Point pattern analysis: an application to the loyalty networks of chain-stores

At the 41th congress of ERSA., Staufer-Steinnocher (2001) proved that kernel density estimation, a technique of spatial analysis belonging to the point pattern methods, can be usefully applied to geomarketing. Following this point of view, the aim of this paper is to show that other point pattern techniques (center-grahic statistics, global and local autocorrelation indexes, clustering methods, 'nearest neighbour index', 'Ripley's K statistic', etc.) are able to suggest important considerations in marketing researches, making explicit the "geographical knowledge" embedded in available informations. Namely this argument is demonstrated, analysing spatial distributions of big stores chained in a promotional network, finalised to improve fidelity in the consumers.

High Doses of Ascorbate Kill Y79 Retinoblastoma Cells In vitro

Objectives: To tests the sensitivity of Y79 retinoblastoma cell lines to high doses of ascorbate, in vitro, and compare its effects with those of some chemotherapeutic agents routinely employed in the treatment of retinoblastoma. Methods: Y79 retinoblastoma cells have been exposed to increasing doses of either sodium ascorbate (SA) or Melphalan (MEL), to define a dose-response curve around the peak plasma concentrations reached by both chemicals when administered according to the existing therapeutic procedures and protocols. The assessment of cell number and viability was performed, before and after exposure, with both the manual (Trypan Blue Exclusion Test) and automated (flow cytometry) methods. Fluorescence microscopy and direct observation of cells in culture, with inverted microscope, were also performed. Results: Y79 cells are highly sensitive to the cytotoxic effect of SA, with cell viability reduced of over 90% in some experiments. As reported in the literature, this effect is directly cytotoxic and most probably mediated by acute oxidative stress on different cellular components. The same does not apply to Melphalan which, at the doses commonly used for therapeutic purposes, did not show any significant effect on cell viability, in vitro. Conclusion: To our knowledge, this is the first report showing that high doses of SA can actively kill retinoblastoma cells in vitro. While it is not surprising for SA, to show direct cytotoxic effect on tumor cells, the data reported herein represent the first evidence in favor of the possible clinical use of high doses of intravenous SA, to treat children affected by retinoblastoma. Given the many advantages of SA over the chemotherapeutic agents commonly employed to treat cancer (including its almost total absence of toxic or side effects, and its exclusive specificity for cancer cells), it is reasonable to assume, from the data reported herein, that the high doses of intravenous ascorbate, have the potential to represent a real revolution in the treatment of retinoblastoma

Case report: Childhood epilepsy and borderline intellectual functioning hiding an AADC deficiency disorder associated with compound heterozygous DDC gene pathogenic variants

Aromatic L-amino acid decarboxylase (AADC) deficiency is a rare autosomal recessive neurometabolic disorder leading to severe combined serotonin, dopamine, norepinephrine, and epinephrine deficiency. We report on a female patient with borderline functioning and sporadic clear-cut focal to bilateral seizures from age 10 years. A neuropsychological assessment highlighted a mild impairment in executive functions, affecting attention span and visual-spatial abilities. Following the diagnosis of epilepsy with a presumed genetic etiology, we applied a diagnostic approach inclusive of a next-generation sequencing (NGS) gene panel, which uncovered two variants in trans in the DOPA decarboxylase (DDC) gene underlying an AADC deficiency. This compound heterozygous genotype was associated with a mild reduction of homovanillic acid, a low level of the norepinephrine catabolite, and a significant reduction of 5-hydroxyindoleacetic acid in cerebrospinal fluid. Remarkably, 3-O-methyldopa (3-OMD) and 5-hydroxytryptophan were instead increased. During the genetically guided re-evaluation process, some mild signs of dysautonomic dysfunction (nasal congestion, abnormal sweating, hypotension and fainting, excessive sleepiness, small hands and feet, and increased levels of prolactin, tiredness, and fatigue), more typical of AADC deficiency, were evaluated with new insight. Of the two AADC variants, the R347Q has already been characterized as a loss-of-function with severe catalytic impairments, while the novel L391P variant has been predicted to have a less severe impact. Bioinformatic analyses suggest that the amino acid substitution may affect affinity for the PLP coenzyme. Thus, the genotype corresponds to a phenotype with mild and late-onset symptoms, of which seizures were the clinical sign, leading to medical attention. This case report expands the spectrum of AADC deficiency phenotypes to encompass a less-disabling clinical condition including borderline cognitive functioning, drug-responsive epilepsy, and mild autonomic dysfunction

Position-based dynamics simulator of vessel deformations for path planning in robotic endovascular catheterization

A major challenge during autonomous navigation in endovascular interventions is the complexity of operating in a deformable but constrained workspace with an instrument. Simulation of deformations for it can provide a cost-effective training platform for path planning. Aim of this study is to develop a realistic, auto-adaptive, and visually plausible simulator to predict vessels’ global deformation induced by the robotic catheter’s contact and cyclic heartbeat motion. Based on a Position-based Dynamics (PBD) approach for vessel modeling, Particle Swarm Optimization (PSO) algorithm is employed for an auto-adaptive calibration of PBD deformation parameters and of the vessels movement due to a heartbeat. In-vitro experiments were conducted and compared with in-silico results. The end-user evaluation results were reported through quantitative performance metrics and a 5-Point Likert Scale questionnaire. Compared with literature, this simulator has an error of 0.23±0.13% for deformation and 0.30±0.85mm for the aortic root displacement. In-vitro experiments show an error of 1.35±1.38mm for deformation prediction. The end-user evaluation results show that novices are more accustomed to using joystick controllers, and cardiologists are more satisfied with the visual authenticity. The real-time and accurate performance of the simulator make this framework suitable for creating a dynamic environment for autonomous navigation of robotic catheters

Genetic markers associated to arbuscular mycorrhizal colonization in durum wheat

In this work we investigated the variability and the genetic basis of susceptibility to arbuscular mycorrhizal (AM) colonization of wheat roots. The mycorrhizal status of wild, domesticated and cultivated tetraploid wheat accessions, inoculated with the AM species Funneliformis mosseae, was evaluated. In addition, to detect genetic markers in linkage with chromosome regions involved in AM root colonization, a genome wide association analysis was carried out on 108 durum wheat varieties and two AM fungal species (F. mosseae and Rhizoglomus irregulare). Our findings showed that a century of breeding on durum wheat and the introgression of Reduced height (Rht) genes associated with increased grain yields did not select against AM symbiosis in durum wheat. Seven putative Quantitative Trait Loci (QTLs) linked with durum wheat mycorrhizal susceptibility in both experiments, located on chromosomes 1A, 2B, 5A, 6A, 7A and 7B, were detected. The individual QTL effects (r2) ranged from 7 to 16%, suggesting a genetic basis for this trait. Marker functional analysis identified predicted proteins with potential roles in host-parasite interactions, degradation of cellular proteins, homeostasis regulation, plant growth and disease/defence. The results of this work emphasize the potential for further enhancement of root colonization exploiting the genetic variability present in wheat

Atypical presentation of anti-N-methyl-D-aspartate receptor encephalitis: Two case reports

Background: Anti-N-methyl-D-aspartate receptor encephalitis is a rare autoimmune disease characterized by severe neurological and psychiatric symptoms and a difficult diagnosis. The disease is often secondary to a neoplastic lesion, seldom diagnosed years later. Psychiatric symptoms are prevalent in adults; neurologic symptoms are more evident in children, who typically present primarily with neurological symptoms. To the best of our knowledge, the association with juvenile idiopathic arthritis has not been described. Case presentation: We report the cases of two caucasian girls with an atypical presentation. The first patient was an 8-year-old girl with normal psychomotor development. Over a 4-month period she developed behavioral problems, speech impairment, and deterioration in academic skills. Within 8 months from the onset of symptoms, choreic movements gradually appeared. Hematological, neuroradiological, and neurophysiological examinations were negative; however, her symptoms worsened and treatment with prednisone was started. Although her choreic movements improved within 1 month, her neuropsychological and behavioral symptoms continued. Anti-N-methyl-D-aspartate receptor antibodies in cerebrospinal fluid and in blood were detected. Therapy with intravenously administered immunoglobulins was administered, without improvement of symptoms. After 2 months of steroid treatment, she suddenly started to pronounce some words with a progressive improvement in language and behavior. The second patient was a 14-year-old girl with classic anti-N-methyl-D-aspartate receptor encephalitis, treated successfully with intravenously administered immunoglobulins and methylprednisolone, followed by orally administered prednisone, who developed chronic arthritis of the hip. The arthritis was confirmed by magnetic resonance imaging and associated to antinuclear antigen antibody positivity. One year after the encephalitis presentation, an ovarian cystic mass was identified as a teratoma. The surgical resection of the mass was followed by the resolution of the psychotic spectrum and arthritis. Conclusions: Anti-N-methyl-D-aspartate receptor encephalitis in pediatric patients can present initially with neuropsychological and behavioral symptoms. In the literature, the association of anti-N-methyl-D-aspartate receptor encephalitis with juvenile idiopathic arthritis is not yet described: to the best of our knowledge, this is the first case reported. The link to a neoplastic lesion can explain the favorable course of encephalitis and arthritis, after the surgical resection of the mass. Early diagnosis and treatment can improve the patient's outcome

Transcriptional profiling in response to terminal drought stress reveals differential responses along the wheat genome

Background: Water stress during grain filling has a marked effect on grain yield, leading to a reduced endosperm cell number and thus sink capacity to accumulate dry matter. The bread wheat cultivar Chinese Spring (CS), a Chinese Spring terminal deletion line (CS_5AL-10) and the durum wheat cultivar Creso were subjected to transcriptional profiling after exposure to mild and severe drought stress at the grain filling stage to find evidences of differential stress responses associated to different wheat genome regions. Results: The transcriptome analysis of Creso, CS and its deletion line revealed 8,552 non redundant probe sets with different expression levels, mainly due to the comparisons between the two species. The drought treatments modified the expression of 3,056 probe sets. Besides a set of genes showing a similar drought response in Creso and CS, cluster analysis revealed several drought response features that can be associated to the different genomic structure of Creso, CS and CS_5AL-10. Some drought-related genes were expressed at lower level (or not expressed) in Creso (which lacks the D genome) or in the CS_5AL- 10 deletion line compared to CS. The chromosome location of a set of these genes was confirmed by PCR-based mapping on the D genome (or the 5AL-10 region). Many clusters were characterized by different level of expression in Creso, CS and CS_AL-10, suggesting that the different genome organization of the three genotypes may affect plant adaptation to stress. Clusters with similar expression trend were grouped and functional classified to mine the biological mean of their activation or repression. Genes involved in ABA, proline, glycine-betaine and sorbitol pathways were found up-regulated by drought stress. Furthermore, the enhanced expression of a set of transposons and retrotransposons was detected in CS_5AL-10. Conclusion: Bread and durum wheat genotypes were characterized by a different physiological reaction to water stress and by a substantially different molecular response. The genome organization accounted for differences in the expression level of hundreds of genes located on the D genome or controlled by regulators located on the D genome. When a genomic stress (deletion of a chromosomal region) was combined with low water availability, a molecular response based on the activation of transposons and retrotransposons was observed

A high-density consensus map of A and B wheat genomes

A durum wheat consensus linkage map was developed by combining segregation data from six mapping populations. All of the crosses were derived from durum wheat cultivars, except for one accession of T. ssp. dicoccoides. The consensus map was composed of 1,898 loci arranged into 27 linkage groups covering all 14 chromosomes. The length of the integrated map and the average marker distance were 3,058.6 and 1.6 cM, respectively. The order of the loci was generally in agreement with respect to the individual maps and with previously published maps. When the consensus map was aligned to the deletion bin map, 493 markers were assigned to specific bins. Segregation distortion was found across many durum wheat chromosomes, with a higher frequency for the B genome. This high-density consensus map allowed the scanning of the genome for chromosomal rearrangements occurring during the wheat evolution. Translocations and inversions that were already known in literature were confirmed, and new putative rearrangements are proposed. The consensus map herein described provides a more complete coverage of the durum wheat genome compared with previously developed maps. It also represents a step forward in durum wheat genomics and an essential tool for further research and studies on evolution of the wheat genome. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00122-012-1939-y) contains supplementary material, which is available to authorized users

Novel heterozygous TREX1 mutation in a juvenile systemic lupus erythematosus patient with severe cutaneous involvement treated successfully with Jak-inhibitors: a case report

Juvenile systemic lupus erythematosus (jSLE) is a complex inflammatory autoimmune disorder. In the last decades, genetic factors and activation pathways have been increasingly studied to understand their potential pathogenetic role better. Genetic and transcriptional abnormalities directly involved in the type I interferon (IFN) signaling cascade have been identified through family-based and genome-wide association studies. IFNs trigger signaling pathways that initiate gene transcription of IFN-stimulated genes through the activation of JAK1, TYK2, STAT1, and STAT2. Thus, the use of therapies that target the IFN pathway would represent a formidable advance in SLE. It is well known that JAK inhibitors have real potential for the treatment of rheumatic diseases, but their efficacy in the treatment of SLE remains to be elucidated. We report the case of a 13-year-old girl affected by jSLE, carrying a novel heterozygous missense variant on Three prime Repair EXonuclease 1 (TREX1), successfully treated with baricitinib on top of mofetil mycophenolate. The TREX1 gene plays an important role in DNA damage repair, and its mutations have been associated with an overproduction of type 1 interferon. This report underlines the role of translational research in identifying potential pathogenetic pathways in rare diseases to optimize treatment

Pattern and determinants of hospitalization during heat waves: an ecologic study

<p>Abstract</p> <p>Background</p> <p>Numerous studies have investigated mortality during a heatwave, while few have quantified heat associated morbidity. Our aim was to investigate the relationship between hospital admissions and intensity, duration and timing of heatwave across the summer months.</p> <p>Methods</p> <p>The study area (Veneto Region, Italy) holds 4577408 inhabitants (on January 1^st, 2003), and is subdivided in seven provinces with 60 hospitals and about 20000 beds for acute care. Five consecutive heatwaves (three or more consecutive days with Humidex above 40°C) occurred during summer 2002 and 2003 in the region. From the regional computerized archive of hospital discharge records, we extracted the daily count of hospital admissions for people aged ≥75, from June 1 through August 31 in 2002 and 2003. Among people aged over 74 years, daily hospital admissions for disorders of fluid and electrolyte balance, acute renal failure, and heat stroke (grouped in a single nosologic entity, heat diseases, HD), respiratory diseases (RD), circulatory diseases (CD), and a reference category chosen a priori (fractures of the femur, FF) were independently analyzed by Generalized Estimating Equations.</p> <p>Results</p> <p>Heatwave duration, not intensity, increased the risk of hospital admissions for HD and RD by, respectively, 16% (p < .0001) and 5% (p < .0001) with each additional day of heatwave duration. At least four consecutive hot humid days were required to observe a major increase in hospital admissions, the excesses being more than twofold for HD (p < .0001) and about 50% for RD (p < .0001). Hospital admissions for HD peaked equally at the first heatwave (early June) and last heatwave (August) in 2004 as did RD. No correlation was found for FF or CD admissions.</p> <p>Conclusion</p> <p>The first four days of an heatwave had only minor effects, thus supporting heat health systems where alerts are based on duration of hot humid days. Although the finding is based on a single late summer heatwave, adaptations to extreme temperature in late summer seem to be unlikely.</p