888 research outputs found

    Prospects of hybrid renewable energy-based power system: A case study, post analysis of Chipendeke Micro-Hydro, Zimbabwe

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    Fossil fuel-based energy sources are the major contributors to greenhouse gas (GHG) emission and thus the use of renewable energy (RE) is becoming the best alternative to cater for the increasing energy demand in both developing and developed nations. Chipendeke is a rural community in Zimbabwe, in which electricity demand is partially served by the only micro-hydro plant and hence, load shedding is a regular practice to keep essential services running. This study explored a suitable opportunity to identify a feasible system with different energy sources that can fulfill the current and projected future load demand of the community. A techno-economic feasibility study for a hybrid RE based power system (REPS) is examined considering various energy sources and cost functions. Six different system configurations have been designed with different sizing combinations to identify the most optimum solution for the locality considering techno-economic and environmental viability. The performance metrics considered to evaluate the best suitable model are; Net Present Cost (NPC), Cost of Energy (COE), Renewable Fraction (RF), excess energy and seasonal load variations. In-depth, sensitivity analyses have been performed to investigate the variations of the studied models with a little variation of input variables. Of the studied configurations, an off-grid hybrid Hydro/PV/DG/Battery system was found to be the most economically feasible compared to other configurations. This system had the lowest NPC and COE of 307,657and 307,657 and 0.165/kWh respectively and the highest RF of 87.5%. The proposed hybrid system could apply to any other remote areas in the region and anywhere worldwide

    Prognostic significance of histopathological response to preoperative chemotherapy in unilateral Wilms' tumor: An analysis of 899 patients treated on the SIOP WT 2001 protocol in the UK-CCLG and GPOH studies

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    In the SIOP Wilms' tumor (WT) studies, preoperative chemotherapy is used as primary treatment, and tumors are classified thereafter by pathologists. Completely necrotic WTs (CN-WTs) are classified as low-risk tumors. The aim of the study was to evaluate whether a subset of regressive type WTs (RT-WTs) (67%-99% chemotherapy-induced changes [CIC]) showing an exceptionally good response to preoperative chemotherapy had comparably excellent survivals as CN-WTs, and to establish a cut-off point of CIC that could define this subset. The study included 2117 patients with unilateral, nonanaplastic WTs from the UK-CCLG and GPOH-WT studies (2001-2020) treated according to the SIOP-WT-2001 protocol. There were 126 patients with CN-WTs and 773 with RT-WTs, stages I-IV. RT-WTs were subdivided into subtotally necrotic WTs (>95% CIC) (STN-WT96-99) (124 patients) and the remaining of RT-WT (RR-WT67-95) (649 patients). The 5-year event-free survival (EFS) and overall survival (OS) for CN-WTs were 95.3% (±2.1% SE) and 97.3% (±1.5% SE), and for RT-WTs 85.7% (±1.14% SE, P < .01) and 95.2% (±0.01% SE, P = .59), respectively. CN-WT and STN-WT96-99 groups showed significantly better EFS than RR-WT67-95 (P = .003 and P = .02, respectively), which remained significantly superior when adjusted for age, local stage and metastasis at diagnosis, in multivariate analysis, whereas OS were superimposable (97.3 ± 1.5% SE for CN-WT; 97.8 ± 1.5% SE for STN-WT96-99; 94.7 ± 1.0% SE for RR-WT67-95). Patients with STN-WT96-99 share the same excellent EFS and OS as patients with CN-WTs, and although this was achieved by more treatment for patients with STN-WT96-99 than for patients with CN-WT, reduction in postoperative treatment of these patients may be justified

    Seizure pathways change on circadian and slower timescales in individual patients with focal epilepsy.

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    Personalized medicine requires that treatments adapt to not only the patient but also changing factors within each individual. Although epilepsy is a dynamic disorder characterized by pathological fluctuations in brain state, surprisingly little is known about whether and how seizures vary in the same patient. We quantitatively compared within-patient seizure network evolutions using intracranial electroencephalographic (iEEG) recordings of over 500 seizures from 31 patients with focal epilepsy (mean 16.5 seizures per patient). In all patients, we found variability in seizure paths through the space of possible network dynamics. Seizures with similar pathways tended to occur closer together in time, and a simple model suggested that seizure pathways change on circadian and/or slower timescales in the majority of patients. These temporal relationships occurred independent of whether the patient underwent antiepileptic medication reduction. Our results suggest that various modulatory processes, operating at different timescales, shape within-patient seizure evolutions, leading to variable seizure pathways that may require tailored treatment approaches

    Association between Glycemic Control and Serum Lipid Profile in type 2 Diabetic Patients: Experience in a Medical College Hospital

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    Impaired lipid metabolism in diabetic patients can lead to cardiovascular complications. Poor glycaemic control is associated with a significant increase in the risk of both patient’s morbidity and mortality. An early intervention to regulate circulating lipids has been found to lower the risk of cardiovascular problems and death. Glycated hemoglobin (HbA1c) is a reliable indicator of rising blood sugar levels. This hospital based observational study was conducted in the Department of Medicine, Sher-E-Bangla Medical College Hospital, Barisal from October 2014 to March 2015 over a period of 6 month to determine the correlation of glycemic control and lipid profile in patients with type 2 diabetes. A total of 110 type 2 diabe- tes mellitus(DM) patients of both sexes admitted to the Deapartment of Medicine of Sher-E- Bangla Medical College Hospital, Barisal, were recruited for this study. Following standard procedures and protocols, fasting blood sugar (FBS), blood sugar two hours after breakfast, Glycosylated Hemoglobin (HbA1c) and fasting lipid profile were measured. The age of respondents ranged from 34 to 70 years with the mean age of 54.35}8.02 years. Among the patients male were 70 (63.6%) and female were 40 (36.4%). Mean age at diagnosis of DM and duration of DM was 47.07}6.03 years and 7.27}3.41 years, respectively. Mean body mass index (BMI), FBS and HbA1c were 25.02}5.22 kg/m2, 8.06}2.01 mmol/L and 8.34}1.9 % respectively. Significant positive correlation of HbA1c and FBS with BMI, total cholester- ol(TC), triglyceride(TG), low density lipoprotein(LDL-C) and negative correlation with high density lipoprotein (HDL-C) was found. Significantly higher TC, TG and LDL-C and lower HDL-C were found in poor glycemic control (HbA1c ≥ 7) group than good glycemic control (HbA1c &lt; 7 ) group. The results of this study showed that , higher levels of glycemic parame- ters are significantly associated with dyslipidemia. These findings also indicate that HbA1c can be utilized for screening of high risk diabetic patients for early diagnosis of dyslipidemia and timely intervention with lipid lowering drugs. BSMMU J 2021; 14(4): 138-14

    Routinely measured haematological markers can help to predict AIS scores following spinal cord injury.

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    Neurological outcomes following spinal cord injury (SCI) are currently difficult to predict. Whilst the initial American Spinal Injury Association (ASIA) Impairment Scale (AIS) grade can give an estimate of outcome, the high remaining degree of uncertainty has stoked recent interest in biomarkers for SCI. This study aimed to assess the prognostic value of routinely measured blood biomarkers by developing prognostic models of AIS scores at discharge and 12-months post-injury. Routine blood and clinical data were collected from SCI patients (n=427) and blood measures that had been assessed in less than 50% of patients were excluded. Outcome neurology was obtained from AIS and Spinal cord independence measure III (SCIM-III) scores at discharge and 12-months post-injury, with motor (AIS) and sensory (AIS, touch and prick) abilities being assessed individually. Linear regression models with and without elastic net penalisation were created for all outcome measures. Blood measures associated with liver function such as alanine transaminase were found to add value to predictions of SCIM-III at discharge and 12-months post-injury. Furthermore, components of a total blood count including haemoglobin were found to add value to predictions of AIS motor and sensory scores at discharge and 12-month post-injury. These findings corroborate the results of our previous preliminary study and thus provide further evidence that routine blood measures can add prognostic value in SCI, and that markers of liver function are of particular interest

    Ribosomal oxygenases are structurally conserved from prokaryotes to humans

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    2-Oxoglutarate (2OG)-dependent oxygenases have important roles in the regulation of gene expression via demethylation of N-methylated chromatin components1,2 and in the hydroxylation of transcription factors3 and splicing factor proteins4. Recently, 2OG-dependent oxygenases that catalyse hydroxylation of transfer RNA5,6,7 and ribosomal proteins8 have been shown to be important in translation relating to cellular growth, TH17-cell differentiation and translational accuracy9,10,11,12. The finding that ribosomal oxygenases (ROXs) occur in organisms ranging from prokaryotes to humans8 raises questions as to their structural and evolutionary relationships. In Escherichia coli, YcfD catalyses arginine hydroxylation in the ribosomal protein L16; in humans, MYC-induced nuclear antigen (MINA53; also known as MINA) and nucleolar protein 66 (NO66) catalyse histidine hydroxylation in the ribosomal proteins RPL27A and RPL8, respectively. The functional assignments of ROXs open therapeutic possibilities via either ROX inhibition or targeting of differentially modified ribosomes. Despite differences in the residue and protein selectivities of prokaryotic and eukaryotic ROXs, comparison of the crystal structures of E. coli YcfD and Rhodothermus marinus YcfD with those of human MINA53 and NO66 reveals highly conserved folds and novel dimerization modes defining a new structural subfamily of 2OG-dependent oxygenases. ROX structures with and without their substrates support their functional assignments as hydroxylases but not demethylases, and reveal how the subfamily has evolved to catalyse the hydroxylation of different residue side chains of ribosomal proteins. Comparison of ROX crystal structures with those of other JmjC-domain-containing hydroxylases, including the hypoxia-inducible factor asparaginyl hydroxylase FIH and histone Nε-methyl lysine demethylases, identifies branch points in 2OG-dependent oxygenase evolution and distinguishes between JmjC-containing hydroxylases and demethylases catalysing modifications of translational and transcriptional machinery. The structures reveal that new protein hydroxylation activities can evolve by changing the coordination position from which the iron-bound substrate-oxidizing species reacts. This coordination flexibility has probably contributed to the evolution of the wide range of reactions catalysed by oxygenases

    The role of mothers-in-law in antenatal care decision-making in Nepal: a qualitative study

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    Background Antenatal care (ANC) has been recognised as a way to improve health outcomes for pregnant women and their babies. However, only 29% of pregnant women receive the recommended four antenatal visits in Nepal but reasons for such low utilisation are poorly understood. As in many countries of South Asia, mothers-in-law play a crucial role in the decisions around accessing health care facilities and providers. This paper aims to explore the mother-in-law’s role in (a) her daughter-in-law’s ANC uptake; and (b) the decision-making process about using ANC services in Nepal. Methods In-depth interviews were conducted with 30 purposively selected antenatal or postnatal mothers (half users, half non-users of ANC), 10 husbands and 10 mothers-in-law in two different (urban and rural) communities. Results Our findings suggest that mothers-in-law sometime have a positive influence, for example when encouraging women to seek ANC, but more often it is negative. Like many rural women of their generation, all mothers-in-law in this study were illiterate and most had not used ANC themselves. The main factors leading mothers-in-law not to support/ encourage ANC check ups were expectations regarding pregnant women fulfilling their household duties, perceptions that ANC was not beneficial based largely on their own past experiences, the scarcity of resources under their control and power relations between mothers-in-law and daughters-in-law. Individual knowledge and social class of the mothers-in-law of users and non-users differed significantly, which is likely to have had an effect on their perceptions of the benefits of ANC. Conclusion Mothers-in-law have a strong influence on the uptake of ANC in Nepal. Understanding their role is important if we are to design and target effective community-based health promotion interventions. Health promotion and educational interventions to improve the use of ANC should target women, husbands and family members, particularly mothers-in-law where they control access to family resources

    Serum and Tissue Biomarkers Associated With Composite of Relevant Endpoints for Sj\uf6gren Syndrome (CRESS) and Sj\uf6gren Tool for Assessing Response (STAR) to B Cell–Targeted Therapy in the Trial of Anti–B Cell Therapy in Patients With Primary Sj\uf6gren Syndrome (TRACTISS)

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    \ua9 2023 The Authors. Arthritis &amp; Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.Objective: This study aimed to identify peripheral and salivary gland (SG) biomarkers of response/resistance to B cell depletion based on the novel concise Composite of Relevant Endpoints for Sj\uf6gren Syndrome (cCRESS) and candidate Sj\uf6gren Tool for Assessing Response (STAR) composite endpoints. Methods: Longitudinal analysis of peripheral blood and SG biopsies was performed pre- and post-treatment from the Trial of Anti–B Cell Therapy in Patients With Primary Sj\uf6gren Syndrome (TRACTISS) combining flow cytometry immunophenotyping, serum cytokines, and SG bulk RNA sequencing. Results: Rituximab treatment prevented the worsening of SG inflammation observed in the placebo arm, by inhibiting the accumulation of class-switched memory B cells within the SG. Furthermore, rituximab significantly down-regulated genes involved in immune-cell recruitment, lymphoid organization alongside antigen presentation, and T cell co-stimulatory pathways. In the peripheral compartment, rituximab down-regulated immunoglobulins and auto-antibodies together with pro-inflammatory cytokines and chemokines. Interestingly, patients classified as responders according to STAR displayed significantly higher baseline levels of C-X-C motif chemokine ligand-13 (CXCL13), interleukin (IL)-22, IL-17A, IL-17F, and tumor necrosis factor-α (TNF-α), whereas a longitudinal analysis of serum T cell–related cytokines showed a selective reduction in both STAR and cCRESS responder patients. Conversely, cCRESS response was better associated with biomarkers of SG immunopathology, with cCRESS-responders showing a significant decrease in SG B cell infiltration and reduced expression of transcriptional gene modules related to T cell costimulation, complement activation, and Fcγ-receptor engagement. Finally, cCRESS and STAR response were associated with a significant improvement in SG exocrine function linked to transcriptional evidence of SG epithelial and metabolic restoration. Conclusion: Rituximab modulates both peripheral and SG inflammation, preventing the deterioration of exocrine function with functional and metabolic restoration of the glandular epithelium. Response assessed by newly developed cCRESS and STAR criteria was associated with differential modulation of peripheral and SG biomarkers, emerging as novel tools for patient stratification. (Figure presented.)

    Development of Derivatives of 3, 3′-Diindolylmethane as Potent Leishmania donovani Bi-Subunit Topoisomerase IB Poisons

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    Background: The development of 3, 39-diindolyl methane (DIM) resistant parasite Leishmania donovani (LdDR50) by adaptation with increasing concentrations of the drug generates random mutations in the large and small subunits of heterodimeric DNA topoisomerase I of Leishmania (LdTOP1LS). Mutation of large subunit of LdTOP1LS at F270L is responsible for resistance to DIM up to 50 mM concentration. Methodology/Principal Findings: In search of compounds that inhibit the growth of the DIM resistant parasite and inhibit the catalytic activity of mutated topoisomerase I (F270L), we have prepared three derivatives of DIM namely DPDIM (2,29diphenyl 3,39-diindolyl methane), DMDIM (2,29-dimethyl 3,39-diindolyl methane) and DMODIM (5,59-dimethoxy 3,39diindolyl methane) from parent compound DIM. All the compounds inhibit the growth of DIM resistant parasites, induce DNA fragmentation and stabilize topo1-DNA cleavable complex with the wild type and mutant enzyme. Conclusion: The results suggest that the three derivatives of DIM can act as promising lead molecules for the generation of new anti-leishmanial agents
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