with lack of SV after 2 doses included: lymphocyte In the univariate model, Ab titers after 1 and 2 doses were significantly lower in pts with diagnosis of CLL/B-NHL, low lymphocyte count, low IgG and on cancer treatment (Figures 1-3). HL and T/NK lymphoma had titers comparable to solid tumors (Figure 1). Conclusions: Pts with CLL and B-NHL had low SV rates and Ab titers after receiving the mRNA-1273 vaccine when compared with ST, HL and T/NK-lymphoma. Current or past treatments with CD20 mAb/BTKi/PI3Ki/venetoclax and CAR-T were associated with lower immune response, with pooled SV rates of 16.7% after 2 doses. In general, LM pts had lower SV rates and Ab titers after the 1 st dose vs ST, but responses improved after the 2 nd dose. Further studies are needed to improve immune responses to COVID19 vaccines in LM pts, including the potential role of a 3 rd booster dose. Figure 1 Figure 1. Disclosures Gaballa: Adaptive Biotechnologies: Research Funding; Epizyme: Consultancy, Research Funding; TG therapeutics: Consultancy, Speakers Bureau; Beigene: Consultancy; ADC Therapeutics: Consultancy. Saeed: Bristol-Myers Squibb Company: Consultancy; sano-aventis U.S.: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen Pharmaceutica Products, LP: Consultancy, Other: investigator; Celgene Corporation: Consultancy, Other: investigator; MEI Pharma Inc: Consultancy, Other: investigator; Kite Pharma: Consultancy, Other: investigator; Other-TG therapeutics: Consultancy, Other: investigator; Nektar Therapeutics: Consultancy, Other: research investigator; MorphoSys AG: Consultancy, Membership on an entity's Board of Directors or advisory committees; Other-Epizyme, Inc.: Consultancy; Other-Secura Bio, Inc.: Consultancy; Seattle Genetics, Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees. Shah: Pharmacyclics/Janssen: Honoraria, Other: Expenses; Pfizer: Consultancy, Other: Expenses; BeiGene: Consultancy, Honoraria; Servier Genetics: Other; Jazz Pharmaceuticals: Research Funding; Precision Biosciences: Consultancy; Amgen: Consultancy; Kite, a Gilead Company: Consultancy, Honoraria, Other: Expenses, Research Funding; Acrotech/Spectrum: Honoraria; Novartis: Consultancy, Other: Expenses; Bristol-Myers Squibb/Celgene: Consultancy, Other: Expenses; Adaptive Biotechnologies: Consultancy; Incyte: Research Funding. Locke: Janssen: Consultancy, Other: Scientific Advisory Role; BMS/Celgene: Consultancy, Other: Scientific Advisory Role; EcoR1: Consultancy; Allogene Therapeutics: Consultancy, Other: Scientific Advisory Role, Research Funding; Calibr: Consultancy, Other: Scientific Advisory Role; Amgen: Consultancy, Other: Scientific Advisory Role; Bluebird Bio: Consultancy, Other: Scientific Advisory Role; Umoja: Consultancy, Other; Cowen: Consultancy; Kite, a Gilead Company: Consultancy, Other: Scientific Advisory Role, Research Funding; Emerging Therapy Solutions: Consultancy; Gerson Lehrman Group: Consultancy; Moffitt Cancer Center: Patents & Royalties: field of cellular immunotherapy; Iovance Biotherapeutics: Consultancy, Other: Scientific Advisory Role; GammaDelta Therapeutics: Consultancy, Other: Scientific Advisory Role; Cellular Biomedicine Group: Consultancy, Other: Scientific Advisory Role; Wugen: Consultancy, Other; Takeda: Consultancy, Other; Novartis: Consultancy, Other, Research Funding; Legend Biotech: Consultancy, Other. Chavez: Abbvie: Consultancy; AstraZeneca: Research Funding; Kite/Gilead: Consultancy; Karyopharm Therapeutics: Consultancy; MorphoSys: Speakers Bureau; Epizyme: Speakers Bureau; Bristol Myers Squibb: Speakers Bureau; Merck: Research Funding; Adaptive: Research Funding; BeiGene: Speakers Bureau; Novartis: Consultancy; ADC Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding. Lancet: AbbVie: Consultancy; ElevateBio Management: Consultancy; Daiichi Sankyo: Consultancy; Celgene/BMS: Consultancy; Millenium Pharma/Takeda: Consultancy; BerGenBio: Consultancy; Agios: Consultancy; Astellas: Consultancy; Jazz: Consultancy. Sokol: Dren Bio: Membership on an entity's Board of Directors or advisory committees; Kyowa-Kirin: Membership on an entity's Board of Directors or advisory committees. Pinilla Ibarz: AbbVie, Janssen, AstraZeneca, Novartis, TG Therapeutics, Takeda: Consultancy, Other: Advisory; Sellas: Other: ), patents/royalties/other intellectual property; MEI, Sunesis: Research Funding; AbbVie, Janssen, AstraZeneca, Takeda: Speakers Bureau. Giuliano: Merck & CO: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding.

Introduction: Cannabis sativa (hemp) seeds are popular for their high nutrient content, and strict regulations are in place to limit the amount of potentially harmful phytocannabinoids, especially Δ9-tetrahydrocannabinol (Δ9-THC). In Canada, this limit is 10 μg of Δ9-THC per gram of hemp seeds (10 ppm), and other jurisdictions in the world follow similar guidelines. Materials and Methods: We investigated three different brands of consumer-grade hemp seeds using four different procedures to extract phytocannabinoids, and quantified total Δ9-THC and cannabidiol (CBD). Discussion: We discovered that Δ9-THC concentrations in these hemp seeds could be as high as 1250% of the legal limit, and the amount of phytocannabinoids depended on the extraction procedure employed, Soxhlet extraction being the most efficient across all three brands of seeds. Δ9-THC and CBD exhibited significant variations in their estimated concentrations even from the same brand, reflecting the inhomogeneous nature of seeds and variability due to the extraction method, but almost in all cases, Δ9-THC concentrations were higher than the legal limit. These quantities of total Δ9-THC may reach as high as 3.8 mg per gram of hemp seeds, if one were consuming a 30-g daily recommended amount of hemp seeds, and is a cause for concern for potential toxicity. It is not clear if these high quantities of Δ9-THC are due to contamination of the seeds, or any other reason. Conclusion: Careful consideration of the extraction method is very important for the measurement of cannabinoids in hemp seeds.

In our previous research we have observed that the fluorescence emission from water solutions of Single-Walled Carbon Nano-Tubes (SWCNT), excited by a laser with a wavelength of 830nm, diminishes with the time. We have already proved that such a fading is a function of the storage time and the storage temperature. In order to study the emission of the SWCNT as a function of these two parameters we have designed and realized a special measurement compartment with a cuvette holder where the SWCNT solutions can be measured and stored at a fixed constant temperature for periods of time as long as several weeks. To maintain the measurement setup under a constant temperature we have designed special experimental setup based on two Peltier cells with electronic temperature control.

Lack of awareness of renal diseases among the parents/care givers of children can contribute to the development of childhood chronic kidney disease (CKD). Awareness of kidney disease by the care givers of children can improve their health seeking behaviour and reduce the significant economic and public health burden. We conducted a cross-sectional descriptive study to assess the knowledge, attitude and practice of renal diseases among the care givers of children attending University of Maiduguri Teaching Hospital. Management of CKD is very expensive especially in the third world where most care givers are poor and cannot afford the cost of renal replacement therapy like dialysis and renal transplant. This underscores the determination of knowledge, attitude and practice of parents/care givers on childhood renal diseases. Objective: To assess the knowledge, attitude and practices on renal diseases among the care givers of children attending a tertiary hospital in north eastern Nigeria. Method: This cross-sectional study was conducted among mothers or caregivers of children receiving care in the Department of Paediatrics of a Teaching Hospital, Borno state. Mothers/caregivers were consecutively selected as they come to the hospital and 420 subjects were interviewed through a self-administered questionnaire. Each subject was interviewed on his or her knowledge, attitude and practice of childhood renal diseases and data was entered appropriately into the different sections of the study questionnaires. Data was analysed using Epi-info statistical software (version 7.0). Informed consent was obtained from the parents and confidentiality to any information disclosed by the mother was ensured. Results: The ages of the respondents ranged from 18 – 67 years with a mean age of 37.2 (SD±13.6) years. Majority 140 (33.3%) of the respondents were aged 31 – 50 years; p less than 0.05. Among the respondents, were 255 (60.7%) females and 165 (39.3%) males with male to female ratio of 1: 1.5. The ages of the children ranged from 1 month to 15 years with 239 (56.9%) males and 181 (43.1%) females and male to female ratio of 1.3: 1. There were 267 (63.6%) Muslims and 153 (36.4%) Christians. There were 98 (23.3%) care givers from the upper social class, 120 (28.6%) from the middle social class and 202 (48.1%) from the lower social class. Most mothers (89.2%) had no factor preventing them from seeking medical care. Many (70.7%) of the caregivers took their children to health facilities once sick or developed any symptom of severe childhood disease. Conclusion: Although most of the care givers that participated in this study had knowledge of one form of kidney disease or the other, most had no knowledge of any treatment modality of these kidney diseases

Autism Spectrum Disorder (ASD), often referred to as Autism, is a clinically heterogeneous neurodevelopmental disorder with core-defining features of impaired socialization, impaired verbal and nonverbal communication, and restricted and repetitive patterns of behaviour. The disorder is presently diagnosed behaviourally, however the search for possible biomarkers that could aid earlier diagnosis have been on the increase. The present study aims to investigate plasma amino acid levels as a potential biomarker in ASD screening. Plasma levels of 20 amino acids (AA) (including neurotransmitters-GABA and glutamate) of autistic individuals and typical age and sex matched control, were determined using reversed-phase high performance liquid chromatography (RPHPLC). All statistical analyses (independent t-test, spearman correlation, cohen’s d effect size) were done using IBM SPSS version 20. A total of 31 plasma samples (18 Autism cases and 13 agesex matched controls) were analyzed with mean ages 8.44±4.87 for cases and 8.15±4.88 for controls. No significant intergroup difference was observed in the individual amino acid levels with the exception of glutamate (t = 5.472, df = 2.324, p = 0.000063), glutamine (t = 8.342, df = 14.780, p = 0.000001) , GABA (t = 6.601, df = 24.593, p = 0.000001), tryptophan (t = 3.568, df = 16.472, p = 0.002) and cysteine (t = 4.000, df = 13.762, p = 0.001).The amino acid profile and the glutamate - GABA levels can serve as biochemical markers for ASD, and can thus be utilized as screening for earlier diagnosis of the disorder. Keywords: Autism Spectrum Disorder (ASD), Biomarkers, Neurotransmitters, GABA, Glutamate, Diagnosis

The presence of skull cups (bowls made from human calvaria) is considered evidence of the ritualistic treatment of human bodies. These artefacts are characterised by careful manufacturing which can be taphonomically observed in bone surface modifications (BSM) as cut marks and percussion marks. These BSM show morphological similarities across Upper Palaeolithic, Neolithic, and Bronze Age assemblages. This study is focused on the analysis of the frequency and spatial distribution of cut marks on skull cups from Gough's Cave (UK), Herxheim (Germany), and El Mirador Cave (Spain), as compared to the frequency and spatial distribution of modifications on human skulls (non-skull cups) from TD6.2 of Gran Dolina (Spain) and Fontbrégoua (France), with the aim of identifying a common pattern related to a symbolic background. Nearest neighbour analysis and Kernel analyses were used to identify the distribution pattern of anthropogenically induced modifications. The results indicate that the frequency and distribution of cut marks on human skulls modified into skull cups are unique and are most likely to be the result of meticulous cleaning of skulls. A similar frequency and distribution pattern of modifications was also observed on skulls from Fontbrégoua, possibly related to the collection of skulls as war trophies. No parallels with the treatment of skulls of Homo antecessor at TD6.2 of Gran Dolina were observed. We suggest that the treatment of human skulls for ritualistic purposes therefore results in a consistent pattern of modification., This work was supported by the Ministerio de Economía, Industria y Competitividad/Fondo Europeo de Desarrollo Regional [PGC2018-093925-B-C32]; the Agència de Gestió d'Ajuts Universitaris i de Recerca project number [SGR 2017-1040]; the Universitat Rovira i Virgili [2014, 2015 and 2016 PFR-URV-B2-17]; and the Departament de Cultura de Generalitat de Catalunya [100576, 2014], and is framed in Centres de Recerca de Catalunya Programme/Generalitat de Catalunya. A. Rodriguez-Hidalgo has the support of the Spanish Ministry of Science, Innovation and Universities [IJC2018-037447-I].