Publications by authors named "Alan Smith"

286 Publications

Lenvatinib plus Pembrolizumab or Everolimus for Advanced Renal Cell Carcinoma.

N Engl J Med 2021 Feb 13. Epub 2021 Feb 13.

From Memorial Sloan Kettering Cancer Center, New York (R.M.); P. Hertsen Moscow Oncology Research Institute, Moscow (B.A.), the State Institution of Health Care Regional Clinical Oncology Dispensary, Omsk (E.K.), the State Budgetary Health Care Institution Novosibirsk Regional Clinical Oncology Dispensary, Novosibirsk (V.K.), and Prevoljskiy Region Medical Center, Novgorod (A.A.) - all in Russia; Yonsei Cancer Center, Yonsei University Health System (S.Y.R.), Seoul St. Mary's Hospital, Catholic University of Korea (S.-H.H.), and Seoul National University Hospital (M.K.), Seoul, South Korea; San Matteo University Hospital Foundation, Pavia (C.P.), Istituto Nazionale dei Tumori IRCCS, Milan (G.P.), and Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori IRCCS, Meldola (U.D.G.) - all in Italy; Kyushu University, Fukuoka (M.E.), and Tokyo Women's Medical University, Tokyo (T.T.) - both in Japan; the Royal Free NHS Trust, London (T.P.), and Eisai, Hatfield (A.D.S.) - both in the United Kingdom; University Hospital Essen, Essen (V.G.), and the University of Tübingen, Tübingen (J.B.) - both in Germany; Texas Oncology, Dallas (T.E.H.); Maimonides Institute for Biomedical Research of Cordoba Hospital Universitario Reina Sofía, Medical Oncology Department, Córdoba (M.J.M.-V.), Hospital Universitario Ramón y Cajal, Madrid (T.A.G.), and Hospital de la Santa Creu i Sant Pau, Barcelona (P.M.) - all in Spain; McMaster University, Hamilton (A.K.), and Western University, London (E.W.) - both in Ontario, Canada; the University of Miami Sylvester Comprehensive Cancer Center, Miami (J.R.M.), and Florida Cancer Specialists, Gainesville (V.P.); ICON Research, South Brisbane, and University of Queensland, St. Lucia, QLD (J.C.G.), Macquarie University, Sydney (H.G.), and Western Health, Melbourne, VIC (S.W.) - all in Australia; Rambam Health Care Campus, Haifa, Israel (A.P.); Palacky University and University Hospital Olomouc, Olomouc, Czech Republic (B.M.); Centre René Gauducheau, Saint Herblain, France (F.R.); the Department of Urology, Medical University of Vienna, Vienna (M.S.); Eisai, Woodcliff Lake (C.E.D., L.D., K.M., D.X.), and Merck, Kenilworth (R.F.P.) - both in New Jersey; and Dana-Farber Cancer Institute, Boston (T.K.C.).

Background: Lenvatinib in combination with pembrolizumab or everolimus has activity against advanced renal cell carcinoma. The efficacy of these regimens as compared with that of sunitinib is unclear.

Methods: In this phase 3 trial, we randomly assigned (in a 1:1:1 ratio) patients with advanced renal cell carcinoma and no previous systemic therapy to receive lenvatinib (20 mg orally once daily) plus pembrolizumab (200 mg intravenously once every 3 weeks), lenvatinib (18 mg orally once daily) plus everolimus (5 mg orally once daily), or sunitinib (50 mg orally once daily, alternating 4 weeks receiving treatment and 2 weeks without treatment). The primary end point was progression-free survival, as assessed by an independent review committee in accordance with Response Evaluation Criteria in Solid Tumors, version 1.1. Overall survival and safety were also evaluated.

Results: A total of 1069 patients were randomly assigned to receive lenvatinib plus pembrolizumab (355 patients), lenvatinib plus everolimus (357), or sunitinib (357). Progression-free survival was longer with lenvatinib plus pembrolizumab than with sunitinib (median, 23.9 vs. 9.2 months; hazard ratio for disease progression or death, 0.39; 95% confidence interval [CI], 0.32 to 0.49; P<0.001) and was longer with lenvatinib plus everolimus than with sunitinib (median, 14.7 vs. 9.2 months; hazard ratio, 0.65; 95% CI, 0.53 to 0.80; P<0.001). Overall survival was longer with lenvatinib plus pembrolizumab than with sunitinib (hazard ratio for death, 0.66; 95% CI, 0.49 to 0.88; P = 0.005) but was not longer with lenvatinib plus everolimus than with sunitinib (hazard ratio, 1.15; 95% CI, 0.88 to 1.50; P = 0.30). Grade 3 or higher adverse events emerged or worsened during treatment in 82.4% of the patients who received lenvatinib plus pembrolizumab, 83.1% of those who received lenvatinib plus everolimus, and 71.8% of those who received sunitinib. Grade 3 or higher adverse events occurring in at least 10% of the patients in any group included hypertension, diarrhea, and elevated lipase levels.

Conclusions: Lenvatinib plus pembrolizumab was associated with significantly longer progression-free survival and overall survival than sunitinib. (Funded by Eisai and Merck Sharp and Dohme; CLEAR ClinicalTrials.gov number, NCT02811861.).
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http://dx.doi.org/10.1056/NEJMoa2035716DOI Listing
February 2021

Autism Spectrum Disorder: Investigating Predictive Adaptive Behavior Skill Deficits in Young Children.

Autism Res Treat 2021 31;2021:8870461. Epub 2021 Jan 31.

Department of Otolaryngology-Head/Neck Surgery-and Communicative Disorders, University of Louisville, Louisville, KY, USA.

Autism spectrum disorder (ASD) is a lifelong neurodevelopmental disorder that consists of difficulties with social communication and language, as well as the presence of restricted and repetitive behaviors. These deficits tend to present in early childhood and usually lead to impairments in functioning across various settings. Moreover, these deficits have been shown to negatively impact adaptive behavior and functioning. Thus, early diagnosis and intervention is vital for future success within this population. The purpose of this study was to further examine the subscales that comprise the adaptive behavior section of the Bayley®-III to determine which of the ten subscales are predictive of ASD in young children (i.e., ≤ three years of age). A retrospective file review of 273 children participating in Kentucky's early intervention program, First Steps, was completed. The children ranged in age from 18 to 35 months. A binary logistic regression was used to assess the subscales that comprise the adaptive behavior of the section of the Bayley®-III to determine which of the ten subscales are predictive of ASD in young children (i.e., ≤ three years of age). The results indicated that individual lower raw scores in communication, community use, functional preacademics, home living, health and safety, leisure, self-care, self-direction, and social subscales were predictive of an autism diagnosis.
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http://dx.doi.org/10.1155/2021/8870461DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7868143PMC
January 2021

Attenuation of the Köhler Effect in Racially Dissimilar Partnered Exercise Reversed Using Team Identity Strategy.

J Sport Exerc Psychol 2021 Feb 10:1-10. Epub 2021 Feb 10.

Michigan State University.

The authors describe two research experiments exploring the influence of race on the Köhler motivation gain effect with exercise tasks. Experiment 1 tested whether partner racial dissimilarity affects individual performance. Experiment 2 created a team identity recategorization intervention to potentially counter the influence on performance observed in Experiment 1. White male participants were partnered with either a Black or Asian partner (Experiment 1) or with a Black partner utilizing team names and shirt colors as a team identity recategorization strategy (Experiment 2). Racially dissimilar dyads completed two sets of abdominal plank exercises with a Köhler conjunctive task paradigm (stronger partner; team performance outcome dependent upon the weaker-ability participant's performance). The results of Experiment 1 suggest attenuation of the previously successful group motivation gain effect in the racially dissimilar condition. The simple recategorization strategy utilized in Experiment 2 appeared to reverse motivation losses under conjunctive-task conditions in racially dissimilar exercise dyads.
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http://dx.doi.org/10.1123/jsep.2020-0085DOI Listing
February 2021

Alginate Hydrogels with Tuneable Properties.

Adv Biochem Eng Biotechnol 2021 Feb 6. Epub 2021 Feb 6.

Department of Pharmacy, School of Applied Sciences, University of Huddersfield, Huddersfield, UK.

Alginate is a material that has many biomedical applications due to its low toxicity and a variety of favourable physical properties. In particular, the ease in which hydrogels are formed from alginate and the variety of mechanical behaviours that can be imparted on the hydrogels, by understanding alginate chemistry and intuitive design, has made alginate the most widely investigated polysaccharide used for tissue engineering. This chapter provides an overview of alginate, from how the source and natural variations in composition can influence mechanical properties of alginate hydrogels, through to some innovative techniques used to modify and functionalise the hydrogels designed specifically for cell-based therapies. The main focus is on how these strategies of understanding and controlling the chemistry of alginates have resulted in the development of hydrogels that can be tuned to deliver the physical behaviours required for successful application. This will also highlight how research on the physicochemical properties has helped alginate evolve from a structural polysaccharide in brown seaweed into a highly tuneable, multifunctional, smart biomaterial, which is likely to find further biomedical applications in the future.
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http://dx.doi.org/10.1007/10_2020_161DOI Listing
February 2021

Adipose Tissue T Regulatory Cells: Implications for Health and Disease.

Adv Exp Med Biol 2021 ;1278:125-139

Diabetes and Metabolism Research Center, Division of Endocrinology, Diabetes and Metabolism, Department of Internal Medicine, The Ohio State University, Columbus, OH, USA.

Obesity dramatically increases the risk of numerous conditions, including type 2 diabetes mellitus and other components of the metabolic syndrome. Pro-inflammatory changes that occur in adipose tissue are critical to the pathogenesis of these obesity-induced complications. Adipose tissue is one of the body's largest endocrine organs, and the cells that comprise the adipose tissue immunoenvironment secrete multiple factors (including adipokines and cytokines) that impact systemic metabolism. In particular, immunosuppressive regulatory T cells (Tregs) decline in obesity, partly in response to its complex interaction with adipocytes, and this decline contributes to disruption of the typical homeostasis observed in lean adipose tissue. Although the regulation of Treg differentiation, function, and enrichment is incompletely understood, factors including various cell-surface co-stimulatory molecules, certain lipid species, and cytokines such as PPARγ, adiponectin, and leptin are important mediators. It is also clear that there may be depot-specific differences in Tregs, rendering adipose tissue Tregs distinct from lymphoid or circulating Tregs, with implications on maintenance and functionality. While most of these findings are derived from studies in murine models, comparatively little is known about the human adipose tissue Treg signature, which requires further investigation.
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http://dx.doi.org/10.1007/978-981-15-6407-9_8DOI Listing
February 2021

Hydrolytic Degradation of Heparin in Acidic Environments: Nuclear Magnetic Resonance Reveals Details of Selective Desulfation.

ACS Appl Mater Interfaces 2021 Feb 20;13(4):5551-5563. Epub 2021 Jan 20.

Biopolymer Research Centre, School of Applied Sciences, University of Huddersfield, Huddersfield HD1 3DH, United Kingdom.

Heparin is a complex glycosaminoglycan, derived mainly from pig mucosa, used therapeutically for its anticoagulant activity. Yet, owing largely to the chain complexity, the progressive effects of environmental conditions on heparin structure have not been fully described. A systematic study of the influence of acidic hydrolysis on heparin chain length and substitution has therefore been conducted. Changes in the sulfation pattern, monitored 2D NMR, revealed initial de-N-sulfation of the molecule (pH 1/ 40 °C) and unexpectedly identified the secondary sulfate of iduronate as more labile than the 6-O-sulfate of glucosamine residues under these conditions (pH 1/ 60 °C). Additionally, the loss of sulfate groups, rather than depolymerization, accounted for most of the reduction in molecular weight. This provides an alternative route to producing partially 2-O-de-sulfated heparin derivatives that avoids using conventional basic conditions and may be of value in the optimization of processes associated with the production of heparin pharmaceuticals.
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http://dx.doi.org/10.1021/acsami.0c20198DOI Listing
February 2021

Significantly Minimizing Drug Wastage and the Cost of Cabazitaxel Used to Treat Metastatic Castration-Resistant Prostate Cancer.

Eur Urol 2021 Feb 21;79(2):177-179. Epub 2020 Oct 21.

Division of Medical Oncology, Department of Medicine, Princess Margaret Cancer Center, University Health Network, University of Toronto, Toronto, Ontario, Canada. Electronic address:

Cabazitaxel is used to treat patients with metastatic castration-resistant prostate cancer progressing after docetaxel. It is prepackaged in 60 mg single-dose vials, a quantity much higher than the average prescribed dose, which leads to, substantial drug wastage (DW) and associated costs. To minimize DW we implemented a cost-saving, cohorting strategy where multiple patients scheduled to receive cabazitaxel (at a dose of 20mg/m every 3 wks) were cohorted and treated on a single weekday whenever possible. Excess drug from each vial was then saved and used for subsequent patients treated on the same day. The drug cost with cohorting was calculated from the actual number of vials used, and the drug cost without cohorting was estimated by assumingthat one vial was used per treatment. The cost of DW was determined based on the amount of drug that was discarded. All cost calculations also accounted for the discount incentives offered by Sanofi-Aventis. Over a 3-yr period, 74 patients received 402 treatments of cabazitaxel. Multiple patients were treated on 67.4% of the treatment days, and grouping of three patients on one day saved one vial. The estimated total drug cost saved was $394 536 CAD (21.1%). Pending further studies on safety and efficacy, this strategy could potentially be adopted to mitigate DW for cabazitaxel and similarly for other oncology drugs. This would significantly decrease the overall financial burden on patients, institutions, and stakeholders. PATIENT SUMMARY: Cabazitaxel chemotherapy is associated with substantial drug wastage and associated costs. By cohorting patients scheduled to receive cabazitaxel on a single weekday, the total drug cost was decreased by $394 536 CAD (21.1%) over a 3-yr period. Similar strategies could be considered to overcome the prohibitory costs associated with drug wastage for cabazitaxel and other cancer drugs.
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http://dx.doi.org/10.1016/j.eururo.2020.09.048DOI Listing
February 2021

Enhancing Trauma Registries by Integrating Traffic Records and Geospatial Analysis to Improve Bicyclist Safety.

J Trauma Acute Care Surg 2021 Jan 11. Epub 2021 Jan 11.

Division of Trauma, Surgical Critical Care, Burns and Acute Care Surgery, Department of Surgery, University of California San Diego Health, San Diego, CA 92103 Lloyd L. Gregory School of Pharmacy, Palm Beach Atlantic University, 901 S Flagler Drive, West Palm Beach, FL 33401.

Background: Trauma registries are used to identify modifiable injury risk factors for trauma prevention efforts. However, these may miss factors useful for prevention of bicycle-automobile collisions such as vehicle speeds, driver intoxication, street conditions and neighborhood characteristics. We hypothesize that geographic information systems (GIS) analysis of trauma registry data matched with a traffic accident database could identify risk factors for bicycle- automobile injuries and better inform injury prevention efforts.

Methods: The trauma registry of a U.S. Level I trauma center was used retrospectively to identify bicycle-motor vehicle collision admissions from 1/1/2010 to 12/31/2018. Data collected included demographics, vitals, injury severity scores, toxicology, helmet use and mortality.Matching with the Statewide Integrated Traffic Records System (SWITRS) was done to provide collision, victim and GIS information. GIS mapping of collisions was done with census tract data including poverty level scoring. Incident hot spot analysis to identify statistically significant incident clusters was done using the Getis Ord Gi* statistic.

Results: Out of 25,535 registry admissions, 531(2.1%) were bicyclists struck by automobiles, 425 (80.0%) were matched to SWITRS. Younger age (OR 1.026, 95% CI: 1.013-1.040, p<0.001), higher census tract poverty level percentage (OR 0.976, 95% CI: 0.959-0.993, p=0.007) and High School or less education (OR: 0.60, 95 CI: 0.381-0.968, p=0.036) were predictive of not wearing a helmet. Higher census tract poverty level percentage (OR 1.019, 95% CI: 1.004-1.034, p=0.012) but not educational level was predictive of toxicology positive- bicyclists in automobile collisions. GIS analysis identified hot spots in the catchment area for toxicology-positive bicyclists and lack of helmet use.

Conclusions: Combining trauma registry data and matched traffic accident records data with GIS analysis identifies additional risk factors for bicyclist injury. Trauma centers should champion efforts to prospectively link public traffic accident data to their trauma registries.

Level Of Evidence: IIIStudy TypePrognostic and Epidemiological.
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http://dx.doi.org/10.1097/TA.0000000000003075DOI Listing
January 2021

The identification and characterisation of novel bioactive peptides derived from porcine liver.

Curr Res Food Sci 2020 Nov 25;3:314-321. Epub 2020 Nov 25.

Department of Chemical Sciences, School of Applied Sciences, University of Huddersfield, Huddersfield, HD1 3DH, UK.

Bioactive peptides (BAPs) can be derived from a variety of sources; these could be from dietary proteins which are then broken down in the gastrointestinal tract to release BAPs, or they can be isolated from various sources . Sources include plant-based proteins such as soy, and chickpeas, and animal proteins from waste from the meat industry and from fish skin. Bioinformatics is also a useful approach to assess the peptides released from digests due to the great number of possible sequences that can be isolated from proteins. Therefore, an analysis of peptides could potentially lead to a more rapid discovery of BAPs. This article investigates a "crude" liver peptide mixture derived from papain hydrolysis of porcine liver and purified peptides derived from the hydrolysates following HPLC fractionation and digestion of the host proteins identified using LC-MS/MS. This allowed the identification of two proteins (cytosol aminopeptidase and haemoglobin subunit alpha) present in the "crude" mixture after LC-MS/MS. hydrolysis of these proteins identified that several peptides were predicted to be both present in the crude mixture using the BIOPEP database and to have potential bioactivity using the Peptide Ranker tool. Peptides (FWG, MFLG and SDPPLVFVG) with the greatest potential bioactivity and which had not previously been reported in the literature were then synthesised. The results indicated that the predicted bioactivity of the synthetic peptides would likely include antioxidant activity. FWG and MFLG derived from the papain hydrolysis of cytosol aminopeptidase showed activity better or comparable to Trolox in the Oxygen Radical Absorbance Capacity (ORAC) assay. The use of these tools, alongside a robust range of biochemical assays which cover a wider range of bioactivities would be a way of improving the discovery of novel bioactive peptides.
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http://dx.doi.org/10.1016/j.crfs.2020.11.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7733001PMC
November 2020

A taxonomic and molecular survey of the pteridophytes of the Nectandra Cloud Forest Reserve, Costa Rica.

PLoS One 2020 18;15(11):e0241231. Epub 2020 Nov 18.

The University Herbarium, University of California at Berkeley, Berkeley, California, United States of America.

Floristic surveys are crucial to the conservation of biodiversity, but the vast majority of such surveys are limited to listing species names, and few take into account the evolutionary history of species. Here, we combine classical taxonomic and molecular phylogenetic (DNA barcoding) approaches to catalog the biodiversity of pteridophytes (ferns and lycophytes) of the Nectandra Cloud Forest Reserve, Costa Rica. Surveys were carried out over three field seasons (2008, 2011, and 2013), resulting in 176 species representing 69 genera and 22 families of pteridophytes. Our literature survey of protected areas in Costa Rica shows that Nectandra has an exceptionally diverse pteridophyte flora for its size. Plastid rbcL was selected as a DNA barcode marker and obtained for >95% of pteridophyte taxa at this site. Combined molecular and morphological analyses revealed two previously undescribed taxa that appear to be of hybrid origin. The utility of rbcL for species identification was assessed by calculating minimum interspecific distances and found to have a failure rate of 18%. Finally we compared the distribution of minimum interspecific rbcL distances with two other areas that have been the focus of pteridophyte molecular surveys: Japan and Tahiti. The comparison shows that Nectandra is more similar to Japan than Tahiti, which may reflect the biogeographic history of these floras.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0241231PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7673574PMC
December 2020

Fractionation of DNA and protein from individual latent fingerprints for forensic analysis.

Forensic Sci Int Genet 2021 Jan 21;50:102405. Epub 2020 Oct 21.

Signature Science, LLC, Austin, TX, USA.

Human touch samples represent a significant portion of forensic DNA casework. Yet, the generally low abundance of genetic material combined with the predominantly extracellular nature of DNA in these samples makes DNA-based forensic analysis exceptionally challenging. Human proteins present in these same touch samples offer an abundant and environmentally-robust alternative. Proteogenomic methods, using protein sequence variants arising from nonsynonymous DNA mutations, have recently been applied to forensic analysis and may represent a viable option looking forward. However, DNA analysis remains the gold standard and any proteomics-based methods would need to consider how DNA could be co-extracted from samples without significant loss. Herein, we describe a simple workflow for the collection, enrichment and fractionation of DNA and protein in latent fingerprint samples. This approach ensures that DNA collected from a latent fingerprint can be analyzed by traditional DNA casework methods, while protein can be proteolytically digested and analyzed via standard liquid chromatography-tandem mass spectrometry-based proteomics methods from the same touch sample. Sample collection from non-porous surfaces (i.e., glass) is performed through the application of an anionic surfactant over the fingermark. The sample is then split into separate DNA and protein fractions following centrifugation to enrich the protein fraction by pelleting skin cells. The results indicate that this workflow permits analysis of DNA within the sample, yet highlights the challenge posed by the trace nature of DNA in touch samples and the potential for DNA to degrade over time. Protein deposited in touch samples does not appear to share this limitation, with robust protein quantities collected across multiple human donors. The quantity and quality of protein remains robust regardless of fingerprint age. The proteomic content of these samples is consistent across individual donors and fingerprint age, supporting the future application of genetically variable peptide (GVP) analysis of touch samples for forensic identification.
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http://dx.doi.org/10.1016/j.fsigen.2020.102405DOI Listing
January 2021

Newly discovered cichlid fish biodiversity threatened by hybridization with non-native species.

Mol Ecol 2021 02 16;30(4):895-911. Epub 2020 Oct 16.

School of Biological Sciences, University of Bristol, Bristol, UK.

Invasive freshwater fishes are known to readily hybridize with indigenous congeneric species, driving loss of unique and irreplaceable genetic resources. Here we reveal that newly discovered (2013-2016) evolutionarily significant populations of Korogwe tilapia (Oreochromis korogwe) from southern Tanzania are threatened by hybridization with the larger invasive Nile tilapia (Oreochromis niloticus). We use a combination of morphology, microsatellite allele frequencies and whole genome sequences to show that O. korogwe from southern lakes (Nambawala, Rutamba and Mitupa) are distinct from geographically disjunct populations in northern Tanzania (Zigi River and Mlingano Dam). We also provide genetic evidence of O. korogwe × niloticus hybrids in three southern lakes and demonstrate heterogeneity in the extent of admixture across the genome. Finally, using the least admixed genomic regions we estimate that the northern and southern O. korogwe populations most plausibly diverged ~140,000 years ago, suggesting that the geographical separation of the northern and southern groups is not a result of a recent translocation, and instead these populations represent independent evolutionarily significant units. We conclude that these newly discovered and phenotypically unique cichlid populations are already threatened by hybridization with an invasive species, and propose that these irreplaceable genetic resources would benefit from conservation interventions.
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http://dx.doi.org/10.1111/mec.15638DOI Listing
February 2021

Toward an Integrated Understanding of the Youth Sport System.

Res Q Exerc Sport 2020 Sep 22:1-15. Epub 2020 Sep 22.

Utah State University.

The aim of the present article is to outline a heuristic model that facilitates movement toward an integrated understanding of the youth sport system. We define the as the set of interdependent persons and contexts that influence and are influenced by an athlete in youth sport. Our model builds directly from a systems perspective, and its tenets of holism, feedback loops, and roles. Specifically, we argue that the persons and contexts that surround an athlete in youth sport should be examined collectively, self-correct over time, and take on certain functions that are negotiated over time. The model extends past contributions toward integration by outlining how proximal and distal processes within youth sport can be studied in a more unified way. Looking forward, research designed to capture the nuanced ways persons and contexts influence and are influenced by one another in youth sport will be best positioned to impact theory and practice in meaningful ways.
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http://dx.doi.org/10.1080/02701367.2020.1810847DOI Listing
September 2020

Concept Analysis of Relatedness in Physical Activity Among Adolescents.

J Pediatr Nurs 2020 Nov - Dec;55:e293-e304. Epub 2020 Jul 16.

Department of Kinesiology, Michigan State University, MI, United States of America.

Aim: This analysis seeks to clarify the concept of relatedness in physical activity (PA) among adolescents.

Background: Health-related behavior research highlights the importance of focusing on individual psychological needs such as relatedness in PA to improve adolescents' motivation toward PA. Although relatedness in PA has been associated with PA participation among adolescents, a thorough analysis of the concept is lacking. Conceptual clarification of relatedness in the context of PA is needed for promoting consistency between conceptual and operational definitions and refining empirical measurement.

Design: The 6-steps of Rodgers' (2000) evolutionary method of concept analysis was used to analyze the data and identify attributes, surrogate/related terms, antecedents, and consequences of the relatedness concept.

Method: Several databases were used to extract relevant articles. A total of 113 were identified. Forty articles met the inclusion criteria. In addition, twenty-six articles were included through other sources. The review process yielded a final set of 66 articles.

Result: A refined definition of relatedness in PA is an adolescent's perception of feeling socially connected with significant people in a reciprocal, caring, and trusting relationship that is a self-system process and promotes a sense of belonging and internalization within PA contexts. Attributes, surrogate/related terms, antecedents and consequences of relatedness in PA were identified from extant literature.

Conclusion: This comprehensive analysis provides a clarification of the conceptual definition of relatedness in PA among adolescents. The concept can guide nurses in designing interventions to improve health behavior or promoting changes in health policy. Future research is needed to refine operational definitions of relatedness so that they represent the defining attributes of the concept.
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http://dx.doi.org/10.1016/j.pedn.2020.06.005DOI Listing
July 2020

A Metabolomics Approach to Screening for Autism Risk in the Children's Autism Metabolome Project.

Autism Res 2020 08 18;13(8):1270-1285. Epub 2020 Jun 18.

The MIND Institute and Department of Psychiatry and Behavioral Sciences, University of California Davis, Davis, California, USA.

Autism spectrum disorder (ASD) is biologically and behaviorally heterogeneous. Delayed diagnosis of ASD is common and problematic. The complexity of ASD and the low sensitivity of available screening tools are key factors in delayed diagnosis. Identification of biomarkers that reduce complexity through stratification into reliable subpopulations can assist in earlier diagnosis, provide insight into the biology of ASD, and potentially suggest targeted interventions. Quantitative metabolomic analysis was performed on plasma samples from 708 fasting children, aged 18 to 48 months, enrolled in the Children's Autism Metabolome Project (CAMP). The primary goal was to identify alterations in metabolism helpful in stratifying ASD subjects into subpopulations with shared metabolic phenotypes (i.e., metabotypes). Metabotypes associated with ASD were identified in a discovery set of 357 subjects. The reproducibility of the metabotypes was validated in an independent replication set of 351 CAMP subjects. Thirty-four candidate metabotypes that differentiated subsets of ASD from typically developing participants were identified with sensitivity of at least 5% and specificity greater than 95%. The 34 metabotypes formed six metabolic clusters based on ratios of either lactate or pyruvate, succinate, glycine, ornithine, 4-hydroxyproline, or α-ketoglutarate with other metabolites. Optimization of a subset of new and previously defined metabotypes into a screening battery resulted in 53% sensitivity (95% confidence interval [CI], 48%-57%) and 91% specificity (95% CI, 86%-94%). Thus, our metabolomic screening tool detects more than 50% of the autistic participants in the CAMP study. Further development of this metabolomic screening approach may facilitate earlier referral and diagnosis of ASD and, ultimately, more targeted treatments. LAY SUMMARY: Analysis of a selected set of metabolites in blood samples from children with autism and typically developing children identified reproducible differences in the metabolism of about half of the children with autism. Testing for these differences in blood samples can be used to help screen children as young as 18 months for risk of autism that, in turn, can facilitate earlier diagnoses. In addition, differences may lead to biological insights that produce more precise treatment options. We are exploring other blood-based molecules to determine if still a higher percentage of children with autism can be detected using this strategy. Autism Res 2020, 13: 1270-1285. © 2020 The Authors. Autism Research published by International Society for Autism Research published by Wiley Periodicals LLC.
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http://dx.doi.org/10.1002/aur.2330DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7496373PMC
August 2020

Is there a glass ceiling at national trauma meetings?

Am J Surg 2021 01 19;221(1):222-226. Epub 2020 May 19.

University of Pennsylvania Division of Traumatology, Surgical Critical Care, and Emergency Surgery, 51 N 39th St, MOB 1st floor Suite 120, Philadelphia, PA, 19104, USA. Electronic address:

Background: The purpose of this study was to evaluate the roles of women at national trauma meetings.

Methods: Available scientific programs for the American Association for the Surgery of Trauma (2013-19), Eastern Association for the Surgery of Trauma (2010-19), and Western Trauma Association (2010-19) as well as the Scudder Oration at the American College of Surgeons (1963-2019), were reviewed for names of participants and categorized by gender.

Results: Women made up 963 of 2746 (35.1%) of presenters, 252 of 1020 (24.7%) of discussants, 116 of 622 (18.6%) of moderators of scientific sessions, 189 of 707 (26.7%) of panelists, and 69 of 254 (27.2%) of panel moderators. Only 12 of 126 (9.5%) of named lectures or presidential addresses were given by women.

Conclusions: The low rate of female named speakers suggests that there remains a "glass ceiling" when it comes to upper-level participation in national trauma meetings.
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http://dx.doi.org/10.1016/j.amjsurg.2020.05.018DOI Listing
January 2021

Adolescent Autonomous Motivation for Physical Activity: A Concept Analysis.

J Pediatr Nurs 2020 Sep - Oct;54:e36-e46. Epub 2020 May 23.

Michigan State University Kinesiology, United States. Electronic address:

Purpose: The purpose of this concept analysis is to develop a clear definition of adolescent autonomous motivation for physical activity (PA) based on all existing theoretical and operational definitions of autonomous motivation noted in the literature. For providers, understanding this is essential to elucidate why some adolescents choose to participate in a health-promoting behavior like PA. Researchers need to identify if they are evaluating autonomous motivation or a different type.

Methods: Rodgers' Evolutionary Method of concept analysis was used. PubMed, CINAHL, ERIC, PsychInfo, and Sport Discus were searched.

Results: No concept analysis of adolescent autonomous motivation for PA was found. Autonomous motivation may include intrinsic motivation and two forms of extrinsic motivation, integrated and identified behavioral regulations. Defining attributes include being: 1) dynamic and 2) on a continuum. Adolescent autonomous motivation for PA is a personal desire to attain PA because the behavior is fun and enjoyable, or it is an important part of how the adolescent self-identifies. The adolescent views the self as being healthy so maintains a healthy lifestyle; or views the self as athletic so needs to attain adequate MVPA.

Conclusion: Findings are that an autonomy-supportive environment and positive perceptions of PA are needed in order to have the outcome of increased PA. The information may be helpful for promoting consistency of measurement across disciplines. Future research with adolescents is warranted to examine underlying differences between males and females, by age, weight status, and developmental stage.

Practice Implications: An in-depth understanding is needed for providers who are interested in developing interventions to assist adolescents in regularly attaining adequate PA.
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http://dx.doi.org/10.1016/j.pedn.2020.04.020DOI Listing
May 2020

An algorithm for random match probability calculation from peptide sequences.

Forensic Sci Int Genet 2020 Jul 6;47:102295. Epub 2020 Apr 6.

Center for Human Identification, University of North Texas Health Science Center, Fort Worth, TX, United states.

For the past three decades, forensic genetic investigations have focused on elucidating DNA signatures. While DNA has a number of desirable properties (e.g., presence in most biological materials, an amenable chemistry for analysis and well-developed statistics), DNA also has limitations. DNA may be in low quantity in some tissues, such as hair, and in some tissues it may degrade more readily than its protein counterparts. Recent research efforts have shown the feasibility of performing protein-based human identification in cases in which recovery of DNA is challenged; however, the methods involved in assessing the rarity of a given protein profile have not been addressed adequately. In this paper an algorithm is proposed that describes the computation of a random match probability (RMP) resulting from a genetically variable peptide signature. The approach described herein explicitly models proteomic error and genetic linkage, makes no assumptions as to allelic drop-out, and maps the observed proteomic alleles to their expected protein products from DNA which, in turn, permits standard corrections for population structure and finite database sizes. To assess the feasibility of this approach, RMPs were estimated from peptide profiles of skin samples from 25 individuals of European ancestry. 126 common peptide alleles were used in this approach, yielding a mean RMP of approximately 10.
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http://dx.doi.org/10.1016/j.fsigen.2020.102295DOI Listing
July 2020

A Targeted Metabolomics-Based Assay Using Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes Identifies Structural and Functional Cardiotoxicity Potential.

Toxicol Sci 2020 04;174(2):218-240

Stemina Biomarker Discovery, Inc, Madison, Wisconsin.

Implementing screening assays that identify functional and structural cardiotoxicity earlier in the drug development pipeline has the potential to improve safety and decrease the cost and time required to bring new drugs to market. In this study, a metabolic biomarker-based assay was developed that predicts the cardiotoxicity potential of a drug based on changes in the metabolism and viability of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM). Assay development and testing was conducted in 2 phases: (1) biomarker identification and (2) targeted assay development. In the first phase, metabolomic data from hiPSC-CM spent media following exposure to 66 drugs were used to identify biomarkers that identified both functional and structural cardiotoxicants. Four metabolites that represent different metabolic pathways (arachidonic acid, lactic acid, 2'-deoxycytidine, and thymidine) were identified as indicators of cardiotoxicity. In phase 2, a targeted, exposure-based biomarker assay was developed that measured these metabolites and hiPSC-CM viability across an 8-point concentration curve. Metabolite-specific predictive thresholds for identifying the cardiotoxicity potential of a drug were established and optimized for balanced accuracy or sensitivity. When predictive thresholds were optimized for balanced accuracy, the assay predicted the cardiotoxicity potential of 81 drugs with 86% balanced accuracy, 83% sensitivity, and 90% specificity. Alternatively, optimizing the thresholds for sensitivity yields a balanced accuracy of 85%, 90% sensitivity, and 79% specificity. This new hiPSC-CM-based assay provides a paradigm that can identify structural and functional cardiotoxic drugs that could be used in conjunction with other endpoints to provide a more comprehensive evaluation of a drug's cardiotoxicity potential.
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http://dx.doi.org/10.1093/toxsci/kfaa015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7098380PMC
April 2020

Molecular level study of hot water extracted green tea buried in soils - a proxy for labile soil organic matter.

Sci Rep 2020 01 30;10(1):1484. Epub 2020 Jan 30.

EaStChem, School of Chemistry, University of Edinburgh, David Brewster Rd, Edinburgh, EH9 3FJ, UK.

Understanding the composition of soil organic matter (SOM) is vital to our understanding of how soils form, evolve and respond to external stimuli. The shear complexity of SOM, an inseparable mixture of thousands of compounds hinders the determination of structure-function relationships required to explore these processes on a molecular level. Litter bags and soil hot water extracts (HWE) have frequently been used to study the transformation of labile SOM, however these are still too complex to examine beyond compound classes. In this work, a much simpler mixture, HWE buried green tea, was investigated by Nuclear Magnetic Resonance (NMR) spectroscopy and Fourier Transform Ion Cyclotron Resonance Mass Spectrometry (FT-ICR-MS), as a proxy for labile SOM. Changes induced by the burial over 90 days in a grassland, woodland and two peatland sites, one damaged by drainage and one undergoing restoration by drain-blocking, were analysed. Major differences between the extracts were observed on the level of compound classes, molecular formulae and specific molecules. The causes of these differences are discussed with reference to abiotic and biotic processes. Despite the vastly different detection limits of NMR and MS, chemometric analysis of the data yielded identical separation of the samples. These findings provide a basis for the molecular level interrogation of labile SOM and C-cycling processes in soils.
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http://dx.doi.org/10.1038/s41598-020-58325-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6992787PMC
January 2020

The Effects of Cross-Border Transport on Patients With Tibia Fractures.

J Surg Res 2020 05 8;249:91-98. Epub 2020 Jan 8.

Division of Trauma, Surgical Critical Care, Burns and Acute Care Surgery, Department of Surgery, University of California San Diego, San Diego, California. Electronic address:

Background: Tibia fractures are common after trauma. Prior studies have shown that delays in treatment are associated with poor outcomes. A subpopulation of our patients are transported from Mexico, adding barriers to prompt care. We hypothesized that patients with tibia fractures crossing from Mexico would have delays in treatment and subsequently worse outcomes.

Methods: The trauma registry of an American College of Surgeons-verified level 1 trauma center was retrospectively reviewed for all tibia fractures admitted from 2010 to 2015. Data collection included demographics, country of injury, characterization of injuries, interventions, complications, and outcomes. Patients were subdivided into those injured in the United States and in Mexico, and the two groups were compared.

Results: A total of 498 patients were identified, 440 from the United States and 58 from Mexico. Mexico patients were more severely injured overall, with higher injury severity scores and a higher percentage of patients with abbreviated injury scale scores ≥3 for both head and chest regions. Mexico patients had longer times from injury to admission, as well as increased times to both debridement of open fractures and operative fixation after admission. On subgroup analysis of patients with isolated tibia fractures (other system abbreviated injury scale < 3), times from arrival to treatment and injury severity score were no longer statistically different.

Conclusions: Patients crossing the border from Mexico with tibia fractures have delays in time to admission and from admission to operative management, although this is primarily due to other severe injuries. Ongoing systems development is required to minimize delays in care and optimize outcomes.
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http://dx.doi.org/10.1016/j.jss.2019.12.011DOI Listing
May 2020

Artificial fingerprints for cross-comparison of forensic DNA and protein recovery methods.

PLoS One 2019 3;14(10):e0223170. Epub 2019 Oct 3.

Signature Science, LLC, Austin, Texas, United States of America.

Quantitative genomic and proteomic evaluation of human latent fingerprint depositions represents a challenge within the forensic field, due to the high variability in the amount of DNA and protein initially deposited. To better assess recovery techniques for touch depositions, we present a method to produce simple and customizable artificial fingerprints. These artificial fingerprint samples include the primary components of a typical latent fingerprint, specifically sebaceous fluid, eccrine perspiration, extracellular DNA, and proteinaceous epidermal skin material (i.e., shed skin cells). A commercially available emulsion of sebaceous and eccrine perspiration material provides a chemically-relevant suspension solution for fingerprint deposition, simplifying artificial fingerprint production. Extracted human genomic DNA is added to accurately mimic the extracellular DNA content of a typical latent print and comparable DNA yields are recovered from the artificial prints relative to human prints across surface types. Capitalizing on recent advancements in the use of protein sequence identification for human forensic analysis, these samples also contain a representative quantity of protein, originating from epidermal skin cells collected from the fingers and palms of volunteers. Proteomic sequencing by liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis indicates a high level of protein overlap between artificial and latent prints. Data are available via ProteomeXchange with identifier PXD015445. By including known quantities of DNA and protein into each artificial print, this method enables total DNA and protein recovery to be quantitatively assessed across different sample collection and extraction methods to better evaluate extraction efficiency. Collectively, these artificial fingerprint samples are simple to make, highly versatile and customizable, and accurately represent the biochemical composition and biological signatures of human fingerprints.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0223170PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6776342PMC
March 2020

Achieving gastroresistance without coating: Formulation of capsule shells from enteric polymers.

Eur J Pharm Biopharm 2019 Nov 18;144:174-179. Epub 2019 Sep 18.

Department of Pharmacy, School of Applied Sciences, University of Huddersfield, Queensgate, Huddersfield HD1 3DH, United Kingdom. Electronic address:

Capsules are a widely used oral dosage form due to their simplicity and ease of manufacture. They are equally popular for both pharmaceutical and nutraceutical products and since they do not need extensive formulation development, it is a dosage form of choice for new drugs undergoing animal or clinical trials. In addition to the standard hard-gelatin or cellulose-based vegetarian capsules, functional capsules such as those with built-in gastroresistance would be of great value. In this work, commonly used enteric polymers were investigated for the production of hard-capsules. The polymers used in this study included cellulose derivatives (HPMC AS-LF and HP-55) and acrylic/methacrylic acid derivatives (EUDRAGIT L100 and S100). A range of concentrations of polymers and plasticisers were tested to optimise the formulation for the production of capsule shells with desirable physicochemical and gastroresistance characteristics. Drug release from optimised capsules produced from HPMC AS-LF, HP-55, EUDRAGIT L100 and S100 was shown to be comparable to drug release from corresponding polymer-coated tablets in both compendial and physiological bicarbonate buffer. In summary, herein we report a simple method for producing enteric capsule shells which do not need an additional coating step which, if validated at large scale, can significantly reduce the cost of manufacturing of conventional enteric coated dosage forms. These capsules are also likely to improve the inter-tablet variability in post-gastric drug release inherent in conventional dosage forms due to coating variability.
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http://dx.doi.org/10.1016/j.ejpb.2019.09.015DOI Listing
November 2019

Nicotiana tabacum pollen-pistil interactions show unexpected spatial and temporal differences in pollen tube growth among genotypes.

Plant Reprod 2019 12 29;32(4):341-352. Epub 2019 Jul 29.

Department of Horticultural Science, University of Minnesota, Saint Paul, MN, 55108, USA.

Key Message: This research revealed diverse PTG rates among intraspecific pollen-pistil interactions that showed variable dependency on the stigma and mature TT. Pollen-pistil interactions regulate pollen tube growth (PTG) rates and are determinants of fertilization and seed set. This research focuses on the diversity of intraspecific PTG rates and the spatial and temporal regulation of PTG among Nicotiana tabacum genotypes. Nonrandom mating within self-compatible species has been noted, but little is known on the mechanisms involved. To begin research on nonrandom mating, we took advantage of the model reproductive system of N. tabacum and used seventeen diverse N. tabacum genotypes in a complete pollination diallel to measure the diversity of intraspecific pollen-pistil interactions. The 289 intraspecific interactions showed surprisingly large differences in PTG rates. The interaction between specific males and females resulted in 18 specific combining abilities that were significantly different, indicating the importance of the specific genotype interaction in regulating intraspecific PTG. No single female or male genotype exerted overall control of PTG rates, as determined by a general combining ability analysis. Slow and fast pollen-pistil interactions showed spatial differences in growth rates along the style. Slower interactions had a slower initial PTG rate while fast interactions had faster consistent rates of growth indicating spatial regulation of PTG in the pistil. Removal of the stigma or the mature transmitting tissue (TT) showed the tissue-specific component of PTG regulation. Stigma removal resulted in slower or no change in PTG rate depending on the pollen and pistil genotypes. Removal of the TT, which necessitated removal of the stigma, showed no change, slower or unexpectedly, increased growth rates relative to growth rates without a stigma. These data show the diverse nature of pollen-pistil interactions in N. tabacum genotypes providing a system to further investigate the regulation of PTG.
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http://dx.doi.org/10.1007/s00497-019-00375-8DOI Listing
December 2019

Respect your elders: effects of ageing on intracranial pressure monitor use in traumatic brain injury.

Trauma Surg Acute Care Open 2019 17;4(1):e000306. Epub 2019 Jun 17.

Division of Trauma, Surgical Critical Care, Burns and Acute Care Surgery, Department of Surgery, UC San Diego School of Medicine, San Diego, California, USA.

Background: The Brain Trauma Foundation recommends intracranial pressure (ICP) monitor placement for patients with severe traumatic brain injury (TBI). Adherence with these guidelines in elderly patients is unknown. We hypothesized that disparities in ICP monitor placement would exist based on patient age.

Methods: Using the National Trauma Data Bank (2010-2014), we identified patients admitted for blunt TBI with admission Glasgow Coma Scale (GCS) scores of 3-8. Patients were excluded if they had a non-Head Abbreviated Injury Scale (AIS) score ≥3, hospital length of stay <24 hours or were discharged from the emergency department. Demographic data, ICP monitor placement, GCS, AIS-Head, Injury Severity Score, and outcome measures were collected. Propensity score matching between ICP monitor and non-ICP monitor patients was used for logistic regression and Cox multivariate regression analyses.

Results: Of the 30 710 patients with blunt TBI with GCS scores of 3-8 included in our study, 4093 were treated with an ICP monitor. ICP monitor placement rates significantly decreased with increasing age. Multivariable analysis demonstrated that patients treated with an ICP monitor were more likely to be younger, male, have private/commercial insurance, and receive care at an institution with three or more neurosurgeons.

Conclusion: Patients ≥65 years of age with severe blunt TBI are less likely to be treated with an ICP monitor than younger patients. Age disparities in adherence to Brain Trauma Foundation guidelines may alter the outcomes for patients with severe TBI.

Level Of Evidence: Level IV.
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http://dx.doi.org/10.1136/tsaco-2019-000306DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6598557PMC
June 2019

Readmissions After Acute Hospitalization for Traumatic Brain Injury.

J Surg Res 2019 12 12;244:332-337. Epub 2019 Jul 12.

Division of Trauma, Surgical Critical Care, Burns and Acute Care Surgery, Department of Surgery, University of California San Diego Health, San Diego, California. Electronic address:

Background: Traumatic brain injury (TBI) is associated with functional deficits, impaired cognition, and medical complications that continue well after the initial injury. Many patients seek medical care at other health care facilities after discharge, rather than returning to the admitting trauma center, making assessment of readmission rates and readmission diagnoses difficult to determine. The objective of this study was to determine the incidence and factors associated with readmission to any acute care hospital after an index admission for TBI.

Materials And Methods: The Nationwide Readmission Database was queried for all patients admitted with a TBI during the first 3 mo of 2015. Nonelective readmissions for this population were then collected for the remainder of 2015. Patients who died during the index admission were excluded. Demographic data, injury mechanism, type of TBI, the number of readmissions, days from discharge to readmission, readmission diagnosis, and mortality were studied.

Results: Of the 15,277 patients with an index admission for TBI, 5296 patients (35%) required at least 1 readmission. Forty percent of readmissions occurred within the first 30 d after discharge from the index trauma admission. The most common primary diagnosis on readmission was SDH, followed by septicemia, urinary tract infection, and aspiration. Readmission rates increased with age, with 75% of readmissions occurring in patients aged >65 y. Initial discharge to a skilled nursing facility (Relative Risk [RR], 1.60) or leaving the hospital against medical advice (RR, 1.59) increased the risk of readmission. Patients with fall as their mechanism of injury and a subdural hematoma were more likely to require readmission compared with other types of mechanisms with TBI (RR, 1.59 and RR, 1.21, respectively; P < 0.001). Notably, the first readmission was to a different hospital for 39.5% of patients and 46.9% of patients had admissions to at least one facility outside that of their original presentation.

Conclusions: Hospital readmission is common for patients discharged after TBI. Elderly patients who fall with resultant subdural hematoma are at especially high risk for complications and readmission. Understanding potentially preventable causes for readmission can be used to guide discharge planning pathways to decrease morbidity in this patient population.
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http://dx.doi.org/10.1016/j.jss.2019.06.071DOI Listing
December 2019

Improving the patient discharge process: implementing actions derived from a soft systems methodology study.

Health Syst (Basingstoke) 2019 2;8(2):117-133. Epub 2018 Oct 2.

UCL Centre for Systems Engineering.

In the period from January 2013 to July 2014, three process change initiatives were undertaken at a major UK hospital to improve the patient discharge process. These initiatives were inspired by the findings of a study of the discharge process using Soft Systems Methodology. The first initiative simplified time-consuming paperwork and the second introduced more regular reviews of patient progress through daily multi-disciplinary "Situation Reports". These two initiatives were undertaken in parallel across the hospital, and for the average patient they jointly led to a 41% reduction between a patient being declared medically stable and their being discharged from the hospital. The third initiative implemented more proactive alerting of Social Care Practitioners to patients with probable social care needs at the front door, and simplified capture of important patient information (using a "SPRING" form). This initiative saw a 20% reduction in total length of stay for 88 patients on three wards where the SPRING form was used, whilst 248 patients on five control wards saw no significant change in total length of stay in the same period. Taken together, these initiatives have reduced total length of stay by 67% from 55.8 days to 18.6 days for the patients studied.
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http://dx.doi.org/10.1080/20476965.2018.1524405DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6598519PMC
October 2018

The co-design, implementation and evaluation of a serious board game 'PlayDecide patient safety' to educate junior doctors about patient safety and the importance of reporting safety concerns.

BMC Med Educ 2019 Jun 25;19(1):232. Epub 2019 Jun 25.

Health Sciences Centre, School of Nursing, Midwifery and Health Systems, College of Health Sciences, University College Dublin, Belfield, Dublin 4, Ireland.

Background: We believe junior doctors are in a unique position in relation to reporting of incidents and safety culture. They are still in training and are also 'fresh eyes' on the system providing valuable insights into what they perceive as safe and unsafe behaviour. The aim of this study was to co-design and implement an embedded learning intervention - a serious board game - to educate junior doctors about patient safety and the importance of reporting safety concerns, while at the same time shaping a culture of responsiveness from senior medical staff.

Methods: A serious game based on the PlayDecide framework was co-designed and implemented in two large urban acute teaching hospitals. To evaluate the educational value of the game voting on the position statements was recorded at the end of each game by a facilitator who also took notes after the game of key themes that emerged from the discussion. A sample of players were invited on a voluntary basis to take part in semi-structured interviews after playing the game using Flanagan's Critical Incident Technique. A paper-based questionnaire on 'Safety Concerns' was developed and administered to assess pre-and post-playing the game reporting behaviour. Dissemination workshops were held with senior clinicians to promote more inclusive leadership behaviours and responsiveness to junior doctors raising of safety concerns from senior clinicians.

Results: The game proved to be a valuable patient safety educational tool and proved effective in encouraging deep discussion on patient safety. There was a significant change in the reporting behaviour of junior doctors in one of the hospitals following the intervention.

Conclusion: In healthcare, limited exposure to patient safety training and narrow understanding of safety compromise patients lives. The existing healthcare system needs to value the role that junior doctors and others could play in shaping a positive safety culture where reporting of all safety concerns is encouraged. Greater efforts need to be made at hospital level to develop a more pro-active safe and just culture that supports and encourages junior doctors and ultimately all doctors to understand and speak up about safety concerns.
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http://dx.doi.org/10.1186/s12909-019-1655-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6593521PMC
June 2019

Atypical lipomatous tumour of the oesophagus.

J Surg Case Rep 2019 Jun 19;2019(6):rjz192. Epub 2019 Jun 19.

The Queen Elizabeth Hospital, Bridgetown, Barbados.

Atypical lipomatous tumours (ALT) of the oesophagus are rare malignant tumours that are found most commonly in the cervical oesophagus. They are commonly misdiagnosed as giant fibrovascular polyps of the oesophagus (GFP). The differentiation between these clinical entities is important as ALTs are malignant tumours with the potential for local recurrence and metastases. We present a case of an ALT which was misdiagnosed as a GFP. The correct diagnosis was made on histological examination of the resected specimen, and confirmed by immunohistochemistry. The tumour cells extended to involve the resection margins, highlighting the need to consider this diagnosis when dealing with all oesophageal polyps, and ensure complete resection of these tumours.
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http://dx.doi.org/10.1093/jscr/rjz192DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6582405PMC
June 2019

Evolution of Video Assisted Thoracoscopic Surgery in the Caribbean.

Int J Surg 2019 Dec 28;72S:19-22. Epub 2019 May 28.

University Hospital of the West Indies, Mona, Jamaica. Electronic address:

Video Assisted Thoracoscopic Surgery (VATS) has become the mainstay of thoracic procedures in developed countries. The benefits of VATS over a thoracotomy, and its equivalency in oncologic resections has been clearly established. The introduction of this minimally invasive approach to thoracic surgery to the Caribbean has been a slow progression. The main restrictions to the full implantation of VATS in the resource poor Caribbean setting has been obtaining material resources, developing the necessary human resources, and the small case loads. Each territory has adopted its own innovative approach to getting VATS programmes started. We review the current status of VATS in the English speaking Caribbean.
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http://dx.doi.org/10.1016/j.ijsu.2019.05.012DOI Listing
December 2019