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1.
Proc Natl Acad Sci U S A ; 118(42)2021 10 19.
Article in English | MEDLINE | ID: mdl-34635596

ABSTRACT

Oceans emit large quantities of dimethyl sulfide (DMS) to the marine atmosphere. The oxidation of DMS leads to the formation and growth of cloud condensation nuclei (CCN) with consequent effects on Earth's radiation balance and climate. The quantitative assessment of the impact of DMS emissions on CCN concentrations necessitates a detailed description of the oxidation of DMS in the presence of existing aerosol particles and clouds. In the unpolluted marine atmosphere, DMS is efficiently oxidized to hydroperoxymethyl thioformate (HPMTF), a stable intermediate in the chemical trajectory toward sulfur dioxide (SO2) and ultimately sulfate aerosol. Using direct airborne flux measurements, we demonstrate that the irreversible loss of HPMTF to clouds in the marine boundary layer determines the HPMTF lifetime (τHPMTF < 2 h) and terminates DMS oxidation to SO2 When accounting for HPMTF cloud loss in a global chemical transport model, we show that SO2 production from DMS is reduced by 35% globally and near-surface (0 to 3 km) SO2 concentrations over the ocean are lowered by 24%. This large, previously unconsidered loss process for volatile sulfur accelerates the timescale for the conversion of DMS to sulfate while limiting new particle formation in the marine atmosphere and changing the dynamics of aerosol growth. This loss process potentially reduces the spatial scale over which DMS emissions contribute to aerosol production and growth and weakens the link between DMS emission and marine CCN production with subsequent implications for cloud formation, radiative forcing, and climate.

2.
Opt Lett ; 48(1): 13-16, 2023 Jan 01.
Article in English | MEDLINE | ID: mdl-36563362

ABSTRACT

Combined lidar and polarimeter retrievals of aerosol, cloud, and ocean microphysical properties involve single-scattering cloud calculations that are time consuming. We create a look-up table to speed up these calculations for water droplets in the atmosphere. In our new Lorenz-Mie look-up table we tabulate the light scattering by an ensemble of homogeneous isotropic spheres at wavelengths starting from 0.35 µm. The look-up table covers liquid water cloud particles with radii in the range of 0.001-500 µm while gaining an increase of up to 104 in computational speed. The covered complex refractive indices range from 1.25 to 1.36 for the real part and from 0 to 0.001 for the imaginary part. We show that we can precisely compute inherent optical properties for the particle size distributions ranging up to 100 µm for the effective radius and up to 0.6 for the effective variance. We test wavelengths from 0.35 to 2.3 µm and find that the elements of the normalized scattering matrix as well as the asymmetry parameter, the absorption, backscatter, extinction, and scattering coefficients are precise to within 1% for 96.7%-100% of cases depending on the inherent optical property. We also provide an example of using the look-up table with in situ measurements to determine agreement with remote sensing. The table together with C++, Fortran, MATLAB, and Python codes to interpolate the complex refractive index and apply different particle size distributions are freely available online.

3.
Pediatr Radiol ; 53(2): 273-281, 2023 02.
Article in English | MEDLINE | ID: mdl-36097227

ABSTRACT

BACKGROUND: Perinatal and childhood postmortem imaging has been accepted as a noninvasive alternative or adjunct to autopsy. However, the variation in funding models from institution to institution is a major factor prohibiting uniform provision of this service. OBJECTIVE: To describe current funding models employed in European and non-European institutions offering paediatric postmortem imaging services and to discuss the perceived barriers to future postmortem imaging service provision. MATERIALS AND METHODS: A web-based 16-question survey was distributed to members of the European Society of Paediatric Radiology (ESPR) and ESPR postmortem imaging task force over a 6-month period (March-August 2021). Survey questions related to the radiologic and autopsy services being offered and how each was funded within the respondent's institute. RESULTS: Eighteen individual responses were received (13/18, 72.2% from Europe). Only one-third of the institutions (6/18, 33.3%) have fully funded postmortem imaging services, with the remainder receiving partial (6/18, 33.3%) or no funding (5/18, 27.8%). Funding (full or partial) was more commonly available for forensic work (13/18, 72%), particularly where this was nationally provided. Where funding was not provided, the imaging and reporting costs were absorbed by the institute. CONCLUSION: Increased access is required for the expansion of postmortem imaging into routine clinical use. This can only be achieved with formal funding on a national level, potentially through health care commissioning and acknowledgement by health care policy makers and pathology services of the value the service provides following the death of a fetus or child. Funding should include the costs involved in training, equipment, reporting and image acquisition.


Subject(s)
Diagnostic Imaging , Radiology , Pregnancy , Female , Child , Humans , Autopsy/methods , Diagnostic Imaging/methods , Forensic Medicine , Surveys and Questionnaires
4.
Geophys Res Lett ; 49(18): e2022GL099175, 2022 Sep 28.
Article in English | MEDLINE | ID: mdl-36591326

ABSTRACT

Aerosol mass extinction efficiency (MEE) is a key aerosol property used to connect aerosol optical properties with aerosol mass concentrations. Using measurements of smoke obtained during the Fire Influence on Regional to Global Environments and Air Quality (FIREX-AQ) campaign we find that mid-visible smoke MEE can change by a factor of 2-3 between fresh smoke (<2 hr old) and one-day-old smoke. While increases in aerosol size partially explain this trend, changes in the real part of the aerosol refractive index (real(n)) are necessary to provide closure assuming Mie theory. Real(n) estimates derived from multiple days of FIREX-AQ measurements increase with age (from 1.40 - 1.45 to 1.5-1.54 from fresh to one-day-old) and are found to be positively correlated with organic aerosol oxidation state and aerosol size, and negatively correlated with smoke volatility. Future laboratory, field, and modeling studies should focus on better understanding and parameterizing these relationships to fully represent smoke aging.

5.
Biochem Biophys Res Commun ; 585: 196-202, 2021 12 31.
Article in English | MEDLINE | ID: mdl-34813980

ABSTRACT

Cancer stem cells have an important role in tumour biology. While their identity in haematological malignancies is clearly defined, stem cell identity remains elusive in some solid tumours. Clear cell renal cell carcinoma (ccRCC) represents the most common form of kidney cancer, but the identity or existence of ccRCC stem cells remains unknown. We aimed to discern their existence using the widely utilised side population approach in ccRCC cell lines. In all cells tested, a well-defined side population was identified, and cell-based assays suggested stem-like properties. However, limiting dilution assays revealed comparable tumour initiating abilities and tumour histology of side and non-side populations, and single cell RNA-sequencing revealed minimal differences between these populations. The results indicate that the side population approach is not sufficient for cancer stem cell discovery in ccRCC.


Subject(s)
Carcinoma, Renal Cell/genetics , Cell Transformation, Neoplastic/genetics , Gene Expression Regulation, Neoplastic , Kidney Neoplasms/genetics , Neoplastic Stem Cells/metabolism , Side-Population Cells/metabolism , Animals , Carcinoma, Renal Cell/metabolism , Carcinoma, Renal Cell/pathology , Cell Line, Tumor , Gene Expression Profiling/methods , Humans , Kidney Neoplasms/metabolism , Kidney Neoplasms/pathology , Mice, Inbred NOD , Mice, SCID , RNA-Seq/methods , Single-Cell Analysis/methods , Transplantation, Heterologous , Tumor Burden/genetics
6.
J Gen Intern Med ; 36(2): 288-295, 2021 02.
Article in English | MEDLINE | ID: mdl-32901440

ABSTRACT

BACKGROUND: Integrating evidence-based innovations (EBIs) into sustained use is challenging; most implementations in health systems fail. Increasing frontline teams' quality improvement (QI) capability may increase the implementation readiness and success of EBI implementation. OBJECTIVES: Develop a QI training program ("Learn. Engage. Act. Process." (LEAP)) and evaluate its impact on frontline obesity treatment teams to improve treatment delivered within the Veterans Health Administration (VHA). DESIGN: This was a pre-post evaluation of the LEAP program. MOVE! coordinators (N = 68) were invited to participate in LEAP; 24 were randomly assigned to four starting times. MOVE! coordinators formed teams to work on improvement aims. Pre-post surveys assessed team organizational readiness for implementing change and self-rated QI skills. Program satisfaction, assignment completion, and aim achievement were also evaluated. PARTICIPANTS: VHA facility-based MOVE! teams. INTERVENTIONS: LEAP is a 21-week QI training program. Core components include audit and feedback reports, structured curriculum, coaching and learning community, and online platform. MAIN MEASURES: Organizational readiness for implementing change (ORIC); self-rated QI skills before and after LEAP; assignment completion and aim achievement; program satisfaction. KEY RESULTS: Seventeen of 24 randomized teams participated in LEAP. Participants' self-ratings across six categories of QI skills increased after completing LEAP (p< 0.0001). The ORIC measure showed no statistically significant change overall; the change efficacy subscale marginally improved (p < 0.08), and the change commitment subscale remained the same (p = 0.66). Depending on the assignment, 35 to 100% of teams completed the assignment. Nine teams achieved their aim. Most team members were satisfied or very satisfied (81-89%) with the LEAP components, 74% intended to continue using QI methods, and 81% planned to continue improvement work. CONCLUSIONS: LEAP is scalable and does not require travel or time away from clinical responsibilities. While QI skills improved among participating teams and most completed the work, they struggled to do so amid competing clinical priorities.


Subject(s)
Mentoring , Quality Improvement , Clinical Competence , Curriculum , Humans , Implementation Science
7.
Geophys Res Lett ; 48(19)2021 Oct 16.
Article in English | MEDLINE | ID: mdl-34776556

ABSTRACT

The warm Gulf Stream sea surface temperatures strongly impact the evolution of winter clouds behind atmospheric cold fronts. Such cloud evolution remains challenging to model. The Gulf Stream is too wide within the ERA5 and MERRA2 reanalyses, affecting the turbulent surface fluxes. Known problems within the ERA5 boundary layer (too-dry and too-cool with too strong westerlies), ascertained primarily from ACTIVATE 2020 campaign aircraft dropsondes and secondarily from older buoy measurements, reinforce surface flux biases. In contrast, MERRA2 winter surface winds and air-sea temperature/humidity differences are slightly too weak, producing surface fluxes that are too low. Reanalyses boundary layer heights in the strongly forced winter cold-air-outbreak regime are realistic, whereas late-summer quiescent stable boundary layers are too shallow. Nevertheless, the reanalysis biases are small, and reanalyses adequately support their use for initializing higher-resolution cloud process modeling studies of cold-air outbreaks.

8.
Geophys Res Lett ; 48(23)2021 Dec 16.
Article in English | MEDLINE | ID: mdl-35136274

ABSTRACT

Leveraging aerosol data from multiple airborne and surface-based field campaigns encompassing diverse environmental conditions, we calculate statistics of the oxalate-sulfate mass ratio (median: 0.0217; 95% confidence interval: 0.0154-0.0296; R = 0.76; N = 2,948). Ground-based measurements of the oxalate-sulfate ratio fall within our 95% confidence interval, suggesting the range is robust within the mixed layer for the submicrometer particle size range. We demonstrate that dust and biomass burning emissions can separately bias this ratio toward higher values by at least one order of magnitude. In the absence of these confounding factors, the 95% confidence interval of the ratio may be used to estimate the relative extent of aqueous processing by comparing inferred oxalate concentrations between air masses, with the assumption that sulfate primarily originates from aqueous processing.

9.
Int J Legal Med ; 134(2): 637-643, 2020 Mar.
Article in English | MEDLINE | ID: mdl-31250083

ABSTRACT

On 14 June 2017 at 00:54 h, the worst residential fire since the conclusion of the Second World War broke out in Flat 16, 4th floor of the 24-storey residential Grenfell Tower Block of flats, North Kensington, West London, UK. Seventy-one adults and children died, including one stillbirth. All victims of the Grenfell Tower disaster who died at the scene underwent post-mortem computed tomography (PMCT) imaging using a mortuary-sited mobile computed tomography scanner. For the first time, to the authors' knowledge, the disaster victim identification (DVI) radiology reporting was undertaken remote to the mortuary scanning. Over an 11-week period, 119 scans were undertaken on 16 days, with up to 18 scans a day. These were delivered to a remote reporting centre at Leicester on 13 days with between 2 and 20 scans arriving each day. Using a disaster-specific process pathway, a team of 4 reporters, with 3 support staff members, trialled a prototype INTERPOL DVI radiology reporting form and produced full radiology reports and supporting image datasets such that they were able to provide 96% of prototype DVI forms, 99% of image datasets and 86% of preliminary reports to the DVI teams in London within one working day of image receipt. This paper describes the first use of remote radiology reporting for DVI and exemplifies how remote PMCT reporting can be used to support a DVI process of this scale.


Subject(s)
Body Remains/diagnostic imaging , Disaster Victims , Documentation , Forensic Anthropology/instrumentation , Tomography Scanners, X-Ray Computed , Tomography, X-Ray Computed/methods , Fires , Humans , United Kingdom
10.
Intern Med J ; 49(7): 867-873, 2019 07.
Article in English | MEDLINE | ID: mdl-30515957

ABSTRACT

BACKGROUND: An increasing prevalence of diabetes mellitus has led to a high risk of diabetic foot infections (DFI) and associated morbidity. However, little is known about the relationship between DFI and mortality. AIM: To investigate the risk of mortality and associated factors in patients with DFI in an Australian context. METHODS: A prospective cohort study of inpatients with DFI between May 2012 and October 2016 was done at Royal Darwin Hospital, a tertiary referral hospital for the Top End of the Northern Territory. Primary outcome was 1-year mortality with Cox regression analysis undertaken to assess risk factors for mortality. RESULTS: Four hundred and thirteen consecutive adult diabetic patients with 737 admissions were referred to the High-Risk Foot Service for DFI. Cumulative risk of mortality at 1 year was 8.9% (95% confidence interval (CI) 6.4-12.2). On univariable analysis, mortality was associated with older age (hazard ratio (HR) per year increase 1.08, 95% CI 1.06-1.11, P = 0.001), haemodialysis (HR 3.64, 1.74-7.62, P < 0.001), isolation of Pseudomonas aeruginosa (HR 2.32, 1.05-5.12, P = 0.04) and ischaemic heart disease (HR 2.05, 1.04-4.07, P = 0.04), while indigenous status (HR 0.48, 0.25-0.95, P = 0.04) and HbA1c > 7% (HR 0.45, 0.20-0.99, P < 0.05) were protective. After adjusting for confounders, independent risk factors for mortality were haemodialysis (adjusted HR 5.76, 95% CI 2.28-14.59, P < 0.001) and older age (adjusted HR 1.09, 1.06-1.13, P < 0.001). Patients on haemodialysis had a cumulative risk of mortality of 24.5% (95% CI 14.0-40.8) at 1 year. CONCLUSION: There is a high risk of mortality associated with DFI, substantially increased in patients undergoing haemodialysis, highlighting the importance of early and dedicated interventions targeted at this high-risk group.


Subject(s)
Diabetic Foot/diagnosis , Diabetic Foot/mortality , Electronic Health Records/trends , Renal Dialysis/mortality , Adult , Aged , Cohort Studies , Diabetic Foot/therapy , Female , Follow-Up Studies , Humans , Male , Middle Aged , Mortality/trends , Prospective Studies , Renal Dialysis/trends , Risk Factors
11.
BMC Health Serv Res ; 19(1): 145, 2019 Mar 04.
Article in English | MEDLINE | ID: mdl-30832649

ABSTRACT

BACKGROUND: An important goal of the patient-centered medical home is increasing timely access for urgent needs, while maintaining continuity. In academic primary care clinics, meeting this goal, along with training medical residents and associated professionals, is challenging. METHODS: The aim of this study was to understand how academic primary care clinics provide continuity to patients requesting same-day access and identify factors that may affect site-level success. We conducted qualitative interviews from December 2013-October 2014 with primary care leadership involved with residency programs at 19 Veterans Health Administration academically-affiliated medical centers. Interview recordings were transcribed verbatim. To analyze the data, we created comprehensive, structured transcript summaries for each site. Site summaries were then entered into NVivo 10 software and coded by main categories to facilitate within-case and cross-case analyses. Themes and patterns across sites were identified using matrix analysis. RESULTS: Interviewees found it challenging to provide continuity for same-day in-person visits. Most sites took a team-based approach to ensure continuity and provide coverage for same-day access, notably using NPs, PAs, and RNs in their coverage algorithms. Further, they reported several adaptations that increased multiple types of continuity for walk-in patients, urgent care between in-person visits, and follow-up care. While this study focused on longitudinal continuity, both by individual PCPs or by a team of professionals, informational continuity and continuity of supervision, as well as, to a lesser extent, relational and management continuity, were also addressed in our interviews. Finally, most interviewees reported clinic intention to provide patient-centered, team-based care and a robust educational experience for trainees, and endeavored to structure their clinics in ways that align these two missions. CONCLUSIONS: In contending with the tension between providing continuity and educating new clinicians, clinics have re-conceptualized continuity as team-based, creating alternative strategies to same-day visits with a usual provider, coupled with communication strategies. Understanding the effect of these strategies on different types of continuity as well as patient experience and outcomes are key next steps in the further development and dissemination of effective models for improving continuity and the transition to team-based care in the academic clinic setting.


Subject(s)
Ambulatory Care Facilities/organization & administration , Continuity of Patient Care/organization & administration , Patient Care Team , Academic Medical Centers , Ambulatory Care/organization & administration , Communication , Humans , Internship and Residency , Primary Health Care , United States , United States Department of Veterans Affairs , Veterans
12.
Lancet ; 390(10090): 145-154, 2017 07 08.
Article in English | MEDLINE | ID: mdl-28551075

ABSTRACT

BACKGROUND: England and Wales have one of the highest frequencies of autopsy in the world. Implementation of post-mortem CT (PMCT), enhanced with targeted coronary angiography (PMCTA), in adults to avoid invasive autopsy would have cultural, religious, and potential economic benefits. We aimed to assess the diagnostic accuracy of PMCTA as a first-line technique in post-mortem investigations. METHODS: In this single-centre (Leicester, UK), prospective, controlled study, we selected cases of natural and non-suspicious unnatural death referred to Her Majesty's (HM) Coroners. We excluded cases younger than 18 years, known to have had a transmittable disease, or who weighed more than 125 kg. Each case was assessed by PMCTA, followed by autopsy. Pathologists were masked to the PMCTA findings, unless a potential risk was shown. The primary endpoint was the accuracy of the cause of death diagnosis from PMCTA against a gold standard of autopsy findings, modified by PMCTA findings only if additional substantially incontrovertible findings were identified. FINDINGS: Between Jan 20, 2010, and Sept 13, 2012, we selected 241 cases, for which PMCTA was successful in 204 (85%). Seven cases were excluded from the analysis because of procedural unmasking or no autopsy data, as were 24 cases with a clear diagnosis of traumatic death before investigation; 210 cases were included. In 40 (19%) cases, predictable toxicology or histology testing accessible by PMCT informed the result. PMCTA provided a cause of death in 193 (92%) cases. A major discrepancy with the gold standard was noted in 12 (6%) cases identified by PMCTA, and in nine (5%) cases identified by autopsy (because of specific findings on PMCTA). The frequency of autopsy and PMCTA discrepancies were not significantly different (p=0·65 for major discrepancies and p=0·21 for minor discrepancies). Cause of death given by PMCTA did not overlook clinically significant trauma, occupational lung disease, or reportable disease, and did not significantly affect the overall population data for cause of death (p≥0·31). PMCTA was better at identifying trauma and haemorrhage (p=0·008), whereas autopsy was better at identifying pulmonary thromboembolism (p=0·004). INTERPRETATION: For most sudden natural adult deaths investigated by HM Coroners, PMCTA could be used to avoid invasive autopsy. The gold standard of post-mortem investigations should include both PMCT and invasive autopsy. FUNDING: National Institute for Health Research.


Subject(s)
Autopsy/methods , Death, Sudden/etiology , Tomography, X-Ray Computed/methods , Adolescent , Adult , Aged , Aged, 80 and over , Cause of Death , Cerebral Hemorrhage/diagnostic imaging , Coronary Angiography , Coroners and Medical Examiners , Double-Blind Method , Female , Humans , Male , Middle Aged , Myocardial Infarction/diagnostic imaging , Prospective Studies , Young Adult
14.
Med Care ; 55 Suppl 7 Suppl 1: S84-S91, 2017 07.
Article in English | MEDLINE | ID: mdl-28614185

ABSTRACT

BACKGROUND: Improving access can increase the providers a patient sees, and cause coordination challenges. For initiatives that increase care across health care settings, measuring patient experiences with access and care coordination will be crucial. OBJECTIVES: Map existing survey measures of patient experiences with access and care coordination expected to be relevant to patients accessing care across settings. Preliminarily examine whether aspects of access and care coordination important to patients are represented by existing measures. RESEARCH DESIGN: Structured literature review of domains and existing survey measures related to access and care coordination across settings. Survey measures, and preliminary themes from semistructured interviews of 10 patients offered VA-purchased Community Care, were mapped to identified domains. RESULTS: We identified 31 existing survey instruments with 279 items representing 6 access and 5 care coordination domains relevant to cross-system care. Domains frequently assessed by existing measures included follow-up coordination, primary care access, cross-setting coordination, and continuity. Preliminary issues identified in interviews, but not commonly assessed by existing measures included: (1) acceptability of distance to care site given patient's clinical situation; (2) burden on patients to access and coordinate care and billing; (3) provider familiarity with Veteran culture and VA processes. CONCLUSIONS: Existing survey instruments assess many aspects of patient experiences with access and care coordination in cross-system care. Systems assessing cross-system care should consider whether patient surveys accurately reflect the level of patients' concerns with burden to access and coordinate care, and adequately reflect the impact of clinical severity and cultural familiarity on patient preferences.


Subject(s)
Continuity of Patient Care/standards , Health Care Surveys/instrumentation , Health Services Accessibility/standards , Patient Satisfaction , Female , Humans , Interviews as Topic , Male
15.
Int J Legal Med ; 131(1): 211-216, 2017 Jan.
Article in English | MEDLINE | ID: mdl-27817167

ABSTRACT

We report for the first time the use of coaxial cutting needle biopsy, guided by post-mortem computed tomography (PMCT), to sample internal body tissues for bacterioplankton PCR analysis to investigate drowning. This technical report describes the biopsy technique, the comparison of the needle biopsy and the invasive autopsy sampling results, as well as the PMCT and autopsy findings. By using this new biopsy sampling approach for bacterioplankton PCR, we have developed on previous papers describing the minimally invasive PMCT approach for the diagnosis of drowning. When such a system is used, the operator must take all precautions to avoid contamination of the core biopsy samples due to the sensitivity of PCR-based analytic systems.


Subject(s)
Aeromonas/genetics , Biopsy, Needle/methods , DNA, Bacterial/isolation & purification , Drowning/diagnosis , Aged, 80 and over , Brain/diagnostic imaging , Brain/microbiology , Brain/pathology , Humans , Kidney/diagnostic imaging , Kidney/microbiology , Kidney/pathology , Lung/diagnostic imaging , Lung/microbiology , Lung/pathology , Male , Polymerase Chain Reaction , Radiography, Interventional , Spleen/diagnostic imaging , Spleen/microbiology , Spleen/pathology , Tomography, X-Ray Computed , Whole Body Imaging
16.
J Nurs Adm ; 47(12): 636-644, 2017 Dec.
Article in English | MEDLINE | ID: mdl-29135855

ABSTRACT

BACKGROUND: In 2010, the Veterans Health Administration issued a Staffing Methodology (SM) Directive to provide a standardized, data-driven method for determining appropriate inpatient nurse staffing. OBJECTIVE: We aimed to describe experiences and factors related to SM implementation. METHODS: We administered a Web-based survey to chief nurse executives to obtain their implementation experiences. Structural, process, and outcome factors and barriers associated with self-reported implementation success were identified. RESULTS: Respondents representing 104 of 117 facilities participated. Almost all facilities (96%) had completed at least 1 cycle of SM, yet only half (52%) rated their implementation highly successful. Early implementation date, higher levels of leadership confidence in SM, and higher frequency in which nursing staff think in terms of hours per patient day were associated with higher SM implementation success. Time, staff training and educational needs, and engagement were common barriers. DISCUSSION: Understanding factors that influence successful implementation of staffing policies is important to ensuring safe staffing.


Subject(s)
Hospitals, Veterans , Models, Nursing , Nurse Administrators/standards , Nursing Staff, Hospital/statistics & numerical data , Personnel Staffing and Scheduling/organization & administration , Humans , Nursing Administration Research , Organizational Objectives , Quality Assurance, Health Care , United States , Workforce , Workload
17.
Hum Mol Genet ; 23(8): 2176-88, 2014 Apr 15.
Article in English | MEDLINE | ID: mdl-24301681

ABSTRACT

Ischemia caused by coronary artery disease and myocardial infarction leads to aberrant ventricular remodeling and cardiac fibrosis. This occurs partly through accumulation of gene expression changes in resident fibroblasts, resulting in an overactive fibrotic phenotype. Long-term adaptation to a hypoxic insult is likely to require significant modification of chromatin structure in order to maintain the fibrotic phenotype. Epigenetic changes may play an important role in modulating hypoxia-induced fibrosis within the heart. Therefore, the aim of the study was to investigate the potential pro-fibrotic impact of hypoxia on cardiac fibroblasts and determine whether alterations in DNA methylation could play a role in this process. This study found that within human cardiac tissue, the degree of hypoxia was associated with increased expression of collagen 1 and alpha-smooth muscle actin (ASMA). In addition, human cardiac fibroblast cells exposed to prolonged 1% hypoxia resulted in a pro-fibrotic state. These hypoxia-induced pro-fibrotic changes were associated with global DNA hypermethylation and increased expression of the DNA methyltransferase (DNMT) enzymes DNMT1 and DNMT3B. Expression of these methylating enzymes was shown to be regulated by hypoxia-inducible factor (HIF)-1α. Using siRNA to block DNMT3B expression significantly reduced collagen 1 and ASMA expression. In addition, application of the DNMT inhibitor 5-aza-2'-deoxycytidine suppressed the pro-fibrotic effects of TGFß. Epigenetic modifications and changes in the epigenetic machinery identified in cardiac fibroblasts during prolonged hypoxia may contribute to the pro-fibrotic nature of the ischemic milieu. Targeting up-regulated expression of DNMTs in ischemic heart disease may prove to be a valuable therapeutic approach.


Subject(s)
DNA Methylation , Epigenomics , Fibrosis/etiology , Heart/physiopathology , Hypoxia/complications , Myofibroblasts/pathology , Aged , Blotting, Western , Cells, Cultured , Collagen/genetics , Collagen/metabolism , DNA (Cytosine-5-)-Methyltransferase 1 , DNA (Cytosine-5-)-Methyltransferases/antagonists & inhibitors , DNA (Cytosine-5-)-Methyltransferases/genetics , DNA (Cytosine-5-)-Methyltransferases/metabolism , Female , Fibrosis/metabolism , Fibrosis/pathology , Flow Cytometry , Humans , Hypoxia/physiopathology , Immunoenzyme Techniques , Male , Myofibroblasts/metabolism , Phenotype , RNA, Messenger/genetics , RNA, Small Interfering/genetics , Real-Time Polymerase Chain Reaction , Reverse Transcriptase Polymerase Chain Reaction , Transforming Growth Factor beta/genetics , Transforming Growth Factor beta/metabolism , DNA Methyltransferase 3B
18.
Lancet ; 385(9964): 253-9, 2015 Jan 17.
Article in English | MEDLINE | ID: mdl-25238931

ABSTRACT

BACKGROUND: Richard III was the last king of England to die in battle, but how he died is unknown. On Sept 4, 2012, a skeleton was excavated in Leicester that was identified as Richard. We investigated the trauma to the skeleton with modern forensic techniques, such as conventional CT and micro-CT scanning, to characterise the injuries and establish the probable cause of death. METHODS: We assessed age and sex through direct analysis of the skeleton and from CT images. All bones were examined under direct light and multi-spectral illumination. We then scanned the skeleton with whole-body post-mortem CT. We subsequently examined bones with identified injuries with micro-CT. We deemed that trauma was perimortem when we recorded no evidence of healing and when breakage characteristics were typical of fresh bone. We used previous data to identify the weapons responsible for the recorded injuries. FINDINGS: The skeleton was that of an adult man with a gracile build and severe scoliosis of the thoracic spine. Standard anthropological age estimation techniques based on dry bone analysis gave an age range between 20s and 30s. Standard post-mortem CT methods were used to assess rib end morphology, auricular surfaces, pubic symphyseal face, and cranial sutures, to produce a multifactorial narrower age range estimation of 30-34 years. We identified nine perimortem injuries to the skull and two to the postcranial skeleton. We identified no healed injuries. The injuries were consistent with those created by weapons from the later medieval period. We could not identify the specific order of the injuries, because they were all distinct, with no overlapping wounds. Three of the injuries-two to the inferior cranium and one to the pelvis-could have been fatal. INTERPRETATION: The wounds to the skull suggest that Richard was not wearing a helmet, although the absence of defensive wounds on his arms and hands suggests he was still otherwise armoured. Therefore, the potentially fatal pelvis injury was probably received post mortem, meaning that the most likely injuries to have caused his death are the two to the inferior cranium. FUNDING: The University of Leicester.


Subject(s)
Facial Injuries/pathology , Head Injuries, Penetrating/pathology , Pelvic Bones/injuries , Ribs/injuries , Skull Fractures/pathology , Weapons , Adult , Autopsy , England , Head Injuries, Penetrating/diagnostic imaging , History, Medieval , Humans , Male , Protective Clothing/history , Skull Fractures/diagnostic imaging , Tomography, X-Ray Computed , Wounds, Penetrating/diagnostic imaging , Wounds, Penetrating/pathology
19.
J Adv Nurs ; 72(8): 1886-98, 2016 Aug.
Article in English | MEDLINE | ID: mdl-27030070

ABSTRACT

AIM/S: To assess implementation of the Veterans Health Administration staffing methodology directive. BACKGROUND: In 2010 the Veterans Health Administration promulgated a staffing methodology directive for inpatient nursing units to address staffing and budget forecasting. DESIGN: A qualitative multi-case evaluation approach assessed staffing methodology implementation. METHODS: Semi-structured telephone interviews were conducted from March - June 2014 with Nurse Executives and their teams at 21 facilities. Interviews focused on the budgeting process, implementation experiences, use of data, leadership support, and training. An implementation score was created for each facility using a 4-point rating scale. The scores were used to select three facilities (low, medium and high implementation) for more detailed case studies. RESULTS/FINDINGS: After analysing interview summaries, the evaluation team developed a four domain scoring structure: (1) integration of staffing methodology into budget development; (2) implementation of the Directive elements; (3) engagement of leadership and staff; and (4) use of data to support the staffing methodology process. The high implementation facility had leadership understanding and endorsement of staffing methodology, confidence in and ability to work with data, and integration of staffing methodology results into the budgeting process. The low implementation facility reported poor leadership engagement and little understanding of data sources and interpretation. CONCLUSION: Implementation varies widely across facilities. Implementing staffing methodology in facilities with complex and changing staffing needs requires substantial commitment at all organizational levels especially for facilities that have traditionally relied on historical levels to budget for staffing.


Subject(s)
Leadership , Nurse Administrators , Humans , United States , United States Department of Veterans Affairs , Veterans
20.
Vet Surg ; 45(1): 115-20, 2016 Jan.
Article in English | MEDLINE | ID: mdl-26731600

ABSTRACT

OBJECTIVE: To describe a technique of canaliculosinostomy into the caudal maxillary sinus to alleviate epiphora secondary to nasolacrimal duct obstruction and to report the long-term outcome in 5 horses. STUDY DESIGN: Case series. ANIMALS: Five client-owned horses. METHODS: Case records of all horses presented for chronic epiphora to a single equine hospital that underwent surgical treatment were reviewed. All included horses had a Jones test or dacryocystography to confirm nasolacrimal duct obstruction. All horses were anesthetized and canaliculosinostomy was created from the medial canthus of the eye into the caudal maxillary sinus using a Steinmann pin and Jacob's chuck. A Foley catheter was placed normograde through the stoma. The inflated bulb held the Foley in place in the sinus, while the proximal end was pulled through the upper eyelid and sutured to the skin on the head. The Foley catheter was maintained in place for 3 weeks and then removed under sedation. RESULTS: Five horses were included. There were no intraoperative difficulties or complications. One horse dislodged the Foley catheter 3 days postoperatively. No other postoperative complications occurred. Followup was available for all horses. One horse was euthanatized for unrelated reasons 10 weeks postoperative at which time epiphora was resolved. The remaining 4 horses had resolution of epiphora at followup (24-46 months postoperative). CONCLUSION: This report describes a simple technique for canaliculosinostomy into the caudal maxillary sinus and long-term outcome in 4 of 5 horses, all of which had resolution of epiphora. This technique can be used to resolve epiphora of various etiologies.


Subject(s)
Horse Diseases/surgery , Lacrimal Apparatus Diseases/veterinary , Maxillary Sinus/surgery , Animals , Horses , Lacrimal Apparatus Diseases/surgery , Postoperative Complications/surgery , Postoperative Complications/veterinary , Retrospective Studies
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