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1.
PLoS Comput Biol ; 20(3): e1011797, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38427633

ABSTRACT

Inclusion at academic events is facing increased scrutiny as the communities these events serve raise their expectations for who can practically attend. Active efforts in recent years to bring more diversity to academic events have brought progress and created momentum. However, we must reflect on these efforts and determine which underrepresented groups are being disadvantaged. Inclusion at academic events is important to ensure diversity of discourse and opinion, to help build networks, and to avoid academic siloing. All of these contribute to the development of a robust and resilient academic field. We have developed these Ten Simple Rules both to amplify the voices that have been speaking out and to celebrate the progress of many Equity, Diversity, and Inclusivity practices that continue to drive the organisation of academic events. The Rules aim to raise awareness as well as provide actionable suggestions and tools to support these initiatives further. This aims to support academic organisations such as the Deep Learning Indaba, Neuromatch Academy, the IBRO-Simons Computational Neuroscience Imbizo, Biodiversity Information Standards (TDWG), Arabs in Neuroscience, FAIRPoints, and OLS (formerly Open Life Science). This article is a call to action for organisers to reevaluate the impact and reach of their inclusive practices.

2.
Ophthalmic Plast Reconstr Surg ; 40(2): 192-197, 2024.
Article in English | MEDLINE | ID: mdl-38427833

ABSTRACT

PURPOSE: Botulinum toxin (BoNTA) lacrimal gland injections are one treatment option for managing epiphora. Outcomes for epiphora in existing studies are subjective and lack grading. This study utilized validated grading instruments to evaluate the efficacy of BoNTA lacrimal gland injections. METHODS: Prospective study evaluating the TEARS score and quality of life in patients receiving incobotulinum toxin (Xeomin) lacrimal gland injections for epiphora. Epiphora was graded using the TEARS score. Quality of life was evaluated using the watery eye quality of life score. Etiology, benefit duration, complications and additional injections were recorded. RESULTS: Of the 28 patients, (median age 67.5 years), 19 (68%) had facial palsy gustatory epiphora (GE). Median effect duration was 13 weeks. Improvements in tearing frequency (T), clinical effects (E), and activity limitation (A) were seen in 57%, 57%, and 71% of patients, respectively. Median watery eye quality of life score improved from 42.4/100 ± 10.1 to 10.6 ± 15.5 (p < 0.001). Alongside crocodile tears, reflex tearing R-scores improved in 68% of patients with GE vs. 11% with non-GE causes (p = 0.004618). In total 89% of patients with GE and 56% with non-GE requested repeat injections. Self-reported percentage improvement ranged from 0% to 100% (median 60%, interquartile range 10%-76.25%). CONCLUSIONS: This is the first study reporting the outcomes of BoNTA lacrimal gland injections using validated TEARS and watery eye quality of life scores. Clinical and quality of life improvements are seen in most patients. Patients with GE achieve an additional improvement in dry eye-related reflex tearing alongside crocodile tears which both improve with BoNTA. TEARS data supports using BoNTA in these patients and is a useful validated grading instrument for epiphora.


Subject(s)
Botulinum Toxins, Type A , Lacrimal Apparatus Diseases , Lacrimal Apparatus , Neuromuscular Agents , Humans , Aged , Prospective Studies , Quality of Life , Neuromuscular Agents/therapeutic use , Botulinum Toxins, Type A/therapeutic use , Tears , Lacrimal Apparatus Diseases/diagnosis , Lacrimal Apparatus Diseases/drug therapy , Lacrimal Apparatus Diseases/etiology
3.
BMJ Open ; 13(11): e076715, 2023 11 21.
Article in English | MEDLINE | ID: mdl-37989364

ABSTRACT

OBJECTIVE: Pembrolizumab is a programmed cell death protein-1 (PD-1) inhibitor used to treat advanced patients with non-small cell lung cancer (NSCLC) with a programmed cell death ligand-1 (PD-L1) tumour proportion score (TPS) ≥50. Further sub-division of TPS-based stratification has not been evaluated in the UK, although smoking-induced tumour mutational burden and the immunogenic effects of prior radiotherapy are suggested to improve response. AIMS: To investigate if PD-L1 TPS ≥80%, smoking status or radiotherapy before or within 2 months of treatment influenced progression-free survival (PFS) in patients with NSCLC treated with pembrolizumab monotherapy. METHODS: PD-L1 TPS, smoking status and radiotherapy exposure were compared in patients with NSCLC in National Health Service (NHS) Tayside (n=100) treated with pembrolizumab monotherapy between 1 November 2017 and 18 February 2022. Survival estimates were compared using log-rank analysis, and Cox proportional hazards analysis was used to investigate the influence of potential confounding factors, including tumour stage and performance status. RESULTS: PFS was not significantly different (log-rank HR=0.330, p=0.566) comparing patients with PD-L1 TPS 50-79% and PD-L1 TPS ≥80%. Smokers had significantly improved PFS (log-rank HR=4.867, p=0.027), while patients receiving radiotherapy had significantly decreased PFS (log-rank HR=6.649, p=0.012). A Cox regression model confirmed that both radiotherapy (p=0.022) and performance status (p=0.009) were independent negative predictors of PFS. CONCLUSIONS: More rigorous PD-L1 TPS stratification did not influence survival outcomes. Smoking history improved PFS, although it was not an independent response predictor, while radiotherapy and performance status independently influenced clinical response. We suggest that further stratification of PD-L1 TPS is not warranted, while performance status and radiotherapy treatment may be additional clinically useful biomarkers of response to pembrolizumab in patients with NSCLC.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Humans , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/pathology , Lung Neoplasms/drug therapy , Lung Neoplasms/pathology , B7-H1 Antigen , Retrospective Studies , State Medicine , United Kingdom
4.
PLoS Comput Biol ; 18(9): e1010534, 2022 09.
Article in English | MEDLINE | ID: mdl-36149893

ABSTRACT

Many neurons in the mammalian central nervous system have complex dendritic arborisations and active dendritic conductances that enable these cells to perform sophisticated computations. How dendritically targeted inhibition affects local dendritic excitability is not fully understood. Here we use computational models of branched dendrites to investigate where GABAergic synapses should be placed to minimise dendritic excitability over time. To do so, we formulate a metric we term the "Inhibitory Level" (IL), which quantifies the effectiveness of synaptic inhibition for reducing the depolarising effect of nearby excitatory input. GABAergic synaptic inhibition is dependent on the reversal potential for GABAA receptors (EGABA), which is primarily set by the transmembrane chloride ion (Cl-) concentration gradient. We, therefore, investigated how variable EGABA and dynamic chloride affects dendritic inhibition. We found that the inhibitory effectiveness of dendritic GABAergic synapses combines at an encircled branch junction. The extent of this inhibitory accumulation is dependent on the number of branches and location of synapses but is independent of EGABA. This inhibitory accumulation occurs even for very distally placed inhibitory synapses when they are hyperpolarising-but not when they are shunting. When accounting for Cl- fluxes and dynamics in Cl- concentration, we observed that Cl- loading is detrimental to inhibitory effectiveness. This enabled us to determine the most inhibitory distribution of GABAergic synapses which is close to-but not at-a shared branch junction. This distribution balances a trade-off between a stronger combined inhibitory influence when synapses closely encircle a branch junction with the deleterious effects of increased Cl- by loading that occurs when inhibitory synapses are co-located.


Subject(s)
Chlorides , Dendrites , Animals , Computer Simulation , Dendrites/physiology , Mammals , Neurons/physiology , Synapses/physiology
5.
Sci Rep ; 12(1): 9234, 2022 06 02.
Article in English | MEDLINE | ID: mdl-35654942

ABSTRACT

In social networks, users often engage with like-minded peers. This selective exposure to opinions might result in echo chambers, i.e., political fragmentation and social polarization of user interactions. When echo chambers form, opinions have a bimodal distribution with two peaks on opposite sides. In certain issues, where either extreme positions contain a degree of misinformation, neutral consensus is preferable for promoting discourse. In this paper, we use an opinion dynamics model that naturally forms echo chambers in order to find a feedback mechanism that bridges these communities and leads to a neutral consensus. We introduce the random dynamical nudge (RDN), which presents each agent with input from a random selection of other agents' opinions and does not require surveillance of every person's opinions. Our computational results in two different models suggest that the RDN leads to a unimodal distribution of opinions centered around the neutral consensus. Furthermore, the RDN is effective both for preventing the formation of echo chambers and also for depolarizing existing echo chambers. Due to the simple and robust nature of the RDN, social media networks might be able to implement a version of this self-feedback mechanism, when appropriate, to prevent the segregation of online communities on complex social issues.


Subject(s)
Social Media , Social Networking , Attitude , Communication , Emotions , Humans
6.
BMC Microbiol ; 22(1): 18, 2022 01 08.
Article in English | MEDLINE | ID: mdl-34996363

ABSTRACT

BACKGROUND: Fe-deficiency chlorosis (FDC) of Asian pear plants is widespread, but little is known about the association between the microbial communities in the rhizosphere soil and leaf chlorosis. The leaf mineral concentration, leaf subcellular structure, soil physiochemical properties, and bacterial species community and distribution had been analysed to gain insights into the FDC in Asian pear plant. RESULTS: The total Fe in leaves with Fe-deficiency was positively correlated with total K, Mg, S, Cu, Zn, Mo and Cl contents, but no differences of available Fe (AFe) were detected between the rhizosphere soil of chlorotic and normal plants. Degraded ribosomes and degraded thylakloid stacks in chloroplast were observed in chlorotic leaves. The annotated microbiome indicated that there were 5 kingdoms, 52 phyla, 94 classes, 206 orders, 404 families, 1,161 genera, and 3,043 species in the rhizosphere soil of chlorotic plants; it was one phylum less and one order, 11 families, 59 genera, and 313 species more than in that of normal plant. Bacterial community and distribution patterns in the rhizosphere soil of chlorotic plants were distinct from those of normal plants and the relative abundance and microbiome diversity were more stable in the rhizosphere soils of normal than in chlorotic plants. Three (Nitrospira defluvii, Gemmatirosa kalamazoonesis, and Sulfuricella denitrificans) of the top five species (N. defluvii, G. kalamazoonesis, S. denitrificans, Candidatus Nitrosoarchaeum koreensis, and Candidatus Koribacter versatilis). were the identical and aerobic in both rhizosphere soils, but their relative abundance decreased by 48, 37, and 22%, respectively, and two of them (G. aurantiaca and Ca. S. usitatus) were substituted by an ammonia-oxidizing soil archaeon, Ca. N. koreensis and a nitrite and nitrate reduction related species, Ca. K. versatilis in that of chlorotic plants, which indicated the adverse soil aeration in the rhizosphere soil of chlorotic plants. A water-impermeable tables was found to reduce the soil aeration, inhibit root growth, and cause some absorption root death from infection by Fusarium solani. CONCLUSIONS: It was waterlogging or/and poor drainage of the soil may inhibit Fe uptake not the amounts of AFe in the rhizosphere soil of chlorotic plants that caused FDC in this study.


Subject(s)
Microbiota , Plant Necrosis and Chlorosis/microbiology , Pyrus/microbiology , Rhizosphere , Bacteria/classification , Bacteria/genetics , Bacteria/isolation & purification , Bacteria/metabolism , Fungi/classification , Fungi/genetics , Fungi/isolation & purification , Fungi/metabolism , Gene Ontology , Iron/analysis , Iron/metabolism , Metagenomics , Minerals/analysis , Minerals/metabolism , Plant Leaves/metabolism , Plant Leaves/microbiology , Plant Leaves/ultrastructure , Plant Roots/growth & development , Plant Roots/microbiology , Pyrus/metabolism , Pyrus/ultrastructure , Soil/chemistry , Soil Microbiology , Water/analysis
7.
Res Sq ; 2022 Dec 29.
Article in English | MEDLINE | ID: mdl-36597548

ABSTRACT

Background: The vast majority of phylogenetic trees are inferred from molecular sequence data (nucleotides or amino acids) using time-reversible evolutionary models which assume that, for any pair of nucleotide or amino acid characters, the relative rate of X to Y substitution is the same as the relative rate of Y to X substitution. However, this reversibility assumption is unlikely to accurately reflect the actual underlying biochemical and/or evolutionary processes that lead to the fixation of substitutions. Here, we use empirical viral genome sequence data to reveal that evolutionary non-reversibility is pervasive among most groups of viruses. Specifically, we consider two non-reversible nucleotide substitution models: (1) a 6-rate non-reversible model (NREV6) in which Watson-Crick complementary substitutions occur at identical relative rates and which might therefor be most applicable to analyzing the evolution of genomes where both complementary strands are subject to the same mutational processes (such as might be expected for double-stranded (ds) RNA or dsDNA genomes); and (2) a 12-rate non-reversible model (NREV12) in which all relative substitution types are free to occur at different rates and which might therefore be applicable to analyzing the evolution of genomes where the complementary genome strands are subject to different mutational processes (such as might be expected for viruses with single-stranded (ss) RNA or ssDNA genomes). Results: Using likelihood ratio and Akaike Information Criterion-based model tests, we show that, surprisingly, NREV12 provided a significantly better fit to 21/31 dsRNA and 20/30 dsDNA datasets than did the general time reversible (GTR) and NREV6 models with NREV6 providing a better fit than NREV12 and GTR in only 5/30 dsDNA and 2/31 dsRNA datasets. As expected, NREV12 provided a significantly better fit to 24/33 ssDNA and 40/47 ssRNA datasets. Next, we used simulations to show that increasing degrees of strand-specific substitution bias decrease the accuracy of phylogenetic inference irrespective of whether GTR or NREV12 is used to describe mutational processes. However, in cases where strand-specific substitution biases are extreme (such as in SARS-CoV-2 and Torque teno sus virus datasets) NREV12 tends to yield more accurate phylogenetic trees than those obtained using GTR. Conclusion: We show that NREV12 should, be seriously considered during the model selection phase of phylogenetic analyses involving viral genomic sequences.

8.
United European Gastroenterol J ; 8(2): 148-156, 2020 03.
Article in English | MEDLINE | ID: mdl-32213077

ABSTRACT

BACKGROUND: Coeliac disease (CD) is associated with an increased risk of other immune-mediated conditions. Aim: To investigate the prevalence of coexistent immune-mediated diseases in CD patients, and changes in the prevalence of autoimmune thyroidal diseases over the last 50 years. METHODS: Medical record data were collected retrospectively from 749 CD patients in Ireland. Prevalence of autoimmune diseases was compared with previously published results from general populations. Patients were divided into four groups based on the year of diagnosis to analyse changes in the prevalence of autoimmune thyroidal disease over time. RESULTS: Median age at the time of CD diagnosis was 56 years (range 18-91 years). A total of 233 (31.1%) patients had a coexistent immune-mediated condition (IMC). Autoimmune thyroidal diseases were seen in 149 (19.9%) patients, hypothyroidism in 110 (14.7%), type 1 diabetes in 27 (3.6%), psoriasis in 20 (2.7%), inflammatory bowel disease in 14 (1.9%) and rheumatoid arthritis in 12 (1.6%). All conditions were more common in CD patients than in the general population. Type 1 diabetes was diagnosed mainly before CD, whereas there was no such trend in other conditions. Autoimmune thyroidal diseases became less common in female CD patients over time. CONCLUSIONS: Prevalence of autoimmune diseases is increased in adult CD patients compared with the general population. However, concomitant autoimmune thyroidal diseases became less common over time in women.


Subject(s)
Celiac Disease/epidemiology , Hypothyroidism/epidemiology , Thyroiditis, Autoimmune/epidemiology , Adolescent , Adult , Aged , Aged, 80 and over , Arthritis, Rheumatoid/epidemiology , Arthritis, Rheumatoid/immunology , Celiac Disease/immunology , Comorbidity/trends , Diabetes Mellitus, Type 1/epidemiology , Diabetes Mellitus, Type 1/immunology , Female , Humans , Hypothyroidism/immunology , Inflammatory Bowel Diseases/epidemiology , Inflammatory Bowel Diseases/immunology , Ireland/epidemiology , Male , Middle Aged , Prevalence , Psoriasis/epidemiology , Psoriasis/immunology , Retrospective Studies , Thyroiditis, Autoimmune/immunology , Young Adult
9.
J Rheumatol ; 47(2): 282-289, 2020 02.
Article in English | MEDLINE | ID: mdl-30988122

ABSTRACT

OBJECTIVE: Accurate automated segmentation of cartilage should provide rapid reliable outcomes for both epidemiological studies and clinical trials. We aimed to assess the precision and responsiveness of cartilage thickness measured with careful manual segmentation or a novel automated technique. METHODS: Agreement of automated segmentation was assessed against 2 manual segmentation datasets: 379 magnetic resonance images manually segmented in-house (training set), and 582 from the Osteoarthritis Initiative with data available at 0, 1, and 2 years (biomarkers set). Agreement of mean thickness was assessed using Bland-Altman plots, and change with pairwise Student t test in the central medial femur (cMF) and tibia regions (cMT). Repeatability was assessed on a set of 19 knees imaged twice on the same day. Responsiveness was assessed using standardized response means (SRM). RESULTS: Agreement of manual versus automated methods was excellent with no meaningful systematic bias (training set: cMF bias 0.1 mm, 95% CI ± 0.35; biomarkers set: bias 0.1 mm ± 0.4). The smallest detectable difference for cMF was 0.13 mm (coefficient of variation 3.1%), and for cMT 0.16 mm(2.65%). Reported change using manual segmentations in the cMF region at 1 year was -0.031 mm (95% CI -0.022, -0.039), p < 10-4, SRM -0.31 (-0.23, -0.38); and at 2 years was -0.071 (-0.058, -0.085), p < 10-4, SRM -0.43 (-0.36, -0.49). Reported change using automated segmentations in the cMF at 1 year was -0.059 (-0.047, -0.071), p < 10-4, SRM -0.41 (-0.34, -0.48); and at 2 years was -0.14 (-0.123, -0.157, p < 10-4, SRM -0.67 (-0.6, -0.72). CONCLUSION: A novel cartilage segmentation method provides highly accurate and repeatable measures with cartilage thickness measurements comparable to those of careful manual segmentation, but with improved responsiveness.


Subject(s)
Cartilage, Articular/diagnostic imaging , Cartilage, Articular/pathology , Data Accuracy , Magnetic Resonance Imaging/methods , Osteoarthritis, Knee/diagnostic imaging , Algorithms , Biomarkers , Disease Progression , Electronic Data Processing , Femur/diagnostic imaging , Femur/pathology , Humans , Knee Joint/diagnostic imaging , Knee Joint/pathology , Reproducibility of Results , Tibia/diagnostic imaging , Tibia/pathology
10.
Eur J Gastroenterol Hepatol ; 31(3): 352-356, 2019 03.
Article in English | MEDLINE | ID: mdl-30334908

ABSTRACT

OBJECTIVES: One of the striking features of splenic imaging is variable heterogeneous gyriform arterial enhancement on dynamic computed tomography (CT). We speculated that these patterns of arterial enhancement may reflect changes in splenic micro-circulation related to changes in portal venous pressure. PATIENTS AND METHODS: To test this hypothesis, we evaluated arterial phase CT scans performed before and after liver transplantation (n=91), as this is the most effective way of alleviating portal hypertension. We developed novel grading systems to assess heterogeneity. Two control groups were used: patients with cirrhosis undergoing transarterial chemoembolization (TACE) (n=28) and patients with cirrhosis on the liver transplant waiting list who had repeated CT scans (n=28). RESULTS: Splenic arterial heterogeneity increased in 55% of transplant patients compared with 14% in the TACE patients and 4% in the waiting list patients (P<0.0001). Mean Hounsfield units in areas of splenic enhancement were 71.7±2 before transplant and 90.1±2.5 after transplant (P<0.01). In contrast, there were no significant changes following TACE (86.3±4.2 vs. 83.5±4.5; P=NS) or in waiting list patients (80.9±4.6 vs. 73.8±3.7; P=NS). CONCLUSION: We have shown the heterogeneous gyriform enhancement patterns significantly increase following liver transplantation but not after TACE or in waiting list patients. We suggest that these changes are due to the reduction in portal venous pressure and likely reflect changes in splenic micro-circulation. These changes may be important in the pathophysiology of hypersplenism.


Subject(s)
Carcinoma, Hepatocellular/diagnostic imaging , Computed Tomography Angiography , Hypertension, Portal/diagnostic imaging , Liver Cirrhosis/diagnostic imaging , Liver Neoplasms/diagnostic imaging , Portal Pressure , Splenic Artery/diagnostic imaging , Splenomegaly/diagnostic imaging , Aged , Carcinoma, Hepatocellular/etiology , Carcinoma, Hepatocellular/physiopathology , Carcinoma, Hepatocellular/therapy , Case-Control Studies , Chemoembolization, Therapeutic , Female , Humans , Hypertension, Portal/etiology , Hypertension, Portal/physiopathology , Hypertension, Portal/therapy , Liver Cirrhosis/complications , Liver Cirrhosis/physiopathology , Liver Cirrhosis/therapy , Liver Neoplasms/etiology , Liver Neoplasms/physiopathology , Liver Neoplasms/therapy , Liver Transplantation , Male , Microcirculation , Middle Aged , Predictive Value of Tests , Splanchnic Circulation , Splenic Artery/physiopathology , Splenomegaly/etiology , Splenomegaly/physiopathology , Treatment Outcome , Waiting Lists
11.
Int J Hyperthermia ; 35(1): 348-360, 2018.
Article in English | MEDLINE | ID: mdl-30295125

ABSTRACT

Three different magnetic resonance imaging (MRI) coils were developed and assessed for use with an experimental platform designed to generate hyperthermia in mice using magnetic resonance-guided focused ultrasound (MRgFUS). An ergonomic animal treatment bed was integrated with MRI coils. Three different coil designs optimized for small targets were tested, and performance in targeting and conducting accurate temperature imaging was evaluated. Two transmit/receive surface coils of different diameters (4 and 7 cm) and a transmit-only/receive-only (TORO) coil were used. A software platform was developed to provide real-time targeting and temperature maps and to deliver controlled ultrasound exposure. MR thermometry was conducted on different targets, including fresh chicken breasts and mouse cadavers. Multiple experiments were performed in which tissues were targeted with high reproducibility. The TORO coil was the most resilient to temperature drift, resulting in an increase in the calculated temperature of 0.29 ± 0.12 °C, compared to 1.27 ± 0.13 °C and 0.47 ± 0.04 °C for the medium and small coils, respectively. Controlled closed-loop hyperthermia exposure was successfully performed with all three coils. Considering all assessments, the TORO coil exhibited the best overall performance for thermometry acquisition when accounting for stability, precision, temperature spread and resilience to temperature drift. B1 maps of the three coils confirmed that the TORO coil exhibited the most homogeneous B1 field, which explained the improved thermometry performance. The use of coils specifically designed for small targets within the proposed experimental platform allowed accurate thermometry during hyperthermia.


Subject(s)
High-Intensity Focused Ultrasound Ablation/methods , Magnetic Resonance Imaging/methods , Animals , Disease Models, Animal , Mice
12.
Clin Gastroenterol Hepatol ; 15(6): 864-871.e3, 2017 Jun.
Article in English | MEDLINE | ID: mdl-28043932

ABSTRACT

BACKGROUND & AIMS: Celiac disease is an immune-mediated enteropathy characterized with high heterogeneity in presentation among genetically predisposed individuals. In recent years, a change in the phenotypic presentation of celiac disease has been reported. We studied clinical presentation, from 1960 through 2015, in Ireland, which has a high incidence of celiac disease. METHODS: We performed a retrospective analysis of medical charts from patients diagnosed with celiac disease at 5 secondary referral centers in Ireland from 1960 through 2015 (n = 749; median age, 56 years; age range, 18-91 years). The cohort was divided into 5 groups based on year of diagnosis (≤1985, 1986-1995, 1996-2005, 2006-2010, or 2011 and later). We collected findings from clinical presentation at diagnosis; serology tests; small intestinal biopsy analyses; and patients' demographic, clinical, and family data. Presentations at diagnosis were classified according to the Oslo criteria as follows: classical (patients presenting with malabsorption), nonclassical (no signs or symptoms of malabsorption at presentation), or subclinical (below the threshold of clinical detection). The primary outcome was change in clinical presentation of celiac disease over time. RESULTS: Of the 749 patients studied, 512 were female and 237 were male (ratio of 2.2:1). Female patients were diagnosed at younger ages than male patients (42 vs 47 years, respectively; P = .004), and had more immune-mediated conditions than male patients (35.7% for female patients vs 21.5% for male patients; P < .001). For patients diagnosed as adults (after the age of 18 years), the median age of diagnosis increased from 34.0 years during the period ≤1985 to median ages of 44-46 years after 1985 (P < .002). A smaller proportion of patients presented with classical features of celiac disease after 2010 (48.4%) than ≤1985 (85.2%); the proportion of patients with nonclassical or subclinical celiac disease increased from 14.8% ≤1985 to 51.6% after 2010 (P = .006 for each). Biopsies categorized as Marsh 3c decreased, from 52.2% in the period 1996-2005 to 22.5% in the period after 2010 (P = .003). The prevalence of associated thyroid disease has decreased during the study period, from 36.6% ≤1985 to 17.1% after 2010 (P = .039), whereas body mass index at diagnosis increased from 21.5 kg/m2 ≤1985 to 24.8 kg/m2 after 2010 (P < .001). CONCLUSIONS: We found the clinical presentation of celiac disease changed significantly in Ireland from 1960 through 2015. The age of presentation in adulthood increased over this time period, as did the proportions of patients with nonclassical or subclinical disease.


Subject(s)
Celiac Disease/pathology , Adolescent , Adult , Aged , Aged, 80 and over , Celiac Disease/epidemiology , Female , Humans , Ireland/epidemiology , Male , Middle Aged , Retrospective Studies , Young Adult
13.
Ann Hum Biol ; 41(4): 312-22, 2014.
Article in English | MEDLINE | ID: mdl-24932746

ABSTRACT

BACKGROUND: Diagnosing Homo sapiens is a critical question in the study of human evolution. Although what constitutes living members of our own species is straightforward, in the fossil record this is still a matter of much debate. The issue is complicated by questions of species diagnoses and ideas about the mode by which a new species is born, by the arguments surrounding the behavioural and cognitive separateness of the species, by the increasing appreciation of variation in the early African H. sapiens record and by new DNA evidence of hybridization with extinct species. METHODS AND RESULTS: This study synthesizes thinking on the fossils, archaeology and underlying evolutionary models of the last several decades with recent DNA results from both H. sapiens and fossil species. CONCLUSION: It is concluded that, although it may not be possible or even desirable to cleanly partition out a homogenous morphological description of recent H. sapiens in the fossil record, there are key, distinguishing morphological traits in the cranium, dentition and pelvis that can be usefully employed to diagnose the H. sapiens lineage. Increasing advances in retrieving and understanding relevant genetic data provide a complementary and perhaps potentially even more fruitful means of characterizing the differences between H. sapiens and its close relatives.


Subject(s)
Biological Evolution , DNA/analysis , Fossils/anatomy & histology , Hybridization, Genetic , Archaeology , Humans , Phenotype
14.
Can J Urol ; 21(2 Supp 1): 28-36, 2014 Apr.
Article in English | MEDLINE | ID: mdl-24775721

ABSTRACT

INTRODUCTION: Intermittent androgen deprivation therapy (IADT) for prostate cancer involves cycles of androgen deprivation therapy (ADT) with a period between cycles where testosterone is allowed to rise above castrate levels. A number of recent randomized controlled trials (RCTs) have compared survival and health-related quality-of-life (HRQOL) between IADT and continuous ADT (CADT). This review seeks to critically analyze these published trials for their relevance to clinical practice. MATERIALS AND METHODS: Published trials were retrieved from a systematic search of MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials databases using relevant keywords. Recent systematic reviews published on this topic were hand-searched for additional applicable references. The evidence was then synthesized for this review. RESULTS: A number of phase III trials have been recently published. IADT was found to be non-inferior in the primary setting for non-metastatic prostate cancer as well as in treatment of biochemical recurrence following radiotherapy. However, these studies overrepresented low risk patients in whom consideration may be given to deferred ADT rather than early treatment with IADT. In the metastatic prostate cancer setting, IADT was not found to be non-inferior to CADT. In most trials, castration related symptoms improved with IADT and overall HRQOL results were mixed. Little data are available on the effect of IADT on long term complications of ADT. CONCLUSIONS: IADT remains a treatment with uncertain outcomes in metastatic prostate cancer and uncertain value over deferring ADT entirely in other prostate cancer clinical states.


Subject(s)
Androgen Antagonists/therapeutic use , Practice Patterns, Physicians' , Prostatic Neoplasms/drug therapy , Randomized Controlled Trials as Topic , Translational Research, Biomedical , Androgen Antagonists/administration & dosage , Drug Administration Schedule , Humans , Male , Neoplasm Metastasis/drug therapy , Quality of Life , Treatment Outcome
15.
Animals (Basel) ; 4(1): 119-30, 2014 Mar 17.
Article in English | MEDLINE | ID: mdl-26479887

ABSTRACT

Urban environments are unique, rapidly changing habitats in which almost half of the world's human population resides. The effects of urbanisation, such as habitat (vegetation) removal, pollution and modification of natural areas, commonly cause biodiversity loss. Long-term ecological monitoring of urban environments is vital to determine the composition and long-term trends of faunal communities. This paper provides a detailed view of long-term changes in avifaunal assemblages of the Adelaide City parklands and discusses the anthropogenic and environmental factors that contributed to the changes between 1976 and 2007. The Adelaide City parklands (ACP) comprise 760 ha of land surrounding Adelaide's central business district. Naturalist Robert Whatmough completed a 32-year survey of the ACP to determine the structure of the urban bird community residing there. Annual species richness and the abundance of birds in March and September months were analysed. Linear regression analysis was applied to species richness and abundance data of each assemblage. Resident parkland birds demonstrated significant declines in abundance. Native and introduced species also exhibited long-term declines in species richness and abundance throughout the 32-year period. Cycles of varying time periods indicated fluctuations in avian biodiversity demonstrating the need for future monitoring and statistical analyses on bird communities in the Adelaide City parklands.

16.
New Solut ; 14(4): 349-55, 2004.
Article in English | MEDLINE | ID: mdl-17208821

ABSTRACT

The prevalence of smoking among Latino immigrant workers needs to be addressed with culturally and linguistically appropriate smoking cessation programs. One innovative approach to reaching these workers is through worker health and safety training programs. These programs offer multiple opportunities to provide smoking cessation messages, a "teachable moment" to focus on health issues, and the likelihood that peers and family members will share these messages. A collaborative effort between an occupational health and safety training facility and a university utilizing Latino and non-Latino personnel developed a smoking cessation program integrated with worker health and safety training. Preliminary results of an evaluation of the program indicate that the program was able to reach a wide range of immigrant workers and improve their knowledge of the risks of smoking and the effectiveness of different methods of quitting smoking.

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