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Biodiesel has become one of the promising alternative fuel resources for petro-diesel. Biodiesel is obtained by mixing oil and alcohol through transesterification reaction. A catalyst (base or acid) is typically added to accelerate the transesterification reaction and yield the maximum biodiesel production. The use of the traditional catalyst has problems like catalyst separation, soap formation, high reaction time, more energy consumption and environmental pollution. Literature shows that the addition of a catalyst from organic sources can overcome these problems. Biocatalysts were produced from different bio-waste like animal bones, plant leaves, fruit and vegetable peels, but there is no work found on the effects of Citrus Limetta peel waste for the biodiesel production. In this work, the feasibility of using Citrus Limetta peel ashes as an eco-friendly biocatalyst was investigated for the biodiesel production from Jatropha oil. The biocatalyst was obtained from Citrus Limetta peel waste after drying, pulverizing and calcination. XRD, SEM and EDX were used for the characterization of the biocatalyst. The biodiesel was tested for conformance with Euro standards. Then, three biodiesel blends (JT90, JT80 and JT70 with 10, 20 and 30 % biodiesel) were tested for determining the engine performance and emission characteristics in a Kirloskar 4-stroke CI diesel engine. SEM and EDX indicated a substantial concentration of potassium (26.8 %) and calcium (71.59 %) in the biocatalyst. The maximum biodiesel yield was achieved with 2 wt% biocatalyst, 15:1 Jatropha-to-methanol molar ratio, 60 °C reaction temperature and 1 h reaction time. Engine performance study showed that the JT80 blend demonstrated a BTE improvement of 1.2 % with a significant BSFC reduction of 11 % when subjected to full load conditions, surpassing that of pure diesel. Emissions study revealed that the JT80 blend demonstrated a substantial decrease in emissions compared to pure diesel. Specifically, there was a noteworthy 10.3 % reduction of carbon monoxide (CO), 14 % of carbon dioxide (CO2), 11 % of unburnt hydrocarbon (HC) and 3 % of nitrogen oxides (NOX), but with an increase of 2 % in smoke emissions.

This study utilized a qualitative design to explore dietitians’ perceptions regarding Ketogenic Diet Therapy (KDT) for patients with drug-resistant epilepsy in Kenya. Dietitians from Kenya were selected and consented. Audio-recorded interviews were conducted, followed by thematic analysis of verbatim transcripts to identify recurring patterns. The study enrolled 18 dietitians, fourteen of whom correctly described their understanding of KDT for managing drug-resistant epilepsy. There was a lack of confidence in their capacity to initiate the KDT with all expressing the need for further training and facilitation. Only one dietitian reported having initiated and maintained KDT. There was an overall positive view regarding KDT and willingness to implement KDT for patients with drug-resistant epilepsy. Dietitians expressed concerns regarding the availability of national policies, inadequate staffing to support families who require KDT, and the cost of implementing this intervention. Dietitians expressed interest in virtual training to enhance their understanding of KDT. Dietitians in Kenya are mostly aware of KDT utilization for the management of drug-resistant epilepsy. However, they cited poor capability and various barriers to implementation. There is a need for policies to facilitate KDT as a treatment option for the benefit of patients with drug-resistant epilepsy.

Aim: Valoctocogene roxaparvovec (AAV5-hFVIII-SQ) is a gene therapy evaluated in the phase 3 GENEr8-1 trial that provides endogenous factor VIII (FVIII) production to prevent bleeding in people with severe hemophilia A and represents an alternative to emicizumab, a recombinant antibody mimicking the function of FVIII. Individuals receiving emicizumab were excluded from GENEr8-1 enrollment since emicizumab was then an investigational therapy. This study aimed to utilize pharmacokinetic simulations to provide guidance on maintaining hemostatic control while transitioning patients from emicizumab to valoctocogene roxaparvovec gene therapy. Methods: A published emicizumab pharmacokinetic model, based on data from the HAVEN clinical trials, was used to simulate in vivo emicizumab concentrations and merged with FVIII activity time-course data for 134 GENEr8-1 participants to estimate bleeding risk at weekly intervals post-infusion with valoctocogene roxaparvovec. The analysis examined 3 approved emicizumab dosing regimens for 2 transition scenarios; first, the last emicizumab dose given the same day as infusion, and second, given 4 weeks after valoctocogene roxaparvovec. Results: Discontinuation of emicizumab the day of valoctocogene roxaparvovec infusion compared with continued dosing for 4 weeks offered similar levels of hemostatic control. The time course for bleeding risk was comparable across the emicizumab dosing regimens for both scenarios. An algorithm to provide guidance for discontinuing emicizumab was developed based on these results. To guide how treatment decisions for emicizumab discontinuation may vary among individuals, theoretical case examples were developed based on participants of GENEr8-1. Conclusions: Regardless of the emicizumab dose or dosing regimen, pharmacokinetic simulations showed no meaningful difference in the risk of bleeding related to FVIII and FVIII equivalent activity determined by the dynamic balance of decaying emicizumab levels and increasing gene therapy–derived endogenous FVIII. These original data suggest individuals on emicizumab prophylaxis can safely transition to valoctocogene roxaparvovec. COIs for presenting author. Suresh Agarwal is an employee and stockholder of BioMarin Pharmaceutical Inc.

Aim: Valoctocogene roxaparvovec delivers a B-domain deleted factor VIII (FVIII) coding sequence with an adeno-associated virus vector to reduce bleeding and FVIII concentrate use in people with severe hemophilia A. This study aimed to characterize the long-term trajectory of transgene-derived FVIII activity using a linear mixed effects (LME) model to estimate mean and median FVIII activity levels 5 years post-infusion. Methods: In GENEr8-1, an open-label, single-arm, multicenter phase 3 trial, 134 participants with severe hemophilia A received a single 6 x 1013 vg/kg dose of valoctocogene roxaparvovec. FVIII activity was assessed using the chromogenic substrate assay and one-stage assay. A previously published quantitative pharmacokinetic (PK) modelwas updated to extrapolate FVIII activity levels to 5 years post-infusion. Ln-transformed FVIII activity values from week 76 to 104 were fit to the LME model with random effects for participants on slope and intercept using a restricted maximum likelihood method with the lmer package in the R statistical computing software (R Foundation for Statistical Computing, Vienna, Austria). The precision of parameter estimates and model diagnostics were evaluated to confirm goodness-of-fit. The model and extrapolation approach was further qualified by comparing to observed FVIII activity at week 156. Results: The final LME model dataset included 928 observations from 120 participants. The long-term trajectory of FVIII activity was consistent with first-order elimination kinetics starting at week 76. Model parameter estimates were consistent with the previously published model; diagnostic plots showed no major deficiencies. FVIII activity was extrapolated to 5 years post-gene transfer. Mean and median FVIII activity extrapolations at week 156 were consistent with observed values, confirming adequacy of the model. Conclusions: Pharmacokinetic modeling indicates valoctocogene roxaparvovec-derived FVIII activity levels will remain in the mild hemophilia range for ≥5 years post-gene transfer for the majority of patients treated. COIs for presenting author: Suresh Agarwal is a paid employee of BioMarin Pharmaceutical Inc. and holds stock ownership with BioMarin Pharmaceutical Inc.

Summary: Background: Identification of convulsive epilepsy in sub-Saharan Africa relies on access to resources that are often unavailable. Infrastructure and resource requirements can further complicate case verification. Using machine-learning techniques, we have developed and tested a region-specific questionnaire panel and predictive model to identify people who have had a convulsive seizure. These findings have been implemented into a free app for health-care workers in Kenya, Uganda, Ghana, Tanzania, and South Africa. Methods: In this retrospective case-control study, we used data from the Studies of the Epidemiology of Epilepsy in Demographic Sites in Kenya, Uganda, Ghana, Tanzania, and South Africa. We randomly split these individuals using a 7:3 ratio into a training dataset and a validation dataset. We used information gain and correlation-based feature selection to identify eight binary features to predict convulsive seizures. We then assessed several machine-learning algorithms to create a multivariate prediction model. We validated the best-performing model with the internal dataset and a prospectively collected external-validation dataset. We additionally evaluated a leave-one-site-out model (LOSO), in which the model was trained on data from all sites except one that, in turn, formed the validation dataset. We used these features to develop a questionnaire-based predictive panel that we implemented into a multilingual app (the Epilepsy Diagnostic Companion) for health-care workers in each geographical region. Findings: We analysed epilepsy-specific data from 4097 people, of whom 1985 (48·5%) had convulsive epilepsy, and 2112 were controls. From 170 clinical variables, we initially identified 20 candidate predictor features. Eight features were removed, six because of negligible information gain and two following review by a panel of qualified neurologists. Correlation-based feature selection identified eight variables that demonstrated predictive value; all were associated with an increased risk of an epileptic convulsion except one. The logistic regression, support vector, and naive Bayes models performed similarly, outperforming the decision-tree model. We chose the logistic regression model for its interpretability and implementability. The area under the receiver operator curve (AUC) was 0·92 (95% CI 0·91–0·94, sensitivity 85·0%, specificity 93·7%) in the internal-validation dataset and 0·95 (0·92–0·98, sensitivity 97·5%, specificity 82·4%) in the external-validation dataset. Similar results were observed for the LOSO model (AUC 0·94, 0·93–0·96, sensitivity 88·2%, specificity 95·3%). Interpretation: On the basis of these findings, we developed the Epilepsy Diagnostic Companion as a predictive model and app offering a validated culture-specific and region-specific solution to confirm the diagnosis of a convulsive epileptic seizure in people with suspected epilepsy. The questionnaire panel is simple and accessible for health-care workers without specialist knowledge to administer. This tool can be iteratively updated and could lead to earlier, more accurate diagnosis of seizures and improve care for people with epilepsy. Funding: The Wellcome Trust, the UK National Institute of Health Research, and the Oxford NIHR Biomedical Research Centre.

Introdução: Testes imuno-hematológicos como determinação da expressão fenotípica de antígenos de diferentes sistemas de grupos sanguíneos, pesquisa de anticorpos irregulares, testes da antiglobulina direto e indireto, prova de compatibilidade e titulação de anticorpos são rotineiramente realizados através de métodos sorológicos com o emprego de reagentes que indicarão a presença ou ausência de antígenos e anticorpos baseados em reações de hemaglutinação. Para a obtenção de resultados confiáveis e consequente garantia da segurança transfusional, entre outras estratégias, é imprescindível a padronização e validação dos processos críticos, treinamento inicial e periódico dos colaboradores. Nesse contexto, deve ser realizada a padronização das leituras e interpretação das reações imuno-hematológicas. A estatística do Kappa é útil para avaliação da confiabilidade entre observadores e é um importante indicador de avaliação da qualidade. No entanto, o teste deve ser utilizado como um instrumento adicional para o aprimoramento da qualidade do exame, não devendo funcionar isoladamente como elemento de avaliação no processo. Objetivos: Determinar a concordância entre duplas de profissionais na leitura e interpretação de reações imuno-hematológicas na técnica de tubo. Materiais e métodos: Três profissionais participaram da análise de concordância de leitura de 54 diferentes reações imuno-hematológicas na técnica de tubo. Um dos profissionais realizou a homogeneização da reação enquanto, simultaneamente, de forma cega e independente, os três profissionais analisaram a intensidade da reação. A leitura das intensidades de reação seguiu os padrões de Judd e colaboradores (2008). A concordância da leitura dos testes entre as duplas de profissionais foi determinada através do teste estatístico Kappa de Cohen, o qual considera a proporção de concordância observada e a estimativa da proporção de concordância esperada pelo acaso. Resultados: Entre as reações estavam: soro de Coombs titulado + hemácia controle de Coombs, soro anti-D titulado + hemácia RhD positiva, soro anti-B titulado + hemácia B, soro anti-AB titulado + hemácia AB. O valor de Kappa de Cohen (0-1) foi calculado para cada dupla de profissionais, considerando as rotinas imuno-hematológicas com leitura e segunda leitura. O índice Kappa calculado foi de 0,97 entre os profissionais 1 e 2, de 0,95 entre os profissionais 1 e 3 e de 0,97 entre os profissionais 2 e 3. Discussão: O valor de Kappa estima a concordância entre observadores, corrigida pela probabilidade de concordância ao acaso, podendo ser interpretado como a melhor proporção de concordância possível além do acaso, considerando o percentual de concordância entre dois observadores. Kappa entre 0,80 e 1,0 indica uma concordância quase perfeita entre os leitores. Embora tenha sido utilizado um número relativamente pequeno de reações para a avaliação, o índice Kappa é uma ferramenta importante para a avaliação da confiabilidade entre observadores e consequentemente garantia da qualidade de exames imuno-hematológicos realizados. Os resultados indicaram a eficácia dos treinamentos realizados e que os processos estão padronizados entre esses profissionais. Conclusão: O valor de Kappa encontrado indica uma concordância excelente entre as duplas de profissionais, o que contribui para a segurança do processo transfusional.

Coalition of the carpal bones is a relatively uncommon anatomic anomaly. The majority of carpal coalitions occur between the lunate and triquetrum. There are rare reports of coalition involving the hamate and pisiform. We report a case of a previously asymptomatic male who sustained minor trauma and was found to have hamate-pisiform coalition complicated by a minimally displaced pisiform fracture. Keywords: Pediatric carpal coalition, Hamate-pisiform, Pisiform-hamate

Focal cortical dysplasia is a congenital abnormality of cortical development and the leading cause of surgically remediable drug-resistant epilepsy in children. Post-surgical outcome is improved by presurgical lesion detection on structural MRI. Automated computational techniques have improved detection of focal cortical dysplasias in adults but have not yet been effective when applied to developing brains. There is therefore a need to develop reliable and sensitive methods to address the particular challenges of a paediatric cohort. We developed a classifier using surface-based features to identify focal abnormalities of cortical development in a paediatric cohort. In addition to established measures, such as cortical thickness, grey-white matter blurring, FLAIR signal intensity, sulcal depth and curvature, our novel features included complementary metrics of surface morphology such as local cortical deformation as well as post-processing methods such as the “doughnut” method - which quantifies local variability in cortical morphometry/MRI signal intensity, and per-vertex interhemispheric asymmetry. A neural network classifier was trained using data from 22 patients with focal epilepsy (mean age = 12.1 ± 3.9, 9 females), after intra- and inter-subject normalisation using a population of 28 healthy controls (mean age = 14.6 ± 3.1, 11 females). Leave-one-out cross-validation was used to quantify classifier sensitivity using established features and the combination of established and novel features. Focal cortical dysplasias in our paediatric cohort were correctly identified with a higher sensitivity (73%) when novel features, based on our approach for detecting local cortical changes, were included, when compared to the sensitivity using only established features (59%). These methods may be applicable to aiding identification of subtle lesions in medication-resistant paediatric epilepsy as well as to the structural analysis of both healthy and abnormal cortical development.

The present investigation focuses on analyzing the microstructure and tensile properties of room temperature quenching and partitioning (RT Q&P) steel manufactured using laser powder bed fusion (LPBF). The as-built specimen reveals a dual-phase microstructure composed of retained austenite (RA) grains within the martensite matrix, with the absence of the conventional Mn banded microstructure. However, the as-built sample demonstrates poor tensile properties, exhibiting only a 2.5% total elongation, largely due to significant residual stress. To mitigate this issue, the as-built sample undergoes tempering at low temperatures (300, 350, and 400 °C) for 10 min. This treatment results in a reduction of the average compressive residual stresses from −214.4 to −132.1 MPa, and a transformation of the residual stresses in RA from a compressive state of −52.4 MPa to a tensile state of 136.4 MPa after tempering at 350 °C. Furthermore, the volume fraction of RA increases by approximately 10%, and there is a slight increase in the C content after tempering. The tempered RT Q&P steel demonstrates an ultra-high tensile strength ranging from 1.3 to 1.5 GPa, coupled with a substantial total elongation of 10–15%. This exceptional combination of strength and ductility is attributed to the transformation-induced plasticity (TRIP) effect and the reduction of residual stresses. Notably, this study marks the first confirmation that strong and ductile RT Q&P steel can be produced through the LPBF process.

In order to facilitate the study of transport processes of unconjugated C-24 bile salts, simple syntheses of 3 alpha, 7 alpha, 12 alpha-trihydroxy-24-nor-5 beta-cholan-23-sulfonate (norcholansulfonate) and 3 alpha, 7 alpha, 12 alpha-trihydroxy-24-nor-5 beta-[7 beta 5H] cholan-23-sulfonate were devised. The hydrophilic-hydrophobic properties of norcholansulfonate, as determined by its chromatographic behavior as well as by its partition between l-octanol and water, are more similar to those of cholyltaurine than to those of cholate. Self-association of norcholansulfonate in phosphate buffer, pH 7.4, with an ionic strength of 150 mM begins at a concentration of about 1 mM, comparable to that of cholyltaurine and cholate, as determined by spectral changes in fluorescence emissions of {N-[7-(4-nitrobenzo-2-oxa-1, 3-diazol)]-7b-amino-3a, 12a-dihydroxy-5b-cholan-24 - oyl}-2'-aminoethanesulfonate (7 beta-NBD-NCT). The apparent CMC value obtained from solubilization of the dye Orange OT, 8.5 mM, is comparable to that of cholytaurine. 7.5 mM, and lower than that of cholate, 9.5 mM. Norcholansulfonate is readily taken up by rat liver and completely excreted unmetabolized into bile with about the same secretion maximum (Tm) as cholyltaurine. Biliary excretion of norcholansulfonate is inhibited by cholyltaurine, and, vice versa, norcholansulfonate inhibits cholyltaurine secretion. Concerning metabolism and excretion, norcholansulfonate with the sulfonate group in the position where cholate has the carboxylate group should behave as an appropriate cholate analogue in mediated transport processes.

The VLDL receptor has been described as a new member of the LDL receptor supergene family that specifically binds VLDL in vitro via apolipoprotein E and lipoprotein lipase. Both apolipoprotein E and lipoprotein lipase are constituents of chylomicron remnants, another triglyceride-rich lipoprotein which has been proposed as a physiological ligand for the VLDL receptor. We used human chylomicron remnants to study their uptake into LDL, receptor-deficient Chinese hamster ovary cells overexpressing the human VLDL receptor. The uptake into these cells was compared to that into cells transfected with an empty transfection vector. Human chylomicron remnants were produced in vitro by hydrolysis with lipoprotein lipase, and were labeled with 125I. The uptake of these remnants into the cells overexpressing the VLDL receptor was found to be about 3-fold higher than the uptake into the control cells. The addition of a surplus of either apolipoprotein E or inactivated lipoprotein lipase to the remnants led to an increase in particle uptake. The chylomicron remnant uptake was inhibited by addition of the 39 kDa receptor associated protein These in vitro experiments strongly support the idea that the VLDL receptor is a physiological receptor for chylomicron remnants. The increase of receptor-mediated uptake induced by the addition of apoE or lipoprotein lipase underlines the role of these two proteins in this process.

Phosphodiesterase III (cyclic GMP-inhibited, particulate, low Km) is believed to play a dominant role in the cyclic AMP breakdown and lipolysis regulation in fat cells. Its importance for lipolysis activity was investigated in situ in humans by comparing the effects of a selective (amrinone) and a nonselective (theophylline) inhibitor of the enzyme. Abdominal subcutaneous adipose tissue of healthy nonobese humans was microdialyzed with solvents containing one or both of these agents, and glycerol (lipolysis index) or the escape of ethanol from the dialysis solvent (blood flow index) was continuously monitored in the perfusate. Both agents caused a dose-dependent and sustained increase in the glycerol level in the perfusate for at least 2.5 h. Although amrinone was 5000 times more potent than theophylline on a molar basis, its maximum activity was only 35% as compared to the maximum activity of theophylline. Half-maximum lipolytic effect of the two drugs occurred at about 0.1 mumol/l and 1 mmol/l, respectively (P < 0.001). At maximum effective concentrations, amrinone stimulated lipolysis by about 63% and theophylline by about 200% (P < 0.01). At these concentrations amrinone increased the rate of disappearance of ethanol from the perfusate by about 20% and theophylline increased the rate by about 75%, the difference being statistically significant (P < 0.01). When the two drugs were added together, the level of lipolysis stimulation was not different from that with theophylline alone both at maximal and submaximal effective concentrations of drug combinations.(ABSTRACT TRUNCATED AT 250 WORDS)

The nutritional components of fermented soybean meal (FSBM) vary because of the complex process of microbial fermentation. The objective of this study was to investigate the nutritional value of FSBM from two sources and explore the mode of actions of FSBM on the improvement of nutrient digestibility with the measurements of digestive enzymes and serum biomarkers. Eight weaned barrows (initial BW: 14.12 ± 0.24 kg) equipped with T-cannula in the distal ileum were allotted to a duplicated 4 × 4 Latin-square design with four experimental diets and four periods. Four experimental diets included a soybean meal control diet, two FSBM diets, and a nitrogen-free diet. The two sources of FSBM increased the contents of CP, amino acid and lactic acid, while decreased the levels of anti-nutritional factors, including glycinin, β-conglycinin and trypsin inhibitors. Compared to soybean meal control diet, both FSBM diets significantly increased the apparent and standardised ileal digestibility of CP and amino acids (P

Summary: Cocaine use is a major comorbidity of HIV-associated neurocognitive disorder (HAND). In this study, we show that cocaine exposure worsens the learning and memory of doxycycline-inducible and brain-specific HIV Tat transgenic mice (iTat) and results in 14,838 hypermethylated CpG-related differentially methylated regions (DMRs) and 15,800 hypomethylated CpG-related DMRs, which are linked to 52 down- and 127 upregulated genes, respectively, in the hippocampus of iTat mice. These genes are mostly enriched at the neuronal function-, cell morphology-, and synapse formation-related extracellular matrix (ECM) receptor-ligand interaction pathway and mostly impacted in microglia. The accompanying neuropathological changes include swollen dendritic spines, increased synaptophysin expression, and diminished glial activation. We also find that sex (female) and age additively worsen the behavioral and pathological changes. These findings together indicate that chronic cocaine and long-term Tat expression interactively contribute to HAND, likely involving changes of DNA methylation and ECM receptor-ligand interactions.

The spatiotemporal structure of functional magnetic resonance imaging (fMRI) signals has provided a valuable window into the network underpinnings of human brain function and dysfunction. Although some cross-regional temporal correlation patterns (functional connectivity; FC) exhibit a high degree of stability across individuals and species, there is growing acknowledgment that measures of FC can exhibit marked changes over a range of temporal scales. Further, FC can co-vary with experimental task demands and ongoing neural processes linked to arousal, consciousness and perception, cognitive and affective state, and brain-body interactions. The increased recognition that such interrelated neural processes modulate FC measurements has raised both challenges and new opportunities in using FC to investigate brain function. Here, we review recent advances in the quantification of neural effects that shape fMRI FC and discuss the broad implications of these findings in the design and analysis of fMRI studies. We also discuss how a more complete understanding of the neural factors that shape FC measurements can resolve apparent inconsistencies in the literature and lead to more interpretable conclusions from fMRI studies.

The Λb0→Λc+K+K−π− decay is observed for the first time using a data sample of proton-proton collisions at centre-of-mass energies of s=7 and 8TeV collected by the LHCb detector, corresponding to an integrated luminosity of 3fb−1. The ratio of branching fractions between the Λb0→Λc+K+K−π− and the Λb0→Λc+Ds− decays is measured to beB(Λb0→Λc+K+K−π−)B(Λb0→Λc+Ds−)=(9.26±0.29±0.46±0.26)×10−2, where the first uncertainty is statistical, the second systematic and the third is due to the knowledge of the Ds−→K+K−π− branching fraction. No structure on the invariant mass distribution of the Λc+K+ system is found, consistent with no open-charm pentaquark signature.

Summary: We presented one eye with a monocular-boundary-contour (MBC) square, created by phase-shifting a central region of grating relative to a larger uniform grating surround, and the fellow eye with the larger uniform grating. In addition, the grating within the MBC region was rendered with lower contrast relative to the remaining stimulus. Despite this, we found the lower contrast MBC region dominated the perceived cyclopean contrast, with the corresponding region in the fellow eye being suppressed. Secondly, we found for dichoptic stimuli with half-images having square grating regions of different BC strengths, the interocular BC strength ratio determined the perceived contrast of the cyclopean square. Thirdly, we found perceived spatial phase of the cyclopean square was dominated by the spatial phase of the MBC half-image. Altogether, these psychophysical findings provided evidence for a border-to-interior representation strategy, that constructing surface begins at the boundary contour (BC), in binocular contrast and phase integration.