Outcome and feasibility of radiotherapy bridging in large B-cell lymphoma patients receiving CD19 CAR T in the UK.

Radiotherapy (RT) has potential synergistic effects with chimeric antigen receptor (CAR) T but is not widely used as bridging therapy due to logistical challenges and lack of standardised protocols. We analysed RT bridging in a multicentre national cohort of large B-cell lymphoma patients approved for 3L axicabtagene ciloleucel or tisagenlecleucel across 12 UK centres. Of 763 approved patients, 722 were leukapheresed, 717 had data available on bridging therapy. 169/717 (24%) received RT bridging, 129 as single modality and 40 as combined modality treatment (CMT). Of 169 patients, 65.7% had advanced stage, 36.9% bulky disease, 86.5% elevated LDH, 41.7% international prognostic index (IPI) ≥3 and 15.2% double/triple hit at the time of approval. Use of RT bridging varied from 11% to 32% between centres and increased over time. Vein-to-vein time and infusion rate did not differ between bridging modalities. RT-bridged patients had favourable outcomes with 1-year progression-free survival (PFS) of 56% for single modality and 47% for CMT (1-year PFS 43% for systemic bridging). This is the largest cohort of LBCL patients receiving RT bridging prior to CAR T reported to date. Our results show that RT bridging can be safely and effectively used even in advanced stage and high-risk disease, with low dropout rates and excellent outcomes.

Mass online training of health care workers during COVID-19: approach, impact, and outcomes for over 10,000 health care providers.

OBJECTIVES: COVID-19 revealed major shortfalls in healthcare workers (HCWs) trained in acute and critical care worldwide, especially in low-resource settings. We aimed to assess mass online courses' efficacy in preparing HCWs to manage COVID-19 patients and to determine whether rapidly deployed e-learning can enhance their knowledge and confidence during a pandemic. STUDY DESIGN: Retrospective cohort study. METHODS: This international retrospective cohort study, led by a large Academic Medical Centre (AMC), was conducted via YouTube and the AMC's online learning platform. From 2020 to 2021, multidisciplinary experts developed and deployed six online training courses based on the latest evidence-based management guidelines. Participants were selected through a voluntary sample following an electronic campaign. Training outcomes were assessed using pre-and post-test questionnaires, evaluation forms, and post-training assessment surveys. Kirkpatrick's Model guided training evaluation to measure self-reported knowledge, clinical skills, and confidence improvement. We also captured the number and type of COVID-19 patients managed by HCWs after the trainings. RESULTS: Every 22.8 reach/impression and every 1.2 engagements led to a course registration. The 10,425 registrants (56.8% female, 43.1% male) represented 584 medical facilities across 154 cities. The largest segments of participants were students/interns (20.6%) and medical officers (13.4%). Of the 2169 registered participants in courses with tests, 66.9% completed post-tests. Test scores from all courses increased from the initial baseline to subsequent improvement post-course. Participants completing post-training assessment surveys reported that the online courses improved their knowledge and clinical skills (83.5%) and confidence (89.4%). Respondents managed over 19,720 COVID-19 patients after attending the courses, with 47.7% patients being moderately/severely ill. CONCLUSIONS: Participants' confidence in handling COVID-19 patients is increased by rapidly deploying mass training to a substantial target population through digital tools. The findings present a virtual education and assessment model that can be leveraged for future global public health issues, and estimates for future electronic campaigns to target.

A nucleic acid-based surface-enhanced Raman scattering of gold nanorods in N-gene integrated principal component analysis for COVID-19 detection.

A rapid, simple, sensitive, and selective point-of-care diagnosis tool kit is vital for detecting the coronavirus disease (COVID-19) based on the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strain. Currently, the reverse transcriptase-polymerase chain reaction (RT-PCR) is the best technique to detect the disease. Although a good sensitivity has been observed in RT-PCR, the isolation and screening process for high sample volume is limited due to the time-consuming and laborious work. This study introduced a nucleic acid-based surface-enhanced Raman scattering (SERS) sensor to detect the nucleocapsid gene (N-gene) of SARS-CoV-2. The Raman scattering signal was amplified using gold nanoparticles (AuNPs) possessing a rod-like morphology to improve the SERS effect, which was approximately 12-15 nm in diameter and 40-50 nm in length. These nanoparticles were functionalised with the single-stranded deoxyribonucleic acid (ssDNA) complemented with the N-gene. Furthermore, the study demonstrates method selectivity by strategically testing the same virus genome at different locations. This focused approach showcases the method's capability to discern specific genetic variations, ensuring accuracy in viral detection. A multivariate statistical analysis technique was then applied to analyse the raw SERS spectra data using the principal component analysis (PCA). An acceptable variance amount was demonstrated by the overall variance (82.4 %) for PC1 and PC2, which exceeded the desired value of 80 %. These results successfully revealed the hidden information in the raw SERS spectra data. The outcome suggested a more significant thymine base detection than other nitrogenous bases at wavenumbers 613, 779, 1219, 1345, and 1382 cm-1. Adenine was also less observed at 734 cm-1, and ssDNA-RNA hybridisations were presented in the ketone with amino base SERS bands in 1746, 1815, 1871, and 1971 cm-1 of the fingerprint. Overall, the N-gene could be detected as low as 0.1 nM within 10 mins of incubation time. This approach could be developed as an alternative point-of-care diagnosis tool kit to detect and monitor the COVID-19 disease.

A comparative study of earthquake disaster management laws between USA and Indonesia.

The frequent occurrence of disasters because of Indonesia's geographical location within the Ring of Fire calls for effective disaster-management efforts. With the issuance of Law No. 24 of 2007 on Disaster Management, the Indonesian National Disaster Management Agency (Badan Nasional Penanggulangan Bencana or BNPB) was subsequently established. Keeping in mind previous disasters in Indonesia which occur in different regions, that is, Palu and Aceh Tsunami, Cianjur earthquake, and Mount Merapi, Indonesia's disaster-management law is general and lacks technical guidelines in addressing the needs of the various regions and the different contours of geography. This article aims to analyse existing Indonesian regulatory and agency problems in disaster management by conducting a normative and comparative approach between the disaster management policy in the United States of America (USA) and Indonesia. The authors chose the USA's disaster-management policy in particular as most comparative studies on disaster management law do not involve the USA despite the State's ability to provide a comprehensive and consistent policy in the midst of the decentralisation of responsibilities with the numerous states. The authors conclude that according to existing disaster-management laws in USA and Indonesia, the government is obligated to fulfil its citizens' rights in the event of natural disasters. Furthermore, noting the issues that exist within the Indonesian disaster-management system, Indonesia can adopt the best practices of the USA to improve its disaster-management system. Among others, Indonesia can learn from the USA in the fields of accountability and transparency amongst agencies, the development of Early Warning Systems, an improved system of interagency cooperation, as well as the provision of specific disaster-management assistance. Contribution: The findings of this study are expected to serve as evaluation material and to improve government effectiveness in dealing with natural disasters.

Cyclic quantum teleportation of two-qubit entangled states by using six-qubit cluster state and six-qubit entangled state.

Cyclic quantum teleportation schemes requires at least the existence of three collaborators acting all as senders and receivers of quantum information, each one of them has an information to be transmitted to the next neighbour in a circular manner. Here, new cyclic quantum teleportation scheme is proposed for perfectly transmitting cyclically three arbitrary unknown two-qubit states ( α , ß and γ ) among the three collaborators. In this scheme, Alice can send to Bob the quantum information contained in her two-qubit state α and receive from Charlie the quantum information contained in the two-qubit state in his possession γ and similarly, Bob can transmit to Charlie the quantum information contained in his two-qubit state ß through a quantum channel of twelve-qubit state consisting of a six-qubit cluster state and a six-qubit entangled state by sequentially and cyclically performing Bell state measurements. Subsequently, each one of the three participants can afterwards retrieve his own desired two-qubit state using classical channel and by performing appropriate unitary Pauli operators and we have shown that our proposed scheme performs efficiently.

Biocontrol potential of salinity tolerant mutants of Trichoderma harzianum against Fusarium oxysporum

A exposição de uma cepa selvagem de Trichoderma harzianum à irradiação gama induziu dois mutantes tolerantes a sal (Th50M6 e Th50M11). Em condições salinas, os dois mutantes foram muito superiores à cepa selvagem em relação à velocidade de multiplicação, esporulação e eficiência contra Fusarium oxysporum, o agente causador da doença wilt do tomate. Os mutantes tolerantes foram capazes de multiplicação e esporulação em meio de cultura contendo NaCl até 69 mM. Em comparação à cepa selvagem, os dois mutantes possuíam conteúdo mais elevado de prolina e hidroxiprolina, conteúdo de sódio superior ao de potássio, cálcio ou magnésio e conteúdo elevado de fenóis totais. A análise eletroforética das proteínas totais solúveis no mutante Th50M6 apresentou bandas diferentes acumuladas em resposta a NaCl 69 mM. Os resultados também indicaram que os mutantes produzem alguns metabólitos ativos como quitinases, celulases, b-galactosidades e antibióticos como tricodermina, gliotoxina e gliovirina. Os mutantes de Trichoderma reduziram significativamente a incidência da doença e melhoraram o rendimento e o conteúdo de minerais do tomate tanto em condições salinas como não-salinas e também em condições naturais e de infestação. Quando comparados à cepa selvagem, os mutantes de Trichoderma foram também mais eficientes em diminuir o crescimento de F. oxysporum na rizosfera.A densidade populacional de ambos mutantes na rizosfera excedeu muito a da cepa selvagem.