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1.
Qual Life Res ; 28(5): 1145-1154, 2019 May.
Article in English | MEDLINE | ID: mdl-30484121

ABSTRACT

PURPOSE: There is concern that some generic preference-based measures (GPMs) of health-related quality of life may be insensitive to interventions that improve hearing. Establishing where sensitivity arises could contribute to the design of improved measures. Accordingly, we compared the sensitivity of four widely used GPMs to a clinically effective treatment-cochlear implantation-which restores material degrees of hearing to adults with little or no functional hearing. METHODS: Participants (N = 147) received implants in any of 13 hospitals in the UK. One month before implantation and 9Ā months after, they completed the HUI2, HUI3, EQ5D3L, and SF-6D questionnaires, together with the EuroQoL visual-analogue scale as a direct measure of health, a performance test of speech reception, and a self-report measure of annoyance due to tinnitus. RESULTS: Implantation was associated with a large improvement in speech reception and a small improvement in tinnitus. HUI2 and HUI3 were sensitive to the improvement in speech reception through their Sensation and Hearing dimensions; EQ5D3L was sensitive to the improvement in tinnitus through its Anxiety/Depression dimension; SF-6D was sensitive to neither. Participants reported no overall improvement in health. Variation in health was associated with variation in tinnitus, not variation in speech reception. CONCLUSIONS: None of the four GPMs was sensitive to the improvements in both speech reception and tinnitus that were associated with cochlear implantation. To capture fully the benefits of interventions for auditory disorders, developments of current GPMs would need to be sensitive to both the health-related and non-health-related aspects of auditory dysfunction.


Subject(s)
Cochlear Implantation/adverse effects , Quality of Life/psychology , Speech/physiology , Tinnitus/etiology , Adult , Cochlear Implantation/methods , Female , Humans , Male , Middle Aged , Surveys and Questionnaires , Tinnitus/pathology
2.
Mol Genet Metab ; 125(1-2): 127-134, 2018 09.
Article in English | MEDLINE | ID: mdl-30055994

ABSTRACT

QUESTION: Does Nitisinone prevent the clinical progression of the Alkaptonuria? FINDINGS: In this observational study on 39 patients, 2Ć¢Ā€ĀÆmg of daily nitisinone inhibited ochronosis and significantly slowed the progression of AKU over a three-year period. MEANING: Nitisinone is a beneficial therapy in Alkaptonuria. BACKGROUND: Nitisinone decreases homogentisic acid (HGA), but has not been shown to modify progression of Alkaptonuria (AKU). METHODS: Thirty-nine AKU patients attended the National AKU Centre (NAC) in Liverpool for assessments and treatment. Nitisinone was commenced at V1 or baseline. Thirty nine, 34 and 22 AKU patients completed 1, 2 and 3Ć¢Ā€ĀÆyears of monitoring respectively (V2, V3 and V4) in the VAR group. Seventeen patients also attended a pre-baseline visit (V0) in the VAR group. Within the 39 patients, a subgroup of the same ten patients attended V0, V1, V2, V3 and V4 visits constituting the SAME Group. Severity of AKU was assessed by calculation of the AKU Severity Score Index (AKUSSI) allowing comparison between the pre-nitisinone and the nitisinone treatment phases. RESULTS: The ALL (sum of clinical, joint and spine AKUSSI features) AKUSSI rate of change of scores/patient/month, in the SAME group, was significantly lower at two (0.32Ć¢Ā€ĀÆĀ±Ć¢Ā€ĀÆ0.19) and three (0.15Ć¢Ā€ĀÆĀ±Ć¢Ā€ĀÆ0.13) years post-nitisinone when compared to pre-nitisinone (0.65Ć¢Ā€ĀÆĀ±Ć¢Ā€ĀÆ0.15) (pĆ¢Ā€ĀÆ<Ć¢Ā€ĀÆ.01 for both comparisons). Similarly, the ALL AKUSSI rate of change of scores/patient/month, in the VAR group, was significantly lower at one (0.16Ć¢Ā€ĀÆĀ±Ć¢Ā€ĀÆ0.08) and three (0.19Ć¢Ā€ĀÆĀ±Ć¢Ā€ĀÆ0.06) years post-nitisinone when compared to pre-nitisinone (0.59Ć¢Ā€ĀÆĀ±Ć¢Ā€ĀÆ0.13) (pĆ¢Ā€ĀÆ<Ć¢Ā€ĀÆ.01 for both comparisons). Combined ear and ocular ochronosis rate of change of scores/patient/month was significantly lower at one, two and three year's post-nitisinone in both VAR and SAME groups compared with pre-nitisinone (pĆ¢Ā€ĀÆ<Ć¢Ā€ĀÆ.05). CONCLUSION: This is the first indication that a 2Ć¢Ā€ĀÆmg dose of nitisinone slows down the clinical progression of AKU. Combined ocular and ear ochronosis progression was arrested by nitisinone.


Subject(s)
Alkaptonuria/drug therapy , Cyclohexanones/administration & dosage , Nitrobenzoates/administration & dosage , Ochronosis/drug therapy , 4-Hydroxyphenylpyruvate Dioxygenase/metabolism , Alkaptonuria/epidemiology , Alkaptonuria/metabolism , Alkaptonuria/pathology , Disease Progression , Female , Homogentisic Acid/metabolism , Humans , Male , Middle Aged , Ochronosis/epidemiology , Ochronosis/metabolism , Ochronosis/pathology , United Kingdom
3.
Allergy ; 73(6): 1182-1195, 2018 06.
Article in English | MEDLINE | ID: mdl-29105788

ABSTRACT

Asthma management, education and environmental interventions have been reported as cost-effective in a previous review (Pharm Pract (Granada), 2014;12:493), but methods used to estimate costs and outcomes were not discussed in detail. This review updates the previous review by providing economic evidence on the cost-effectiveness of studies identified after 2012, and a detailed assessment of the methods used in all identified studies. Twelve databases were searched from 1990 to January 2016, and studies included economic evaluations, asthma subjects and nonpharmacological interventions written in English. Sixty-four studies were included. Of these, 15 were found in addition to the earlier review; 53% were rated fair in quality and 47% high. Education and self-management interventions were the most cost-effective, in line with the earlier review. Self-reporting was the most common method used to gather resource-use data, accompanied by bottom-up approaches to estimate costs. Main outcome measures were asthma-related hospitalizations (69%), quality of life (41%) and utility (38%), with AQLQ and the EQ-5D being the most common questionnaires measured prospectively at fixed time points. More rigorous costing methods are needed with a more common quality of life tool to aid greater replicability and comparability amongst asthma studies.


Subject(s)
Asthma/epidemiology , Asthma/prevention & control , Asthma/therapy , Cost-Benefit Analysis , Disease Management , Health Care Costs , Hospitalization , Humans , Public Health Surveillance , Quality of Life , Surveys and Questionnaires
4.
Acta Neurol Scand ; 136(4): 310-321, 2017 Oct.
Article in English | MEDLINE | ID: mdl-28028819

ABSTRACT

OBJECTIVE: Pilot trial to compare prism therapy and visual search training, for homonymous hemianopia, to standard care (information only). METHODS: Prospective, multicentre, parallel, single-blind, three-arm RCT across fifteen UK acute stroke units. PARTICIPANTS: Stroke survivors with homonymous hemianopia. INTERVENTIONS: Arm a (Fresnel prisms) for minimum 2Ā hours, 5Ā days per week over 6Ā weeks. Arm b (visual search training) for minimum 30Ā minutes, 5Ā days per week over 6Ā weeks. Arm c (standard care-information only). INCLUSION CRITERIA: Adult stroke survivors (>18Ā years), stable hemianopia, visual acuity better than 0.5 logMAR, refractive error within Ā±5 dioptres, ability to read/understand English and provide consent. OUTCOMES: Primary outcomes were change in visual field area from baseline to 26Ā weeks and calculation of sample size for a definitive trial. Secondary measures included Rivermead Mobility Index, Visual Function Questionnaire 25/10, Nottingham Extended Activities of Daily Living, Euro Qual, Short Form-12 questionnaires and Radner reading ability. Measures were post-randomization at baseline and 6, 12 and 26Ā weeks. RANDOMIZATION: Randomization block lists stratified by site and partial/complete hemianopia. BLINDING: Allocations disclosed to patients. Primary outcome assessor blind to treatment allocation. RESULTS: Eighty-seven patients were recruited: 27-Fresnel prisms, 30-visual search training and 30-standard care; 69% male; mean age 69Ā years (SD 12). At 26Ā weeks, full results for 24, 24 and 22 patients, respectively, were compared to baseline. Sample size calculation for a definitive trial determined as 269 participants per arm for a 200 degree2 visual field area change at 90% power. Non-significant relative change in area of visual field was 5%, 8% and 3.5%, respectively, for the three groups. Visual Function Questionnaire responses improved significantly from baseline to 26Ā weeks with visual search training (60 [SD 19] to 68.4 [SD 20]) compared to Fresnel prisms (68.5 [SD 16.4] to 68.2 [18.4]: 7% difference) and standard care (63.7 [SD 19.4] to 59.8 [SD 22.7]: 10% difference), P=.05. Related adverse events were common with Fresnel prisms (69.2%; typically headaches). CONCLUSIONS: No significant change occurred for area of visual field area across arms over follow-up. Visual search training had significant improvement in vision-related quality of life. Prism therapy produced adverse events in 69%. Visual search training results warrant further investigation.


Subject(s)
Activities of Daily Living , Eyeglasses , Hemianopsia/rehabilitation , Quality of Life , Stroke Rehabilitation/methods , Stroke/complications , Adult , Aged , Aged, 80 and over , Female , Hemianopsia/etiology , Humans , Male , Middle Aged , Pilot Projects , Prospective Studies , Single-Blind Method , Surveys and Questionnaires , Treatment Outcome , Visual Acuity/physiology , Visual Fields/physiology
5.
Br J Cancer ; 110(6): 1622-33, 2014 Mar 18.
Article in English | MEDLINE | ID: mdl-24548857

ABSTRACT

BACKGROUND: Proteomics-based approaches for biomarker discovery are promising strategies used in cancer research. We present state-of-art label-free quantitative proteomics method to assess proteome of renal cell carcinoma (RCC) compared with noncancer renal tissues. METHODS: Fresh frozen tissue samples from eight primary RCC lesions and autologous adjacent normal renal tissues were obtained from surgically resected tumour-bearing kidneys. Proteins were extracted by complete solubilisation of tissues using filter-aided sample preparation (FASP) method. Trypsin digested proteins were analysed using quantitative label-free proteomics approach followed by data interpretation and pathways analysis. RESULTS: A total of 1761 proteins were identified and quantified with high confidence (MASCOT ion score threshold of 35 and P-value <0.05). Of these, 596 proteins were identified as differentially expressed between cancer and noncancer tissues. Two upregulated proteins in tumour samples (adipose differentiation-related protein and Coronin 1A) were further validated by immunohistochemistry. Pathway analysis using IPA, KOBAS 2.0, DAVID functional annotation and FLink tools showed enrichment of many cancer-related biological processes and pathways such as oxidative phosphorylation, glycolysis and amino acid synthetic pathways. CONCLUSIONS: Our study identified a number of differentially expressed proteins and pathways using label-free proteomics approach in RCC compared with normal tissue samples. Two proteins validated in this study are the focus of on-going research in a large cohort of patients.


Subject(s)
Biomarkers, Tumor/analysis , Carcinoma, Renal Cell/chemistry , Kidney Neoplasms/chemistry , Proteomics/methods , Aged , Aged, 80 and over , Biomarkers, Tumor/biosynthesis , Biomarkers, Tumor/urine , Carcinoma, Renal Cell/metabolism , Carcinoma, Renal Cell/pathology , Carcinoma, Renal Cell/urine , Female , Humans , Kidney Neoplasms/metabolism , Kidney Neoplasms/pathology , Kidney Neoplasms/urine , Male , Mass Spectrometry , Middle Aged , Neoplasm Proteins/analysis , Neoplasm Proteins/biosynthesis , Neoplasm Proteins/urine , Signal Transduction
6.
J Public Health (Oxf) ; 36(4): 635-43, 2014 Dec.
Article in English | MEDLINE | ID: mdl-24277778

ABSTRACT

BACKGROUND: Cardiovascular disease (CVD) accounts for 30% of UK deaths. It is associated with modifiable lifestyle factors, including insufficient consumption of fruit and vegetables (F&V). Lay health trainers (LHTs) offer practical support to help people develop healthier behaviour and lifestyles. Our two-group pilot randomized controlled trial (RCT) investigated the effectiveness of LHTs at promoting a heart-healthy lifestyle among adults with at least one risk factor for CVD to inform a full-scale RCT. METHODS: Eligible adults (aged 21-78 years), recruited from five practices serving deprived populations, were randomized to health information leaflets plus LHTs' support for 3 months (n = 76) versus health information leaflets alone (n = 38). RESULTS: We recruited 114 participants, with 60% completing 6 month follow-up. Both groups increased their self-reported F&V consumption and we found no evidence for LHTs' support having significant added impact. Most participants were relatively less deprived, as were the LHTs we were able to recruit and train. CONCLUSIONS: Our pilot demonstrated that an LHT's RCT whilst feasible faces considerable challenges. However, to justify growing investment in LHTs, any behaviour changes and sustained impact on those at greatest need should be demonstrated in an independently evaluated, robust, fully powered RCT.


Subject(s)
Cardiovascular Diseases/prevention & control , Feeding Behavior , Fruit , Health Behavior , Vegetables , Adult , Aged , Analysis of Variance , Cultural Deprivation , Diet , England , Female , Health Knowledge, Attitudes, Practice , Health Personnel , Health Status , Humans , Life Style , Male , Middle Aged , Nutrition Policy , Pilot Projects , Primary Health Care , Risk Factors , Young Adult
8.
Gait Posture ; 91: 312-317, 2022 01.
Article in English | MEDLINE | ID: mdl-34800924

ABSTRACT

BACKGROUND: Alkaptonuria is a rare genetic disease that leads to structural joint damage and impaired movement function. Previous research indicates that alkaptonuria affects gait, however the detailed mechanisms are unknown. RESEARCH QUESTION: What are the joint-specific gait mechanisms which contribute to impaired gait in alkaptonuria patients? METHODS: The gait of 36 alkaptonuria patients were compared to those of 21 unimpaired controls. The AKU patients were split into three age groups (young 16-29 years, nĀ =Ā 9, middle 30-49 years, nĀ =Ā 16 and old 50Ā + years, nĀ =Ā 11), and the kinematic and kinetic gait profiles were compared to speed-matched controls using a spm1d two-sample t-test. RESULTS: The young AKU group showed significant differences in the sagittal plane of the knee joint compared to speed-matched controls. The middle group showed deviations in the knee and hip joints. The old group showed significant differences in multiple joints and planes and exhibited gait mechanisms which may be compensation strategies. SIGNIFICANCE: This study is the first to identify and describe joint-specific mechanisms during gait in alkaptonuria patients. Gait deviations were evident even in young AKU patients, including a 16-year-old, much earlier than previously thought. The knee joint is an important focus of future research and potential interventions as deviations were found across all three AKU age groups.


Subject(s)
Alkaptonuria , Adolescent , Adult , Alkaptonuria/complications , Biomechanical Phenomena , Gait , Hip Joint , Humans , Knee Joint , Young Adult
9.
Pilot Feasibility Stud ; 8(1): 210, 2022 Sep 16.
Article in English | MEDLINE | ID: mdl-36114558

ABSTRACT

BACKGROUND: Having a stammer can have a significant effect on a child's social, emotional and educational development. With approximately 66,000 children in the UK having a stammer, there is a need to establish an adequate evidence base to inform clinical practice. We describe a feasibility trial to explore the effectiveness of a new therapy programme for children aged 8-14: Palin Stammering Therapy for School Children (Palin STSC(8-14)). Preliminary data from the Michael Palin Centre, where the programme was developed, indicate that Palin STSC(8-14) is effective in reducing stammering frequency and impact for children, with beneficial effects for parents too. We will investigate the feasibility of the methods required for a definitive randomised controlled trial to investigate the application of this therapy by NHS speech and language therapists (SLTs), compared with 'treatment as usual' (TAU), beyond the specialist context in which it was developed. METHODS: This is a two-arm feasibility cluster-randomised controlled trial of Palin STSC(8-14) with TAU control arm, and randomisation at the level of the SLT. Quantitative and qualitative data will be collected to examine the following: the recruitment and retention of therapists and families, the acceptability of the research processes and the therapeutic intervention and the appropriateness of the therapy outcome measures. Assessments will be completed by children and parents at baseline and 6 months later, including measures of stammering severity; the impact of child's stammering on both children and parents; child temperament, behaviour and peer relations, anxiety; quality of life; and economic outcomes. There will also be a qualitative process evaluation, including interviews with parents, children, SLTs and SLT managers to explore the acceptability of both the research and therapy methods. Treatment fidelity will be examined through analysis of therapy session records and recordings. DISCUSSION: The findings of this feasibility trial will inform the decision as to whether to progress to a full-scale randomised controlled trial to explore the effectiveness of Palin STSC(8-14) when compared to Treatment as Usual in NHS SLT services. There is a strong need for an evidence-based intervention for school age children who stammer. TRIAL REGISTRATION: ISRCTN. ISRCTN17058884 . Registered on 18 December 2019.

10.
J Exp Med ; 193(10): 1179-87, 2001 May 21.
Article in English | MEDLINE | ID: mdl-11369789

ABSTRACT

Intrathymic self-peptide-major histocompatibility complex class II (MHC) molecules shape the T cell repertoire through positive and negative selection of immature CD4(+)CD8(+) thymocytes. By analyzing the development of MHC class II-restricted T cell receptor (TCR) transgenic T cells under conditions in which the endogenous peptide repertoire is altered, we show that self-peptide-MHC complexes are also involved in setting T cell activation thresholds. This occurs through changes in the expression level of molecules on thymocytes that influence the sensitivity of TCR signaling. Our results suggest that the endogenous peptide repertoire modulates T cell responsiveness in the thymus in order to enforce tolerance to self-antigens.


Subject(s)
Histocompatibility Antigens Class II/immunology , Immune Tolerance/immunology , Peptides/immunology , Receptors, Antigen, T-Cell/immunology , T-Lymphocytes/immunology , Thymus Gland/immunology , Animals , Antigens, CD , Antigens, Differentiation, T-Lymphocyte , CD2 Antigens , CD5 Antigens , Female , Lectins, C-Type , Mice , Mice, Transgenic , Selection, Genetic , Spleen/cytology , Spleen/immunology , Thymus Gland/cytology
12.
Spinal Cord ; 48(8): 619-27, 2010 Aug.
Article in English | MEDLINE | ID: mdl-20065989

ABSTRACT

STUDY DESIGN: Cross-sectional study. OBJECTIVES: To quantify three-dimensional (3D) reachable workspace in different groups of tetraplegic participants and to assess their reaching performance within this workspace. SETTING: Northwest Regional Spinal Injuries Centre, UK. METHODS: The 3D reachable workspace of three groups of tetraplegics (NON-OP, operated group (OP) and tetraplegic control group (CON(Tetraplegic)) with varying levels of triceps function together with a healthy control group (CON(Healthy))) was defined by reaching to five target positions (anterior, medial, lateral, superior and inferior) located on the periphery of their workspace. Joint angles and inter-joint co-ordination were analysed after a 3D reconstruction of the thorax, humerus and forearm. The performance related variables of movement time, peak velocity, time-to-peak velocity and curvature index were also examined. RESULTS: The reachable volumes covered were consistent with the level of triceps function as CON(Healthy) covered a significantly greater volume than the tetraplegic groups and in turn the OP covered a larger workspace volume than NON-OP. The reduced workspace of tetraplegics was identified as being due to restrictions in workspace above shoulder height and across the body. Co-ordination data identified some differences in movement patterns but when reaching to targets on the workspace there were no significant differences between the OP and NON-OP groups. CONCLUSION: This study provided a detailed assessment of reachable workspace and target reaching. Tetraplegic participants found the superior and medial parts of the workspace were the most challenging directions. Standardised biomechanical analysis of tetraplegic upper-limb function is required for objective assessment.


Subject(s)
Disability Evaluation , Outcome Assessment, Health Care/methods , Quadriplegia/diagnosis , Quadriplegia/physiopathology , Spinal Cord Injuries/physiopathology , Tendon Transfer/rehabilitation , Adult , Arm/physiopathology , Arm/surgery , Cross-Sectional Studies , Humans , Male , Middle Aged , Muscle, Skeletal/physiopathology , Muscle, Skeletal/surgery , Quadriplegia/surgery , Range of Motion, Articular/physiology , Shoulder Joint/physiology , Spinal Cord Injuries/surgery , Tendon Transfer/methods , Young Adult
13.
J Environ Qual ; 39(3): 1028-35, 2010.
Article in English | MEDLINE | ID: mdl-20400598

ABSTRACT

Concern over the enrichment of agricultural runoff with phosphorus (P) from land applied livestock manures has prompted the development of manure amendments that minimize P solubility. In this study, we amended poultry, dairy, and swine manures with two rare earth chlorides, lanthanum chloride (LaCl(3).7H(2)O) and ytterbium chloride (YbCl(3).6H(2)O), to evaluate their effects on P solubility in the manure following incubation in the laboratory as well as on the fate of P and rare earth elements (REEs) when manures were surface-applied to packed soil boxes and subjected to simulated rainfall. In terms of manure P solubility, La:water-extractable P (WEP) ratios close to 1:1 resulted in maximum WEP reduction of 95% in dairy manure and 98% in dry poultry litter. Results from the runoff study showed that REE applications to dry manures such as poultry litter were less effective in reducing dissolved reactive phosphorus (DRP) in runoff than in liquid manures and slurries, which was likely due to mixing limitations. The most effective reductions of DRP in runoff by REEs were observed in the alkaline pH soil, although reductions of DRP in runoff from the acidic soil were still >50%. Particulate REEs were strongly associated with particulate P in runoff, suggesting a potentially useful role in tracking the fate of P and other manure constituents from manure-amended soils. Finally, REEs that remained in soil following runoff had a tendency to precipitate WEP, especially in soils receiving manure amendments. The findings have valuable applications in water quality protection and the evaluation of P site assessment indices.


Subject(s)
Environmental Monitoring/methods , Lanthanum/chemistry , Manure/analysis , Phosphorus/chemistry , Ytterbium/chemistry , Animals , Cattle , Poultry , Soil/analysis , Swine , Water Movements , Water Pollutants
14.
Water Sci Technol ; 61(12): 3221-7, 2010.
Article in English | MEDLINE | ID: mdl-20555220

ABSTRACT

The impact of electrode corrosion behaviour, reactor geometry and current density on electrocoagulation efficiency were investigated for the treatment of molasses process wastewater. Two laboratory-scale vertical plate electrocoagulation reactors were used for this investigation: the first being a low aspect ratio bath reactor with a low specific electrode area, while the other was a high aspect ratio column reactor with a high specific electrode area. Anomalous anodic dissolution and cathodic corrosion of the aluminium electrodes both contributed significantly to overall metal consumption. Increasing specific electrode area and aspect ratio each led to improved treatment efficiency, whereas the impact of current density was more complicated involving the combined influences of several competing effects. The space-time yields of coagulant and bubbles (both functions of specific electrode area, current density and current efficiency) were found to influence mixing within the reactor and thus treatment efficiency.


Subject(s)
Electrocoagulation/methods , Waste Disposal, Fluid/methods , Water Purification/methods , Aluminum/analysis , Chlorides/analysis , Electrocoagulation/instrumentation , Electrocoagulation/standards , Electrodes , Equipment Design , Food , Hydrogen-Ion Concentration , Iron/analysis , Waste Disposal, Fluid/instrumentation , Water Purification/standards
15.
Science ; 283(5398): 67-70, 1999 Jan 01.
Article in English | MEDLINE | ID: mdl-9872742

ABSTRACT

Whether a single major histocompatibility complex (MHC)-bound peptide can drive the positive selection of large numbers of T cells has been a controversial issue. A diverse population of self peptides was shown to be essential for the in vivo development of CD4 T cells. Mice in which all but 5 percent of MHC class II molecules were bound by a single peptide had wild-type numbers of CD4 T cells. However, when the diversity within this 5 percent was lost, CD4 T cell development was impaired. Blocking the major peptide-MHC complex in thymus organ culture had no effect on T cell development, indicating that positive selection occurred on the diverse peptides present at low levels. This requirement for peptide diversity indicates that the interaction between self peptides and T cell receptors during positive selection is highly specific.


Subject(s)
CD4-Positive T-Lymphocytes/immunology , Histocompatibility Antigens Class II/immunology , Peptides/immunology , Receptors, Antigen, T-Cell/immunology , Animals , Antigen Presentation , CD4-Positive T-Lymphocytes/cytology , CD4-Positive T-Lymphocytes/metabolism , CD8-Positive T-Lymphocytes/cytology , CD8-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/metabolism , Cells, Cultured , Histocompatibility Antigens Class II/metabolism , Lymphocyte Activation , Lymphocyte Culture Test, Mixed , Mice , Mice, Knockout , Mice, Transgenic , Peptides/metabolism , Recombinant Fusion Proteins/metabolism , Spleen/immunology , Thymus Gland/immunology
16.
Science ; 190(4210): 167-9, 1975 Oct 10.
Article in English | MEDLINE | ID: mdl-1166310

ABSTRACT

Rhesus monkeys inhibited their feeding in response to intragastric nutrient preloads, so as to maintain a constant caloric intake. There is a definite dose- response relationship to calories which does not depend on the volume, caloric concentration, or nature of the nutrient. This accurate control is accomplished even though some of the preload remains in the stomach throughout the feeding period.


Subject(s)
Appetite Regulation , Satiation/physiology , Animals , Hypothalamus/physiology , Macaca mulatta , Male
17.
Gait Posture ; 70: 48-52, 2019 05.
Article in English | MEDLINE | ID: mdl-30822655

ABSTRACT

BACKGROUND: Complex clinical gait analysis results can be expressed as single number gait deviations by applying multivariate processing methods. The original Movement Deviation Profile (MDP) quantifies the deviation of abnormal gait using the most trusted nine dynamic joint angles of lower limbs. RESEARCH QUESTION: Which subset of joint angles maximises the ability of the MDP to separate abnormal gait from normality? What is the effect of using the best subset in a large group of patients, and in individuals? METHODS: A self-organising neural network was trained using normal gait data from 166 controls, and then the MDP of 1923 patients with cerebral palsy (3846 legs) was calculated. The same procedure was repeated with 511 combinations of the nine joint angles. The standardised distances of abnormal gait from normality were then calculated as log-transformed Z-scores to select the best combination. A mixed design ANOVA was used to assess how removing the least discriminating angle improved the separation of patients from controls. The effect of using the optimal subset of angles was also quantified for each individual leg by comparing the change in MDP to the independent FAQ levels of patients. RESULTS: Removal of hip rotation significantly (p<0.0005) increased the separation of the patient group from normality (ΔZ-score 0.24) and also at FAQ levels 7-10 (ΔZ-score 0.38, 0.27, 0.22, 0.14). The MDP of individual patients changed in a wider range of -4.65 to 1.12 Z-scores and their change matched their independent FAQ scores, with less functional patients moving further from, and more functional patients moving closer to normality. SIGNIFICANCE: In existing gait databases we recommend excluding hip rotation from data used to calculate the MDP. Alternatively, the calculation of hip rotation can be improved by post-hoc correction, but the ultimate solution is to use more accurate and reliable models of hip rotation.


Subject(s)
Cerebral Palsy/physiopathology , Gait Disorders, Neurologic/physiopathology , Hip Joint/physiopathology , Neural Networks, Computer , Rotation , Child , Gait Analysis/methods , Humans , Movement
18.
PLoS One ; 14(2): e0211932, 2019.
Article in English | MEDLINE | ID: mdl-30811430

ABSTRACT

Sublethal effects of oil spills may dampen seabird rehabilitation success due to lingering negative impacts of contamination and stress on reproduction and long-term survival. These effects can be difficult to measure while birds are in care as well as once birds are released. Expression of sexually selected traits that are sensitive to condition can provide information on physiological status of birds. We evaluated plumage molt and gular pouch skin color of California brown pelicans (Pelecanus occidentalis californicus) following oil contamination and rehabilitation to test for differences between previously oiled and rehabilitated (post-spill) and presumably uncontaminated pelicans. Post-spill pelicans released with either color leg bands alone, or bands plus harness-mounted satellite GPS tags, were relocated and visually assessed in the field at non-breeding communal roosts and compared to surrounding unmarked pelicans in the general population. Non-oiled pelicans bearing GPS tags were also included in the study. Post-spill pelicans lagged the general population in molt of ornamental yellow crown feathers but hind neck transition into white plumage was not significantly different. Both post-spill and non-oiled pelicans wearing GPS tags had lower gular redness scores than the unmarked, non-oiled population. Pre-breeding gular pouch redness of post-spill pelicans was more strongly influenced by wearing of a GPS tag than a history of oil contamination and rehabilitation. Gular pouch redness of post-spill pelicans in the first 18 months after release was positively correlated with long term survivorship. If gular pouch color is a condition-dependent sexual signal and overall health influences plumage molt progression, our results indicate that many post-spill pelicans marked with bands alone were in relatively good condition going into the next breeding season, but those released with electronic tags experienced additional stress due to wearing the equipment, introducing a confounding variable to the post-release study.


Subject(s)
Birds , Environmental Monitoring , Feathers , Petroleum Pollution , Pigmentation , Reproduction , Animals , California , Female , Male
19.
BMC Bioinformatics ; 9: 493, 2008 Nov 25.
Article in English | MEDLINE | ID: mdl-19032776

ABSTRACT

BACKGROUND: Microarray experimentation requires the application of complex analysis methods as well as the use of non-trivial computer technologies to manage the resultant large data sets. This, together with the proliferation of tools and techniques for microarray data analysis, makes it very challenging for a laboratory scientist to keep up-to-date with the latest developments in this field. Our aim was to develop a distributed e-support system for microarray data analysis and management. RESULTS: EMAAS (Extensible MicroArray Analysis System) is a multi-user rich internet application (RIA) providing simple, robust access to up-to-date resources for microarray data storage and analysis, combined with integrated tools to optimise real time user support and training. The system leverages the power of distributed computing to perform microarray analyses, and provides seamless access to resources located at various remote facilities. The EMAAS framework allows users to import microarray data from several sources to an underlying database, to pre-process, quality assess and analyse the data, to perform functional analyses, and to track data analysis steps, all through a single easy to use web portal. This interface offers distance support to users both in the form of video tutorials and via live screen feeds using the web conferencing tool EVO. A number of analysis packages, including R-Bioconductor and Affymetrix Power Tools have been integrated on the server side and are available programmatically through the Postgres-PLR library or on grid compute clusters. Integrated distributed resources include the functional annotation tool DAVID, GeneCards and the microarray data repositories GEO, CELSIUS and MiMiR. EMAAS currently supports analysis of Affymetrix 3' and Exon expression arrays, and the system is extensible to cater for other microarray and transcriptomic platforms. CONCLUSION: EMAAS enables users to track and perform microarray data management and analysis tasks through a single easy-to-use web application. The system architecture is flexible and scalable to allow new array types, analysis algorithms and tools to be added with relative ease and to cope with large increases in data volume.


Subject(s)
Computational Biology/methods , Internet , Oligonucleotide Array Sequence Analysis/methods , Software , Computer Communication Networks
20.
Heliyon ; 4(5): e00629, 2018 May.
Article in English | MEDLINE | ID: mdl-29872763

ABSTRACT

A study was conducted to identify habitat characteristics associated with age 0+ White Sturgeon (Acipenser transmontanus Richardson, 1863) recruitment in three reaches of the Columbia River Basin: Skamania reach (consistent recruitment), John Day reach (intermittent/inconsistent recruitment), and Kootenai reach (no recruitment). Our modeling approach involved numerous steps. First, we collected information about substrate, embeddedness, and hydrodynamics in each reach. Second, we developed a set of spatially explicit predictor variables. Third, we built two habitat (probability) models with Skamania reach training data where White Sturgeon recruitment was consistent. Fourth, we created spawning maps of each reach by populating the habitat models with in-reach physical metrics (substrate, embeddedness, and hydrodynamics). Fifth, we examined model accuracy by overlaying spawning locations in Skamania and Kootenai reaches with habitat predictions obtained from probability models. Sixth, we simulated how predicted habitat changed in each reach after manipulating physical conditions to more closely match Skamania reach. Model verification confirmed White Sturgeon generally spawned in locations with higher model probabilities in Skamania and Kootenai reaches, indicating the utility of extrapolating the models. Model simulations revealed significant gains in White Sturgeon habitat in all reaches when spring flow increased, gravel/cobble composition increased, or embeddedness decreased. The habitat models appear well suited to assist managers when identifying reach-specific factors limiting White Sturgeon recruitment in the Columbia River Basin or throughout its range.

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