Project description:This paper puts forward a framework for probabilistic and holistic cost-effectiveness analysis to provide support in selecting the least-cost set of measures to reach a multidimensional environmental objective. Following the principles of ecosystem-based management, the framework includes a flexible methodology for deriving and populating criteria for effectiveness and costs and analyzing complex ecological-economic trade-offs under uncertainty. The framework is applied in the development of the Finnish Programme of Measures (PoM) for reaching the targets of the EU Marine Strategy Framework Directive (MSFD). The numerical results demonstrate that substantial cost savings can be realized from careful consideration of the costs and multiple effects of management measures. If adopted, the proposed PoM would yield improvements in the state of the Baltic Sea, but the overall objective of the MSFD would not be reached by the target year of 2020; for various environmental and administrative reasons, it would take longer for most measures to take full effect.
Project description:Introduction:While conventional mechanical ventilation is a common therapy in the neonatal intensive care unit (NICU), pediatric residents receive insufficient instruction. This stand-alone computer module provides an interactive method of learning basic infant pulmonary physiology and principles of mechanical ventilation. Methods:This module runs offline and is compatible with a variety of operating systems. Participants complete a six-question, case-based pretest. The seven-section instructional module is self-paced, narrated, animated, and interactive. Learners can repeat each section as needed. At the conclusion of the module, participants complete the same six-question test and receive feedback. In total, the module requires 15-20 minutes to complete. Results:The curriculum has been implemented at the beginning of the NICU rotation over a 2-year period within our pediatric residency program. Participants preferred this interactive module and had higher posttest scores when compared to a PowerPoint presentation. After 4 months, there was evidence of knowledge decay. Discussion:The interactive module is enjoyable, effective, and convenient. It engages participants in active learning and allows them to control the time and pace of their instruction. We have implemented the curriculum within our residency program and believe it would be useful for a variety of NICU health care providers.
Project description:OBJECTIVE:To determine the cost-effectiveness of Gynaecology Teaching Associate (GTA) teaching versus conventional pelvic model (manikin) teaching of pelvic examination skills for final year medical students within a UK undergraduate obstetrics and gynaecology (O&G) curriculum. METHODS:An economic evaluation was carried out alongside a randomised controlled trial involving 492 final year medical students. 240 students received manikin teaching, and 241 GTA-led teaching. 418 (85%) students completed their assessment. Proficiency in gynaecological pelvic examination on GTAs was estimated by a senior clinical examiner, blinded to the method of teaching, using a standardised assessment tool. University of Birmingham Medical School thresholds were applied to determine proficiency levels; competence (pass) 50%, merit 60% and distinction 70%. Costs incurred in the delivery of both the educational pathways (control and intervention) were combined. All costs are reported in 2013-2014 prices and earlier costs adjusted using inflation indices. OUTCOME MEASURES:Cost per student competent in pelvic examination at completion of a 5-week clinical O&G placement. RESULTS:GTA teaching was more effective compared with conventional teaching with 12 more students considered competent at pass level and 28 more students competent at merit and distinction levels, respectively. However, the average cost of GTA teaching was £45.06 per student compared with £7.40 per student for conventional teaching, with an increased cost of £37.66 per student. The incremental cost-effectiveness ratio demonstrated that it cost an additional £640.20 per competent student and £274.37 per student competent at merit level and £274.37 at distinction level compared with conventional manikin-based teaching. CONCLUSIONS:GTA teaching of female pelvic examination at the start of undergraduate medical student O&G clinical placements is shown to cost more and be more effective. GTA teaching is likely to be considered cost-effective in the context of other tests, and over the lifespan of a competent doctor's career. TRIAL REGISTRATION NUMBER:NCT01944592.
Project description:Case-based approaches have been used extensively in STEM classrooms to enhance the real-world applicability of course content. Prior research in the bioeducation field indicates, specifically, that such methods lead to increases in students' conceptual understanding and affect in the discipline relative to more traditional methods. Despite these outcomes, the majority of case study exercises are formatted in a generalist manner. In other words, the content and context of the case study itself are not framed around the communities in which the students live. In an effort to address this concern, we developed and implemented a series of place-based case study (PBCS) exercises within the introductory cell and molecular biology courses at our institutions. A comparative, quasi-experimental approach was used to evaluate the impact of PBCSs versus non-PBCSs on cognitive and non-cognitive student outcomes. Results indicated that both PBCSs and non-PBCSs led to increases in students' content knowledge; however, no statistically significant difference existed in post-exercise performance between the PBCS and non-PBCS cohorts at the University of Texas, for instance, after controlling for confounding factors. Importantly, data also revealed that students within the PBCS cohort agreed more strongly that the case studies provided them with a better understanding of how scientific advancements and research impacted the community in which they lived than did their peers in the non-PBCS cohort. Collectively, these outcomes suggest that PBCSs offer a scalable, classroom-based approach to engage students in relevant, practical experiences that are of direct interest to them and, ideally, the broader scientific community.
Project description:Advances in single-cell genomics enable commensurate improvements in methods for uncovering lineage relations among individual cells. Current sequencing based methods for cell lineage analysis depend on low resolution bulk analysis or rely on extensive single cell sequencing which is not scalable and could be biased by functional dependencies. Here we show an integrated biochemical-computational platform for generic single-cell lineage analysis that is retrospective, cost-effective and scalable. It consists of a biochemical-computational pipeline that inputs individual cells, produces targeted single-cell sequencing data and uses it to generate a lineage tree of the input cells. We validated the platform by applying it to cells sampled from an ex vivo grown tree and analyzed its feasibility landscape by computer simulations. We conclude that the platform may serve as a generic tool for lineage analysis and thus pave the way towards large-scale human cell lineage discovery.
Project description:Construction of substitute antigens based on alternative scaffold proteins is a promising strategy in bioassay technology. In this study, we proposed a strategy for constructing substitute antigens derived from 10th human fibronectin type III (FN3) using two peptide epitopes of terminal pro-brain natriuretic peptide (NT-proBNP) as an example. The base sequences encoding the two antigenic epitopes of NT-proBNP were recombined into the FG loop region and the C-terminus of FN3, fused by 4 GS or polyN linker. The fusion proteins (named FN3-epitopes-4GS and FN3-epitopes-polyN, respectively) were expressed and purified cost-effectively using an Escherichia coli expression system. The immunoreactivity of recombinant substitutes was preliminarily confirmed by western blot analysis using epitope-specific antibodies. The sandwich enzyme-linked immunosorbent assay demonstrated that either FN3-epitopes-polyN or FN3-epitopes-4GS was highly sensitive, and FN3-epitopes-polyN exhibited better kinetics to specific antibodies than FN3-epitopes-4GS, showing a linear dose-response relationship in the concentration range of 0.06–12.85 ng/ml, which suggest that the polyN linker was more suitable for constructing the FN3-based substitute antigens compared to the 4 GS linker. Furthermore, the serum stability test and differential scanning calorimetry analysis showed that the recombinant FN3-epitopes-polyN maintained the original stability of FN3. Therefore, it was confirmed that FN3 could be engineered to construct a stable biomacromolecular substitute for displaying double epitopes of antigen proteins, such as NT-proBNP. In summary, a cost-effective strategy to produce NT-proBNP substitute antigens with good immunoreactivity and physicochemical stability was established in this work, which may provide potential uses for the production of other substitute antigens in the future.
Project description:Over 20,000 rabies deaths occur annually in India, representing one-third of global human rabies. The Indian state of Tamil Nadu has pioneered a "One Health" committee to address the challenge of rabies in dogs and humans. Currently, rabies control in Tamil Nadu involves postexposure vaccination of humans after dog bites, whereas potential supplemental approaches include canine vaccination and sterilization. We developed a data-driven rabies transmission model fit to human rabies autopsy data and human rabies surveillance data from Tamil Nadu. Integrating local estimates for canine demography and costs, we predicted the impact of canine vaccination and sterilization on human health outcomes and evaluated cost-effectiveness according to the WHO criteria for India, which correspond to thresholds of $1,582 and $4,746 per disability-adjusted life-years (DALYs) for very cost-effective and cost-effective strategies, respectively. We found that highly feasible strategies focused on stray dogs, vaccinating as few as 7% of dogs annually, could very cost-effectively reduce human rabies deaths by 70% within 5 y, and a modest expansion to vaccinating 13% of stray dogs could cost-effectively reduce human rabies by almost 90%. Through integration over parameter uncertainty, we find that, for a cost-effectiveness threshold above $1,400 per DALY, canine interventions are at least 95% likely to be optimal. If owners are willing to bring dogs to central point campaigns at double the rate that campaign teams can capture strays, expanded annual targets become cost-effective. This case study of cost-effective canine interventions in Tamil Nadu may have applicability to other settings in India and beyond.
Project description:BACKGROUND: Primary immunodeficiencies (PIDs) are a diverse group of disorders caused by multiple genetic defects. Obtaining a molecular diagnosis for PID patients using a phenotype-based approach is often complex, expensive, and not always successful. Next-generation sequencing (NGS) methods offer an unbiased genotype-based approach, which can facilitate molecular diagnostics. OBJECTIVE: To develop an efficient NGS method to identify variants in PID-related genes. METHODS: We performed HaloPlex custom target enrichment and NGS using the Ion Torrent PGM to screen 173 genes in 11 healthy controls, 13 PID patients previously evaluated with either an identified mutation or SNP, and 120 patients with undiagnosed PIDs. Sensitivity and specificity were determined by comparing NGS and Sanger sequencing results for 33 patients. Run metrics and coverage analyses were done to identify systematic deficiencies. RESULTS: A molecular diagnosis was identified for 18 of 120 patients who previously lacked a genetic diagnosis, including 9 who had atypical presentations and extensive previous genetic and functional studies. Our NGS method detected variants with 98.1% sensitivity and >99.9% specificity. Uniformity was variable (72-89%), and we were not able to reliably sequence 45 regions (45/2455 or 1.8% of total regions) due to low (<20) average read depth or <90% region coverage; thus, we optimized probe hybridization conditions to improve read-depth and coverage for future analyses, and established criteria to help identify true positives. CONCLUSION: While NGS methods are not as sensitive as Sanger sequencing for individual genes, targeted NGS is a cost-effective, first-line genetic test for the evaluation of patients with PIDs. This approach decreases time to diagnosis, increases diagnostic rate, and provides insight into the genotype-phenotype correlation of PIDs in a cost-effective way.
Project description:The effective exploitation of the intriguing theranostic features of noble metal nanoparticles for therapeutic applications is far from being a routine practice due to the persistence issue. In this regard, passion fruit-like nano-architectures (NAs), biodegradable and excretable all-in-one, nature-inspired platforms which jointly combine these characteristics with the appealing optical behaviors of noble metal nanoparticles, can offer a new alternative for theranostic applications. Besides the need for efficacious and innovative systems, the reliable and cost-effective production of nanomaterials is a pivotal subject for their translation to the clinical setting. Here, we demonstrate the production of a new cheaper class of degradable, ultrasmall-in-nano-architectures (dragon fruit NAs, dNAs) using polyethyleneimine (PEI) as a cationic polymer without affecting either their compositions or their physiological behaviors, compared to the previous NAs. In particular, the standardized protocol characterized in this work ensures the preparation of high gold-loading capacity nanoparticles, a peculiar characteristic that, synergically with the interesting properties of PEI, may unlock new possible applications previously precluded to the first version of NAs while reducing the hand-made production cost by three orders of magnitude.