Publications by authors named "Alison Smith"

451 Publications

Mass shootings in the United States: Results from a five-year demographic analysis.

Injury 2022 Jan 5. Epub 2022 Jan 5.

Louisiana State University Health Sciences Center - New Orleans, LA USA. Electronic address:

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http://dx.doi.org/10.1016/j.injury.2022.01.004DOI Listing
January 2022

Management of Renal Artery-Inferior Vena Cava Fistula Following Nephrectomy for Penetrating Trauma.

Vasc Endovascular Surg 2022 Jan 13:15385744211068623. Epub 2022 Jan 13.

Department of Surgery, Louisiana State University Health Sciences Center, New Orleans, LA, USA.

Renal artery to inferior vena cava fistula is a rare event postnephrectomy. We report a case of an adult male in whom a renal artery to inferior vena cava fistula was detected on non-invasive studies following nephrectomy for penetrating trauma. A fistula between the right renal artery and inferior vena cava was confirmed with diagnostic angiography. The fistula was successfully embolized using microcoils. This case highlights the importance of exploring retroperitoneal hematomas secondary to penetrating trauma.
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http://dx.doi.org/10.1177/15385744211068623DOI Listing
January 2022

How Did the COVID-19 Pandemic Affect Trauma Volume at an Urban Level I Trauma Center?

Am Surg 2022 Jan 3:31348211054075. Epub 2022 Jan 3.

Department of Surgery, 12258LSU New Orleans, New Orleans, LA, USA.

Introduction: The COVID-19 pandemic changed the face of health care worldwide. While the impacts from this catastrophe are still being measured, it is important to understand how this pandemic impacted existing health care systems. As such, the objective of this study was to quantify its effects on trauma volume at an urban Level 1 trauma center in one of the earliest and most significantly affected US cities.

Methods: A retrospective chart review of consecutive trauma patients admitted to a Level 1 trauma center from January 1, 2017 to December 31, 2020 was completed. The total trauma volume in the years prior to the pandemic (2017-2019) was compared to the volume in 2020. These data were then further stratified to compare quarterly volume across all 4 years.

Results: A total of 4138 trauma patients were treated in the emergency room throughout 2020 with 4124 seen during 2019, 3774 during 2018, and 3505 during 2017 in the pre-COVID-19 time period. No significant difference in the volume of minor trauma or trauma transfers was observed ( < .05). However, there was a significant increase in the number of major traumas in 2020 as compared to prior years (38.5% vs 35.6%, < .01) and in the volume of penetrating trauma (29.1% vs 24.0%, < .01).

Discussion: During the COVID-19 outbreak, trauma remained a significant health care concern. This study found an increase in volume of penetrating trauma, specifically gunshot wounds throughout 2020. It remains important to continue to devote resources to trauma patients during the ongoing COVID-19 pandemic.
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http://dx.doi.org/10.1177/00031348211054075DOI Listing
January 2022

A dominant mutation in β-AMYLASE1 disrupts nighttime control of starch degradation in Arabidopsis leaves.

Plant Physiol 2021 Dec 27. Epub 2021 Dec 27.

John Innes Centre, Norwich Research Park, Norwich NR4 7UH, United Kingdom.

Arabidopsis (Arabidopsis thaliana) leaves possess a mechanism that couples the rate of night-time starch degradation to the anticipated time of dawn, thus preventing premature exhaustion of starch and night-time starvation. To shed light on the mechanism, we screened a mutagenized population of a starvation reporter line and isolated a mutant that starved prior to dawn. The mutant had accelerated starch degradation, and the rate was not adjusted to time of dawn. The mutation responsible led to a single amino acid change (S132N) in the starch degradation enzyme BETA-AMYLASE1 (BAM1, mutant allele named bam1-2D), resulting in a dominant, gain-of-function phenotype. Complete loss of BETA-AMYLASE1 (in bam1-1) did not affect rates of starch degradation, while expression of BAM1(S132N) in bam1-1 recapitulated the accelerated starch degradation phenotype of bam1-2D. In vitro analysis of recombinant BAM1 and BAM1(S132N) proteins revealed no differences in kinetic or stability properties, but in leaf extracts BAM1(S132N) apparently had a higher affinity than BAM1 for an established binding partner required for normal rates of starch degradation, LIKE SEX FOUR1 (LSF1). Genetic approaches showed that BAM1(S132N) itself is likely responsible for accelerated starch degradation in bam1-2D and that this activity requires LSF1. Analysis of plants expressing BAM1 with alanine or aspartate rather than serine at position 132 indicated that the gain-of-function phenotype is not related to phosphorylation status at this position. Our results strengthen the view that control of starch degradation in wild-type plants involves dynamic physical interactions of degradative enzymes and related proteins with a central role for complexes containing LSF1.
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http://dx.doi.org/10.1093/plphys/kiab603DOI Listing
December 2021

Information Based Diagnostic for Genetic Variance Parameter Estimation in Multi-Environment Trials.

Front Plant Sci 2021 7;12:785430. Epub 2021 Dec 7.

Centre for Biometrics and Data Science for Sustainable Primary Industries, School of Mathematics and Applied Statistics, National Institute for Applied Statistics Research Australia, University of Wollongong, Wollongong, NSW, Australia.

Plant breeding programs evaluate varieties in series of field trials across years and locations, referred to as multi-environment trials (METs). These are an essential part of variety evaluation with the key aim of the statistical analysis of these datasets to accurately estimate the variety by environment (VE) effects. It has previously been thought that the number of varieties in common between environments, referred to as "variety connectivity," was a key driver of the reliability of genetic variance parameter estimation and that this in turn affected the reliability of predictions of VE effects. In this paper we have provided the link between the objectives of this work and those in model-based experimental design. We propose the use of the -optimality criterion as a diagnostic to capture the information available for the residual maximum likelihood (REML) estimation of the genetic variance parameters. We demonstrate the methods for a dataset with pedigree information as well as evaluating the performance of the diagnostic using two simulation studies. This measure is shown to provide a superior diagnostic to the traditional connectivity type measure in the sense of better forecasting the uncertainty of genetic variance parameter estimates.
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http://dx.doi.org/10.3389/fpls.2021.785430DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8688772PMC
December 2021

Cycloserine and Linezolid for Tuberculosis Meningitis: Pharmacokinetic Evidence of Potential Usefulness.

Clin Infect Dis 2021 Nov 29. Epub 2021 Nov 29.

National Center for Tuberculosis and Lung Diseases, Tbilisi, Georgia.

Background: The ability of anti-tuberculosis drugs to cross the blood brain barrier and reach the central nervous system (CNS) is critical to their effectiveness in treating tuberculosis meningitis (TBM). We sought to fill a critical knowledge gap by providing data on the ability of new and repurposed anti-tuberculosis drugs to penetrate into the cerebrospinal fluid (CSF).

Methods: We conducted a clinical pharmacology study among patients treated for TBM in Tbilisi,Georgia from January 2019 until January 2020. Serial serum and CSF samples were collected while patients were hospitalized. CSF was collected from routine lumbar punctures with the timing of the lumbar puncture alternating between 2 and 6 hours to capture early and late CSF penetration.

Results: A total of seventeen patients treated for TBM (8 with confirmed diease) were included; all received linezolid, with a subset receiving cycloserine (5), clofazimine (5), delamanid (4) and bedaquiline (2). All CSF measurements of bedaquiline (12), clofazimine (24), and delaminid (19) were below the limit of detection. The median CSF concentrations of cycloserine at 2 and 6 hours were 15.90 and 15.10 µg/ml with adjusted CSF/serum ratios of 0.52 and 0.66. CSF concentrations of linezolid were 0.90 and 3.14 µg/ml at 2 and 6 hours, with adjusted CSF/serum ratios of 0.25 and 0.59, respectively. CSF serum linezolid concentrations were not impacted by rifampin coadministration.

Conclusions: Based on moderate to high CSF penetration, linezolid and cycloserine may be effective drugs for TBM treatment while the utility of bedaquiline, delaminid and clofazimine is uncertain given their low CSF penetration.
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http://dx.doi.org/10.1093/cid/ciab992DOI Listing
November 2021

Gender disparities among medical students choosing to pursue careers in medical research: a secondary cross-sectional cohort analysis.

BMC Med Educ 2021 Nov 25;21(1):591. Epub 2021 Nov 25.

Department of Interventional Radiology, Massachusetts General Hospital, 55 Fruit Street, Boston, MA, 02114, USA.

Background: Though the proportion of women in medical schools has increased, gender disparities among those who pursue research careers still exists. In this study, we seek to better understand the main factors contributing to the existing gender disparities among medical students choosing to pursue careers in medical research.

Methods: A secondary cross-sectional cohort analysis of previously published data was conducted using a 70-item survey that was sent to 16,418 medical students at 32 academic medical centers, and was IRB exempt from the need for ethical approval at the University of Illinois at Chicago and the University of Pennsylvania. Data was collected from September 2012 to December 2014. Survey results were analyzed using chi-square tests and Cramer's V to determine gender differences in demographic characteristics (training stage, race/ethnicity, marital status, parental status, financial support, and parental career background), career sector choice, career content choice, specialty choice, foreseeable career obstacles, and perceptions about medical research careers.

Results: Female respondents were more likely to be enrolled in MD-only programs, while male respondents were more likely to be enrolled in MD/PhD programs. More male students selected academia as their first-choice career sector, while more female respondents selected hospitalist as their first-choice career sector. More female respondents identified patient care and opportunities for community service as their top career selection factors, while more male respondents identified research and teaching as their top career selection factors. Student loan burden, future compensation, and work/life balance were the most reported obstacles to pursuing a career in medical research.

Conclusions: There are many factors from a medical student's perspective that may contribute to the existing gender disparities in pursuing a career in medical research. While much progress has been made in attracting nearly equal numbers of men and women to the field of medicine, active efforts to bridge the gap between men and women in medical research careers are needed.
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http://dx.doi.org/10.1186/s12909-021-03004-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8620216PMC
November 2021

Does Time to Pelvic Fixation Influence Outcomes in Trauma Patients?

Am Surg 2021 Nov 19:31348211056266. Epub 2021 Nov 19.

Department of Surgery, 12258Louisiana State University Health Sciences Center, New Orleans, LA, USA.

Background: Pelvic fractures cause significant morbidity in the trauma population. Many factors influence time to fracture fixation. No previous study has determined the optimal time window for pelvic fixation.

Methods: A retrospective review of trauma patients with pelvic fractures from 2016 to 2020 was performed. Patients were stratified into EARLY and LATE groups, by time to fixation within 3 days or greater than 3 days whether from admission or from completion of a life-saving procedure. Unpaired Student's -test and Fisher's exact test were performed with multiple linear regression for variables with < .2 on univariate analysis.

Results: 287 patients were identified with a median fixation time of 3 days. There was no significant difference in demographics, incidence of preceding life-saving procedure, angioembolization, or mechanism of injury in the 2 groups ( > .05). Length of stay in the EARLY group was significantly reduced at 11.9 +/- .7 days compared to 18.0 +/-1.2 days in the LATE group ( < .001). There was no significant difference in rates of ventilator-associated pneumonia, deep vein thrombosis, pulmonary embolism (PE), acute kidney injury (AKI), pressure ulcer, or acute respiratory distress syndrome (ARDS) ( > .05). There were significantly more SSIs (surgical site infections) in the LATE group. After multiple linear regression adjusting for covariates of age and ISS, the difference in hospital LOS was 5.5 days (95% CI -8.0 to -3.1, < .001).

Discussion: Fixation of traumatic pelvic fractures within 3 days reduced LOS. Prospective multi-center studies will help identify additional factors to decrease time to surgery and improve patient outcomes.
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http://dx.doi.org/10.1177/00031348211056266DOI Listing
November 2021

HER2 + breast cancers evade anti-HER2 therapy via a switch in driver pathway.

Nat Commun 2021 11 18;12(1):6667. Epub 2021 Nov 18.

Human Oncology and Pathogenesis Program (HOPP), Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.

Inhibition of HER2 in HER2-amplified breast cancer has been remarkably successful clinically, as demonstrated by the efficacy of HER-kinase inhibitors and HER2-antibody treatments. Whilst resistance to HER2 inhibition is common in the metastatic setting, the specific programs downstream of HER2 driving resistance are not established. Through genomic profiling of 733 HER2-amplified breast cancers, we identify enrichment of somatic alterations that promote MEK/ERK signaling in metastatic tumors with shortened progression-free survival on anti-HER2 therapy. These mutations, including NF1 loss and ERBB2 activating mutations, are sufficient to mediate resistance to FDA-approved HER2 kinase inhibitors including tucatinib and neratinib. Moreover, resistant tumors lose AKT dependence while undergoing a dramatic sensitization to MEK/ERK inhibition. Mechanistically, this driver pathway switch is a result of MEK-dependent activation of CDK2 kinase. These results establish genetic activation of MAPK as a recurrent mechanism of anti-HER2 therapy resistance that may be effectively combated with MEK/ERK inhibitors.
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http://dx.doi.org/10.1038/s41467-021-27093-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8602441PMC
November 2021

Setting analytical performance specifications using HbA1c as a model measurand.

Clin Chim Acta 2021 Dec 16;523:407-414. Epub 2021 Oct 16.

Department of Clinical Chemistry and Endocrinology, New South Wales Health Pathology, Prince of Wales Hospital, Sydney, Australia.

Analytical performance specifications (APS) for measurands describe the minimum analytical quality requirements for their measurement. These APS are used to monitor and contain the systematic (trueness/bias) and random errors (precision/imprecision) of a laboratory measurement to ensure the results are "fit for purpose" in informing clinical decisions about managing a patient's health condition. In this review, we highlighted the wide variation in the setting of APS, using different levels of evidence, as recommended by the Milan Consensus, and approaches. The setting of a priori defined outcome-based APS for HbA1c remains challenging. Promising indirect alternatives seek to link the clinical utility of HbA1c and APS by defining statistical confidence for interpreting the laboratory values, or through simulation of clinical performance at varying levels of analytical performance. APS defined based on biological variation estimates in healthy individuals using the current formulae are unachievable by nearly all routine laboratory methods for HbA1c testing. On the other hand, the APS employed in external quality assurance programs have been progressively tightened, and greatly facilitate the improved quality of HbA1c testing. Laboratories should select the APS that fits their intended clinical use and should document the data and rationale underpinning those selections. Where possible common APS should be adopted across a region or country to facilitate the movement of patients and patient data across health care facilities.
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http://dx.doi.org/10.1016/j.cca.2021.10.016DOI Listing
December 2021

Re-visiting Drain Use in Operative Liver Trauma: A Retrospective Analysis.

J Surg Res 2022 Feb 10;270:76-84. Epub 2021 Oct 10.

Tulane University School of Medicine, Department of Surgery, New Orleans, Los Angeles.

Background: Despite the liver being one of the most frequently injured abdominal organs in trauma patients, clinical management strategies differ between trauma surgeons. Few studies have critically evaluated current practice patterns in the operative management of liver trauma. Historical studies recommended against the use of drains but there has not been a modern investigation of this issue. The objective of this study was to analyze outcomes associated with intra-operative drain use for liver trauma.

Methods: A retrospective chart review of all adult trauma patients presenting to a Level I trauma center from 2012 to 2018 was performed. Patients who underwent operative management of liver trauma were divided into groups based on whether an intra-abdominal drain was utilized and differences in outcomes between the groups were analyzed. The primary endpoint evaluated was post-operative intra-abdominal abscesses. Univariate and multivariate analyses were performed.

Results: 184 patients with operative management of liver trauma were included in the study. Closed suction drains were utilized in 26.1% of post-operative patients. Rate of intra-abdominal abscesses was significantly higher in the drain group (35.4% versus 8.8%, P < 0.001). Drains were more commonly used in patients receiving more units of PRBCs (median, 9 units [IQR 4-20] versus median 5.5 units, [IQR 2-14], P = 0.03). Drain use was found to be an independent risk factor for post-operative intra-abdominal abscess on multivariate analysis (OR 4.9, 95% CI 1.7-14, P = 0.003).

Conclusions: The results of this study support previous conclusions that drain placement for operative liver trauma is associated with increased risks of infectious complications. Drains were used in patients with more severe liver injury, intra-operative bile leaks, penetrating trauma, and increased blood transfusion requirements. Future studies should focus on the development of specific guidelines for the use of drains in liver trauma.
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http://dx.doi.org/10.1016/j.jss.2021.08.039DOI Listing
February 2022

The Algal Chloroplast as a Testbed for Synthetic Biology Designs Aimed at Radically Rewiring Plant Metabolism.

Front Plant Sci 2021 24;12:708370. Epub 2021 Sep 24.

Department of Structural and Molecular Biology, University College London, London, United Kingdom.

Sustainable and economically viable support for an ever-increasing global population requires a paradigm shift in agricultural productivity, including the application of biotechnology to generate future crop plants. Current genetic engineering approaches aimed at enhancing the photosynthetic efficiency or composition of the harvested tissues involve relatively simple manipulations of endogenous metabolism. However, radical rewiring of central metabolism using new-to-nature pathways, so-called "synthetic metabolism", may be needed to really bring about significant step changes. In many cases, this will require re-programming the metabolism of the chloroplast, or other plastids in non-green tissues, through a combination of chloroplast and nuclear engineering. However, current technologies for sophisticated chloroplast engineering ("transplastomics") of plants are limited to just a handful of species. Moreover, the testing of metabolic rewiring in the chloroplast of plant models is often impractical given their obligate phototrophy, the extended time needed to create stable non-chimeric transplastomic lines, and the technical challenges associated with regeneration of whole plants. In contrast, the unicellular green alga, is a facultative heterotroph that allows for extensive modification of chloroplast function, including non-photosynthetic designs. Moreover, chloroplast engineering in is facile, with the ability to generate novel lines in a matter of weeks, and a well-defined molecular toolbox allows for rapid iterations of the "Design-Build-Test-Learn" (DBTL) cycle of modern synthetic biology approaches. The recent development of combinatorial DNA assembly pipelines for designing and building transgene clusters, simple methods for marker-free delivery of these clusters into the chloroplast genome, and the pre-existing wealth of knowledge regarding chloroplast gene expression and regulation in further adds to the versatility of transplastomics using this organism. Herein, we review the inherent advantages of the algal chloroplast as a simple and tractable testbed for metabolic engineering designs, which could then be implemented in higher plants.
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http://dx.doi.org/10.3389/fpls.2021.708370DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8497815PMC
September 2021

Efficacy and Safety of Whole Blood Transfusion in Non-Trauma Patients.

Am Surg 2021 Sep 30:31348211048831. Epub 2021 Sep 30.

Department of Surgery, 14742University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.

Whole blood (WB) transfusion for trauma patients with severe hemorrhage has demonstrated early successful outcomes compared to conventional component therapy. The objective of this study was to demonstrate WB transfusion in the non-trauma patient. Consecutive adult patients receiving WB transfusion at a single academic institution were reviewed from February 2018 to January 2020. Outcomes measured were mortality and transfusion-related reactions. A total of 237 patients who received WB were identified with 55 (23.2%) non-trauma patients. Eight patients (14.5%) received pre-hospital WB. The most common etiology of non-traumatic hemorrhage was gastrointestinal bleeding (43.6%, n = 24/55). Approximately half of the non-trauma patients (n = 28/55) received component therapy. Transfusion-related events occurred in 3 patients. This study demonstrated that non-trauma patients could receive WB transfusions safely with infrequent transfusion-related events. Future studies should focus on determining if outcomes are improved in non-trauma patients who receive WB transfusions and defining specific transfusion criteria for this population.
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http://dx.doi.org/10.1177/00031348211048831DOI Listing
September 2021

Intent to Vaccinate SARS-CoV-2 Infected Children in US Households: A Survey.

Vaccines (Basel) 2021 Sep 21;9(9). Epub 2021 Sep 21.

Department of Pediatrics, Emory University School of Medicine, Children's Healthcare of Atlanta, Atlanta, GA 30322, USA.

A paucity of data exists evaluating a guardian's intent to vaccinate their child against COVID-19 in the United States. We administered 102 first (April-November 2020) and 45 second (December-January 2020-2021) surveys to guardians of children (<18 years) who had a laboratory-confirmed diagnosis of COVID-19 and assessed their intent to give a COVID-19 vaccine to their child, when one becomes available. The first and second surveys of the same cohort of guardians were conducted before and following the press releases detailing the adult Pfizer-BioNTech and Moderna Phase 3 results. Both surveys included an intent-to-vaccinate question using the subjective language of "if a safe and effective vaccine" became available, and a second question was added to second surveys using the objective language of "would prevent 19 of 20 people from getting disease". When using subjective language, 24 of 45 (53%) guardians endorsed vaccine administration for their children in the first survey, which decreased to 21 (46%) in the second survey. When adding objective language, acceptance of vaccination increased to 31 (69%, = 0.03). Common reasons for declining vaccination were concerns about adverse effects and/or vaccine safety. Providing additional facts on vaccine efficacy increased vaccine acceptance. Evidence-based strategies are needed to increase pediatric COVID-19 vaccine uptake.
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http://dx.doi.org/10.3390/vaccines9091049DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8473386PMC
September 2021

Exploring the Impact of Terminators on Transgene Expression in with a Synthetic Biology Approach.

Life (Basel) 2021 Sep 14;11(9). Epub 2021 Sep 14.

Department of Plant Sciences, University of Cambridge, Downing Street, Cambridge CB2 3EA, UK.

has many attractive features for use as a model organism for both fundamental studies and as a biotechnological platform. Nonetheless, despite the many molecular tools and resources that have been developed, there are challenges for its successful engineering, in particular to obtain reproducible and high levels of transgene expression. Here we describe a synthetic biology approach to screen several hundred independent transformants using standardised parts to explore different parameters that might affect transgene expression. We focused on terminators and, using a standardised workflow and quantitative outputs, tested 9 different elements representing three different size classes of native terminators to determine their ability to support high level expression of a GFP reporter gene. We found that the optimal size reflected the median size of element found in the genome. The behaviour of the terminator parts was similar with different promoters, in different host strains and with different transgenes. This approach is applicable to the systematic testing of other genetic elements, facilitating comparison to determine optimal transgene design.
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http://dx.doi.org/10.3390/life11090964DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8471596PMC
September 2021

Plant Variety Selection Using Interaction Classes Derived From Factor Analytic Linear Mixed Models: Models With Independent Variety Effects.

Front Plant Sci 2021 9;12:737462. Epub 2021 Sep 9.

Centre for Biometrics and Data Science for Sustainable Primary Industries, School of Mathematics and Applied Statistics, National Institute for Applied Statistics Research Australia, University of Wollongong, Wollongong, NSW, Australia.

A major challenge in the analysis of plant breeding multi-environment datasets is the provision of meaningful and concise information for variety selection in the presence of variety by environment interaction (VEI). This is addressed in the current paper by fitting a factor analytic linear mixed model (FALMM) then using the fundamental factor analytic parameters to define groups of environments in the dataset within which there is minimal crossover VEI, but between which there may be substantial crossover VEI. These groups are consequently called interaction classes (iClasses). Given that the environments within an iClass exhibit minimal crossover VEI, it is then valid to obtain predictions of overall variety performance (across environments) for each iClass. These predictions can then be used not only to select the best varieties within each iClass but also to match varieties in terms of their patterns of VEI across iClasses. The latter is aided with the use of a new graphical tool called an iClass Interaction Plot. The ideas are introduced in this paper within the framework of FALMMs in which the genetic effects for different varieties are assumed independent. The application to FALMMs which include information on genetic relatedness is the subject of a subsequent paper.
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http://dx.doi.org/10.3389/fpls.2021.737462DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8460066PMC
September 2021

Rare sugars: Metabolic Impacts and Mechanisms of Action - a Scoping Review.

Br J Nutr 2021 Sep 10:1-77. Epub 2021 Sep 10.

Division of Food, Nutrition and Dietetics, School of Biosciences, University of Nottingham Sutton Bonington campus, Loughborough LE12 5RD, UK.

Food manufacturers are under increasing pressure to limit the amount of free sugars in their products. Many have reformulated products to replace sucrose, glucose and fructose with alternative sweeteners, but some of these have been associated with additional health concerns. Rare sugars are "monosaccharides and their derivatives that hardly exist in nature", and there is increasing evidence that they could have health benefits. This review aimed to scope the existing literature in order to identify the most commonly researched rare sugars, to ascertain their proposed health benefits, mechanisms of action and potential uses, and to highlight knowledge gaps. A process of iterative database searching identified 55 relevant articles. The reported effects of rare sugars were noted, along with details of the research methodologies conducted. Our results indicated that the most common rare sugars investigated are D-psicose and D-tagatose, with the potential health benefits divided into three topics: glycaemic control, body composition and cardiovascular disease. All the rare sugars investigated have the potential to suppress postprandial elevation of blood glucose and improve glycaemic control in both human and animal models. Some animal studies have suggested that certain rare sugars may also improve lipid profiles, alter the gut microbiome and reduce pro-inflammatory cytokine expression. The present review demonstrates that rare sugars could play a role in reducing the development of obesity, type 2 diabetes, and/or cardiovascular disease. However, understanding of the mechanisms by which rare sugars may exert their effects is limited, and their effectiveness when used in reformulated products is unknown.
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http://dx.doi.org/10.1017/S0007114521003524DOI Listing
September 2021

A Multi-Environment Trial Analysis of Frost Susceptibility in Wheat and Barley Under Australian Frost-Prone Field Conditions.

Front Plant Sci 2021 19;12:722637. Epub 2021 Aug 19.

School of Agriculture, Food and Wine, Waite Research Institute, The University of Adelaide, Urrbrae, SA, Australia.

Low temperatures during the flowering period of cereals can lead to floret sterility, yield reduction, and economic losses in Australian crops. In order to breed for improved frost susceptibility, selection methods are urgently required to identify novel sources of frost tolerant germplasm. However, the presence of genotype by environment interactions (i.e. variety responses to a change in environment) is a major constraint to select the most appropriate varieties in any given target environment. An advanced method of analysis for multi-environment trials that includes factor analytic selection tools to summarize overall performance and stability to a specific trait across the environments could deliver useful information to guide growers and plant breeding programs in providing the most appropriate decision making-strategy. In this study, the updated selection tools approached in this multi-environment trials (MET) analysis have allowed variety comparisons with similar frost susceptibility but which have a different response to changes in the environment or vice versa. This MET analysis included a wide range of sowing dates grown at multiple locations from 2010 to 2019, respectively. These results, as far as we are aware, show for the first-time genotypic differences to frost damage through a MET analysis by phenotyping a vast number of accurate empirical measurements that reached in excess of 557,000 spikes. This has resulted in a substantial number of experimental units (10,317 and 5,563 in wheat and barley, respectively) across a wide range of sowing times grown at multiple locations from 2010 to 2019. Varieties with low frost overall performance (OP) and low frost stability (root mean square deviation -RMSD) were less frost susceptible, with performance more consistent across all environments, while varieties with low OP and high RMSD were adapted to specific environmental conditions.
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http://dx.doi.org/10.3389/fpls.2021.722637DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8417324PMC
August 2021

Compression of the Right Atrium and Inferior Vena Cava from an Extrahepatic Biloma Following Liver Trauma.

Am Surg 2021 Jul 27:31348211034757. Epub 2021 Jul 27.

Department of Surgery, 12258Louisiana State University Health Sciences Center, New Orleans, LA, USA.

A 26-year-old male presented to a Level 1 trauma center following a motorcycle crash. Workup of his injuries demonstrated a grade 5 liver laceration with active extravasation, grade 5 kidney laceration, right apical pneumothorax, and a sternal fracture. The patient underwent hepatic artery embolization with interventional radiology (IR) followed by an exploratory laparotomy, liver packing, and small bowel resection with primary anastomosis. Four days post-op, the patient developed dyspnea, tachycardia, and decreasing oxygen saturation. Computed tomography pulmonary angiography demonstrated perihepatic fluid compressing the right atrium and inferior vena cava. Percutaneous perihepatic drain placement with aspiration of 700 mL bilious fluid resulted in immediate resolution of the compression. He subsequently underwent endoscopic retrograde cholangiopancreatography (ERCP) with stenting of the ampulla nine days later. The patient was discharged ten days post-ERCP with oral amoxicillin/clavulanic acid for polymicrobial coverage and follow-up with gastroenterology and IR for stent removal and drain maintenance.
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http://dx.doi.org/10.1177/00031348211034757DOI Listing
July 2021

Prehospital whole blood reduces early mortality in patients with hemorrhagic shock.

Transfusion 2021 07;61 Suppl 1:S15-S21

Department of Surgery, UT Health San Antonio, San Antonio, Texas, USA.

Background: Low titer O+ whole blood (LTOWB) is being increasingly used for resuscitation of hemorrhagic shock in military and civilian settings. The objective of this study was to identify the impact of prehospital LTOWB on survival for patients in shock receiving prehospital LTOWB transfusion.

Study Design And Methods: A single institutional trauma registry was queried for patients undergoing prehospital transfusion between 2015 and 2019. Patients were stratified based on prehospital LTOWB transfusion (PHT) or no prehospital transfusion (NT). Outcomes measured included emergency department (ED), 6-h and hospital mortality, change in shock index (SI), and incidence of massive transfusion. Statistical analyses were performed.

Results: A total of 538 patients met inclusion criteria. Patients undergoing PHT had worse shock physiology (median SI 1.25 vs. 0.95, p < .001) with greater reversal of shock upon arrival (-0.28 vs. -0.002, p < .001). In a propensity-matched group of 214 patients with prehospital shock, 58 patients underwent PHT and 156 did not. Demographics were similar between the groups. Mean improvement in SI between scene and ED was greatest for patients in the PHT group with a lower trauma bay mortality (0% vs. 7%, p = .04). No survival benefit for patients in prehospital cardiac arrest receiving LTOWB was found (p > .05).

Discussion: This study demonstrated that trauma patients who received prehospital LTOWB transfusion had a greater improvement in SI and a reduction in early mortality. Patient with prehospital cardiac arrest did not have an improvement in survival. These findings support LTOWB use in the prehospital setting. Further multi-institutional prospective studies are needed.
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http://dx.doi.org/10.1111/trf.16528DOI Listing
July 2021

Does Gender Matter: A Multi-Institutional Analysis of Viscoelastic Profiles for 1565 Trauma Patients With Severe Hemorrhage.

Am Surg 2021 Jul 15:31348211033542. Epub 2021 Jul 15.

Department of Surgery, 12255Tulane University School of Medicine, New Orleans, LA, USA.

Background: Viscoelastic tests including thromboelastography (TEG) and rotational thromboelastometry (ROTEM) are being used in patients with severe hemorrhage at trauma centers to guide resuscitation. Several recent studies demonstrated hypercoagulability in female trauma patients that was associated with a survival advantage. The objective of our study was to elucidate the effects of gender differences in TEG/ROTEM values on survival in trauma patients with severe hemorrhage.

Methods: A retrospective review of consecutive adult patients receiving massive transfusion protocol (MTP) at 7 Level I trauma centers was performed from 2013 to 2018. Data were stratified by gender and then further examined by TEG or ROTEM parameters. Results were analyzed using univariate and multi-variate analyses.

Results: A total of 1565 patients were included with 70.9% male gender (n = 1110/1565). Female trauma patients were older than male patients (43.5 ± .9 vs 41.1 ± .6 years, = .01). On TEG, females had longer reaction times (6.1 ± .9 min vs 4.8 ± .2 min, = .03), increased alpha angle (68.6 ± .8 vs 65.7 ± .4, < .001), and higher maximum amplitude (59.8 ± .8 vs 56.3 ± .4, < .001). On ROTEM, females had significantly longer clot time (99.2 ± 13.7 vs 75.1 ± 2.6 sec, = .09) and clot formation time (153.6 ± 10.6 sec vs 106.9 ± 3.8 sec, < .001). When comparing by gender, no difference for in-hospital mortality was found for patients in the TEG or ROTEM group ( > .05). Multivariate analysis showed no survival difference for female patients (OR 1.11, 95% CI .83-1.50, = .48).

Conclusions: Although a difference between male and females was found on TEG/ROTEM for certain clotting parameters, no difference in mortality was observed. Prospective multi-institutional studies are needed.
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http://dx.doi.org/10.1177/00031348211033542DOI Listing
July 2021

Remote Sensing Phenology of Antarctic Green and Red Snow Algae Using WorldView Satellites.

Front Plant Sci 2021 16;12:671981. Epub 2021 Jun 16.

Department of Plant Sciences, University of Cambridge, Cambridge, United Kingdom.

Snow algae are an important group of terrestrial photosynthetic organisms in Antarctica, where they mostly grow in low lying coastal snow fields. Reliable observations of Antarctic snow algae are difficult owing to the transient nature of their blooms and the logistics involved to travel and work there. Previous studies have used Sentinel 2 satellite imagery to detect and monitor snow algal blooms remotely, but were limited by the coarse spatial resolution and difficulties detecting red blooms. Here, for the first time, we use high-resolution WorldView multispectral satellite imagery to study Antarctic snow algal blooms in detail, tracking the growth of red and green blooms throughout the summer. Our remote sensing approach was developed alongside two Antarctic field seasons, where field spectroscopy was used to build a detection model capable of estimating cell density. Global Positioning System (GPS) tagging of blooms and life cycle analysis was used to validate and verify our model output. WorldView imagery was then used successfully to identify red and green snow algae on Anchorage Island (Ryder Bay, 67°S), estimating peak coverage to be 9.48 × 10 and 6.26 × 10 m, respectively. Combined, this was greater than terrestrial vegetation area coverage for the island, measured using a normalized difference vegetation index. Green snow algae had greater cell density and average layer thickness than red blooms (6.0 × 10 vs. 4.3 × 10 cells ml) and so for Anchorage Island we estimated that green algae dry biomass was over three times that of red algae (567 vs. 180 kg, respectively). Because the high spatial resolution of the WorldView imagery and its ability to detect red blooms, calculated snow algal area was 17.5 times greater than estimated with Sentinel 2 imagery. This highlights a scaling problem of using coarse resolution imagery and suggests snow algal contribution to net primary productivity on Antarctica may be far greater than previously recognized.
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http://dx.doi.org/10.3389/fpls.2021.671981DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8254402PMC
June 2021

Retropharyngeal Edema and Neck Pain in Multisystem Inflammatory Syndrome in Children (MIS-c).

J Pediatric Infect Dis Soc 2021 Oct;10(9):922-925

Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia, USA.

We defined the prevalence of neck pain, trismus, or dysphagia (28.4%) and retropharyngeal edema (2.9%) among 137 patients with multisystem inflammatory syndrome in children (MIS-c). Retropharyngeal edema or phlegmon has been documented radiologically in at least 9 children. Symptoms of neck inflammation are common in MIS-c.
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http://dx.doi.org/10.1093/jpids/piab050DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8557366PMC
October 2021

Integrating Early Economic Evaluation into Target Product Profile development for medical tests: advantages and potential applications.

Int J Technol Assess Health Care 2021 Jun 7;37(1):e68. Epub 2021 Jun 7.

Test Evaluation Group, Academic Unit of Health Economics, University of Leeds, Leeds, UK.

Target Product Profiles (TPPs) outline the characteristics that new health technologies require to address an unmet clinical need. To date, published TPPs for medical tests have focused on infectious diseases, mostly in the context of low- and middle-income countries. Recently, there have been calls for a broader use of TPPs as a mechanism to ensure that diagnostic innovation is aligned with clinical needs, yet the methodology underpinning TPP development remains suboptimal. Here, we propose that early economic evaluation (EEE) should be integrated within the TPP methodology to create a more rigorous framework for the development of "fit-for-purpose" tests. We discuss the potential benefits that EEE could bring to the core activities underpinning TPP development-scoping, drafting, consensus building, and updating-and argue that using EEE to help inform TPPs provides a more objective, evidence-based, and transparent approach to defining test specifications.
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http://dx.doi.org/10.1017/S0266462321000374DOI Listing
June 2021

Droplet-based microfluidic screening and sorting of microalgal populations for strain engineering applications.

Algal Res 2021 Jun;56:None

Department of Plant Sciences, University of Cambridge, Downing Street, Cambridge CB2 3EA, UK.

The application of microfluidic technologies to microalgal research is particularly appealing since these approaches allow the precise control of the extracellular environment and offer a high-throughput approach to studying dynamic cellular processes. To expand the portfolio of applications, here we present a droplet-based microfluidic method for analysis and screening of and , which can be integrated into a genetic transformation workflow. Following encapsulation of single cells in picolitre-sized droplets, fluorescence signals arising from each cell can be used to assess its phenotypic state. In this work, the chlorophyll fluorescence intensity of each cell was quantified and used to identify populations of cells grown in different light conditions. Further, individual or cells engineered to express green fluorescent protein were distinguished and sorted from wild-type cells. This has been exploited as a rapid screen for transformed cells within a population, bypassing a major bottleneck in algal transformation workflows and offering an alternative strategy for the identification of genetically modified strains.
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http://dx.doi.org/10.1016/j.algal.2021.102293DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8139872PMC
June 2021

Controlling High Blood Pressure: An Evidence-Based Blueprint for Change.

Am J Med Qual 2022 Jan-Feb 01;37(1):22-31

Jefferson College of Population Health, Thomas Jefferson University, Philadelphia, PA Department of Medicine, Rush Medical College, Rush University, Chicago, IL University of Minnesota, Institute for Healthcare Informatics, Minneapolis, MN Booz Allen Hamilton Inc, Bethesda, MD University of Illinois at Chicago, School of Public Health, Chicago, IL Department of Medicine, University of Virginia Health System, Charlottesville, VA Johns Hopkins University, School of Nursing, Baltimore, MD Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD Rutgers University School of Nursing, New Brunswick, NJ American Heart Association, Dallas, TX American Medical Association, Chicago, IL Division of Nephrology and Hypertension, University Hospitals Cleveland Medical Center, Case Western Reserve University, Cleveland, OH.

Recently published national data demonstrate inadequate and worsening control of high blood pressure (HBP) in the United States, outcomes that likely have been made even worse by the coronavirus disease 2019 (COVID-19) pandemic. This major public health crisis exposes shortcomings of the US health care delivery system and creates an urgent opportunity to reduce mortality, major cardiovascular events, and costs for 115 million Americans. Ending this crisis will require a more coherent and systemic change to traditional patterns of care. The authors present an evidence-based Blueprint for Change for comprehensive health delivery system redesign based on current national clinical practice guidelines and quality measures. This innovative model includes a systems-based approach to ensuring proper BP measurement, assessment of cardiovascular risk, effective patient-centered team-based care, addressing social determinants of health, and shared decision-making. The authors also propose building on current national quality improvement initiatives designed to better control HBP.
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http://dx.doi.org/10.1097/01.JMQ.0000749856.90491.43DOI Listing
January 2022

Combining SIMS and mechanistic modelling to reveal nutrient kinetics in an algal-bacterial mutualism.

PLoS One 2021 20;16(5):e0251643. Epub 2021 May 20.

Cavendish Laboratory, University of Cambridge, Cambridge, United Kingdom.

Microbial communities are of considerable significance for biogeochemical processes, for the health of both animals and plants, and for biotechnological purposes. A key feature of microbial interactions is the exchange of nutrients between cells. Isotope labelling followed by analysis with secondary ion mass spectrometry (SIMS) can identify nutrient fluxes and heterogeneity of substrate utilisation on a single cell level. Here we present a novel approach that combines SIMS experiments with mechanistic modelling to reveal otherwise inaccessible nutrient kinetics. The method is applied to study the onset of a synthetic mutualistic partnership between a vitamin B12-dependent mutant of the alga Chlamydomonas reinhardtii and the B12-producing, heterotrophic bacterium Mesorhizobium japonicum, which is supported by algal photosynthesis. Results suggest that an initial pool of fixed carbon delays the onset of mutualistic cross-feeding; significantly, our approach allows the first quantification of this expected delay. Our method is widely applicable to other microbial systems, and will contribute to furthering a mechanistic understanding of microbial interactions.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0251643PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8136852PMC
October 2021

The climate benefits, co-benefits, and trade-offs of green infrastructure: A systematic literature review.

J Environ Manage 2021 Aug 28;291:112583. Epub 2021 Apr 28.

Environmental Change Institute, University of Oxford, Dyson Perrins Building, South Parks Road, Oxford, OX1 3QY, UK.

Climate change increases risks to natural and human systems. Green infrastructure (GI) has been increasingly recognized as a promising nature-based solution for climate change adaptation, mitigation, and other societal objectives for sustainable development. Although the climate contribution of GI has been extensively addressed in the literature, the linkages between the climate benefits and associated co-benefits and trade-offs remain unclear. We systematically reviewed the evidence from 141 papers, focusing on their climate benefits, relevant co-benefits and trade-offs, and the GI types that provide such climate (co-)benefits. This study presents a comprehensive overview of the links between climate benefits, co-benefits and types of GI, categorized along a green-grey continuum so that researchers/practitioners can find information according to their topic of interest. We further provide an analysis of trade-offs between various GI benefits. 'Bundles' of major co-benefits and trade-offs for each climate benefit can be identified with recommendations for strategies to maximize benefits and minimize trade-offs. To promote climate-resilient pathways through GI, it is crucial for decision-makers to identify opportunities to deliver multiple ecosystem services and benefits while recognizing disservices and trade-offs that need to be avoided or managed.
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http://dx.doi.org/10.1016/j.jenvman.2021.112583DOI Listing
August 2021

Introduction of glucan synthase into the cytosol in wheat endosperm causes massive maltose accumulation and represses starch synthesis.

Plant J 2021 06 4;106(5):1431-1442. Epub 2021 May 4.

John Innes Centre, Norwich Research Park, Norwich, NR4 7UH, UK.

We expressed a bacterial glucan synthase (Agrobacterium GlgA) in the cytosol of developing endosperm cells in wheat grains, to discover whether it could generate a glucan from cytosolic ADP-glucose. Transgenic lines had high glucan synthase activity during grain filling, but did not accumulate glucan. Instead, grains accumulated very high concentrations of maltose. They had large volumes during development due to high water content, and very shrivelled grains at maturity. Starch synthesis was severely reduced. We propose that cytosolic glucan synthesized by the glucan synthase was immediately hydrolysed to maltose by cytosolic β-amylase(s). Maltose accumulation resulted in a high osmotic potential in developing grain, drawing in excess water that stretched the seed coat and pericarp. Loss of water during grain maturation then led to shrinkage when the grains matured. Maltose accumulation is likely to account for the reduced starch synthesis in transgenic grains, through signalling and toxic effects. Using bioinformatics, we identify an isoform of β-amylase likely to be responsible for maltose accumulation. Removal of this isoform through identification of TILLING mutants or genome editing, combined with co-expression of heterologous glucan synthase and a glucan branching enzyme, may in future enable elevated yields of carbohydrate through simultaneous accumulation of starch and cytosolic glucan.
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http://dx.doi.org/10.1111/tpj.15246DOI Listing
June 2021

Genetic analysis of wheat (Triticum aestivum) adaptation to heat stress.

Theor Appl Genet 2021 May 6;134(5):1387-1407. Epub 2021 Mar 6.

School of Agriculture, Food and Wine, The University of Adelaide, Waite Campus, PMB 1 Glen Osmond, Adelaide, SA, 5064, Australia.

Key Message: Adaptation to abiotic stresses such as high-temperature conditions should be considered as its independent components of total performance and responsiveness. Understanding and identifying improved adaptation to abiotic stresses such as heat stress has been the focus of a number of studies in recent decades. However, confusing and potentially misleading terminology has made progress difficult and hard to apply within breeding programs selecting for improved adaption to heat stress conditions. This study proposes that adaption to heat stress (and other abiotic stresses) be considered as the combination of total performance and responsiveness to heat stress. In this study, 1413 doubled haploid lines from seven populations were screened through a controlled environment assay, subjecting plants to three consecutive eight hour days of an air temperature of 36 °C and a wind speed of 40 km h, 10 days after the end of anthesis. QTL mapping identified a total of 96 QTL for grain yield determining traits and anthesis date with nine correlating to responsiveness, 72 for total performance and 15 for anthesis date. Responsiveness QTL were found both collocated with other performance QTL as well as independently. A sound understanding of genomic regions associated with total performance and responsiveness will be important for breeders. Genomic regions of total performance, those that show higher performance that is stable under both stressed and non-stressed conditions, potentially offer significant opportunities to breeders. We propose this as a definition and selection target that has not previously been defined for heat stress adaptation.
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http://dx.doi.org/10.1007/s00122-021-03778-2DOI Listing
May 2021
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