Spatial analysis of leprosy incidence and associated socioeconomic factors

OBJECTIVE: To identify clusters of the major occurrences of leprosy and their associated socioeconomic and demographic factors. METHODS: Cases of leprosy that occurred between 1998 and 2007 in Sao Jose do Rio Preto (southeastern Brazil) were geocodified and the incidence rates were calculated by census tract. A socioeconomic classification score was obtained using principal component analysis of socioeconomic variables. Thematic maps to visualize the spatial distribution of the incidence of leprosy with respect to socioeconomic levels and demographic density were constructed using geostatistics. RESULTS: While the incidence rate for the entire city was 10.4 cases per 100,000 inhabitants annually between 1998 and 2007, the incidence rates of individual census tracts were heterogeneous, with values that ranged from 0 to 26.9 cases per 100,000 inhabitants per year. Areas with a high leprosy incidence were associated with lower socioeconomic levels. There were identified clusters of leprosy cases, however there was no association between disease incidence and demographic density. There was a disparity between the places where the majority of ill people lived and the location of healthcare services. CONCLUSIONS: The spatial analysis techniques utilized identified the poorer neighborhoods of the city as the areas with the highest risk for the disease. These data show that health departments must prioritize politico-administrative policies to minimize the effects of social inequality and improve the standards of living, hygiene, and education of the population in order to reduce the incidence of leprosy.

Comparative analysis of the anterior and posterior length and deflection angle of the cranial base, in individuals with facial pattern I, II and III

Objective: This study evaluated the variations in the anterior cranial base (S-N), posterior cranial base (S-Ba) and deflection of the cranial base (SNBa) among three different facial patterns (Pattern I, II and III). Method: A sample of 60 lateral cephalometric radiographs of Brazilian Caucasian patients, both genders, between 8 and 17 years of age was selected. The sample was divided into 3 groups (Pattern I, II and III) of 20 individuals each. The inclusion criteria for each group were the ANB angle, Wits appraisal and the facial profile angle (G’.Sn.Pg’). To compare the mean values obtained from (SNBa, S-N, S-Ba) each group measures, the ANOVA test and Scheffé’s Post-Hoc test were applied. Results and Conclusions: There was no statistically significant difference for the deflection angle of the cranial base among the different facial patterns (Patterns I, II and III). There was no significant difference for the measures of the anterior and posterior cranial base between the facial Patterns I and II. The mean values for S-Ba were lower in facial Pattern III with statistically significant difference. The mean values of S-N in the facial Pattern III were also reduced, but without showing statistically significant difference. This trend of lower values in the cranial base measurements would explain the maxillary deficiency and/or mandibular prognathism features that characterize the facial Pattern III.

Polymorphous low-grade adenocarcinoma: an analysis of epidemiological studies and hints for pathologists

Abstract Background This study is an analysis of the prevalence of polymorphous low grade adenocarcinoma (PLGA) in epidemiological surveys of salivary tumors published in the English language from 1992 to 2012. Methods These surveys included studies from different researchers, countries and continents. The 57 surveys for which it was possible to calculate the percentage of PLGAs among all malignant minor salivary gland tumors (MMSGT) were included in this review. Results The statistical analyses show significant differences in the PLGA percentage by time period, country and continent in the studies included in this review. The percentage of PLGAs among MMSGTs varied among the studies, ranging from 0.0% to 46.8%. PLGA rates have varied over the period studied and have most recently increased. The frequency of reported PLGA cases also varied from 0.0% to 24.8% by the country in which the MMSGT studies were performed. The PLGA percentages also varied significantly by continent, with frequencies ranging from 3.9% in Asia to 20.0% in Oceania Conclusion Based on these results, we concluded that although the accuracy of PLGA diagnoses has improved, they remain a challenge for pathologists. To facilitate PLGA diagnoses, we have therefore made some suggestions for pathologists regarding tumors composed of single-layer strands of cells that form all of the histological patterns present in the tumor, consistency of the cytological appearance and uniformly positive CK7, vimentin and S100 immunohistochemistry, which indicate a single PLGA phenotype. Virtual slide The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1059098656858324

Morphological analysis of Mecosarthron Buquet and Xixuthrus Thomson and Reevaluation of Generic Assignment of Xixuthrus domingoensis Fisher (Coleoptera, Cerambycidae, Prioninae)

The characters defining Mecosarthron Buquet, 1840 and Xixuthrus Thomson 1864 are discussed, along with a historical review of the literature that described and classified these taxa. Through morphological examination of these genera and most of the included species, we addressed the systematic placement of Xixuthrus domingoensis Fisher, 1932 that was placed in Mecosarthron by Ivie (1985). We restore its placement in the genus Xixuthrus. The first description of the female of X. domingoensis is provided, along with comparative redescriptions of Mecosarthron gounellei (Lameere, 1903), and M. buphagus Buquet, 1840. We include a key to the species currently in Mecosarthron.

Analysis of 16S rRNA and mxaF genes reveling insights into Methylobacterium niche-specific plant association

The genus Methylobacterium comprises pink-pigmented facultative methylotrophic (PPFM) bacteria, known to be an important plant-associated bacterial group. Species of this group, described as plant-nodulating, have the dual capacity of producing cytokinin and enzymes, such as pectinase and cellulase, involved in systemic resistance induction and nitrogen fixation under specific plant environmental conditions. The aim hereby was to evaluate the phylogenetic distribution of Methylobacterium spp. isolates from different host plants. Thus, a comparative analysis between sequences from structural (16S rRNA) and functional mxaF (which codifies for a subunit of the enzyme methanol dehydrogenase) ubiquitous genes, was undertaken. Notably, some Methylobacterium spp. isolates are generalists through colonizing more than one host plant, whereas others are exclusively found in certain specific plant-species. Congruency between phylogeny and specific host inhabitance was higher in the mxaF gene than in the 16S rRNA, a possible indication of function-based selection in this niche. Therefore, in a first stage, plant colonization by Methylobacterium spp. could represent generalist behavior, possibly related to microbial competition and adaptation to a plant environment. Otherwise, niche-specific colonization is apparently impelled by the host plant.

Texture analysis of cold rolled and annealed aluminum alloy produced by twin-roll casting

A 7.4 mm thick strip of 3003 aluminum alloy produced by the industrial twin-roll casting (TRC) process was homogenized at 500 °C for 12 hours, after which it was cold rolled in two conditions: 1) to reduce the strip's thickness by 67%, and 2) to reduce it by 91%. The alloy was annealed at 400 °C for 1 hour in both conditions. The results revealed that a rotated cube texture, the {001}<110> component, predominated in the as-cast condition and was transformed into brass, copper and S type textures during the cold rolling process. There was practically no difference between the deformation textures at the two thickness reductions.

Analysis of genetic lineages and their correlation with virulence genes in enterococcus faecalis clinical isolates from root canal and systemic infections

Introduction: Enterococcus faecalis is a member of the mammalian gastrointestinal microbiota but has been considered a leading cause of hospital-acquired infections. In the oral cavity, it is commonly detected from root canals of teeth with failed endodontic treatment. However, little is known about the virulence and genetic relatedness among E. faecalis isolates from different clinical sources. This study compared the presence of enterococcal virulence factors among root canal strains and clinical isolates from hospitalized patients to identify virulent clusters of E. faecalis. Methods: Multilocus sequence typing analysis was used to determine genetic lineages of 40 E. faecalis clinical isolates from different sources. Virulence clusters were determined by evaluating capsule (cps) locus polymorphisms, pathogenicity island gene content, and antibiotic resistance genes by polymerase chain reaction. Results: The clinical isolates from hospitalized patients formed a phylogenetically separate group and were mostly grouped in the clonal complex 2, which is a known virulent cluster of E. faecalis that has caused infection outbreaks globally. The clonal complex 2 group comprised capsule-producing strains harboring multiple antibiotic resistance and pathogenicity island genes. On the other hand, the endodontic isolates were more diverse and harbored few virulence and antibiotic resistance genes. In particular, although more closely related to isolates from hospitalized patients, capsuleproducing E. faecalis strains from root canals did not carry more virulence/antibiotic genes than other endodontic isolates. Conclusions: E. faecalis isolates from endodontic infections have a genetic and virulence profile different from pathogenic clusters of hospitalized patients’ isolates, which is most likely due to niche specialization conferred mainly by variable regions in the genome.

Image analysis in the morphological and morphometric study of teeth

The subject of this doctoral dissertation concerns the definition of a new methodology for the morphological and morphometric study of fossilized human teeth, and therefore strives to provide a contribution to the reconstruction of human evolutionary history that proposes to extend to the different species of hominid fossils. Standardized investigative methodologies are lacking both regarding the orientation of teeth subject to study and in the analysis that can be carried out on these teeth once they are oriented. The opportunity to standardize a primary analysis methodology is furnished by the study of certain early Neanderthal and preneanderthal molars recovered in two caves in southern Italy [Grotta Taddeo (Taddeo Cave) and Grotta del Poggio (Poggio Cave), near Marina di Camerata, Campania]. To these we can add other molars of Neanderthal and modern man of the upper Paleolithic era, specifically scanned in the paleoanthropology laboratory of the University of Arkansas (Fayetteville, Arkansas, USA), in order to increase the paleoanthropological sample data and thereby make the final results of the analyses more significant. The new analysis methodology is rendered as follows: 1. Standardization of an orientation system for primary molars (superior and inferior), starting from a scan of a sample of 30 molars belonging to modern man (15 M1 inferior and 15 M1 superior), the definition of landmarks, the comparison of various systems and the choice of a system of orientation for each of the two dental typologies. 2. The definition of an analysis procedure that considers only the first 4 millimeters of the dental crown starting from the collar: 5 sections parallel to the plane according to which the tooth has been oriented are carried out, spaced 1 millimeter between them. The intention is to determine a method that allows for the differentiation of fossilized species even in the presence of worn teeth. 3. Results and Conclusions. The new approach to the study of teeth provides a considerable quantity of information that can better be evaluated by increasing the fossil sample data. It has been demonstrated to be a valid tool in evolutionary classification that has allowed (us) to differentiate the Neanderthal sample from that of modern man. In a particular sense the molars of Grotta Taddeo, which up until this point it has not been possible to determine with exactness their species of origin, through the present research they are classified as Neanderthal.

Computational methods for the analysis of protein structure and function

The vast majority of known proteins have not yet been experimentally characterized and little is known about their function. The design and implementation of computational tools can provide insight into the function of proteins based on their sequence, their structure, their evolutionary history and their association with other proteins. Knowledge of the three-dimensional (3D) structure of a protein can lead to a deep understanding of its mode of action and interaction, but currently the structures of <1% of sequences have been experimentally solved. For this reason, it became urgent to develop new methods that are able to computationally extract relevant information from protein sequence and structure. The starting point of my work has been the study of the properties of contacts between protein residues, since they constrain protein folding and characterize different protein structures. Prediction of residue contacts in proteins is an interesting problem whose solution may be useful in protein folding recognition and de novo design. The prediction of these contacts requires the study of the protein inter-residue distances related to the specific type of amino acid pair that are encoded in the so-called contact map. An interesting new way of analyzing those structures came out when network studies were introduced, with pivotal papers demonstrating that protein contact networks also exhibit small-world behavior. In order to highlight constraints for the prediction of protein contact maps and for applications in the field of protein structure prediction and/or reconstruction from experimentally determined contact maps, I studied to which extent the characteristic path length and clustering coefficient of the protein contacts network are values that reveal characteristic features of protein contact maps. Provided that residue contacts are known for a protein sequence, the major features of its 3D structure could be deduced by combining this knowledge with correctly predicted motifs of secondary structure. In the second part of my work I focused on a particular protein structural motif, the coiled-coil, known to mediate a variety of fundamental biological interactions. Coiled-coils are found in a variety of structural forms and in a wide range of proteins including, for example, small units such as leucine zippers that drive the dimerization of many transcription factors or more complex structures such as the family of viral proteins responsible for virus-host membrane fusion. The coiled-coil structural motif is estimated to account for 5-10% of the protein sequences in the various genomes. Given their biological importance, in my work I introduced a Hidden Markov Model (HMM) that exploits the evolutionary information derived from multiple sequence alignments, to predict coiled-coil regions and to discriminate coiled-coil sequences. The results indicate that the new HMM outperforms all the existing programs and can be adopted for the coiled-coil prediction and for large-scale genome annotation. Genome annotation is a key issue in modern computational biology, being the starting point towards the understanding of the complex processes involved in biological networks. The rapid growth in the number of protein sequences and structures available poses new fundamental problems that still deserve an interpretation. Nevertheless, these data are at the basis of the design of new strategies for tackling problems such as the prediction of protein structure and function. Experimental determination of the functions of all these proteins would be a hugely time-consuming and costly task and, in most instances, has not been carried out. As an example, currently, approximately only 20% of annotated proteins in the Homo sapiens genome have been experimentally characterized. A commonly adopted procedure for annotating protein sequences relies on the "inheritance through homology" based on the notion that similar sequences share similar functions and structures. This procedure consists in the assignment of sequences to a specific group of functionally related sequences which had been grouped through clustering techniques. The clustering procedure is based on suitable similarity rules, since predicting protein structure and function from sequence largely depends on the value of sequence identity. However, additional levels of complexity are due to multi-domain proteins, to proteins that share common domains but that do not necessarily share the same function, to the finding that different combinations of shared domains can lead to different biological roles. In the last part of this study I developed and validate a system that contributes to sequence annotation by taking advantage of a validated transfer through inheritance procedure of the molecular functions and of the structural templates. After a cross-genome comparison with the BLAST program, clusters were built on the basis of two stringent constraints on sequence identity and coverage of the alignment. The adopted measure explicity answers to the problem of multi-domain proteins annotation and allows a fine grain division of the whole set of proteomes used, that ensures cluster homogeneity in terms of sequence length. A high level of coverage of structure templates on the length of protein sequences within clusters ensures that multi-domain proteins when present can be templates for sequences of similar length. This annotation procedure includes the possibility of reliably transferring statistically validated functions and structures to sequences considering information available in the present data bases of molecular functions and structures.

Parametric Sensitivity Analysis of the Most Recent Computational Models of Rabbit Cardiac Pacemaking

The cellular basis of cardiac pacemaking activity, and specifically the quantitative contributions of particular mechanisms, is still debated. Reliable computational models of sinoatrial nodal (SAN) cells may provide mechanistic insights, but competing models are built from different data sets and with different underlying assumptions. To understand quantitative differences between alternative models, we performed thorough parameter sensitivity analyses of the SAN models of Maltsev & Lakatta (2009) and Severi et al (2012). Model parameters were randomized to generate a population of cell models with different properties, simulations performed with each set of random parameters generated 14 quantitative outputs that characterized cellular activity, and regression methods were used to analyze the population behavior. Clear differences between the two models were observed at every step of the analysis. Specifically: (1) SR Ca2+ pump activity had a greater effect on SAN cell cycle length (CL) in the Maltsev model; (2) conversely, parameters describing the funny current (If) had a greater effect on CL in the Severi model; (3) changes in rapid delayed rectifier conductance (GKr) had opposite effects on action potential amplitude in the two models; (4) within the population, a greater percentage of model cells failed to exhibit action potentials in the Maltsev model (27%) compared with the Severi model (7%), implying greater robustness in the latter; (5) confirming this initial impression, bifurcation analyses indicated that smaller relative changes in GKr or Na+-K+ pump activity led to failed action potentials in the Maltsev model. Overall, the results suggest experimental tests that can distinguish between models and alternative hypotheses, and the analysis offers strategies for developing anti-arrhythmic pharmaceuticals by predicting their effect on the pacemaking activity.

Neurolinguistic analysis: aspects of language and speech deviations in Palestinian Arabic aphasics

The characteristics of aphasics’ speech in various languages have been the core of numerous studies, but Arabic in general, and Palestinian Arabic in particular, is still a virgin field in this respect. However, it is of vital importance to have a clear picture of the specific aspects of Palestinian Arabic that might be affected in the speech of aphasics in order to establish screening, diagnosis and therapy programs based on a clinical linguistic database. Hence the central questions of this study are what are the main neurolinguistic features of the Palestinian aphasics’ speech at the phonetic-acoustic level and to what extent are the results similar or not to those obtained from other languages. In general, this study is a survey of the most prominent features of Palestinian Broca’s aphasics’ speech. The main acoustic parameters of vowels and consonants are analysed such as vowel duration, formant frequency, Voice Onset Time (VOT), intensity and frication duration. The deviant patterns among the Broca’s aphasics are displayed and compared with those of normal speakers. The nature of deficit, whether phonetic or phonological, is also discussed. Moreover, the coarticulatory characteristics and some prosodic patterns of Broca’s aphasics are addressed. Samples were collected from six Broca’s aphasics from the same local region. The acoustic analysis conducted on a range of consonant and vowel parameters displayed differences between the speech patterns of Broca’s aphasics and normal speakers. For example, impairments in voicing contrast between the voiced and voiceless stops were found in Broca’s aphasics. This feature does not exist for the fricatives produced by the Palestinian Broca’s aphasics and hence deviates from data obtained for aphasics’ speech from other languages. The Palestinian Broca’s aphasics displayed particular problems with the emphatic sounds. They exhibited deviant coarticulation patterns, another feature that is inconsistent with data obtained from studies from other languages. However, several other findings are in accordance with those reported from various other languages such as impairments in the VOT. The results are in accordance with the suggestions that speech production deficits in Broca’s aphasics are not related to phoneme selection but rather to articulatory implementation and some speech output impairments are related to timing and planning deficits.

Genetic analysis of tumour initiation and progression in a Drosophila model of epithelial cancer

Neoplastic overgrowth depends on the cooperation of several mutations ultimately leading to major rearrangements in cellular behaviour. The molecular crosstalk occurring between precancerous and normal cells strongly influences the early steps of the tumourigenic process as well as later stages of the disease. Precancerous cells are often removed by cell death from normal tissues but the mechanisms responsible for such fundamental safeguard processes remain in part elusive. To gain insight into these phenomena I took advantage of the clonal analysis methods available in Drosophila for studying the phenotypes due to loss of function of the neoplastic tumour suppressor lethal giant larvae (lgl). I found that lgl mutant cells growing in wild-type imaginal wing discs are subject to the phenomenon of cell competition and are eliminated by JNK-dependent cell death because they express very low levels of dMyc oncoprotein compared to those in the surrounding tissue. Indeed, in non-competitive backgrounds lgl mutant clones are able to overgrow and upregulate dMyc, overwhelming the neighbouring tissue and forming tumourous masses that display several cancer hallmarks. These phenotypes are completely abolished by reducing dMyc abundance within mutant cells while increasing it in lgl clones growing in a competitive context re-establishes their tumourigenic potential. Similarly, the neoplastic growth observed upon the oncogenic cooperation between lgl mutation and activated Ras/Raf/MAPK signalling was found to be characterised by and dependent on the ability of cancerous cells to upregulate dMyc with respect to the adjacent normal tissue, through both transcriptional and post-transcriptional mechanisms, thereby confirming its key role in lgl-induced tumourigenesis. These results provide first evidence that the dMyc oncoprotein is required in lgl mutant tissue to promote invasive overgrowth in developing and adult epithelial tissues and that dMyc abundance inside versus outside lgl mutant clones plays a key role in driving neoplastic overgrowth.

An interdisciplinary analysis of obesity: theory and empirical evidence

The dissertation is structured in three parts. The first part compares US and EU agricultural policies since the end of WWII. There is not enough evidence for claiming that agricultural support has a negative impact on obesity trends. I discuss the possibility of an exchange in best practices to fight obesity. There are relevant economic, societal and legal differences between the US and the EU. However, partnerships against obesity are welcomed. The second part presents a socio-ecological model of the determinants of obesity. I employ an interdisciplinary model because it captures the simultaneous influence of several variables. Obesity is an interaction of pre-birth, primary and secondary socialization factors. To test the significance of each factor, I use data from the National Longitudinal Survey of Adolescent Health. I compare the average body mass index across different populations. Differences in means are statistically significant. In the last part I use the National Survey of Children Health. I analyze the effect that family characteristics, built environment, cultural norms and individual factors have on the body mass index (BMI). I use Ordered Probit models and I calculate the marginal effects. I use State and ethnicity fixed effects to control for unobserved heterogeneity. I find that southern US States tend have on average a higher probability of being obese. On the ethnicity side, White Americans have a lower BMI respect to Black Americans, Hispanics and American Indians Native Islanders; being Asian is associated with a lower probability of being obese. In neighborhoods where trust level and safety perception are higher, children are less overweight and obese. Similar results are shown for higher level of parental income and education. Breastfeeding has a negative impact. Higher values of measures of behavioral disorders have a positive and significant impact on obesity, as predicted by the theory.

13C NMR of a single molecule magnet: analysis of pseudocontact shifts and residual dipolar couplings

Paramagnetic triple decker complexes of lanthanides are promising Single Molecule Magnets (SMMs), with many potential uses. Some of them show preferable relaxation behavior, which enables the recording of well resolved NMR spectra. These axially symmetric complexes are also strongly magnetically anisotropic, and this property can be described with the axial component of the magnetic susceptibility tensor, χa. For triple decker complexes with phthalocyanine based ligands, the Fermi˗contact contribution is small. Hence, together with the axial symmetry, the experimental chemical shifts in 1H and 13C NMR spectra can be modeled easily by considering pseudocontact and orbital shifts alone. This results in the determination of the χa value, which is also responsible for molecular alignment and consequently for the observation of residual dipolar couplings (RDCs). A detailed analysis of the experimental 1H-13C and 1H-1H couplings revealed that contributions from RDCs (positive and negative) and from dynamic frequency shifts (negative for all observed couplings) have to be considered. Whilst the pseudocontact shifts depend on the average positions of 1H and 13C nuclei relative to the lanthanide ions, the RDCs are related to the mobility of nuclei they correspond to. This phenomenon allows for the measurement of the internal mobility of the various groups in the SMMs.

New regularization method for EXAFS analysis: Application to uranium and plutonium sorption onto kaolinite

Die Röntgenabsorptionsspektroskopie (Extended X-ray absorption fine structure (EXAFS) spectroscopy) ist eine wichtige Methode zur Speziation von Schwermetallen in einem weiten Bereich von umweltrelevanten Systemen. Um Strukturparameter wie Koordinationszahl, Atomabstand und Debye-Waller Faktoren für die nächsten Nachbarn eines absorbierenden Atoms zu bestimmen, ist es für experimentelle EXAFS-Spektren üblich, unter Verwendung von Modellstrukturen einen „Least-Squares-Fit“ durchzuführen. Oft können verschiedene Modellstrukturen mit völlig unterschiedlicher chemischer Bedeutung die experimentellen EXAFS-Daten gleich gut beschreiben. Als gute Alternative zum konventionellen Kurven-Fit bietet sich das modifizierte Tikhonov-Regularisationsverfahren an. Ergänzend zur Tikhonov-Standardvariationsmethode enthält der in dieser Arbeit vorgestellte Algorithmus zwei weitere Schritte, nämlich die Anwendung des „Method of Separating Functionals“ und ein Iterationsverfahren mit Filtration im realen Raum. Um das modifizierte Tikhonov-Regularisationsverfahren zu testen und zu bestätigen wurden sowohl simulierte als auch experimentell gemessene EXAFS-Spektren einer kristallinen U(VI)-Verbindung mit bekannter Struktur, nämlich Soddyit (UO2)2SiO4 x 2H2O, untersucht. Die Leistungsfähigkeit dieser neuen Methode zur Auswertung von EXAFS-Spektren wird durch ihre Anwendung auf die Analyse von Proben mit unbekannter Struktur gezeigt, wie sie bei der Sorption von U(VI) bzw. von Pu(III)/Pu(IV) an Kaolinit auftreten. Ziel der Dissertation war es, die immer noch nicht voll ausgeschöpften Möglichkeiten des modifizierten Tikhonov-Regularisationsverfahrens für die Auswertung von EXAFS-Spektren aufzuzeigen. Die Ergebnisse lassen sich in zwei Kategorien einteilen. Die erste beinhaltet die Entwicklung des Tikhonov-Regularisationsverfahrens für die Analyse von EXAFS-Spektren von Mehrkomponentensystemen, insbesondere die Wahl bestimmter Regularisationsparameter und den Einfluss von Mehrfachstreuung, experimentell bedingtem Rauschen, etc. auf die Strukturparameter. Der zweite Teil beinhaltet die Speziation von sorbiertem U(VI) und Pu(III)/Pu(IV) an Kaolinit, basierend auf experimentellen EXAFS-Spektren, die mit Hilfe des modifizierten Tikhonov-Regularisationsverfahren ausgewertet und mit Hilfe konventioneller EXAFS-Analyse durch „Least-Squares-Fit“ bestätigt wurden.