Rapid Access Research Articles

Rapid Access to Novel Antimalarials by a Cross-Electrophile Coupling Oxidation Sequence

Rapid Access to Novel Antimalarials by a Cross-Electrophile Coupling Oxidation Sequence

Study on Fault Monitoring Technology of Photovoltaic Panel Based on Thermal Infrared and Optical Remote Sensing

Abstract. Rapid access to the operating status of Photovoltaic (PV) panels and troubleshooting can save management and maintenance costs for the development of PV power plants, which is important for PV power plant management and power generation capacity assurance. The use of remote sensing technology to identify the faults of photovoltaic panels has developed rapidly, however, current research usually relies only on a single optical data source to identify and count the area of PV panels in a PV electric field, although there are literature on PV panel fault detection, only the surface fault identification of PV panels is tested, while the internal faults (such as panel bad points or bad lines) cannot be identified because of the limitations of optical remote sensing. In this paper, a photovoltaic panel fault monitoring technology based on multi-source remote sensing is proposed. The optical and thermal infrared hybrid data combined with deep learning technology are used to achieve rapid and accurate fault identification and localization of PV panel arrays. It can not only automatically identify PV panels that are obscured by dust and foreign objects, but also locate PV panels that have bad dots or bad lines, which greatly improves the ability and effectiveness of remote sensing PV panel fault monitoring. The high-resolution unmanned air vehicle (UAV) optical image and thermal infrared image are applied in this experiment. The Mask RCNN algorithm is used to accurately locate and number the photovoltaic panel of the optical image. Then, the fault scene classification model is established for the multi-type fault characteristics of the optical image and thermal infrared image within the panel range, so as to identify five types of faults, such as dust cover, branch cover, bird droppings cover, internal bad points and bad lines of PV panel, which effectively solves the problem that the single optical remote sensing image cannot identify the internal component faults of the photovoltaic panel under normal conditions.

Synthesis of (Hetero)biaryls via Nickel Catalyzed Reductive Cross‐Electrophile Coupling Between (Hetero)aryl Iodides and Bromides

(Hetero)biaryls are fundamental building blocks in the pharmaceutical industry and rapid access to these scaffolds is imperative for the success of numerous medicinal chemistry campaigns. Herein, a highly general, mild, and chemoselective reductive cross‐electrophile coupling between (hetero)aryl iodides and heteroaryl bromides is reported. By employing more reactive (hetero)aryl halides, a broad range of successful substrates (45 examples) were identified. The reaction was also found to be chemoselective for C(sp2)–C(sp2) bond formation between (hetero)aryl iodides and bromides over (hetero)aryl chlorides, which were generally inert under the described reaction conditions. The efficiency of the procedure is also further demonstrated in parallel synthesis library format, on gram scale, as well as in the formal synthesis of Ruxolitinib, a potent JAK inhibitor. As such, we anticipate this method will find widespread utility in the assembly of (hetero)biaryls for medicinal chemistry efforts.

Analysis of The Feasibility of Hydrogen Injection in Pipeline Gas Challenges in The Management of Acute Myocardial Infarction in Patients With Associated Comorbidities: A Review of The Literature

Objective: The objective of this study is to investigate the challenges in the management of Acute Myocardial Infarction in patients with associated comorbidities, with the aim of identifying gaps in treatment and proposing strategies to improve care. Theoretical Framework: Modifiable risk factors play a significant role in the incidence of myocardial infarction, as evidenced by a relevant international study. Understanding the epidemiology of heart attack, including its prevalence, incidence and geographic distribution, is essential to develop effective prevention and control strategies. Identifying and managing traditional risk factors, such as smoking, hypertension, hyperlipidemia and obesity, is crucial in the preventive approach to this condition. Method: Through an integrative literature review, recent studies are explored that cover everything from epidemiology and risk factors to prevention and treatment strategies. An initial selection of 153 articles was refined to 10 studies that met all criteria. Results and Discussion: The results highlight an increasing trend in the prevalence of Coronary Artery Disease (CAD), with a stabilization in the age-standardized prevalence rate, suggesting advances in prevention and treatment. The analysis emphasizes the importance of robust and inclusive public health strategies, focused on educating the population about the risks, ensuring rapid access to treatment, and reducing inequalities in access to healthcare. Research Implications: The practical and theoretical implications of this research are discussed, providing insights into how results can influence healthcare management, public policy formation, and clinical practice in cardiology. These implications may include the need for continuing education programs for healthcare professionals, the implementation of integrated care models, and the adaptation of healthcare systems to meet the specific needs of patients with comorbidities associated with AMI. Originality/Value: This study contributes to the literature by highlighting the specific challenges faced in the management of AMI in patients with comorbidities, providing valuable insights to improve the quality of AMI care and reduce disparities in treatment. The relevance and value of this research are evidenced by its contribution to a more comprehensive understanding of the factors that influence the prognosis and quality of life of these patients.

Using Twitter (X) to mobilise knowledge for First Contact Physiotherapists: A qualitative study.

Twitter (now X) is a virtual social network commonly used by healthcare professionals. Little is known about whether it helps healthcare professionals to share, mobilise and co-create knowledge, or reduce the time between research knowledge being created and used in clinical practice (the evidence-to-practice gap). Musculoskeletal First Contact Physiotherapists (FCPs) are primary care specialists who diagnose and treat people with musculoskeletal conditions without needing to see their General Practitioner (family physician) first. They often work as a sole FCP in practice, hence are an ideal healthcare professional group with whom to explore knowledge mobilisation using Twitter. To explore how Twitter is, and can be used to mobilise knowledge, including research findings, to inform FCP clinical practice. Semi-structured interviews of FCPs with experience of working in English primary care. FCPs were purposively sampled based on employment arrangements and Twitter use. Recruitment was via known FCP networks and Twitter, supplemented by snowball sampling. Online interviews used a topic guide exploring FCP's perceptions and experiences of accessing knowledge, via Twitter, for clinical practice. Data were analysed thematically and informed by the knowledge mobilisation mindlines model. Public contributors were involved throughout. Nineteen FCPs consented to interview (Twitter users n=14, female n=9). Three themes were identified: 1) How Twitter meets the needs of FCPs, 2) Twitter and a journey of knowledge to support clinical practice and 3) Factors impeding knowledge sharing on Twitter. FCPs described needs relating to isolated working practice, time demands and role uncertainty. Twitter provided rapid access to succinct knowledge, opportunity to network and peer reassurance regarding clinical cases, evidence and policy. FCPs took a journey of knowledge exchange on Twitter, including scrolling for knowledge, filtering for credibility and adapting knowledge for in-service training and clinical practice. Participants engaged best with images and infographics. FCPs described misinformation, bias, echo chambers, unprofessionalism, hostility, privacy concerns and blurred personal boundaries as factors impeding knowledge sharing on Twitter. Consequently, many did not feel confident to actively participate with Twitter. This study explores how Twitter is, and can be used to mobilise knowledge to inform FCP clinical practice. Twitter can meet knowledge needs of FCPs through rapid access to succinct knowledge, networking opportunities and professional reassurance. The journey of knowledge exchange from Twitter to clinical practice can be explained by considering the mindlines model, which describes how FCPs exchange knowledge in online and offline contexts. Findings demonstrate that Twitter can be a useful adjunct to FCP practice although several factors impeded knowledge sharing on the platform. We recommend social media training and enhanced governance guidance from professional bodies to support the use of Twitter for knowledge mobilisation.

Modular chemoenzymatic synthesis of ten fusicoccane diterpenoids.

Fusicoccane diterpenoids display intriguing biological activities, including the ability to act as modulators of 14-3-3 protein-protein interactions. However, their innate structural complexity and diverse oxygenation patterns present enormous synthetic challenges. Here we develop a modular chemoenzymatic approach that combines de novo skeletal construction and late-stage hybrid C-H oxidations to achieve the synthesis of ten complex fusicoccanes in 8-13 steps each. A convergent fragment coupling strategy allowed rapid access to a key tricyclic intermediate, which was subjected to chemical and enzymatic C-H oxidations to modularly prepare five oxidized family members. We also conceived a complementary biomimetic skeletal remodelling strategy to synthetically access five rearranged fusicoccanes with unusual bridgehead double bonds. This work may facilitate future investigation into the biological activities of the fusicoccanes and also inspire the implementation of similar hybrid strategies to provide family-level synthetic solutions to other natural product scaffolds.

Copper-Catalyzed Sulfur Alkylation of Sulfenamides with N-Sulfonylhydrazones.

Sulfilimines are valuable compounds in both organic synthesis and pharmaceuticals. In this study, we present a copper-catalyzed sulfur alkylation of sulfenamides with N-sulfonylhydrazones. In contrast to prior findings, hydrazones derived from aldehydes act as donor-type carbene precursors, effectively engaging in coupling with sulfenamides via a copper catalyst, demonstrating exclusive S selectivity. The utility of the protocol was highlighted in the rapid access to a wide range of sulfoximine derivatives.

Revolutionizing Hospital Operations: A Comprehensive Analysis of Hospital Management System Implementation

Hospital Management System (HMS) technology will transform hospital operations. This summary summarizes HMS implementation's main components, goals, advantages, and drawbacks. Patient registration, appointment scheduling, EMR, billing, inventory management, and analytics are integrated into the HMS. Its main goal is to improve hospital efficiency, automate operations, and centralize information management. Implementing an HMS improves patient care by providing rapid access to precise information, operational efficiency, financial procedures, and data accuracy. The challenges include comprehensive staff training, strong data security, and smooth healthcare system connection. Healthcare organizations are developing digitally, making the hospital administration system essential for patient outcomes and hospital administration

Benzoxaborole Catalyst Embedded with a Lewis Base: A Highly Active and Selective Catalyst for cis-1,2-diol Modification.

The regioselective modification of polyols allows rapid access to their derivatives, thereby accelerating the polyol-related biology and drug discovery. We previously reported that benzoxaborole is a potent catalyst for the regioselective modification of polyols containing a cis-1,2-diol structure. In this study, we developed a bifunctional benzoxaborole catalyst embedded with a Lewis base. Benzoxaborole and Lewis base groups were designed to cooperatively activate a substrate (cis-1,2-diol) and reactant (electrophile), respectively, hence lowering the reaction barrier for the cis-1,2-diol moiety. The bifunctional catalyst indeed exhibited a significantly higher catalytic activity and selectivity for cis-1,2-diol modifications rather than a benzoxaborole catalyst without a Lewis base group. Mechanistic analyses, using both experimental and theoretical methods, supported the design of our catalyst. The bifunctional catalyst reported herein would be a new tool for the straightforward synthesis of polyol derivatives.

A multi-objective optimization model for planning emergency shelters after a tsunami

Vertical evacuation helps people escape tsunami risks by elevating them above the level of tsunami inundation, usually by moving to higher ground or taking refuge in tall buildings or other elevated structures. Unlike horizontal evacuation, which involves moving away from the coast to higher ground, vertical evacuation reduces the demand for horizontal evacuation routes that can become congested and impede evacuation efforts. Therefore, investing in critical infrastructure that enables vertical evacuation is crucial in tsunami-prone areas. This study proposes a multi-objective optimization model to help decision-makers assign critical infrastructure for vertical evacuation in tsunami-prone areas. Critical infrastructure includes buildings that can provide shelter during a tsunami and road networks for rapid access to shelter points. The proposed model balances three objectives: (1) minimizing investment costs in critical infrastructure, (2) maximizing the population covered by shelters, and (3) minimizing the evacuation time for evacuees to reach the shelters. This model is tested on real-world data from the Coquimbo-La Serena coastal conurbation in the Coquimbo region of Chile. The study contributes to the literature on tsunami evacuation modeling and provides valuable information for decision-makers to plan and invest in critical infrastructure for vertical evacuation during tsunamis. A sensitivity analysis of various parameters is conducted, and managerial insights are provided.

Challenges and opportunities in achieving secure hospital clinical mobility management: An illustrative use case

Objective: To qualitatively describe a use case at Yale New Haven Health System (YNHHS) illustrating the need for and effective deployment of innovative technologies to manage an enterprise-owned shared device (EOSD) management program. EOSD management provides clinicians with secure, rapid access to enterprise mobile devices and applications, maintains devices in functional, use ready condition for clinicians, and enables enterprise tracking and reduced loss of devices.Methods: Executive leaders in clinical information technology and informatics management at YNHHS were interviewed through written and telephonic communication. Qualitative data was gathered through communications between clinical and information technology executives and the implementation support team of a leading identity and access management (IAM) solutions and EOSD management solution provider. Use case information was gathered, integrated and shared with health system executives and health IT/informatics leaders to verify the description of unmet needs, solution objectives and impact/value delivered after implementation of the EOSD management solution.Results: Benefits realized from implementation of an enterprise-shared mobility management solution included establishment of a cohesive and comprehensive enterprise-owned, shared device management strategy. This included effective monitoring and dynamic management of the system’s mobile device fleet, and better IT resource management with reduced mobile device loss. The IT administrative burden was reduced. While not surveyed systematically, improved clinician experience and satisfaction were reported to IT leaders anecdotally. EOSD management solution deployment was rapid, as was the time to improved clinician mobile experience and clear demonstration of value.Conclusions: A leading US health system was able to rapidly deploy a shared mobile device management solution that enabled effective monitoring and dynamic management of the enterprise mobile device fleet, with easier and faster clinician device access and workflows, and reduced IT administrative demand and costs. While the complexities associated with increased clinical mobility in healthcare will likely continue to grow, issuing future device and mobile management challenges that require effective hospital system response, technologies have emerged that enable more effective, efficient and satisfactory organizational mobility performance.

P006 A new digital front door for existing rheumatology patient queries

Abstract Background/Aims NICE guidelines recommend people with rheumatological conditions need rapid access to specialist care to manage flares and to advise on medication. With growing demand for NHS services, rheumatology advice lines are coming under pressure. We carried out an audit on our advice line queries over four clinics in summer 2021 with a view to developing a triaging system to improve response time. Over four advice line clinics, there were 44 calls averaging 13 minutes per call. The response time was two to three weeks. 34% of calls were deemed to be inappropriate. Inappropriate calls were considered ones that could be better directed elsewhere. Methods In 2022 we started working with DrDoctor, a digital health company to design a digital nurse advice line form to redirect inappropriate calls away from the nurse advice line call backs. This involved designing a digital pathway addressing common inappropriate themes from our audit including redirection of calls to secretaries, patient booking team, prescription management and a digital booking form for phlebotomy appointments. The new digital tool enabled us to expand the service and we used the opportunity to adopt patient assessment tools and educational videos as part of the service. We promoted the digital pathway through patient information leaflets, department website and sent a text with the link to all rheumatology patients. We continued to offer the traditional contact telephone number into the service as well. Results The digital nurse advice line went live at the end of July 2023 and after two months the response time has reduced to 1.5- 2 weeks. Since then there have been 529 form submissions from 417 unique patients. 47% of submissions were inappropriate and redirected. 97 patients called to book a blood test and 76 patients opted for the online self-service clinic. 151 patients had a query about their condition. 50% of patient had RA or inflammatory arthritis. 5% AS. 5% SLE. 17% PsA. 23% selected ‘other’ and a free text box captured conditions such as fibromyalgia, osteoporosis, PMR and OA. 26% of patients with rheumatoid arthritis opted to see the educational video on self-examination and 17% watched the educational video on rheumatoid arthritis. Based on 251 submissions that were inappropriate for the advice line, assuming each inappropriate call takes an average of nine minutes based from our previous audit, 39 hours of phone time was saved from avoiding booking inappropriate nurse advice line appointments in two months. Conclusion The digital rheumatology advice service is an efficient and effective method of responding to patient queries and can be a source of patient education and self assessment. Informal patient and staff feedback has been positive and we will be collecting formal feedback as the service becomes more established. Disclosure K. Nadesalingam: None. C. Short: None. K. Christian: None. P. Helliwell: None.

P003 A fast track giant cell arteritis pathway incorporating ultrasonography improves service provision in a District General Hospital

Abstract Background/Aims Giant cell arteritis (GCA) is the most common form of adult vasculitis with comorbidities including blindness. Early identification and initiation of treatment is therefore essential. The 2020 BSR guideline suggests specialist review within three days of suspected GCA. In Ipswich Hospital, there was previously no universal referral pathway for GCA. Patients were referred to the acute medicine, A&E, rheumatology or ophthalmology clinics. An audit in 2018 over 18 months highlighted a significant delay in specialist reviews. In 2021 we designed a rapid access referral pathway for direct specialist review (protected one-stop slots in rheumatology or ophthalmology), including the use of a dedicated score for assessing the risk for GCA (GCAPS) and vascular ultrasonography in specialist clinics. Our aims for this quality improvement project were to: 1) Audit referral times for suspected GCA patients 2) Optimise the percentage of suspected GCA cases receiving a confirmatory test, notably ultrasound or temporary artery biopsy. Methods We audited the new GCA referrals from January 2022 to June 2023, and compared to the 2018 data. Data were retrospectively collected from electronic health records. Results 44 patients were included (women=29, mean age=68). In 2023, 89% of patients were seen within three days, compared to 47% previously. In 2023, patients were reviewed within a median of two days by a specialist compared to 19 in 2018. Finally, 100% of our patients received a diagnostic test, compared to 79% previously (table 1). A total of 34% of new referrals were diagnosed as GCA. 40 patients had an ultrasound which was positive in 27%, equivocal in 25% and negative in 48%. For the remaining four patients, GCA was excluded without imaging tests/biopsy. 17 patients had biopsy, with 24% being positive for GCA. 52% of referred cases had high GCAPs score and 32% normal inflammatory markers. Conclusion Our fast-track referral pathway facilitated an earlier review for our patients. These results indicate the enhanced safety afforded for suspected GCA patients via a dedicated Fast Track GCA assessment clinic with access to ultrasonography. This also led to a significant reduction in the number of temporal artery biopsies required. Disclosure D. Ioannidis: None. S. Premraj: None. E. Ntatsaki: None.

Palladium-Catalyzed Carbohalogenation of Olefins with Alkynyl Oxime Ethers: Rapid Access to Chlorine-Containing Isoxazoles.

A palladium-catalyzed carbohalogenation of olefins with alkynyl oxime ethers has been described, which provides efficient and practical access to various chlorine-containing isoxazoles. This method exhibits excellent regioselectivity, good functional group compatibility, and mild reaction conditions. The mechanistic studies suggest that the reaction proceeds via a stabilized π-benzyl palladium intermediate, which is essential for the formation of C(sp3)-Cl bonds.

Access to γ‐Iodo‐<i>gem</i>‐Diborylated Cyclopentanes and to Bicyclic Cyclopropanes

A formal atom transfer radical [3+2] annulation (ATRAn) reaction between different homoallyl radical precursors and 1,1‐diborylethene was developed. It provides a rapid access to polysubstituted cyclopentanes containing a gem‐diboronic ester moiety. The synthetic utility of theses uniquely functionalized 5‐membered rings is highlighted by their easy conversion to attractive borylated building blocks such as 1‐borylated bicyclo[3.1.0]hexanes. The ATRAn reaction was extended to homopropagylic radicals giving access to unique allylic gem‐diboronic esters that could be used in allylboration of aldehydes. Furthermore, this work highlights that 1,1‐diborylethene represents a synthetic equivalent to ketene, a so far elusive radical trap due to its daunting reactivity.

Impact of Early Access Reform on Oncology Innovation in France: Approvals, Patients, and Costs.

An ambitious reform of the early access (EA) process was set up in July 2021 in France, aiming to simplify procedures and accelerate access to innovative drugs. This study analyzes the characteristics of oncology drug approvals through the EA process and its impact on real-life data for oncology patients. The number and characteristics of EA demands concerning oncology drugs submitted to the National Health Authority (HAS, Haute Autorité de Santé) were reviewed until 31 December 2022. A longitudinal retrospective study on patients treated with an EA oncology drug between 1 January 2019 and 31 December 2022 was also performed using the French nationwide claims database (Systeme National des Données de Santé [SNDS]) to assess the impact of the reform on the number of indications and patients, and the costs. Among 110 published decisions, the HAS granted 88 (80%) EA indications within 70 days of assessment on average, including 46 (52%) in oncology (67% in solid tumors and 33% in hematological malignancies). Approved indications were mostly supported by randomized phase III trials (67%), whereas refused EA relied more on non-randomized (57%) trials. Overall survival was the primary endpoint of 28% of EA approvals versus none of denied EAs. In the SNDS data, the annual number of patients with cancer treated with an EA drug increased from 3137 patients in 2019 to 18,341 in 2022 (+ 484%), whereas the number of indications rose from 12 to 62, mainly in oncohematology (n=17), lung (n=12), digestive (n=9) and breast cancer (n=9). Reimbursement costs for EA treatments surged from €42 to €526 million (+ 1159%). The French EA reform contributed to enabling rapid access to innovations in a wide range of indications for oncology patients. However, the findings highlight ongoing challenges in financial sustainability, warranting continued evaluation and adjustments.

Photoinduced Decarboxylative Difluoroalkylation and Perfluoroalkylation of α-Fluoroacrylic Acids.

Herein, a novel and practical methodology for the photoinduced decarboxylative difluoroalkylation and perfluoroalkylation of α-fluoroacrylic acids is reported. A wide range of α-fluoroacrylic acids can be used as applicable feedstocks, allowing for rapid access to structurally important difluoroalkylated and polyfluoroalkylated monofluoroalkenes with high Z-stereoselectivity under mild conditions. The protocol demonstrates excellent functional group compatibility and provides a platform for modifying complex biologically active molecules.

Materials design for hypersonics.

Hypersonic vehicles must withstand extreme conditions during flights that exceed five times the speed of sound. These systems have the potential to facilitate rapid access to space, bolster defense capabilities, and create a new paradigm for transcontinental earth-to-earth travel. However, extreme aerothermal environments create significant challenges for vehicle materials and structures. This work addresses the critical need to develop resilient refractory alloys, composites, and ceramics. We will highlight key design principles for critical vehicle areas such as primary structures, thermal protection, and propulsion systems; the role of theory and computation; and strategies for advancing laboratory-scale materials tomanufacturable flight-ready components.

Development of a Human B7-H3-Specific Antibody with Activity against Colorectal Cancer Cells through a Synthetic Nanobody Library.

Nanobodies have emerged as promising tools in biomedicine due to their single-chain structure and inherent stability. They generally have convex paratopes, which potentially prefer different epitope sites in an antigen compared to traditional antibodies. In this study, a synthetic phage display nanobody library was constructed and used to identify nanobodies targeting a tumor-associated antigen, the human B7-H3 protein. Combining next-generation sequencing and single-clone validation, two nanobodies were identified to specifically bind B7-H3 with medium nanomolar affinities. Further characterization revealed that these two clones targeted a different epitope compared to known B7-H3-specific antibodies, which have been explored in clinical trials. Furthermore, one of the clones, dubbed as A6, exhibited potent antibody-dependent cell-mediated cytotoxicity (ADCC) against a colorectal cancer cell line with an EC50 of 0.67 nM, upon conversion to an Fc-enhanced IgG format. These findings underscore a cost-effective strategy that bypasses the lengthy immunization process, offering potential rapid access to nanobodies targeting unexplored antigenic sites.

Cationic [1,5]‐Aryl Migrations of Propargyl Benzyl Ethers – A Stereospecific Approach to E‐ and Z‐Tetrasubstituted Olefins

AbstractHerein we report the discovery and development of the first example of a cationic [1,5]‐aryl migration reaction, through an unprecedented phenonium ions. This reaction does not require any acid, base, transition metal‐based catalyst or promoter, instead promoted by the water activated NXS reagents. It provides a highly diastereoselective and rapid access to the medicinally and biologically important tetra‐substituted olefins (allyl alcohols). The involvement of an ipso‐carbon, as well as the phenonium ion during this novel, cationic [1,5]‐aryl migration was strongly supported by the isolation of 2‐oxaspiro[5.5]undecane‐9‐ones. This methodology is highly tolerable for a wide range of propargyl‐benzyl ethers, resulting in a selective construction of structurally divergent library of mono‐halo‐tricarbon‐substituted alkenes. Synthetic application has also been demonstrated by converting two isomeric‐iodo‐olefins to respective E‐ and Z‐isomers of tamoxifen in a stereospecific manner.