Shortened Time Frame Research Articles

How to Conclude a Suspended Sports League?

Problem definition: Professional sports leagues may be suspended because of various reasons, such as the recent coronavirus disease 2019 pandemic. A critical question that the league must address when reopening is how to appropriately select a subset of the remaining games to conclude the season in a shortened time frame. Despite the rich literature on scheduling an entire season starting from a blank slate, concluding an existing season is quite different. Our approach attempts to achieve team rankings similar to those that would have resulted had the season been played out in full. Methodology/results: We propose a data-driven model that exploits predictive and prescriptive analytics to produce a schedule for the remainder of the season composed of a subset of originally scheduled games. Our model introduces novel rankings-based objectives within a stochastic optimization model, whose parameters are first estimated using a predictive model. We introduce a deterministic equivalent reformulation along with a tailored Frank–Wolfe algorithm to efficiently solve our problem as well as a robust counterpart based on min-max regret. We present simulation-based numerical experiments from previous National Basketball Association seasons 2004–2019, and we show that our models are computationally efficient, outperform a greedy benchmark that approximates a nonrankings-based scheduling policy, and produce interpretable results. Managerial implications: Our data-driven decision-making framework may be used to produce a shortened season with 25%–50% fewer games while still producing an end-of-season ranking similar to that of the full season, had it been played. Supplemental Material: The online appendix is available at https://doi.org/10.1287/msom.2022.0558 .

MAGIK: A rapid and efficient method to create lineage-specific reporters in human pluripotent stem cells

Precise insertion of fluorescent proteins into lineage-specific genes in human pluripotent stem cells (hPSCs) presents challenges due to low knockin efficiency and difficulties in isolating targeted cells. To overcome these hurdles, we present the modified mRNA (ModRNA)-based Activation for Gene Insertion and Knockin (MAGIK) method. MAGIK operates in two steps: first, it uses a Cas9-2A-p53DD modRNA with a mini-donor plasmid (without a drug selection cassette) to significantly enhance efficiency. Second, a deactivated Cas9 activator modRNA and a 'dead' guide RNA are used to temporarily activate the targeted gene, allowing for live cell sorting of targeted cells. Consequently, MAGIK eliminates the need for drug selection cassettes or labor-intensive single-cell colony screening, expediting precise gene editing. We showed MAGIK can be utilized to insert fluorescent proteins into various genes, including SOX17, NKX6.1, NKX2.5, and PDX1, across multiple hPSC lines. This underscores its robust performance and offers a promising solution for achieving knockin in hPSCs within a significantly shortened time frame.

Copper-catalyzed synthesis of pyrazolo[1,5-a]pyrimidine based triazole-linked glycohybrids: mechanistic insights and bio-applications

Hybrid molecules maintain their stronghold in the drug market, with over 60% of drug candidates in pharmaceutical industries. The substantial expenses for developing and producing biologically privileged drugs are expected to create opportunities for producing hybrid molecule-based drugs. Therefore, we have developed a simple and efficient copper-catalyzed approach for synthesizing a wide range of triazole-linked glycohybrids derived from pyrazolo[1,5-a]pyrimidines. Employing a microwave-assisted copper-catalyzed approach, we developed a concise route using various 7-O-propargylated pyrazolo[1,5-a]pyrimidines and 1-azidoglycosides. This strategy afforded a series of twenty-seven glycohybrids up to 98% yield with diverse stereochemistry. All were achieved within a remarkably shortened time frame. Our investigation extends to evaluating the anticancer potential of these synthesized triazole-linked pyrazolo[1,5-a] pyrimidine-based glycohybrids. In-vitro assays against MCF-7, MDA-MB231, and MDA-MB453 cell lines reveal intriguing findings. (2R,3S,4S,5R,6R)-2-(acetoxymethyl)-6-(4-(((5-(4-chlorophenyl)pyrazolo[1,5-a]pyrimidin-7-yl)oxy)methyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,4,5-triyl triacetate emerges as a standout with better anticancer activity against MDA-MB231 cells (IC50 = 29.1 µM), while (2R,3R,4S,5R,6R)-2-(acetoxymethyl)-6-(4-(((5-(4-chlorophenyl)pyrazolo[1,5-a]pyrimidin-7-yl)oxy)methyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,4,5-triyl triacetate demonstrates the best inhibitory effects against MCF-7 cells (IC50 = 15.3 µM) in all derived compounds. These results align with our docking analysis and structure–activity relationship (SAR) investigations, further validating the in-vitro outcomes. This work not only underscores the synthetic utility of our devised protocol but also highlights the promising potential of these glycohybrids as candidates for further anticancer therapeutic exploration.

Mouse models of chronic wasting disease: A review

Animal models are essential tools for investigating and understanding complex prion diseases like chronic wasting disease (CWD), an infectious prion disease of cervids (elk, deer, moose, and reindeer). Over the past several decades, numerous mouse models have been generated to aid in the advancement of CWD knowledge and comprehension. These models have facilitated the investigation of pathogenesis, transmission, and potential therapies for CWD. Findings have impacted CWD management and disease outcomes, though much remains unknown, and a cure has yet to be discovered. Studying wildlife for CWD effects is singularly difficult due to the long incubation time, subtle clinical signs at early stages, lack of convenient in-the-field live testing methods, and lack of reproducibility of a controlled laboratory setting. Mouse models in many cases is the first step to understanding the mechanisms of disease in a shortened time frame. Here, we provide a comprehensive review of studies with mouse models in CWD research. We begin by reviewing studies that examined the use of mouse models for bioassays for tissues, bodily fluids, and excreta that spread disease, then address routes of infectivity and infectious load. Next, we delve into studies of genetic factors that influence protein structure. We then move on to immune factors, possible transmission through environmental contamination, and species barriers and differing prion strains. We conclude with studies that make use of cervidized mouse models in the search for therapies for CWD.

The Effects of Hydroxyapatite Nanoparticles on the Growth and Yield of Ginger (Zingiber officinale Roscoe) from Seedling to Tillering Stage

Ginger (Zingiber officinale Roscoe) is one of the economically important crops in the domestic and global markets due to its versatile properties as a spice, flavoring agent and traditional medicine. Conventional ginger cultivation required a longer time frame to harvest and for soil restoration, which limited the productivity of ginger. Hydroponic systems represent a valuable solution for the problem of land availability with the benefits of shortened time frame, increased production yield and thereby increase the productivity of ginger farming. Besides that, many synthetic fertilizers have low nutrient use efficiency (NUE). Nanofertilizers with the characteristic of delivering nutrients in a controlled manner showed the potential to overcome this problem. The study aims to determine the effects of hydroxyapatite nanoparticles (HANP) on the growth and yield of ginger. In this study, hydroxyapatite nanoparticles were synthesized and characterized. Experiments were conducted to study the effect of different concentrations of hydroxyapatite nanoparticles on the growth, yield, chlorophyll contents and photosynthetic rate of hydroponically cultivated ginger. Cocopeat was selected as the planting medium and the Hoagland solution with modified formula was used for regular fertigation. The results showed that the increment (P<0.05) in number of leaves and chlorophyll content in HANP-treated plants (200 ppm HANP) from week 9 to week 13 and the higher percentage increment in photosynthetic rate from week 11 to week 13 (20-54%) in HANP-treated plants (200-1000 ppm) as compared to the control (10%). This showed the potential use of the HANP treatments for the next developmental stage of ginger.

The Tulane accelerated physician training program (TAP-TP): A novel combination of scholarship and service

Introduction In spite of a projected shortage of physicians in the USA, the relatively long time and duration of training and high expense, the education of U.S. physicians has changed little over the past 120 years. Methods To address these issues, Tulane University developed a program, the Tulane accelerated physician training program (TAP-TP). This unique program allows selected Tulane undergraduate students to complete two years of undergraduate studies, followed by a mandatory year of public service, prior to four years of medical school. Results Students almost exclusively major in Cell and Molecular Biology (CMB), and used credits earned in Medical School to complete the required hours for their Bachelor’s degree. The program was judged to be successful based on its ability to attract, retain, and graduate students into medical residency programs. The shortened time frame needed to complete the undergraduate program is associated with significant cost savings for the students. Educational outcomes were not statistically different between TAP-TP and traditional students despite the accelerated curriculum. Conclusions TAP-TP is a unique model to graduate physicians in an accelerated fashion at significant cost savings.

Pediatric Consultation-Liaison: Patient Characteristics and Considerations for Training in Evidence-Based Practices.

Consultation-liaison services are an integral part of many pediatric hospital settings, yet characteristics of this patient population have not been extensively documented. The current study is a retrospective one-year chart review of the consultation-liaison service at a large pediatric hospital in the Southwestern United States. The purpose of this study is twofold: (1) to characterize this hospital's CL population and (2) to use these characteristics to identify preliminary evidence-based practices that should be considered for CL provider training. Identifying evidence-based practice elements that align with the characteristics of consultation-liaison patient populations may inform trainings for consultation-liaison staff. This would help to ensure that youth seen in hospital consultation-liaison services are getting the best available services, which is critical given the shortened time frame available to work with this patient population.

An Evaluation Of Skeletal Muscle Aging Using A Novel Guinea Pig Model

Maintenance of the musculoskeletal system is critical to prevent falls and loss of mobility with aging. Sarcopenia, the age-related loss of muscle mass and function, affects 10% of those over 65 years and as much as 50% of people over 80 years of age. Aging is a major risk factor for osteoarthritis (OA) which is characterized by a concomitant loss of skeletal muscle, further contributing to decreased mobility. The “inflammaging” phenotype, (i.e., age-related increases in low-grade inflammation and oxidative stress) is common to both OA and sarcopenia. While progress has been made in understanding the mechanisms of sarcopenia a preclinical model that capitulates human conditions is lacking. Dunkin Hartley (DH) guinea pigs rapidly and spontaneously develop primary knee OA beginning at about 4 months of age. Thus, we speculate that DH guinea pigs may also be a valuable model of sarcopenia. PURPOSE: To determine if DH guinea pigs can serve as a model to understand human skeletal muscle aging. METHODS: We compared skeletal muscle age-related changes in the gastrocnemius (GAS) and soleus (SOL) from 5, 9, and 15-mo DH guinea pigs. We also compared these changes to a strain of guinea pig, strain 13, that does not develop knee OA at an early age. Magnetic resonance imaging was used to examine volume and then used to calculate muscle density. Immunofluorescent histochemistry was used to assess myofiber size distribution. Formalin fixed muscles were stained in India ink to measure pennation angle. Fibrosis was assessed using muscles paraffin embedded and stained with Masson’s Trichrome to quantify % collagen. Analyses are ongoing to identify if DH pigs are characterized by an inflammaging phenotype similar to aging human muscle. RESULTS: DH guinea pigs had a significant decrease in GAS density between 5 and 15-mo that was not present in the SOL (p<0.05). Both in the GAS and SOL, DH guinea pigs also demonstrated a shift towards a smaller average myofiber size with age. However, there were no age-related changes in pennation angle or fibrosis. CONCLUSION: Based on these analyses, the DH guinea pig appears to be a potentially valuable model of musculoskeletal aging. Identifying a model to study muscular aging that mimics human conditions but in a shortened time frame, will potentially allow for effective screening and treatment interventions.

A quasimetagenomics method for concerted detection and subtyping of Salmonella enterica and E. coli O157:H7 from romaine lettuce

Quasimetagenomics refers to the sequencing of a modified food microbiome to facilitate combined detection and subtyping of targeted pathogens in a single workflow. Through quasimetagenomic sequencing, pathogens are detected and subtyped in a shortened time frame compared to traditional culture enrichment and whole genome sequencing-based analyses. While this method was previously used to detect and subtype Salmonella enterica from chicken, iceberg lettuce, and black pepper, it has not been applied to investigate multiple pathogens in one workflow. A quasimetagenomic method to concertedly detect and subtype Salmonella enterica and Escherichia coli O157:H7 from artificially contaminated romaine lettuce in a single workflow was developed. All quasimetagenomic samples with initial target pathogen inoculum levels of ~1 CFU/g were detected and serotyped after co-enrichment of the two pathogens for 12 h. Single nucleotide polymorphism typing was achievable for some initial pathogen inoculum levels as low as ~0.1 CFU/g. Our results suggest that this method can be used for concerted detection and subtyping of multiple bacterial pathogens from romaine lettuce even at low contamination levels.

Targeting CXCR4, VLA4, and CXCR2 for Hematopoietic Stem Cell Mobilization

Background: Hematopoietic stem cell (HSC) transplant is an essential treatment for a variety of blood disorders and malignancies. A key step in this procedure is the mobilization of donor stem cells. The most commonly used regimen for donor mobilization is a 5-day course of G-CSF. The length of this regimen coupled with the associated side effects emphasizes a need for superior alternatives. In recent years, there has been a growing understanding of mechanisms governing stem cell retention within the bone marrow niche. This has led to the development of new mobilization drugs that specifically target these processes. Two examples of previously described drugs that target mechanisms of stem cell retention are Plerixafor (a CXCR4 inhibitor already in clinical use), and truncated Gro-Beta (tGroβ; a CXCR2 agonist). Another potential target for inducing mobilization is disruption of the interaction between the VLA-4 integrin and its ligand VCAM-1. In this study, we evaluate the efficacy of novel VLA-4 inhibitors (VLA4i) alone and in combination with Plerixafor and/or tGroβ for the purposes of hematopoietic stem cell mobilization. Methods: We synthesized over 15 novel VLA-4 inhibitor molecules and tested their potency using soluble VCAM-1 binding assays. The 5 inhibitors determined to be most potent were then tested in vivo in DBA mice for their ability to mobilize HSCs alone and in combination with tGroβ and/or Plerixafor (n=5). HSC mobilization was measured in wild-type and splenectomized mice via flow cytometry to quantify the proportion of LSK (Lineage- Sca+ cKit+) cells as well as via Colony Forming Unit (CFU) assays. For competitive transplant, mobilized CD45.1+ BALB/c mouse blood (10 uL) was injected into lethally irradiated CD45.2+ BALB/c recipients alongside 2.5x105 CD45.2+ BALB/c bone marrow cells (n=10 / cohort). HSC engraftment was monitored monthly via flow cytometry for ratio of 45.1+ vs. 45.2+ cells in peripheral blood. Results: Firetagrast and BIO5192 are previously characterized VLA4i that have been administered to humans for indications unrelated to HSC mobilization. Our best VLA4i to date, LGB-2019, exhibited similar potency as BIO5192 in preventing the binding of sVCAM-1 to VLA-4 (IC50: 1.7nM) and was &gt;200-fold more potent than firategrast. LGB-2019 showed increased aqueous solubility and mobilized 1.5-fold more murine LSK cells for a longer time period (peak HSC mobilization maintained for 4 hours) than BIO5192 when administered alone. Simultaneous injection of C57BL/6 mice with LGB-2019 (VLA4i), Plerixafor (CXCR4i) and tGro-β (CXCR2a) resulted in a synergistic increase in circulating CFUs (Fig. 1A; 9.8 x 103 CFUs/mL) and LSKs (Fig. 1B; 12.8 LSKs/uL) at 4 hours post-injection. In contrast, 5 days of G-CSF treatment mobilized approximately 3-fold and 8-fold less CFUs and LSKs, respectively (Fig. 1A-B). We saw no significant difference in mobilization for splenectomized vs. wildtype mice (23.4 x 103 CFUs/mL vs. 23.0 x 103 CFUs/mL) when mobilizing DBA/2 mice via VLA4i+CXCR4i+CXCR2a. Three months after competitive transplantation, blood obtained from BALB/c mice mobilized with the triple combination engrafted significantly better than blood obtained from mice treated with G-CSF or the dual combinations (Fig. 1C). Summary: New insights about the stem cell niche have allowed for the development of targeted drugs for the purposes of mobilization. Here, we show that a novel VLA-4 receptor inhibitor in combination with two other known mobilizers induces mobilization of hematopoietic stem and progenitor cells (CFU/LSK) at levels superior to the standard of care G-CSF and in a dramatically shortened time frame. Mouse transplant data also show superior engraftment in lethally irradiated recipients when using the triple cocktail regimen compared to the G-CSF mobilized graft. Secondary transplants are ongoing and will provide a more complete picture of primitive HSC mobilization and serial engraftment properties of the cells. Disclosures Rettig: WashU: Patents &amp; Royalties: Patent Application 16/401,950. Karpova:WashU: Patents &amp; Royalties: Patent Application 16/401,950. Ruminski:WahU: Patents &amp; Royalties: Patent Application 16/401,950. Morrow:Magenta Therapeutics: Employment, Equity Ownership, Patents &amp; Royalties. DiPersio:Cellworks Group, Inc.: Membership on an entity's Board of Directors or advisory committees; RiverVest Venture Partners Arch Oncology: Consultancy, Membership on an entity's Board of Directors or advisory committees; Magenta Therapeutics: Equity Ownership; Incyte: Consultancy, Research Funding; Bioline Rx: Research Funding, Speakers Bureau; Macrogenics: Research Funding, Speakers Bureau; Karyopharm Therapeutics: Consultancy; Celgene: Consultancy; Amphivena Therapeutics: Consultancy, Research Funding; WUGEN: Equity Ownership, Patents &amp; Royalties, Research Funding; NeoImmune Tech: Research Funding.

High-throughput cell analysis based protocol for ploidy determination in anther-derived rice callus

The study provides high-throughput protocol for ploidy determination which may accelerate the production of double haploids in rice. Advancements in anther-culture technique have accelerated the production of completely homozygous breeding lines in a shortened time frame. However, the success is dependent upon several factors including precise and accurate determination of ploidy status at callus stage. In the present study, we describe a protocol for nuclei isolation and performed DNA content based ploidy analysis in anther-derived rice callus. Tris-MgCl2 buffer (200 mM Tris, 4 mM MgCl2·6H2O, 0.5% (vol/vol) Triton X-100, adjusted pH to 7.5 with 1 N HCl) was used for isolating high-density nuclei suspension. The nuclei were stained with propidium iodide and fluorescence image was captured using Cellista-Acumen Software in high throughput cell analyser (HTCA). The region of interest was defined on stored image and DNA content was calculated on the basis of fluorescence intensity as well as volume. The protocol was validated using anther callus from different indica rice varieties. Thus, the adoption of high-throughput protocol for ploidy determination will accelerate the development of successful double haploids in rice.

Regional Practice Patterns for Newly Diagnosed Inflammatory Bowel Disease in Baton Rouge

Introduction: Due to the ambiguity in clinical presentation of inflammatory bowel disease (IBD), there can be significant delays in diagnosis. Previous studies found that diagnostic delays are associated with an increased risk of bowel stenosis and Crohn's disease (CD)-related intestinal surgeries. With earlier diagnosis and treatment, it may be possible to modify the natural history of the disease and prevent complications. Although treatment strategies can be argued, there is proof that early therapy reduces steroid use, improves maintenance of remission, and may decrease hospitalizations.Figure. IBD: Treatment Patterns.Table. 5: ASA Compound Use by Crohn's Disease LocationMethods: A retrospective chart review of all newly diagnosed patients with IBD at a private practice in Baton Rouge since 2013 was conducted. Patients diagnosed elsewhere were excluded. We collected basic demographic data, symptoms at onset, complications, time to diagnosis, disease characteristics, and initial treatment strategies. Results: Of 55 patients diagnosed with IBD, 32 had CD and 23 had ulcerative colitis (UC). Initial treatment therapies of 32 CD patients included 16 with steroids, 12 with mesalamine compounds, 6 with immunomodulators, 12 with biologic therapies, and 2 with other therapies. Average time to diagnosis was 194.7 and there were 10 hospitalizations, 5 ED visits, and 5 surgeries. Mesalamine use in CD was seen in 2 patients with L1 disease location, 4 with L2 disease location, 6 with L3 disease location, and 1 with L1 + L4 concurrent disease location. In the UC population, average time from symptom onset to diagnosis was 451.22. There were 4 hospitalizations, 4 ED visits, and 0 surgeries. Conclusion: Our cohort, though small, is indicative of the variance in practice patterns for the treatment of IBD. Although clinical trials have not consistently shown mesalamine to be effective in the treatment of Crohn's disease, it appears to be routinely used within the cohort. We speculate our results are reflective of IBD practice patterns across private clinics in the country. We did not find a correlation between diagnostic delay and complications. However our small sample size may have exaggerated the variation in times to diagnosis/treatment. We recognize the limitations in our study, most notably, small sample size and lack of diversity. For this reason, we have expanded our IRB to include the LSU public clinics in Baton Rouge. Additionally, we speculate a shortened time frame limited the risk of complications in the mesalamine cohort.

Is the delivery of a quality improvement education programme in obstetrics and gynaecology for final year medical students feasible and still effective in a shortened time frame?

BackgroundTeaching clinical audit skills to nascent health professionals is one strategy to improve frontline care. The undergraduate medical curriculum at the University of Auckland provides improvement science theory and skills in Year 5 teaching, and the opportunity to put this into practice during an Obstetrics and Gynaecology (O&G) clinical attachment in Year 6. In 2015, a revised medical school curriculum at the university resulted in a planned reduction of the O&G attachment from five weeks to four, necessitating revision of the Year 6 Quality Improvement (QI) project. The aim of this study was to evaluate if the revised programme provided an important experiential learning opportunity for medical students without imposing an unsustainable burden on clinical services.MethodsBased on a CIPP (Context/Input/Process/Product) evaluation model, the study was conducted in several stages to get a sense of the context as the new programme was being planned (Context evaluation), the feasibility of an alternative approach to meet the educational need (Input evaluation), the implementation of the revised programme (Process evaluation) and finally, the programme outcomes (Product evaluation). We used multiple data sources (supervisors, students, academic administrators, and hospital staff) and data collection methods (questionnaires, focus groups, individual interviews, consultative workshops, student reports and oral presentations).ResultsThe context evaluation revealed the Year 6 QI programme to be valuable and contributed to O&G service improvements, however, the following concerns were identified: time to complete the project, timely topic selection and access to data, recognition of student achievement, and staff workload. The evaluation of the revised QI project indicated improvement in student perceptions of their QI knowledge and skills, and most areas previously identified as challenging, despite the concurrent reduction in the duration of the O&G attachment.ConclusionsApplying the CIPP model for evaluation to our revised QI programme enabled streamlining of procedures to achieve greater efficiency without compromising the quality of the learning experience, or increasing pressure on staff. A four week clinical rotation is adequate for medical educators to consider opportunities for including QI projects as part of student experiential learning.

Labour Arbitration in Mainland China: Its Current State, Characteristics, and Tendencies

Since the implementation of the “Labour Dispute Mediation and Arbitration Law (LDMAL)” in 2008, there has been a substantial increase in the number of labour disputes in China, which to some extent shows workers’ growing awareness of labour rights. However, while new legislation was laudable, it also brought about tremendous pressure on labour dispute mediation, arbitration, and litigation. On one hand, the labour dispute arbitration legislation essentially meets the needs of the current labour disputes. But on the other hand, China’s labour dispute arbitration system is still challenged by more complicated labour relations, group-based litigations, diverse demands, intricate problems, and other factors. The system, therefore, is in urgent need of improvement. This paper analyses the following main characteristics of the current labour arbitration system in China: (i) arbitration as the pre-trial procedure for some types of labor disputes under certain conditions; (ii) free labour arbitration; (iii) reasonable time limits for labour arbitration application and a shortened time frame to reach an arbitration reward; (iv) a tripartite regulatory mechanism; and (v) the dual nature of the labour arbitration system as quasi-judicial and quasi-administrative. Furthermore, this paper focuses on the tendencies and future possibilities for the labour dispute arbitration system in China that include, but are not limited to, separation of labour arbitration and labour litigation, socialization of labour arbitration system, unified law application and coordinated jurisdiction in labour arbitration and civil litigation, and lastly, strengthening of multiple approaches to oversight labour arbitration.

Longitudinal cohort study on medical student retention of anatomical knowledge in an integrated problem-based learning curriculum

Background: When modifying a curriculum to accommodate changes in the methods of subject matter presentation or fit within a shortened time frame, student retention of knowledge remains an important issue.Aim: This study evaluates medical student retention of anatomical knowledge as they matriculate through an anatomy curriculum where the instruction hours are less than half of the current national average.Method: Medical students completed an assessment tool developed to evaluate their baseline level of anatomical knowledge at the beginning of the first year. They then completed the instrument at the end of their 1st, 2nd, 3rd, and 4th years to assess their retention of anatomical knowledge during medical school. Data collection began in September 2010 and concluded in June 2015.Results: Results demonstrate that students began medical school with a low level of anatomical knowledge (baseline), that knowledge increased during their first year (p < 0.001), continued to increase during their second year (p < 0.001), but was over 90% maintained through years 3 and 4.Conclusion: In conclusion, an anatomy course with reduced hours (∼60), using active learning methods, contextual learning, cadaver demonstrations, increased exposure to imaging, and longitudinal reinforcement can help students build a strong foundation of anatomical knowledge.

032 Rapid Guidelines: A Systematic Review

BackgroundGuidelines often take two or more years to be developed. This timeframe is not practical for providing guidance in situations when rapid advice is needed.ObjectivesTo describe current practices about the...

Transfer to a patient centred, carbohydrate counting and insulin matching programme in a shortened time frame

AbstractPatients wishing to transfer to intensified insulin therapy through a shortened skills‐based learning programme were offered both an insulin matching carbohydrate counting programme (ICT) and continuous subcutaneous insulin infusion (CSII). In total 70 patients transferred to ICT following a median of 90 minutes of professional input. In a prospective audit, improved glycaemic control was maintained for one year on ICT (initial HbA1c 9.3±1.5%, 6/12 HbA1c 8.3±1.4%, n = 67, p&lt;0.001; one year 8.3±1.4%, n=64, p&lt;0.001). In 12 patients who switched to CSII after a period on ICT, a significant improvement in HbA1c was seen following ICT (pre‐ICT HbA1c 9.6±1.5%, post‐ICT HbA1c 8.3±1.4%, t = 2.9, p&lt;0.02), but no further improvement was seen after a further year of CSII (HbA1c 8.4±0.8%, n = 9).CSII does not appear to offer significant glycaemic control advantages over ICT in this programme. Patient satisfaction with both therapies is high, but the ease of transfer and success of ICT make this our preferred option. Copyright ©2004 John Wiley &amp; Sons, Ltd.

Against the clock – time-limited dynamic group work in a student counselling service

Time-limited, dynamic group work is a comparatively new discipline, challenging both conductor and group members to work within a shortened time frame. Outlining this mode of practice, this paper seeks to present an overview of its historical development, and to detail some of the relevant literature. Special reference is made to its use in a student counselling service setting. The paper describes some theoretical aspects of a twelve-week model found useful when working with undergraduates. Despite the paper's focus being on student counselling services, much of what is written is equally applicable to work with young adults in health service settings; indeed, many of the articles quoted and referred to, relate to that setting.

57 The role of brachytherapy in the treatment of breast cancer: The American Brachytherapy Society Recommendations

Whole-breast external-beam radiation therapy (EBRT) involves a 6-week course of fractionated treatments. In contrast, brachytherapy can be completed in a 4- to 5-day treatment course. Because of this shortened time frame, there has been interest in breast brachytherapy as a sole modality after lumpectomy. The American Brachytherapy Society (ABS) has issued guidelines specifically for the use of brachytherapy in breast carcinoma. In these guidelines, the ABS addresses important areas of controversy related to the indications, execution, and evaluation of breast implants when utilized in the following settings: as the sole treatment modality following lumpectomy, as an alternative to a 6-week course of EBRT following lumpectomy, as a boost following whole-breast irradiation, and for the treatment of local recurrences following breast-conservation treatment. The ABS recommends a precise definition and meticulous delineation of the clinical target volume. In addition, the Society recommends the routine use of dose-volume histograms and a dose-homogeneity index as tools to ensure reproducible brachytherapy and to allow interinstitutional comparisons. Brachytherapy as a sole modality is currently considered investigational and should be performed in the context of a controlled clinical trial. Practitioners and cooperative groups are encouraged to use these guidelines to formulate treatment and dose-reporting policies, but responsibility for medical decisions ultimately rests with the treating radiation oncologist.

Transgenic modeling of a cardiac troponin I mutation linked to familial hypertrophic cardiomyopathy.

Multiple mutations in cardiac troponin I (cTnI) have been associated with familial hypertrophic cardiomyopathy. Two mutations are located in the cTnI inhibitory domain, a highly negatively charged region that alternately binds to either actin or troponin C, depending on the intracellular concentration of calcium. This region is critical to the inhibition of actin-myosin crossbridge formation when intracellular calcium is low. We modeled one of the inhibitory domain mutations, arginine145-->glycine (TnI(146Gly) in the mouse sequence), by cardiac-specific expression of the mutated protein in transgenic mice. Multiple lines were generated with varying degrees of expression to establish a dose relationship; the severity of phenotype could be correlated directly with transgene expression levels. Transgenic mice overexpressing wild-type cTnI were generated as controls and analyzed in parallel with the TnI(146Gly) animals. The control mice showed no abnormalities, indicating that the phenotype of TnI(146Gly) was not simply an artifact of transgenesis. In contrast, TnI(146Gly) mice showed cardiomyocyte disarray and interstitial fibrosis and suffered premature death. The functional alterations that seem to be responsible for the development of cardiac disease include increased skinned fiber sensitivity to calcium and, at the whole organ level, hypercontractility with diastolic dysfunction. Severely affected lines develop a pathology similar to human familial hypertrophic cardiomyopathy but within a dramatically shortened time frame. These data establish the causality of this mutation for cardiac disease, provide an animal model for understanding the resultant pathogenic structure-function relationships, and highlight the differences in phenotype severity of the troponin mutations between human and mouse hearts.