Geophysical investigation and dynamic modelling of unstable slopes: case-study of Kainama (Kyrgyzstan)

The presence of massive Quaternary loess units at the eastern border of the Fergana Basin (Kyrgyzstan, Central Asia) makes this area particularly prone to the development of catastrophic loess earthflows, causing damages and injuries almost every year. Efficient disaster management requires a good understanding of the main causes of these mass movements, that is, increased groundwater pressure and seismic shaking. This paper focuses on the Kainama earthflow, mainly composed of loess, which occurred in 2004 April. Its high velocity and the long run-out zone caused the destruction of 12 houses and the death of 33 people. In summer 2005, a field survey consisting of geophysical and seismological measurements was carried out along the adjacent slope. By combination and geostatistical analysis of these data, a reliable 3-D model of the geometry and properties of the subsurface layers, as shown in the first part of the paper, was created. The analysis of the seismological data allowed us to point out a correlation between the thickness of the loess cover and the measured resonance frequencies and associated amplification potential. The second part of this paper is focused on the study of the seismic response of the slope by numerical simulations, using a 2-D finite difference code named FLAC. Modelling of the seismic amplification potential along the slope confirmed the results obtained from the seismological survey—strong amplifications at the crest and bottom of the slope where there is a thick loess cover and almost no amplification in the middle part of the slope. Furthermore, dynamic slope stability analyses were conducted to assess the influence of local amplifications and increased groundwater pressures on the slope failure. The results of the dynamic modelling, although preliminary, show that a combination of seismic and hydrologic origin (pore pressure build-up during the seismic shaking) is the most probable scenario responsible for the 2004 failur

Recovery of adrenal insufficiency is frequent after adjuvant mitotane therapy in patients with adrenocortical carcinoma

Mitotane is a steroidogenesis inhibitor and adrenolytic drug used for treatment of adrenocortical cancer (ACC). Mitotane therapy causes adrenal insufficiency requiring glucocorticoid replacement in all patients. However, it is unclear whether chronic therapy with mitotane induces complete destruction of zona fasciculata and whether hypothalamic-pituitary-adrenal (HPA) axis can recover after treatment cessation. Our objective was to assess the HPA axis recovery in a cohort of patients after cessation of adjuvant mitotane therapy for ACC. We retrospectively reviewed patient files with stage I-II-III ACC in two referral centers in Canada and Italy. Data on demographics, tumor characteristics, hormonal profile, and HPA axis were collected. Data from 23 patients with pathologically proven ACC treated with adjuvant mitotane for a minimum of two years were analyzed. Eight patients were males and 15 were females and the median age was 41 years old (range 18 to 73). After mitotane cessation, 18/23 (78.3%) patients achieved a complete HPA axis recovery while 3/23 (13.0%) were unable to tolerate glucocorticoid withdrawal despite having normal hormonal test values and 2/23 (8.7%) never achieved recovery. The mean time interval between mitotane cessation and HPA axis recovery was 2.7 years. A high proportion of patients achieved HPA axis recovery following cessation of mitotane adjuvant therapy. However, complete recovery was often delayed up to 2.5 years and regular assessment of the hormonal profile is required

Path integrals on a flux cone

This paper considers the Schroedinger propagator on a cone with the conical singularity carrying magnetic flux (``flux cone''). Starting from the operator formalism and then combining techniques of path integration in polar coordinates and in spaces with constraints, the propagator and its path integral representation are derived. "Quantum correction" in the Lagrangian appears naturally and no a priori assumption is made about connectivity of the configuration space.Comment: LaTeX file, 9 page

Problems with Extraction of the Nucleon to Delta(1232) Photonic Amplitudes

We investigate the model dependence and the importance of choice of database in extracting the {\it physical} nucleon-Delta(1232) electromagnetic transition amplitudes, of interest to QCD and baryon structure, from the pion photoproduction observables. The model dependence is found to be much smaller than the range of values obtained when different datasets are fitted. In addition, some inconsistencies in the current database are discovered, and their affect on the extracted transition amplitudes is discussed.Comment: Revtex, 2 figs., submitted to PR

Nucleon to Delta Weak Excitation Amplitudes in the Non-relativistic Quark Model

We investigate the nucleon to Delta(1232) vector and axial vector amplitudes in the non-relativistic quark model of the Isgur-Karl variety. A particular interest is to investigate the SU(6) symmetry breaking, due to color hyperfine interaction. We compare the theoretical estimates to recent experimental investigation of the Adler amplitudes by neutrino scattering.Comment: \documentstyle[aps]{revtex}, 21pages; 11 postscript figures. Accepted for publication by Phys. Rev.

Perturbative Renormalizations of Anyon Quantum Mechanics

In bosonic end perturbative calculations for quantum mechanical anyon systems a regularization and renormalization procedure, analogous to those used in field theory, is necessary. I examine the reliability and the physical interpretation of the most commonly used bosonic end regularization procedures. I then use the regularization procedure with the most transparent physical interpretation to derive some bosonic end perturbation theory results on anyon spectra, including a 3-anyon ground state energy.Comment: 19 pages, Plain LaTex, MIT-CTP-232

Approach to Perturbative Results in the N-Delta Transition

We show that constraints from perturbative QCD calculations play a role in the nucleon to Delta(1232) electromagnetic transition even at moderate momentum transfer scales. The pQCD constraints, tied to real photoproduction data and unseparated resonance response functions, lead to explicit forms for the helicity amplitudes wherein the E2/M1 ratio remains small at moderately large momentum transfer.Comment: 4 pages, 2 figures, ReVTe

Primary pigmented nodular adrenocortical disease presenting with a unilateral adrenocortical nodule treated with bilateral laparoscopic adrenalectomy: a case report

<p>Abstract</p> <p>Introduction</p> <p>Primary pigmented nodular adrenocortical disease is a rare cause of adrenocorticotropic hormone-independent Cushing's syndrome. We report an uncommon primary pigmented nodular adrenocortical disease case presenting with a unilateral adrenocortical nodule and provide a brief overview of the existing literature.</p> <p>Case presentation</p> <p>A 27-year-old Caucasian woman was admitted to our Department with adrenocorticotropic hormone-independent Cushing's syndrome. Its cause was initially considered a left adrenocortical adenoma based on computer tomography imaging. The patient underwent left laparoscopic adrenalectomy and histological examination revealed pigmented micronodular adrenal hyperplasia. Evaluation for the presence of Carney complex was negative. Six months later recurrence of hypercortisolism was documented and a right laparoscopic adrenalectomy was performed further establishing the diagnosis of primary pigmented nodular adrenocortical disease. After a nine-year follow-up there is no evidence of residual disease.</p> <p>Conclusions</p> <p>Even though primary pigmented nodular adrenocortical disease is a rare cause of Cushing's syndrome, it should be included in the differential diagnosis of adrenocorticotropic hormone-independent Cushing's syndrome, especially because adrenal imaging can be misleading mimicking other adrenocortical diseases. Bilateral laparoscopic adrenalectomy is the preferred treatment in these subjects.</p

PTPN2, a Candidate Gene for Type 1 Diabetes, Modulates Interferon-γ–Induced Pancreatic β-Cell Apoptosis

OBJECTIVE: The pathogenesis of type 1 diabetes has a strong genetic component. Genome-wide association scans recently identified novel susceptibility genes including the phosphatases PTPN22 and PTPN2. We hypothesized that PTPN2 plays a direct role in beta-cell demise and assessed PTPN2 expression in human islets and rat primary and clonal beta-cells, besides evaluating its role in cytokine-induced signaling and beta-cell apoptosis. RESEARCH DESIGN AND METHODS: PTPN2 mRNA and protein expression was evaluated by real-time PCR and Western blot. Small interfering (si)RNAs were used to inhibit the expression of PTPN2 and downstream STAT1 in beta-cells, allowing the assessment of cell death after cytokine treatment. RESULTS: PTPN2 mRNA and protein are expressed in human islets and rat beta-cells and upregulated by cytokines. Transfection with PTPN2 siRNAs inhibited basal- and cytokine-induced PTPN2 expression in rat beta-cells and dispersed human islets cells. Decreased PTPN2 expression exacerbated interleukin (IL)-1beta + interferon (IFN)-gamma-induced beta-cell apoptosis and turned IFN-gamma alone into a proapoptotic signal. Inhibition of PTPN2 amplified IFN-gamma-induced STAT1 phosphorylation, whereas double knockdown of both PTPN2 and STAT1 protected beta-cells against cytokine-induced apoptosis, suggesting that STAT1 hyperactivation is responsible for the aggravation of cytokine-induced beta-cell death in PTPN2-deficient cells. CONCLUSIONS: We identified a functional role for the type 1 diabetes candidate gene PTPN2 in modulating IFN-gamma signal transduction at the beta-cell level. PTPN2 regulates cytokine-induced apoptosis and may thereby contribute to the pathogenesis of type 1 diabetes

Adjuvant mitotane versus surveillance in low-grade, localised adrenocortical carcinoma (ADIUVO): an international, multicentre, open-label, randomised, phase 3 trial and observational study

BACKGROUND: Adjuvant treatment with mitotane is commonly used after resection of adrenocortical carcinoma; however, treatment remains controversial, particularly if risk of recurrence is not high. We aimed to assess the efficacy and safety of adjuvant mitotane compared with surveillance alone following complete tumour resection in patients with adrenocortical carcinoma considered to be at low to intermediate risk of recurrence. METHODS: ADIUVO was a multicentre, open-label, parallel, randomised, phase 3 trial done in 23 centres across seven countries. Patients aged 18 years or older with adrenocortical carcinoma and low to intermediate risk of recurrence (R0, stage I-III, and Ki67 ≤10%) were randomly assigned to adjuvant oral mitotane two or three times daily (the dose was adjusted by the local investigator with the target of reaching and maintaining plasma mitotane concentrations of 14-20 mg/L) for 2 years or surveillance alone. All consecutive patients at 14 study centres fulfilling the eligibility criteria of the ADIUVO trial who refused randomisation and agreed on data collection via the European Network for the Study of Adrenal Tumors adrenocortical carcinoma registry were included prospectively in the ADIUVO Observational study. The primary endpoint was recurrence-free survival, defined as the time from randomisation to the first radiological evidence of recurrence or death from any cause (whichever occurred first), assessed in all randomly assigned patients by intention to treat. Overall survival, defined as time from the date of randomisation to the date of death from any cause, was a secondary endpoint analysed by intention to treat in all randomly assigned patients. Safety was assessed in all patients who adhered to the assigned regimen, which was defined by taking at least one tablet of mitotane in the mitotane group and no mitotane at all in the surveillance group. The ADIUVO trial is registered with ClinicalTrials.gov, NCT00777244, and is now complete. FINDINGS: Between Oct 23, 2008, and Dec 27, 2018, 45 patients were randomly assigned to mitotane and 46 to surveillance alone. Because the study was discontinued prematurely, 5-year recurrence-free and overall survival are reported instead of recurrence-free and overall survival as defined in the protocol. 5-year recurrence-free survival was 79% (95% CI 67-94) in the mitotane group and 75% (63-90) in the surveillance group (hazard ratio 0·74 [95% CI 0·30-1·85]). Two people in the mitotane group and five people in the surveillance group died, and 5-year overall survival was not significantly different (95% [95% CI 89-100] in the mitotane group and 86% [74-100] in the surveillance group). All 42 patients who received mitotane had adverse events, and eight (19%) discontinued treatment. There were no grade 4 adverse events or treatment-related deaths. INTERPRETATION: Adjuvant mitotane might not be indicated in patients with low-grade, localised adrenocortical carcinoma considering the relatively good prognosis of these patients, and no significant improvement in recurrence-free survival and treatment-associated toxicity in the mitotane group. However, the study was discontinued prematurely due to slow recruitment and cannot rule out an efficacy of treatment. FUNDING: AIFA, ENSAT Cancer Health F2-2010-259735 programme, Deutsche Forschungsgemeinschaft, Cancer Research UK, and the French Ministry of Health