Family history as a risk factor for recurrent hospitalization for lone atrial fibrillation: a nationwide family study in Sweden.

ABSTRACT: BACKGROUND: Although the heritability of atrial fibrillation (AF) has been determined, the relevance of family history of AF for the likelihood of recurrent hospitalization for AF is unknown. The aim of this nationwide study was to determine whether family history of AF is a risk factor of recurrent hospitalization for lone AF (LAF), i.e., AF with unknown etiology. The familial risk for first time LAF hospitalization was also determined and compared to the risk of recurrent hospitalization for LAF. METHODS: We examined whether family history of AF is a risk factor for recurrent hospitalization for LAF in the whole Swedish population. We linked Multigeneration Register data on individuals aged 0-60 years to Hospital Discharge Register data for the period 1987-2009 to compare LAF recurrent hospitalization risk among individuals with and without parental or sibling history of AF. We calculated hazard ratios (HRs) to determine the familial HR of recurrent hospitalization for LAF. Odds ratios (OR) were calculated for familial risk of first time LAF hospitalization. RESULTS: The risk of recurrent LAF hospitalization was 1.23 (95% CI 1.17-1.30) for individuals with affected parents compared to 1.30 (95% CI 1.22-1.38) for those with affected siblings. After 10 years of follow up 50% of those without and 60% of those with family history had recurrent hospitalization for LAF. The risk of recurrent LAF hospitalization in individuals with two affected parents was 1.65 (95% CI 1.44-1.90). There was an interaction between age and family history, with family history having a weaker effect on LAF hospitalization risk in older age groups. The OR for first time LAF hospitalization was 2.08 (95% CI 2.02-2.15) for offspring with affected parents and 3.23 (95% CI 3.08-3.39) for individuals with affected siblings. CONCLUSIONS: Family history of AF is a novel risk factor for recurrent LAF hospitalization. The higher recurrence hospitalization risk in multiplex families and younger individuals suggests a genetic contribution. However, the familial risk for recurrent LAF hospitalization was much lower than the risk for first time LAF hospitalization, suggesting that familial and possibly genetic factors are more important for first time LAF hospitalization than recurrent LAF hospitalization

Treatment with Unlabeled mAb BR96 After Radioimmunotherapy with (177)Lu-DOTA-BR96 in a Syngeneic Rat Colon Carcinoma Model.

Metastatic disease after successful treatment of the primary tumor continues to be a therapeutic challenge. Enhancement of therapeutic effects by the administration of unlabeled monoclonal antibodies (mAbs) after radioimmunotherapy (RIT) may provide a means of preventing or delaying the development of metastatic disease. In the present study, Brown Norway rats with syngeneic grafted colon carcinomas were administered the minimal effective therapeutic dose of 400 MBq/kg lutetium-177 ((177)Lu)-DOTA-BR96. After 2 weeks, half of the animals were given 15 mg/kg unlabeled mAb BR96 as consolidation therapy. Treatment response and toxicity were monitored 100 days after the treatment with unlabeled BR96. The treatment with unlabeled mAb after RIT resulted in a complete response (CR) in 19 of 19 animals, while RIT alone resulted in a CR in 17 of 19 animals. The additional treatment did not affect the number of animals with metastatic disease or the time to clinical symptoms of metastases. RIT resulted in reversible myelotoxicity. The unlabeled mAb BR96 did not cause any additional toxicity, making it possible to repeat the consolidation therapy

Monocyte Chemoattractant Protein 1 is a Prognostic Marker in ANCA-Associated Small Vessel Vasculitis

Background. The (anti neutrophil cytoplasmatic autoantibody ANCA), associated small vessel vasculitides (ASVV) are relapsing-remitting inflammatory disorders, involving various organs, such as the kidneys. (Monocyte chemoattractant protein 1 MCP-1) has been shown to be locally up regulated in glomerulonephritis and recent studies have pointed out MCP-1 as a promising marker of renal inflammation. Here we measure urinary cytokine levels in different phases of disease, exploring the possible prognostic value of MCP-1, together with (interleukin 6 IL-6), (interleukin 8 IL-8) and (immunoglobulin M IgM). Methods. MCP-1, IL-6 and IL-8 were measured using commercially available ELISA kits, whereas IgM in the urine was measured by an in-house ELISA. Results. The MCP-1 levels in urine were significantly higher in patients in stable phase of the disease, compared with healthy controls. Patients in stable phase, with subsequent adverse events; had significantly higher MCP-1 values than patients who did not. MCP-1 and IgM both tended to be higher in patients relapsing within three months, an observation, however, not reaching statistical significance. Urinary levels of IL-6 correlated with relapse tendency, and IL-8 was associated with disease outcome. Conclusions. Patients with ASVV have raised cytokine levels in the urine compared to healthy controls, even during remission. Raised MCP-1 levels are associated with poor prognosis and possibly also with relapse tendency. The association with poor prognosis was stronger for U-MCP-1 than for conventional markers of disease like CRP, BVAS, and ANCA, as well as compared to candidate markers like U-IgM and U-IL-8. We thus consider U-MCP-1 to have promising potential as a prognostic marker in ASVV

Pattern of antigen expression in metastases after radioimmunotherapy of a syngeneic rat colon carcinoma utilizing the BR96 antibody.

Abstract ABSTRACT: BACKGROUND: Repeated administration of antibody-based therapies such as radioimmunotherapy depends on preserved antigen expression in tumor lesions. The purpose of this study was to evaluate whether the antigen expression in metastases observed after radioimmunotherapy differs from that of untreated primary tumors. FINDINGS: 30 of the 35 Brown Norway rats with syngeneic colon carcinoma treated with 400 MBq/kg 177Lu-DOTA-BR96 exhibited consistent complete response of the primary tumor. 13 animals developed metastases that were detected after treatment. The antigen expression was reduced in 17 of 23 metastases detected after radioimmunotherapy compared with untreated tumors. No tumors completely lacked positively stained tumor cells. CONCLUSIONS: Although it was not possible to demonstrate that the antigen reduction is triggered by the radioimmunotherapy this result stress the importance of considering the risk of reduced antigen expression in metastases after radioimmunotherapy prior to further targeted therapies

The association between cannabis abuse and subsequent schizophrenia: a Swedish national co-relative control study.

Although cannabis abuse (CA) is known to be associated with schizophrenia, the causal nature of this association is unclear, with prodromal effects complicating its interpretation

Recherche de nouveaux phénomènes dans les événements diphoton avec le détecteur ATLAS

Dans cette thèse, je présente mes travaux de recherche réalisés avec les données de collision proton-proton enregistrées par le détecteur ATLAS. Les événements étudiés possèdent un état final avec au moins deux photons et une grande masse invariante du système diphoton. Le lot de données enregistré pendant l'année 2011 dans des collisions avec une énergie de 7 TeV dans le centre de masse proton-proton correspond à une luminosité intégrée d'environ 5 fb-1. Ces données ont été comparées aux prédictions du Modèle Standard de la Physique des Particules. En l'absence de différences significatives, des contraintes ont été imposées sur les paramètres de modèles prévoyant l'existence de dimensions supplémentaires. A titre d'exemple, le premier graviton de Kaluza-Klein du modèle de Randall-Sundrum a été contraint d'être plus massif que 2.23 TeV, améliorant d'environ 1 TeV la contrainte du Tevatron. Les résultats obtenus ont fait l'objet d'une publication de la part de la collaboration ATLAS. En 2012, le LHC a réalisé des collisions proton-proton avec une énergie dans le centre de masse de 8 TeV. En outre, la luminosité intégrée a été environ quatre fois supérieure qu'en 2011. Les résultats préliminaires obtenus avec ce lot de données sont présentés dans ce document. La revue interne de ces résultats au sein de la collaboration ATLAS est en cours en vue d'une publication en 2013. La détection et la caractérisation des électrons et des photons reposent essentiellement sur le calorimètre à argon liquide du détecteur ATLAS. La procédure qui permet d'évaluer la qualité des mesures de ces particules a été mise en place au début de la prise de données. Ma contribution à son élaboration est décrite dans ce document.In this thesis, I describe my research based on proton-proton collision data collected by the ATLAS detector. The study uses events with at least two photons in the final state and a large invariant mass of the diphoton system. A dataset of proton-proton collisions at a center-of-mass energy of 7 TeV corresponding to an integrated luminosity of approximately 5 fb-1 has been recorded in 2011. This sample has been compared to the predictions of the Standard Model of Particle Physics. Given the good agreement of the data with these predictions, limits have been set on the parameters of models that postulate extra spatial dimensions. As an example, the lightest Kaluza-Klein graviton in the Randall-Sundrum model has been constrained to be more massive than 2.23 TeV, superseding the Tevatron limits by approximately 1 TeV. These results have been published by the ATLAS collaboration. In 2012, the LHC has delivered proton-proton collisions at a center-of-mass energy of 8 TeV. The corresponding integrated luminosity is four times larger than that of the 2011 dataset. Preliminary results based on this dataset are presented in this document. The ATLAS-internal review of these results is ongoing, and a publication is targeted for 2013. The detection and the characterization of electrons and photons are mainly based on the liquid argon calorimeter of the ATLAS detector. A procedure to assess the quality of the measurements of these particles has been established at the beginning of the data taking. My contributions to its development are described in this document.SAVOIE-SCD - Bib.électronique (730659901) / SudocGRENOBLE1/INP-Bib.électronique (384210012) / SudocGRENOBLE2/3-Bib.électronique (384219901) / SudocSudocFranceF

Geometric deep learning and equivariant neural networks

We survey the mathematical foundations of geometric deep learning, focusing on group equivariant and gauge equivariant neural networks. We develop gauge equivariant convolutional neural networks on arbitrary manifolds M using principal bundles with structure group K and equivariant maps between sections of associated vector bundles. We also discuss group equivariant neural networks for homogeneous spaces M= G/ K , which are instead equivariant with respect to the global symmetry G on M . Group equivariant layers can be interpreted as intertwiners between induced representations of G, and we show their relation to gauge equivariant convolutional layers. We analyze several applications of this formalism, including semantic segmentation and object detection networks. We also discuss the case of spherical networks in great detail, corresponding to the case M= S2= SO (3) / SO (2) . Here we emphasize the use of Fourier analysis involving Wigner matrices, spherical harmonics and Clebsch–Gordan coefficients for G= SO (3) , illustrating the power of representation theory for deep learning

HEAL-SWIN: A Vision Transformer On The Sphere

High-resolution wide-angle fisheye images are becoming more and more important for robotics applications such as autonomous driving. However, using ordinary convolutional neural networks or vision transformers on this data is problematic due to projection and distortion losses introduced when projecting to a rectangular grid on the plane. We introduce the HEAL-SWIN transformer, which combines the highly uniform Hierarchical Equal Area iso-Latitude Pixelation (HEALPix) grid used in astrophysics and cosmology with the Hierarchical Shifted-Window (SWIN) transformer to yield an efficient and flexible model capable of training on high-resolution, distortion-free spherical data. In HEAL-SWIN, the nested structure of the HEALPix grid is used to perform the patching and windowing operations of the SWIN transformer, resulting in a one-dimensional representation of the spherical data with minimal computational overhead. We demonstrate the superior performance of our model for semantic segmentation and depth regression tasks on both synthetic and real automotive datasets. Our code is available at https://github.com/JanEGerken/HEAL-SWIN.Comment: Main body: 10 pages, 7 figures. Appendices: 4 pages, 2 figure

The Intratumoral Distribution of Radiolabeled 177Lu-BR96 Monoclonal Antibodies Changes in Relation to Tumor Histology over Time in a Syngeneic Rat Colon Carcinoma Model.

The therapeutic effect of radioimmunotherapy depends on the distribution of the absorbed dose in relation to viable cancer cells within the tumor, which in turn is a function of the activity distribution. The aim of this study was to investigate the distribution of (177)Lu-DOTA-BR96 monoclonal antibodies targeting the Lewis Y antigen over 7 d using a syngeneic rat model of colon carcinoma