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1.
Ann Surg ; 273(6): 1051-1059, 2021 06 01.
Article in English | MEDLINE | ID: mdl-33378302

ABSTRACT

The emergence of coronavirus disease 2019 (COVID-19) that is caused by the SARS-CoV-2 virus has led to an overwhelming strain on healthcare delivery. This pandemic has created a sustained stress on the modern healthcare system, with unforeseen and potential drastic effects. Although the initial focus during this pandemic has been preparedness and response directed to the pandemic itself, traumatic injury has continued to remain a common problem that requires immediate evaluation and care to provide optimal outcomes. The State of Washington had the first reported case and death related to COVID-19 in the United States. Harborview Medical Center, which serves as the sole Level-1 adult and pediatric trauma center for the state, was rapidly affected by COVID-19, but still needed to maintain preparedness and responses to injured patients for the region. Although initially the focus was on the emerging pandemic on institutional factors, it became obvious that sustained efforts for regional trauma care required a more global focus. Because of these factors, Harborview Medical Center was quickly entrusted to serve as the coordinating center for the regions COVID-19 response, while also continuing to provide optimal care for injured patients during the pandemic. This response allowed the care of injured patients to be maintained within designated trauma centers during this pandemic. This present report summarizes the evolution of trauma care delivery during the first phase of this pandemic and provides informative recommendations for sustained responses to the care of injured patients during the pandemic based on lessons learned during the initial response.


Subject(s)
COVID-19/epidemiology , Delivery of Health Care/trends , Disaster Planning , Pneumonia, Viral/epidemiology , Trauma Centers/organization & administration , Humans , Pandemics , Pneumonia, Viral/virology , SARS-CoV-2 , United States/epidemiology , Washington/epidemiology
2.
Sensors (Basel) ; 19(5)2019 Feb 28.
Article in English | MEDLINE | ID: mdl-30823431

ABSTRACT

Condition monitoring of an operating apparatus is essential for lifespan assessment and maintenance planning in a power system. Electrical insulation is a critical aspect to be monitored, since it is susceptible to failure under high electrical stress. To avoid unexpected breakdowns, the level of partial discharge (PD) activity should be continuously monitored because PD occurrence can accelerate the aging process of insulation in high voltage equipment and result in catastrophic failure if the associated defects are not treated at an early stage. For on-site PD detection, the ultra-high frequency (UHF) method was employed in the field and showed its effectiveness as a detection technique. The main advantage of the UHF method is its immunity to external electromagnetic interference with a high signal-to-noise ratio, which is necessary for on-site monitoring. Considering the detection process, sensors play a critical role in capturing signals from PD sources and transmitting them onto the measurement system. In this paper, UHF sensors applied in PD detection were comprehensively reviewed. In particular, for power transformers, the effects of the physical structure on UHF signals and practical applications of UHF sensors including PD localization techniques were discussed. The aim of this review was to present state-of-the-art UHF sensors in PD detection and facilitate future improvements in the UHF method.

3.
Xenobiotica ; 47(8): 731-740, 2017 Aug.
Article in English | MEDLINE | ID: mdl-27560772

ABSTRACT

1. Thianthrene is a sulfur-containing tricyclic molecule distributed widely within the macrostructure of hydrocarbon fossil fuels. Identified nearly 150 years ago, its chemistry has been widely explored leading to insights into reaction mechanisms and radical ion formation. 2. It has been claimed to have therapeutic application in the treatment of dermal infections and to interfere with enzyme and nucleic acid function, but appears to have little toxicity. 3. Following its oral administration to the rat, the majority remained within the gastrointestinal tract. After three days, about 88% was detected in the combined excreta with the remainder still within the animal. It is readily taken up into fish from the surrounding aqueous environment and has been placed within the "bioaccumulative category" to be regarded with concern. 4. Mammalian metabolism appeared to be restricted to ring carbon oxidation and subsequent glucuronic acid conjugation. Small amounts of sulfoxide and disulfoxide were also formed. No ring degradation was evident. Microorganisms similarly undertook aromatic ring hydroxylation but were able also to rupture the ring system by attacking the carbon-sulfur linkages and thereby degrading the molecule.


Subject(s)
Heterocyclic Compounds/metabolism , Animals , Fishes/metabolism , Oxidation-Reduction , Rats
4.
Emerg Radiol ; 24(1): 47-53, 2017 Feb.
Article in English | MEDLINE | ID: mdl-27623691

ABSTRACT

The aims of this article are to describe the events of a recent mass casualty incident (MCI) at our level 1 trauma center and to describe the radiology response to the event. We also describe the findings and recommendations of our radiology department after-action review. An MCI activation was triggered after an amphibious military vehicle, repurposed for tourist activities, carrying 37 passengers, collided with a charter bus carrying 45 passengers on a busy highway bridge in Seattle, WA, USA. There were 4 deaths at the scene, and 51 patients were transferred to local hospitals following prehospital scene triage. Nineteen patients were transferred to our level 1 trauma center. Eighteen casualties arrived within 72 min. Sixteen arrived within 1 h of the first patient arrival, and 1 casualty was transferred 3 h later having initially been assessed at another hospital. Eighteen casualties (94.7 %) underwent diagnostic imaging in the emergency department. Of these 18 casualties, 15 had a trauma series (portable chest x-ray and x-ray of pelvis). Whole-body trauma computed tomography scans (WBCT) were performed on 15 casualties (78.9 %), 12 were immediate and performed during the initial active phase of the MCI, and 3 WBCTs were delayed. The initial 12 WBCTs were completed in 101 min. The mean number of radiographic studies performed per patient was 3 (range 1-8), and the total number of injuries detected was 88. The surge in imaging requirements during an MCI can be significant and exceed normal operating capacity. This report of our radiology experience during a recent MCI and subsequent after-action review serves to provide an example of how radiology capacity and workflow functioned during an MCI, in order to provide emergency radiologists and response planners with practical recommendations for implementation in the event of a future MCI.


Subject(s)
Accidents, Traffic , Mass Casualty Incidents , Tomography, X-Ray Computed , Trauma Centers/organization & administration , Wounds and Injuries/diagnostic imaging , Adult , Contrast Media , Disaster Planning , Female , Humans , Male , Triage , Washington , Whole Body Imaging , Workflow
5.
Plant Physiol ; 161(4): 1595-603, 2013 Apr.
Article in English | MEDLINE | ID: mdl-23457228

ABSTRACT

Fluorescent proteins (FPs) were developed for live-cell imaging and have revolutionized cell biology. However, not all plant tissues are accessible to live imaging using confocal microscopy, necessitating alternative approaches for protein localization. An example is the phloem, a tissue embedded deep within plant organs and sensitive to damage. To facilitate accurate localization of FPs within recalcitrant tissues, we developed a simple method for retaining FPs after resin embedding. This method is based on low-temperature fixation and dehydration, followed by embedding in London Resin White, and avoids the need for cryosections. We show that a palette of FPs can be localized in plant tissues while retaining good structural cell preservation, and that the polymerized block face can be counterstained with cell wall probes. Using this method we have been able to image green fluorescent protein-labeled plasmodesmata to a depth of more than 40 µm beneath the resin surface. Using correlative light and electron microscopy of the phloem, we were able to locate the same FP-labeled sieve elements in semithin and ultrathin sections. Sections were amenable to antibody labeling, and allowed a combination of confocal and superresolution imaging (three-dimensional-structured illumination microscopy) on the same cells. These correlative imaging methods should find several uses in plant cell biology.


Subject(s)
Imaging, Three-Dimensional/methods , Luminescent Proteins/metabolism , Resins, Plant/metabolism , Arabidopsis/cytology , Desiccation , Fluorescence , Fluorescent Antibody Technique , Glucans/metabolism , Green Fluorescent Proteins/metabolism , Microscopy, Confocal , Phloem/ultrastructure , Plant Leaves/ultrastructure , Tissue Embedding , Tissue Fixation , Nicotiana/ultrastructure
6.
Biochem Biophys Res Commun ; 438(4): 666-72, 2013 Sep 06.
Article in English | MEDLINE | ID: mdl-23933253

ABSTRACT

Multipotent progenitor cells have shown promise for use in biomedical applications and regenerative medicine. The implementation of such cells for clinical application requires a synchronized, phenotypically and/or genotypically, homogenous cell population. Here we have demonstrated the implementation of a biological tag-free dielectrophoretic device used for discrimination of multipotent myoblastic C2C12 model. The multipotent capabilities in differentiation, for these cells, diminishes with higher passage number, so for cultures above 70 passages only a small percentage of cells is able to differentiate into terminal myotubes. In this work we demonstrated that we could recover, above 96% purity, specific cell types from a mixed population of cells at high passage number without any biological tag using dielectrophoresis. The purity of the samples was confirmed by cytometric analysis using the cell specific marker embryonic myosin. To further investigate the dielectric properties of the cell plasma membrane we co-culture C2C12 with similar size, when in suspension, GFP-positive fibroblast as feeder layer. The level of separation between the cell types was above 98% purity which was confirmed by flow cytometry. These levels of separation are assumed to account for cell size and for the plasma membrane morphological differences between C2C12 and fibroblast unrelated to the stages of the cell cycle which was assessed by immunofluorescence staining. Plasma membrane conformational differences were further confirmed by scanning electron microscopy.


Subject(s)
Cell Membrane/ultrastructure , Multipotent Stem Cells/cytology , Myoblasts/cytology , Animals , Cell Cycle , Cell Line , Cell Membrane/chemistry , Cell Separation/instrumentation , Coculture Techniques , Electric Capacitance , Electrophoresis/instrumentation , Equipment Design , Fibroblasts/cytology , Mice , Microscopy, Electron, Scanning
7.
J Proteome Res ; 11(2): 631-42, 2012 Feb 03.
Article in English | MEDLINE | ID: mdl-22029865

ABSTRACT

With successes of genome-wide association studies, molecular phenotyping systems are developed to identify genetically determined disease-associated biomarkers. Genetic studies of the human metabolome are emerging but exclusively apply targeted approaches, which restricts the analysis to a limited number of well-known metabolites. We have developed novel technical and statistical methods for systematic and automated quantification of untargeted NMR spectral data designed to perform robust and accurate quantitative trait locus (QTL) mapping of known and previously unreported molecular compounds of the metabolome. For each spectral peak, six summary statistics were calculated and independently tested for evidence of genetic linkage in a cohort of F2 (129S6xBALB/c) mice. The most significant evidence of linkages were obtained with NMR signals characterizing the glycerate (LOD10-42) at the mutant glycerate kinase locus, which demonstrate the power of metabolomics in quantitative genetics to identify the biological function of genetic variants. These results provide new insights into the resolution of the complex nature of metabolic regulations and novel analytical techniques that maximize the full utilization of metabolomic spectra in human genetics to discover mappable disease-associated biomarkers.


Subject(s)
Chromosome Mapping/methods , Genomics/methods , Glyceric Acids/urine , Metabolome/genetics , Phosphotransferases (Alcohol Group Acceptor)/genetics , Quantitative Trait Loci , Analysis of Variance , Animals , Computer Simulation , Lod Score , Male , Metabolomics , Mice , Mice, Inbred BALB C , Nuclear Magnetic Resonance, Biomolecular , Phosphotransferases (Alcohol Group Acceptor)/deficiency , Phosphotransferases (Alcohol Group Acceptor)/metabolism
8.
Drug Metab Rev ; 44(2): 129-47, 2012 May.
Article in English | MEDLINE | ID: mdl-22497630

ABSTRACT

S-carboxymethyl-L-cysteine, the side-chain carboxymethyl derivative of the sulfur-containing amino acid, cysteine, has been known and available for almost 80 years. During this time, it has been put to a variety of uses, but it is within the field of respiratory medicine that, presently, it has found a clinical niche. Early studies indicated that this compound underwent a rather simplistic, predictable pattern of metabolism, whereas later investigations alluded to more subtle interactions with the pathways of intermediary metabolism, as may be expected for an amino acid derivative. In addition, suggestions of polymorphic influences and circadian rhythms within metabolic profiles have emerged. These latter factors may underlie the conflicting reports regarding the therapeutic efficacy of this compound: that it appears to work well in some patients, but has no measurable effects in others. The relevant literature pertaining to the fate of this compound within living systems has been reviewed and a comprehensive précis advanced. Hopefully, this article will serve as a vade mecum for those interested in S-carboxymethyl-L-cysteine and as a catalyst for future research.


Subject(s)
Carbocysteine/pharmacokinetics , Acetylation , Animals , Carbocysteine/chemical synthesis , Carbocysteine/pharmacology , Carbocysteine/therapeutic use , Circadian Rhythm , Glucuronides/metabolism , Humans , Respiratory Tract Diseases/drug therapy , Respiratory Tract Diseases/metabolism , Sulfoxides/metabolism
9.
Integr Comp Biol ; 62(2): 332-344, 2022 08 25.
Article in English | MEDLINE | ID: mdl-35612997

ABSTRACT

Understanding the processes that shaped the distribution of species richness across the Tree of Life is a central macroevolutionary research agenda. Major ecological innovations, including transitions between habitats, may help to explain the striking asymmetries of diversity that are often observed between sister clades. Here, we test the impact of such transitions on speciation rates across decapod crustaceans, modeling diversification dynamics within a phylogenetic framework. Our results show that, while terrestrial lineages have higher speciation rates than either marine or freshwater lineages, there is no difference between mean speciation rates in marine and freshwater lineages across Decapoda. Partitioning our data by infraorder reveals that those clades with habitat heterogeneity have higher speciation rates in freshwater and terrestrial lineages, with freshwater rates up to 1.5 times faster than marine rates, and terrestrial rates approximately four times faster. This averaging out of marine and freshwater speciation rates results from the varying contributions of different clades to average speciation rates. However, with the exception of Caridea, we find no evidence for any causal relationship between habitat and speciation rate. Our results demonstrate that while statistical generalizations about ecological traits and evolutionary rates are valuable, there are many exceptions. Hence, while freshwater and terrestrial lineages typically speciate faster than their marine relatives, there are many atypically slow freshwater lineages and fast marine lineages across Decapoda. Future work on diversification patterns will benefit from the inclusion of fossil data, as well as additional ecological factors.


Subject(s)
Biological Evolution , Decapoda , Animals , Decapoda/genetics , Ecosystem , Fresh Water , Phylogeny
10.
AIDS Care ; 23(3): 378-82, 2011 Mar.
Article in English | MEDLINE | ID: mdl-21347901

ABSTRACT

Tanzania has a generalised AIDS epidemic but the estimated adult HIV prevalence of 6% is much lower than in many countries in Southern Africa. HIV infection rates are reportedly higher in urban areas, among women and among those with more education. Stigma has been found to be more common in poorer, less-educated people, and those in rural areas. We examined associations between poverty and other variables and a stigmatising attitude (belief that HIV/AIDS is punishment for sinning). The variables we examined in a multivariate model included: food sufficiency (as an indicator of poverty), age, sex, marital status, education, experience of intimate partner violence, condom-related choice disability, discussion about HIV/AIDS, sources of information about HIV/AIDS and urban or rural residence. Of the 1,130 men and 1,803 women interviewed, more than half (58%) did not disagree that "HIV/AIDS is punishment for sinning". Taking other variables into account, people from the poorest households (without enough food in the last week) were more likely to believe HIV/AIDS is punishment for sinning (Odds Ratio [OR] 1.29, 95% confidence intervals [CI] 1.06-1.59). Others factors independently associated with this stigmatising attitude were: having less than primary education (OR 1.29, 95% CI 1.03-1.62); having experienced intimate partner violence in the last year (OR 1.40, 95% CI 1.12-1.75); being choice disabled for condom use (OR 1.36, 95% CI 1.08-1.71); and living in rural areas (OR 1.76, 95% CI 1.06-2.90). The level of HIV and AIDS stigma in Tanzania is high with independent associations with several disadvantages: poverty, less education and living in rural areas. Other vulnerable groups, such as survivors of intimate partner violence, are also more likely to have a stigmatising attitude. HIV prevention programmes should take account of stigma, especially among the disadvantaged, and take care not to increase it.


Subject(s)
HIV Infections/psychology , Religion , Social Stigma , Socioeconomic Factors , Adolescent , Adult , Aged , Female , HIV Infections/epidemiology , Health Knowledge, Attitudes, Practice , Humans , Male , Middle Aged , Morals , Poverty , Risk Factors , Tanzania/epidemiology , Young Adult
11.
Xenobiotica ; 41(10): 837-43, 2011 Oct.
Article in English | MEDLINE | ID: mdl-21726171

ABSTRACT

The existence of racemic compounds, comprised of pairs of opposite enantiomers as discrete molecular entities, has been accepted for over a century. However, their ability to remain as associated dimers when in solution is uncertain, if not generally doubted. In this article, data has been assembled to provide evidence for the presence of intact dimeric heterochiral assemblies in solution and presents DL-thalidomide as a probable example of this phenomenon.


Subject(s)
Teratogens/chemistry , Thalidomide/chemistry , Dimerization , Molecular Structure , Structure-Activity Relationship
12.
Int Orthop ; 35(3): 413-8, 2011 Mar.
Article in English | MEDLINE | ID: mdl-20352430

ABSTRACT

A series of 49 pilon fractures in a tertiary referral centre treated definitively by open reduction and internal fixation have been assessed and the complications of such injuries examined. A retrospective analysis of case notes, radiographs and computerised tomographs over a seven-year period from 1999-2006 was performed. Infection was the most common postoperative problem. There were seven cases of superficial infection. There was a single case of deep infection requiring intravenous antibiotics and removal of metalwork. Other notable complications were those of secondary osteoarthritis (three cases) and malunion (one case). The key finding of this paper is the 2% incidence of deep infection following the direct operative approach to these fractures. The traditional operative approach to such injuries (initially advocated by Rüedi and Allgöwer in Injury 2:92-99, 1969) consisted of extensive soft tissue dissection to gain access to the distal tibia. Our preferred method is to access the tibia via the "direct approach" which involves direct access to the fracture site with minimal disturbance of the soft tissue envelope. We therefore believe that open reduction and internal fixation of pilon fractures via the direct approach to be a safe technique in the treatment of such devastating injuries.


Subject(s)
Fracture Fixation, Internal/methods , Fractures, Open/surgery , Minimally Invasive Surgical Procedures/methods , Tibial Fractures/surgery , Adolescent , Adult , Aged , Female , Fracture Fixation, Internal/adverse effects , Fractures, Malunited/surgery , Fractures, Open/diagnostic imaging , Humans , Male , Middle Aged , Osteoarthritis/etiology , Radiography , Retrospective Studies , Surgical Wound Infection/etiology , Surgical Wound Infection/prevention & control , Tibial Fractures/diagnostic imaging , Young Adult
13.
Front Plant Sci ; 10: 672, 2019.
Article in English | MEDLINE | ID: mdl-31178883

ABSTRACT

The caryopses of barley become firmly adhered to the husk during grain development through a cuticular cementing layer on the caryopsis surface. The degree of this attachment varies among cultivars, with poor quality adhesion causing "skinning", an economically significant grain quality defect for the malting industry. Malting cultivars encompassing a range of husk adhesion qualities were grown under a misting treatment known to induce skinning. Development of the cementing layer was examined by electron microscopy and compositional changes of the cementing layer were investigated with gas-chromatography followed by mass spectroscopy. Changes in gene expression during adhesion development were examined with a custom barley microarray. The abundance of transcripts involved early in cuticular lipid biosynthesis, including those encoding acetyl-CoA carboxylase, and all four members of the fatty acid elongase complex of enzymes, was significantly higher earlier in caryopsis development than later. Genes associated with subsequent cuticular lipid biosynthetic pathways were also expressed higher early in development, including the decarbonylation and reductive pathways, and sterol biosynthesis. Changes in cuticular composition indicate that lowered proportions of alkanes and higher proportions of fatty acids are associated with development of good quality husk adhesion, in addition to higher proportions of sterols.

14.
BMC Health Serv Res ; 8: 15, 2008 Jan 21.
Article in English | MEDLINE | ID: mdl-18208604

ABSTRACT

BACKGROUND: Cross-country comparisons of unofficial payments in the health sector are sparse. In 2002 we conducted a social audit of the health sector of the three Baltic States. METHODS: Some 10,320 household interviews from a stratified, last-stage-random, sample of 30 clusters per country, together with institutional reviews, produced preliminary results. Separate focus groups of service users, nurses and doctors interpreted these findings. Stakeholder workshops in each country discussed the survey and focus group results. RESULTS: Nearly one half of the respondents did not consider unofficial payments to health workers to be corruption, yet one half (Estonia 43%, Latvia 45%, Lithuania 64%) thought the level of corruption in government health services was high. Very few (Estonia 1%, Latvia 3%, Lithuania 8%) admitted to making unofficial payments in their last contact with the services. Around 14% of household members across the three countries gave gifts in their last contact with government services. CONCLUSION: This social audit allowed comparison of perceptions, attitudes and experience regarding unofficial payments in the health services of the three Baltic States. Estonia showed least corruption. Latvia was in the middle. Lithuania evidenced the most unofficial payments, the greatest mistrust towards the system. These findings can serve as a baseline for interventions, and to compare each country's approach to health service reform in relation to unofficial payments.


Subject(s)
Attitude to Health , Health Care Sector/ethics , Health Expenditures , National Health Programs/ethics , Public Opinion , Trust , Baltic States , Cross-Cultural Comparison , Financing, Personal/ethics , Focus Groups , Gift Giving/ethics , Health Care Sector/organization & administration , Health Services Accessibility/ethics , Health Services Research , Humans , National Health Programs/organization & administration , Patient Rights/ethics , Social Responsibility , Surveys and Questionnaires
15.
Front Psychol ; 9: 2492, 2018.
Article in English | MEDLINE | ID: mdl-30618928

ABSTRACT

It is accepted knowledge that, for a given equivalent sound pressure level, sounds produced by planes are worse received from local communities than other sources related to transportation. Very little is known on the reasons for this special status, including any interactions that non-acoustical factors may have in listener assessments. Here we focus on one of such factors, the multisensory aspect of aircraft events. We propose a method to assess the visual impact of perceived aircraft height and size, beyond the objective increase in sound pressure level for a plane flying lower than another. We utilize a soundscape approach, based on acoustical indicators (dBs, L A, max, background sound pressure level) and social surveys: a combination of postal questionnaires (related to long-term exposure) and field interviews (related to the contextual perception), complementing well-established questions with others designed to capture new multisensory relationships. For the first time, we report how the perceived visual height of airplanes can be established using a combination of visual size, airplane size, reading distance, and airplane distance. Visual and acoustic assessments are complemented and contextualized by additional questions probing the subjective, objective, and descriptive assessments made by observers as well as how changes in airplane height over time may have influenced these perceptions. The flexibility of the proposed method allows a comparison of how participant reporting can vary across live viewing and memory recall conditions, allowing an examination of listeners' acoustic memory and expectations. The compresence of different assessment methods allows a comparison between the "objective" and the "perceptual" sphere and helps underscore the multisensory nature of observers' perceptual and emotive evaluations. In this study, we discuss pro and cons of our method, as assessed during a community survey conducted in the summer 2017 around Gatwick airport, and compare the different assessments of the community perception.

16.
BMC Womens Health ; 7: 11, 2007 Jul 16.
Article in English | MEDLINE | ID: mdl-17631689

ABSTRACT

BACKGROUND: The baseline to assess impact of a mass education-entertainment programme offered an opportunity to identify risk factors for domestic physical violence. METHODS: In 2002, cross-sectional household surveys in a stratified urban/rural last-stage random sample of enumeration areas, based on latest national census in Botswana, Lesotho, Malawi, Mozambique, Namibia, Swaziland, Zambia and Zimbabwe. Working door to door, interviewers contacted all adults aged 16-60 years present on the day of the visit, without sub-sampling. 20,639 adults were interviewed. The questionnaire in 29 languages measured domestic physical violence by the question "In the last year, have you and your partner had violent arguments where your partner beat, kicked or slapped you?" There was no measure of severity or frequency of physical violence. RESULTS: 14% of men (weighted based on 1,294/8,113) and 18% of women (weighted based on 2,032/11,063) reported being a victim of partner physical violence in the last year. There was no convincing association with age, income, education, household size and remunerated occupation. Having multiple partners was strongly associated with partner physical violence. Other associations included the income gap within households, negative attitudes about sexuality (for example, men have the right to sex with their girlfriends if they buy them gifts) and negative attitudes about sexual violence (for example, forcing your partner to have sex is not rape). Particularly among men, experience of partner physical violence was associated with potentially dangerous attitudes to HIV infection. CONCLUSION: Having multiple partners was the most consistent risk factor for domestic physical violence across all countries. This could be relevant to domestic violence prevention strategies.


Subject(s)
Health Knowledge, Attitudes, Practice , Health Surveys , Sexual Partners , Spouse Abuse/statistics & numerical data , Adolescent , Adult , Africa, Southern/epidemiology , Censuses , Cross-Cultural Comparison , Cross-Sectional Studies , Educational Status , Family Characteristics , Female , HIV Seropositivity/psychology , Humans , Male , Middle Aged , Odds Ratio , Risk Factors , Rural Population , Sexual Behavior/psychology , Sexual Behavior/statistics & numerical data , Sexual Partners/classification , Sexual Partners/psychology , Socioeconomic Factors , Spouse Abuse/psychology , Surveys and Questionnaires , Urban Population
17.
Genome Med ; 8(1): 101, 2016 09 30.
Article in English | MEDLINE | ID: mdl-27716393

ABSTRACT

BACKGROUND: The genetic regulation of metabolic phenotypes (i.e., metabotypes) in type 2 diabetes mellitus occurs through complex organ-specific cellular mechanisms and networks contributing to impaired insulin secretion and insulin resistance. Genome-wide gene expression profiling systems can dissect the genetic contributions to metabolome and transcriptome regulations. The integrative analysis of multiple gene expression traits and metabolic phenotypes (i.e., metabotypes) together with their underlying genetic regulation remains a challenge. Here, we introduce a systems genetics approach based on the topological analysis of a combined molecular network made of genes and metabolites identified through expression and metabotype quantitative trait locus mapping (i.e., eQTL and mQTL) to prioritise biological characterisation of candidate genes and traits. METHODS: We used systematic metabotyping by 1H NMR spectroscopy and genome-wide gene expression in white adipose tissue to map molecular phenotypes to genomic blocks associated with obesity and insulin secretion in a series of rat congenic strains derived from spontaneously diabetic Goto-Kakizaki (GK) and normoglycemic Brown-Norway (BN) rats. We implemented a network biology strategy approach to visualize the shortest paths between metabolites and genes significantly associated with each genomic block. RESULTS: Despite strong genomic similarities (95-99 %) among congenics, each strain exhibited specific patterns of gene expression and metabotypes, reflecting the metabolic consequences of series of linked genetic polymorphisms in the congenic intervals. We subsequently used the congenic panel to map quantitative trait loci underlying specific mQTLs and genome-wide eQTLs. Variation in key metabolites like glucose, succinate, lactate, or 3-hydroxybutyrate and second messenger precursors like inositol was associated with several independent genomic intervals, indicating functional redundancy in these regions. To navigate through the complexity of these association networks we mapped candidate genes and metabolites onto metabolic pathways and implemented a shortest path strategy to highlight potential mechanistic links between metabolites and transcripts at colocalized mQTLs and eQTLs. Minimizing the shortest path length drove prioritization of biological validations by gene silencing. CONCLUSIONS: These results underline the importance of network-based integration of multilevel systems genetics datasets to improve understanding of the genetic architecture of metabotype and transcriptomic regulation and to characterize novel functional roles for genes determining tissue-specific metabolism.


Subject(s)
Diabetes Mellitus, Type 2/genetics , Diabetes Mellitus, Type 2/metabolism , Metabolome , Quantitative Trait Loci , Quantitative Trait, Heritable , Transcriptome , Animals , Animals, Congenic , Chromosome Mapping , Diabetes Mellitus, Type 2/pathology , Disease Models, Animal , Female , Gene Expression Profiling , Gene Expression Regulation , Gene Ontology , Gene Regulatory Networks , Genetic Association Studies , Genetic Predisposition to Disease , Humans , Male , Metabolic Networks and Pathways , Molecular Sequence Annotation , Rats, Inbred BN , Systems Biology
18.
Biochem Mol Biol Educ ; 33(6): 394-8, 2005 Nov.
Article in English | MEDLINE | ID: mdl-21638608

ABSTRACT

Upper level college students majoring in biochemistry at the University of New Mexico have the opportunity to participate in an advanced biochemistry course entitled "Biochemistry Education." This course introduces theories of teaching and learning, provides opportunities for participation in course organization, design, and assessment strategies, and requires practice in lecturing, exam writing, and grading. One component of this course required the biochemistry majors to act as educational assistants, leading problem-based learning sessions in a cooperative learning introductory survey biochemistry course for nonmajors. Problem-based learning scenarios used in this course were based on real-life biochemistry problems. As a result of their participation, the educational assistants increased their understanding of the biochemistry principles, gained an appreciation for the difficulty of the job of a "good teacher," developed new approaches to their own learning, and became more confident speakers. The participating biochemistry faculty were also positively affected by the collaborative approach they were attempting to model for the two sets of students and realized the benefits of truly cooperative team teaching.

19.
Biologist (London) ; 49(5): 217-21, 2002 Oct.
Article in English | MEDLINE | ID: mdl-12391413

ABSTRACT

Occasionally, a new idea emerges that has the potential to revolutionize an entire field of scientific endeavour. It is now within our grasp to be able to detect subtle perturbations within the phenomenally complex biochemical matrix of living organisms. The discipline of metabonomics promises an all-encompassing approach to understanding total, yet fundamental, changes occurring in disease processes, drug toxicity and cell function.


Subject(s)
Molecular Biology , Animals , Genome , Humans , Magnetic Resonance Spectroscopy , Research
20.
Clin Teach ; 11(3): 165-9, 2014 Jun.
Article in English | MEDLINE | ID: mdl-24802914

ABSTRACT

BACKGROUND: Shortcomings in non-technical skills have frequently been shown to play a role in adverse events during surgery. Human-factors training has an increasing role to play in enhancing patient safety and reducing medical errors. Programmes in non-technical skills are promoted by the surgical Royal Colleges in the UK and Ireland, and are currently aimed at consultants, senior trainees and theatre teams. Since 2009, the Severn Postgraduate Deanery School of Surgery in the UK has developed a 1-day human-factors training course specifically designed for junior surgical trainees. METHODS: Analysis of post-course feedback on self-assessed confidence in the use of non-technical skills was undertaken for all junior surgical trainees undertaking the course in 2012/13. RESULTS: Thirty-three junior surgical trainees attended the 1-day human-factors training course. In all, 91 per cent of trainees reported that the course would change their practice. There was a statistically significant difference between the self-assessed confidence of trainees in the use of all four categories of non-technical skills (p ≤ 0.001) before and after the course. DISCUSSION: The Severn Deanery offers a compulsory human-factors training course for surgeons at the start of their career. Given the importance of reducing human error, maintaining patient safety and the introduction of competency-based training with an emphasis on simulation, human-factors training has a vital place in surgical training, and is highly recommended to others involved in training junior surgical trainees.


Subject(s)
Clinical Competence , Education, Medical, Graduate/organization & administration , Medical Staff, Hospital , Surgical Procedures, Operative/education , Communication , Curriculum , Decision Making , Humans , Patient Care Team
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