Purpose
This study was conducted to prospectively investigate the interobserver reproducibility of controlled attenuation parameter (CAP) measurements and the relationship among the CAP and body mass ...index (BMI), gender and age.
Methods
Consecutive subjects were studied using the M+ probe of the FibroScan device (Echosens, Paris, France). Measurements were performed by two raters (rater1 and rater2). Interobserver agreement was assessed by using the concordance correlation coefficient (CCC). The Pearson
r
coefficient was used to test correlation between two study variables, and linear regression was used for the multivariate model.
Results
Three hundred fifty-one subjects (227 males and 124 females) were prospectively studied. The CCC was 0.82 (95 % CI 0.78–0.85) overall, 0.80 (95 % CI 0.75–0.85) for BMI <25 kg/m
2
, 0.76 (95 % CI 0.69–0.84) for BMI 25–29 kg/m
2
and 0.65 (95 % CI 0.41–0.88) for BMI ≥30 kg/m
2
. The CCC was 0.44 (95 % CI 0.31–0.56) for CAP values ≤240 dB/m and 0.72 (95 % CI 0.65–0.79) for CAP values >240 dB/m. In univariate analysis, age and BMI by gender were correlated with the CAP. Multiple regression analysis confirmed the relationship of the CAP with age and BMI, but not with gender.
Conclusions
The results of this study show that the interreader agreement in CAP measurement is good. In healthy volunteers, the CAP is strongly correlated with age and BMI.
Antibody engineering is important for many diagnostic and clinical applications of monoclonal antibodies. We recently reported a series of fragment crystallizable (Fc) mutations targeting the ...neonatal Fc receptor (FcRn) site on a Lewis Y (Le
) binding IgG1, hu3S193. The hu3S193 variants displayed shortened
half-lives and may have potential for radioimaging or radiotherapy of Le
-positive tumors. Here, we report Fc crystal structures of wild-type hu3S193, seven FcRn-binding site variants, and a variant lacking C1q binding or complement-dependent cytotoxicity (CDC) activity. The Fc conformation of the FcRn-binding sites was similar for wild-type and all mutants of hu3S193 Fc, which suggests that FcRn interactions were directly affected by the amino acid substitutions. The C1q-binding site mutant Fc was nearly identical with the wild-type Fc. Surprisingly, several hu3S193 Fc variants showed large changes in global structure compared with wild-type Fc. All hu3S193 Fc mutants had similar antibody-dependent cellular cytotoxicity, despite some with conformations expected to diminish Fc gamma receptor binding. Several hu3S193 variants displayed altered CDC, but there was no correlation with the different Fc conformations. All versions of hu3S193, except the C1q-binding site mutant, bound C1q, suggesting that the altered CDC of some variants could result from different propensities to form IgG hexamers after engaging Le
on target cells. Overall, our findings support the concept that the antibody Fc is both flexible and mobile in solution. Structure-based design approaches should take into account the conformational plasticity of the Fc when engineering antibodies with optimal effector properties.
Starting from the failure of the R&D-patents traditional relationship, when time-series and/or within-industry dimensions are included in the empirical analysis, the present work tries to contribute ...to the empirical literature from two directions. First, it performs a Granger causality test based on the theoretical presumption of a reverse patents→R&D link as an explanation for the failure of the traditional relationship. Second, assuming the reverse patents-R&D causality, we test and interpret the lag structure of such a relationship which shows the effective patent life that firms can expect within the two Schumpeterian patterns of innovations they belong to. In the light of the effective patent life, we offer a further explanation of innovation persistence which overturns the findings of the existing literature on persistence.
Changes in D(2) receptors during antidepressant therapy have been reported in patients with major depressive disorder using PET/SPET. The aim of this study was to evaluate modifications in D(2) ...receptors that might occur in patients affected by obsessive-compulsive disorder (OCD) during serotonin reuptake sites inhibitors (SSRIs). To this purpose, we measured the in vivo binding of (11)Craclopride ((11)CRac)in the brain of a group of OCD naïve patients before and after the repeated administration of the inhibitor SSRI fluvoxamine. Eight patients with a Diagnostic and Statistical Manual of Mental Disorders IVth edition diagnosis of OCD completed the study undergoing a PET scan and a complete clinical evaluation before and during treatment with fluvoxamine. Patients have been compared also with a group of nine age-matched normal volunteers. Fluvoxamine treatment significantly improved clinical symptoms and increased (11)CRac binding potential (BP) in the basal ganglia of OCD patients (7.5+/-5.2, 6.9+/-6.9, and 9.9+/-9.3% in dorsal caudate, dorsal putamen, and ventral basal ganglia, respectively; p<0.01) to values closer to those observed in the group of normal subjects. Chronic treatment with fluvoxamine induces a slight but significant increase in striatal (11)CRac BP of previously drug-naïve OCD patients. The modifications in D(2) receptor availability might be secondary to fluvoxamine effects on serotoninergic activity.
Introduction
Dementia with Lewy bodies (DLB) may represent a diagnostic challenge, since its clinical picture overlaps with other dementia. Two toolkits have been developed to aid the clinician to ...diagnose DLB: the Lewy Body Composite Risk Score (LBCRS) and the Assessment Toolkit for DLB (AT-DLB). We aim to evaluate the reliability of these two questionnaires, and their ability to enhance the interpretation of the international consensus diagnostic criteria.
Methods
LBCRS and AT-DLB were distributed to 135 Italian Neurological Centers for Cognitive Decline and Dementia (CDCDs), with the indication to administer them to all patients with dementia referred within the subsequent 3 months. We asked to subsequently apply consensus criteria for DLB diagnosis, to validate the diagnostic accuracy of the two toolkits.
Results
A total of 23 Centers joined the study; 1854 patients were enrolled. We found a prevalence of possible or probable DLB of 13% each (26% total), according to the consensus criteria. LBCRS toolkit showed good reliability, with a Cronbach alpha of 0.77, stable even after removing variables from the construct. AT-DLB toolkit Cronbach alpha was 0.52 and, after the subtraction of the “cognitive fluctuation” criterion, was only 0.31. Accuracy, sensitivity, and specificity were higher for LBCRS vs. AT-DLB. However, when simultaneously considered in the logistic models, AT-DLB showed a better performance (
p
< 0.001). Overall, the concordance between LBCRS positive and AT-DLB possible/probable was of 78.02%
Conclusions
In a clinical setting, the LBCRS and AT-DLB questionnaires have good accuracy for DLB diagnosis.
Purpose
The aim of the study was to evaluate extrastriatal dopaminergic and serotonergic pathways in patients with Parkinson’s disease (PD) and dementia with Lewy bodies (DLB) using
123
I-FP-CIT ...SPECT imaging.
Methods
The study groups comprised 56 PD patients without dementia, 41 DLB patients and 54 controls. Each patient underwent a standardized neurological examination and
123
I-FP-CIT SPECT. Binding in nigrostriatal and extrastriatal regions of interest was calculated in each patient from spatially normalized images. The occipital-adjusted specific to nondisplaceable binding ratio (SBR) in the different regions was compared among the PD patients, DLB patients and controls adjusting for the effects of age, sex, disease duration and serotonergic/dopaminergic treatment. Covariance analysis was used to determine the correlates of local and long-distance regions with extrastriatal
123
I-FP-CIT deficits.
Results
Both PD and DLB patients showed lower
123
I-FP-CIT SPECT SBR in several regions beyond the nigrostriatal system, especially the insula, cingulate and thalamus. DLB patients showed significantly lower
123
I-FP-CIT SBR in the thalamus than controls and PD patients. Thalamic and cingulate
123
I-FP-CIT SBR deficits were correlated, respectively, with limbic serotonergic and widespread cortical monoaminergic projections only in DLB patients but exhibited only local correlations in PD patients and controls.
Conclusion
PD and DLB patients both showed insular dopamine deficits, whereas impairment of thalamic serotonergic pathways was specifically associated with DLB. Longitudinal studies are necessary to determine the clinical value of the assessment of extrastriatal
123
I-FP-CIT SPECT.
The sharing of human neuroimaging data has great potential to accelerate the development of imaging biomarkers in neurological and psychiatric disorders; however, major obstacles remain in terms of ...how and why to share data in the Open Science context. In this Health Policy by the European Cluster for Imaging Biomarkers, we outline the current main opportunities and challenges based on the results of an online survey disseminated among senior scientists in the field. Although the scientific community fully recognises the importance of data sharing, technical, legal, and motivational aspects often prevent active adoption. Therefore, we provide practical advice on how to overcome the technical barriers. We also call for a harmonised application of the General Data Protection Regulation across EU countries. Finally, we suggest the development of a system that makes data count by recognising the generation and sharing of data as a highly valuable contribution to the community.
Starting from the failure of the RandD-patents traditional relationship, when time-series and/or within-industry dimensions are included in the empirical analysis, the present work tries to ...contribute to the empirical literature from two directions. First, it performs a Granger causality test based on the theoretical presumption of a reverse patents→RandD link as an explanation for the failure of the traditional relationship. Second, assuming the reverse patents-RandD causality, we test and interpret the lag structure of such a relationship which shows the effective patent life that firms can expect within the two Schumpeterian patterns of innovations they belong to. In the light of the effective patent life, we offer a further explanation of innovation persistence which overturns the findings of the existing literature on persistence. Reprinted by permission of Routledge, Taylor and Francis Ltd.
Abstract Background In recent years, significant efforts have been directed towards the research and development of disease-modifying therapies for dementia. These drugs focus on prodromal (mild ...cognitive impairment, MCI) and/or early stages of Alzheimer’s disease (AD). Literature evidence indicates that a considerable proportion of individuals with MCI do not progress to dementia. Identifying individuals at higher risk of developing dementia is essential for appropriate management, including the prescription of new disease-modifying therapies expected to become available in clinical practice in the near future. Methods The ongoing INTERCEPTOR study is a multicenter, longitudinal, interventional, non-therapeutic cohort study designed to enroll 500 individuals with MCI aged 50–85 years. The primary aim is to identify a biomarker or a set of biomarkers able to accurately predict the conversion from MCI to AD dementia within 3 years of follow-up. The biomarkers investigated in this study are neuropsychological tests (mini-mental state examination (MMSE) and delayed free recall), brain glucose metabolism ( 18 FFDG-PET), MRI volumetry of the hippocampus, EEG brain connectivity, cerebrospinal fluid (CSF) markers (p-tau, t-tau, Aβ1-42, Aβ1-42/1–40 ratio, Aβ1-42/p-Tau ratio) and APOE genotype. The baseline visit includes a full cognitive and neuropsychological evaluation, as well as the collection of clinical and socio-demographic information. Prognostic models will be developed using Cox regression, incorporating individual characteristics and biomarkers through stepwise selection. Model performance will be evaluated in terms of discrimination and calibration and subjected to internal validation using the bootstrapping procedure. The final model will be visually represented as a nomogram. Discussion This paper contains a detailed description of the statistical analysis plan to ensure the reproducibility and transparency of the analysis. The prognostic model developed in this study aims to identify the population with MCI at higher risk of developing AD dementia, potentially eligible for drug prescriptions. The nomogram could provide a valuable tool for clinicians for risk stratification and early treatment decisions. Trial registration ClinicalTrials.gov NCT03834402. Registered on February 8, 2019
We used 18FFDG and PET in patients with obsessive-compulsive disorder (OCD) to evaluate cerebral metabolic involvement before and after treatment with serotonin-specific reuptake inhibitors.
In 11 ...untreated, drug-free adults, regional cerebral metabolic rate for glucose (rCMRglu) was compared with that of 15 age-matched normal controls.
rCMRglu values were significantly increased in the cingulate cortex, thalamus and pallidum/putamen complex. After treatment a significant improvement in obsessive-compulsive symptoms on the Y-BOC scale (t = 3.59, P < 0.01) was associated with a significant bilateral decrease of metabolism in the whole cingulate cortex (P < 0.001). Clinical and metabolic data were significantly intercorrelated (Kendall's tau = 0.65; P < 0.01).
These findings indicate that OCD is associated with functional hyperactivity of a selected neuronal network and that treatment to reduce symptoms may have a selective neuromodulatory effect on cingulate cortex.
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