Exploring Periodic Orbit Expansions and Renormalisation with the Quantum Triangular Billiard

A study of the quantum triangular billiard requires consideration of a boundary value problem for the Green's function of the Laplacian on a trianglar domain. Our main result is a reformulation of this problem in terms of coupled non--singular integral equations. A non--singular formulation, via Fredholm's theory, guarantees uniqueness and provides a mathematically firm foundation for both numerical and analytic studies. We compare and contrast our reformulation, based on the exact solution for the wedge, with the standard singular integral equations using numerical discretisation techniques. We consider in detail the (integrable) equilateral triangle and the Pythagorean 3-4-5 triangle. Our non--singular formulation produces results which are well behaved mathematically. In contrast, while resolving the eigenvalues very well, the standard approach displays various behaviours demonstrating the need for some sort of ``renormalisation''. The non-singular formulation provides a mathematically firm basis for the generation and analysis of periodic orbit expansions. We discuss their convergence paying particular emphasis to the computational effort required in comparision with Einstein--Brillouin--Keller quantisation and the standard discretisation, which is analogous to the method of Bogomolny. We also discuss the generalisation of our technique to smooth, chaotic billiards.Comment: 50 pages LaTeX2e. Uses graphicx, amsmath, amsfonts, psfrag and subfigure. 17 figures. To appear Annals of Physics, southern sprin

Morphometric evaluation of the pedicles of the lumbar spine according to L5 lateral tilt classification

A classification of the lumbar spine according to the pedicle lateral tilt (PLT) of L5 pedicle was recently proposed [1]. In this work the sample was divided into three categories, the first or Wing Type (WT) includes people with a PLT >36° (41,8%), the second or V Type (VT) includes people with a PLT between 30° and 36° (48%) and the third or U Type (UT) includes people with a PL

Does Pelvic Incidence Influence the Morphology of the Sacroiliac Joint?

Pelvic Incidence is defined as the angle between the perpendicular line to the upper plate of S1 at its midpoint and the line between this point and the center of bicoxofemoral line, it describes the position of femural heads in relation to sacrum. Recently some authors described a direct correlation between high values of PI and large AP pelvic axis (horizontal pelvis) and a wide pelvic ring [1]. Also the acetabular orientation is influenced by PI ; high values of PI means a more vertical acetabulum. Having regard to the relationship between PI and the main structures involved in the load transfer, to date no studies that correlate the morphology of the Sacroiliac Joint (SiJ) and PI were performed. The aim of this study is to evaluate the different morphology of the auricular surface of the sacrum comparing two groups of healthy young people with low (40°) PI. We retrospectively analysed 51 consecutive young (between 20 and 35 y.o.) people. After the evaluation of PI the sample was divided into two groups: 31 people belong to the group A (PI 40°). The following morphological parameters of the SiJ were analysed: length of long axis (LLA), length of short axis (LSA), length of oblique axis (LOA), ratio between long and short axis (RLSA), angle between axis (ABA) and surface; global shape of the joint was evaluated; two new parameters were introduced, SiJ Tilt (SiJT), defined as the angle between the vertical line and the long axis of the SiJ and SiJ Slope (SiJS), defined as the angle between the horizontal line and the short axis of the SiJ. We found a strong statistically significant correlations (p-value 0.05) between PI and RLSA, shape, ABA, SiJT and SiJS; a weaker correlations (p-value 0.10) between PI and LLA, LSA were observed; no statistically significant correlation between PI and LOA and surface were observed. The results underline that there is a strong correlation between pelvic morphology and SiJ anatomy. Further studies, about the different pattern of forces distribution among SiJ, will need to be performed to have a better knowledge that could help to understand the biomechanics and pathophysiology of normal and pathological SiJ

Role of NLRP3 in an experimental model of testicular ischemia and reperfusion in mice

Inflammasomes are multi-protein complexes composed of one of several leucinerich repeat receptors (NLRs) including NLRP1, NLRP3, NLRC4 and AIM2: NLRP3 is currently the most fully characterized inflammasome. Testicular torsion leads to tissue degeneration and, after reperfusion, results in production of reactive oxygen species and triggers the apoptosis machinery. To better understand the role of NLRP3 during testicular ischemia/reperfusion (TI/R), we investigated the morphological aspects of spermatogenesis underlying the effects of inflammasome in KO mice during TI/R. KO (Nlrp3tm1bhk) and wild-type (WT: C57Bl6) animals underwent 1h testicular-ischemia followed by reperfusion. The mice were killed after 1 day and 7 days of reperfusion and the determination of caspase-3 activity was executed. Furthermore, both the tubular (mean seminiferous tubule diameter and Johnsen’s scoring system [1]) and extratubular (edema, hemorrhagic extravasation, vessels dilation, and Leydig cells changes [2]) compartments were evaluated. The TUNEL assay for apoptosis was also performed. After 1 and 7 days of reperfusion in WT mice an increase of caspase-3 was observed. Structurally, marked histological damages characterized by altered spermatogenesis, evident extratubular changes and increased TUNEL activity were observed. In KO mice caspase-3 was inhibited. Histological damages were significantly decreased, TUNEL activity was reduced and extratubular changes were significantly milder. We suggest that NLRP3 inhibition might have a protective role on spermatogenesis and it can be proposed in patients with unilateral testicular torsion

Spheres Derived from Lung Adenocarcinoma Pleural Effusions: Molecular Characterization and Tumor Engraftment

Malignant pleural effusions (MPEs) could represent an excellent source to culture a wide variety of cancer cells from different donors. In this study, we set up culture conditions for cancer cells deriving from MPEs of several patients affected by the most frequent form of lung cancer, namely the subset of non small cell lung cancers (NSCLC) classified as Lung Adenocarcinomas (AdenoCa) which account for approximately 40% of lung cancer cases. AdenoCa malignant pleural effusions gave rise to in vitro cultures both in adherent and/or in spheroid conditions in almost all cases analyzed. We characterized in greater detail two samples which showed the most efficient propagation in vitro. In these samples we also compared gene profiles of spheroid vs adherent cultures and identified a set of differentially expressed genes. Finally we achieved efficient tumor engraftment in recipient NOD/SCID mice, also upon inoculation of small number of cells, thus suggesting indirectly the presence of tumor initiating cells

Quality of life of palliative chemotherapy naive patients with advanced adenocarcinoma of the stomach or esophagogastric junction treated with irinotecan combined with 5-fluorouracil and folinic acid: results of a randomised phase III trial

41st Annual Meeting of the American-Society-of-Clinical-Oncology -- MAY 13-17, 2005 -- Orlando, FLWOS: 000268881000007PubMed ID: 19568958The quality of life (QL) of advanced gastric cancer patients receiving irinotecan, folinic acid and 5-fluorouracil (5-FU) (IF arm) or cisplatin with 5-FU (CF arm) is presented. Patients with measurable or evaluable advanced gastric cancer received IF weekly for 6/7 weeks or CF q4 weeks. QL was assessed using the EORTC QLQ-C30 at baseline, subsequently every 8 weeks until progression and thereafter every 3 months until death. The QL data were analysed using several statistical methods including summary measures and pattern-mixture modelling. A total of 333 patients were randomised and treated (IF 170, CF 163). The time-to-progression for IF and CF was 5.0 and 4.2 months (P = 0.088), respectively. The overall compliance rates for QL questionnaire completion were 60 and 56% in the IF and CF arms, respectively. Significant treatment differences were observed for the physical functioning scale (P = 0.024), nausea\vomiting (P = 0.001) and EQ-5D thermometer (P = 0.020) in favour of the IF treatment arm. There was a trend in favour of IF over CF in time-to-progression. The IF group also demonstrated a better safety profile than CF and a better QL on a number of multi-item scales, suggesting that IF offers an alternative first-line platinum-free treatment option for advanced gastric cancer.Amer Soc Clin Onco

Carriers of ADAMTS13 Rare Variants Are at High Risk of Life-Threatening COVID-19

Thrombosis of small and large vessels is reported as a key player in COVID-19 severity. However, host genetic determinants of this susceptibility are still unclear. Congenital Thrombotic Thrombocytopenic Purpura is a severe autosomal recessive disorder characterized by uncleaved ultra-large vWF and thrombotic microangiopathy, frequently triggered by infections. Carriers are reported to be asymptomatic. Exome analysis of about 3000 SARS-CoV-2 infected subjects of different severities, belonging to the GEN-COVID cohort, revealed the specific role of vWF cleaving enzyme ADAMTS13 (A disintegrin-like and metalloprotease with thrombospondin type 1 motif, 13). We report here that ultra-rare variants in a heterozygous state lead to a rare form of COVID-19 characterized by hyper-inflammation signs, which segregates in families as an autosomal dominant disorder conditioned by SARS-CoV-2 infection, sex, and age. This has clinical relevance due to the availability of drugs such as Caplacizumab, which inhibits vWF-platelet interaction, and Crizanlizumab, which, by inhibiting P-selectin binding to its ligands, prevents leukocyte recruitment and platelet aggregation at the site of vascular damage

An explainable model of host genetic interactions linked to COVID-19 severity

We employed a multifaceted computational strategy to identify the genetic factors contributing to increased risk of severe COVID-19 infection from a Whole Exome Sequencing (WES) dataset of a cohort of 2000 Italian patients. We coupled a stratified k-fold screening, to rank variants more associated with severity, with the training of multiple supervised classifiers, to predict severity based on screened features. Feature importance analysis from tree-based models allowed us to identify 16 variants with the highest support which, together with age and gender covariates, were found to be most predictive of COVID-19 severity. When tested on a follow-up cohort, our ensemble of models predicted severity with high accuracy (ACC = 81.88%; AUCROC = 96%; MCC = 61.55%). Our model recapitulated a vast literature of emerging molecular mechanisms and genetic factors linked to COVID-19 response and extends previous landmark Genome-Wide Association Studies (GWAS). It revealed a network of interplaying genetic signatures converging on established immune system and inflammatory processes linked to viral infection response. It also identified additional processes cross-talking with immune pathways, such as GPCR signaling, which might offer additional opportunities for therapeutic intervention and patient stratification. Publicly available PheWAS datasets revealed that several variants were significantly associated with phenotypic traits such as "Respiratory or thoracic disease", supporting their link with COVID-19 severity outcome.A multifaceted computational strategy identifies 16 genetic variants contributing to increased risk of severe COVID-19 infection from a Whole Exome Sequencing dataset of a cohort of Italian patients

Gain- and Loss-of-Function CFTR Alleles Are Associated with COVID-19 Clinical Outcomes

Carriers of single pathogenic variants of the CFTR (cystic fibrosis transmembrane conductance regulator) gene have a higher risk of severe COVID-19 and 14-day death. The machine learning post-Mendelian model pinpointed CFTR as a bidirectional modulator of COVID-19 outcomes. Here, we demonstrate that the rare complex allele [G576V;R668C] is associated with a milder disease via a gain-of-function mechanism. Conversely, CFTR ultra-rare alleles with reduced function are associated with disease severity either alone (dominant disorder) or with another hypomorphic allele in the second chromosome (recessive disorder) with a global residual CFTR activity between 50 to 91%. Furthermore, we characterized novel CFTR complex alleles, including [A238V;F508del], [R74W;D1270N;V201M], [I1027T;F508del], [I506V;D1168G], and simple alleles, including R347C, F1052V, Y625N, I328V, K68E, A309D, A252T, G542*, V562I, R1066H, I506V, I807M, which lead to a reduced CFTR function and thus, to more severe COVID-19. In conclusion, CFTR genetic analysis is an important tool in identifying patients at risk of severe COVID-19

The polymorphism L412F in TLR3 inhibits autophagy and is a marker of severe COVID-19 in males

The polymorphism L412F in TLR3 has been associated with several infectious diseases. However, the mechanism underlying this association is still unexplored. Here, we show that the L412F polymorphism in TLR3 is a marker of severity in COVID-19. This association increases in the sub-cohort of males. Impaired macroautophagy/autophagy and reduced TNF/TNFα production was demonstrated in HEK293 cells transfected with TLR3L412F-encoding plasmid and stimulated with specific agonist poly(I:C). A statistically significant reduced survival at 28 days was shown in L412F COVID-19 patients treated with the autophagy-inhibitor hydroxychloroquine (p = 0.038). An increased frequency of autoimmune disorders such as co-morbidity was found in L412F COVID-19 males with specific class II HLA haplotypes prone to autoantigen presentation. Our analyses indicate that L412F polymorphism makes males at risk of severe COVID-19 and provides a rationale for reinterpreting clinical trials considering autophagy pathways. Abbreviations: AP: autophagosome; AUC: area under the curve; BafA1: bafilomycin A1; COVID-19: coronavirus disease-2019; HCQ: hydroxychloroquine; RAP: rapamycin; ROC: receiver operating characteristic; SARS-CoV-2: severe acute respiratory syndrome coronavirus 2; TLR: toll like receptor; TNF/TNF-α: tumor necrosis factor