5,205 research outputs found

    The relationship between external job mobility and salary attainment across career stages

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    The current study examines the relationship between external job mobility and salary for employees in different career stages. Based on career stage and career timetable theories, we predict that external job mobility would generate the greatest salary benefits for early-career employees whereas external job mobility would generate fewer salary benefits for employees in mid- and late career stages. Data collected from multiple industries in Hong Kong and the United States consistently show that, as expected, highly mobile early-career employees earn significantly greater salaries than their less mobile peers do. The positive effects of external job mobility on salary were stronger for early-career workers than for mid-and late-career workers.postprin

    On the potential for mapping apparent neural soma density via a clinically viable diffusion MRI protocol

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    Diffusion MRI is a valuable tool for probing tissue microstructure in the brain noninvasively. Today, model-based techniques are widely available and used for white matter characterisation where their development is relatively mature. Conversely, tissue modelling in grey matter is more challenging, and no generally accepted models exist. With advances in measurement technology and modelling efforts, a clinically viable technique that reveals salient features of grey matter microstructure, such as the density of quasi-spherical cell bodies and quasi-cylindrical cell projections, is an exciting prospect. As a step towards capturing the microscopic architecture of grey matter in clinically feasible settings, this work uses a biophysical model that is designed to disentangle the diffusion signatures of spherical and cylindrical structures in the presence of orientation heterogeneity, and takes advantage of B-tensor encoding measurements, which provide additional sensitivity compared to standard single diffusion encoding sequences. For the fast and robust estimation of microstructural parameters, we leverage recent advances in machine learning and replace conventional fitting techniques with an artificial neural network that fits complex biophysical models within seconds. Our results demonstrate apparent markers of spherical and cylindrical geometries in healthy human subjects, and in particular an increased volume fraction of spherical compartments in grey matter compared to white matter. We evaluate the extent to which spherical and cylindrical geometries may be interpreted as correlates of neural soma and neural projections, respectively, and quantify parameter estimation errors in the presence of various departures from the modelling assumptions. While further work is necessary to translate the ideas presented in this work to the clinic, we suggest that biomarkers focussing on quasi-spherical cellular geometries may be valuable for the enhanced assessment of neurodevelopmental disorders and neurodegenerative diseases

    p63 is a key regulator of iRHOM2 signalling in the keratinocyte stress response.

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    Hyperproliferative keratinocytes induced by trauma, hyperkeratosis and/or inflammation display molecular signatures similar to those of palmoplantar epidermis. Inherited gain-of-function mutations in RHBDF2 (encoding iRHOM2) are associated with a hyperproliferative palmoplantar keratoderma and squamous oesophageal cancer syndrome (termed TOC). In contrast, genetic ablation of rhbdf2 in mice leads to a thinning of the mammalian footpad, and reduces keratinocyte hyperproliferation and migration. Here, we report that iRHOM2 is a novel target gene of p63 and that both p63 and iRHOM2 differentially regulate cellular stress-associated signalling pathways in normal and hyperproliferative keratinocytes. We demonstrate that p63-iRHOM2 regulates cell survival and response to oxidative stress via modulation of SURVIVIN and Cytoglobin, respectively. Furthermore, the antioxidant compound Sulforaphane downregulates p63-iRHOM2 expression, leading to reduced proliferation, inflammation, survival and ROS production. These findings elucidate a novel p63-associated pathway that identifies iRHOM2 modulation as a potential therapeutic target to treat hyperproliferative skin disease and neoplasia

    Cancer and systemic inflammation: treat the tumour and treat the host

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    Determinants of cancer progression and survival are multifactorial and host responses are increasingly appreciated to have a major role. Indeed, the development and maintenance of a systemic inflammatory response has been consistently observed to confer poorer outcome, in both early and advanced stage disease. For patients, cancer-associated symptoms are of particular importance resulting in a marked impact on day-to-day quality of life and are also associated with poorer outcome. These symptoms are now recognised to cluster with one another with anorexia, weight loss and physical function forming a recognised cluster whereas fatigue, pain and depression forming another. Importantly, it has become apparent that these symptom clusters are associated with presence of a systemic inflammatory response in the patient with cancer. Given the understanding of the above, there is now a need to intervene to moderate systemic inflammatory responses, where present. In this context the rationale for therapeutic intervention using nonselective anti-inflammatory agents is clear and compelling and likely to become a part of routine clinical practice in the near future. The published literature on therapeutic intervention using anti-inflammatory agents for cancer-associated symptoms was reviewed. There are important parallels with the development of useful treatments for the systemic inflammatory response in patients with rheumatological disease and cardiovascular disease

    Hyperparameter Selection

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    A practical measurement of thoracic sarcopenia: Correlation with clinical parameters and outcomes in advanced lung cancer

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    Thoracic sarcopenia can feasibly be measured from routine CT scans but does not correlate to patient-centred outcomes http://ow.ly/102UkQ

    Multifocal VEP (mfVEP) reveals abnormal neuronal delays in diabetes

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    This pilot study examined the diagnostic role of multifocal visually evoked potentials (mfVEP) in a small number of patients with diabetes. mfVEP, mfERG, and fundus photographs of both eyes of five patients with diabetes, three with nonproliferative diabetic retinopathy (NPDR) and two without NPDR were examined. Thirteen control subjects were also examined. Eighteen zones were constructed from the 60-element mfVEP stimulus array. mfVEP implicit time (IT) and amplitude (SNR) differences were tested between subject groups. We also examined whether there was a difference in function for patches with and without retinopathy in the NPDR group. Lastly, we compared mfVEP and mfERG results in the same patients. We found significant mfVEP IT differences between controls and all patients with diabetes, controls and diabetics without retinopathy, and between controls and diabetics with retinopathy. The subject groups did not differ significantly in terms of SNR. In the retinopathy group, ITs from zones with retinopathy were significantly longer than ITs from zones without retinopathy (P = 0.016). mfERG IT was more frequently abnormal than mfVEP IT. In addition, mfERG hexagons were twice as likely to be abnormal if the corresponding mfVEP zone was abnormal (P < 0.05). mfVEP implicit times are significantly delayed in patients with diabetes even when there is no retinopathy. These cortical response results are similar, albeit considerably less abnormal, than those previously reported for retinal (mfERG) responses in patients with diabetes. A correlation exists between the location of abnormal mfERG hexagons and abnormal mfVEP zones

    Hidden Diversity Hampers Conservation Efforts in a Highly Impacted Neotropical River System.

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    Neotropical Rivers host a highly diverse ichthyofauna, but taxonomic uncertainty prevents appropriate conservation measures. The Doce River Basin (DRB), lying within two Brazilian threatened hotspots (Atlantic Forest and Brazilian Savanna) in south-east Brazil, faced the worst ever environmental accident reported for South American catchments, due to a dam collapse that spread toxic mining tailings along the course of its main river. Its ichthyofauna was known to comprise 71 native freshwater fish species, of which 13 endemic. Here, we build a DNA barcode library for the DRB ichthyofauna, using samples obtained before the 2015 mining disaster, in order to provide a more robust biodiversity record for this basin, as a baseline for future management actions. Throughout the whole DRB, we obtained a total of 306 barcodes, assigned to 69 putative species (with a mean of 4.54 barcodes per species), belonging to 45 genera, 18 families, and 5 orders. Average genetic distances within species, genus, and families were 2.59, 11.4, and 20.5%, respectively. The 69 species identified represent over 76% of the known DRB ichthyofauna, comprising 43 native (five endemic, of which three threatened by extinction), 13 already known introduced species, and 13 unknown species (such as Characidium sp., Neoplecostomus sp., and specimens identified only at the sub-family level Neoplecostominae, according to morphological identification provided by the museum collections). Over one fifth of all analyzed species (N = 16) had a mean intraspecific genetic divergence higher than 2%. An integrative approach, combining NND (nearest neighbor distance), BIN (barcode index number), ABGD (automatic barcode gap discovery), and bPTP (Bayesian Poisson Tree Processes model) analyses, suggested the occurrence of potential cryptic species, species complex, or historical errors in morphological identification. The evidence presented calls for a more robust, DNA-assisted cataloging of biodiversity-rich ecosystems, in order to enable effective monitoring and informed actions to preserve and restore these delicate habitats

    Pre-dialysis clinic attendance improves quality of life among hemodialysis patients

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    BACKGROUND: Although previous research has demonstrated that referral to pre-dialysis clinics is associated with favourable objective outcomes, the benefit of a pre-dialysis clinic from the perspective of patient-perceived subjective outcomes, such as quality of life (QOL), is less well defined. METHODS: A retrospective incident cohort study was conducted to determine if pre-dialysis clinic attendance was a predictor of better QOL scores measured within the first six months of hemodialysis (HD) initiation. Inclusion criteria were HD initiation from January 1 1998 to January 1 2000, diagnosis of chronic renal failure, and completion of the QOL questionnaire within six months of HD initiation. Patients receiving HD for less than four weeks were excluded. An incident cohort of 120 dialysis patients was identified, including 74 patients who attended at least one pre-dialysis clinic and 46 patients who did not. QOL was measured using the SF 36-Item Health Survey. Independent variables included age, sex, diabetes, pre-dialysis clinic attendance and length of attendance, history of ischemic heart disease, stroke, peripheral vascular disease, heart failure, malignancy, and chronic lung disease, residual creatinine clearance at dialysis initiation, and kt/v, albumin and hemoglobin at the time of QOL assessment. Bivariate and multivariate linear regression analyses were used to identify predictors of QOL scores. RESULTS: Multivariate analysis suggested that pre-dialysis clinic attendance was an independent predictor of higher QOL scores in four of eight health domains (physical function, p < 0.01; emotional role limitation, p = 0.01; social function, p = 0.01; and general health, p = 0.03), even after statistical adjustment for age, sex, residual renal function, kt/v, albumin, and co-morbid disease. Pre-dialysis clinic attendance was also an independent predictor of the physical component summary score (p = 0.03). CONCLUSIONS: We conclude that pre-dialysis clinic attendance favourably influences patient-perceived quality of life within six months of dialysis initiation
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