Significantly enhanced critical current density and pinning force in nanostructured, (RE)BCO-based, coated conductor.

High-temperature superconducting wires have many large-scale, niche applications such as commercial nuclear fusion as well as numerous other large-scale applications in the electric power industry and in the defense, medical and transportation industries. However, the price/performance metric of these coated conductor wires is not yet favorable to enable and realize most large-scale applications. Here we report on probing the limits of Jc (H, T) possible via defect engineering in heteroepitaxially deposited high-temperature superconducting thin-films on coated conductor substrates used for long-length wire fabrication. We report record values of Jc (H, T) and pinning force, Fp (H, T) in (RE)BCO films with self-assembled BaZrO3 nanocolumns deposited on a coated conductor substrate. A Jc of ~190 MA/cm2 at 4.2 K, self-field and ~90 MA/cm2, at 4.2 K, 7 T was measured. At 20 K, Jc of over 150 MA/cm2 at self-field and over 60 MA/cm2 at 7 T was observed. A very high pinning force, Fp, of ~6.4 TN/m3 and ~4.2 TN/m3 were observed at 7 T, 4.2 K and 7 T, 20 K respectively. We report on the highest values of Jc and Fp obtained to date for all fields and operating temperatures from 4.2 K to 77 K. These results demonstrate that significant performance enhancements and hence far more favorable price/performance metrics are possible in commercial high-temperature superconducting wires.

Factors Affecting Survival in Severe and Very Severe COPD after Admission in ICUs of Tertiary Care Centers of India (FAST COPD): Study Protocol for a Multicentric Cohort Study.

Background: Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide. However, there is a lack of comprehensive data from low- and middle-income countries (LMICs) regarding factors influencing COPD outcomes, particularly in regions where biomass exposure is prevalent. Objective: The Factors Affecting Survival in Severe and Very Severe COPD Patients Admitted to Tertiary Centers of India (FAST) study aims to address this gap by evaluating factors impacting survival and exacerbation rates among COPD patients in LMICs like India, with a specific focus on biomass exposure, clinical phenotypes, and nutritional status in patients admitted to the Intensive Care Unit (ICU). Methods: The FAST study is an observational cohort study conducted in university teaching hospitals across India. The study aims to enroll 1000 COPD patients admitted to the ICU meeting specific inclusion criteria, with follow-up assessments conducted every 6 months over a 2-year period. Data collection includes demographic information, clinical manifestations, laboratory investigations, pulmonary function tests, medications, nutritional status, mental health, and health-related quality of life. Adjudication of exacerbations and mortality will also be undertaken. The FAST study seeks to provide crucial insights into COPD outcomes in LMICs, informing more precise management strategies and mitigating the burden of COPD in these settings. By evaluating factors such as biomass exposure, clinical phenotypes, and nutritional status, the study aims to address key knowledge gaps in COPD research. How to cite this article: Arunachala S, Devapal S, Swamy DSN, Greeshma MV, Ul Hussain I, Siddaiah JB, et al. Factors Affecting Survival in Severe and Very Severe COPD after Admission in ICUs of Tertiary Care Centers of India (FAST COPD): Study Protocol for a Multicentric Cohort Study. Indian J Crit Care Med 2024;28(6):552-560.

Source attribution of carbon monoxide over Northern India during crop residue burning period over Punjab.

National Capital Territory of Delhi and its satellite cities suffer from poor air quality during the post-monsoon months of October-November. In this study, a novel attempt is made to estimate the contribution of different emission sources (industrial, residential, power generation, transportation, biomass burning, photochemical production, lateral transport, etc.) towards the criteria air pollutant carbon monoxide (CO) concentration over North India. Multiple simulations of the WRF-Chem model with a tagged tracer approach with different inputs (6 anthropogenic emission inventories and 3 biomass burning emission inventories) were used. The model performance was evaluated against the MOPITT retrieved CO surface concentration. Analysis of model simulated CO over North India suggests that anthropogenic emissions contribute around 32-49% to surface CO concentration while crop residue burning contributes 27-44% of which 80% originates from Punjab. For Delhi, the contribution from anthropogenic sources is dominant (53-77%) of which 10-28% is from the domestic sector and 14-55% is from the transport sector. Agricultural waste burning contributes about 15-30% to Delhi's surface CO concentration (of which 75% originates from Punjab). Crop residue burning emission is a chief source of CO over Punjab with a contribution of about 56-76%. The results suggest that industrial, transport, and domestic sector activities are more responsible for increased CO levels over New Delhi and surrounding regions than crop residue burning over Punjab. Furthermore, critical meteorological parameters like 10 m wind speed, boundary layer height, 2 m temperature, total precipitation, and relative humidity were evaluated against CO concentration to understand their impact on CO distribution. Results conclude that deteriorating air quality over the North Indian region is caused by a combination of prevailing meteorological factors (such as slow winds, shallow mixing layer, and cold temperatures) and man-made emissions.

Computational studies on the catalytic potential of the double active site for enzyme engineering.

Proteins possessing double active sites have the potential to revolutionise enzyme design strategies. This study extensively explored an enzyme that contains both a natural active site (NAS) and an engineered active site (EAS), focusing on understanding its structural and functional properties. Metadynamics simulations were employed to investigate how substrates interacted with their respective active sites. The results revealed that both the NAS and EAS exhibited similar minimum energy states, indicating comparable binding affinities. However, it became apparent that the EAS had a weaker binding site for the substrate due to its smaller pocket and constrained conformation. Interestingly, the EAS also displayed dynamic behaviour, with the substrate observed to move outside the pocket, suggesting the possibility of substrate translocation. To gain further insights, steered molecular dynamics (SMD) simulations were conducted to study the conformational changes of the substrate and its interactions with catalytic residues. Notably, the substrate adopted distinct conformations, including near-attack conformations, in both the EAS and NAS. Nevertheless, the NAS demonstrated superior binding minima for the substrate compared to the EAS, reinforcing the observation that the engineered active site was less favourable for substrate binding due to its limitations. The QM/MM (Quantum mechanics and molecular mechanics) analyses highlight the energy disparity between NAS and EAS. Specifically, EAS exhibited elevated energy levels due to its engineered active site being located on the surface. This positioning exposes the substrate to solvents and water molecules, adding to the energy challenge. Consequently, the engineered enzyme did not provide a significant advantage in substrate binding over the single active site protein. Further, the investigation of internal channels and tunnels within the protein shed light on the pathways facilitating transport between the two active sites. By unravelling the complex dynamics and functional characteristics of this double-active site protein, this study offers valuable insights into novel strategies of enzyme engineering. These findings establish a solid foundation for future research endeavours aimed at harnessing the potential of double-active site proteins in diverse biotechnological applications.

Data-driven dentistry: Computational revelations redefining pulp capping.

Introduction: Pulpal and periradicular diseases stem from immune reactions to microbiota, causing inflammation. Limited blood supply hampers dental pulp self-healing. Managing inflammation involves eliminating bacteria and reducing pro-inflammatory mediators especially MMP-9, which has a significant correlation with pulpitis. s. Flavonoids like Hesperidin, Baicalein, Epigallocatechin gallate, Genistein, Icariin, and Quercetin show potential for pulp capping. Aim: This in-silico study compares various Flavonoids for their anti-inflammatory effects on MMP-9, with Chlorhexidine as a control, a known MMP-9 inhibitor. Materials and Methods: Protein and Ligand Preparation: The human MMP-9 catalytic domain (PDB ID: 4XCT) structure was retrieved, and necessary modifications were made. Flavonoids from PubChem database were prepared for docking using AutoDock Vina. A grid for docking was created, and molecular dynamics simulations were conducted using Gromacs-2019.4 with GROMOS96 force field. Trajectory analysis was performed, and MM-PBSA calculation determined binding free energies. Results: Analysis of MMP-9 and ligand interactions revealed Hesperidin's high binding affinity, forming numerous hydrogen bonds with specific amino acids. Molecular dynamics simulations confirmed stability, with RMSD, RMSF, Rg, and SASA indicating consistent complex behaviour over 100 ns. MM-PBSA calculation affirmed favourable energy contributions in MMP-9-Hesperidin interactions. Conclusion: MMP-9 plays a crucial role in prognosis of pulpitis. Incorporating MMP-9 inhibitors into pulp capping agents may enhance therapeutic efficacy. Hesperidin emerges as a potent MMP-9 inhibitor, warranting further in vivo validation against other agents.

Expert Consensus on Dipeptidyl Peptidase-4 Inhibitor-Based Therapies in the Modern Era of Type 2 Diabetes Mellitus Management in India.

India has a high prevalence of type 2 diabetes mellitus (T2DM) with unique clinical characteristics compared to other populations. Despite advancements in diabetes therapy, a significant number of patients in India still experience poor glycemic control and complications. Dipeptidyl peptidase-4 (DPP-4) inhibitors continue to be an important component of T2DM treatment due to their favorable efficacy and tolerability profile. Given the current scenario, there is a need to revisit the role of DPP-4 inhibitors in T2DM management in Indian patients. This consensus paper aims to provide guidance on the utilization of DPP-4 inhibitors in T2DM management from an Indian perspective. A consensus group of 100 experts developed recommendations based on an extensive literature review and discussions. The expert group emphasized the importance of timely glycemic control, combination therapy, and targeting the underlying pathophysiology of T2DM. The combinations of DPP-4 inhibitors with metformin and/or sodium-glucose transport protein-2 inhibitors are rationalized in this paper, considering their complementary mechanisms of action. This paper provides valuable insights for clinicians in optimizing the management of T2DM in the Indian population with the use of DPP-4 inhibitors and proposes an algorithm for selecting DPP-4 inhibitor-based therapies.

The analytical study of double diffusive convection in a rectangular enclosure bounded by porous lining with thermal radiation.

The current analytical study is dedicated to the boundary layer regime where heat and mass transfer rates are ruled by natural convection. A rectangular enclosure filled with a combination of an arbitrary buoyancy ratio has an Oseen-linear solution, and the position of Beavers and Joseph's condition is employed at the porous fluid interface. Thermal radiation's interaction with a porous lining influences overall heat transfer in a system. Porous linings and radiation are employed in many applications, such as furnaces, insulation, heat exchangers, solar energy collecting and storage, and heat control in electronics. The effect of slip and radiation is to increase the flow rate because of the reduction in friction at the surface. It indicates the fact that temperature and concentration are rapidly lowering. As the slip parameter and radiation parameter increase, the heat and mass transport increase due to the rise in velocity. The Nusselt and Sherwood numbers reach their maximum when the radiation parameter, Rayleigh number, and slip parameter are increased. The findings of the Nusslet number and Sherwood numbers are related to the finite situations of the slip parameter tending to infinity, the radiation parameter going to zero and the angle 90°.

Investigating the impact of alumina nanoparticles in coconut oil distillate biodiesel to lessen emissions in direct injection diesel engine.

Petroleum fuels are commonly used for automobiles. However, the continuous depletion and exhaust gas emission causes serious problems. So, there is a need for an alternative eco-friendly fuel. Biodiesel is a type of fuel manufactured through a process called transesterification, which involves converting vegetable oils into a usable form. The process parameters of the transesterification process were optimized using the Taguchi method to achieve maximum biodiesel yield. However, the main problem of biodiesel is its high cost which could be reduced by using low-cost feedstock. To address this challenge, biodiesel (BCFAD) is derived from coconut fatty acid distillate (CFAD), a by-product obtained from refining coconut oil. This work uses BCFAD and BCFAD with Alumina nanoparticles as fuels. Alumina nanoparticles in the mass fraction of 25 ppm, 50 ppm, and 100 ppm are dispersed in BCFAD. The investigation results reveal an increase of 6.5% in brake thermal efficiency for BCFAD with 100 ppm nanoparticles when compared to BCFAD. There is a reduction of 29.29% of hydrocarbon and 34% of Carbon monoxide emissions with BCFAD100 in comparison with diesel. However, there is a marginal increase in NOx emission with the increase in nanoparticles. The heat release rate and cylinder pressure of BCFAD100 are comparable to diesel fuel. It was concluded that the utilization of BCFAD with a nanoparticle dispersion of 100 ppm is suitable for direct use as fuel in diesel engines.

Pharmacological Effect of Copper Oxide Nanoparticles of Azadirachta indica Leaf Extract and Application for its Antibacterial Properties.

Nanoparticles prepared from bio-reduction agents are of keen interest to researchers around the globe due to their ability to mitigate the harmful effects of chemicals. In this regard, the present study aims to synthesize copper oxide nanoparticles (CuO NPs). CuNPs show a characteristic absorption peak at 347 nm, while SEM reveals the spherical but agglomerated shape of CuNPs of the size within the range of 51.26-56.66 nm. The crystallite size measured by using XRD was found to be within a range of 23.38-46.64 nm for ginger-doped CuO and 26-56 nm for garlic-doped CuO. The X-ray diffraction analysis shows the crystalline structure of copper nanoparticles with prominent peaks. Bragg's reflection of copper nanoparticles shows diffraction peaks around 2θ =43.4°, 50.3°, and 74.39°, representing [111], [200], and [220] crystallographic planes of face-centered cubic (fcc). The synthesized CuO NPs tested antibacterial properties against various strains of microorganisms, including Escherichia coli, 25 µg/mL 2.3 ± 0.21 and 100 µg/mL 6.5 ± 0.17, Staphylococcus aureus, 25 µg/mL 2.3 ± 0.29 and 100 µg/mL 11.5 ± 1.17, Streptococcus mutans, 25 µg/mL 01.05 ± 0.21 and 100 µg/mL 15.8 ± 0.17, Enterococcus faecalis). The short novelty of Azadirachta indica lies in its potential relevance to human health, as it has been found to possess bioactive compounds with various medicinal properties, such as antimicrobial, antioxidant, and anti-inflammatory activities, making it a promising natural resource for therapeutic applications.

Comparing the posture and comfort of anaesthesiologists during laryngoscopy and tracheal intubation in the head-elevated laryngoscopy position in supine position and with a 25° backup: A randomised clinical crossover trial.

Background and Aims: The head-elevated laryngoscopy position (HELP) and a 25° backup have been proposed to enhance glottic visualisation, yet concerns about ergonomic discomfort hinder their widespread adoption. This study compares the comfort and posture adopted by anaesthesiologists while performing laryngoscopy and tracheal intubation with patients in HELP while in a supine position or with 25° backup. Methods: The study included 48 patients aged 18-60 years with normal airways and 12 experienced anaesthesiologists. Patients were randomised into two groups using permuted block randomisation. Anaesthesiologists performed laryngoscopy and intubation in supine HELP and 25° backup HELP positions. Anaesthesiologist's posture was determined by measuring the angles of neck, wrist, elbow, back and knee joints, which were compared using Student's t-test, and subjective comfort assessed on a Likert scale was compared using the Chi-square test. As mentioned by the anaesthesiologist, Cormack- Lehane grading was also noted and compared using a Chi-square test between groups, taking a P value <0.05 as significant. Results: Both positions demonstrated comparable anaesthesiologist posture (P = 0.919) and comfort (P = 0.644). However, the 25° backup HELP positions significantly improved Cormack-Lehane grades, with 68% achieving grade 1 compared to 31% in the supine HELP group (P = 0.012). Haemodynamic stability and tracheal intubation time showed no significant differences between the groups (P = 0.475 and 0.117, respectively), and no complications were reported in either group. Conclusion: Anaesthesiologists' posture and comfort during laryngoscopy and tracheal intubation are similar between supine and 25° backup in patients with easy airways.

A phase II study (AARDVARC) of AZD4635 in combination with durvalumab and cabazitaxel in patients with progressive, metastatic, castration-resistant prostate cancer.

BACKGROUND: This phase II nonrandomized study evaluated the efficacy and safety of AZD4635 in combination with durvalumab (Arm A) or durvalumab plus cabazitaxel (Arm B) in patients with metastatic castration-resistant prostate cancer (mCRPC) previously treated with docetaxel and ≥1 novel hormonal agent. PATIENTS AND METHODS: The primary endpoint was radiographic progression-free survival (rPFS) per RECIST v1.1 (soft tissue) or the Prostate Cancer Clinical Trials Working Group 3 (bone). Secondary endpoints included safety, tolerability, overall survival, confirmed prostate-specific antigen (PSA50) response, pharmacokinetics, and objective response rate. Enrollment in Arm A was stopped following a sponsor decision unrelated to safety. The study was stopped based on the planned futility analysis due to low PSA50 response in Arm B. RESULTS: In the final analysis (1 November 2021), 30 patients were treated (Arm A, n = 2; Arm B, n = 28). The median rPFS in Arm B was 5.8 months (95% confidence interval 4.2-not calculable). Median rPFS was 5.8 months versus 4.2 months for patients with high versus low blood-based adenosine signature. The most common treatment-related adverse events in Arm B were nausea (50.0%), diarrhea (46.4%), anemia and neutropenia (both 35.7%), asthenia (32.1%), and vomiting (28.6%). Overall, AZD4635 in combination with durvalumab or AZD4635 in combination with cabazitaxel and durvalumab showed limited efficacy in patients with mCRPC. CONCLUSIONS: Although the safety profile of both combinations was consistent with known safety data of the individual agents, the results of this trial do not support further development of the combinations.

Temporary Anchorage Device Misplaced into Infratemporal Space - A Case Report.

INTRODUCTION: During orthodontic treatment, temporary anchoring devices (TADs) are used to restrain tooth movement. They are a relatively recent addition to the dental toolkit. AIM: As TADs have limitations, Dr. Eric Lieu of Taiwan developed Infra Zygomatic Crest (IZC) screws which are placed between the maxillary second premolar at the bony crest. TREATMENT PLANNING: The goal of this case study is to emphasize the value of anatomy, site selection, and IZC retrieval in the event of an accident. Cone beam computed tomography was used as a diagnostic tool for the precise location of the displaced IZC and immediate surgical retrieval was done under local anesthesia from the infratemporal space to prevent further complications. TAKEAWAY LESSONS: Orthodontists knowledge of soft tissue and hard tissue anatomy and precise positioning is crucial for successful TAD implantation.

An Unusual Case of Cryoglobulinemic Vasculitis and Acute Disseminating Encephalomyelitis in a 21-Year-Old Caucasian Male.

Cryoglobulinemic vasculitis and acute disseminated encephalomyelitis (ADEM) are characterized by damage to either blood vessels or grey matter. For both diseases, infections can be an etiology. In cryoglobulinemic vasculitis, the initial insult causes damage to the glomerulus, and in the case of ADEM, damage leads to a central nervous system demyelinating disorder. Infective endocarditis can be associated with both diseases and can be challenging to diagnose. Individuals on antibiotics may present with negative blood cultures, making underlying infective endocarditis difficult to diagnose. In this report, we describe a 21-year-old male who presented to the hospital after an assault with splenic laceration and was subsequently found to have infective endocarditis associated with cryoglobulinemic vasculitis and ADEM.

Enriched characteristics of poultry collagen over other sources of collagen and its extraction methods: A review.

Collagen is the most abundant protein in animals and is extensively studied for its structural and thermal stability, biocompatibility, and healing properties which enables them to be widely applied in various fields. Collagen extracted from poultry sources have shown improved structural stability and reduced risk of triggering allergic responses and transmitting animal diseases onto humans. Furthermore, poultry collagen is widely accepted by consumers of diverse beliefs in comparison to collagen extracted from bovine and porcine sources. The review aims to compare different sources of collagen, focusing on the various beneficial characteristics of poultry collagen over the other sources. Moreover, the review explains various pre-treatment and extraction methods of poultry collagen and its versatile applications in different industrial sectors.

Microporous Materials in Polymer Electrolytes: The Merit of Order.

Solid-state batteries (SSBs) have garnered significant attention in the critical field of sustainable energy storage due to their potential benefits in safety, energy density, and cycle life. The large-scale, cost-effective production of SSBs necessitates the development of high-performance solid-state electrolytes. However, the manufacturing of SSBs relies heavily on the advancement of suitable solid-state electrolytes. Composite polymer electrolytes (CPEs), which combine the advantages of ordered microporous materials (OMMs) and polymer electrolytes, meet the requirements for high ionic conductivity/transference number, stability with respect to electrodes, compatibility with established manufacturing processes, and cost-effectiveness, making them particularly well-suited for mass production of SSBs. This review delineates how structural ordering dictates the fundamental physicochemical properties of OMMs, including ion transport, thermal transfer, and mechanical stability. The applications of prominent OMMs are critically examined, such as metal-organic frameworks, covalent organic frameworks, and zeolites, in CPEs, highlighting how structural ordering facilitates the fulfillment of property requirements. Finally, an outlook on the field is provided, exploring how the properties of CPEs can be enhanced through the dimensional design of OMMs, and the importance of uncovering the underlying "feature-function" mechanisms of various CPE types is underscored.

Pott's puffy tumor: An unusual complication of rhino-orbito-cerebral mucormycosis.

Objective: To describe clinicoradiological features and surgical outcomes in a series of nine patients with rhino-orbito-cerebral mucormycosis (ROCM) who presented with Pott's puffy tumor (ROCM-PPT). Methods: The records of nine patients with ROCM-PPT seen between March 2020 and December 2021 were analysed. Clinical features, radiology, histopathology, operative findings, management and outcome were noted. Frontal sinus pneumatisation and outflow tract configuration was compared between patients and controls with ROCM and no PPT. Results: ROCM-PPT was diagnosed in 9 of 284 (3.2 %) patients with ROCM seen during the study period. There were six (66.7 %) males and the median age was 54 (IQR 46-60) years. Eight (88.9 %) patients had diabetes mellitus and seven (77.8 %) had been COVID-19 positive. Radiological features of osteomyelitis, subperiosteal abscess formation and dural enhancement were seen in all patients. No significant differences in pneumatisation or frontal sinus outflow tract configuration were noted between patients and controls. All patients underwent a craniectomy with frontal bone debridement and frontal sinus exteriorisation. All patients were treated with anti-fungal agents for several months. All patients had symptomatic improvement at a median follow-up of 21 (IQR 18-23) months. Repeat CT/MRI scans showed disease regression/resolution in six out of eight (75 %) patients with follow-up imaging, and stable disease in two others. Conclusions: ROCM-PPT is a rare, delayed complication of mucormycosis that was seen in larger numbers during the recent COVID-19 pandemic. Aggressive debridement of osteomyelitic bone and antifungal therapy results in a good outcome.

Unusual presentation of Sjogren's syndrome during pregnancy: a case report.

BACKGROUND: Pregnancy imposes significant physiological changes, including alterations in electrolyte balance and renal function. This is especially important because certain disorders might worsen and make people more susceptible to electrolyte abnormalities. One such condition is Sjogren's syndrome (SS), an autoimmune disease that can cause distal renal tubular acidosis (dRTA). This case report offers a unique perspective on the intricate physiological interplay during pregnancy, emphasizing the critical importance of recognizing and managing electrolyte abnormalities, particularly in the context of autoimmune disorders such as Sjogren's syndrome. CASE PRESENTATION: We report a case of a 31-year-old pregnant Indian woman at 24 weeks gestation presenting with fever, gastrointestinal symptoms, and progressive quadriparesis followed by altered sensorium. Severe hypokalaemia and respiratory acidosis necessitated immediate intubation and ventilatory support. Investigations revealed hypokalaemia, normal anion gap metabolic acidosis, and positive autoimmune markers for SS. Concurrently, she tested positive for IgM Leptospira. Management involved aggressive correction of electrolyte imbalances and addressing the underlying SS and leptospirosis. CONCLUSION: This case underscores that prompt recognition and management are paramount to prevent life-threatening complications in pregnant patients with autoimmune disease. This report sheds light on the unique challenge of managing hypokalaemic quadriparesis in the context of Sjogren's syndrome during pregnancy.

Designing an operational research TB training program in Zambia.

BACKGROUND: The USAID-funded Eradicate TB Project (ETB) partnered with the National Tuberculosis and Leprosy Control Program (NTLP) to establish an operational research (OR) training program in order to generate local evidence to enhance TB care in Zambia. METHOD: Between 2017 and 2021, healthcare workers (HCWs) from district teams underwent two 10-day intensive training sessions. The program evolved to include a competitive application process and an additional primer workshop on developing feasible research questions. RESULTS: Of the 36 enrollees in the OR training program, 26 (72.2%) completed it, leading to nine OR studies that informed interventions for TB care improvement. Notable achievements include reduced TB mortality, increased pediatric notifications, and enhanced sputum courier systems, with all studies disseminated at national and international conferences, four submitted to peer-reviewed journals, of which three were published. Two studies were replicated by the NTLP at provincial and national levels. CONCLUSIONS: Integrating OR training into TB initiatives is feasible and beneficial. The program's phased execution and adaptive strategies provide valuable insights for similar settings, although challenges in sustainability of mentorship and funding persist. This success underscores the importance of continuous OR capacity strengthening among HCWs in Zambia.

CONTEXTE: Le projet Eradicate TB (ETB) financé par l'USAID s'est associé au programme National de contrôle de la Tuberculose et de la Lèpre (NTLP) pour mettre en place un programme de formation à la recherche opérationnelle (OR), afin de générer des preuves locales pour améliorer les soins de la TB en Zambie. MÉTHODE: Entre 2017 et 2021, des travailleurs de la santé (HCWs) provenant d'équipes de district ont suivi deux sessions de formation intensive de 10 jours. Le programme a évolué pour inclure un processus de candidature concurrentiel et un atelier d'initiation supplémentaire sur l'élaboration de questions de recherche réalisables. RÉSULTATS: Vingt-six (72,2%) des HCW inscrits au programme ont terminé leur formation, ce qui a donné lieu à neuf études de OR qui ont servi de base à des interventions visant à améliorer les soins antituberculeux. Parmi les réalisations notables, citons la réduction de la mortalité due à la TB, l'augmentation des notifications pédiatriques et l'amélioration des systèmes de messagerie des expectorations. Toutes les études ont été diffusées lors de conférences nationales et internationales, quatre ont été soumises à des revues à comité de lecture et trois ont été publiées. Deux études ont été reproduites par le NTLP aux niveaux provincial et national. CONCLUSIONS: L'intégration de la formation OR dans les initiatives de lutte contre la TB est faisable et bénéfique. L'exécution progressive du programme et les stratégies adaptatives fournissent des indications précieuses pour des contextes similaires, bien que les défis liés à la durabilité du mentorat et du financement persistent. Ce succès souligne l'importance d'un renforcement continu des capacités OR parmi les HCW en Zambie.

Prospective Phase II Study of Radiotherapy Dose Escalation in Grade 4 Glioma Using 68Ga-Pentixafor PET Scan.

AIMS: Local failure remains the major concern in grade 4 glioma or glioblastoma (GBM). Pilot studies have shown a radiotherapy (RT) dose-response relationship in GBM. Here we present our preliminary data of RT dose escalation using 68Ga-Pentixafor PET scan. High 68Ga-pentixafor uptake in glioma cells helps in sharp demarcation between tumour and normal brain. MATERIALS AND METHODS: This phase II prospective study was conducted from 2018 to 2020. Thirty, biopsy-proven cases of grade 4 glioma were included. All patients underwent post-operative MRI of the brain and 68Ga-Pentixafor PET scan. RT was planned in 2-phases. Phase-1 GTV (GTV1) comprised of T2/flair abnormality, PET-avid disease and post-op cavity. A margin of 2cm was given to GTV-1 to create phase-1 CTV (CTV1), which was further expanded to 0.5cm to generate phase-1 PTV (PTV1). A radiation dose of 46Gy/23fr was prescribed to PTV-1. Phase-2 GTV (GTV2) consisted of CT/MRI contrast-enhancing lesion, PET avid disease and post-op cavity. A margin of 0.5 cm was given to GTV2 to create phase-2 CTV (CTV2) which was expanded to 0.5 cm to create phase-2 PTV (PTV2). RT dose of 14 Gy/7 fr was prescribed to PTV2. PET avid disease was delineated as GTV PET and a margin of 3mm was given to generate PTV-PET which received escalated RT dose of 21 Gy/7fr by simultaneous integrated boost (SIB) in phase 2 (Total dose to PTV PET = 67 Gy/30 fr). All patients received concurrent and adjuvant temozolomide. The data was prospectively maintained in Microsoft Excel sheet. SPSS v 23 was used for statistical analysis. The primary endpoints were estimation of the overall survival (OS) and progression-free survival (PFS), and secondary endpoint was to measure the incidence of radiation necrosis. Categorical variables were reported as frequency and percentage and quantitative variables were reported as median and range. RESULTS: Data from thirty patients were analysed. A median OS of 23 months was observed with estimated 1, 2 and 3 years OS of 90%, 40% and 17.8% respectively. A significant association of OS was seen with the extent of surgery (p = 0.04) and kernofsky performance status (p = 0.007). No patient developed significant radiation necrosis. CONCLUSIONS: The index study did not show any survival benefit from dose escalation RT. However, all of the patients tolerated the treatment well and none of them developed radiation necrosis. Considering the small sample size as a limitation of the index study, the role of 68Ga-pentixafor PET scan for radiation dose escalation should be further explored. CLINICAL TRIAL NUMBER: CTRI/2019/05/019146.