Historical reconstruction of polychlorinated biphenyl (PCB) exposures for workers in a capacitor manufacturing plant

We developed a semiquantitative job exposure matrix (JEM) for workers exposed to polychlorinated biphenyls (PCBs) at a capacitor manufacturing plant from 1946 to 1977. In a recently updated mortality study, mortality of prostate and stomach cancer increased with increasing levels of cumulative exposure estimated with this JEM (trend p values = 0.003 and 0.04, respectively). Capacitor manufacturing began with winding bales of foil and paper film, which were placed in a metal capacitor box (pre-assembly), and placed in a vacuum chamber for flood-filling (impregnation) with dielectric fluid (PCBs). Capacitors dripping with PCB residues were then transported to sealing stations where ports were soldered shut before degreasing, leak testing, and painting. Using a systematic approach, all 509 unique jobs identified in the work histories were rated by predetermined process- and plant-specific exposure determinants; then categorized based on the jobs' similarities (combination of exposure determinants) into 35 job exposure categories. The job exposure categories were ranked followed by a qualitative PCB exposure rating (baseline, low, medium, and high) for inhalation and dermal intensity. Category differences in other chemical exposures (solvents, etc.) prevented further combining of categories. The mean of all available PCB concentrations (1975 and 1977) for jobs within each intensity rating was regarded as a representative value for that intensity level. Inhalation (in microgram per cubic milligram) and dermal (unitless) exposures were regarded as equally important. Intensity was frequency adjusted for jobs with continuous or intermittent PCB exposures. Era-modifying factors were applied to the earlier time periods (1946-1974) because exposures were considered to have been greater than in later eras (1975-1977). Such interpolations, extrapolations, and modifying factors may introduce non-differential misclassification; however, we do believe our rigorous method minimized misclassification, as shown by the significant exposure-response trends in the epidemiologic analysis.

Digestibilidad in situ de dietas con harina de nopal deshidratado conteniendo un preparado de enzimas fibrolíticas exógenas

Se evaluó el efecto de un preparado de enzimas fibrolíticas exógenas (celulasas y xilanasas) en la degradabilidad in situ de la materia seca (DisMS), fibra detergente neutro (DFDNr) y fibra detergente ácido residual (DFDAr), en dietas altas o bajas en harina de nopal deshidratado. Se aplicaron concentraciones de 0, 1, 2 y 3 g de enzima por kilogramo de materia seca al inicio y 24 horas antes de la degradación in situ. Se determinó la concentración de ácidos grasos volátiles totales y de nitrógeno amoniacal a las 0, 3, 6, 9, 12 y 24 horas después de aplicarse la enzima. No se observaron efectos en DisMS, DFDNr y DFDAr; la aplicación al inicio de la degradación in situ mostró valores más altos que a 24 horas para DisMS y DFDNr, pero fue menor para DFDAr. No se observaron diferencias en las interacciones entre niveles de enzima, tipo de dieta y tiempo de pretratamiento. La aplicación de 1 y 3 g de enzima, en la dieta con bajo contenido de harina de nopal, tuvo efectos en el incremento de los ácidos grasos volátiles totales; para el nitrógeno amoniacal, los mejores resultados ocurrieron con 0 y 1 g de enzima.

Pathogenesis of adult-onset Still's disease: new insights from the juvenile counterpart.

Adult-onset Still's disease (AOSD) is a rare inflammatory disease characterized by the classical triad of daily fever, arthritis, and typical salmon-colored rash. Recent accumulation of knowledge, mostly arising from hereditary autoinflammatory diseases and from the systemic-onset juvenile idiopathic arthritis (sJIA), has given raise to new hypotheses on the pathophysiology of AOSD. In this review, we first discuss on the continuum between AOSD and sJIA. Then, we summarize current hypotheses on the underlying pathogenesis: (1) an infectious hypothesis; (2) an autoinflammatory hypothesis; (3) a lymphohistiocytic hypothesis; and (4) a hyperferritinemic hypothesis. Finally, we present the recent data suggesting that patients with AOSD fall into two distinct subgroups with different courses, one with prominent systemic features and one with chronic arthritis.

La metàfora en les teories de la imatge: l’«analogia universal» i el «correlat objectiu»

Aquest treball posa en funcionament una gran xarxa d’intertextualitat generada al voltant d’un fenomen molt complex, que és la metàfora. La metàfora és segurament el motiu pel qual avui ens expressem i pel qual avui escrivim textos. Ja no ho diem pel fet que la metàfora sigui una figura literària molt eficaç per crear bellesa estètica, sinó perquè està implicada en la formació del llenguatge i en l’estructuració de la ment per assimilar i per figurar el coneixement. Per aquest motiu, en el nostre treball, hem volgut donar un enfocament pluridisciplinar a l’estudi de la metàfora, perquè, creiem, que sense aquesta visió àmplia, no es pot arribar a copsar ni entendre aquesta figura retòrica, que és molt més que això.

Membrane lipid composition affects plant heat sensing and modulates Ca ( 2+) -dependent heat shock response.

Understanding how plants sense and respond to heat stress is central to improve crop tolerance and productivity. Recent findings in Physcomitrella patensdemonstrated that the controlled passage of calcium ions across the plasma membrane regulates the heat shock response (HSR). To investigate the effect of membrane lipid composition on the plant HSR, we acclimated P. patens to a slightly elevated yet physiological growth temperature and analysed the signature of calcium influx under a mild heat shock. Compared to tissues grown at 22°C, tissues grown at 32°C had significantly higher overall membrane lipid saturation level and, when submitted to a short heat shock at 35°C, displayed a noticeably reduced calcium influx and a consequent reduced heat shock gene expression. These results show that temperature differences, rather than the absolute temperature, determine the extent of the plant HSR and indicate that membrane lipid composition regulates the calcium-dependent heat-signaling pathway.

Maximising the duration of disease control in metastatic renal cell carcinoma with targeted agents: an expert agreement.

With six targeted agents approved (sorafenib, sunitinib, temsirolimus, bevacizumab [+interferon], everolimus and pazopanib), many patients with metastatic renal cell carcinoma (mRCC) will receive multiple therapies. However, the optimum sequencing approach has not been defined. A group of European experts reviewed available data and shared their clinical experience to compile an expert agreement on the sequential use of targeted agents in mRCC. To date, there are few prospective studies of sequential therapy. The mammalian target of rapamycin (mTOR) inhibitor everolimus was approved for use in patients who failed treatment with inhibitors of vascular endothelial growth factor (VEGF) and VEGF receptors (VEGFR) based on the results from a Phase III placebo-controlled study; however, until then, the only licensed agents across the spectrum of mRCC were VEGF(R) inhibitors (sorafenib, sunitinib and bevacizumab + interferon), and as such, a large body of evidence has accumulated regarding their use in sequence. Data show that sequential use of VEGF(R) inhibitors may be an effective treatment strategy to achieve prolonged clinical benefit. The optimal place of each targeted agent in the treatment sequence is still unclear, and data from large prospective studies are needed. The Phase III AXIS study of second-line sorafenib vs. axitinib (including post-VEGF(R) inhibitors) has completed, but the data are not yet published; other ongoing studies include the Phase III SWITCH study of sorafenib-sunitinib vs. sunitinib-sorafenib (NCT00732914); the Phase III 404 study of temsirolimus vs. sorafenib post-sunitinib (NCT00474786) and the Phase II RECORD 3 study of sunitinib-everolimus vs. everolimus-sunitinib (NCT00903175). Until additional data are available, consideration of patient response and tolerability to treatment may facilitate current decision-making regarding when to switch and which treatment to switch to in real-life clinical practice.

Visuospatial working memory deficits and visual pursuit impairments are not directly related in schizophrenia.

OBJECTIVE: Patients with schizophrenia show deficits in visuospatial working memory and visual pursuit processes. It is currently unclear, however, whether both impairments are related to a common neuropathological origin. The purpose of the present study was therefore to examine the possible relations between the encoding and the discrimination of dynamic visuospatial stimuli in schizophrenia. METHOD: Sixteen outpatients with schizophrenia and 16 control subjects were asked to encode complex disc displacements presented on a screen. After a delay, participants had to identify the previously presented disc trajectory from a choice of six static linear paths, among which were five incorrect paths. The precision of visual pursuit eye movements during the initial presentation of the dynamic stimulus was assessed. The fixations and scanning time in definite regions of the six paths presented during the discrimination phase were investigated. RESULTS: In comparison with controls, patients showed poorer task performance, reduced pursuit accuracy during incorrect trials and less time scanning the correct stimulus or the incorrect paths approximating its global structure. Patients also spent less time scanning the leftmost portion of the correct path even when making a correct choice. The accuracy of visual pursuit and head movements, however, was not correlated with task performance. CONCLUSIONS: The present study provides direct support for the hypothesis that active integration of visuospatial information within working memory is deficient in schizophrenia. In contrast, a general impairment of oculomotor mechanisms involved in smooth pursuit did not appear to be directly related to lower visuospatial working memory performance in schizophrenia.

Inequality measurement for ordered response health data

Because self-reported health status [SRHS] is an ordered response variable, inequality measurement for SRHS data requires a numerical scale for converting individual responses into a summary statistic. The choice of scale is however problematic, since small variations in the numerical scale may reverse the ordering of a given pair of distributions of SRHS data in relation to conventional inequality indices such as the variance. This paper introduces a parametric family of inequality indices, founded on an inequality ordering proposed by Allison and Foster [Allison, R.A., Foster, J., 2004. Measuring health inequalities using qualitative data. Journal of Health Economics 23, 505-524], which satisfy a suitable invariance property with respect to the choice of numerical scale. Several key members of the parametric family are also derived, and an empirical application using data from the Swiss Health Survey illustrates the proposed methodology. [Authors]

Oviposition-induced changes in Arabidopsis genome expression: anticipating your enemy?

Plants have evolved exquisite ways to detect their enemies and are able to induce defenses responses tailored to their specific aggressors. Insect eggs deposited on a leaf represent a future threat as larvae hatching from the egg will ultimately feed on the plant. Although direct and indirect defenses towards oviposition have been documented, our knowledge of the molecular changes triggered by egg deposition is limited. Using a whole-genome microarray, we recently analyzed the expression profile of Arabidopsis thaliana leaves after oviposition by two pierid butterflies. Eggs laid by the large white Pieris brassicae modified the expression of hundreds of genes. The transcript signature included defense and stress-related genes that were also induced in plants experiencing localized cell death. Further analyses revealed that cellular changes associated with a hypersensitive response occur at the site of egg deposition and that they are triggered by egg-derived elicitors. Our study brings molecular evidence for previous observations of oviposition-induced necrosis in other plant species and might illustrate a direct defense of the plant against the egg. In this addendum, we discuss the relevance of the oviposition-induced gene expression changes and the possibility that plants use eggs as cues to anticipate their enemies.

Suprachoroidal electrotransfer: a nonviral gene delivery method to transfect the choroid and the retina without detaching the retina.

Photoreceptors and retinal pigment epithelial cells (RPE) targeting remains challenging in ocular gene therapy. Viral gene transfer, the only method having reached clinical evaluation, still raises safety concerns when administered via subretinal injections. We have developed a novel transfection method in the adult rat, called suprachoroidal electrotransfer (ET), combining the administration of nonviral plasmid DNA into the suprachoroidal space with the application of an electrical field. Optimization of injection, electrical parameters and external electrodes geometry using a reporter plasmid, resulted in a large area of transfected tissues. Not only choroidal cells but also RPE, and potentially photoreceptors, were efficiently transduced for at least a month when using a cytomegalovirus (CMV) promoter. No ocular complications were recorded by angiographic, electroretinographic, and histological analyses, demonstrating that under selected conditions the procedure is devoid of side effects on the retina or the vasculature integrity. Moreover, a significant inhibition of laser induced-choroidal neovascularization (CNV) was achieved 15 days after transfection of a soluble vascular endothelial growth factor receptor-1 (sFlt-1)-encoding plasmid. This is the first nonviral gene transfer technique that is efficient for RPE targeting without inducing retinal detachment. This novel minimally invasive nonviral gene therapy method may open new prospects for human retinal therapies.

A prospective development study investigating focal irreversible electroporation in men with localised prostate cancer: Nanoknife Electroporation Ablation Trial (NEAT).

INTRODUCTION: Focal therapy may reduce the toxicity of current radical treatments while maintaining the oncological benefit. Irreversible electroporation (IRE) has been proposed to be tissue selective and so might have favourable characteristics compared to the currently used prostate ablative technologies. The aim of this trial is to determine the adverse events, genito-urinary side effects and early histological outcomes of focal IRE in men with localised prostate cancer. METHODS: This is a single centre prospective development (stage 2a) study following the IDEAL recommendations for evaluating new surgical procedures. Twenty men who have MRI-visible disease localised in the anterior part of the prostate will be recruited. The sample size permits a precision estimate around key functional outcomes. Inclusion criteria include PSA ≤ 15 ng/ml, Gleason score ≤ 4 + 3, stage T2N0M0 and absence of clinically significant disease outside the treatment area. Treatment delivery will be changed in an adaptive iterative manner so as to allow optimisation of the IRE protocol. After focal IRE, men will be followed during 12 months using validated patient reported outcome measures (IPSS, IIEF-15, UCLA-EPIC, EQ-5D, FACT-P, MAX-PC). Early disease control will be evaluated by mpMRI and targeted transperineal biopsy of the treated area at 6 months. DISCUSSION: The NEAT trial will assess the early functional and disease control outcome of focal IRE using an adaptive design. Our protocol can provide guidance for designing an adaptive trial to assess new surgical technologies in the challenging landscape of health technology assessment in prostate cancer treatment.

Newton - filosofi vai tiedemies?

Vastine kosmologian professori Kari Enqvistin kysymykseen artikkelissa "Onko fysiikka filosofiaa?" (TT-lehdessä 2/2006)