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1.
Radiography (Lond) ; 30(5): 1243-1248, 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38959619

ABSTRACT

INTRODUCTION: Advanced practice is well established in the health professions with multiprofessional capabilities in place in England. To recognise achievement of these capabilities an ePortfolio (supported) route was initiated in 2022. This study aimed to review the demographics and experiences of radiographers applying for recognition in the first year of operation. METHODS: The multi method evaluation consisted of quantitative data analysis of information regarding the first three cohorts of radiographers (n = 40) participating in the NHS England (NHSE) scheme. Interviews with 12 participants was undertaken with thematic analysis of the transcripts. RESULTS: Self-rated scores of expertise were significantly higher by therapeutic radiographers (n = 8) compared to their 32 diagnostic colleagues (t = 5.556; p < 0.01). Radiographers saw the ePortfolio as an opportunity to validate their experience and to evidence parity with other professions. Participants felt the process also enabled critical reflection and gave unseen insight into themselves and their roles. The support of experienced educational supervisors was felt to be vital in this process and for successful completion of portfolio. CONCLUSIONS: Several radiographers have now achieved the necessary standards to achieve NHSE recognition. The evaluation exposed that most radiographers did not have the relevant evidence to hand and the ongoing collection of evidence around capabilities and impact is critical to evidencing advanced practice capabilities. IMPLICATIONS FOR PRACTICE: Radiographers are able to achieve the capabilities expected for multiprofessional practice. Cultural change is required to normalise recording of evidence within practice including case-based discussions, clinical supervision and feedback from colleagues and patients. The support of an experienced educational supervisor aided the critical reflection on practice level.

2.
Clin Oncol (R Coll Radiol) ; 33(12): e561-e569, 2021 12.
Article in English | MEDLINE | ID: mdl-34226113

ABSTRACT

AIMS: Induction ipilimumab and nivolumab followed by maintenance nivolumab improve overall survival compared with ipilimumab alone in patients with advanced melanoma, but immune-related adverse events (irAE) occur commonly. The need for induction discontinuation because of irAE and the relationship between irAE and survival in non-trials patients are unclear. MATERIALS AND METHODS: Patients with unresectable stage III-IV melanoma receiving first-line combination immunotherapy at one of six centres between December 2017 and February 2020 outside of trials were identified retrospectively. Landmark 12-week Kaplan-Meier analyses and log-rank tests were used to evaluate associations between discontinuation of induction therapy on overall survival and time to treatment failure (TTF). Multivariable analysis of factors influencing overall survival and TTF was undertaken. RESULTS: Among 95 patients, the median age was 62 years, 38.9% had Eastern Cooperative Oncology Group performance status ≥1 and 22.1% had brain metastases. The median follow-up for the whole cohort was 19.8 months by the reverse Kaplan-Meier method. Any grade and grade 3-4 irAE were noted in 78.9% and 44.2% of the cohort, respectively. 44.2% of patients completed induction immunotherapy, whereas 41.1% did not due to irAE. Twelve-week landmark overall survival and TTF were similar in patients who completed induction versus those who did not due to irAE. On multivariable analysis, any grade irAE (versus none) was associated with longer overall survival (hazard ratio = 0.35, 95% confidence interval 0.15-0.82, P = 0.02) and TTF (hazard ratio = 0.38, 95% confidence interval = 0.17-0.81, P = 0.01). Grade 3-4 irAE correlated with longer TTF (hazard ratio = 0.45, 95% confidence interval = 0.20-1.01, P = 0.05). CONCLUSION: In this population-based cohort, discontinuation of induction immunotherapy as a result of irAE did not adversely affect overall survival or TTF. irAE observed during ipilimumab and nivolumab induction were associated with improved survival outcomes.


Subject(s)
Melanoma , Nivolumab , Antineoplastic Combined Chemotherapy Protocols , Humans , Ipilimumab/adverse effects , Melanoma/drug therapy , Middle Aged , Nivolumab/adverse effects , Retrospective Studies
3.
Int J Tuberc Lung Dis ; 25(8): 614-619, 2021 08 01.
Article in English | MEDLINE | ID: mdl-34330345

ABSTRACT

Mathematical modelling is increasingly used to inform budgeting and strategic decision-making by national TB programmes. Despite the importance of these decisions, there is currently no mechanism to review and confirm the appropriateness of modelling analyses. We have developed a benchmarking, reporting, and review (BRR) approach and accompanying tools to allow constructive review of country-level TB modelling applications. This approach has been piloted in five modelling applications and the results of this study have been used to revise and finalise the approach. The BRR approach consists of 1) quantitative benchmarks against which model assumptions and results can be compared, 2) standardised reporting templates and review criteria, and 3) a multi-stage review process providing feedback to modellers during the application, as well as a summary evaluation after completion. During the pilot, use of the tools prompted important changes in the approaches taken to modelling. The pilot also identified issues beyond the scope of a review mechanism, such as a lack of empirical evidence and capacity constraints. This approach provides independent evaluation of the appropriateness of modelling decisions during the course of an application, allowing meaningful changes to be made before results are used to inform decision-making. The use of these tools can improve the quality and transparency of country-level TB modelling applications.


Subject(s)
Benchmarking , Models, Theoretical , Tuberculosis , Humans , Tuberculosis/epidemiology
5.
Surg Endosc ; 34(10): 4702-4711, 2020 10.
Article in English | MEDLINE | ID: mdl-32780240

ABSTRACT

BACKGROUND: The laparoscopic approach to liver resection may reduce morbidity and hospital stay. However, uptake has been slow due to concerns about patient safety and oncological radicality. Image guidance systems may improve patient safety by enabling 3D visualisation of critical intra- and extrahepatic structures. Current systems suffer from non-intuitive visualisation and a complicated setup process. A novel image guidance system (SmartLiver), offering augmented reality visualisation and semi-automatic registration has been developed to address these issues. A clinical feasibility study evaluated the performance and usability of SmartLiver with either manual or semi-automatic registration. METHODS: Intraoperative image guidance data were recorded and analysed in patients undergoing laparoscopic liver resection or cancer staging. Stereoscopic surface reconstruction and iterative closest point matching facilitated semi-automatic registration. The primary endpoint was defined as successful registration as determined by the operating surgeon. Secondary endpoints were system usability as assessed by a surgeon questionnaire and comparison of manual vs. semi-automatic registration accuracy. Since SmartLiver is still in development no attempt was made to evaluate its impact on perioperative outcomes. RESULTS: The primary endpoint was achieved in 16 out of 18 patients. Initially semi-automatic registration failed because the IGS could not distinguish the liver surface from surrounding structures. Implementation of a deep learning algorithm enabled the IGS to overcome this issue and facilitate semi-automatic registration. Mean registration accuracy was 10.9 ± 4.2 mm (manual) vs. 13.9 ± 4.4 mm (semi-automatic) (Mean difference - 3 mm; p = 0.158). Surgeon feedback was positive about IGS handling and improved intraoperative orientation but also highlighted the need for a simpler setup process and better integration with laparoscopic ultrasound. CONCLUSION: The technical feasibility of using SmartLiver intraoperatively has been demonstrated. With further improvements semi-automatic registration may enhance user friendliness and workflow of SmartLiver. Manual and semi-automatic registration accuracy were comparable but evaluation on a larger patient cohort is required to confirm these findings.


Subject(s)
Augmented Reality , Liver/surgery , Surgery, Computer-Assisted/methods , Adult , Aged , Aged, 80 and over , Feasibility Studies , Female , Humans , Male , Middle Aged
6.
Comput Methods Programs Biomed ; 195: 105534, 2020 Oct.
Article in English | MEDLINE | ID: mdl-32480190

ABSTRACT

BACKGROUND AND OBJECTIVE: Total Variation (TV) minimization algorithms have achieved great attention due to the virtue of decreasing noise while preserving edges. The purpose of this work is to implement and evaluate two TV minimization methods in 3D. Their performance is analyzed through 3D visualization of digital breast tomosynthesis (DBT) data with volume rendering. METHODS: Both filters were studied with real phantom and one clinical DBT data. One algorithm was applied sequentially to all slices and the other was applied to the entire volume at once. The suitable Lagrange multiplier used in each filter equation was studied to reach the minimum 3D TV and the maximum contrast-to-noise ratio (CNR). Imaging blur was measured at 0° and 90° using two disks with different diameters (0.5 mm and 5.0 mm) and equal thickness. The quality of unfiltered and filtered data was analyzed with volume rendering at 0° and 90°. RESULTS: For phantom data, with the sequential filter, a decrease of 25% in 3D TV value and an increase of 19% and 30% in CNR at 0° and 90°, respectively, were observed. When the filter is applied directly in 3D, TV value was reduced by 35% and an increase of 36% was achieved both for CNR at 0° and 90°. For the smaller disk, variations of 0% in width at half maximum (FWHM) at 0° and a decrease of about 2.5% for FWHM at 90° were observed for both filters. For the larger disk, there was a 2.5% increase in FWHM at 0° for both filters and a decrease of 6.28% and 1.69% in FWHM at 90° with the sequential filter and the 3D filter, respectively. When applied to clinical data, the performance of each filter was consistent with that obtained with the phantom. CONCLUSIONS: Data analysis confirmed the relevance of these methods in improving quality of DBT images. Additionally, this type of 3D visualization showed that it may play an important complementary role in DBT imaging. It allows to visualize all DBT data at once and to analyze properly filters applied to all the three dimensions. Concise Abstract Total Variation (TV) minimization algorithms are one compressed sensing technique that has achieved great attention due to the virtue of decrease noise while preserve edges transitions. The purpose of this work is to solve the same TV minimization problem in DBT data, by studying two 3D filters. The obtained results were analyzed at 0° and 90° with a 3D visualization through volume rendering. The filters differ in their application. One considers a slice-by-slice optimization, sequentially traversing all slices of the data. The other considers the intensity values of adjacent slices to make this optimization on each voxel. The performance of each filter was also tested with a clinical case. The results obtained were very encouraging with a significantly increased contrast to noise ratio at 0° and 90° and a small reduction in blur at 90° (slight reduction of the out-of-plane artifact).


Subject(s)
Breast , Mammography , Algorithms , Artifacts , Breast/diagnostic imaging , Phantoms, Imaging
7.
Radiography (Lond) ; 25(1): 4-9, 2019 02.
Article in English | MEDLINE | ID: mdl-30599829

ABSTRACT

INTRODUCTION: In the current clinical working environment it is important that therapeutic radiography students are fully prepared not just clinically but emotionally for a working professional life. Mindfulness has shown promise, as a self-care strategy, in the improvement of burnout, resilience and compassion fatigue in other professions; however, it has not been used with therapeutic radiography students. METHODS: Eight pre-registration therapeutic radiography students were recruited to undergo a five week mindfulness course; six students from the year below were recruited to act as a control arm (no mindfulness). Data was collected using a series of validated tools at baseline, week five, month three and 12 months after the start of the study: RESULTS: The MBI-SS scale demonstrated 29% of the sample experienced emotional exhaustion and 43% increased cynicism. The other tools showed a positive trend with the intervention; however, these were not statistically significant. CONCLUSION: Although no statistically significant differences were demonstrated between the study arms, some interesting trends have been noted. The key finding was the identification of burnout experienced by almost a third of the study sample. This suggests that a new area of study is warranted to further investigate the factors contributing to burnout in the student population.


Subject(s)
Burnout, Psychological/prevention & control , Compassion Fatigue/prevention & control , Mindfulness/methods , Radiology/education , Resilience, Psychological , Students, Medical/psychology , Adult , Burnout, Psychological/psychology , Compassion Fatigue/psychology , Female , Humans , Male , Outcome Assessment, Health Care , Pilot Projects , Radiography , Young Adult
8.
Aquaculture ; 490: 329-343, 2018 Mar 01.
Article in English | MEDLINE | ID: mdl-29681666

ABSTRACT

In order to assess the effect of dietary phosphorus (P) in reducing vertebral malformations and improving freshwater (FW) performance in triploid Atlantic salmon (Salmo salar), both triploid and diploid Atlantic salmon were fed three different dietary P inclusion levels (low: 4.9, medium: 7.7, and high: 9.7 g available P kg-1) from first feeding until smolt. Somatic and skeletal response was assessed at fry (~0.5 g), parr (~5 g) and smolt (~45 g) stages. Triploid parr initially grew faster on the high P diet, while groups fed low P resulted in a significantly higher weight at smolt. Image analysis of double stained Alcian blue and Alizarin red S fry revealed that low P fed triploid fish presented less well mineralised vertebrae, and significantly more malformed vertebrae in both parr and smolt stages following x-ray radiographic assessment. Triploid parr fed high and medium P had similar numbers of malformed vertebrae relative to their diploid counterparts but greater numbers than at smolt. Low P fed triploids had the highest prevalence of jaw and vertebral malformations as well as the highest number of deformed vertebrae in the central caudal vertebral region, which was more pronounced at parr than at smolt. Shorter vertebrae dorso-ventral lengths were observed throughout the spinal column (R1-R4) in parr fed low P and only in the caudal region (R3) at smolt. In parr, both ploidies showed reduced phosphate homeostasis protein fgf23 gene expression in vertebrae when fed low P diets, while triploids showed greater down-regulation of osteogenic factors (alp, opn and igf1r) between diets relative to diploids, suggesting possible greater active suppression of mineralisation and reduced osteogenic potential in triploids. No effects of diet or ploidy on gene expression were evident at smolt. Comparisons between development stages suggest early P supplementation in triploids is crucial for skeletal development. Ultimately, reducing vertebral deformities observed at smolt with higher P supplementation in triploids could contribute towards improving skeletal performance and welfare of the stocks in the marine phase.

9.
BMC Genomics ; 18(1): 886, 2017 Nov 17.
Article in English | MEDLINE | ID: mdl-29149845

ABSTRACT

BACKGROUND: To ensure sustainability of aquaculture, plant-based ingredients are being used in feeds to replace marine-derived products. However, plants contain secondary metabolites which can affect food intake and nutrient utilisation of fish. The application of nutritional stimuli during early development can induce long-term changes in animal physiology. Recently, we successfully used this approach to improve the utilisation of plant-based diets in diploid and triploid Atlantic salmon. In the present study we explored the molecular mechanisms occurring in the liver of salmon when challenged with a plant-based diet in order to determine the metabolic processes affected, and the effect of ploidy. RESULTS: Microarray analysis revealed that nutritional history had a major impact on the expression of genes. Key pathways of intermediary metabolism were up-regulated, including oxidative phosphorylation, pyruvate metabolism, TCA cycle, glycolysis and fatty acid metabolism. Other differentially expressed pathways affected by diet included protein processing in endoplasmic reticulum, RNA transport, endocytosis and purine metabolism. The interaction between diet and ploidy also had an effect on the hepatic transcriptome of salmon. The biological pathways with the highest number of genes affected by this interaction were related to gene transcription and translation, and cell processes such as proliferation, differentiation, communication and membrane trafficking. CONCLUSIONS: The present study revealed that nutritional programming induced changes in a large number of metabolic processes in Atlantic salmon, which may be associated with the improved fish performance and nutrient utilisation demonstrated previously. In addition, differences between diploid and triploid salmon were found, supporting recent data that indicate nutritional requirements of triploid salmon may differ from those of their diploid counterparts.


Subject(s)
Diploidy , Liver/metabolism , Salmo salar/genetics , Transcriptome , Triploidy , Animals , Cell Cycle Proteins/genetics , Cell Cycle Proteins/metabolism , DNA Methylation , Diet , Fish Proteins/genetics , Fish Proteins/metabolism , Salmo salar/immunology , Salmo salar/metabolism
10.
Nat Commun ; 7: 12818, 2016 Sep 23.
Article in English | MEDLINE | ID: mdl-27659064

ABSTRACT

The oceans at the start of the Neoproterozoic Era (1,000-541 million years ago, Ma) were dominantly anoxic, but may have become progressively oxygenated, coincident with the rise of animal life. However, the control that oxygen exerted on the development of early animal ecosystems remains unclear, as previous research has focussed on the identification of fully anoxic or oxic conditions, rather than intermediate redox levels. Here we report anomalous cerium enrichments preserved in carbonate rocks across bathymetric basin transects from nine localities of the Nama Group, Namibia (∼550-541 Ma). In combination with Fe-based redox proxies, these data suggest that low-oxygen conditions occurred in a narrow zone between well-oxygenated surface waters and fully anoxic deep waters. Although abundant in well-oxygenated environments, early skeletal animals did not occupy oxygen impoverished regions of the shelf, demonstrating that oxygen availability (probably >10 µM) was a key requirement for the development of early animal-based ecosystems.

11.
Nat Commun ; 7: 12236, 2016 07 19.
Article in English | MEDLINE | ID: mdl-27433855

ABSTRACT

The end-Permian mass extinction, ∼252 million years ago, is notable for a complex recovery period of ∼5 Myr. Widespread euxinic (anoxic and sulfidic) oceanic conditions have been proposed as both extinction mechanism and explanation for the protracted recovery period, yet the vertical distribution of anoxia in the water column and its temporal dynamics through this time period are poorly constrained. Here we utilize Fe-S-C systematics integrated with palaeontological observations to reconstruct a complete ocean redox history for the Late Permian to Early Triassic, using multiple sections across a shelf-to-basin transect on the Arabian Margin (Neo-Tethyan Ocean). In contrast to elsewhere, we show that anoxic non-sulfidic (ferruginous), rather than euxinic, conditions were prevalent in the Neo-Tethys. The Arabian Margin record demonstrates the repeated expansion of ferruginous conditions with the distal slope being the focus of anoxia at these times, as well as short-lived episodes of oxia that supported diverse biota.

12.
Nat Commun ; 6: 7284, 2015 Jun 15.
Article in English | MEDLINE | ID: mdl-26073309

ABSTRACT

The interconversion between inactive and active protein states, traditionally described by two static structures, is at the heart of signalling. However, how folded states interconvert is largely unknown due to the inability to experimentally observe transition pathways. Here we explore the free energy landscape of the bacterial response regulator NtrC by combining computation and nuclear magnetic resonance, and discover unexpected features underlying efficient signalling. We find that functional states are defined purely in kinetic and not structural terms. The need of a well-defined conformer, crucial to the active state, is absent in the inactive state, which comprises a heterogeneous collection of conformers. The transition between active and inactive states occurs through multiple pathways, facilitated by a number of nonnative transient hydrogen bonds, thus lowering the transition barrier through both entropic and enthalpic contributions. These findings may represent general features for functional conformational transitions within the folded state.


Subject(s)
Bacterial Proteins/metabolism , PII Nitrogen Regulatory Proteins/metabolism , Bacterial Proteins/chemistry , Entropy , Hydrogen Bonding , Kinetics , Magnetic Resonance Spectroscopy , Markov Chains , Models, Molecular , Molecular Dynamics Simulation , PII Nitrogen Regulatory Proteins/chemistry , Protein Structure, Tertiary , Signal Transduction , Thermodynamics
13.
Science ; 348(6231): 229-32, 2015 Apr 10.
Article in English | MEDLINE | ID: mdl-25859043

ABSTRACT

Ocean acidification triggered by Siberian Trap volcanism was a possible kill mechanism for the Permo-Triassic Boundary mass extinction, but direct evidence for an acidification event is lacking. We present a high-resolution seawater pH record across this interval, using boron isotope data combined with a quantitative modeling approach. In the latest Permian, increased ocean alkalinity primed the Earth system with a low level of atmospheric CO2 and a high ocean buffering capacity. The first phase of extinction was coincident with a slow injection of carbon into the atmosphere, and ocean pH remained stable. During the second extinction pulse, however, a rapid and large injection of carbon caused an abrupt acidification event that drove the preferential loss of heavily calcified marine biota.


Subject(s)
Aquatic Organisms , Carbon , Extinction, Biological , Seawater/chemistry , Animals , Atmosphere , Boron , Carbon Cycle , Carbon Isotopes , Ecosystem , Hydrogen-Ion Concentration , Isotopes , Oceans and Seas , Time
14.
Int J Comput Assist Radiol Surg ; 10(11): 1873-91, 2015 Nov.
Article in English | MEDLINE | ID: mdl-25559760

ABSTRACT

PURPOSE: Realistic modelling of soft tissue biomechanics and mechanical interactions between tissues is an important part of biomechanically-informed surgical image-guidance and surgical simulation. This submission details a contact-modelling pipeline suitable for implementation in explicit matrix-free FEM solvers. While these FEM algorithms have been shown to be very suitable for simulation of soft tissue biomechanics and successfully used in a number of image-guidance systems, contact modelling specifically for these solvers is rarely addressed, partly because the typically large number of time steps required with this class of FEM solvers has led to a perception of them being a poor choice for simulations requiring complex contact modelling. METHODS: The presented algorithm is capable of handling most scenarios typically encountered in image-guidance. The contact forces are computed with an evolution of the Lagrange-multiplier method first used by Taylor and Flanagan in PRONTO 3D extended with spatio-temporal smoothing heuristics for improved stability and edge-edge collision handling, and a new friction model. For contact search, a bounding-volume hierarchy (BVH) is employed, which is capable of identifying self-collisions by means of the surface-normal bounding cone of Volino and Magnenat-Thalmann, in turn computed with a novel formula. The BVH is further optimised for the small time steps by reducing the number of bounding-volume refittings between iterations through identification of regions with mostly rigid motion and negligible deformation. Further optimisation is achieved by integrating the self-collision criterion in the BVH creation and updating algorithms. RESULTS: The effectiveness of the algorithm is demonstrated on a number of artificial test cases and meshes derived from medical image data. It is shown that the proposed algorithm reduces the cost of BVH refitting to the point where it becomes a negligible part of the overall computation time of the simulation. It is also shown that the proposed surface-normal cone computation formula leads to about 40 % fewer BVH subtrees that must be checked for self-collisions compared with the widely used method of Provot. The proposed contact-force formulation and friction model are evaluated on artificial test cases that allow for a comparison with a ground truth. The quality of the proposed contact forces is assessed in terms of trajectories and energy conservation; a [Formula: see text]0.4 % drop off in total energy and highly plausible trajectories are found in the experiments. The friction model is evaluated through a benchmark problem with an analytical solution and a maximum displacement error of 8.2 %, and excellent agreement in terms of the stick/slip boundary is found. Finally, we show with realistic image-guidance examples that the entire contact-modelling pipeline can be executed within a timeframe that is of the same order of magnitude as that required for standard FEM computations.


Subject(s)
Algorithms , Computer Simulation , Models, Anatomic , Biomechanical Phenomena , Breast/physiology , Diaphragm/physiology , Female , Finite Element Analysis , Humans , Liver/physiology , Male , Models, Theoretical , Prostate/physiology
15.
Case Rep Nephrol Urol ; 3(1): 69-73, 2013.
Article in English | MEDLINE | ID: mdl-24167515

ABSTRACT

We present a case of type 1 cryoglobulinemia with an underlying hematological malignancy. Unusually, the entire unifying diagnosis was made on the basis of the renal biopsy. Initially, serum cryoglobulin was not identified; repeat samples were positive. It is important to note that there is a significant false-negative rate with laboratory testing for cryoglobulin, due, at least in part, to the specific conditions required for collection and processing. With that in mind, in all cases with strong clinical or histological evidence of cryoglobulin but negative testing, carefully repeated samples should be sent.

16.
Am J Med Genet C Semin Med Genet ; 163C(4): 232-45, 2013 Nov.
Article in English | MEDLINE | ID: mdl-24124010

ABSTRACT

We introduce the Ontology of Craniofacial Development and Malformation (OCDM) as a mechanism for representing knowledge about craniofacial development and malformation, and for using that knowledge to facilitate integrating craniofacial data obtained via multiple techniques from multiple labs and at multiple levels of granularity. The OCDM is a project of the NIDCR-sponsored FaceBase Consortium, whose goal is to promote and enable research into the genetic and epigenetic causes of specific craniofacial abnormalities through the provision of publicly accessible, integrated craniofacial data. However, the OCDM should be usable for integrating any web-accessible craniofacial data, not just those data available through FaceBase. The OCDM is based on the Foundational Model of Anatomy (FMA), our comprehensive ontology of canonical human adult anatomy, and includes modules to represent adult and developmental craniofacial anatomy in both human and mouse, mappings between homologous structures in human and mouse, and associated malformations. We describe these modules, as well as prototype uses of the OCDM for integrating craniofacial data. By using the terms from the OCDM to annotate data, and by combining queries over the ontology with those over annotated data, it becomes possible to create "intelligent" queries that can, for example, find gene expression data obtained from mouse structures that are precursors to homologous human structures involved in malformations such as cleft lip. We suggest that the OCDM can be useful not only for integrating craniofacial data, but also for expressing new knowledge gained from analyzing the integrated data.


Subject(s)
Computational Biology , Craniofacial Abnormalities/genetics , Databases, Factual , Translational Research, Biomedical , Animals , Craniofacial Abnormalities/classification , Craniofacial Abnormalities/physiopathology , Epigenomics , Genomics , Humans , Mice
17.
Am J Nephrol ; 36(6): 554-60, 2012.
Article in English | MEDLINE | ID: mdl-23221061

ABSTRACT

BACKGROUND: The nephrotic syndrome is associated with an increased risk of venous and arterial thrombosis. There are little published data on the distribution, interpretation or determinants of serum D-dimer levels in patients with the nephrotic syndrome. We aimed to describe this relationship. METHODS: This was a cross-sectional study of 100 patients with the nephrotic syndrome. Multivariate linear regression was used to evaluate for independent predictors of elevated D-dimer levels. Patients were observed for a period of 2 years after the baseline measurement of D-dimer level to assess for subsequent clinically evident thrombosis. RESULTS: On univariate linear regression, D-dimer elevation was associated with age in years ß (95% CI) 0.02 (0.016, 0.03), log-transformed urinary protein:creatinine ratio in g/g 0.439 (0.32, 0.558) and inversely with serum albumin in g/l -0.05 (-0.073, -0.035) and estimated glomerular filtration rate (eGFR) in ml/min/1.73 m(2) -0.01 (-0.016, -0.003). On multivariate linear regression, age in years ß (95% CI) 0.019 (0.012, 0.026), serum albumin in g/l -0.023 (-0.043, -0.003), and log-transformed urinary protein:creatinine ratio in g/g 0.266 (0.124, 0.408) were independently associated with elevated D-dimer levels. CONCLUSION: D-dimer levels are commonly raised in the nephrotic syndrome in the absence of clinically evident thrombosis, and are independently associated with age, degree of proteinuria and serum albumin, but not with eGFR. Baseline levels of D-dimer did not predict subsequent episodes of clinically evident thrombosis after 2 years of follow-up.


Subject(s)
Albuminuria/blood , Fibrin Fibrinogen Degradation Products/metabolism , Nephrotic Syndrome/blood , Adult , Age Factors , Aged , Creatinine/urine , Cross-Sectional Studies , Female , Glomerular Filtration Rate , Humans , Linear Models , Male , Middle Aged , Multivariate Analysis , Nephrotic Syndrome/urine , Proteinuria/blood , Serum Albumin/metabolism
18.
Science ; 336(6086): 1301-4, 2012 Jun 08.
Article in English | MEDLINE | ID: mdl-22555435

ABSTRACT

Records of atmospheric carbon dioxide concentration (P(CO(2))) and Antarctic temperature have revealed an intriguing change in the magnitude of interglacial warmth and P(CO(2)) at around 430,000 years ago (430 ka), but the global climate repercussions of this change remain elusive. Here, we present a stalagmite-based reconstruction of tropical West Pacific hydroclimate from 570 to 210 ka. The results suggest similar regional precipitation amounts across the four interglacials contained in the record, implying that tropical hydroclimate was insensitive to interglacial differences in P(CO(2)) and high-latitude temperature. In contrast, during glacial terminations, drying in the tropical West Pacific accompanied cooling events in northern high latitudes. Therefore, the tropical convective heat engine can either stabilize or amplify global climate change, depending on the nature of the climate forcing.

19.
J Neurol Neurosurg Psychiatry ; 83(1): 109-14, 2012 Jan.
Article in English | MEDLINE | ID: mdl-21849340

ABSTRACT

BACKGROUND: The human prion diseases are a group of universally fatal neurodegenerative disorders associated with the auto-catalytic misfolding of the normal cell surface prion protein (PrP). Mutations causative of inherited human prion disease (IPD) include an insertion of six additional octapeptide repeats (6-OPRI) and a missense mutation (P102L) with large families segregating for each mutation residing in southern England. Here we report for the first time the neuropsychological and clinical assessments in these two groups. METHOD: The cognitive profiles addressing all major domains were obtained for 26 patients (18 6-OPRI, 8 P102L) and the cortical thickness determined using 1.5T MRI in a subset of 10 (six 6-OPRI, four P102L). RESULTS: The cognitive profiles were different in patients with the two mutations in the symptomatic phase of the disease. The 6-OPRI group had lower premorbid optimal levels of functioning (assessed on the NART) than the P102L group. In the symptomatic phase of the disease the 6-OPRI patients had significantly more executive dysfunction than the P102L group and were more impaired on tests of perception and nominal functions. There was anecdotal evidence of low premorbid social performance in the 6-OPRI but not P102L patients. Cortical thinning distribution correlated with the neuropsychological profile in the 6-OPRI group principally involving the parietal, occipital and posterior frontal regions. The small number of patients in the P102L group precluded statistical comparison between the groups. CONCLUSIONS: The 6-OPRI patients had more widespread and severe cognitive dysfunction than the P102L group and this correlated with cortical thinning distribution.


Subject(s)
Brain/pathology , Mutagenesis, Insertional/genetics , Prion Diseases/genetics , Prions/genetics , Adult , Cognition Disorders/etiology , Executive Function , Female , Humans , Magnetic Resonance Imaging , Male , Memory Disorders/etiology , Middle Aged , Neuroimaging , Neuropsychological Tests , Prion Diseases/complications , Prion Diseases/pathology , United Kingdom , Young Adult
20.
Ir J Med Sci ; 180(3): 661-5, 2011 Sep.
Article in English | MEDLINE | ID: mdl-21516355

ABSTRACT

BACKGROUND: Lithium is a commonly prescribed pharmacological treatment for mood disorders. It is associated with a number of side effects and potentially serious toxicity. To date, there is little data from Irish samples on the subject of Lithium toxicity. AIM: To examine the incidence and clinical correlates of lithium toxicity in Cork, Ireland. RESULTS: Our study identified 130 cases of biochemical lithium toxicity over 5 years, with an incidence rate of approximately 5.4 cases per 100,000 per year. Mean toxic lithium level was 2.16 mmol/L ±SD 0.87 mmol/L. Of these, 36% cases were reviewed medically in the general hospital at the time of toxicity. A number of issues in relation to lithium toxicity were identified. Neurological symptoms were common, including tremor, confusion, ataxia, drowsiness. However, only 4.2% patients were reviewed by a neurologist while in hospital. Medications that interact with lithium were found in 50% cases, with significant polypharmacy in 15%. The psychiatric services were involved in patient care in 76% cases, and 85% patients presenting with toxicity were reviewed by a psychiatrist. Rates of admission to hospital and haemodialysis were 70 and 11%, respectively. CONCLUSION: Improvements in the standards of care in relation to lithium prescribing are required.


Subject(s)
Lithium/toxicity , Adult , Aged , Aged, 80 and over , Confusion/chemically induced , Female , Humans , Lithium/blood , Lithium/therapeutic use , Male , Middle Aged , Mood Disorders/drug therapy , Retrospective Studies , Standard of Care , Tremor/chemically induced
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