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1.
J Dairy Sci ; 2024 Apr 18.
Article in English | MEDLINE | ID: mdl-38642653

ABSTRACT

In countries with pasture-based dairy systems and relatively cold winters, such as New Zealand, it is common to manage pregnant, nonlactating cows on forage crop paddocks rather than pasture due to slow pasture growth rates. Wintering dairy cattle on grazed crops can compromise welfare if wet and muddy underfoot conditions occur, which can reduce lying. This study investigated behavioral and physiological indicators of welfare of cows under 2 wintering practices: cows managed on and grazed kale crop (Brassica oleracea), and cows managed on pasture with baled hay. Following dry-off (d 0), 80 cows were randomly assigned to one of the 2 wintering practices (40 cows/practice) and monitored between d 4 and d 32 (phase 1). During this period, lying and stepping behavior was continuously recorded using leg-based accelerometers. Blood samples were obtained at d 0 and 32 for measurements of thyroxine (T4), nonesterified fatty acids (NEFA), white blood cells (WBC), and red blood cells (RBC). All data for phase 1 were presented descriptively due to the lack of treatment replication. Daily mean air temperature during this period was 5.2°C (range: 0.0 to 10.7°C), and rainfall was 1.1mm/d (range: 0 to 5.6mm/d). Between d 4 and 32, cows in both groups spent similar amounts of time lying (pasture with hay cows: 8.9h/24h ± 2.57, kale crop cows: 8.7h/24h ± 3.06, mean ± SEM). Both groups reduced their lying on wet and cold days and there was evidence of rebound lying once unfavorable weather conditions stopped. Cows on kale crop had numerically higher NEFA and lower WBC compared with cows managed on pasture, although most physiological values were within normal ranges. In a second phase of the study (d 34 and 35), cows were managed under controlled, replicated conditions in the 2 wintering practices using typical on-farm stocking rates (2 or 4 cows per group in the pasture with hay and kale crop treatments, respectively; n = 10 groups/treatment). During this period, cow behavior, skin and surface temperatures, hygiene scores, feed intakes and ground conditions were measured. Weather conditions during the 48-h exposure were mostly cold and dry (mean air temperature: 7.8°C, range: -2.2 to 20.5°C). Cows managed on pasture with hay spent more time lying down on the first day of exposure, however, this was likely due to less space being available to kale cows on this day. Cows managed on pasture with hay ruminated more than cows on kale crop on both days of observations (Day 1: 37.9% vs 30.9% of observations, Day 2: 36.8% vs 28.7% of observations for pasture with hay and kale crop groups, respectively) and were lying more often in postures indicative of greater thermal comfort. Cows managed on pasture with hay had higher skin and surface temperatures compared with cows on kale crop, whereas cows on kale crop had dirtier coats. Results suggest that opportunities for thermal comfort were greater for cows managed on pasture with hay bales, which may be due to increased rumination activities and more insulated lying areas.

2.
Nat Commun ; 14(1): 7551, 2023 Nov 20.
Article in English | MEDLINE | ID: mdl-37985758

ABSTRACT

Glial-cell line derived neurotrophic factor (GDNF) bound to its co-receptor GFRα1 stimulates the RET receptor tyrosine kinase, promoting neuronal survival and neuroprotection. The GDNF-GFRα1 complex also supports synaptic cell adhesion independently of RET. Here, we describe the structure of a decameric GDNF-GFRα1 assembly determined by crystallography and electron microscopy, revealing two GFRα1 pentamers bridged by five GDNF dimers. We reconsitituted the assembly between adhering liposomes and used cryo-electron tomography to visualize how the complex fulfils its membrane adhesion function. The GFRα1:GFRα1 pentameric interface was further validated both in vitro by native PAGE and in cellulo by cell-clustering and dendritic spine assays. Finally, we provide biochemical and cell-based evidence that RET and heparan sulfate cooperate to prevent assembly of the adhesion complex by competing for the adhesion interface. Our results provide a mechanistic framework to understand GDNF-driven cell adhesion, its relationship to trophic signalling, and the central role played by GFRα1.


Subject(s)
Glial Cell Line-Derived Neurotrophic Factor , Proto-Oncogene Proteins c-ret , Proto-Oncogene Proteins c-ret/genetics , Proto-Oncogene Proteins c-ret/metabolism , Proto-Oncogene Proteins/metabolism , Signal Transduction
3.
Adv Exp Med Biol ; 1404: 195-211, 2023.
Article in English | MEDLINE | ID: mdl-36792877

ABSTRACT

Vibrio cholerae, the agent of cholera, is a natural inhabitant of aquatic environments. Over the past decades, the importance of specific nutrients and micronutrients in the environmental survival, host colonization, and pathogenesis of this species has become increasingly clear. For instance, V. cholerae has evolved ingenious mechanisms that allow the bacterium to colonize and establish a niche in the intestine of human hosts, where it competes with commensals (gut microbiota) and other pathogenic bacteria for available nutrients. Here, we discuss the carbon and energy sources utilized by V. cholerae and what is known about the role of nutrition in V. cholerae colonization. We examine how nutritional signals affect virulence gene regulation and how interactions with intestinal commensal species can affect intestinal colonization.


Subject(s)
Cholera , Vibrio cholerae , Humans , Vibrio cholerae/genetics , Cholera/microbiology , Intestines/microbiology , Virulence , Nutrients , Bacterial Proteins/metabolism , Gene Expression Regulation, Bacterial
4.
Blood ; 136(22): 2535-2547, 2020 11 26.
Article in English | MEDLINE | ID: mdl-32589703

ABSTRACT

Expansion of human hematopoietic stem cells (HSCs) is a rapidly advancing field showing great promise for clinical applications. Recent evidence has implicated the nervous system and glial family ligands (GFLs) as potential drivers of hematopoietic survival and self-renewal in the bone marrow niche; how to apply this process to HSC maintenance and expansion has yet to be explored. We show a role for the GFL receptor, RET, at the cell surface of HSCs in mediating sustained cellular growth, resistance to stress, and improved cell survival throughout in vitro expansion. HSCs treated with the key RET ligand/coreceptor complex, glial-derived neurotrophic factor and its coreceptor, exhibit improved progenitor function at primary transplantation and improved long-term HSC function at secondary transplantation. Finally, we show that RET drives a multifaceted intracellular signaling pathway, including key signaling intermediates protein kinase B, extracellular signal-regulated kinase 1/2, NF-κB, and p53, responsible for a wide range of cellular and genetic responses that improve cell growth and survival under culture conditions.


Subject(s)
Cell Proliferation , Hematopoietic Stem Cells/metabolism , MAP Kinase Signaling System , Proto-Oncogene Proteins c-ret/metabolism , Animals , Cell Culture Techniques , Cell Survival , Enzyme Activation , Female , Hematopoietic Stem Cells/cytology , Humans , Male , Mice
5.
Phys Rev E ; 101(1-1): 013101, 2020 Jan.
Article in English | MEDLINE | ID: mdl-32069619

ABSTRACT

A numerical procedure based on the Schwarz-Christoffel map suitable for the study of the Laplacian growth of thin two-dimensional protrusions is presented. The protrusions take the form of either straight needles or curved fingers satisfying Loewner's equation, and are represented by slits in the complex plane. Particular use is made of Driscoll's numerical procedure, the SC Toolbox, for computing the Schwarz-Christoffel map from a half plane to a slit half plane. Since the Schwarz-Christoffel map applies only to polygonal regions, the growth of curved fingers is approximated by an increasing number of short straight line segments. The growth rate is given by a fixed power η of the harmonic measure at the finger or needle tips and so includes the possibility of "screening" as the needles of fingers interact with themselves and with boundaries. The method is illustrated with examples of multiple needle and finger growth in half-plane and channel geometries. The effect of η on the trajectories of asymmetric bifurcating fingers is also studied.

6.
Infant Behav Dev ; 57: 101337, 2019 11.
Article in English | MEDLINE | ID: mdl-31450025

ABSTRACT

Behavioral signs of Autism Spectrum Disorder (ASD) are typically observable by the second year of life and a reliable diagnosis of ASD is possible by 2 to 3 years of age. Studying infants with familial risk for ASD allows for the investigation of early signs of ASD risk within the first year. Brain abnormalities such as hyper-connectivity within the first year may precede the overt signs of ASD that emerge later in life. In this preliminary study, we use functional near-infrared spectroscopy (fNIRS), an infant-friendly neuroimaging tool that is relatively robust against motion artifacts, to examine functional activation and connectivity during naturalistic social interactions in 9 high-risk (HR; older sibling with ASD) and 6 low-risk (LR; no family history of ASD) infants from 6 to 9 months of age. We obtained two 30-second baseline periods and a 5-minute social interaction period. HR infants showed reduced right and left-hemispheric activation compared to LR infants based on oxy (HbO2) and deoxy (HHb) signal trends. HR infants also had greater functional connectivity than LR infants during the pre- and post-social periods and showed a drop in connectivity during the social period. Our findings are consistent with previous work suggesting early differences in cortical activation associated with familial risk for ASD, and highlight the promise of fNIRS in evaluating potential markers of ASD risk during naturalistic social contexts.


Subject(s)
Autism Spectrum Disorder/diagnostic imaging , Autism Spectrum Disorder/genetics , Cerebral Cortex/diagnostic imaging , Genetic Predisposition to Disease/genetics , Interpersonal Relations , Nerve Net/diagnostic imaging , Autism Spectrum Disorder/psychology , Female , Genetic Predisposition to Disease/psychology , Humans , Infant , Male , Parent-Child Relations , Proof of Concept Study , Risk Factors , Siblings/psychology , Spectroscopy, Near-Infrared/methods
7.
Aliment Pharmacol Ther ; 48(4): 423-430, 2018 08.
Article in English | MEDLINE | ID: mdl-29971829

ABSTRACT

BACKGROUND: Hyaluronic acid is a recognised noninvasive marker of liver fibrosis. However, its prognostic ability has not been extensively studied. AIMS: To investigate the ability of an index serum hyaluronic acid measurement to independently predict transplant-free survival in patients with liver disease of varying aetiology and severity. METHODS: This was a retrospective single-centre cohort study. Serum hyaluronic acid was measured at the discretion of the attending clinicians, in patients attending the liver clinic, to assess disease severity. Patients with a hyaluronic acid measurement between 1995 and 2010 were identified. Patient characteristics at the point of hyaluronic acid measurement were recorded from medical records. Follow-up was from date of index hyaluronic acid measurement to date of death, date of transplant or censor date (July 01, 2015). Primary outcomes were all-cause and liver-related mortality. Kaplan-Meier analysis was used to compare survival in 3 patient groups with hyaluronic acid levels of <100 µg/L, 100-300 µg/L and >300 µg/L. Survival models were constructed using Cox proportional hazard and prediction accuracy was assessed by Harrell's C-statistic. RESULTS: Five hundred and eighty nine patients fulfilled inclusion criteria. Median follow-up was 5.6 years (range 0.1-19.7). Transplant-free survival was significantly different between patients with hyaluronic acid <100 µg/L, 100-300 µg/L and >300 µg/L for liver-related as well as all-cause mortality (P < 0.001). Hyaluronic acid level was an independent predictor of survival (liver-related: HR 1.39, 95% CI 1.20-1.60, P < 0.001; all-cause: HR 1.04, 95% CI 1.02-1.06, P = 0.001). The liver-related prediction accuracy of hyaluronic acid was 0.74 (Standard error 0.03). CONCLUSION: Index hyaluronic acid measurement can accurately and independently predict liver-related and all-cause mortality in patients with liver disease.


Subject(s)
Biomarkers/blood , Hyaluronic Acid/blood , Liver Cirrhosis/diagnosis , Adult , Aged , Aged, 80 and over , Biomarkers/analysis , Cohort Studies , Female , Follow-Up Studies , Graft Survival , Humans , Hyaluronic Acid/analysis , Kaplan-Meier Estimate , Liver Cirrhosis/blood , Liver Cirrhosis/mortality , Liver Cirrhosis/therapy , Liver Transplantation/adverse effects , Liver Transplantation/mortality , Male , Middle Aged , Predictive Value of Tests , Prognosis , Retrospective Studies , Young Adult
8.
Aliment Pharmacol Ther ; 47(5): 631-644, 2018 03.
Article in English | MEDLINE | ID: mdl-29271504

ABSTRACT

BACKGROUND: Validated diagnostic tools that are accurate, cost effective and acceptable to patients are required for disease stratification and monitoring in NAFLD. AIMS: To investigate the performance and cost of multiparametric MRI alongside existing biomarkers in the assessment of NAFLD. METHODS: Adult patients undergoing standard of care liver biopsy for NAFLD were prospectively recruited at two UK liver centres and underwent multiparametric MRI, blood sampling and transient elastography withing 2 weeks of liver biopsy. Non-invasive markers were compared to histology as the gold standard. RESULTS: Data were obtained in 50 patients and 6 healthy volunteers. Corrected T1 (cT1) correlated with NAFLD activity score (ρ = 0.514, P < .001). cT1, enhanced liver fibrosis (ELF) test and liver stiffness differentiated patients with simple steatosis and NASH with AUROC (95% CI) of 0.69 (0.50-0.88), 0.87 (0.77-0.79) and 0.82 (0.70-0.94) respectively and healthy volunteers from patients with AUROC (95% CI) of 0.93 (0.86-1.00), 0.81 (0.69-0.92) and 0.89 (0.77-1.00) respectively. For the risk stratification of NAFLD, multiparametric MRI could save £150,218 per 1000 patients compared to biopsy. Multiparametric MRI did not discriminate between individual histological fibrosis stages in this population (P = .068). CONCLUSIONS: Multiparametric MRI accurately identified patients with steatosis, stratifies those with NASH or simple steatosis and reliably excludes clinically significant liver disease with superior negative predictive value (83.3%) to liver stiffness (42.9%) and ELF (57.1%). For the risk stratification of NAFLD, multiparametric MRI was cost effective and, combined with transient elastography, had the lowest cost per correct diagnosis.


Subject(s)
Liver/diagnostic imaging , Magnetic Resonance Imaging , Non-alcoholic Fatty Liver Disease/diagnosis , Adolescent , Adult , Aged , Biopsy , Cost-Benefit Analysis , Elasticity Imaging Techniques/economics , Elasticity Imaging Techniques/methods , Female , Healthy Volunteers , Humans , Liver/pathology , Liver Cirrhosis/diagnosis , Liver Cirrhosis/economics , Magnetic Resonance Imaging/economics , Magnetic Resonance Imaging/methods , Male , Middle Aged , Non-alcoholic Fatty Liver Disease/economics , Non-alcoholic Fatty Liver Disease/pathology , Predictive Value of Tests , Young Adult
9.
J Dairy Sci ; 99(12): 9925-9930, 2016 Dec.
Article in English | MEDLINE | ID: mdl-27743667

ABSTRACT

Indwelling rumen temperature bolus (RTB) systems have the potential to offer a convenient and timely method of detecting pyrexia, indicative of active infectious disease. The aim of this pilot study was to evaluate the utility of using RTB systems in preweaned dairy calves. First, an in vitro study was performed to evaluate the accuracy of the RTB in its immediate environment. Thirteen RTB were immersed in a hot water bath (WB). Variably collected RTB temperatures were then matched to WB temperatures, which varied from 36 to 41°C, with 1h spent at each temperature. Second, an in vivo study was performed to evaluate the ability of the RTB to predict a rectal thermometer (RT) temperature. Ten healthy heifer calves less than 1wk of age were administered an RTB. Rectal thermometer and matched RTB temperatures were taken hourly, over a 6-h period, 1 day per week during wk 1, 3, 5, 7, and 9 of age. During each 6-h observation period, calves were offered both water and milk feedings and temperatures recorded every 15min for 1h thereafter. For both studies, the relationship between RTB and one of WB (in vitro) or RT temperature (in vivo) was described by calculating a concordance correlation coefficient (CCC) and by use of a multivariable linear regression model with repeated measures. For the in vivo study, the model also controlled for week and breed. Diagnostic test characteristics were calculated for the ability of individual RTB measures to detect pyrexia (RT ≥39.5°C). For the in vitro study, the association between the RTB and a known temperature was strong (CCC=0.95), but the RTB measures underestimated the temperature of the water bath by 0.43±0.08°C. For the in vivo study, the association between RT and the RTB temperature measurement in a calf was weaker (CCC=0.29); the average RTB temperature was 0.33±0.06°C lower than the RT temperature. The sensitivity (29%) and positive predictive value (17%) of using individual RTB measures to detect a fever was low. The results of this pilot study suggest that an individual RTB measurement may not be a good diagnostic test to detect pyrexia in calves.


Subject(s)
Cattle Diseases/diagnosis , Dairying/methods , Fever/veterinary , Rumen/physiopathology , Temperature , Animals , Cattle , Cattle Diseases/physiopathology , Female , Fever/diagnosis , Fever/physiopathology , Pilot Projects
10.
Sci Total Environ ; 556: 276-90, 2016 Jun 15.
Article in English | MEDLINE | ID: mdl-26974575

ABSTRACT

Identifying critical source areas (CSAs) of diffuse pollution in agricultural catchments requires the accurate identification of hydrologically sensitive areas (HSAs) at highest propensity for generating surface runoff and transporting pollutants. A new GIS-based HSA Index is presented that improves the identification of HSAs at the sub-field scale by accounting for microtopographic controls. The Index is based on high resolution LiDAR data and a soil topographic index (STI) and also considers the hydrological disconnection of overland flow via topographic impediment from flow sinks. The HSA Index was applied to four intensive agricultural catchments (~7.5-12km(2)) with contrasting topography and soil types, and validated using rainfall-quickflow measurements during saturated winter storm events in 2009-2014. Total flow sink volume capacities ranged from 8298 to 59,584m(3) and caused 8.5-24.2% of overland-flow-generating-areas and 16.8-33.4% of catchment areas to become hydrologically disconnected from the open drainage channel network. HSA maps identified 'breakthrough points' and 'delivery points' along surface runoff pathways as vulnerable points where diffuse pollutants could be transported between fields or delivered to the open drainage network, respectively. Using these as proposed locations for targeting mitigation measures such as riparian buffer strips reduced potential costs compared to blanket implementation within an example agri-environment scheme by 66% and 91% over 1 and 5years respectively, which included LiDAR DEM acquisition costs. The HSA Index can be used as a hydrologically realistic transport component within a fully evolved sub-field scale CSA model, and can also be used to guide the implementation of 'treatment-train' mitigation strategies concurrent with sustainable agricultural intensification.

11.
Sci Total Environ ; 541: 292-302, 2016 Jan 15.
Article in English | MEDLINE | ID: mdl-26410704

ABSTRACT

Two groundwater dominated catchments with contrasting land use (Grassland and Arable) and soil chemistry were investigated for influences on P transfer below the rooting zone, via the aquifer and into the rivers. The objective was to improve the understanding of hydrochemical process for best management practise and determine the importance of P transfer via groundwater pathways. Despite the catchments having similar inorganic P reserves, the iron-rich soils of the Grassland catchment favoured P mobilisation into soluble form and transfer to groundwater. Sites in that catchment had elevated dissolved reactive P concentrations in groundwater (>0.035 mg l(-1)) and the river had flow-weighted mean TRP concentrations almost three times that of the aluminium-rich Arable catchment (0.067 mg l(-1) compared to 0.023 mg l(-1)). While the average annual TRP flux was low in both catchments (although three times higher in the Grassland catchment; 0.385 kg ha(-1) compared to 0.128 kg ha(-1)), 50% and 59% of TRP was lost via groundwater, respectively, during winter periods that were closed for fertiliser application. For policy reviews, slow-flow pathways and associated time-lags between fertiliser application, mobilisation of soil P reserves and delivery to the river should be carefully considered when reviewing mitigating strategies and efficacy of mitigating measures in groundwater fed catchments. For example, while the Grassland catchment indicated a soil-P chemistry susceptibility, the Arable catchment indicated a transient point source control; both resulted in sustained or transient periods of elevated low river-flow P concentrations, respectively.

12.
Gen Dent ; 63(5): 33-7, 2015.
Article in English | MEDLINE | ID: mdl-26325639

ABSTRACT

The aim of this study was to evaluate, using microcomputed tomography (µCT), the frequency of conjoined mesial canals in first and second mandibular molars with a single distal canal. Mandibular first (n = 114) and second molars (n = 114) with mature apices were randomly selected from a pool of extracted teeth. The specimens were decoronated to establish clinically the existence of a single distal canal. Teeth with C-shaped canals were discarded. Each tooth was scanned with a µCT system and evaluated in 3 dimensions. Of 228 examined teeth, 206 were included in the study. Of these, 129 (62.6%) displayed conjoined mesial canals with a single portal of exit, and 77 (37.4%) displayed 2 distinct mesial canals with 2 separate portals of exit. Of the teeth with conjoined mesial canals, 71 (55.0%) were second molars and 58 (45.0%) were first molars. Conjoined mesial canals exhibited a mean interorifice distance of less than 3.00 mm. These data regarding morphological patterns alert clinicians to the possible need to modify endodontic techniques in mandibular molars with single distal canals.


Subject(s)
Dental Pulp Cavity/abnormalities , Molar/abnormalities , X-Ray Microtomography , Dental Pulp Cavity/diagnostic imaging , Humans , Mandible , Molar/diagnostic imaging , Root Canal Therapy/methods , Tooth Root/abnormalities , Tooth Root/diagnostic imaging
13.
J Dent Res ; 94(7): 998-1003, 2015 Jul.
Article in English | MEDLINE | ID: mdl-25904140

ABSTRACT

A dental appointment commonly prompts fear of a painful experience, yet we have never fully understood how our brains react to the expectation of imminent tooth pain once in a dental chair. In our study, 21 patients with hypersensitive teeth were tested using nonpainful and painful stimuli in a clinical setting. Subjects were tested in a dental chair using functional near-infrared spectroscopy to measure cortical activity during a stepwise cold stimulation of a hypersensitive tooth, as well as nonpainful control stimulation on the same tooth. Patients' sensory-discriminative and emotional-cognitive cortical regions were studied through the transition of a neutral to a painful stimulation. In the putative somatosensory cortex contralateral to the stimulus, 2 well-defined hemodynamic peaks were detected in the homuncular orofacial region: the first peak during the nonpainful phase and a second peak after the pain threshold was reached. Moreover, in the upper-left and lower-right prefrontal cortices, there was a significant active hemodynamic response in only the first phase, before the pain. Subsequently, the same prefrontal cortical areas deactivated after a painful experience had been reached. Our study indicates for the first time that pain perception and expectation elicit different hemodynamic cortical responses in a dental clinical setting.


Subject(s)
Brain/physiology , Dentin Sensitivity/physiopathology , Attitude to Health , Cognition/physiology , Cold Temperature , Dental Anxiety/physiopathology , Dental Anxiety/psychology , Dentin Sensitivity/psychology , Emotions , Evoked Potentials/physiology , Female , Hemodynamics/physiology , Humans , Male , Pain Measurement/methods , Pain Perception/physiology , Pain Threshold/physiology , Percussion , Prefrontal Cortex/physiopathology , Sensory Thresholds/physiology , Somatosensory Cortex/physiopathology , Spectroscopy, Near-Infrared
14.
J Psychiatr Ment Health Nurs ; 22(3): 208-18, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25490860

ABSTRACT

Burnout negatively impacts the delivery of mental health services. Psychiatric nurses face stressors that are distinct from other nursing specialities. The research was conducted in Ireland and captured a relatively large sample of respondents. The results compared the stressors, coping strategies and burnout levels between hospital and community-based psychiatric nurses. Occupational stress can negatively impact on the well-being of psychiatric nurses, which in turn can lead to poor client care. There is a dearth of published research conducted in Ireland that examines stress within the discipline. A between-groups study, undertaken in February 2011, investigated stressors, burnout and coping strategies between hospital and community-based psychiatric nurses in a Dublin region. Sixty-nine participants (8 males and 61 females), aged between 18 to 60 years voluntarily completed the Mental Health Professional Stress Scale, the Maslach Burnout Inventory and the PsychNurse Methods of Coping Scale. The findings revealed that nurses were operating in a moderately stressful environment. Stressors focused on organizational issues as opposed to client issues. The main stressors identified were lack of resources, workload and organizational structures/processes. Both groups reported average levels of emotional exhaustion, low levels of depersonalization and average levels of personal accomplishment. A Mann-Whitney U-test and Independent Samples t-test found significant differences between hospital and community-based nurses regarding depersonalization and personal accomplishment, respectively. Hospital nurses reported higher depersonalization scores, and community nurses had a greater sense of personal accomplishment. The personal accomplishment scores of hospital nurses were below mental health professional norms. No significant differences emerged regarding coping strategies. Avoidant coping strategies were favoured by both groups. It is recommended that interventions aimed at increasing personal accomplishment be implemented for both groups of nurses. An investigation of perceived job control and the use of social support would also be insightful.


Subject(s)
Adaptation, Psychological , Burnout, Professional/psychology , Nursing Staff/psychology , Occupational Diseases/psychology , Psychiatric Nursing , Adult , Burnout, Professional/epidemiology , Community Mental Health Services , Female , Humans , Ireland , Male , Middle Aged , Nursing Staff, Hospital/psychology , Occupational Diseases/epidemiology
15.
Cell Signal ; 26(8): 1743-52, 2014 Aug.
Article in English | MEDLINE | ID: mdl-24705026

ABSTRACT

De-regulation of RET signaling by oncogenic mutation, gene rearrangement, overexpression or transcriptional up-regulation is implicated in several human cancers of neuroendocrine and epithelial origin (thyroid, breast, lung). Understanding how RET signaling mechanisms associated with these oncogenic events are deregulated, and their impact in the biological processes driving tumor formation and progression, as well as response to treatment, will be crucial to find and develop better targeted therapeutic strategies. In this review we emphasie the distinct mechanisms of RET signaling in cancer and summarise current knowledge on small molecule inhibitors targeting the tyrosine kinase domain of RET as therapeutic drugs in RET-positive cancers.


Subject(s)
Proto-Oncogene Proteins c-ret/metabolism , Angiogenesis Inhibitors/therapeutic use , Humans , Lung Neoplasms/metabolism , Lung Neoplasms/pathology , Multiple Endocrine Neoplasia Type 2a/metabolism , Multiple Endocrine Neoplasia Type 2a/pathology , Neoplasms/drug therapy , Neoplasms/metabolism , Neoplasms/pathology , Protein Kinase Inhibitors/therapeutic use , Proto-Oncogene Proteins c-ret/antagonists & inhibitors , Proto-Oncogene Proteins c-ret/genetics , RNA Interference , Signal Transduction , Thyroid Neoplasms/metabolism , Thyroid Neoplasms/pathology
16.
Article in English | MEDLINE | ID: mdl-23944416

ABSTRACT

The statistics of a neutral point-vortex gas in an arbitrary two-dimensional simply connected and bounded container are investigated in the framework of the microcanonical ensemble, following the cumulant expansion method of Pointin and Lundgren [Phys. Fluids 19, 1459 (1976)]. The equation for vorticity fluctuations, obtained when a thermodynamic scaling limit is taken, is solved explicitly. The solution depends on an infinite sequence of negative "domain inverse temperatures," determined by the domain shape, which are obtained from solutions of a "vorticity mode" eigenvalue problem. An explicit expression for the thermodynamic curve relating inverse temperature and energy is found and is shown to depend on the geometry and not on the scale of the domain. Explicit formulas are then obtained for the time variance of the projection of the vorticity field onto each vorticity mode. The results are verified by two methods. First, for a chosen single-parameter family of domains, direct sampling of the microcanonical ensemble is used to demonstrate the accuracy of the formula for the thermodynamic curve. Second, direct numerical simulations are used to verify the formulas for the variance of the projections of the vorticity field, with convincing results.

17.
J Dairy Sci ; 95(1): 83-90, 2012 Jan.
Article in English | MEDLINE | ID: mdl-22192186

ABSTRACT

Up to 3% of young children develop milk allergy and this may influence the development of immune-mediated diseases in later life. One protein that has been associated with allergic reactions to ruminant milk is α(S1)-casein (CN). Studies suggest that goat milk with low levels of α(S1)-CN may reduce allergenicity of milk, but the dose response to α(S1)-CN has not been confirmed. In this study, we examined the immune response to varying levels of goat α(S1)-CN in a mouse model of gastrointestinal allergy. BALB/c mice (aged 5 wk) were given intraperitoneal injections with α(S1)-CN and aluminum as adjuvant at 1 and 3 wk to sensitize mice to the antigen. In wk 5, groups of fasting mice (n=8/group) were challenged 4 times on alternate days by intragastric gavage with saline or 2, 10, or 20mg of α(S1)-CN. Serum levels of specific IgE, IgG(1), and IgG(2a) antibodies and mouse mast cell protease-I were determined. Interleukin-4, IL-10, and IFN-γ responses to 48-h activation with antigen were measured in cultured splenocytes. We determined that mice sensitized with α(S1)-CN had higher titers of specific IgG(1) and IgE antibodies compared with controls; however, groups challenged with differing doses of α(S1)-CN did not differ. The group challenged with the highest dose of α(S1)-CN had a 10-fold increase in mouse mast cell protease-I compared with the group challenged with saline. Both IL-4 and IL-10 were produced in a dose-dependent manner by cultured splenocytes incubated with α(S1)-CN. Overall, α(S1)-CN stimulated the production of cytokines associated with allergic disease in a dose-dependent manner. Thus, milk with lower levels of α(S1)-CN should contribute to a lesser antigenic burden.


Subject(s)
Caseins/immunology , Gastrointestinal Tract/immunology , Milk Hypersensitivity/etiology , Animals , Caseins/pharmacology , Disease Models, Animal , Dose-Response Relationship, Immunologic , Female , Gastrointestinal Tract/drug effects , Goats , Immunoglobulin E/blood , Immunoglobulin G/blood , Interferon-gamma/blood , Interleukin-10/blood , Interleukin-4/blood , Mice , Mice, Inbred BALB C , Milk Hypersensitivity/immunology
18.
Ergonomics ; 53(2): 164-83, 2010 Feb.
Article in English | MEDLINE | ID: mdl-20099172

ABSTRACT

This paper presents the findings of research relating to the specification of a new human factors report, conducted as part of the work requirements for the Human Integration into the Lifecycle of Aviation Systems project, sponsored by the European Commission. Specifically, it describes the proposed concept for a unique report, which will form the basis for all operational and safety reports completed by flight crew. This includes all mandatory and optional reports. Critically, this form is central to the advancement of improved processes and technology tools, supporting airline performance management, safety management, organisational learning and knowledge integration/information-sharing activities. Specifically, this paper describes the background to the development of this reporting form, the logic and contents of this form and how reporting data will be made use of by airline personnel. This includes a description of the proposed intelligent planning process and the associated intelligent flight plan concept, which makes use of airline operational and safety analyses information. Primarily, this new reporting form has been developed in collaboration with a major Spanish airline. In addition, it has involved research with five other airlines. Overall, this has involved extensive field research, collaborative prototyping and evaluation of new reports/flight plan concepts and a number of evaluation activities. Participants have included both operational and management personnel, across different airline flight operations processes. Statement of Relevance: This paper presents the development of a reporting concept outlined through field research and collaborative prototyping within an airline. The resulting reporting function, embedded in the journey log compiled at the end of each flight, aims at enabling employees to audit the operations of the company they work for.


Subject(s)
Aviation/standards , Ergonomics , Mandatory Reporting , Safety Management/methods , Humans
19.
Article in English | MEDLINE | ID: mdl-19164053

ABSTRACT

This paper describes a compact, lightweight and ultra-low power ambulatory wireless EEG system based upon QUASAR's innovative noninvasive bioelectric sensor technologies. The sensors operate through hair without skin preparation or conductive gels. Mechanical isolation built into the harness permits the recording of high quality EEG data during ambulation. Advanced algorithms developed for this system permit real time classification of workload during subject motion. Measurements made using the EEG system during ambulation are presented, including results for real time classification of subject workload.


Subject(s)
Algorithms , Brain/physiology , Electrodes , Electroencephalography/instrumentation , Monitoring, Ambulatory/instrumentation , Telemetry/instrumentation , Workload , Electroencephalography/methods , Equipment Design , Equipment Failure Analysis , Monitoring, Ambulatory/methods , Reproducibility of Results , Sensitivity and Specificity
20.
Biochem Soc Trans ; 35(Pt 5): 1013-7, 2007 Nov.
Article in English | MEDLINE | ID: mdl-17956266

ABSTRACT

The PKB (protein kinase B) and PKC (protein kinase C) families display highly related catalytic domains that require a largely conserved series of phosphorylations for the expression of their optimum activities. However, in cells, the dynamics of these modifications are quite distinct. Based on experimental evidence, it is argued that the underlying mechanisms determining these divergent behaviours relate to the very different manner in which their variant regulatory domains interact with their respective catalytic domains. It is concluded that the distinct behaviours of PKB and PKC proteins are defined by the typical ground states of these proteins.


Subject(s)
Protein Kinase C/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Catalytic Domain , Enzyme Activation , Phosphorylation
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