Genetic Architecture and Molecular,Imaging and Prodromic Markers in Dementia with Lewy Bodies: State of the Art,Opportunities and Challenges

Dementia with Lewy bodies (DLB) is one of the most common causes of dementia and belongs to the group of α-synucleinopathies. Due to its clinical overlap with other neurodegenerative disorders and its high clinical heterogeneity, the clinical differential diagnosis of DLB from other similar disorders is often difficult and it is frequently underdiagnosed. Moreover, its genetic etiology has been studied only recently due to the unavailability of large cohorts with a certain diagnosis and shows genetic heterogeneity with a rare contribution of pathogenic mutations and relatively common risk factors. The rapid increase in the reported cases of DLB highlights the need for an easy, efficient and accurate diagnosis of the disease in its initial stages in order to halt or delay the progression. The currently used diagnostic methods proposed by the International DLB consortium rely on a list of criteria that comprises both clinical observations and the use of biomarkers. Herein, we summarize the up-to-now reported knowledge on the genetic architecture of DLB and discuss the use of prodromal biomarkers as well as recent promising candidates from alternative body fluids and new imaging techniques.     

HMAP– A temporal data model managing intervals with different granularities and indeterminacy from natural language sentences

The granularity of given temporal information is the level of abstraction at which information is expressed. Different units of measure allow one to represent different granularities. Indeterminacy is often present in temporal information given at different granularities: temporal indeterminacy is related to incomplete knowledge of when the considered fact happened. Focusing on temporal databases, different granularities and indeterminacy have to be considered in expressing valid time, i.e., the time at which the information is true in the modeled reality. In this paper, we propose HMAP (The term is the transliteration of an ancient Greek poetical word meaning “day”.), a temporal data model extending the capability of defining valid times with different granularity and/or with indeterminacy. In HMAP, absolute intervals are explicitly represented by their start,end, and duration: in this way, we can represent valid times as “in December 1998 for five hours”, “from July 1995, for 15 days”, “from March 1997 to October 15, 1997, between 6 and 6:30 p.m.”. HMAP is based on a three-valued logic, for managing uncertainty in temporal relationships. Formulas involving different temporal relationships between intervals, instants, and durations can be defined, allowing one to query the database with different granularities, not necessarily related to that of data. In this paper, we also discuss the complexity of algorithms, allowing us to evaluate HMAP formulas, and show that the formulas can be expressed as constraint networks falling into the class of simple temporal problems, which can be solved in polynomial time. Received 6 August 1998 / Accepted 13 July 2000 Published online: 13 February 2001     

TEODOLINDA. A communication architecture for hospital information systems

This paper is focused on a system for the release and distribution of messages and services among hospital units, which extends hospital information systems features in the field of communication and supports hospital organisation to fulfil healthcare commitments.     

Picosecond GaAs photoconductors on silicon substrates for localintegration with silicon devices and circuits

A fabrication procedure for local integration of GaAs photoconductive devices with processed silicon circuits is discussed. The process allows isolated regions of GaAs to be epitaxially grown by MBE at temperatures which are compatible with already processed silicon circuits with first-level metallization. GaAs photoconductors with 15-μm gap lengths fabricated on silicon substrates have exhibited >16-mA sampling-oscilloscope-limited responses, with electrical pulse widths less than 20 ps as determined by autocorrelation measurements     

Guar gum methyl ethers. Part I. Synthesis and macromolecular characterization

Guar gum (GG) has been partially methyl-etherified under heterogeneous reaction conditions. The resulting products, (methyl ether guar: MG) with different degrees of substitution, have been characterized by means of viscosity, ¹H NMR, and FTIR measurements. The introduction of methoxyl groups along the polysaccharidic chains reduces the hydrogen bonding sites on the guar backbone reducing primarely the extent of hydrogen bonding between guar macromolecules, hence their aggregation tendency. A comparative analysis of Mark–Houwink–Sakurada parameters and of the characteristic ratio (C_∞) of GG and MG samples in aqueous solution has been carried out using the Burchard–Stockmayer–Fixman method for flexible and semiflexible chains. The MG chains exhibit more flexibility than those of native guar gum which is traceable to a disruption of intrachain hydrogen bonds.     

An anion-permeable polymeric coating for the protection of a semiconductor photoelectrode against decomposition

An anion-permeable polymeric film has been applied to the surfaces of cadmium sulfide photoanodes to decrease the rate of electrode corrosion which is observed during the photoelectro-chemical oxidation of aqueous species. Although the rate of surface corrosion was reduced, film adhesion problems were observed.     

The imaginary,the computer,artificial intelligence: A cultural anthropological approach

The role of the cultural anthropologist in studying the results of information technology and artificial intelligence should be to contribute and reaffirm a sense of life which considers the human being in his or her totality, and to recognize the role of diversity and the imaginary. Technical revolutions have also proved to be cultural revolutions. The skills required by one culture, the identification and creation of problems and the solutions are interrelated. These interrelationships are worked out in a cultural context endowed with its own experiences, knowledge and needs which define and make it different from other societies. The advanced technologies require new competences and new skills. This paper examines imaginary from two different viewpoints: (a) the imaginary aspect of body-mind relations, influenced by research into artificial intelligence and its prospects for the future; and (b) the roles and forms assumed by the imaginary in human-computer relations.     

Detection of Germline Variants in 450 Breast/Ovarian Cancer Families with a Multi-Gene Panel Including Coding and Regulatory Regions

With the progress of sequencing technologies, an ever-increasing number of variants of unknown functional and clinical significance (VUS) have been identified in both coding and non-coding regions of the main Breast Cancer (BC) predisposition genes. The aim of this study is to identify a mutational profile of coding and intron-exon junction regions of 12 moderate penetrance genes (ATM, BRIP1, CDH1, CHEK2, NBN, PALB2, PTEN, RAD50, RAD51C, RAD51D, STK11, TP53) in a cohort of 450 Italian patients with Hereditary Breast/Ovarian Cancer Syndrome, wild type for germline mutation in BRCA1/2 genes. The analysis was extended to 5′UTR and 3′UTR of all the genes listed above and to the BRCA1 and BRCA2 known regulatory regions in a subset of 120 patients. The screening was performed through NGS target resequencing on the Illumina platform MiSeq. 8.7% of the patients analyzed is carriers of class 5/4 coding variants in the ATM (3.6%), BRIP1 (1.6%), CHEK2 (1.8%), PALB2 (0.7%), RAD51C (0.4%), RAD51D (0.4%), and TP53 (0.2%) genes, while variants of uncertain pathological significance (VUSs)/class 3 were identified in 9.1% of the samples. In intron-exon junctions and in regulatory regions, variants were detected respectively in 5.1% and in 32.5% of the cases analyzed. The average age of disease onset of 44.4 in non-coding variant carriers is absolutely similar to the average age of disease onset in coding variant carriers for each proband’s group with the same cancer type. Furthermore, there is not a statistically significant difference in the proportion of cases with a tumor onset under age of 40 between the two groups, but the presence of multiple non-coding variants in the same patient may affect the aggressiveness of the tumor and it is worth underlining that 25% of patients with an aggressive tumor are carriers of a PTEN 3′UTR-variant. This data provides initial information on how important it might be to extend mutational screening to the regulatory regions in clinical practice.     

Influence of sketch types on distributed design team work

Product development is a collaborative activity more often than ever carried out by distributed design teams. It is critical to determine how sketches are used in such environments in order to improve the design process. Sketches produced by students participating in a collaborative design project of three European Universities are classified according to the intention of the designer when producing a sketch, the level of detail shown in the sketch and the phase when the sketch was produced. The adapted classification system used in this paper helps to analyse type of sketches with most variety of ideas. Furthermore, this paper reviews which type of sketches offers the most potential to be further developed. Results show that persuasive sketches offer the broadest range of ideas since they are produced as a combination of ideas from brainstorming sessions. Shared sketches help to achieve consensus in decision-making since the sketches are most likely to be produced by the entire group rather than individually.