Effects of MRI scan acceleration on brain volume measurement consistency.

PURPOSE: To evaluate the effects of recent advances in magnetic resonance imaging (MRI) radiofrequency (RF) coil and parallel imaging technology on brain volume measurement consistency. MATERIALS AND METHODS: In all, 103 whole-brain MRI volumes were acquired at a clinical 3T MRI, equipped with a 12- and 32-channel head coil, using the T1-weighted protocol as employed in the Alzheimer's Disease Neuroimaging Initiative study with parallel imaging accelerations ranging from 1 to 5. An experienced reader performed qualitative ratings of the images. For quantitative analysis, differences in composite width (CW, a measure of image similarity) and boundary shift integral (BSI, a measure of whole-brain atrophy) were calculated. RESULTS: Intra- and intersession comparisons of CW and BSI measures from scans with equal acceleration demonstrated excellent scan-rescan accuracy, even at the highest acceleration applied. Pairs-of-scans acquired with different accelerations exhibited poor scan-rescan consistency only when differences in the acceleration factor were maximized. A change in the coil hardware between compared scans was found to bias the BSI measure. CONCLUSION: The most important findings are that the accelerated acquisitions appear to be compatible with the assessment of high-quality quantitative information and that for highest scan-rescan accuracy in serial scans the acquisition protocol should be kept as consistent as possible over time. J. Magn. Reson. Imaging 2012;36:1234-1240. ©2012 Wiley Periodicals, Inc.

Evaluation of the direct agglutination test and the rK39 dipstick test for the sero-diagnosis of visceral leishmaniasis

The direct agglutination test (DAT) based on a freeze-dried antigen and the rK39 dipstick test were evaluated for the sero-diagnosis of visceral leishmaniasis (VL). The sensitivity and specificity of both tests were determined using sera from confirmed VL patients (n = 21), healthy controls (n = 19) and from patients with other confirmed infectious diseases (n = 42). The DAT had a sensitivity and a specificity of 100%. The rK39 had a sensitivity of 85.7% and a specificity of 82%. Both tests were also used to screen blood samples of confirmed VL patients (n = 15) and serum samples of VL suspects (n = 61). The DAT found all blood samples of confirmed VL patients positive and tested 98.4% of the serum samples of the VL suspects positive. In contrast, rK39 detected in 9/15 blood samples (60%) antibodies against Leishmania chagasi and found 85.3% of the serum samples of the suspected patients positive. Although the rK39 dipstick is more rapid and user friendlier than the DAT, the latter has a superior sensitivity and specificity. Furthermore, the reagents used for DAT do not require cold storage, whereas the buffer of the rK39 must be stored at 4ºC. Therefore, the DAT is the most suitable test for the sero-diagnosis of VL under field conditions.

Evaluation of two immunoassays for the measurement of human chorionic gonadotropin in urine for anti-doping purposes.

Background: Urinary human chorionic gonadotropin (hCG) concentration is routinely measured in all anti-doping laboratories to exclude the misuse of recombinant or urinary hCG preparations. In this study, extended validation of two commercial immunoassays for hCG measurements in urine was performed. Both tests were initially designed for hCG determination in human serum/plasma. Methods: Access (R) and Elecsys (R) 1010 are two automated immunoanalysers for central laboratories. The limits of detection and quantification, as well as intra-laboratory and inter-technique correlation, precision, and accuracy, were determined. Stability studies of hCG in urine following freezing and thawing cycles (n = 3) as well as storage conditions at room temperature, 4 degrees C and 20 degrees C, were performed. Results: Statistical evaluation of hCG concentrations in male urine samples (n = 2429) measured with the Elecsys (R) 1010 system enabled us to draw a skewed frequency histogram and establish a far outside value equal to 2.3 IU/L. This decision limit corresponds to the concentration at which a sportsman will be considered positive for hCG. Intra-assay precision for the Access (R) analyser was less than 4.0 A, whereas the inter-assay precision was closer to 4.5 % (concentrations of the official external controls contained between 5.5 and 195.0 IU/L). Intra and inter-assay precision for the Elecsys (R) 1010 analyser was slightly better. A good inter-technique correlation was obtained when measuring various urine samples (male and female). No urinary hCG loss was observed after two freeze/thaw cycles. On the other hand, time and inappropriate storage conditions, such as temperatures above 10 degrees C for more than 5 days, can deteriorate urinary hCG. Conclusions: Both analysers showed acceptable performances and are suitable for screening urine for anti-doping analyses. Each laboratory should validate and establish its own reference values because hCG concentrations measured in urine can be different from one immunoassay to another. The time delay between urine collection and analysis should be reduced as much as possible, and urine samples should be transported in optimal conditions to avoid a loss of hCG immunoreactivity.

Report on the baseline measurement of the administrative burden from the Department of Health

The Irish Government in March 2008 set a target to identify measure and reduce the Administrative Burden (AB) of domestic regulation for businesses by 25% by the end of 2012 – on foot of a European Council invitation to all member states in March 2007. As part of a cross-Government process led by the Business Regulation Unit of the Department of Jobs, Enterprise and Innovation (DJEI), the Department of Health carried out a measurement exercise in 2012 on the main Information Obligations placed on business by legislation in the areas of Food, Nursing Homes and Pharmacy sectors.The AB baseline measurement for those information obligations is described in this report. Click here to download PDF 322KB  

Melanopsin as a sleep modulator: circadian gating of the direct effects of light on sleep and altered sleep homeostasis in Opn4(-/-) mice.

Light influences sleep and alertness either indirectly through a well-characterized circadian pathway or directly through yet poorly understood mechanisms. Melanopsin (Opn4) is a retinal photopigment crucial for conveying nonvisual light information to the brain. Through extensive characterization of sleep and the electrocorticogram (ECoG) in melanopsin-deficient (Opn4(-/-)) mice under various light-dark (LD) schedules, we assessed the role of melanopsin in mediating the effects of light on sleep and ECoG activity. In control mice, a light pulse given during the habitual dark period readily induced sleep, whereas a dark pulse given during the habitual light period induced waking with pronounced theta (7-10 Hz) and gamma (40-70 Hz) activity, the ECoG correlates of alertness. In contrast, light failed to induce sleep in Opn4(-/-) mice, and the dark-pulse-induced increase in theta and gamma activity was delayed. A 24-h recording under a LD 1-hratio1-h schedule revealed that the failure to respond to light in Opn4(-/-) mice was restricted to the subjective dark period. Light induced c-Fos immunoreactivity in the suprachiasmatic nuclei (SCN) and in sleep-active ventrolateral preoptic (VLPO) neurons was importantly reduced in Opn4(-/-) mice, implicating both sleep-regulatory structures in the melanopsin-mediated effects of light. In addition to these acute light effects, Opn4(-/-) mice slept 1 h less during the 12-h light period of a LD 12ratio12 schedule owing to a lengthening of waking bouts. Despite this reduction in sleep time, ECoG delta power, a marker of sleep need, was decreased in Opn4(-/-) mice for most of the (subjective) dark period. Delta power reached after a 6-h sleep deprivation was similarly reduced in Opn4(-/-) mice. In mice, melanopsin's contribution to the direct effects of light on sleep is limited to the dark or active period, suggesting that at this circadian phase, melanopsin compensates for circadian variations in the photo sensitivity of other light-encoding pathways such as rod and cones. Our study, furthermore, demonstrates that lack of melanopsin alters sleep homeostasis. These findings call for a reevaluation of the role of light on mammalian physiology and behavior.

Real-time dual-wavelength digital holographic microscopy for extended measurement range with enhanced axial resolution

We report on advanced dual-wavelength digital holographic microscopy (DHM) methods, enabling single-acquisition real-time micron-range measurements while maintaining single-wavelength interferometric resolution in the nanometer regime. In top of the unique real-time capability of our technique, it is shown that axial resolution can be further increased compared to single-wavelength operation thanks to the uncorrelated nature of both recorded wavefronts. It is experimentally demonstrated that DHM topographic investigation within 3 decades measurement range can be achieved with our arrangement, opening new applications possibilities for this interferometric technique. ©2008 COPYRIGHT SPIE

In vitro measurement of enzymatic markers as a tool to detect mouse cardiomyocytes injury

Primary cultures of cardiomyocytes represent a useful model for analyzing cardiac cell biology as well as pathogenesis of several cardiovascular disorders. Our aim was to standardize protocols for determining the damage of cardiac cells cultured in vitro by measuring the creatine kinase and its cardiac isotype and lactate dehydrogenase activities in the supernatants of mice cardiomyocytes submitted to different protocols of cell lysis. Our data showed that due to its higher specificity, the cardiac isotype creatine kinase was the most sensitive as compared to the others studied enzymatic markers, and can be used to monitor and evaluate cardiac damage in in vitro assays.

Instrumental leadership: Measurement and extension of transformational-transactional leadership theory.

Leaders must scan the internal and external environment, chart strategic and task objectives, and provide performance feedback. These instrumental leadership (IL) functions go beyond the motivational and quid-pro quo leader behaviors that comprise the full-range-transformational, transactional, and laissez faire-leadership model. In four studies we examined the construct validity of IL. We found evidence for a four-factor IL model that was highly prototypical of good leadership. IL predicted top-level leader emergence controlling for the full-range factors, initiating structure, and consideration. It also explained unique variance in outcomes beyond the full-range factors; the effects of transformational leadership were vastly overstated when IL was omitted from the model. We discuss the importance of a "fuller full-range" leadership theory for theory and practice. We also showcase our methodological contributions regarding corrections for common method variance (i.e., endogeneity) bias using two-stage least squares (2SLS) regression and Monte Carlo split-sample designs.

Health-related quality of life and functioning in bipolar disorder: the impact of pharmacotherapy.

Bipolar disorder has a major deleterious impact on many aspects of a patient's functioning and health-related quality of life. Although the formal measurement of these deficits has been neglected until recently, many well-designed trials now include an assessment of functioning and health-related quality of life using one or more rating scales. This review describes recent developments in the measurement of functioning and health-related quality of life in bipolar disorder, and discusses the evidence that medications that improve symptoms in bipolar disorder also offer clinically relevant benefits in functioning and health-related quality of life. Direct comparisons of the benefits of medications including atypical antipsychotics are problematic due to differences in trial populations, study durations and rating scales. Data from quetiapine trials indicate that this medication offers prompt and sustained improvement of functioning in patients with mania and enhancement of health-related quality of life in patients with bipolar depression, to accompany the significant improvements in mood episodes.

Renal and hormonal responses to direct renin inhibition with aliskiren in healthy humans.

BACKGROUND: Pharmacological interruption of the renin-angiotensin system focuses on optimization of blockade. As a measure of intrarenal renin activity, we have examined renal plasma flow (RPF) responses in a standardized protocol. Compared with responses with angiotensin-converting enzyme inhibition (rise in RPF approximately 95 mL x min(-1) x 1.73 m(-2)), greater renal vasodilation with angiotensin receptor blockers (approximately 145 mL x min(-1) x 1.73 m(-2)) suggested more effective blockade. We predicted that blockade with the direct oral renin inhibitor aliskiren would produce renal vascular responses exceeding those induced by angiotensin-converting enzyme inhibitors and angiotensin receptor blockers. METHODS AND RESULTS: Twenty healthy normotensive subjects were studied on a low-sodium (10 mmol/d) diet, receiving separate escalating doses of aliskiren. Six additional subjects received captopril 25 mg as a low-sodium comparison and also received aliskiren on a high-sodium (200 mmol/d) diet. RPF was measured by clearance of para-aminohippurate. Aliskiren induced a remarkable dose-related renal vasodilation in low-sodium balance. The RPF response was maximal at the 600-mg dose (197+/-27 mL x min(-1) x 1.73 m(-2)) and exceeded responses to captopril (92+/-20 mL x min(-1) x 1.73 m(-2); P<0.01). Furthermore, significant residual vasodilation was observed 48 hours after each dose (P<0.01). The RPF response on a high-sodium diet was also higher than expected (47+/-17 mL x min(-1) x 1.73 m(-2)). Plasma renin activity and angiotensin levels were reduced in a dose-related manner. As another functional index of the effect of aliskiren, we found significant natriuresis on both diets. CONCLUSIONS: Renal vasodilation in healthy people with the potent renin inhibitor aliskiren exceeded responses seen previously with angiotensin-converting enzyme inhibitors and angiotensin receptor blockers. The effects were longer lasting and were associated with significant natriuresis. These results indicate that aliskiren may provide more complete and thus more effective blockade of the renin-angiotensin system.

Alzheimer's Disease Biomarkers, 2009

This report gives a comprehensive and up-to-date review of Alzheimer's disease biomarkers. Recent years have seen significant advances in this field. Whilst considerable effort has focused on A�_ and tau related markers, a substantial number of other molecules have been identified, that may offer new opportunities.This Report : Identifies 60 candidate Alzheimer's (AD) biomarkers and their associated studies. Of these, 49 are single species or single parameters, 7 are combinations or panels and 4 involve the measurement of two species or parameters or their ratios. These include proteins (n=34), genes (n=11), image-based parameters (n=7), small molecules (n=3), proteins + genes (n=2) and others (n=3). Of these, 30 (50%) relate to species identified in CSF and 19 (32%) were found in the blood. These candidate may be classified on the basis of their diagnostic utility, namely those which i) may allow AD to be detected when the disease has developed (48 of 75†= 64%), ii) may allow early detection of AD (18 of 75† = 24%) and iii) may allow AD to be predicted before the disease has begun to develop (9 of 75†= 12%). † Note: Of these, 11 were linked to two or more of these capabilities (e.g. allowed both early-stage detection as well as diagnosis after the disease has developed).Biomarkers: AD biomarkers identified in this report show significant diversity, however of the 60 described, 18 (30%) are associated with amyloid beta (A�_) and 9 (15%) relate to Tau. The remainder of the biomarkers (just over half) fall into a number of different groups. Of these, some are associated with other hypotheses on the pathogenesis of AD however the vast majority are individually unique and not obviously linked with other markers. Analysis and discussion presented in this report includes summaries of the studies and clinical trials that have lead to the identification of these markers. Where it has been calculated, diagnostic sensitivity, specificity and the capacity of these markers to differentiate patients with suspected AD from healthy controls and individuals believed to be suffering from other neurodegenerative conditions, have been indicated. These findings are discussed in relation to existing hypotheses on the pathogenesis of the AD and the current drug development pipeline. Many uncertainties remain in relation to the pathogenesis of AD, in diagnosing and treating the disease and many of the studies carried out to identify disease markers are at an early stage and will require confirmation through larger and longer investigations. Nevertheless, significant advances in the identification of AD biomarkers have now been made. Moreover, whilst much of the research on AD biomarkers has focused on amyloid and tau related species, it is evident that a substantial number of other species may provide important opportunities.Purpose of Report: To provide a comprehensive review of important and recently discovered candidate biomarkers of AD, in particular those with potential to reliably detect the disease or with utility in clinical development, drug repurposing, in studies of the pathogenesis and in monitoring drug response and the course of the disease. Other key goals were to identify markers that support current pipeline developments, indicate new potential drug targets or which advance understanding of the pathogenesis of this disease.Drug Repurposing: Studies of the pathogenesis of AD have identified aberrant changes in a number of other disease areas including inflammation, diabetes, oxidative stress, lipid metabolism and others. These findings have prompted studies to evaluate some existing approved drugs to treat AD. This report identifies studies of 9 established drug classes currently being investigated for potential repurposing.Alzheimer’s Disease: In 2005, the global prevalence of dementia was estimated at 25 million, with more than 4 million new cases occurring each year. It is also calculated that the number of people affected will double every 20 years, to 80 million by 2040, if a cure is not found. More than 50% of dementia cases are due to AD. Today, approximately 5 million individuals in the US suffer from AD, representing one in eight people over the age of 65. Direct and indirect costs of AD and other forms of dementia in the US are around $150 billion annually. Worldwide, costs for dementia care are estimated at $315 billion annually. Despite significant research into this debilitating and ultimately fatal disease, advances in the development of diagnostic tests for AD and moreover, effective treatments, remain elusive.Background: Alzheimer's disease is the most common cause of dementia, yet its clinical diagnosis remains uncertain until an eventual post-mortem histopathology examination is carried out. Currently, therapy for patients with Alzheimer disease only treats the symptoms; however, it is anticipated that new disease-modifying drugs will soon become available. The urgency for new and effective treatments for AD is matched by the need for new tests to detect and diagnose the condition. Uncertainties in the diagnosis of AD mean that the disease is often undiagnosed and under treated. Moreover, it is clear that clinical confirmation of AD, using cognitive tests, can only be made after substantial neuronal cell loss has occurred; a process that may have taken place over many years. Poor response to current therapies may therefore, in part, reflect the fact that such treatments are generally commenced only after neuronal damage has occurred. The absence of tests to detect or diagnose presymptomatic AD also means that there is no standard that can be applied to validate experimental findings (e.g. in drug discovery) without performing lengthy studies, and eventual confirmation by autopsy.These limitations are focusing considerable effort on the identification of biomarkers that advance understanding of the pathogenesis of AD and how the disease can be diagnosed in its early stages and treated. It is hoped that developments in these areas will help physicians to detect AD and guide therapy before the first signs of neuronal damage appears. The last 5-10 years have seen substantial research into the pathogenesis of AD and this has lead to the identification of a substantial number of AD biomarkers, which offer important insights into this disease. This report brings together the latest advances in the identification of AD biomarkers and analyses the opportunities they offer in drug R&D and diagnostics.��

Relevé des consultations et des transferts de patients par enquête directe auprès des médecins: méthode d'une enquête, acceptabilité et limites d'interprétation. [Summary of consultations and transfer of patients by a direct survey of physicians: survey methods, acceptability and limits of interpretation].

A survey of medical ambulatory practice was carried out in February-March 1981 in the two Swiss cantons of Vaud and Fribourg (total population: 700,000), in which 205 physicians participated. The methodology used was inspired from the U.S. National Ambulatory Medical Care Survey, the data collection instrument of which was adapted to our conditions; in addition, data were gathered on all referrals prescribed by 154 physicians during two weeks. (The instruments used are presented.) The potential and limits of this type of survey are discussed, as well as the representativity of the participating physicians and of the recorded visits, which are a systematic sample of over 43,000 visits.