Digital mediation in the transition from a discrete model to large-scale archaeological survey: Survey of the archaeological site of Merida

Trabajo presentado a la 38th Annual Conference on Computer Applications and Quantitative Methods in Archaeology (CAA), celebrada en Granada (España) en abril de 2010.Architectural survey applied to the archaeological research. The research applied to the archaeological site of Merida, trys to define a methodological and practical“Protocol“ for the survey applied to large-scale archaeological sites. The digital way for the surveying and survey.Peer Reviewe

Protective personality traits: High openness and low neuroticism linked to better memory in multiple sclerosis

Memory impairment in multiple sclerosis (MS) is common, although few risk/protective factors are known

Tract-specific white matter correlates of fatigue and cognitive impairment in benign multiple sclerosis

Background: Although benign multiple sclerosis (BMS) is traditionally defined by the presence of mild motor involvement decades after disease onset, symptoms of fatigue and cognitive impairment are very common. Objective: To investigate the association between micro-structural damage in the anterior thalamic (AT) tracts and in the corpus callosum (CC), as measured by diffusion tensor imaging (DTI) tractography, and fatigue and cognitive deficits. Methods: DTI data were acquired from 26 BMS patients and 24 sex- and age-matched healthy controls. Results: General and mental fatigue scores were significantly impaired in patients compared with controls (p≤0.05 for both) and 38% of patients resulted cognitively impaired. Mean diffusivity (MD) of the AT and CC tracts was significantly higher and fractional anisotropy (FA) was lower in patients compared with controls (p<0.001 for all). Fatigue was associated with increased MD (p=0.01) of the AT tracts whereas deficit of executive functions and verbal learning were associated with decreased FA in the body (p=0.004) and genu (p=0.008) of the CC. Deficits in processing speed and attention were associated with the T2 lesion volume of the AT tracts (p<0.01 for all). Discussion: These findings suggest that fatigue and cognitive impairment are quite frequent in BMS patients and are, at least in part, related to micro-structural damage and T2LV of WM tracts connecting the brain cortical and sub-cortical regions of the two hemispheres

Greasing the protein biosynthesis machinery of photoreceptor neurons: Role for postprenylation processing of proteins

Daily phagocytosis of outer segments (OS) places extraordinary demands on protein biosynthesis and trafficking in photoreceptor neurons. While the members and roles of the phototransduction pathway in the OS are well characterized, details about protein trafficking are just beginning to emerge. Phosphodiesterase6 (PDE6), the effector enzyme in phototransduction cascade, serves as an example of the steps multimeric proteins must pass through to achieve their functional state in the OS. Genetic model systems have recently provided snapshots of various steps in the pathway, as experimental difficulties such as an inability to maintain ciliated photoreceptor outer segments or express functional PDE6 holoenzyme in vitro necessitate in vivo studies. We will highlight the significant findings, their implications to blinding diseases, as well as discuss the gaps requiring further investigation

A composite measure to explore visual disability in primary progressive multiple sclerosis

Background: Optical coherence tomography (OCT) and magnetic resonance imaging (MRI) can provide complementary information on visual system damage in multiple sclerosis (MS). Objectives: The objective of this paper is to determine whether a composite OCT/MRI score, reflecting cumulative damage along the entire visual pathway, can predict visual deficits in primary progressive multiple sclerosis (PPMS). Methods: Twenty-five PPMS patients and 20 age-matched controls underwent neuro-ophthalmologic evaluation, spectral-domain OCT, and 3T brain MRI. Differences between groups were assessed by univariate general linear model and principal component analysis (PCA) grouped instrumental variables into main components. Linear regression analysis was used to assess the relationship between low-contrast visual acuity (LCVA), OCT/MRI-derived metrics and PCA-derived composite scores. Results: PCA identified four main components explaining 80.69% of data variance. Considering each variable independently, LCVA 1.25% was significantly predicted by ganglion cell-inner plexiform layer (GCIPL) thickness, thalamic volume and optic radiation (OR) lesion volume (adjusted R2 0.328, p = 0.00004; adjusted R2 0.187, p = 0.002 and adjusted R2 0.180, p = 0.002). The PCA composite score of global visual pathway damage independently predicted both LCVA 1.25% (adjusted R2 value 0.361, p = 0.00001) and LCVA 2.50% (adjusted R2 value 0.323, p = 0.00003). Conclusion: A multiparametric score represents a more comprehensive and effective tool to explain visual disability than a single instrumental metric in PPMS

Clinical translation of [18F]ICMT-11 for measuring chemotherapy-induced caspase 3/7 activation in breast and lung cancer

Background: Effective anticancer therapy is thought to involve induction of tumour cell death through apoptosis and/or necrosis. [18F]ICMT-11, an isatin sulfonamide caspase-3/7-specific radiotracer, has been developed for PET imaging and shown to have favourable dosimetry, safety, and biodistribution. We report the translation of [18F]ICMT-11 PET to measure chemotherapy-induced caspase-3/7 activation in breast and lung cancer patients receiving first-line therapy. Results: Breast tumour SUVmax of [18F]ICMT-11 was low at baseline and unchanged following therapy. Measurement of M30/M60 cytokeratin-18 cleavage products showed that therapy was predominantly not apoptosis in nature. While increases in caspase-3 staining on breast histology were seen, post-treatment caspase-3 positivity values were only approximately 1%; this low level of caspase-3 could have limited sensitive detection by [18F]ICMT-11-PET. Fourteen out of 15 breast cancer patients responded to first–line chemotherapy (complete or partial response); one patient had stable disease. Four patients showed increases in regions of high tumour [18F]ICMT-11 intensity on voxel-wise analysis of tumour data (classed as PADS); response was not exclusive to patients with this phenotype. In patients with lung cancer, multi-parametric [18F]ICMT-11 PET and MRI (diffusion-weighted- and dynamic contrast enhanced-MRI) showed that PET changes were concordant with cell death in the absence of significant perfusion changes. Conclusion: This study highlights the potential use of [18F]ICMT-11 PET as a promising candidate for non-invasive imaging of caspase3/7 activation, and the difficulties encountered in assessing early-treatment responses. We summarize that tumour response could occur in the absence of predominant chemotherapy-induced caspase-3/7 activation measured non-invasively across entire tumour lesions in patients with breast and lung cancer

A Better Characterization of Spinal Cord Damage in Multiple Sclerosis: A Diffusional Kurtosis Imaging Study

BACKGROUND AND PURPOSE: The spinal cord is a site of predilection for MS lesions. While diffusion tensor imaging is useful for the study of anisotropic systems such as WM tracts, it is of more limited utility in tissues with more isotropic microstructures (on the length scales studied with diffusion MR imaging) such as gray matter. In contrast, diffusional kurtosis imaging, which measures both Gaussian and non-Gaussian properties of water diffusion, provides more biomarkers of both anisotropic and isotropic structural changes. The aim of this study was to investigate the cervical spinal cord of patients with MS and to characterize lesional and normal-appearing gray matter and WM damage by using diffusional kurtosis imaging. MATERIALS AND METHODS: Nineteen patients (13 women, mean age = 41.1 ± 10.7 years) and 16 controls (7 women, mean age = 35.6 ± 11.2-years) underwent MR imaging of the cervical spinal cord on a 3T scanner (T2 TSE, T1 magnetization-prepared rapid acquisition of gradient echo, diffusional kurtosis imaging, T2 fast low-angle shot). Fractional anisotropy, mean diffusivity, and mean kurtosis were measured on the whole cord and in normal-appearing gray matter and WM. RESULTS: Spinal cord T2-hyperintense lesions were identified in 18 patients. Whole spinal cord fractional anisotropy and mean kurtosis ( P = .0009, P = .003), WM fractional anisotropy ( P = .01), and gray matter mean kurtosis ( P = .006) were significantly decreased, and whole spinal cord mean diffusivity ( P = .009) was increased in patients compared with controls. Mean spinal cord area was significantly lower in patients ( P = .04). CONCLUSIONS: Diffusional kurtosis imaging of the spinal cord can provide a more comprehensive characterization of lesions and normal-appearing WM and gray matter damage in patients with MS. Diffusional kurtosis imaging can provide additional and complementary information to DTI on spinal cord pathology

An MRI evaluation of grey matter damage in African Americans with MS

Objective: Multiple sclerosis (MS) is less prevalent in African Americans (AAs) than Caucasians (CAs) but in the former the disease course tends to be more severe. In order to clarify the MRI correlates of disease severity in AAs, we performed a multimodal brain MRI study to comprehensively assess the extent of grey matter (GM) damage and the degree of functional adaptation to structural damage in AAs with MS. Methods: In this cross-sectional study, we characterized GM damage in terms of focal lesions and volume loss and functional adaptation during the execution of a simple motor task on a sample of 20 AAs and 20 CAs with MS and 20 healthy controls (CTRLs). Results: In AAs, we observed a wider range of EDSS scores than CAs, with multisystem involvement being more likely in AAs (p < 0.01). While no significant differences were detected in lesion loads and global brain volumes, AAs showed regional atrophy in the posterior lobules of cerebellum, temporo-occipital and frontal regions in comparison with CAs (p < 0.01), with cerebellar atrophy being the best metric in differentiating AAs from CAs (p = 0.007, AUC = 0.96 and p = 0.005, AUC = 0.96, respectively for right and left cerebellar clusters). In AAs, the functional analysis of cortical activations showed an increase in task-related activation of areas involved in high level processing and a decreased activation in the medial prefrontal cortex compared to CAs. Interpretation: In our study, the direct comparison of AAs and CAs points to cerebellar atrophy as the main difference between subgroups

Phase-sensitive inversion-recovery MRI improves longitudinal cortical lesion detection in progressive MS

Previous studies comparing phase sensitive inversion recovery (PSIR) to double inversion recovery (DIR) have demonstrated that use of PSIR improves cross-sectional in vivo detection of cortical lesions (CL) in multiple sclerosis. We studied the utility of PSIR in detection/characterization of accrual of CL over time in a 1-year longitudinal study in primary progressive multiple sclerosis (PPMS) compared to DIR. PSIR and DIR images were acquired with 3T magnetic resonance imaging (MRI) in 25 patients with PPMS and 19 healthy controls at baseline, and after 1 year in 20 patients with PPMS. CL were classified as intracortical, leu-cocortical or juxtacortical. Lesion counts and volumes were calculated for both time points from both sequences and compared. Correlations with measures of physical and cognitive disability were determined as well as new CL counts and volumes. Compared to DIR, PSIR led to detection of a higher number of CL involving a larger proportion of patients with PPMS both cross-sectionally (p = 0.006, 88%) and longitudinally (p = 0.007, 95%), and led to the reclassification of a third of CL seen on DIR at each time point. Interestingly, PSIR was more sensitive to new CL accumulation over time compared to DIR. PSIR is a promising technique to monitor cortical damage and disease progression in patients with PPMS over a short-term follow-up

Mass spectrometry: from imaging to metabolic networks

A deeper understanding of inter-tumorand intra-tumorheterogeneity is a critical factor for the advancement of next generation strategies against cancer. Under the hypothesis that heterogeneous progression of tumorsis mirrored by their metabolic heterogeneity, detection of biochemical mechanisms responsible of the local metabolism becomes crucial.We show that network analysis of co-localized ions from mass spectrometry imaging data provides a detailed chemo-spatial insightinto the metabolic heterogeneity of tumor. Furthermore, module preservation analysis between colorectal cancer patients with and without metastatic recurrence suggests hypotheses on the nature of the different local metabolic pathways