Mortality study of 18 000 patients treated with omeprazole.

Background: The long term safety of potent gastric acid suppressive therapy has yet to be established. Method: General practice record review at a median interval of 26 months followed by retrieval of details of all deaths within four years using the UK National Health Service Central Registers in 17 936 patients prescribed omeprazole in 1993–1995. Death rates were compared with general population rates. Results: Records of 17 489 patients (97.5%) were examined. A total of 12 703 patients received further scripts for antisecretory drugs, 8097 for omeprazole only (65.6%): 3097 patients have died. All cause mortality was higher in the first year (observed/expected (O/E) 1.44 (95% confidence intervals (CI) 1.34–1.55); p<0.0001) but had fallen to population expectation by the fourth year. There were significant mortality increases in the first year, falling to or below population expectation by the fourth year, for deaths ascribed to neoplasms (1.82 (95% CI 1.58–2.08); p<0.0001), circulatory diseases (1.27 (95% CI 1.13–1.43); p<0.0001), and respiratory diseases (1.37 (95% CI 1.12–1.64); p<0.001). Increased mortality ascribed to digestive diseases (2.56 (95% CI 1.87–3.43); p<0.0001) persisted, although reduced. Increased mortality rates for cancers of the stomach (4.06 (95% CI 2.60–6.04); p<0.0001), colon and rectum (1.40 (95% CI 0.84–2.18); p=0.075), and trachea, bronchus, and lung (1.64 (95% CI 1.19–2.19); p<0.01) seen in the first year had disappeared by the fourth year but that for cancer of the oesophagus had not (O/E 7.35 (95% CI 5.20–10.09) (p<0.0001) in year 1; 2.88 (95% CI 1.62–4.79) (p<0.001) in year 4). Forty of 78 patients dying of oesophageal cancer had the disease present at registration. Twenty seven of those remaining cases had clinical evidence of Barrett’s disease, stricture, ulcer, or oesophagitis at registration (O/E 3.30 (95% CI 2.17–4.80)). Six deaths occurred in patients with hiatal hernia or reflux only (O/E 1.02 (95% CI 0.37–2.22)) and five in patients without oesophageal disease (O/E 0.77 (95% CI 0.25–1.80)). No relationships were detected with numbers of omeprazole scripts received. Conclusions: Increases in mortality associated with treatment are due to pre- existing illness, including pre-existing severe oesophageal disease. There was no evidence of an increased risk of oesophageal adenocarcinoma in those without oesophageal mucosal damage recorded at registration

A titanium-nitride near-infrared kinetic inductance photon-counting detector and its anomalous electrodynamics

We demonstrate single-photon counting at 1550 nm with titanium-nitride (TiN) microwave kinetic inductance detectors. Energy resolution of 0.4 eV and arrival-time resolution of 1.2 microseconds are achieved. 0-, 1-, 2-photon events are resolved and shown to follow Poisson statistics. We find that the temperature-dependent frequency shift deviates from the Mattis-Bardeen theory, and the dissipation response shows a shorter decay time than the frequency response at low temperatures. We suggest that the observed anomalous electrodynamics may be related to quasiparticle traps or subgap states in the disordered TiN films. Finally, the electron density-of-states is derived from the pulse response.Comment: 4 pages, 3 figure

A model for hysteretic magnetic properties under the application of noncoaxial stress and field

Although descriptions of the effect of stress on spontaneous magnetization within a single domain already exist, there remains no adequate mathematical model for the effects of noncoaxial magnetic field and stress on bulk magnetization in a multidomained specimen. This article addresses the problem and provides a phenomenological theory that applies to the case of bulk isotropic materials. The magnetomechanical hysteresis model of Sablik and Jiles is thus extended to treat magnetic properties in the case of noncoaxial stress and magnetic field in an isotropic, polycrystalline medium. In the modeling, noncollinearity between magnetization and magnetic field is taken into account. The effect of roll‐axis anisotropy is also considered. Both magnetic and magnetostrictive hysteresis are describable by the extended model. Emphasis in this article is on describing properties like coercivity, remanence,hysteresis loss, maximum flux density, and maximum differential permeability as a function of stress for various angular orientations between field and stress axis. The model predictions are compared with experimental results

Prospective, double-blind, placebo-controlled randomized trial of cimetidine in gastric cancer

Cimetidine is thought to inhibit suppressor T-lymphocyte function and preliminary evidence from a randomized trial indicated that it might prolong survival for patients with operable and inoperable gastric cancer. The British Stomach Cancer Group conducted a randomized, double-blind, placebo-controlled trial examining the effects of cimetidine (400 mg or 800 mg twice a day) on the survival of patients with early (stages I, II and III: n = 229) and advanced (stages IVa and IVb: n = 201) gastric cancer. The primary end point was death. A total of 442 patients were randomized by 59 consultants in 39 hospitals between February 1990 and March 1995. Log-rank survival analysis was used to assess differences between the groups. Three hundred and forty patients died during the study: 166 (49%) in the cimetidine treatment groups and 174 (51%) in the placebo groups. Median survival for patients receiving cimetidine was 13 months (95% confidence interval (CI) 9–16 months) and 11 months in the placebo arm (95% CI 9–14 months). There was no significant difference in survival between the two treatment groups (P = 0.42) or between different doses of cimetidine tablets (P = 0.46). Five-year survival of those patients randomized to cimetidine was 21% compared to 18% for those patients randomized to placebo. Cimetidine at a dose of 400 mg or 800 mg twice a day does not have a significant influence on the survival of patients with gastric cancer compared to placebo. © 1999 Cancer Research Campaig

Focal Segmental Glomerulosclerosis Complicating Therapy With Inotersen, an Antisense Oligonucleotide Inhibitor: A Case Report

Inotersen is an antisense oligonucleotide inhibitor licensed for the treatment of polyneuropathy complicating hereditary transthyretin amyloidosis (ATTRv). Nephrotoxicity has been reported with inotersen, including progression to end stage renal disease. We describe the first reported case of inotersen-associated nephrotic syndrome secondary to focal segmental glomerulosclerosis (FSGS) and review the literature concerning inotersen-induced nephrotoxicity. We report a woman in her early 30s with ATTRv associated with the (p.V50M) transthyretin (TTR) variant, who presented with nephrotic syndrome 7 months after commencement of inotersen. Renal histology demonstrated focal segmental glomerulosclerosis and scanty glomerular amyloid deposition. Discontinuation of inotersen alone resulted in complete clinical and biochemical resolution of nephrotic syndrome. Inotersen is associated with significant nephrotoxicity. In the phase III NEURO-TTR clinical trial, 3% of patients in the treatment arm developed a crescentic glomerulonephritis. All affected patients carried the (p.V50M) TTR variant which is known to be associated with renal amyloid deposition. This case adds to spectrum of renal disease associated with inotersen and indicates that discontinuation of the drug alone may result in resolution of renal complications without additional immunosuppression. Monitoring of renal function is essential in patients with ATTRv receiving inotersen, particularly if there is evidence of existing renal amyloid

Precision Dual-Aquifer Dewatering at a Low Level Radiological Cleanup in New Jersey

Cleanup of low-level radioactive wastes at the Wayne Interim Storage Site (WISS), Wayne, New Jersey during the period October, 2000 through November, 2001 required the design, installation and operation of a dual-aquifer dewatering system to support excavation of contaminated soils. Waste disposal pits from a former rare-earth processing facility at the WISS had been in contact with the water table aquifer, resulting in moderate levels of radionuclides being present in the upper aquifer groundwater. An uncontaminated artesian aquifer underlies the water table aquifer, and is a localized drinking water supply source. The lower aquifer, confined by a silty clay unit, is flowing artesian and exhibits potentiometric heads of up to 4.5 meters above grade. This high potentiometric head presented a strong possibility that unloading due to excavation would result in a ''blowout'', particularly in areas where the confining unit was &lt; 1 meter thick. Excavation of contaminated materials w as required down to the surface of the confining unit, potentially resulting in an artesian aquifer head of greater than 8 meters above the excavation surface. Consequently, it was determined that a dual-aquifer dewatering system would be required to permit excavation of contaminated material, with the water table aquifer dewatered to facilitate excavation, and the deep aquifer depressurized to prevent a ''blowout''. An additional concern was the potential for vertical migration of contamination present in the water table aquifer that could result from a vertical gradient reversal caused by excessive pumping in the confined system. With these considerations in mind, a conceptual dewatering plan was developed with three major goals: (1) dewater the water table aquifer to control radionuclide migration and allow excavation to proceed; (2) depressurize the lower, artesian aquifer to reduce the potential for a ''blowout''; and (3) develop a precise dewatering level control mechanism to insure a vertical gradient reversal did not result in cross-contamination. The plan was executed through a hydrogeologic investigation culminating with the design and implementation of a complex, multi-phased dual-aquifer dewatering system equipped with a state of the art monitoring network

The Self Model and the Conception of Biological Identity in Immunology

The self/non-self model, first proposed by F.M. Burnet, has dominated immunology for sixty years now. According to this model, any foreign element will trigger an immune reaction in an organism, whereas endogenous elements will not, in normal circumstances, induce an immune reaction. In this paper we show that the self/non-self model is no longer an appropriate explanation of experimental data in immunology, and that this inadequacy may be rooted in an excessively strong metaphysical conception of biological identity. We suggest that another hypothesis, one based on the notion of continuity, gives a better account of immune phenomena. Finally, we underscore the mapping between this metaphysical deflation from self to continuity in immunology and the philosophical debate between substantialism and empiricism about identity

Potential Use of American College of Radiology BI-RADS Mammography Atlas for Reporting and Assessing Lesions Detected on Dedicated Breast CT Imaging: Preliminary Study

Rationale and Objectives Dedicated breast computed tomography (DBCT) is an emerging and promising modality for breast lesions. The objective of this study was to evaluate the potential use of applying the BI-RADS Mammography Atlas 5th Edition for reporting and assessing breast lesions on DBCT. Currently, no atlas exists for DBCT. Materials and Methods Four radiologists trained in breast imaging were recruited in this institutional review board-approved, Health Insurance Portability and Accountability Act-compliant study. The enrolled radiologists, who were blinded to mammographic and histopathologic findings, individually reviewed 30 randomized DBCT cases that contained marked lesions. Thirty-four lesions were included in this study: 24 (70.6%) masses, 7 (20.6%) calcifications, and 3 (8.8%) architectural distortions. Eight (23.5%) lesions were malignant and 26 (76.5%) were benign. The reader was asked to specify according to the BI-RADS Mammography Atlas for each marked DBCT lesion: primary findings, features, breast density, and final assessment. We calculated readers' diagnostic performances for differentiating between benign and malignant lesions and interobserver variability for reporting and assessing lesions using a generalized estimating equation and the Fleiss kappa (κ) statistic. Results The estimated overall sensitivity of the readers was 0.969, and the specificity was 0.529. There were no significant differences in the sensitivity and the specificity between lesion types. For reporting the presence of a primary finding, the overall substantial agreement (κ = 0.70) was seen. In assigning the breast density and the final assessment, the overall agreement was moderate (κ = 0.53) and fair (κ = 0.30). Conclusion The use of the BI-RADS Mammography Atlas 5th Edition for DBCT showed high performance and good agreement among readers

Something in the atmosphere? Michael Chekhov, Deirdre Hurst Du Prey, and a web of practices between acting and dance

This article contextualises principles of Chekhov’s technique within convergent developments in dance by bringing into focus the interesting web of connections between Chekhov’s female colleagues — specifically his associate Deirdre Hurst Du Prey — and key pioneers in the field of dance and dance-mime, including Mary Wigman, Isadora Duncan, Martha Graham and Margaret Barr. Their cross-connections broaden our view on the canon of embodied theatre practice, and also open up reflection on how overlaps between acting- and dance principles may be useful for contemporary embodied theatre practice and its efforts to work across these currently (in the Western conservatoire context) quite segregated disciplines

Effect of diverse supercritical extraction procedures on the odour profile of chía (Salvia hispanica L.) oil

La semilla (Salvia hispanica L.) de chía contiene alrededor de 32-39% de aceite, con un alto contenido de ácido a-linolénico (C18:3) (61–70%). La extracción mediante fluidos supercríticos (EFSC) utilizando CO2 es una alternativa interesante para la extracción de aceites vegetales ya que no presenta los inconvenientes asociados al empleo de disolventes orgánicos logrando un producto de mayor calidad. Por ello, es importante la determinación de las condiciones de presión y temperatura operativas óptimas de este proceso. Así, los valores aplicados de estos parámetros pueden afectar el perfil de olor (atributo de calidad organoléptica) del producto obtenido. El objetivo del presente trabajo fue evaluar el perfil de olor de aceite de chía obtenido por EFSC en función de las condiciones de extracción empleadas. La EFSC fue llevada cabo a presiones operativas de 250 y 450 bar, temperaturas de 40 y 60ºC, con y sin la adición de etanol como co-solvente, flujo másico de fluido supercrítico de 8 kg/h. El perfil de olor se analizó mediante una Nariz Electrónica acoplada a un Espectrómetro de Masa (NE-MS) (a-Prometheus, Alpha MOS, Francia) utilizando la metodología de espacio de cabeza estático y 18 sensores semiselectivos frente a los distintos grupos de compuestos volátiles pertenecientes al alimento. La señal generada en cada sensor es el valor de la resistencia eléctrica causada por adsorción de los compuestos volátiles. El conjunto de respuestas obtenidas en cada sensor produce un patrón característico del perfil de olor de la matriz alimenticia en estudio. Se analizaron 2,0±0,1ml de muestra previamente incubada a 35ºC durante 90s. Para el análisis, se consideró la relación entre el máximo de la variación en la resistencia de cada sensor y su resistencia base El rango de relaciones masa/carga analizados con el MS fue 50-200amu, utilizando impacto electrónico como técnica de ionización y un cuadrupolo como analizador. Los perfiles de olor determinados por NE-MS se analizaron mediante Análisis de Componentes Principales (PCA) con selección de variables (Alphasoft V8®), obteniéndose 2 componentes, los cuales explicaron el 50,3 y el 43,1% de la varianza total, respectivamente. Se observó que la tecnología NE-MS es capaz de discriminar los aceites provenientes en función de sus respectivos tratamientos, por lo que las condiciones operativas de obtención de aceite por EFSC pueden ejercer su influencia sobre el olor de un producto. A través de la tecnología NE-MS es posible diferenciar el perfil de olor de los aceites de chía obtenidos bajo diferentes condiciones operativas por lo que resulta primordial la selección y el control de las variables aplicadas al proceso.Chia seed (Salvia hispanica L.) contains about 32-39% of oil by weight, with a high content of a- linolenic acid (C18:3) (61–70%). The extraction with supercritical fluids (EFSC) using CO2 results an interesting alternative to the extraction of vegetable oils because it does not present the problems associated with the use of organic solvents, obtaining a high quality product. Therefore, the selection of the optimum pressure and temperature conditions of this process is important. Thus, the values of these parameters can affect the smell profile (organoleptic quality parameter) of the final product. The objective of this work was to evaluate the smell profile of the chia oil obtained by EFSC depending on the extraction conditions used. The EFSC was carried out under the following operative conditions: pressure (250 and 450 bar), temperatures (40 and 60ºC), with and without the use of ethanol as cosolvent, with a flow rate of 8 kg/h CO2. The smell profile was analyzed with an Electronic Nose coupled with a Mass Spectrometer (NE-MS) (a-Prometheus, Alpha MOS, France) using the methodology of the static head space and 18 semi selective sensors against to the different groups of volatile compounds of the food. The signal generated in each sensor is the value of the electric resistance caused by adsorption of the volatile compounds. The set of responses obtained in each sensor produces a characteristic pattern of the smell profile of the food matrix assayed. Samples of 2.0 ± 0.1 ml previously incubated at 35 ºC for 90 s were analyzed. For the study, the ratio between the maximum variation of the resistance of each sensor and its base resistance was considered. Mass/charge ratio assayed with the MS was 50-200 amu, using electronic impact as ionization technique and a quadrupole analyzer. The smell profiles determined by NE-MS were analyzed by Principal Component Analyses (PCA) with a selection of variables (Alphasoft V8®), obtaining 2 components that explained 50.3 and 43.1% of total variance, respectively. It was observed that NE-MS technology could discriminate the oils according to the different treatments, so the operative conditions of the oil extraction by EFSC influence the smell of the product. Therefore, the selection and control of the applied variables in the EFSC is very relevant.Centro de Investigación y Desarrollo en Criotecnología de Alimento