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Find video protocols related to scientific articles indexed in Pubmed.
Electrochemical Study of the Catechol-modified Chitosan System for Clozapine Treatment Monitoring.
Langmuir
PUBLISHED: 11-11-2014
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This work presents a thorough electrochemical and reliability analysis of a sensing scheme for the antipsychotic clozapine. We have previously demonstrated a novel detection approach for this redox-active drug, highly effective in schizophrenia treatment, based on a catechol-modified chitosan film. The biomaterial film enables amplification of the oxidative charge current generated by clozapine through redox cycling. Here, we study critical electrochemical and material aspects of the redox cycling system to overcome barriers in point-of-care monitoring in complex biological samples. Specifically, we explore the electrochemical parameter space, showing that enhanced sensing performance depends on the presence of a reducing mediator as well as the electrochemical technique applied. These factors account for up to 1.75-fold and 2.47-fold signal enhancement, respectively. Looking potential interferents, we illustrate that the redox cycling system allows for differentiation between selected redox-active species, clozapine's structurally largely analogous metabolite norclozapine as well as the representative catecholamine dopamine. Furthermore, we investigate material stability and fouling with re-use as well as storage. We find no evidence of film fouling due to clozapine; slow overall biomaterial degradation with successive use accounts for a 2.2% absolute signal loss and can be controlled for. Storage of the redox cycling system appears feasible over weeks when kept in solution with only 0.26%/day clozapine signal degradation, while ambient air exposure of three or more days reduces performance by 58%. This study not only advances our understanding of the catechol-modified chitosan system, but also further establishes the viability of applying it toward sensing clozapine in a clinical setting. Such point-of-care monitoring will allow for broader use of clozapine by increasing convenience to patients as well as medical professionals, thus improving the lives of people affected by schizophrenia through personalized medicine.
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[Intraoperative radiotherapy (IORT) in early breast cancer].
Harefuah
PUBLISHED: 10-08-2014
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Breast-conservation therapy is widely accepted as an effective treatment option for patients with early stage carcinoma of the breast. The proportion of patients with recurrence after receiving partial breast irradiation is the same as that seen in patients treated with whole breast irradiation. Therefore, the necessity of whole breast irradiation has been questioned, and partial breast irradiation has emerged as a reasonable alternative.
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A Microfluidic-based Electrochemical Biochip for Label-free DNA Hybridization Analysis.
J Vis Exp
PUBLISHED: 10-07-2014
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Miniaturization of analytical benchtop procedures into the micro-scale provides significant advantages in regards to reaction time, cost, and integration of pre-processing steps. Utilizing these devices towards the analysis of DNA hybridization events is important because it offers a technology for real time assessment of biomarkers at the point-of-care for various diseases. However, when the device footprint decreases the dominance of various physical phenomena increases. These phenomena influence the fabrication precision and operation reliability of the device. Therefore, there is a great need to accurately fabricate and operate these devices in a reproducible manner in order to improve the overall performance. Here, we describe the protocols and the methods used for the fabrication and the operation of a microfluidic-based electrochemical biochip for accurate analysis of DNA hybridization events. The biochip is composed of two parts: a microfluidic chip with three parallel micro-channels made of polydimethylsiloxane (PDMS), and a 3 x 3 arrayed electrochemical micro-chip. The DNA hybridization events are detected using electrochemical impedance spectroscopy (EIS) analysis. The EIS analysis enables monitoring variations of the properties of the electrochemical system that are dominant at these length scales. With the ability to monitor changes of both charge transfer and diffusional resistance with the biosensor, we demonstrate the selectivity to complementary ssDNA targets, a calculated detection limit of 3.8 nM, and a 13% cross-reactivity with other non-complementary ssDNA following 20 min of incubation. This methodology can improve the performance of miniaturized devices by elucidating on the behavior of diffusion at the micro-scale regime and by enabling the study of DNA hybridization events.
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HMG-coenzyme A reductase inhibition, type 2 diabetes, and bodyweight: evidence from genetic analysis and randomised trials.
Daniel I Swerdlow, David Preiss, Karoline B Kuchenbaecker, Michael V Holmes, Jorgen E L Engmann, Tina Shah, Reecha Sofat, Stefan Stender, Paul C D Johnson, Robert A Scott, Maarten Leusink, Niek Verweij, Stephen J Sharp, Yiran Guo, Claudia Giambartolomei, Christina Chung, Anne Peasey, Antoinette Amuzu, KaWah Li, Jutta Palmen, Philip Howard, Jackie A Cooper, Fotios Drenos, Yun R Li, Gordon Lowe, John Gallacher, Marlene C W Stewart, Ioanna Tzoulaki, Sarah G Buxbaum, Daphne L van der A, Nita G Forouhi, N Charlotte Onland-Moret, Yvonne T van der Schouw, Renate B Schnabel, Jaroslav A Hubacek, Růžena Kubinova, Miglė Bacevičienė, Abdonas Tamosiunas, Andrzej Pająk, Romanvan Topor-Madry, Urszula Stepaniak, Sofia Malyutina, Damiano Baldassarre, Bengt Sennblad, Elena Tremoli, Ulf de Faire, Fabrizio Veglia, Ian Ford, J Wouter Jukema, Rudi G J Westendorp, Gert Jan de Borst, Pim A de Jong, Ale Algra, Wilko Spiering, Anke H Maitland-van der Zee, Olaf H Klungel, Anthonius de Boer, Pieter A Doevendans, Charles B Eaton, Jennifer G Robinson, David Duggan, , John Kjekshus, John R Downs, Antonio M Gotto, Anthony C Keech, Roberto Marchioli, Gianni Tognoni, Peter S Sever, Neil R Poulter, David D Waters, Terje R Pedersen, Pierre Amarenco, Haruo Nakamura, John J V McMurray, James D Lewsey, Daniel I Chasman, Paul M Ridker, Aldo P Maggioni, Luigi Tavazzi, Kausik K Ray, Sreenivasa Rao Kondapally Seshasai, JoAnn E Manson, Jackie F Price, Peter H Whincup, Richard W Morris, Debbie A Lawlor, George Davey Smith, Yoav Ben-Shlomo, Pamela J Schreiner, Myriam Fornage, David S Siscovick, Mary Cushman, Meena Kumari, Nick J Wareham, W M Monique Verschuren, Susan Redline, Sanjay R Patel, John C Whittaker, Anders Hamsten, Joseph A Delaney, Caroline Dale, Tom R Gaunt, Andrew Wong, Diana Kuh, Rebecca Hardy, Sekar Kathiresan, Berta A Castillo, Pim van der Harst, Eric J Brunner, Anne Tybjaerg-Hansen, Michael G Marmot, Ronald M Krauss, Michael Tsai, Josef Coresh, Ronald C Hoogeveen, Bruce M Psaty, Leslie A Lange, Hakon Hakonarson, Frank Dudbridge, Steve E Humphries, Philippa J Talmud, Mika Kivimäki, Nicholas J Timpson, Claudia Langenberg, Folkert W Asselbergs, Mikhail Voevoda, Martin Bobak, Hynek Pikhart, James G Wilson, Alex P Reiner, Brendan J Keating, Aroon D Hingorani, Naveed Sattar.
Lancet
PUBLISHED: 09-29-2014
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Statins increase the risk of new-onset type 2 diabetes mellitus. We aimed to assess whether this increase in risk is a consequence of inhibition of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), the intended drug target.
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From potential donor to actual donation: does socioeconomic position affect living kidney donation? A systematic review of the evidence.
Transplantation
PUBLISHED: 09-25-2014
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Evidence from Europe, Australia and the United States demonstrates that socioeconomically deprived individuals with advanced chronic kidney disease are less likely to receive a living kidney transplant compared with less deprived individuals. This systematic review focuses on how socioeconomic position (SEP) may influence hypothetical and actual living kidney donors and where appropriate, summarizes the quantitative evidence.In the general population, a higher SEP appears to be associated with an increased 'hypothetical' willingness to be a living kidney donor but with marked heterogeneity in the absolute differences (I = 95.9%, P < 0.001). In a commercial setting, lower SEP motivates people to donate. Outside of this setting, there is no evidence of discordance in the SEP of donors and recipients that would suggest undisclosed financial exchange. There is evidence for a complex interaction between SEP and other variables, such as ethnicity, sex, and the national economic climate. Some evidence suggests that measures to remove financial disincentives to donation are associated with an increase in living donation rates. Future research needs to study how SEP impacts the potential donor population from willingness to donate, progression through donor assessment to actual donor nephrectomy.
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Assessment of body composition in Indian adults: comparison between dual-energy X-ray absorptiometry and isotope dilution technique.
Br. J. Nutr.
PUBLISHED: 08-11-2014
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Dual-energy X-ray absorptiometry (DXA) and isotope dilution technique have been used as reference methods to validate the estimates of body composition by simple field techniques; however, very few studies have compared these two methods. We compared the estimates of body composition by DXA and isotope dilution (18O) technique in apparently healthy Indian men and women (aged 19-70 years, n 152, 48 % men) with a wide range of BMI (14-40 kg/m2). Isotopic enrichment was assessed by isotope ratio mass spectroscopy. The agreement between the estimates of body composition measured by the two techniques was assessed by the Bland-Altman method. The mean age and BMI were 37 (sd 15) years and 23·3 (sd 5·1) kg/m2, respectively, for men and 37 (sd 14) years and 24·1 (sd 5·8) kg/m2, respectively, for women. The estimates of fat-free mass were higher by about 7 (95 % CI 6, 9) %, those of fat mass were lower by about 21 (95 % CI - 18, - 23) %, and those of body fat percentage (BF%) were lower by about 7·4 (95 % CI - 8·2, - 6·6) % as obtained by DXA compared with the isotope dilution technique. The Bland-Altman analysis showed wide limits of agreement that indicated poor agreement between the methods. The bias in the estimates of BF% was higher at the lower values of BF%. Thus, the two commonly used reference methods showed substantial differences in the estimates of body composition with wide limits of agreement. As the estimates of body composition are method-dependent, the two methods cannot be used interchangeably.
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45-day mortality after 467,779 knee replacements for osteoarthritis from the National Joint Registry for England and Wales: an observational study.
Lancet
PUBLISHED: 07-12-2014
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Understanding the risk factors for early death after knee replacement could help to reduce the risk of mortality after this procedure. We assessed secular trends in death within 45 days of knee replacement for osteoarthritis in England and Wales, with the aim of investigating whether any change that we recorded could be explained by alterations in modifiable perioperative factors.
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A controlled microfluidic electrochemical lab-on-a-chip for label-free diffusion-restricted DNA hybridization analysis.
Biosens Bioelectron
PUBLISHED: 07-01-2014
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Lab-on-a-chip (LOC) devices for electrochemical analysis of DNA hybridization events offer a technology for real-time and label-free assessment of biomarkers at the point-of-care. Here, we present a microfluidic LOC, with 3×3 arrayed electrochemical sensors for the analysis of DNA hybridization events. A new dual layer microfluidic valved manipulation system is integrated providing controlled and automated capabilities for high throughput analysis. This feature improves the repeatability, accuracy, and overall sensing performance (Fig. 1). The electrochemical activity of the fabricated microfluidic device is validated and demonstrated repeatable and reversible Nernstian characteristics. System design required detailed analysis of energy storage and dissipation as our sensing modeling involves diffusion-related electrochemical impedance spectroscopy. The effect of DNA hybridization on the calculated charge transfer resistance and the diffusional resistance components is evaluated. We demonstrate a specific device with an average cross-reactivity value of 27.5%. The device yields semilogarithmic dose response and enables a theoretical detection limit of 1nM of complementary ssDNA target. This limit is lower than our previously reported non-valved device by 74% due to on-chip valve integration providing controlled and accurate assay capabilities.
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Electronic modulation of biochemical signal generation.
Nat Nanotechnol
PUBLISHED: 06-25-2014
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Microelectronic devices that contain biological components are typically used to interrogate biology rather than control biological function. Patterned assemblies of proteins and cells have, however, been used for in vitro metabolic engineering, where coordinated biochemical pathways allow cell metabolism to be characterized and potentially controlled on a chip. Such devices form part of technologies that attempt to recreate animal and human physiological functions on a chip and could be used to revolutionize drug development. These ambitious goals will, however, require new biofabrication methodologies that help connect microelectronics and biological systems and yield new approaches to device assembly and communication. Here, we report the electrically mediated assembly, interrogation and control of a multi-domain fusion protein that produces a bacterial signalling molecule. The biological system can be electrically tuned using a natural redox molecule, and its biochemical response is shown to provide the signalling cues to drive bacterial population behaviour. We show that the biochemical output of the system correlates with the electrical input charge, which suggests that electrical inputs could be used to control complex on-chip biological processes.
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Associations between APOE and low-density lipoprotein cholesterol genotypes and cognitive and physical capability: the HALCyon programme.
Age (Dordr)
PUBLISHED: 06-18-2014
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The APOE ?2/3/4 genotype has been associated with low-density lipoprotein cholesterol (LDL-C) and Alzheimer disease. However, evidence for associations with measures of cognitive performance in adults without dementia has been mixed, as it is for physical performance. Associations may also be evident in other genotypes implicated in LDL-C levels. As part of the Healthy Ageing across the Life Course (HALCyon) collaborative research programme, genotypic information was obtained for APOE ?2/3/4, rs515135 (APOB), rs2228671 (LDLR) and rs629301 (SORT1) from eight cohorts of adults aged between 44 and 90 + years. We investigated associations with four measures of cognitive (word recall, phonemic fluency, semantic fluency and search speed) and physical capability (grip strength, get up and go/walk speed, timed chair rises and ability to balance) using meta-analyses. Overall, little evidence for associations between any of the genotypes and measures of cognitive capability was observed (e.g. pooled beta for APOE ?4 effect on semantic fluency z score = -0.02; 95 % CI = -0.05 to 0.02; p value = 0.3; n = 18,796). However, there was borderline evidence within studies that negative effects of APOE ?4 on nonverbal ability measures become more apparent with age. Few genotypic associations were observed with physical capability measures. The findings from our large investigation of middle-aged to older adults in the general population suggest that effects of APOE on cognitive capability are at most modest and are domain- and age-specific, while APOE has little influence on physical capability. In addition, other LDL-C-related genotypes have little impact on these traits.
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Modelling the natural history of primary progressive multiple sclerosis.
J. Neurol. Neurosurg. Psychiatr.
PUBLISHED: 05-14-2014
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A minority of patients with multiple sclerosis (MS) have primary progressive disease (PPMS). Treatment options are currently limited, but as prospects for interventional studies become more realistic, understanding contemporary outcome data will be key to successful trial design.
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The role of IGF-I, IGF-II, and IGFBP-3 in male cognitive aging and dementia risk: the Caerphilly Prospective Study.
J. Alzheimers Dis.
PUBLISHED: 04-08-2014
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The increasing incidence of cognitive impairment and dementia in an aging population poses a significant burden on healthcare. Consequently, identifying modifiable physiological factors which may influence the onset of cognitive decline are becoming increasingly important. Previous studies have suggested an association between levels of insulin-like growth factors and cognitive function.
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Life-course determinants of bone mass in young adults from a transitional rural community in India: the Andhra Pradesh Children and Parents Study (APCAPS).
Am. J. Clin. Nutr.
PUBLISHED: 04-02-2014
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Undernutrition and physical inactivity are both associated with lower bone mass.OBJECTIVE: This study aimed to investigate the combined effects of early-life undernutrition and urbanized lifestyles in later life on bone mass accrual in young adults from a rural community in India that is undergoing rapid socioeconomic development.DESIGN: This was a prospective cohort study of participants of the Hyderabad Nutrition Trial (1987-1990), which offered balanced protein-calorie supplementation to pregnant women and preschool children younger than 6 y in the intervention villages. The 2009-2010 follow-up study collected data on current anthropometric measures, bone mineral density (BMD) measured by dual-energy X-ray absorptiometry, blood samples, diet, physical activity, and living standards of the trial participants (n = 1446, aged 18-23 y).RESULTS: Participants were generally lean and had low BMD [mean hip BMD: 0.83 (women), 0.95 (men) g/cm(2); lumbar spine: 0.86 (women), 0.93 (men) g/cm(2)]. In models adjusted for current risk factors, no strong evidence of a positive association was found between BMD and early-life supplementation. On the other hand, current lean mass and weight-bearing physical activity were positively associated with BMD. No strong evidence of an association was found between BMD and current serum 25-hydroxyvitamin D or dietary intake of calcium, protein, or calories.CONCLUSIONS: Current lean mass and weight-bearing physical activity were more important determinants of bone mass than was early-life undernutrition in this population. In transitional rural communities from low-income countries, promotion of physical activity may help to mitigate any potential adverse effects of early nutritional disadvantage.
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Cortisol and cognitive function in midlife: the role of childhood cognition and educational attainment.
Psychoneuroendocrinology
PUBLISHED: 03-11-2014
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Adult cognition and age-related cognitive decline can be influenced by dysregulation of the hypothalamic pituitary adrenal axis with concomitant changes in cortisol levels. However, very little is known about the role of childhood cognition and educational attainment in this relationship. Using data from the British 1946 birth cohort, the present study investigated: (1) associations between cortisol levels and patterns and cognitive function in midlife; (2) direct and interactive effects of childhood cognition, educational attainment and cortisol on cognitive function in midlife. Verbal memory, letter search speed and reaction time were assessed at age 60-64 years. Salivary cortisol samples (wakening, 30 min after wakening and evening) were collected at the same age. Childhood cognitive ability was measured at ages 8, 11, and 15, and educational level was reported at age 26. Associations between cortisol, childhood cognition, educational attainment and cognitive function in midlife were tested using linear regression and structural equation modelling approaches. Higher evening cortisol level was associated with slower reaction time and lower verbal memory. These associations were independent of childhood cognition and education as well as a range of other potential confounders. Childhood cognition and education were not directly associated with evening cortisol. However, there was a significant interaction effect between childhood cognition and evening cortisol on reaction time (p=.002): higher evening cortisol was associated with slower reaction time only among those with low childhood cognitive ability. There was little evidence of associations between the other cortisol measures and cognitive function.
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The association of early life supplemental nutrition with lean body mass and grip strength in adulthood: evidence from APCAPS.
Am. J. Epidemiol.
PUBLISHED: 02-19-2014
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In the present study, we examined the associations of early nutrition with adult lean body mass (LBM) and muscle strength in a birth cohort that was established to assess the long-term impact of a nutrition program. Participants (n = 1,446, 32% female) were born near Hyderabad, India, in 29 villages from 1987 to 1990, during which time only intervention villages (n = 15) had a government program that offered balanced protein-calorie supplementation to pregnant women and children. Participants' LBM and appendicular skeletal muscle mass were measured using dual energy x-ray absorptiometry; grip strength and information on lifestyle indicators, including diet and physical activity level, were also obtained. Ages (mean = 20.3 years) and body mass indexes (weight (kg)/height (m)(2); mean = 19.5) of participants in 2 groups were similar. Current dietary energy intake was higher in the intervention group. Unadjusted LBM and grip strength were similar in 2 groups. After adjustment for potential confounders, the intervention group had lower LBM (? = -0.75; P = 0.03), appendicular skeletal muscle mass, and grip strength than did controls, but these differences were small in magnitude (<0.1 standard deviation). Multivariable regression analyses showed that current socioeconomic position, energy intake, and physical activity level had a positive association with adult LBM and muscle strength. This study could not detect a "programming" effect of early nutrition supplementation on adult LBM and muscle strength.
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Mendelian randomization of blood lipids for coronary heart disease.
Eur. Heart J.
PUBLISHED: 01-30-2014
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To investigate the causal role of high-density lipoprotein cholesterol (HDL-C) and triglycerides in coronary heart disease (CHD) using multiple instrumental variables for Mendelian randomization.
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Predictors of cognitive impairment in an early stage Parkinson's disease cohort.
Mov. Disord.
PUBLISHED: 01-06-2014
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The impact of Parkinson's disease (PD) dementia is substantial and has major functional and socioeconomic consequences. Early prediction of future cognitive impairment would help target future interventions. The Montreal Cognitive Assessment (MoCA), the Mini-Mental State Examination (MMSE), and fluency tests were administered to 486 patients with PD within 3.5 years of diagnosis, and the results were compared with those from 141 controls correcting for age, sex, and educational years. Eighteen-month longitudinal assessments were performed in 155 patients with PD. The proportion of patients classified with normal cognition, mild cognitive impairment (MCI), and dementia varied considerably, depending on the MoCA and MMSE thresholds used. With the MoCA total score at screening threshold, 47.7%, 40.5%, and 11.7% of patients with PD were classified with normal cognition, MCI, and dementia, respectively; by comparison, 78.7% and 21.3% of controls had normal cognition and MCI, respectively. Cognitive impairment was predicted by lower education, increased age, male sex, and quantitative motor and non-motor (smell, depression, and anxiety) measures. Longitudinal data from 155 patients with PD over 18 months showed significant reductions in MoCA scores, but not in MMSE scores, with 21.3% of patients moving from normal cognition to MCI and 4.5% moving from MCI to dementia, although 13.5% moved from MCI to normal; however, none of the patients with dementia changed their classification. The MoCA may be more sensitive than the MMSE in detecting early baseline and longitudinal cognitive impairment in PD, because it identified 25.8% of those who experienced significant cognitive decline over 18 months. Cognitive decline was associated with worse motor and non-motor features, suggesting that this reflects a faster progressive phenotype.
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Role of IGF-I, IGF-II and IGFBP-3 in lung function of males: the Caerphilly Prospective Study.
Int J Mol Epidemiol Genet
PUBLISHED: 01-01-2014
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Insulin-like growth factors are peptide hormones that have an endocrine role in the development, growth and repair of human tissues including the respiratory tract. To date, only one population study exists which found positive cross-sectional associations with IGF-I and higher lung volumes. We hypothesised that higher IGF-I, IGF-II, IGFBP-3 and IGF molar ratio would be associated with better cross-sectional and longitudinal lung function. We examined cross-sectional (n=843) and prospective associations (n=717) between IGF-I, IGF-II, IGFBP-3 and IGF molar ratio with lung function in the Caerphilly Prospective Study (CaPS) from blood samples obtained around 1986, with spirometry (forced expiratory volume in one second (FEV1) and forced vital capacity (FVC)) performed in the same year and around 2003. Higher IGF molar ratio was associated with improved FEV1/FEV ratio cross-sectionally in both simple (0.007, 95% CI 0.001-0.013, P=0.02) and fully adjusted (0.001, 95% CI 0.001-0.012, P=0.03) models. With the exception of IGFBP-3 and FEV1/FVC in the simple model (0.009, 95% CI 0.001-0.018, P=0.04) all prospective associations between IGF and spirometric measures were consistent with chance. In this study of men, higher IGF molar ratio was associated with improved cross-sectional lung function, although these findings were not replicated prospectively. Further work is required with repeat IGF sampling during follow up to see if IGF levels play any role in predicting future lung function through the life course.
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Cortisol awakening response and subsequent depression: prospective longitudinal study.
Br J Psychiatry
PUBLISHED: 12-05-2013
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Some studies have found an association between elevated cortisol and subsequent depression, but findings are inconsistent. The cortisol awakening response may be a more stable measure of hypothalamic-pituitary-adrenal function and potentially of stress reactivity.
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Association between pre- and perinatal exposures and Tourette syndrome or chronic tic disorder in the ALSPAC cohort.
Br J Psychiatry
PUBLISHED: 11-21-2013
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Tourette syndrome and chronic tic disorder are heritable but aetiologically complex. Although environment plays a role in their development, existing studies of non-genetic risk factors are inconsistent.
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The ReSPonD trial - rivastigmine to stabilise gait in Parkinsons disease a phase II, randomised, double blind, placebo controlled trial to evaluate the effect of rivastigmine on gait in patients with Parkinsons disease who have fallen.
BMC Neurol
PUBLISHED: 11-04-2013
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Gait impairment is common in people with Parkinsons disease. There is a lack of effective interventions to target this debilitating complication and therefore a need to identify new therapeutic options. An underlying cholinergic deficit contributes to both the gait and cognitive dysfunction seen in Parkinsons disease. The combined impact of both impairments can be assessed in gait tasks performed with concomitant cognitive tasks. The aim of this trial is to evaluate the impact of a cholinesterase inhibitor on cognitive function and gait performance in people with established Parkinsons disease.Methods/design: This is a single centre, double-blind, randomised placebo-controlled trial in 130 people with Hoehn and Yahr stage 2--3 idiopathic Parkinsons disease who have fallen in the past year. Participants will be randomised to two groups, receiving either rivastigmine capsules or identical placebo capsules for 8 months. Assessment will be undertaken at baseline and at the end of medication prescription (i.e. 8 months) with participants remaining enrolled in the trial for a further 4 months to monitor for falls and adverse events. The primary outcome is step time variability, assessed with and without the addition of concurrent cognitive tasks. Secondary outcomes will include other gait parameters, sensorimotor and balance performances, cognitive indices, falls and fall related injury, fear of falling, Parkinsons symptoms and data pertaining to possible harms.
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REM sleep behaviour disorder is associated with worse quality of life and other non-motor features in early Parkinsons disease.
J. Neurol. Neurosurg. Psychiatr.
PUBLISHED: 11-01-2013
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Concomitant REM sleep behaviour disorder (RBD) is commonly observed in patients with Parkinsons disease (PD). Although the brainstem structures responsible for the symptoms of RBD correspond to the premotor stages of PD, the association of RBD with motor and non-motor features in early PD remains unclear.
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90-day mortality after 409,096 total hip replacements for osteoarthritis, from the National Joint Registry for England and Wales: a retrospective analysis.
Lancet
PUBLISHED: 10-01-2013
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Death within 90 days after total hip replacement is rare but might be avoidable dependent on patient and treatment factors. We assessed whether a secular decrease in death caused by hip replacement has occurred in England and Wales and whether modifiable perioperative factors exist that could reduce deaths.
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Cohort Profile: Andhra Pradesh Children and Parents Study (APCAPS).
Int J Epidemiol
PUBLISHED: 09-09-2013
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The Andhra Pradesh Children and Parents Study (APCAPS) was originally established to study the long-term effects of early-life undernutrition on risk of cardiovascular disease. Its aims were subsequently expanded to include trans-generational influences of other environmental and genetic factors on chronic diseases in rural India. It builds on the Hyderabad Nutrition Trial (HNT) conducted in 1987-90 to compare the effects on birthweight of a protein-calorie supplement for pregnant women and children. The index children of HNT and their mothers were retraced and examined in 2003-05, and the children re-examined as young adults aged 18-21 years in 2009-10. The cohort was expanded to include both parents and siblings of the index children in a recently completed follow-up conducted in 2010-12 (N = ?6225 out of 10 213 participants). Recruitment of the remaining residents of these 29 villages (N = ?55 000) in Ranga Reddy district of Andhra Pradesh is now under way. Extensive data on socio-demographic, lifestyle, medical, anthropometric, physiological, vascular and body composition measures, DNA, stored plasma, and assays of lipids and inflammatory markers on APCAPS participants are available. Details of how to access these data are available from the corresponding author.
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Tourette syndrome and chronic tic disorder are associated with lower socio-economic status: findings from the Avon Longitudinal Study of Parents and Children cohort.
Dev Med Child Neurol
PUBLISHED: 08-26-2013
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Only a few studies have examined the relationship between Tourette syndrome or chronic tic disorder and socio-economic status (SES). Existing studies are primarily cross-sectional, arise from specialty clinics, and use single measures of SES. In this study we examine this relationship in a longitudinal, population-based sample.
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Development and validation of anthropometric prediction equations for estimation of lean body mass and appendicular lean soft tissue in Indian men and women.
J. Appl. Physiol.
PUBLISHED: 08-15-2013
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Lean body mass (LBM) and muscle mass remain difficult to quantify in large epidemiological studies due to the unavailability of inexpensive methods. We therefore developed anthropometric prediction equations to estimate the LBM and appendicular lean soft tissue (ALST) using dual-energy X-ray absorptiometry (DXA) as a reference method. Healthy volunteers (n = 2,220; 36% women; age 18-79 yr), representing a wide range of body mass index (14-44 kg/m(2)), participated in this study. Their LBM, including ALST, was assessed by DXA along with anthropometric measurements. The sample was divided into prediction (60%) and validation (40%) sets. In the prediction set, a number of prediction models were constructed using DXA-measured LBM and ALST estimates as dependent variables and a combination of anthropometric indices as independent variables. These equations were cross-validated in the validation set. Simple equations using age, height, and weight explained >90% variation in the LBM and ALST in both men and women. Additional variables (hip and limb circumferences and sum of skinfold thicknesses) increased the explained variation by 5-8% in the fully adjusted models predicting LBM and ALST. More complex equations using all of the above anthropometric variables could predict the DXA-measured LBM and ALST accurately, as indicated by low standard error of the estimate (LBM: 1.47 kg and 1.63 kg for men and women, respectively), as well as good agreement by Bland-Altman analyses (Bland JM, Altman D. Lancet 1: 307-310, 1986). These equations could be a valuable tool in large epidemiological studies assessing these body compartments in Indians and other population groups with similar body composition.
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The influence of age and gender on motor and non-motor features of early Parkinsons disease: Initial findings from the Oxford Parkinson Disease Center (OPDC) discovery cohort.
Parkinsonism Relat. Disord.
PUBLISHED: 08-12-2013
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Identifying factors influencing phenotypic heterogeneity in Parkinsons Disease is crucial for understanding variability in disease severity and progression. Age and gender are two most basic epidemiological characteristics, yet their effect on expression of PD symptoms is not fully defined. We aimed to delineate effects of age and gender on the phenotype in an incident cohort of PD patients and healthy controls from the Oxford Parkinson Disease Centre (OPDC).
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The effect of rural-to-urban migration on renal function in an Indian population: cross-sectional data from the hyderabad arm of the Indian migration study.
BMC Nephrol
PUBLISHED: 07-09-2013
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Urban migration is associated with an increased risk of hypertension, obesity and diabetes in Indian migrants. This study assessed the relationship between internal migration and renal function in the Hyderabad arm of the Indian Migration Study.
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Area deprivation across the life course and physical capability in midlife: findings from the 1946 British Birth cohort.
Am. J. Epidemiol.
PUBLISHED: 06-20-2013
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Physical capability in later life is influenced by factors occurring across the life course, yet exposures to area conditions have only been examined cross-sectionally. Data from the National Survey of Health and Development, a longitudinal study of a 1946 British birth cohort, were used to estimate associations of area deprivation (defined as percentage of employed people working in partly skilled or unskilled occupations) at ages 4, 26, and 53 years (residential addresses linked to census data in 1950, 1972, and 1999) with 3 measures of physical capability at age 53 years: grip strength, standing balance, and chair-rise time. Cross-classified multilevel models with individuals nested within areas at the 3 ages showed that models assessing a single time point underestimate total area contributions to physical capability. For balance and chair-rise performance, associations with area deprivation in midlife were robust to adjustment for individual socioeconomic position and prior area deprivation (mean change for a 1-standard-deviation increase: balance, -7.4% (95% confidence interval (CI): -12.8, -2.8); chair rise, 2.1% (95% CI: -0.1, 4.3)). In addition, area deprivation in childhood was related to balance after adjustment for childhood socioeconomic position (-5.1%, 95% CI: -8.7, -1.6). Interventions aimed at reducing midlife disparities in physical capability should target the socioeconomic environment of individuals-for standing balance, as early as childhood.
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Renal centre characteristics and physician practice patterns associated with home dialysis use.
Nephrol. Dial. Transplant.
PUBLISHED: 06-04-2013
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There is a wide variation in home dialysis use (peritoneal dialysis and home haemodialysis) between renal centres. This study identifies which centre characteristics and practice patterns are associated with home dialysis use.
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Apolipoprotein E genotype, cardiovascular biomarkers and risk of stroke: systematic review and meta-analysis of 14,015 stroke cases and pooled analysis of primary biomarker data from up to 60,883 individuals.
Int J Epidemiol
PUBLISHED: 04-10-2013
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At the APOE gene, encoding apolipoprotein E, genotypes of the ?2/?3/?4 alleles associated with higher LDL-cholesterol (LDL-C) levels are also associated with higher coronary risk. However, the association of APOE genotype with other cardiovascular biomarkers and risk of ischaemic stroke is less clear. We evaluated the association of APOE genotype with risk of ischaemic stroke and assessed whether the observed effect was consistent with the effects of APOE genotype on LDL-C or other lipids and biomarkers of cardiovascular risk.
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Temporal growth and geographic variation in the use of laboratory tests by NHS general practices: using routine data to identify research priorities.
Br J Gen Pract
PUBLISHED: 04-02-2013
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Laboratory tests are extensively used for diagnosis and monitoring in UK primary care. Test usage by GPs, and associated costs, have grown substantially in recent years.
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Genetic variants influencing biomarkers of nutrition are not associated with cognitive capability in middle-aged and older adults.
J. Nutr.
PUBLISHED: 03-06-2013
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Several investigations have observed positive associations between good nutritional status, as indicated by micronutrients, and cognitive measures; however, these associations may not be causal. Genetic polymorphisms that affect nutritional biomarkers may be useful for providing evidence for associations between micronutrients and cognitive measures. As part of the Healthy Ageing across the Life Course (HALCyon) program, men and women aged between 44 and 90 y from 6 UK cohorts were genotyped for polymorphisms associated with circulating concentrations of iron [rs4820268 transmembrane protease, serine 6 (TMPRSS6) and rs1800562 hemochromatosis (HFE)], vitamin B-12 [(rs492602 fucosyltransferase 2 (FUT2)], vitamin D ([rs2282679 group-specific component (GC)] and ?-carotene ([rs6564851 beta-carotene 15,15-monooxygenase 1 (BCMO1)]. Meta-analysis was used to pool within-study effects of the associations between these polymorphisms and the following measures of cognitive capability: word recall, phonemic fluency, semantic fluency, and search speed. Among the several statistical tests conducted, we found little evidence for associations. We found the minor allele of rs1800562 was associated with poorer word recall scores [pooled ? on Z-score for carriers vs. noncarriers: -0.05 (95% CI: -0.09, -0.004); P = 0.03, n = 14,105] and poorer word recall scores for the vitamin D-raising allele of rs2282679 [pooled ? per T allele: -0.03 (95% CI: -0.05, -0.003); P = 0.03, n = 16,527]. However, there was no evidence for other associations. Our findings provide little evidence to support associations between these genotypes and cognitive capability in older adults. Further investigations are required to elucidate whether the previous positive associations from observational studies between circulating measures of these micronutrients and cognitive performance are due to confounding and reverse causality.
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Study of living kidney donor-recipient relationships: variation with socioeconomic deprivation in the white population of England.
Clin Transplant
PUBLISHED: 02-20-2013
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Socioeconomic deprivation is associated with higher renal replacement therapy acceptance rates in the UK but lower rates of living kidney transplantation. This study examines donor-recipient relationship patterns with socioeconomic deprivation in the white population of England.
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Neuron-specific expression of tomosyn1 in the mouse hippocampal dentate gyrus impairs spatial learning and memory.
Neuromolecular Med.
PUBLISHED: 02-16-2013
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Tomosyn, a syntaxin-binding protein, is known to inhibit vesicle priming and synaptic transmission via interference with the formation of SNARE complexes. Using a lentiviral vector, we specifically overexpressed tomosyn1 in hippocampal dentate gyrus neurons in adult mice. Mice were then subjected to spatial learning and memory tasks and electrophysiological measurements from hippocampal slices. Tomosyn1-overexpression significantly impaired hippocampus-dependent spatial memory while tested in the Morris water maze. Further, tomosyn1-overexpressing mice utilize swimming strategies of lesser cognitive ability in the Morris water maze compared with control mice. Electrophysiological measurements at mossy fiber-CA3 synapses revealed impaired paired-pulse facilitation in the mossy fiber of tomosyn1-overexpressing mice. This study provides evidence for novel roles for tomosyn1 in hippocampus-dependent spatial learning and memory, potentially via decreased synaptic transmission in mossy fiber-CA3 synapses. Moreover, it provides new insight regarding the role of the hippocampal dentate gyrus and mossy fiber-CA3 synapses in swimming strategy preference, and in learning and memory.
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Physical capability and subsequent positive mental wellbeing in older people: findings from five HALCyon cohorts.
Age (Dordr)
PUBLISHED: 02-14-2013
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Objective measures of physical capability are being used in a growing number of studies as biomarkers of healthy ageing. However, very little research has been done to assess the impact of physical capability on subsequent positive mental wellbeing, the maintenance of which is widely considered to be an essential component of healthy ageing. We aimed to test the associations of grip strength and walking, timed get up and go and chair rise speeds (assessed at ages 53 to 82 years) with positive mental wellbeing assessed using the Warwick-Edinburgh Mental Wellbeing Scale (WEMWBS) 5 to 10 years later. Data were drawn from five British cohorts participating in the Healthy Ageing across the Life Course research collaboration. Data from each study were analysed separately and then combined using random-effects meta-analyses. Higher levels of physical capability were consistently associated with higher subsequent levels of wellbeing; for example, a 1SD increase in grip strength was associated with an age and sex-adjusted mean difference in WEMWBS score of 0.81 (0.25, 1.37), equivalent to 10 % of a standard deviation (three studies, N?=?3,096). When adjusted for body size, health status, living alone, socioeconomic position and neuroticism the associations remained albeit attenuated. The finding of these consistent modest associations across five studies, spanning early and later old age, highlights the importance of maintaining physical capability in later life and provides additional justification for using objective measures of physical capability as markers of healthy ageing.
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Lower respiratory tract infection in the first year of life is associated with worse lung function in adult life: prospective results from the Barry Caerphilly Growth study.
Ann Epidemiol
PUBLISHED: 02-07-2013
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We examined the association between childhood respiratory infections and adult lung function and how this association varies depending on the age at infection.
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Social isolation and diurnal cortisol patterns in an ageing cohort.
Psychoneuroendocrinology
PUBLISHED: 02-01-2013
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Social isolation may operate as a psychosocial stressor which disrupts functioning of the hypothalamic-pituitary-adrenocortical axis.
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Differences in estimation of creatinine generation between renal function estimating equations in an Indian population: cross-sectional data from the Hyderabad arm of the Indian migration study.
BMC Nephrol
PUBLISHED: 01-31-2013
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Creatinine based formulae for estimating renal function developed in white populations may be less valid in other ethnic groups. We assessed the performance of various estimating formulae in an Indian population.
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The effect of secular trends and specialist neurocritical care on mortality for patients with intracerebral haemorrhage, myasthenia gravis and Guillain-Barré syndrome admitted to critical care : an analysis of the Intensive Care National Audit & Research
Intensive Care Med
PUBLISHED: 01-17-2013
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To analyse mortality for spontaneous intracerebral haemorrhage (ICH), myasthenia gravis (MG) and Guillain-Barré syndrome (GBS) from 1996 to 2009 in UK intensive care units (ICUs).
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Association study of 25 type 2 diabetes related Loci with measures of obesity in Indian sib pairs.
PLoS ONE
PUBLISHED: 01-17-2013
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Obesity is an established risk factor for type 2 diabetes (T2D) and they are metabolically related through the mechanism of insulin resistance. In order to explore how common genetic variants associated with T2D correlate with body mass index (BMI), we examined the influence of 25 T2D associated loci on obesity risk. We used 5056 individuals (2528 sib-pairs) recruited in Indian Migration Study and conducted within sib-pair analysis for six obesity phenotypes. We found associations of variants in CXCR4 (rs932206) and HHEX (rs5015480) with higher body mass index (BMI) (?=0.13, p=0.001) and (?=0.09, p=0.002), respectively and weight (?=0.13, p=0.001) and (?=0.09, p=0.001), respectively. CXCR4 variant was also strongly associated with body fat (?=0.10, p=0.0004). In addition, we demonstrated associations of CXCR4 and HHEX with overweight/obesity (OR=1.6, p=0.003) and (OR=1.4, p=0.002), respectively, in 1333 sib-pairs (2666 individuals). We observed marginal evidence of associations between variants at six loci (TCF7L2, NGN3, FOXA2, LOC646279, FLJ39370 and THADA) and waist hip ratio (WHR), BMI and/or overweight which needs to be validated in larger set of samples. All the above findings were independent of daily energy consumption and physical activity level. The risk score estimates based on eight significant loci (including nominal associations) showed associations with WHR and body fat which were independent of BMI. In summary, we establish the role of T2D associated loci in influencing the measures of obesity in Indian population, suggesting common underlying pathophysiology across populations.
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Prenatal maternal mood is associated with altered diurnal cortisol in adolescence.
Psychoneuroendocrinology
PUBLISHED: 01-14-2013
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Experimental animal work shows that prenatal stress has a persisting effect on the hypothalamic-pituitary-adrenal (HPA) axis of offspring. The implications of these findings for human health and development are not yet clear.
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How to apply the results of a research paper on diagnosis to your patient.
JRSM Short Rep
PUBLISHED: 01-14-2013
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Interpreting information on diagnostic accuracy is an area that health professionals struggle with. In this paper, we use the example of Mr Samways, a 45-year-old man with joint symptoms, to illustrate how to apply the results of a diagnostic accuracy study in clinical practice. We consider the various measures used to quantify diagnostic accuracy and discuss their clinical utility. We provide an overview of potential biases to consider when evaluating a diagnostic accuracy study and consider how to determine whether the results can be applied to a particular patient.
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Body mass index, muscle strength and physical performance in older adults from eight cohort studies: the HALCyon programme.
PLoS ONE
PUBLISHED: 01-12-2013
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To investigate the associations of body mass index (BMI) and grip strength with objective measures of physical performance (chair rise time, walking speed and balance) including an assessment of sex differences and non-linearity.
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Healthy lifestyles reduce the incidence of chronic diseases and dementia: evidence from the caerphilly cohort study.
PLoS ONE
PUBLISHED: 01-01-2013
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Healthy lifestyles based on non-smoking, an acceptable BMI, a high fruit and vegetable intake, regular physical activity, and low/moderate alcohol intake, are associated with reductions in the incidence of certain chronic diseases, but to date there is limited evidence on cognitive function and dementia.
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Population genomics of cardiometabolic traits: design of the University College London-London School of Hygiene and Tropical Medicine-Edinburgh-Bristol (UCLEB) Consortium.
PLoS ONE
PUBLISHED: 01-01-2013
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Substantial advances have been made in identifying common genetic variants influencing cardiometabolic traits and disease outcomes through genome wide association studies. Nevertheless, gaps in knowledge remain and new questions have arisen regarding the population relevance, mechanisms, and applications for healthcare. Using a new high-resolution custom single nucleotide polymorphism (SNP) array (Metabochip) incorporating dense coverage of genomic regions linked to cardiometabolic disease, the University College-London School-Edinburgh-Bristol (UCLEB) consortium of highly-phenotyped population-based prospective studies, aims to: (1) fine map functionally relevant SNPs; (2) precisely estimate individual absolute and population attributable risks based on individual SNPs and their combination; (3) investigate mechanisms leading to altered risk factor profiles and CVD events; and (4) use Mendelian randomisation to undertake studies of the causal role in CVD of a range of cardiovascular biomarkers to inform public health policy and help develop new preventative therapies.
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Telomere length and physical performance at older ages: an individual participant meta-analysis.
PLoS ONE
PUBLISHED: 01-01-2013
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Telomeres are involved in cellular ageing and shorten with increasing age. If telomere length is a valuable biomarker of ageing, then telomere shortening should be associated with worse physical performance, an ageing trait, but evidence for such an association is lacking. The purpose of this study was to examine whether change in telomere length is associated with physical performance.
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Associations between a polymorphism in the pleiotropic GCKR and Age-related phenotypes: the HALCyon programme.
PLoS ONE
PUBLISHED: 01-01-2013
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The glucokinase regulatory protein encoded by GCKR plays an important role in glucose metabolism and a single nucleotide polymorphism (SNP) rs1260326 (P446L) in the gene has been associated with several age-related biomarkers, including triglycerides, glucose, insulin and apolipoproteins. However, associations between SNPs in the gene and other ageing phenotypes such as cognitive and physical capability have not been reported.
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Anti-hypertensive drugs as disease-modifying agents for Parkinsons disease: evidence from observational studies and clinical trials.
Cochrane Database Syst Rev
PUBLISHED: 11-11-2011
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Current treatment for Parkinsons disease (PD) is focused on relieving symptoms, at present there is nothing that is widely accepted to halt or slow disease progression. Potential neuroprotective or disease modifying agents have been identified from preclinical studies. One such group of compounds are anti-hypertensive drugs.
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Non-steroidal anti-inflammatory drugs as disease-modifying agents for Parkinsons disease: evidence from observational studies.
Cochrane Database Syst Rev
PUBLISHED: 11-11-2011
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Neuroinflammation may play a key role in the neurodegeneration associated with Parkinsons disease (PD). Non-steroidal anti-inflammatory drugs (NSAIDs) may be beneficial in the primary and secondary prevention of PD.
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Helicobacter pylori eradication for Parkinsons disease.
Cochrane Database Syst Rev
PUBLISHED: 11-11-2011
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Levodopa is the mainstay of treatment for alleviating the motor symptoms associated with Parkinsons disease. However, patients often experience fluctuations in their symptoms over time and wearing off which may be partly related to variable absorption of the drug. There is some evidence that treatment of the common gastrointestinal infection Helicobacter pylori (H pylori) with antibiotics may improve levodopa absorption in the gut and hence improve symptoms.
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Benzodiazepine use and risk of dementia: evidence from the Caerphilly Prospective Study (CaPS).
J Epidemiol Community Health
PUBLISHED: 10-27-2011
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Benzodiazepine use is widespread in older people, although its benefit is uncertain.
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Is infant weight associated with childhood blood pressure? Analysis of the Promotion of Breastfeeding Intervention Trial (PROBIT) cohort.
Int J Epidemiol
PUBLISHED: 09-03-2011
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Weight gain during infancy may programme later health outcomes, but examination of this hypothesis requires appropriate lifecourse methods and detailed weight gain measures during childhood. We examined associations between weight gain in infancy and early childhood and blood pressure at the age of 6.5 years in healthy children born at term.
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Inequalities in rates of renal replacement therapy in England: does it matter who you are or where you live?
Nephrol. Dial. Transplant.
PUBLISHED: 08-30-2011
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Introduction. This study explores the geographical variation in renal replacement therapy (RRT) incidence and prevalence after adjusting for general population socio-demographics, renal unit treatment patterns and travel times.
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UK Renal Registry 13th Annual Report (December 2010): Chapter 15: UK renal centre survey results 2010: RRT incidence and use of home dialysis modalities.
Nephron Clin Pract
PUBLISHED: 08-26-2011
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RRT incidence rates and the proportion of patients using a home dialysis modality (peritoneal or home haemodialysis) varies widely between centres and persists even after area differences in age, ethnicity and social deprivation structure are taken into account. A nationwide survey was undertaken to identify possible drivers of this variation.
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Prevalence of Tourette syndrome and chronic tics in the population-based Avon longitudinal study of parents and children cohort.
J Am Acad Child Adolesc Psychiatry
PUBLISHED: 08-16-2011
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Recent epidemiologic studies have demonstrated that Tourette syndrome (TS) and chronic tic disorder (CT) are more common than previously recognized. However, few population-based studies have examined the prevalence of co-occurring neuropsychiatric conditions such as obsessive-compulsive disorder (OCD) and attention-deficit/hyperactivity disorder (ADHD). We evaluated the prevalence of TS, CT, and their overlap with OCD and ADHD in the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort.
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Diurnal cortisol patterns are associated with physical performance in the Caerphilly Prospective Study.
Int J Epidemiol
PUBLISHED: 07-19-2011
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Cross-sectional studies have suggested that elevated cortisol is associated with worse physical performance, a surrogate of ageing. We examined the relationship between repeat cortisol measures over 20 years and physical performance in later life.
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Pre-natal and post-natal growth trajectories and childhood cognitive ability and mental health.
Int J Epidemiol
PUBLISHED: 07-15-2011
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Most studies of the associations between pre-natal or post-natal growth and cognitive ability have been based on children with pathologically slow growth measured between two time points only, rather than children with normal growth trajectories estimated from multiple measures of growth.
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Age and gender differences in physical capability levels from mid-life onwards: the harmonisation and meta-analysis of data from eight UK cohort studies.
PLoS ONE
PUBLISHED: 07-01-2011
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Using data from eight UK cohorts participating in the Healthy Ageing across the Life Course (HALCyon) research programme, with ages at physical capability assessment ranging from 50 to 90+ years, we harmonised data on objective measures of physical capability (i.e. grip strength, chair rising ability, walking speed, timed get up and go, and standing balance performance) and investigated the cross-sectional age and gender differences in these measures. Levels of physical capability were generally lower in study participants of older ages, and men performed better than women (for example, results from meta-analyses (N?=?14,213 (5 studies)), found that men had 12.62 kg (11.34, 13.90) higher grip strength than women after adjustment for age and body size), although for walking speed, this gender difference was attenuated after adjustment for body size. There was also evidence that the gender difference in grip strength diminished with increasing age, whereas the gender difference in walking speed widened (p<0.01 for interactions between age and gender in both cases). This study highlights not only the presence of age and gender differences in objective measures of physical capability but provides a demonstration that harmonisation of data from several large cohort studies is possible. These harmonised data are now being used within HALCyon to understand the lifetime social and biological determinants of physical capability and its changes with age.
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The centre effect in nephrology: what do differences between nephrology centres tell us about clinical performance in patient management?
Nephron Clin Pract
PUBLISHED: 06-09-2011
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Improving the quality of care provided by nephrology centres to patients with kidney disease requires a clear understanding of how to compare performance after adjustment for case mix, combined with a detailed understanding of the structure and processes that are associated with the achievement of good clinical results. In this review, we discuss how to measure quality of care (using process or outcome measures), how to take case mix into account, how best to display comparisons between nephrology centres, and how to study the causes of real variations in quality between centres. This is a narrative review; we include examples from other fields in which the centre effect has been studied, including education.
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Associations of growth trajectories in infancy and early childhood with later childhood outcomes.
Am. J. Clin. Nutr.
PUBLISHED: 06-01-2011
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Weight and length at birth (which represent fetal growth) and weight and length or height gain during childhood (which potentially represent catch-up growth) may be related to later health outcomes. However, methods for the assessment of such relations are complex and underdeveloped.
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Association between urban life-years and cardiometabolic risk: the Indian migration study.
Am. J. Epidemiol.
PUBLISHED: 05-27-2011
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Urban living is associated with an increase in cardiometabolic risks, but the speed at which these risks are accrued over time is unknown. Using a cross-sectional sibling-pair design, the authors surveyed migrant factory workers and their spouses from 4 cities in India together with their rural-dwelling siblings and examined the associations between urban life-years and cardiometabolic risk factors. Data on 4,221 participants (39% women; mean age = 41 years) were available (2005-2007). In regression models, a 2-slope pattern for body fat (with a marked shift at 10 years) was found, whereas a common slope could be accepted for other risk factors. In men, the regression coefficients (per decade of urban life) were 2.5% in the first decade and 0.1% thereafter for body fat; 1.4 mm Hg for systolic blood pressure; and 7% for fasting insulin. Age, gender, marital status, household structure, and occupation did not influence the patterns appreciably; however, stronger gradients for adiposity were noted in migrants from lower socioeconomic positions. The findings suggest that body fat increases rapidly when one first moves to an urban environment, whereas other cardiometabolic risk factors evolve gradually. Public health interventions focused on the control of obesity in newer migrants to urban areas, particularly those from lower socioeconomic positions, may be beneficial.
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Is relative leg length a biomarker of childhood nutrition? Long-term follow-up of the Hyderabad Nutrition Trial.
Int J Epidemiol
PUBLISHED: 05-10-2011
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Relative leg length is frequently used as a biomarker of childhood nutrition in epidemiological studies, but evidence is lacking. We examined the association between supplemental nutrition in pregnancy and childhood and relative proportions of components of height in adolescence.
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The CRP genotype, serum levels and lung function in men: the Caerphilly Prospective Study.
Clin. Sci.
PUBLISHED: 05-07-2011
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Systemic CRP (C-reactive protein) has been associated with impaired lung function. A causal relationship would increase the value of CRP as both a diagnostic and therapeutic tool. We assessed the association between lung function parameters, circulating CRP and CRP polymorphisms using Mendelian randomization in efforts to attribute causality to known associations. Spirometric parameters of FEV1 (forced expiratory volume in 1 s) and FVC (forced vital capacity) were determined in 2173 men participating in the Caerphilly Prospective Study. Lung function measures on 1021 participants were available at follow-up (mean, 16.8 years later). Serum CRP levels were measured at baseline, and three CRP polymorphisms were analysed. Haplotype analysis was performed. Serum CRP levels at baseline were inversely associated with contemporaneous FEV1 and FVC as well as at follow-up (P<0.001) even after adjustment for conventional confounders. Serum CRP was associated with FEV1 decline (P=0.04). All three CRP polymorphisms (rs1800947, rs1130864 and rs1205) predicted serum CRP; however, there were no clear associations of the polymorphisms or haplotypes with lung function or with lung function decline. In conclusion, serum CRP was associated with lung function cross-sectionally; however, CRP polymorphisms were not associated with lung function or decline, suggesting that the CRP-lung function relationship is due to reverse causality, an unmeasured confounding factor or only has a modest causal effect.
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Life course trajectories of systolic blood pressure using longitudinal data from eight UK cohorts.
PLoS Med.
PUBLISHED: 05-04-2011
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Much of our understanding of the age-related progression of systolic blood pressure (SBP) comes from cross-sectional data, which do not directly capture within-individual change. We estimated life course trajectories of SBP using longitudinal data from seven population-based cohorts and one predominantly white collar occupational cohort, each from the United Kingdom and with data covering different but overlapping age periods.
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JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.