Incremental Improvements Research Articles

Small extracellular vesicle CA1 as a promising diagnostic biomarker for nasopharyngeal carcinoma

Nasopharyngeal carcinoma (NPC), a malignant cancer originating from the epithelial cells of the nasopharynx, presents diagnostic challenges with current methods such as plasma Epstein-Barr virus (EBV) DNA testing showing limited efficacy. This study focused on identifying small extracellular vesicle (sEV) proteins as potential noninvasive biomarkers to enhance NPC diagnostic accuracy. We isolated sEVs from plasma and utilized 4D label-free proteomics to identify differentially expressed proteins (DEPs) among healthy controls (NC = 10), early-stage NPC (E-NPC = 10), and late-stage NPC (L-NPC = 10). Eighteen sEV proteins were identified as potential biomarkers. Subsequently, parallel reaction monitoring (PRM) proteomic analysis preliminarily confirmed sEV carbonic anhydrase 1 (CA1) as a highly promising biomarker for NPC, particularly in early-stage diagnosis (NC = 15; E-NPC = 10; L-NPC = 15). To facilitate this, we developed an automated, high-throughput and highly sensitive CA1 immune-chemiluminescence chip technology characterized by a broad linear detection range and robust controls. Further validation in an independent retrospective cohort (NC = 89; E-NPC = 39; L-NPC = 172) using this technology confirmed sEV CA1 as a reliable diagnostic biomarker for NPC (AUC = 0.9809) and E-NPC (AUC = 0.9893), independent of EBV-DNA testing. Notably, sEV CA1 exhibited superior diagnostic performance compared to EBV-DNA, with a significant incremental net reclassification improvement of 27.61 % for NPC and 72.11 % for E-NPC detection. Thus, this study identifies sEV CA1 as an innovative diagnostic biomarker for NPC and E-NPC independent of EBV-DNA. Additionally, it establishes an immune-chemiluminescence chip technology for the detection of sEV CA1 protein, paving the way for further validation and clinical application.

Assessing Outcomes in HIV Prevention and Treatment Programs With Female Sex Workers and Men Who Have Sex With Men: Expanded Polling Booth Survey Protocol.

Assessing HIV outcomes in key population prevention programs is a crucial component of the program cycle, as it facilitates improved planning and monitoring of anticipated results. The Joint United Nations Programme on HIV and AIDS recommends using simple, rapid methods to routinely measure granular and differentiated program outcomes for key populations. Following a program science approach, Partners for Health and Development in Africa, in partnership with the Nairobi County Government and the University of Manitoba, aims to conduct an outcome assessment using a novel, expanded polling booth survey (ePBS) method with female sex workers and men who have sex with men in Nairobi County, Kenya. This study aims to (1) estimate the incidence and prevalence of HIV; (2) assess biomedical, behavioral, and structural outcomes; and (3) understand barriers contributing to gaps in access and use of available prevention and treatment services among female sex workers and men who have sex with men in Nairobi. The novel ePBS approach employs complementary data collection methods, expanding upon the traditional polling booth survey (PBS) method by incorporating additional quantitative, qualitative, and biological data collection components and an improved sampling methodology. Quantitative methods will include (1) PBS, a group interview method in which individuals provide responses through a ballot box in an unlinked and anonymous way, and (2) a behavioral and biological survey (BBS), including a face-to-face individual interview and collection of linked biological samples. Qualitative methods will include focus group discussions. The ePBS study uses a 2-stage, population- and location-based random sampling approach involving the random selection of locations from which random participants are selected at a predetermined time on a randomly selected day. PBS data will be analyzed at the group level, and BBS data will be analyzed at an individual level. Qualitative data will be analyzed thematically. Data were collected from April to May 2023. The study has enrolled 759 female sex workers (response rate: 759/769, 98.6%) and 398 men who have sex with men (response rate: 398/420, 94.7%). Data cleaning and analyses are ongoing, with a focus on assessing gaps in program coverage and inequities in program outcomes. The study will generate valuable HIV outcome data to inform program improvement and policy development for Nairobi County's key population HIV prevention program. This study served as a pilot for the novel ePBS method, which combines PBS, BBS, and focus group discussions to enhance its programmatic utility. The ePBS method holds the potential to fill an acknowledged gap for a rapid, low-cost, and simple method to routinely measure HIV outcomes within programs and inform incremental program improvements through embedded learning processes.

Suppression of pathological neovascularization by anti-Flt1 peptide functionalized DNA tetrahedron

Angiogenesis is an important and necessary process in tissue regeneration and recovery, but suppressing such process is also a critical therapeutic consideration in some diseases including tumor and corneal neovascularization. Currently, pathological angiogenesis is mainly inhibited through the blockade of the interaction between vascular endothelial growth factor receptor (VEGFR) and its ligands. Compared to traditional anti-angiogenic agents such as monoclonal antibody and tyrosine kinase inhibitor, polypeptide has gained growing interests for high unit activity, few adverse reactions, and low costs. Among them, anti-Flt1 (AF) peptide could inhibit VEGFR1-induced endothelial cell migration and tube formation, showing excellent anti-angiogenic activity. Addressing the issues of low water solubility, instability, and poor bioavailability would significantly hinder the applications of AF. Herein, we prepared an AF functionalized tetrahedral framework nucleic acid (tFNA@AF) to overcome the abovementioned limitations of AF. The tFNA@AF presented enhanced structural stability and cellular uptake of AF, and exhibited superior bioavailability and satisfying anti-angiogenic effectiveness in vitro. Furthermore, tFNA@AF also demonstrated high-efficiency pathological angiogenesis inhibition on tumor-bearing mice of triple-negative breast cancer and corneal neovascularization of cornea cauterized rats, two typical models of tumor and traumatic cornea where angiogenesis is not anticipant. Our tFNA@AF as a novel polypeptide-nucleic acid conjugated nanomaterials showed superior bioavailability and high anti-angiogenic effectiveness, suggesting that with incremental improvements the nanomedicine may offer potentially useful treatment aid for anti-angiogenic therapy to prevent tumor growth and corneal neovascularization.

Role of Al2O3 reinforcements in polymer-based nanocomposites for enhanced nanomechanical properties: Time-dependent modeling of creep and stress relaxation

Alumina (Al2O3) based nanocomposites mark a paradigm shift in materials science, offering unprecedented opportunities for multifunctional applications. This study meticulously examines the mechanical properties of polymer nanocomposites (PNCs), with a specific focus on the impact of varying sizes and concentrations of Al2O3 nanoparticles. By investigating these parameters, the research enables the tailoring of mechanical properties to meet specific requirements. The study reveals remarkable enhancements in the reduced modulus (Er), reaching up to 350%, 175%, and 100% under load and displacement control modes for 25 nm, 80 nm, and 200 nm average particle sizes, respectively. Beyond mechanical strength, the research delves into the nanocomposites resistance to long-term deformation (creep) and their ability to maintain consistent performance under load (stress relaxation). Additionally, the tribological performance lays the groundwork for the development of high-performance materials. The insights gained from this study represent more than an incremental improvement; they signify a transformative leap forward in addressing the multifaceted challenges of advanced material technology, with the potential to revolutionize various industries.

Consistency of the Signature of Phonotraumatic Vocal Hyperfunction Across Different Ambulatory Voice Measures.

Although different factors and voice measures have been associated with phonotraumatic vocal hyperfunction (PVH), it is unclear what percentage of individuals with PVH exhibit such differences during their daily lives. This study used a machine learning approach to quantify the consistency with which PVH manifests according to ambulatory voice measures. Analyses included acoustic parameters of phonation as well as temporal aspects of phonation and rest, with the goal of determining optimally consistent signatures of PVH. Ambulatory neck-surface acceleration signals were recorded over 1 week from 116 female participants diagnosed with PVH and age-, sex-, and occupation-matched vocally healthy controls. The consistency of the manifestation of PVH was defined as the percentage of participants in each group that exhibited an atypical signature based on a target voice measure. Evaluation of each machine learning model used nested 10-fold cross-validation to improve the generalizability of findings. In Experiment 1, we trained separate logistic regression models based on the distributional characteristics of 14 voice measures and durations of voicing and resting segments. In Experiments 2 and 3, features of voicing and resting duration augmented the existing distributional characteristics to examine whether more consistent signatures would result. Experiment 1 showed that the difference in the magnitude of the first two harmonics (H1-H2) exhibited the most consistent signature (69.4% of participants with PVH and 20.4% of controls had an atypical H1-H2 signature), followed by spectral tilt over eight harmonics (73.6% participants with PVH and 32.1% of controls had an atypical spectral tilt signature) and estimated sound pressure level (SPL; 66.9% participants with PVH and 27.6% of controls had an atypical SPL signature). Additionally, 77.6% of participants with PVH had atypical resting duration, with 68.9% exhibiting atypical voicing duration. Experiments 2 and 3 showed that augmenting the best-performing voice measures with univariate features of voicing or resting durations yielded only incremental improvement in the classifier's performance. Females with PVH were more likely to use more abrupt vocal fold closure (lower H1-H2), phonate louder (higher SPL), and take shorter vocal rests. They were also less likely to use higher fundamental frequency during their daily activities. The difference in the voicing duration signature between participants with PVH and controls had a large effect size, providing strong empirical evidence regarding the role of voice use in the development of PVH.

Scalable Primal Heuristics Using Graph Neural Networks for Combinatorial Optimization

By examining the patterns of solutions obtained for various instances, one can gain insights into the structure and behavior of combinatorial optimization (CO) problems and develop efficient algorithms for solving them. Machine learning techniques, especially Graph Neural Networks (GNNs), have shown promise in parametrizing and automating this laborious design process. The inductive bias of GNNs allows for learning solutions to mixed-integer programming (MIP) formulations of constrained CO problems with a relational representation of decision variables and constraints. The trained GNNs can be leveraged with primal heuristics to construct high-quality feasible solutions to CO problems quickly. However, current GNN-based end-to-end learning approaches have limitations for scalable training and generalization on larger-scale instances; therefore, they have been mostly evaluated over small-scale instances. Addressing this issue, our study builds on supervised learning of optimal solutions to the downscaled instances of given large-scale CO problems. We introduce several improvements on a recent GNN model for CO to generalize on instances of a larger scale than those used in training. We also propose a two-stage primal heuristic strategy based on uncertainty-quantification to automatically configure how solution search relies on the predicted decision values. Our models can generalize on 16x upscaled instances of commonly benchmarked five CO problems. Unlike the regressive performance of existing GNN-based CO approaches as the scale of problems increases, the CO pipelines using our models offer an incremental performance improvement relative to CPLEX. The proposed uncertainty-based primal heuristics provide 6-75% better optimality gap values and 45-99% better primal gap values for the 16x upscaled instances and brings immense speedup to obtain high-quality solutions. All these gains are achieved through a computationally efficient modeling approach without sacrificing solution quality.

49‐5: Invited Paper: Innovative Systems Approach to Reduce Power for High‐Bright LCD Digital Signage

Sustainability is not just a buzzword, but a real and increasing requirement for outdoor advertisers, media companies and network operators. This paper describes a systems approach to make incremental efficiency improvements to components of large‐format, high‐bright LCD displays. The result is a quantum leap in LCD power efficiency, creating a low‐power LCD display system that consumes only 1/3 to 1/2 the power of conventional high‐bright LCDs in the 55”‐86” range. The result is not only lower power, but also reduced heat, longer life, and little or no compromises in optical quality or cost.

Challenging the orthodoxy in international business research: Directions for “new” research areas

A strong critique of the international business field is that it has been “running out of steam” because IB scholars have failed to engage with emerging paradigm shifts in IB practice and management theory. IB research requires rejuvenation with timely, unique, controversial, and challenging new research questions. IB scholars need to move beyond incremental improvements to existing research agendas and focus on questions that are fundamentally new to the field. With this essay, we address four pressing topics (Buckley, Doh, & Benischke, 2017), namely: (1) the resurgence of populism, decoupling, and globalization; (2) disruptive technologies and digitalization; (3) sustainable development goals; and (4) the changing power relationships between firms, and between firms and governments. Our aim is to provide direct avenues for relevant new research that challenges the existing orthodoxy across the IB field. As part of this process, we introduce the papers in this special issue.

Impact of Multidisciplinary Prehabilitation Interventions on Postoperative Hospital Length of Stay and Functional Capacity in Patients Undergoing Resection of Colorectal Cancer: A Systematic Review and Meta-analysis.

Although surgery is commonly regarded as the primary curative treatment for colorectal cancer, it could potentially be associated with postoperative morbidity and mortality. To determine the pooled effect of exercise and multidisciplinary prehabilitation interventions on postoperative hospital length of stay and functional capacity in patients undergoing resection of colorectal cancer. A systematic search was conducted in MEDLINE (via PubMed) and Web of Science databases from inception to November 2022. The original systematic search retrieved 2005 studies. After the removal of duplicates and screening by title and abstract, 77 eligible full-text documents were evaluated for final inclusion in the meta-analysis. A total of 12 randomized controlled trials, 5 nonrandomized controlled trials, and 3 uncontrolled before-and-after studies were selected. Postoperative hospital length of stay (in days) and functional capacity (assessed with the peak of oxygen consumption [VO2 peak] and 6-minute walking test) were the outcome measures. The meta-analysis was conducted on 20 studies (3805 participants). Randomized controlled trials and nonrandomized controlled trials showed significant reductions in postoperative hospital length of stay (d = -0.10, nearly 2 days) and significant incremental improvements in VO2 peak (d = 0.27) and 6-minute walking test (d = 0.31). Regarding the before-and-after studies, the pooled effect of multidisciplinary prehabilitation interventions was positively significant for VO2 peak (d = 0.29) and 6-minute walking test (d = 0.29). There was no risk of publication bias (Egger test: p > 0.05), with a score of 0.71 (0-1) on average. There was a high between-studies heterogeneity, and several outcomes did not have the required number of studies for a desirable statistical power. These findings suggest that multidisciplinary prehabilitation interventions might be effective at decreasing postoperative hospital length of stay (nearly 2 days) and improving functional capacity. PROSPERO registration number CRD42022373982.

Advocacy, experience sharing and action planning toward raising additional financing for primary health care: spending more and spending better towards universal health coverage.

Reallocation of funding to respond the covid-19 pandemic, against a backdrop of longstanding underfunded health systems and high out of pocket expenditures for health, affected access to health services for households, especially those without social protection. These highlighted the urgency in curbing the impact of disruptions on progress towards Universal Health Coverage (UHC) goals. Strategic investments in Primary Health Care (PHC) can help spur the necessary momentum. Under the collaborative platform of the Harmonization for Health in Africa's Health Financing Technical Working Group; UNICEF Regional Office for East and Southern Africa and WHO Regional Office for Africa convened the first PHC financing forum for 21 countries across the Eastern and Southern Africa Region. The three-day forum engaged key health and financing decision makers in constructive dialogue to identify practical actions and policy changes needed to accelerate delivery of UHC through improvements in PHC financing mechanisms and arrangements. The forum was attended by over 130 senior policy makers and technicians from governments, United Nations agencies and nonstate actors drawn from within country, regional and affiliating headquarter institutions. The Regional Forum engaged participants in meaningful, and constructive discussions. Five themes emerged (1) regular measurement and monitoring of PHC services and spending (2) increasing investments in PHC (3) enhancing efficiency, effectiveness, and equity of PHC spending, (4) ensuring an enabling environment to invest more and better in PHC, and (5) better partnerships for the realization of commitments. An outcome statement summarizing the main recommendations of the meeting was approved at the end of the forum, and action plans were developed by 14 government delegations to improve PHC financing within country-specific context and priorities. The aims of this meeting in augmenting the political will created through the Africa Leadership Meeting (ALM), by catalyzing technical direction for increased momentum for improved health financing across all African countries was achieved. Peer exchanges offered practical approaches countries can take to improve health financing in ways that are suited to regional context providing a channel for incremental improvements to health outcomes in the countries.

Rewarding performance through sustainability‐linked bonds

AbstractGreen bonds and the broad category of environmental, social, and governance (ESG) debt are market initiatives designed to tie environmental goals to the funding mechanism of the firm. Although there is an evolving certification process for green and social bonds, it does not currently include monetary consequences for a deviation from the proposed green uses of the funding. This article provides an overview of the green/social bond market to highlight these shortcomings. After a review of the green bond literature, we note the shortcomings of the existing debt market and illustrate the benefits of sustainability‐linked bonds (SLB), which reward incremental improvements in relevant performance indicators.

Barriers and facilitators to implementing evidence-based integrated HIV and behavioral health care: perspectives from seven federal ending the HIV epidemic jurisdictions

ABSTRACT The federal Ending the HIV Epidemic (EHE) initiative was created to reduce new US HIV infections, largely through pre-exposure prophylaxis and HIV treatments that reduce HIV transmissibility to zero. Behavioral health disorders (mental health and substance use) remain significant barriers to achieving EHE goals. Addressing behavioral health (BH) disorders within HIV primary care settings has been promoted as a critical EHE strategy. Implementation of efficacious HIV-BH care integration and its impact on HIV-related health outcomes is not well documented. In a federally-funded, exploratory phase implementation science study, we used the Collective Impact Framework to engage partners in seven EHE jurisdictions about the feasibility, acceptability, and sustainability of implementing HIV-BH integration interventions within local HIV settings. Partners concluded that full integration will remain the exception unless health systems invest in collaborative practice, professional training, appropriate health technology, and inter-system communication. Partners supported smaller incremental improvements including transdiagnostic approaches to reinforce each team member’s sense of value in the shared endeavor. This early phase implementation science study identified research and implementation gaps that are critical to fill to end the HIV epidemic. Both the Collective Impact Framework and implementation science show promise for guiding future implementation of evidence-based HIV-BH intervention integration.

MONAI Label: A framework for AI-assisted interactive labeling of 3D medical images

The lack of annotated datasets is a major bottleneck for training new task-specific supervised machine learning models, considering that manual annotation is extremely expensive and time-consuming. To address this problem, we present MONAI Label, a free and open-source framework that facilitates the development of applications based on artificial intelligence (AI) models that aim at reducing the time required to annotate radiology datasets. Through MONAI Label, researchers can develop AI annotation applications focusing on their domain of expertise. It allows researchers to readily deploy their apps as services, which can be made available to clinicians via their preferred user interface. Currently, MONAI Label readily supports locally installed (3D Slicer) and web-based (OHIF) frontends and offers two active learning strategies to facilitate and speed up the training of segmentation algorithms. MONAI Label allows researchers to make incremental improvements to their AI-based annotation application by making them available to other researchers and clinicians alike. Additionally, MONAI Label provides sample AI-based interactive and non-interactive labeling applications, that can be used directly off the shelf, as plug-and-play to any given dataset. Significant reduced annotation times using the interactive model can be observed on two public datasets.

A Practical Method for Synthesizing Iptacopan.

Iptacopan, the first orally available small-molecule complement factor B inhibitor, was developed by Novartis AG of Switzerland. Iptacopan for the treatment of PNH was just approved by the FDA in December 2023. Other indications for treatment are still in phase III clinical trials. Iptacopan is a small-molecule inhibitor targeting complement factor B, showing positive therapeutic effects in the treatment of PNH, C3 glomerulonephritis, and other diseases. Although Iptacopan is already on the market, there has been no detailed synthesis process or specific parameter report on the intermediates during the synthesis of its compounds except for the original research patent. In this study, a practical synthesis route for Iptacopan was obtained through incremental improvement while a biosynthesis method for ketoreductase was used for the synthesis of the pivotal intermediate 12. Moreover, by screening the existing enzyme library of our research group on the basis of random as well as site-directed mutagenesis methods, an enzyme (M8) proven to be of high optical purity with a high yield for biocatalectic reduction was obtained. This enzyme was used to prepare the compound benzyl (2S,4S)-4-hydroxy-2-(4-(methoxycarbonyl)-phenyl)-piperidine-1-carboxylate) white powder (36.8 g HPLC purity: 98%, ee value: 99%). In the synthesis of intermediate 15, the reaction was improved from two-step to one-step, which indicated that the risk of chiral allosterism was reduced while the scale was expanded. Finally, Iptacopan was synthesized in a seven-step reaction with a total yield of 29%. Since three chiral intermediate impurities were synthesized directionally, this paper lays a solid foundation for the future of pharmaceutical manufacturing.

An exploration of generativity in faculty group processes in post-secondary.

Like most organizations, a university needs to plan for its success. The environment in which universities operate continues to shift and change consequent to economic realities, changing demographics, changes in technology, and most recently a global pandemic. Planning in higher education must be creative and responsive to address multifaceted demands. To sustain post-secondary education, institutional leaders need to develop skill sets that promote effective dialogue, group work, and generativity within internal organizations. Concepts of leadership for the 21st century shift focus away from the previous approaches of making incremental improvements to already existing processes toward discovering possibilities, exploring potential innovations, and generating actions (Burgess & Newton, 2015; Webber, 2016). Building on existing frameworks for understanding generativity in group work and planning, this study sought to understand generative processes and conversations that compel people to act upon thoughts and feelings arising from social interactions. A descriptive study design was utilized to explore and summarize the experiences of faculty involved in three different group planning processes: brainstorming (Osborn 1953, 1957, 1963), a force field analysis (Lewin, 1947), and a variation of an appreciative inquiry process (Cooperrider & Srivastva, 1987). The development of a generative conversations survey tool focused on how the faculty participants perceived the qualities of their experiences. A key outcome of the research was the creation of a set of recommendations for thinking about the design of group sessions and meetings that can transmethodologically enhance chances for generative results.

Islamic religious education learning innovations in strengthening character education in the Industrial Revolution Era 4.0

<p>This research is based on the role of Islamic Religious Education (PAI) subjects in strengthening student character in the era of Industrial Revolution 4.0 at SMK Muhammadiyah 1 Bantul. In connection with this, this research aims to determine Islamic religious education (PAI) learning innovations in strengthening the character of the Industrial Revolution 4.0 at SMK Muhammadiyah 1 Bantul. This research uses qualitative research methods, which are delivered descriptively. Sources of information in this research include school principals, teachers, education staff, and students who participate in learning activities in class XI of the Automotive Light Vehicle Engineering Skills Program (TKRO) at SMK Muhammadiyah 1 Bantul. The primary data source is in the form of the words and actions of the subject, which is the focus of the research; the rest is in the form of additional data such as documents, photos, and others. This research concluded that the "Kaizen" method, which originates from Japanese, the Japanese concept of Continuous Incremental Improvement, can strengthen character education and become a PAI learning innovation in the era of the Industrial Revolution 4.0. The "Kaizen" method includes five stages with the prefix "S": Seiri, Seiton, Seiso, Seiketsu, and Shitsuke.</p>

Unlocking success: key elements of sustainable business models in the wooden multistory building sector

Few studies have investigated the processes and strategic interactions among the Wooden Multistory Construction (WMC) industry actors, its customers, and local policymakers. Further insights into this field are needed for a sustainability transition in the construction sector. This study aims to explain WMC’s corporate sustainability strategies for co-creation with customers and municipalities. This was based on interviews with key informants in the sector and WMC actors using three case studies in Sweden. Our interviews focused on business processes, interactions with users and municipalities, sustainability, and innovation in the WMC market. The findings reflect the notion of a slow transition in the Swedish WMC market toward using more wood as a bearing structure, which is supported by the competitive advantages and climate performance of wood. The three case studies indicated that the corporate focus is currently placed on incremental improvements in operations, price competitiveness, and successful project management. However, in contexts where wood construction is seen as a unique advantage, collaborations between the construction industry and end users have developed and served as novel platforms for WMC market development. The study concludes that WMCl growth hinges on the industry’s housing offerings prioritizing quality, affordability, and swift construction.

An Efficient Design of 2-BIT Arithmetic Logical Unit in Quantum Dot Cellular Automata

For the past two decades, CMOS technology has reigned supreme in the world of Very Large Scale Integration (VLSI). But Quantum Dot Cellular Automata (QCA) is stepping into the spotlight, offering a fresh solution to the growing challenges of CMOS. This paper delves into the potential of QCA circuits by presenting a 2-bit Arithmetic Logic Unit (ALU) crafted with this groundbreaking technology, while also benchmarking it against conventional CMOS designs. The proposed QCA-based ALU delivers a trifecta of benefits: streamlined circuit design, exceptional space efficiency, and reduced quantum cost—all while keeping performance sharp in terms of latency and area usage. This 2-bit ALU encompasses a suite of operations: addition, subtraction, multiplication, division, bitwise AND, OR, XOR, and XNOR. QCA technology addresses some of CMOS's major pain points, like slow switching speeds, and doesn't require additional power sources, making it both efficient and environmentally friendly. This is not just an incremental improvement; it's a bold leap into the future of circuit design

Decoding the Environmental Synergy in BRI Nations: Analyzing the Influence of Renewable Energy Adoption, Financial Evolution, FDI, and Capital Resilience on Sustainability

In response to escalating global concerns over environmental degradation, this study explores the intricate relationships between financial development (FD), foreign direct investment (FDI), capital adequacy, renewable energy consumption (REC) and environmental sustainability in BRI. We aim to provide nuanced insights into how these economic variables impact environmental quality, contributing to a comprehensive understanding of the complex interplay between economic development and environmental conservation. We aim to explore the associations between FD, FDI, REC, and capital adequacy, and environmental quality, emphasizing short-term and long-term dynamics. We employ the Autoregressive Distributed Lag (ARDL) model and conduct D-H causality tests to discern these variables' temporal and causal relationships. This methodology allows us to capture the complexities of the relationships and provide a robust analysis of their impacts on environmental sustainability. The findings reveal a positive long-run association between FD and environmental quality, suggesting that a well-developed financial sector may contribute positively to environmental outcomes. However, the short-run dynamics introduce complexity, indicating a potential immediate positive impact and raising questions about contextual factors influencing FD's contribution to increased carbon emissions. Shifting the focus to FDI and REC, our research uncovers a potential positive association with environmental quality in the long run. The short-run analysis introduces nuances, suggesting a potential negative impact, reflecting the mixed effects observed in previous studies, which underscores the importance of considering temporal dimensions and policy interventions to enhance the positive contributions of FDI and REC to environmental sustainability. Further, our study delves into the impact of capital adequacy on environmental sustainability, revealing a positive long-run association, which challenges negative associations, underlining the need for tailored policies to balance economic growth and environmental conservation. As a whole, our findings contribute quantitative evidence to guide policymakers in fostering incremental improvements over time, acknowledging the multifaceted nature of the relationships under consideration.

Comparative evaluation of intensified short course regimen and standard regimen for adults TB meningitis: a protocol for an open label, multi-center, parallel arms, randomized controlled superiority trial (INSHORT trial)

BackgroundDespite several incremental improvements in the management of tuberculous meningitis (TBM), the mortality rates remain high. In spite of national and international guidelines, variation in the choice, dose, and duration of drugs exist between countries and clinicians. We propose to evaluate a shorter and more effective regimen containing agents with augmented intracerebral drug exposure and anti-inflammatory approaches to improve disability-free survival among patients with TBM. Our strategy incorporates the various developments in the field of TBM over the last two decades and only few trials have evaluated a composite of these strategies in the overall outcomes of TBM.MethodsAn open label, parallel arms, randomized controlled superiority trial will be conducted among 372 participants across 6 sites in India. Eligible participants will be randomly allocated in 1:1:1 ratio into one of the three arms. The intervention arm consists of 2 months of high-dose rifampicin (25 mg/kg), moxifloxacin (400 mg), pyrazinamide, isoniazid, aspirin (150 mg), and steroids followed by rifampicin, isoniazid, and pyrazinamide for 4 months. The second intervention arm includes all the drugs as per the first arm except aspirin and the patients in the control arm will receive treatment according to the National TB Elimination Program guidelines. All participants will be followed up for 1 year after the treatment. DiscussionCurrent WHO regimens have agents with poor central nervous system drug exposure and is too long. It does not reflect the accumulating evidence in the field. We propose a comprehensive clinical trial incorporating the emerging evidence accrued over the last two decades to shorten the duration and improve the treatment outcomes. This multi-centric trial may generate crucial evidence with policy and practice implications in the treatment of TBM.Trial registrationClinical Trial Registry India CTRI/2023/05/053314. Registered on 31 May 2023 (https://ctri.nic.in/Clinicaltrials/pmaindet2.php?EncHid=ODYzMzg=&Enc=&userName=CTRI/2023/05/053314). ClinicalTrials.gov NCT05917340. Registered on 6 August 2023 (https://classic.clinicaltrials.gov/ct2/show/NCT05917340).Protocol versionVersion 1.3 dated 12 July 2023.