Search

In response to concerns about depleting natural resources, organisations are developing eco-friendly products and services. This study examines the role of manufacturing industries and services in sustainable resource utilisation, focusing on the Micro, Small, Medium Enterprises (MSME) sector, a significant contributor to global Gross Domestic Product (GDP). Using Life Cycle Assessment (LCA) methodology, the research identifies hotspots within the production processes of three companies manufacturing bathroom fittings, specifically the ‘Wall mixer’ component used in households and hotels. The study calculates In response to concerns about depleting natural resources, organisations are developing eco-friendly products and services. This study examines the role of manufacturing industries and services in sustainable resource utilisation, focusing on the MSME sector, a significant contributor to global GDP. Using Life Cycle Assessment (LCA) methodology, the research identifies hotspots within the production processes of three companies manufacturing bathroom fittings, specifically the ‘Wall mixer’ component used in households and hotels. The study calculates CO2 equivalents for each phase of the product lifecycle, identifying average gate-to-gate process values across the companies. This comparison reveals specific hotspots, with a significant one identified, leading to recommendations for industries to prioritise this issue for immediate energy savings. The primary focus is to establish an initial benchmarking system to reduce CO2 equivalents in cradle-to-gate or gate-to-gate systems. Implementing these measures is expected to reduce the carbon footprint, energy consumption, and raw material usage, ultimately enhancing profitability for the three companies. equivalents for each phase of the product lifecycle, identifying average gate-to-gate process values across the companies. This comparison reveals specific hotspots, with a significant one identified, leading to recommendations for industries to prioritise this issue for immediate energy savings. The primary focus is to establish an initial benchmarking system to reduce CO2 equivalents in cradle-to-gate or gate-to-gate systems. Implementing these measures is expected to reduce the carbon footprint, energy consumption, and raw material usage, ultimately enhancing profitability for the three companies.

Purpose – The paper proposes a framework for the successful deployment of Industry 4.0 (I4.0) principles in the aerospace industry, based on identified success factors. The paper challenges the perception of I4.0 being aligned with de-skilling and personnel reduction and instead promotes a route to successful deployment centred on upskilling and retaining personnel for future role requirements. Design/methodology/approach – The research methodology involved a literature review and industrial data collection via questionnaires to develop and validate the framework. The questionnaire was sent to a purposive sample of 50 respondents working in operations, and a response rate of 90% was achieved. Content analysis was used to identify patterns, themes, or biases, and the data were tabulated based on specific common attributes. The proposed framework consists of a series of gates and criteria that must be met before progressing to the next gate. Findings – The proposed framework provides a feedback mechanism to review minimum standards for successful deployment, aligned with new developments in capability and technology, and ensures quality assessment at each gate. The paper highlights the potential benefits of I4.0 implementation in the aerospace industry, including reducing operational costs and improving competitiveness by eliminating variation in manufacturing processes. The identified success factors were used to define the framework, and the identified failure points were used to form mitigation actions or controls for inclusion in the framework. Originality/value – The paper provides a framework for the successful deployment of I4.0 principles in the aerospace industry, based on identified success factors. The framework challenges the perception of I4.0 as being aligned with de-skilling and personnel reduction and instead promotes a route to successful deployment centred on upskilling and retaining personnel for future role requirements. The framework can be used as a guideline for organizations to deploy I4.0 principles successfully and improve competitiveness.

Abstract This study explores the relationship between Key Performance Indicators (KPIs) and environmental performance improvement within the Saudi chemical industry. Against the backdrop of global sustainability imperatives and Saudi Arabia’s Vision 2030, which promotes sustainability for economic diversification, this research aims to assess the effectiveness of KPIs in driving environmental sustainability practices. The motivation for this study stems from the identified gaps in the systematic implementation and utilisation of KPIs and the lack of awareness regarding certain aspects of environmental impact management within the industry in the Kingdom. The methodology involved a structured survey administered to a diverse range of chemical manufacturing companies, followed by rigorous data analysis using descriptive evaluation, Analysis of Variance (ANOVA), reliability analysis, and t-tests. The results revealed insights into pollution areas, KPI utilisation, methods for pollution assessment, alignment with strategic goals, and governance regulations. Descriptive analysis highlighted air quality management as a priority, with notable attention to water and land pollution, while quantitative analysis confirmed the significance of KPIs in driving environmental performance improvement in the area. However, it also unveiled the absence of a systematic approach to implementing and utilising KPIs effectively, coupled with a lack of awareness regarding certain aspects of environmental impact management, consequently leading to uncertainty. Overall, this study contributes to advancing sustainability efforts within the Saudi chemical sector, providing actionable insights for industry stakeholders and policymakers.

Abstract This paper aims to study how firms must be agile to overcome risks and manage cost repercussions. Specifically, it focuses on promoting digitalization in Indian food SMEs for greater competitiveness. The main purpose is to design a model for implementing robust interventions in a rational manner. To achieve this, a mixed approach, including a literature review and the Decision-Making Trial and Evaluation Laboratory (DEMATEL) method, was chosen. This approach is recommended for addressing barriers to digital transformation in SMEs. The results suggest that the absence of internet connectivity and problems related to organization impede the efficiency of operations in small and medium-sized Indian food businesses. By overcoming these obstacles and allocating resources to enhance their digital capacities, stakeholders can effectively shape their future business operations. In addition, it is imperative for the stakeholders to actively adopt and utilize a range of digital tools such as blockchain, IoT, Big Data, and cloud computing. To implement and sustain digital transformation effectively, three foundational elements are crucial: internet availability, financial resources, and employee training. This research offers an innovative approach to the practiceners and mangers to adopt digital transformation of Indian food SMEs.

Abstract Vietnam faces a heightened susceptibility to natural disasters stemming from climate change, yet the impact of these disasters varies markedly across its regions. Consequently, it is imperative to scrutinize the climatic factors affecting the regional economy, with a particular dearth of research addressing the nexus between natural threats and the economies of the Mekong River Delta and the Southeast region of Vietnam. The primary objective is to investigate how temperature fluctuations, rising sea levels, storms, and forest fires can detrimentally affect agriculture, forestry, and infrastructure in these regions. The present research uses the secondary data from Vietnam's General Statistics Office and the German Agency for International Cooperation. Employing quantitative analysis, the study endeavours to assess and compare the influence of climate change elements on the economic trajectories of the Mekong River Delta and the Southeast region. The findings reveal that the Mekong River Delta is disproportionately impacted by economic losses attributed to rising sea levels when juxtaposed with other regions in Vietnam. Firstly, the escalating sea levels significantly jeopardize residential and agricultural land in the Mekong River Delta (1). Secondly, while wildfires inflict damage on forestry in both the Mekong River Delta and the Southeast area, their overall impact is deemed negligible (2). Thirdly, the study ascertains that houses in the Mekong River Delta and the Southeast region remain relatively unscathed by storms (3). However, it is noted that specific storms have inflicted substantial damage on both regions (4). In light of these findings, future research should delve deeper into the analysis of storm risks in the Mekong River Delta and the Southeast region. Such insights are crucial for enhancing our understanding of the vulnerabilities and devising effective strategies to mitigate the economic repercussions of climate change in these pivotal areas.

The primary aim of this study is to assess the significance of top management commitment in the context of Lean 4.0 implementation within the pharmaceutical manufacturing industry in Ghana. The study seeks to understand and evaluate the overall effectiveness and achievements associated with adopting Lean 4.0. Employing a positivist mindset, the research utilizes an explanatory quantitative research design and a survey technique. Data collected from 181 employees of pharmaceutical companies in Ghana undergo analysis using SmartPLS (version 4) and IBM SPSS version 26. The study employs a combination of descriptive statistics to summarise data characteristics and inferential statistics to test various hypotheses related to Lean 4.0 adoption. The analysis reveals that the successful integration of lean methods and Industry 4.0 technologies requires meticulous management. Simultaneously, individual implementations of lean principles and Industry 4.0 technologies positively impact business performance. Surprisingly, the study does not observe a substantial positive influence of Lean 4.0 on corporate performance, suggesting that immediate improvements in efficiency or profitability may not result from the adoption of this framework. This research contributes to the field by highlighting the need for careful management in integrating lean methods and Industry 4.0 technologies. It also emphasizes the positive impacts of lean principles and Industry 4.0 technology on business performance. The unexpected finding regarding the lack of immediate improvements in corporate efficiency or profitability with Lean 4.0 adoption prompts considerations of initial implementation challenges or the organization's need for time to adapt to this integrated approach.

Abstract Cell-penetrating peptides show promise as versatile tools for intracellular delivery of therapeutic agents. Various peptides have originated from natural proteins with antimicrobial activity. We investigated the mammalian cell-penetrating properties of a 16-residue peptide with the sequence GRCRGFRRRCFCTTHC from the C-terminus tail of the Medicago truncatula defensin MtDef4. We evaluated the peptide’s ability to penetrate multiple cell types. Our results demonstrate that the peptide efficiently penetrates mammalian cells within minutes and at a micromolar concentration. Moreover, upon N-terminal fusion to the fluorescent protein GFP, the peptide efficiently delivers GFP into the cells. Despite its remarkable cellular permeability, the peptide has only a minor effect on cellular viability, making it a promising candidate for developing a cell-penetrating peptide with potential therapeutic applications.

Abstract Background Childhood cancer treatment while often curative, leads to elevated risks of morbidity and mortality. Survivors require lifelong periodic surveillance for late effects of treatment, yet adherence to guideline-recommended tests is suboptimal. We created ONLOOP to provide adult survivors of childhood cancer with detailed health information, including summaries of their childhood cancer treatment and recommended surveillance tests for early detection of cardiomyopathy, breast cancer, and/or colorectal cancer, with personalized reminders over time. Methods This is an individually randomized, registry-based pragmatic trial with an embedded process and economic evaluation to understand ONLOOP’s impact and whether it can be readily implemented at scale. All adult survivors of childhood cancer in Ontario overdue for guideline-recommended tests will be randomly assigned to one of two arms: (1) intervention or (2) delayed intervention. A letter of information and invitation will detail the ONLOOP program. Those who sign up will receive a personalized toolkit and a screening reminder 6 months later. With the participants’ consent, ONLOOP will also send their primary care clinician a letter detailing the recommended tests and a reminder 6 months later. The primary outcome will be the proportion of survivors who complete one or more of the guideline-recommended cardiac, breast, or colon surveillance tests during the 12 months after randomization. Data will be obtained from administrative databases. The intent-to-treat principle will be followed. Based on our analyses of administrative data, we anticipate allocating at least 862 individuals to each trial arm, providing 90% power to detect an absolute increase of 6% in targeted surveillance tests completed. We will interview childhood cancer survivors and family physicians in an embedded process evaluation to examine why and how ONLOOP achieved success or failed. A cost-effectiveness evaluation will be performed. Discussion The results of this study will determine if ONLOOP is effective at helping adult survivors of childhood cancer complete their recommended surveillance tests. This study will also inform ongoing provincial programs for this high-risk population. Trial registration ClinicalTrials.gov NCT05832138.

Abstract Survival rates for pediatric acute lymphoblastic leukemia (pALL) have improved dramatically; relapsed/refractory (r/r) acute lymphoblastic leukemia (ALL) remains challenging. Immunotherapies are rapidly evolving treatments for r/r ALL with limited cost‐effectiveness data. This study identifies existing economic evaluations of immunotherapy in pALL and summarizes cost‐effectiveness. Medline, Embase, and other databases were searched from inception to October 2022. Cost‐effectiveness analyses evaluating immunotherapy in pALL were included. Costs reported in 2021 USD. Of 2960 studies, 11 met inclusion criteria. Tisagenlecleucel was compared to standard of care, clofarabine monotherapy, clofarabine combination therapy, or blinatumomab. No studies have evaluated blinatumomab or inotuzumab ozogamicin. Six studies found tisagenlecleucel to be cost‐effective, five of which were supported by Novartis. Four found that it had the potential to be cost‐effective, and one found that it was not cost‐effective. The cost‐effectiveness of tisagenlecleucel was highly dependent on list price and cure rates. This study can inform the use of tisagenlecleucel in pALL.

Lean 4.0, a fusion of lean manufacturing and digital technologies, is a powerful tool for implementing Industry 4.0. Its widespread use across sectors is driven by its ability to eliminate waste, reduce errors, boost revenue, and enhance customer care and efficiency. In the healthcare sector, this fourth lean revolution is particularly beneficial, as it helps to curb wastage and enhance efficiency, leading to more effective outcomes. Lean 4.0, a globally recognized best practice for industrial organisations, has proven its worth in enhancing performance and competitiveness. Its success has led to its adoption not only in manufacturing but also in non-manufacturing sectors such as Healthcare, finance, telecommunications, construction, and logistics. Its ease of use and effectiveness make it a superior alternative to traditional medical waste management techniques. Relevant papers on Lean 4.0 for Healthcare in the current literature are identified and studied to evaluate the impact of Lean 4.0 principles in Healthcare. This review-based research studies Lean 4.0 technologies and their needs in Healthcare. It discusses sustainable support for the healthcare sphere through Lean 4.0. Paper briefs several modalities of Lean 4.0 for the healthcare domain. Finally, the paper identifies and discusses the significant applications of Lean 4.0 in Healthcare. Lean 4.0 is essential to lowering errors that lead to medical mistakes since this business deals with life-or-death situations. Healthcare institutions need to reduce their overall waste reduction. With Lean 4.0, staff members working in quality management, clinical operations, consulting, and patient experience can progress into leadership roles in the healthcare sector. Lean 4.0 technologies can reduce waste production, including employing reusable medical equipment or cutting down on packaging waste. The possible difficulty of integrating digital technologies with healthcare systems and practices is Lean 4.0's limitations for the healthcare industry. Healthcare institutions can use refillable syringes and other disposable items to reduce waste rather than disposable plastic syringes. In future, healthcare institutions may save costs and lessen their environmental effect by minimising trash by using lean 4.0 technologies.

In industrial landscapes, spool fabrication industries play a crucial role in the successful completion of numerous industrial projects by providing prefabricated modules. However, the implementation of digitalized sustainable practices in spool fabrication industries is progressing slowly and is still in its embryonic stage due to several challenges. To implement digitalized sustainable manufacturing (SM), digital technologies such as Internet of Things, Cloud computing, Big data analytics, Cyber-physical systems, Augmented reality, Virtual reality, and Machine learning are required in the context of sustainability. The scope of the present study entails prioritization of the enablers that promote the implementation of digitalized sustainable practices in spool fabrication industries using the Improved Fuzzy Stepwise Weight Assessment Ratio Analysis (IMF-SWARA) method integrated with Triangular Fuzzy Bonferroni Mean (TFBM). The enablers are identified through a systematic literature review and are validated by a team of seven experts through a questionnaire survey. Then the finally identified enablers are analyzed by the IMF-SWARA and TFBM integrated approach. The results indicate that the most significant enablers are management support, leadership, governmental policies and regulations to implement digitalized SM. The study provides a comprehensive analysis of digital SM enablers in the spool fabrication industry and offers guidelines for the transformation of conventional systems into digitalized SM practices.

This report describes the status of childhood cancer control initiatives in Latin America and the Caribbean (LAC). Progress between 2017 and 2023 is measured using the outcome indicators from the Pan American Health Organization (PAHO) childhood cancer logic model aligned with the World Health Organization Global Initiative for Childhood Cancer (GICC). This report also describes the advances, barriers, and facilitators for the implementation of the GICC at the Regional level. Methods used in this report encompassed a comprehensive approach, incorporating a literature review, interviews, surveys, and a Delphi study developed by the technical team of the PAHO Non-Communicable Diseases and Mental Health Department and by the GICC LAC working group. Since 2017, there has been a substantial increase in the number of countries that have included childhood cancer in their national regulations. Currently, 21 LAC countries are involved in the GICC implementation, activities, and dialogues. However, the objectives for 2030 will only be achieved if Member States overcome the barriers to accelerating the pace of initiative implementation. There is an urgent need to increase the efforts in childhood cancer control in LAC, especially regarding the prioritization of timely detection, essential diagnostics, access to cancer treatment, palliative care, and close follow-up of children and adolescents with cancer.

Abstract Hematologic malignancy is a risk factor for severe coronavirus disease 2019 (COVID‐19) in adults; however, data specific to children with leukemia are limited. High‐quality infectious adverse event data from the ongoing Children's Oncology Group (COG) standard‐risk B acute lymphoblastic leukemia/lymphoma (ALL/LLy) trial, AALL1731, were analyzed to provide a disease‐specific estimate of SARS‐CoV‐2 infection outcomes in pediatric ALL. Of 253 patients with reported infections, the majority (77.1%) were asymptomatic or mildly symptomatic (CTCAE grade 1/2) and there was a single COVID‐19‐related death. These data suggest SARS‐CoV‐2 infection does not confer substantial morbidity among young patients with B‐lymphoblastic leukemia/lymphoma (B‐ALL/LLy).

Abstract Background Children with life-threatening conditions frequently experience high intensity care at the end of life, though most of this research only focused on children with cancer. Some research suggests inequities in care provided based on age, disease type, socioeconomic status, and distance that the child lives from a tertiary hospital. We examined: 1) the prevalence of indicators of high intensity end-of-life care (e.g., hospital stays, intensive care unit [ICU] stays, death in ICU, use of cardiopulmonary resuscitation [CPR], use of mechanical ventilation) and 2) the association between demographic and diagnostic factors and each indicator for children with any life-threatening condition in Canada. Methods We conducted a population-based retrospective cohort study using linked health administrative data to examine care provided in the last 14, 30, and 90 days of life to children who died between 3 months and 19 years of age from January 1, 2008 to December 31, 2014 from any underlying life-threatening medical condition. Logistic regression was used to model the association between demographic and diagnostic variables and each indicator of high intensity end-of-life care except number of hospital days where negative binomial regression was used. Results Across 2435 child decedents, the most common diagnoses included neurology (51.1%), oncology (38.0%), and congenital illness (35.9%), with 50.9% of children having diagnoses in three or more categories. In the last 30 days of life, 42.5% (n = 1035) of the children had an ICU stay and 36.1% (n = 880) died in ICU. Children with cancer had lower odds of an ICU stay (OR = 0.47; 95% CI = 0.36–0.62) and ICU death (OR = 0.37; 95%CI = 0.28–0.50) than children with any other diagnoses. Children with 3 or more diagnoses (vs. 1 diagnosis) had higher odds of > 1 hospital stay in the last 30 days of life (OR = 2.08; 95%CI = 1.29–3.35). Living > 400 km (vs

Abstract High strength and ductility are highly desired in fiber‐reinforced composites, yet achieving both simultaneously remains elusive. A hierarchical architecture is developed utilizing high aspect ratio chemically transformable thermoplastic nanofibers that form covalent bonding with the matrix to toughen the fiber‐matrix interphase. The nanoscale fibers are electrospun on the micrometer‐scale reinforcing carbon fiber, creating a physically intertwined, randomly oriented scaffold. Unlike conventional covalent bonding of matrix molecules with reinforcing fibers, here, the nanofiber scaffold is utilized ‒ interacting non‐covalently with core fiber but bridging covalently with polymer matrix ‒ to create a high volume fraction of immobilized matrix or interphase around core reinforcing elements. This mechanism enables efficient fiber‐matrix stress transfer and enhances composite toughness. Molecular dynamics simulation reveals enhancement of the fiber‐matrix adhesion facilitated by nanofiber‐aided hierarchical bonding with the matrix. The elastic modulus contours of interphase regions obtained from atomic force microscopy clearly indicate the formation of stiffer interphase. These nanoengineered composites exhibit a ≈60% and ≈100% improved in‐plane shear strength and toughness, respectively. This approach opens a new avenue for manufacturing toughened high‐performance composites.

The present research work investigates the barriers of weak IoT adoption in agrifood transportation, with special reference to India. It is built on a premise that few barriers upshots from the other more impactful ones. Thus, it is important to identify their linkages and classify them based on their strength of relationship. The data collected from 13 agricultural technology (AgriTech) firms of India were subjected to integrated techniques of M-TISM and Fuzzy MICMAC. As a result, a unique position of autonomous, dependent, linkage, and independent barriers was obtained which revealed that inadequate Internet connectivity, interoperability, and unclear roadmaps are precarious to the use of IoT in agrifood transportation. They are responsible for creating issues like data processing, vehicle tracking, and data privacy. This study offers a contextual phenomenon of barriers that may assist AgriTech stakeholders in developing appropriate strategies to embrace IoT transformation. It extends the theoretical literature by providing critical connections that aspiring researchers can examine through hypothesis testing or building a hierarchical framework. A sensitivity analysis is suggested to optimise decision-making and bring out a robust and reliable set of obstacles.

Abstract Background Symptom burden in adolescents and young adults (AYA) with cancer is poorly characterized but impacts quality of life. Methods All Ontario, Canada AYA aged 15–29 years at diagnosis between 2010 and 2018 were linked to population‐based healthcare databases, including to Edmonton Symptom Assessment System‐revised (ESAS) scores, an 11‐point scale routinely obtained at the time of cancer‐related outpatient visits and collected provincially. Multistate models estimated mean duration of symptom severity states [none (0) vs. mild (1 vs. 2 vs. 3) vs. moderate (4–6) vs. severe (7–10)], trajectories, and subsequent mortality risk. Variables associated with severe symptoms were also determined. Results In total, 4296 AYA with ≥1 ESAS score within a year of diagnosis were included (median age 25 years). Prevalent moderate/severe symptoms included fatigue (59% of AYA) and anxiety (44%). Across symptom type, AYA reporting moderate symptoms were likelier to subsequently experience improvement versus worsening. Risk of death within 6 months increased with increasing symptom burden and was highest in AYA with severe dyspnea (9.0%), pain (8.0%), or drowsiness (7.5%). AYA in the poorest urban neighborhoods were more likely to experience severe symptoms than in the wealthiest areas, with twice the odds of reporting severe depression [adjusted odds ratio (OR) 1.95, 95th confidence interval (95% CI) 1.37–2.78], pain (OR: 1.94, 95% CI: 1.39–2.70), and dyspnea (OR: 1.96, 95% CI: 1.27–3.02). Conclusions AYA with cancer experience substantial symptom burden. Risk of death increased with symptom severity. Interventions targeting cancer fatigue and anxiety, and targeting AYA in lower‐income neighborhoods, are likely to improve quality of life in this population.

Antibody responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are multi-targeted and variable over time. Multiplex quantitative serological assays are needed to provide accurate and robust seropositivity data for the establishment of serological signatures during vaccination and or infection. We describe here the validation and evaluation of an electro-chemiluminescence (ECL)-based Mesoscale Discovery assay (MSD) for estimation of total and functional IgG relative to SARS-CoV-2 spike, nucleocapsid and receptor binding (RBD) proteins in human serum samples to establish serological signatures of SARS-CoV-2 natural infection and breakthrough cases. The 9-PLEX assay was validated as per ICH, EMA, and US FDA guidelines using a panel of sera samples, including the NIBSC/WHO reference panel (20/268). The assay demonstrated high specificity and selectivity in inhibition assays, wherein the homologous inhibition was more than 85% and heterologous inhibition was below 10%. The assay also met predetermined acceptance criteria for precision (CV < 20%), accuracy (70–130%) and dilutional linearity. The method’s applicability to serological signatures was demonstrated using sera samples (n = 45) representing vaccinated, infected and breakthrough cases. The method was able to establish distinct serological signatures and thus provide a potential tool for seroprevalence of SARS-CoV-2 during vaccination or infection.

IntroductionB-cell acute lymphoblastic leukemia (B-ALL) is the most common malignancy in children. The current conventional chemotherapy regimens have high overall survival but with significant short- and long-term toxicities, sometimes requiring delay and termination of chemotherapy. Bispecific T-cell engager antibody blinatumomab has been successful in achieving bone marrow remission and acting as bridging therapy in minimal residual disease (MRD)-positive relapsed adult and pediatric B-ALL patients. Its role as upfront therapy is being explored. Here, we report the first case to our knowledge showing the feasibility, tolerability, and sustained remission using blinatumomab upfront as consolidation and maintenance therapy for 2 years in a pediatric patient with high-risk B-ALL who had significant toxicities with conventional chemotherapy.'Case presentationAn 11-year-old Hispanic girl presented with complaints of fever, abdominal pain, and fatigue. On further evaluation, she had tachycardia, pallor, cervical lymphadenopathy, and pancytopenia. Bone marrow studies confirmed high-risk B-ALL. The patient was started on induction chemotherapy per AALL1131. Her induction course was complicated by syncope, febrile neutropenia, and invasive cryptococcal fungal infection. End-of-induction bone marrow results were MRD negative. Further chemotherapy was withheld due to cardiopulmonary and renal failure, along with ventricular arrhythmias requiring intensive care. The patient received two cycles of blinatumomab as consolidation therapy and then transitioned back to conventional consolidation therapy; however, it was terminated mid-consolidation due to Pseudomonas and Aspergillus sepsis. She was then given blinatumomab maintenance therapy for 2 years and tolerated it well without any irreversible toxicity. She had an episode of Staphylococcus epidermidis sepsis and pneumonia treated by antibiotics and a single episode of a seizure while on blinatumomab therapy. At the time of publication, she is 25 months off treatment and in sustained remission without any further transplant or chemotherapy. She received monthly intravenous immunoglobulin G during the blinatumomab maintenance.ConclusionBlinatumomab given upfront as consolidation and maintenance therapy for 2 years in a pediatric high-risk B-ALL patient with significant toxicities to conventional chemotherapy was feasible and very well tolerated without any irreversible toxicity and led to sustained remission without any bridging transplant or further chemotherapy.

Summary: In 2013, the SickKids-Caribbean Initiative (SCI) was formalised among The Hospital for Sick Children in Toronto, Canada, the University of the West Indies, and Ministries of Health in six Caribbean countries (Barbados, The Bahamas, Jamaica, St. Lucia, St. Vincent and the Grenadines, and Trinidad and Tobago). The aim was to improve the outcomes and quality of life of children (

IntroductionVariation in stage at diagnosis of childhood cancers (CC) may explain differences in survival rates observed across geographical regions. The BENCHISTA project aims to understand these differences and to encourage the application of the Toronto Staging Guidelines (TG) by Population-Based Cancer Registries (PBCRs) to the most common solid paediatric cancers.MethodsPBCRs within and outside Europe were invited to participate and identify all cases of Neuroblastoma, Wilms Tumour, Medulloblastoma, Ewing Sarcoma, Rhabdomyosarcoma and Osteosarcoma diagnosed in a consecutive three-year period (2014-2017) and apply TG at diagnosis. Other non-stage prognostic factors, treatment, progression/recurrence, and cause of death information were collected as optional variables. A minimum of three-year follow-up was required. To standardise TG application by PBCRs, on-line workshops led by six tumour-specific clinical experts were held. To understand the role of data availability and quality, a survey focused on data collection/sharing processes and a quality assurance exercise were generated. To support data harmonization and query resolution a dedicated email and a question-and-answers bank were created.Results67 PBCRs from 28 countries participated and provided a maximally de-personalized, patient-level dataset. For 26 PBCRs, data format and ethical approval obtained by the two sponsoring institutions (UCL and INT) was sufficient for data sharing. 41 participating PBCRs required a Data Transfer Agreement (DTA) to comply with data protection regulations. Due to heterogeneity found in legal aspects, 18 months were spent on finalizing the DTA. The data collection survey was answered by 68 respondents from 63 PBCRs; 44% of them confirmed the ability to re-consult a clinician in cases where stage ascertainment was difficult/uncertain. Of the total participating PBCRs, 75% completed the staging quality assurance exercise, with a median correct answer proportion of 92% [range: 70% (rhabdomyosarcoma) to 100% (Wilms tumour)].ConclusionDifferences in interpretation and processes required to harmonize general data protection regulations across countries were encountered causing delays in data transfer. Despite challenges, the BENCHISTA Project has established a large collaboration between PBCRs and clinicians to collect detailed and standardised TG at a population-level enhancing the understanding of the reasons for variation in overall survival rates for CC, stimulate research and improve national/regional child health plans.

Coronary artery calcium (CAC) is a marker of coronary atherosclerosis, and the presence and severity of CAC have been shown to be powerful predictors of future cardiovascular events. Due to its value in risk discrimination and reclassification beyond traditional risk factors, CAC has been supported by recent guidelines, particularly for the purposes of informing shared decision-making regarding the use of preventive therapies. In addition to dedicated ECG-gated CAC scans, the presence and severity of CAC can also be accurately estimated on non-contrast chest computed tomography scans performed for other clinical indications. However, the presence of such “incidental” CAC is rarely reported. Advances in artificial intelligence have now enabled automatic CAC scoring for both cardiac and non-cardiac CT scans. Various AI approaches, from rule-based models to machine learning algorithms and deep learning, have been applied to automate CAC scoring. Convolutional neural networks, a deep learning technique, have had the most successful approach, with high agreement with manual scoring demonstrated in multiple studies. Such automated CAC measurements may enable wider and more accurate detection of CAC from non-gated CT studies, thus improving the efficiency of healthcare systems to identify and treat previously undiagnosed coronary artery disease.

BackgroundLuminex bead-based assays offer multiplexing to test antibodies against multiple antigens simultaneously; however, this requires validation using internationally certified reference standards. Therefore, there is an urgent need to characterize existing reference standards for the standardization of multiplex immunoassays (MIAs). Here, we report the development and validation of an MIA for the simultaneous estimation of levels of human serum immunoglobulin G (IgG) antibodies for pertussis toxin (PT), filamentous hemagglutinin (FHA), pertactin (PRN), diphtheria toxoid (DT), and tetanus toxoid (TT).MethodsThe MIA was assessed using a panel of human serum samples and WHO reference standards. The WHO reference standards were also studied for suitability in the MIA. Purified antigens (PT, FHA, PRN, DT, and TT) were coupled to the spectrally unique magnetic carboxylated microspheres. The method was validated in accordance with the United States Food and Drug Administration (US FDA), European Medicines Agency (EMA), and the International Committee of Harmonization Multidisciplinary (ICH M10) guidelines, and parameters such as precision, accuracy, dilutional linearity, assay range, robustness, and stability were assessed. Method agreements with commercially available IgG enzyme-linked immunosorbent assay (ELISA) assays were also evaluated. In addition, the study assessed the level of correlation between the IgG levels estimated by the MIA and the cell-based neutralizing antibody assays for PT and DT.ResultsWe identified that an equimix of WHO international standards (i.e., 06/142, 10/262, and TE-3) afforded the best dynamic range for all the antigens in the MIA. For all five antigens, we observed that the back-fitted recoveries using the four-parameter logistic (4-PL) regression fits ranged between 80% and 120% for all calibration levels, and the percentage coefficient of variation (% CV) was < 20%. In addition, the difference in mean fluorescence intensity (MFI) between the monoplex and multiplex format was < 10% for each antigen, indicating no crosstalk among the beads. The MIA also showed good agreement with conventional and commercially available assays, and a positive correlation (> 0.75) with toxin neutralization assays for PT and DT was observed.ConclusionThe MIA that was calibrated in accordance with WHO reference standards demonstrated increased sensitivity, reproducibility, and high throughput capabilities, allowing for the design of robust studies that evaluate both natural and vaccine-induced immunity.

Summary: Background: Access to essential cancer medicines is a key determinant of childhood cancer survival. WHO published the Model List of Essential Medicine for Children (EMLc) and updated it every two years since 2007 to promote better access to medicines for children. This study aimed to assess whether the inclusion of essential anticancer medicines for respective indications for children was based on evidence of significant clinical benefit between 2011 and 2021. Methods: We identified all anticancer medicine indications added to the WHO EMLc Section 8 since 2011 and extracted evidence of benefit documented in the corresponding technical reports. Evidence in children was defined as evidence that included participants under 12, and graded into five levels, according to the Oxford Centre for Evidence-Based Medicine Levels of Evidence. We analyzed whether each anticancer medicine indication was listed with documented OS benefit or improvements in surrogate measures based on the highest level of documented evidence in children. Findings: A total of 115 anticancer medicine indications were added to the EMLc from 2011 to 2021, of which 101 (87.8%) had some clinical evidence in children and 4 (3.5%) were added without any clinical evidence. Among the 101 medicine indications, none were added with level-1 evidence in children, and 43 (42.6%), 11 (10.9%), 41 (40.6%), and 6 (5.9%) were listed with level-2, level-3, level-4, and level-5 evidence in children, respectively. Only eight (7.9%) medicine indications were reported to have OS benefit, another 12 (11.9%) were reported to have improvements on surrogate measures, and 81 (80.2%) were listed in the EMLc without documented improvements in either OS or surrogate measures. Interpretation: Most anticancer medicine indications of the WHO EMLc were added based on limited evidence of statistically significant clinical benefit in children. Our results suggest that WHO should refine requirements for clinical benefit criteria and permissible forms, quality, and reporting of evidence of essential anticancer medicines for children, specify whether anticancer medicine indications have required evidence of clinical benefit in children, and provide further details in its technical reports that summarise the available evidence. Funding: Not applicable.

An electrically conducting nanofluid saturated with a uniform porous media has been tested to determine how rotation affects thermal convection. Utilizing the Oldroydian model, which incorporates the specific effects of the electric field, Brownian motion, thermophoresis, and rheological factors for the distribution of nanoparticles that are top- and bottom-heavy, one may use linear stability theory to ensure stability. Analysis and graphical representation of the effects of the AC electric field Rayleigh number, Taylor number, Lewis number, modified diffusivity ratio, concentration Rayleigh number, and medium porosity are provided for both bottom-heavy and top-heavy distribution.

Abstract Background Symptom control is prioritized by cancer patients and may improve overall survival. Ontario, Canada thus offers all cancer patients screening using the Edmonton Symptom Assessment System (ESAS) at outpatient cancer‐related visits. We determined whether this initiative reached adolescents and young adults (AYA) and factors associated with screening in this population. Methods We linked all Ontario AYA diagnosed with cancer 2010–2018 aged 15–29 years to population‐based databases identifying outpatient visits and ESAS screening. For each 2‐week period in the year post‐diagnosis, AYA with cancer‐related visits were categorized as “unscreened” (no ESAS score) versus “screened” (≥1 ESAS score). Demographic and disease‐related covariates were examined. Results Among 5435 AYA, 4204 (77.4%) had ≥1 ESAS screen. Within any 2‐week period, only 30%–44% of AYA attending cancer‐related visits were screened. Patients with hematologic malignancies were least likely to be screened [odds ratio (OR) vs. breast cancer 0.77, 95% confidence interval (95% CI) 0.67–0.88; p

Apparel and textile sector is one of the most polluting sectors. It is majorly responsible for air, water, soil pollution and other negative effect. To counter this, implementing the sustainability practices play the major role. This study identified the various barriers that hinders, implementation of sustainability across the different stages of supply chain management. Moreover, opinion from the experts is taken for distinguishing the critical barriers. ISM and fuzzy MICMAC decision making techniques are used for the identification of critical barriers. It was found out that Communication gap among stakeholders, Barriers that effect performance of this sector, Lack of training and education about sustainability, Capacity constraints and Lack of reverse logistics practices are the critical barriers of sustainable supply chain management. In addition to this DEMATEL is used to classified the barriers into two groups i,e cause based and effect based. It was found out that all the cause-based barriers are exactly match with level 5 barriers of ISM model. DEMATEL method support the result of ISM and fuzzy MICMAC technique-based result. This study is useful for industry professional and managers in the Apparel & Textile sector.

Introduction The diagnosis, progression or recurrence of cancer is often highly traumatic for family caregivers (FCs), but systematic assessments of distress and approaches for its prevention and treatment are lacking. Acute leukaemia (AL) is a life-threatening cancer of the blood, which most often presents acutely, requires intensive treatment and is associated with severe physical symptoms. Consequently, traumatic stress may be common in the FCs of patients with AL. We aim to determine the prevalence, severity, longitudinal course and predictors of traumatic stress symptoms in FCs of patients with AL in the first year after diagnosis, and to understand their lived experience of traumatic stress and perceived support needs.Methods and analysis This two-site longitudinal, observational, mixed methods study will recruit 223 adult FCs of paediatric or adult patients newly diagnosed with AL from two tertiary care centres. Quantitative data will be collected from self-report questionnaires at enrolment, and 1, 3, 6, 9 and 12 months after admission to hospital for initial treatment. Quantitative data will be analysed using descriptive and machine learning approaches and a multilevel modelling (MLM) approach will be used to confirm machine learning findings. Semi-structured qualitative interviews will be conducted at 3, 6 and 12 months and analysed using a grounded theory approach.Ethics and dissemination This study is funded by the Canadian Institutes of Health Research (CIHR number PJT 173255) and has received ethical approval from the Ontario Cancer Research Ethics Board (CTO Project ID: 2104). The data generated have the potential to inform the development of targeted psychosocial interventions for traumatic stress, which is a public health priority for high-risk populations such as FCs of patients with haematological malignancies. An integrated and end-of-study knowledge translation strategy that involves FCs and other stakeholders will be used to interpret and disseminate study results.

PURPOSEThis study sought to (1) evaluate the perceived effectiveness of an early childhood cancer warning signs and symptoms (EWSS) training intervention on health care worker (HCW) knowledge, attitudes, and clinical practice; (2) evaluate the ease of implementation of training received, including potential barriers and facilitators; and (3) provide insights into program improvements for future iterations of the intervention.METHODUsing a qualitative descriptive study design, we conducted in-depth, semistructured interviews with 23 purposively sampled Ghanaian HCW recipients of the EWSS training intervention. We undertook iterative thematic analysis of data concurrently with interviews and used a modified version of the theoretical framework of acceptability to guide the evaluation of the training intervention.RESULTSWe identified six themes—affective attitude, burden, intervention coherence, perceived effectiveness, self-efficacy, and quality improvement—that structure participant perceptions of the effectiveness of the EWSS training. Participants generally had a positive attitude to the training intervention, found the content relatively easy to understand, and communicated the positive impacts of the training on their day-to-day practice. However, they also identified patient- and system-level challenges to the real-world implementation of intervention components, including patients' cultural and religious beliefs about illnesses, patients' financial constraints, and inadequately funded health systems.CONCLUSIONOur findings suggest that although an HCW-focused training intervention has the potential to improve timely diagnosis and referral for childhood cancers in Ghana and comparable health system contexts, complementary interventions to address patient- and system-level implementation challenges are required to translate improvements in HCW knowledge to sustained impact on health outcomes for children with cancer.

The Agri-Food Supply Chain (AFSC) faces several barriers in developing economies, hindering the adoption of blockchain technology. However, the adoption of these technologies can transform traditional supply chains by incorporating transparency, traceability, transaction records, and enhanced security. This paper aims to evaluate the barriers impacting the adoption of blockchain in the AFSC and provide insights to improve performance and facilitate their effective implementation in emerging economies. Therefore, a comprehensive literature survey was conducted to identify the barriers, which were further validated through experts’ opinions. The integrated interpretive structural modeling (ISM) and decision-making trial and evaluation laboratory (DEMATEL) technique were then employed to develop a structural model and determine the cause–effect relationships between the identified barriers. The study revealed several key barriers affecting the adoption of blockchain technology in the AFSC of developing economies. These barriers were analyzed using the ISM and DEMATEL technique, which provided insights into their interdependencies and impact on each other. The results offer a comprehensive understanding of the barriers and their causal relationships. This study provides unique insights for the agri-food sector to improve performance by addressing the identified barriers. The results can guide agri-food managers, blockchain technology service providers, and the government in formulating strategies and policies to effectively adopt blockchain technologies in the AFSC.

Abstract Purpose Adolescent and young adult cancer survivors require lifelong healthcare to address the late effects of therapy. We examined the impact of different provider models of long‐term follow‐up (LTFU) care on adherence to recommended surveillance. Methods We conducted a retrospective cohort study using administrative health databases in Ontario, Canada. Five‐year survivors were identified from IMPACT, a database of patients aged 15–20.9 years at diagnosis of six cancers between 1992 and 2010. We defined three models of LTFU care hierarchically: specialized survivor clinics (SCCs), general cancer clinics (GCCs), and family physician (FP). We assessed adherence to the Children's Oncology Group surveillance guidelines for cardiomyopathy and breast cancer. Multistate models assessed adherence transitions and impacts of LTFU attendance. Results A total of 1574 survivors were followed for a mean of 9.2 years (range 4.3–13.9 years) from index (5‐year survival). The highest level of LTFU attended in the first 2‐years post‐index was a GCC (47%); only 16.7% attended a SCC. By the end of study, 72% no longer attended any of the models of care and only 2% still attended an SCC. Among 188 survivors requiring breast cancer surveillance, 6.9% were adherent to their first required surveillance testing. Attendance at a SCC in the previous year and higher cumulative FP or GCC visits increased the rate of subsequently becoming adherent. Among 857 survivors requiring cardiomyopathy surveillance, 11% were adherent at study entry. Each subsequent SCC visit led to an 11.3% (95% CI: 1.05–1.18) increase in the rate of becoming adherent. Conclusion LTFU attendance and surveillance adherence are sub‐optimal. SCC follow‐up is associated with greater adherence, but few survivors receive such care, and this proportion diminished over time. Interventions are needed to improve LTFU attendance and promote surveillance adherence.

Abstract Chronic obstructive pulmonary disease (COPD) is a destructive inflammatory disease and the genes expressed within the lung are crucial to its pathophysiology. We have determined the RNAseq transcriptome of bronchial brush cells from 312 stringently defined ex-smoker patients. Compared to healthy controls there were for males 40 differentially expressed genes (DEGs) and 73 DEGs for females with only 26 genes shared. The gene ontology (GO) term “response to bacterium” was shared, with several different DEGs contributing in males and females. Strongly upregulated genes TCN1 and CYP1B1 were unique to males and females, respectively. For male emphysema (E)-dominant and airway disease (A)-dominant COPD (defined by computed tomography) the term “response to stress” was found for both sub-phenotypes, but this included distinct up-regulated genes for the E-sub-phenotype (neutrophil-related CSF3R, CXCL1, MNDA) and for the A-sub-phenotype (macrophage-related KLF4, F3, CD36). In E-dominant disease, a cluster of mitochondria-encoded (MT) genes forms a signature, able to identify patients with emphysema features in a confirmation cohort. The MT-CO2 gene is upregulated transcriptionally in bronchial epithelial cells with the copy number essentially unchanged. Both MT-CO2 and the neutrophil chemoattractant CXCL1 are induced by reactive oxygen in bronchial epithelial cells. Of the female DEGs unique for E- and A-dominant COPD, 88% were detected in females only. In E-dominant disease we found a pronounced expression of mast cell-associated DEGs TPSB2, TPSAB1 and CPA3. The differential genes discovered in this study point towards involvement of different types of leukocytes in the E- and A-dominant COPD sub-phenotypes in males and females.

Background: Viruses cause many life threatening human diseases. Recently, COVID-19 pandemic has challenged the health care systems worldwide. As a disease preventive approach and to bring relief to the severity of the symptoms, a infusion termed as Bhabha Anti-Viral Infusion-23 (‘BhAVI-23’) was conceptualized and formulated which comprised of 23 selected spices and herbals. Objective: The present study was conducted to assess the in vitro antiviral potential of the formulation, BhaAVI-23. Material and methods: The in-vitro anti-viral potential of BhAVI-23 was assessed through inhibition of HIV1 reverse transcriptase (RT) as well as through a novel P1 (virulent) bacteriphage based screening assay system. Anti-diabetic potential was assessed by non-enzymatic glycosylation of haemoglobin and the bioactive volatile components were detected through headspace gas chromatography followed by molecular docking analysis. Results: The infusion displayed prominent anti-viral activity as evident from significant (57%) inhibition of the HIV1-RT as well as through reduction in the infectivity of P1 (virulent) bacteriophage. The infusion also exerted profound protection (∼64%) to non-enzymatic glycosylation of haemoglobin. Headspace gas chromatography and mass spectrometric analysis confirmed the presence of at least 47 major compounds. Docking analysis indicated possible interaction of α-pinene and eugenol with SARS-CoV spike protein. Conclusion: This ‘BhAVI-23’ infusion displayed prominent in-vitro anti-viral and anti-diabetic potential in different model systems. These attributes have relevance as diabetic patients are more prone to COVID-19 morbidity. ‘BhAVI-23’ opens the avenue for its potential inclusion as a supportive health care system upon due regulatory approval during the current pandemic.

Virtual and Augmented Reality applications demand low-latency rendering. Adaptive Frameless Rendering (AFR) techniques offer a potential alternative to currently dominating non-adaptive double-buffered real-time 3D rendering techniques. However, due to their adaptive non-contiguous importance sampling, AFR does not benefit fully from the performance improvements offered by caching the local scene information, resulting in a lower sampling rate. This article presents an experimental, followed by an information-theoretic analysis, of this coherence vs. adaptivity trade-off in AFR. It introduces a novel way to utilize entropy to evaluate the efficiency of a rendering technique. It also presents various spatial coherence exploiting techniques in 3D path tracing and their application to AFR, paving the way to future research in the field.

Diffuse intrinsic pontine gliomas (DIPGs) are aggressive pediatric brain tumors, and patient survival has not changed despite many therapeutic efforts, emphasizing the urgent need for effective treatments. Here, we evaluated the anti-DIPG effect of the oncolytic adenovirus Delta-24-ACT, which was engineered to express the costimulatory ligand 4-1BBL to potentiate the antitumor immune response of the virus. Delta-24-ACT induced the expression of functional 4-1BBL on the membranes of infected DIPG cells, which enhanced the costimulation of CD8+ T lymphocytes. In vivo, Delta-24-ACT treatment of murine DIPG orthotopic tumors significantly improved the survival of treated mice, leading to long-term survivors that developed immunological memory against these tumors. In addition, Delta-24-ACT was safe and caused no local or systemic toxicity. Mechanistic studies showed that Delta-24-ACT modulated the tumor-immune content, not only increasing the number, but also improving the functionality of immune cells. All of these data highlight the safety and potential therapeutic benefit of Delta-24-ACT the treatment of patients with DIPG.

PURPOSE Improving access to essential medicines is necessary to reduce global mortality resulting from childhood cancer. However, there is a lack of context-specific data in many low- to middle-income countries on the determinants of access to essential childhood cancer medicines. We conducted a mixed-methods case study of the barriers to and enablers of access to WHO essential medicines for childhood cancer care in Trinidad and Tobago, in response to domestic calls for policy attention and reform. METHODS We interviewed stakeholders (N = 9) across the pharmaceutical supply system using a novel analytic framework and qualitative interview guide. Interviews were recorded, transcribed, and analyzed with constant comparative methods to capture emergent themes. Quantitatively, we examined alignment of the national essential medicines list with the 2017 WHO Essential Medicines List for Children (EMLc). National buyer prices for EMLc cancer medicines were compared with median international prices, with calculation of median price ratios to assess procurement efficiency. RESULTS Principal barriers identified included a lack of data-driven procurement, low supplier incentive to engage in tenders, reactive rather than proactive processes in response to stockouts, and siloed information systems. Recurring themes of regionalization, standardization, and proactivity emerged as priorities for policy reform. Quantitative analysis of the national essential medicines list and median price ratios for procured medicines aligned with findings reported qualitatively. CONCLUSION Our study contributes to global efforts to improve childhood cancer care by identifying policy-relevant evidence on access to essential childhood cancer medicines and providing a model for future studies in other jurisdictions.

Abstract Hodgkin lymphoma (HL) is a common adolescent and young adult (AYA) cancer. While outcome disparities between pediatric vs. adult centers [locus of care (LOC)] have been demonstrated in other AYA cancers such as acute lymphoblastic leukemia, they have not been well studied in HL. We therefore compared population‐based treatment patterns and outcomes in AYA HL by LOC. The IMPACT Cohort includes data on all Ontario, Canada AYA (15‐21 years) diagnosed with HL between 1992 and 2012. Linkage to population‐based health administrative data identified late effects. We examined LOC‐based differences in treatment modalities, cumulative doses, event‐free survival (EFS), overall survival (OS), and late effects. Among 954 AYA, 711 (74.5%) received therapy at adult centers. Pediatric center AYA experienced higher rates of radiation therapy but lower cumulative doses of doxorubicin and bleomycin. 10‐year EFS did not differ between pediatric vs. adult cancer vs. community centers (83.8% ± 2.4% vs. 82.8% ± 1.6% vs. 82.7%±3.0%; P = .71); LOC was not significantly associated with either EFS or OS in multivariable analyses. Higher incidences of second malignancies in pediatric center AYA and of cardiovascular events in adult center AYA were observed, but were not significant. In conclusion, while pediatric and adult centers used different treatment strategies, outcomes were equivalent. Differences in treatment exposures are however likely to result in different late‐effect risks. Protocol choice should be guided by individual late‐effect risk.

Improvements in survival for children with cancer residing in high-income countries have been driven by the results of successive clinical trials conducted by large multi-center cooperative groups. These survival improvements have not translated to low- and middle-income countries (LMICs), where the majority of children with cancer live. The emergence of LMIC cooperative trial groups will help define the optimal treatment for their populations and improve survival. In this manuscript, we outline recent trends in the results of studies conducted by the Children’s Oncology Group (COG) Acute Lymphoblastic Leukemia (ALL) Committee as an example of what can be accomplished through collaborative multi-institutional trials. We also discuss what implications the COG ALL experience holds for trial groups in LMIC settings.

Proximal muscle weakness is a common presentation in paediatric-orthopaedic clinics and is frequently paired with a vitamin D deficiency diagnosis. Recently, side effects of the extensive use of antiepileptic and antipsychotic drugs such as sodium valproate in childhood disorders are being documented. Sodium valproate causes a time-dependent, drug-induced proximal myopathy. We report a 13-year-old female patient who presented at the Orthopaedic Outpatient Department at Lady Hardinge Medical College, New Delhi, India, in 2019 with an abnormal gait. The patient was taking a combination therapy of sodium valproate, risperidone and trihexyphenidyl for absence seizures and a mood disorder. Following clinical investigations, the patient was diagnosed with proximal myopathy. As a result of elevated serum alkaline phosphatase and creatine kinase myocardial band levels, sodium valproate was replaced with ethosuximide and a carnitine supplementation was prescribed. The patient fully recovered and regained full mobility. Proximal myopathy had been incorrectly managed and assumed to be caused by a vitamin D deficiency. Keywords: Muscle Weakness; Carnitine; Myopathy; Valproic Acid; Vitamin D Deficiency; Gait; Case Report; India.

Alopecia areata (AA) is an autoimmune, nonscarring, inflammatory disorder of the scalp and/or body resulting in hair loss. Extensive AA such as alopecia totalis is increasingly unresponsive to conventional treatment modalities. We report a case of alopecia totalis showing a promising response with the application of platelet-rich plasma therapy modified with triamcinolone acetonide.

Abstract Background Chest computed tomography (CT) scans have a recognised role in investigating adults with severe asthma to exclude alternative diagnoses, but its role in children is less clear. The objective of this study was to review the CT findings of our local cohort of children with severe asthma and to explore whether clinical or pathobiological parameters predicted CT changes. Methods Retrospective observational single centre study including all children attending the Leicester difficult asthma clinic (DAC) who underwent a chest CT from 2006 to 2011. Additionally, we recruited eight age-matched, non-asthmatic controls to compare differences in CT findings between asthmatic and non-asthmatic children. All CT images were independently scored by two radiologists. The DAC patients were sub-divided into binary groups for each abnormality identified so that comparisons could be made against recorded clinical variables including age, lung function, serum total IgE levels, and sputum leukocyte differential cell counts. Results Thirty DAC patients (median 12 yrs., range 5–16) were included. The most common abnormalities were bronchial wall thickening (BWT) and air trapping (AT), observed in 80 and 60% of DAC patients. Bronchiectasis (BE) was identified in 27% of DAC patients. DAC patients with evidence of BE on CT images were older than those without BE (13.9 ± 0.67 vs 11.5 ± 0.61, p = 0.038). We also identified a positive correlation between increasing BE severity and extent with age (r = 0.400, p = 0.028). Conclusion Abnormal CT findings were highly prevalent in our cohort of children with severe asthma, with bronchiectasis identified in approximately one third of children. We found no alternative diagnoses that resulted in a change in clinical management.

In this work, we apply an efficient analytical algorithm namely homotopy perturbation Sumudu transform method (HPSTM) to find the exact and approximate solutions of linear and nonlinear time-fractional regularized long wave (RLW) equations. The RLW equations describe the nature of ion acoustic waves in plasma and shallow water waves in oceans. The derived results are very significant and imperative for explaining various physical phenomenons. The suggested method basically demonstrates how two efficient techniques, the Sumudu transform scheme and the homotopy perturbation technique can be integrated and applied to find exact and approximate solutions of linear and nonlinear time-fractional RLW equations. The nonlinear expressions can be simply managed by application of He's polynomials. The result shows that the HPSTM is very powerful, efficient, and simple and it eliminates the round-off errors. It has been observed that the proposed technique can be widely employed to examine other real world problems. Keywords: Sumudu transform scheme, Homotopy perturbation technique, RLW equations, Ion acoustic wave, Shallow water waves in oceans

Abstract Background Retrospective studies have shown adolescents and young adults (AYA) with acute lymphoblastic leukemia (ALL) have superior survival when treated in pediatric versus adult centers (locus of care; LOC). Several adult centers recently adopted pediatric protocols. Whether this has narrowed LOC disparities in real–world settings is unknown. Methods The IMPACT Cohort is an Ontario population–based cohort that captured demographic, disease and treatment (treatment protocol, chemotherapy doses) data for all 15‐21 year olds diagnosed with ALL 1992‐2011. Cancer outcomes were determined by chart abstraction and linkage to provincial healthcare databases. Treatment protocols were classified as pediatric‐ or adult‐based. We examined predictors of outcome, including LOC, protocol, disease biology, and time period. Results Of 271 patients, 152 (56%) received therapy at adult centers. 5‐year event‐free survival (EFS ± SE) among AYA at pediatric vs adult centers was 72% ± 4% vs 56% ± 4% (P = 0.03); 5‐year overall survival (OS) was 82% ± 4% vs 64% ± 4% (P

Chimeric antigen receptor T-cell (CAR T) therapy is a revolutionary treatment for pediatric, adolescent and young adult patients (AYA) with relapsed/refractory B-cell acute lymphoblastic leukemia. While the landscape of immunotherapy continues to rapidly evolve, widespread use of CAR T therapy is limited and many questions remain regarding the durability of CAR T therapy, methods to avoid CAR T therapy resistance and the role of consolidative stem cell transplant. Modified strategies to develop effective and persistent CAR T cells at lower costs and decreased toxicities are warranted. In this review we present current indications, limitations and future directions of CAR T therapy for ALL in the pediatric and AYA population.