Cardiovascular disease is a significant and ever-growing problem in the United Kingdom, accounting for nearly one-third of all deaths and leading to significant morbidity. It is also of particular ...and pressing interest as developing countries experience a change in lifestyle which introduces novel risk factors for cardiovascular disease, leading to a boom in cardiovascular disease risk throughout the developing world. The burden of cardiovascular disease can be ameliorated by careful risk reduction and, as such, primary prevention is an important priority for all developers of health policy. Strong consensus exists between international guidelines regarding the necessity of smoking cessation, weight optimisation and the importance of exercise, whilst guidelines vary slightly in their approach to hypertension and considerably regarding their approach to optimal lipid profile which remains a contentious issue. Previously fashionable ideas such as the polypill appear devoid of in-vivo efficacy, but there remain areas of future interest such as the benefit of serum urate reduction and utility of reduction of homocysteine levels.
Age-related alterations in immunity have been linked to increased incidence of infections and decreased responses to vaccines in the aging population. Human peripheral blood monocytes are known to ...promote Ag presentation and antiviral activities; however, the impact of aging on monocyte functions remains an open question. We present an in-depth global analysis examining the impact of aging on classical (CD14
CD16
), intermediate (CD14
CD16
), and nonclassical (CD14
CD16
) monocytes. Monocytes sorted from nonfrail healthy adults (21-40 y) and old (≥65 y) individuals were analyzed after stimulation with TLR4, TLR7/8, and retinoic acid-inducible gene I agonists. Our data showed that under nonstimulated conditions, monocyte subsets did not reveal significant age-related alternations; however, agonist stimulated-monocytes from adults and old subjects did show differences at the transcriptional and functional levels. These alternations in many immune-related transcripts and biological processes resulted in reduced production of IFN-α, IFN-γ, IL-1β, CCL20, and CCL8, and higher expression of CX3CR1 in monocytes from old subjects. Our findings represent a comprehensive analysis of the influence of human aging on pattern recognition receptors signaling and monocyte functions, and have implications for strategies to enhance the immune response in the context of infection and immunization.
Limited data are available on the characteristics, clinical management, and outcomes of patients with atrial fibrillation at risk of stroke, from a worldwide perspective. The aim of this study was to ...describe the baseline characteristics and initial therapeutic management of patients with non-valvular atrial fibrillation across the spectrum of sites at which these patients are treated.
The Global Anticoagulant Registry in the FIELD (GARFIELD) is an observational study of patients newly diagnosed with non-valvular atrial fibrillation. Enrollment into Cohort 1 (of 5) took place between December 2009 and October 2011 at 540 sites in 19 countries in Europe, Asia-Pacific, Central/South America, and Canada. Investigator sites are representative of the distribution of atrial fibrillation care settings in each country. Cohort 1 comprised 10,614 adults (≥18 years) diagnosed with non-valvular atrial fibrillation within the previous 6 weeks, with ≥1 investigator-defined stroke risk factor (not limited to those in existing risk-stratification schemes), and regardless of therapy. Data collected at baseline included demographics, medical history, care setting, nature of atrial fibrillation, and treatments initiated at diagnosis. The mean (SD) age of the population was 70.2 (11.2) years; 43.2% were women. Mean±SD CHADS2 score was 1.9±1.2, and 57.2% had a score ≥2. Mean CHA2DS2-VASc score was 3.2±1.6, and 8,957 (84.4%) had a score ≥2. Overall, 38.0% of patients with a CHADS2 score ≥2 did not receive anticoagulant therapy, whereas 42.5% of those at low risk (score 0) received anticoagulant therapy.
These contemporary observational worldwide data on non-valvular atrial fibrillation, collected at the end of the vitamin K antagonist-only era, indicate that these drugs are frequently not being used according to stroke risk scores and guidelines, with overuse in patients at low risk and underuse in those at high risk of stroke.
ClinicalTrials.gov TRI08888.
A highly flexible, stacked, switch module is proposed, wherein multiple independent 1 × N wavelength selective switches (WSSs) can be realized on a single 4k liquid crystal on silicon device. The ...stacked WSS module can be configured in different ways for application at either the transit side or the add/drop side of a colorless, directionless, and contentionless (CDC) reconfigurable optical add/drop multiplexer (ROADM). TwoROADMarchitectures are proposed based on the stacked WSS modules. Their costs are analyzed for both a 4-deg network node and a larger 8-deg node. The first proposed ROADM architecture with full CDC features is shown to realize a cost reduction of at least 35% in these two test network nodes, when compared with the conventional CDC ROADMarchitecture based on the standalone WSSs and multicasting switches (MCSs). The second ROADM architecture proposed has a small probability of wavelength contention, which could be prevented by a local wavelength assignment algorithm. According to our cost estimation, we are able to aggressively reduce the number of components at the add/drop side and make an overall cost reduction of >70% and >80% in the 4- and 8-deg network nodes, respectively.
The DNA cytosine deaminase APOBEC3B (A3B) is a newly recognized endogenous source of mutations in a range of human tumors, including head/neck cancer. A3B inflicts C-to-T and C-to-G base ...substitutions in 5′-TCA/T trinucleotide motifs, contributes to accelerated rates of tumor development, and affects clinical outcomes in a variety of cancer types. High-risk human papillomavirus (HPV) infection causes A3B overexpression, and HPV-positive cervical and head/neck cancers are among tumor types with the highest degree of APOBEC signature mutations. A3B overexpression in HPV-positive tumor types is caused by the viral E6/E7 oncoproteins and may be an early off-to-on switch in tumorigenesis. In comparison, less is known about the molecular mechanisms responsible for A3B overexpression in HPV-negative head/neck cancers. Here, we utilize an immunohistochemical approach to determine whether A3B is turned from off-to-on or if it undergoes a more gradual transition to overexpression in HPV-negative head/neck cancers. As positive controls, almost all HPV-positive oral epithelial dysplasias and oropharyngeal cancers showed high levels of nuclear A3B staining regardless of diagnosis. As negative controls, A3B levels were low in phenotypically normal epithelium adjacent to cancer and oral epithelial hyperplasias. Interestingly, HPV-negative and low-grade oral epithelial dysplasias showed intermediate A3B levels, while high-grade oral dysplasias showed high A3B levels similar to oral squamous cell carcinomas. A3B levels were highest in grade 2 and grade 3 oral squamous cell carcinomas. In addition, a strong positive association was found between nuclear A3B and Ki67 scores suggesting a linkage to the cell cycle. Overall, these results support a model in which gradual activation of A3B expression occurs during HPV-negative tumor development and suggest that A3B overexpression may provide a marker for advanced grade oral dysplasia and cancer.
Primary intraosseous xanthomas of the jaws (PIXJ) are rare and predominantly affect the posterior mandible (86%) of normolipemic patients, with a mean age of 30 years and no gender predilection. ...Clinically, PIXJ exhibit indolent biologic behavior; curettage is considered treatment of choice. Only 36 PIXJ have been reported. Apoptosis-related hyaline globules (HGs), also known as “thanatosomes”, have not been previously reported in PIXJ. Cases diagnosed as xanthoma of bone were retrieved. Six cases fulfilling currently accepted criteria were identified and their clinicopathologic and immunohistochemical properties are presented herein. Mean age for PIXJ was 21.8 years (range = 12–33) and F:M ratio = 2:1. All cases presented as well-demarcated, unilocular or multilocular radiolucencies. Microscopically, PIXJ featured sheets of lipid-laden macrophages with eosinophilic or foamy cytoplasm. A secondary fibroblastic population lacking storiform pattern was evident in two cases. Adipocytes (3/6), peripheral neurovascular bundles (1/6), bone fragments (3/6) and dystrophic calcifications (3/6) were observed enclosed by the xanthoma cells. Notably, one case exhibited numerous, spherical, eosinophilic HGs containing apoptotic nuclei. PIXJ were consistently CD68(+) and negative for CD1α and S100. CD45 decorated lymphocytes and the membrane of foamy histiocytes. Xanthoma cells stained for lysozyme and plasma proteins including alpha-1 antitrypsin (AAT), IgG and IgA in one probed case. HGs were lysozyme(+), AAT(+), IgG(+), IgA(+), PAS(+) and diastase-resistant, and fuchsinophilic with Masson’s trichrome. PIXJ represent infrequent, solitary, mandibular lesions with a predilection for the second and third decade of life. Thanatosomes associated with cell injury and death can be present in PIXJ.
Purpose
The purpose of this paper is to introduce and explore stuckness as a felt phenomenon in psychiatric practice in order to stimulate clinicians in mental health settings to be on the lookout ...for stuckness and on the lookout for unexpected solutions to difficult clinical scenarios.
Design/methodology/approach
Signs of stuckness are looked at and then proposed causal factors of stuckness in clinical practice are reviewed. These are divided conceptually into four main groupings: patient factors, clinician factors, service factors and societal factors.
Findings
Although clinicians are encouraged to acknowledge when stuckness is present and to try to address possible causes with their patients, clinicians are also advised to work on understanding stuckness as a natural part of creative processes. It is suggested that services should draw on a psychoanalytic ethos to support staff to tolerate and respond to stuckness better.
Originality/value
Feeling stuck with patients’ partial recoveries or “revolving door” cycles is uncomfortable. In stretched psychiatric services in particular stuckness may go unnoticed, and instead the difficulty of the work with patients may inadvertently drive therapeutic mania or rejection of the patients, which can lead to harm. This paper offers a simple scheme to use when thinking about stuck patients in the psychiatric setting with the hope that this can stimulate clinicians to search for new creative solutions for patients.
Biofouling is the accumulation of organisms on surfaces immersed in water. It is of particular concern to the international shipping industry because it increases fuel costs and presents a ...biosecurity risk by providing a pathway for non-indigenous marine species to establish in new areas. There is growing interest within jurisdictions to strengthen biofouling risk-management regulations, but it is expensive to conduct in-water inspections and assess the collected data to determine the biofouling state of vessel hulls. Machine learning is well suited to tackle the latter challenge, and here we apply deep learning to automate the classification of images from in-water inspections to identify the presence and severity of fouling. We combined several datasets to obtain over 10,000 images collected from in-water surveys which were annotated by a group biofouling experts. We compared the annotations from three experts on a 120-sample subset of these images, and found that they showed 89% agreement (95% CI: 87-92%). Subsequent labelling of the whole dataset by one of these experts achieved similar levels of agreement with this group of experts, which we defined as performing at most 5% worse (p Formula: see text 0.009-0.054). Using these expert labels, we were able to train a deep learning model that also agreed similarly with the group of experts (p Formula: see text 0.001-0.014), demonstrating that automated analysis of biofouling in images is feasible and effective using this method.
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