Unlocking stray light mysteries in the CoRot baffle with the time-of-flight method.

Stray light (SL) has emerged as a primary limiting factor for space telescopes. Pre-launch testing is essential for validating performance and identifying potential issues. However, traditional methods do not enable the decomposition and identification of individual SL contributors. Consequently, when problems arise, resolving them often involves a cumbersome and risky trial-and-error approach. The time-of-flight (ToF) method was recently introduced, employing a pulsed laser source and ultrafast sensor to characterize individual SL contributors. A proof of concept was achieved using a simple three-lens system. In this paper, we apply the ToF method to a real space optical system: the spare model of the CoRoT baffle. We successfully measured individual SL contributors over a dynamic range of 10-11, identifying direct scattering on vane edges and two-step scattering paths. Our results provide a performance breakdown, differentiating intrinsic baffle SL from contributions arising from experimental conditions. Notably, the ToF method allowed us to discriminate air scattering, eliminating the need for expensive vacuum testing. The ToF provides unparallel insights, including defects identification. For instance, we identified the presence of localized dust particles causing significant SL. These results confirm the utility of the ToF method even for the most challenging space systems.

Trichloroethylene and its metabolite TaClo lead to degeneration of substantia nigra dopaminergic neurones: Effects in wild type and human A30P mutant α-synuclein mice.

Parkinson's disease (PD) is characterised pathologically by degeneration of the dopaminergic (DA) neurones of the substantia nigra pars compacta (SNpc) and the presence of α-synuclein containing Lewy body inclusions. Trichloroethylene (TCE) has been suggested as a potential environmental chemical that may contribute to the development of PD, via conversion to the neurotoxin, 1-Trichloromethyl-1,2,3,4-tetrahydro-ß-carboline (TaClo). We investigated the effect of an 8 week exposure to TCE or TaClo on wild type and, as an experimental model of PD, A30P mutant α-synuclein overexpressing mice using a combination of behaviour and pathology. TCE or TaClo exposure caused significant DA neuronal loss within the SNpc in both wild type and transgenic mice. Cell numbers were lower in A30P animals than wild type, however, no additive effect of TCE or TaClo exposure and A30P overexpression was found. TCE or TaClo did not appear to lead to acceleration of motor or cognitive deficits in either wild type or A30P mutant mice, potentially because of the modest reductions of DA neuronal number in the SNpc. Our results do however suggest that TCE exposure could be a possible factor in development of PD like changes following exposure.

The Far Ultra-Violet imager on the ICON mission.

ICON Far UltraViolet (FUV) imager contributes to the ICON science objectives by providing remote sensing measurements of the daytime and nighttime atmosphere/ionosphere. During sunlit atmospheric conditions, ICON FUV images the limb altitude profile in the shortwave (SW) band at 135.6 nm and the longwave (LW) band at 157 nm perpendicular to the satellite motion to retrieve the atmospheric O/N2 ratio. In conditions of atmospheric darkness, ICON FUV measures the 135.6 nm recombination emission of O+ ions used to compute the nighttime ionospheric altitude distribution. ICON Far UltraViolet (FUV) imager is a CzernyTurner design Spectrographic Imager with two exit slits and corresponding back imager cameras that produce two independent images in separate wavelength bands on two detectors. All observations will be processed as limb altitude profiles. In addition, the ionospheric 135.6 nm data will be processed as longitude and latitude spatial maps to obtain images of ion distributions around regions of equatorial spread F. The ICON FUV optic axis is pointed 20 degrees below local horizontal and has a steering mirror that allows the field of view to be steered up to 30 degrees forward and aft, to keep the local magnetic meridian in the field of view. The detectors are micro channel plate (MCP) intensified FUV tubes with the phosphor fiber-optically coupled to Charge Coupled Devices (CCDs). The dual stack MCP-s amplify the photoelectron signals to dominate the CCD noise and the rapidly scanned frames are co-added to digitally create 12-second integrated images. Digital on-board signal processing is used to compensate for geometric distortion and satellite motion and to achieve data compression. The instrument was originally aligned in visible light by using a special grating and visible cameras. Final alignment, functional and environmental testing and calibration were performed in a large vacuum chamber with a UV source. The test and calibration program showed that ICON FUV meets its design requirements and is ready to be launched on the ICON spacecraft.

Diquat causes caspase-independent cell death in SH-SY5Y cells by production of ROS independently of mitochondria.

Evidence indicates that Parkinson's disease (PD), in addition to having a genetic aetiology, has an environmental component that contributes to disease onset and progression. The exact nature of any environmental agent contributing to PD is unknown in most cases. Given its similarity to paraquat, an agrochemical removed from registration in the EU for its suspected potential to cause PD, we have investigated the in vitro capacity of the related herbicide Diquat to cause PD-like cell death. Diquat showed greater toxicity towards SH-SY5Y neuroblastoma cells and human midbrain neural cells than paraquat and also MPTP, which was independent of dopamine transporter-mediated uptake. Diquat caused cell death independently of caspase activation, potentially via RIP1 kinase, with only a minor contribution from apoptosis, which was accompanied by enhanced reactive oxygen species production in the absence of major inhibition of complex I of the mitochondrial respiratory chain. No changes in α-synuclein expression were observed following 24-h or 4-week exposure. Diquat may, therefore, kill neural tissue by programmed necrosis rather than apoptosis, reflecting the pathological changes seen following high-level exposure, although its ability to promote PD is unclear.

Use of a human skin in vitro model to investigate the influence of 'every-day' clothing and skin surface decontamination on the percutaneous penetration of organophosphates.

UNLABELLED: Organophosphates (OPs) are widely used in agriculture. Many studies have investigated the capability of personal protective equipment (PPE) to reduce chemical exposure; however, investigations into the protective effect of 'every-day' clothing are rare. The purpose of this study was to investigate the protective effect of 'every-day' clothing against dermal exposure and to measure early decontamination of skin following exposure to chlorpyrifos and dichlorvos. Using human skin in vitro, absorption of (14)C-labelled chlorpyrifos (500 ng/cm(2)), was shown to be significantly reduced when applied to clothed skin (cotton shirt), regardless of application vehicle (isopropanol (IPA) or propylene glycol (PG)). The majority of applied dose was retained within the clothing after 4 h exposure. Significant reduction in absorption of chlorpyrifos (in PG) was seen through clothed skin when supplemented with skin decontamination at 4 h, compared with clothed skin decontaminated after 24 h, however, this was not observed with IPA. Absorption of dichlorvos (5 µg/cm(2)) was greater through unclothed skin than chlorpyrifos for all vehicles (IPA, isopropyl myristate (IPM) and PG). Significant reduction in absorption was observed when decontaminating clothed skin at 30 min, compared with decontamination at 24 h (post-exposure) for all vehicles. RESULT: indicate that 'every-day' clothing is effective at reducing exposure to chemicals in contact with skin. Washing the skin surface immediately following removal of exposed clothing can further reduce exposure, depending on the properties of the chemical and vehicle applied.

Percutaneous absorption and distribution of organophosphates (chlorpyrifos and dichlorvos) following dermal exposure and decontamination scenarios using in vitro human skin model.

To date, there has been little research investigating low-level human exposure to chemicals, and so the aim of this study was to examine the percutaneous penetration of organophosphates (dichlorvos and chlorpyrifos) using low-level exposure scenarios in vitro. Dermal absorption of chlorpyrifos applied in different vehicles was measured at 0, 4, 8 and 24 h, after dose application for 4 and 24 h exposure (finite dose, 500 ng/cm(2)) in isopropanol (IPA), isopropyl myristate (IPM) and propylene glycol (PG). Dichlorvos was applied to the skin for 24 h (infinite dose, 1 mg/cm(2) and 10 mg/cm(2); finite dose, 5 µg/cm(2)) using the same vehicles. Human skin was mounted in flow through diffusion cells with minimum essential medium eagle pH 7.4 (supplemented with 2% BSA) as receptor fluid. Following exposure, the skin surface dose was removed by tissue swabbing, the stratum corneum removed by sequential tape stripping, and the skin digested prior to scintillation counting (chlorpyrifos), or GC/MS analysis (dichlorvos). The dermal absorption of chlorpyrifos was the greatest following application in PG (19.5% of dose), when compared with absorption from the IPA and IPM vehicles (10.3% and 1.9% absorbed respectively). However, dichlorvos showed greater dermal absorption than chlorpyrifos from all vehicles used, with greatest absorption from the IPA vehicle (38.6% absorbed). Although dichlorvos exhibited a short lag time (0.6 h from IPA and IP vehicles, and 0.4 h from PG), chlorpyrifos displayed greater propensity to accumulate in the stratum corneum and epidermis/dermis. These results demonstrate that prompt skin surface decontamination would be required for both dichlorvos and chlorpyrifos (and chemicals with similar properties) in the event of skin contact. The magnitude of the skin reservoir formed with chlorpyrifos was time dependent, therefore, prompt decontamination of this and similar chemicals would be required to reduce delayed systemic absorption.

Blood metal ion testing is an effectivescreening tool to identify poorly performing metal-on-metal bearingsurfaces.

OBJECTIVES: The aims of this piece of work were to: 1) record the background concentrations of blood chromium (Cr) and cobalt (Co) concentrations in a large group of subjects; 2) to compare blood/serum Cr and Co concentrations with retrieved metal-on-metal (MoM) hip resurfacings; 3) to examine the distribution of Co and Cr in the serum and whole blood of patients with MoM hip arthroplasties; and 4) to further understand the partitioning of metal ions between the serum and whole blood fractions. METHODS: A total of 3042 blood samples donated to the local transfusion centre were analysed to record Co and Cr concentrations. Also, 91 hip resurfacing devices from patients who had given pre-revision blood/serum samples for metal ion analysis underwent volumetric wear assessment using a coordinate measuring machine. Linear regression analysis was carried out and receiver operating characteristic curves were constructed to assess the reliability of metal ions to identify abnormally wearing implants. The relationship between serum and whole blood concentrations of Cr and Co in 1048 patients was analysed using Bland-Altman charts. This relationship was further investigated in an in vitro study during which human blood was spiked with trivalent and hexavalent Cr, the serum then separated and the fractions analysed. RESULTS: Only one patient in the transfusion group was found to have a blood Co > 2 µg/l. Blood/Serum Cr and Co concentrations were reliable indicators of abnormal wear. Blood Co appeared to be the most useful clinical test, with a concentration of 4.5 µg/l showing sensitivity and specificity for the detection of abnormal wear of 94% and 95%, respectively. Generated metal ions tended to fill the serum compartment preferentially in vivo and this was replicated in the in vitro study when blood was spiked with trivalent Cr and bivalent Co. CONCLUSIONS: Blood/serum metal ion concentrations are reliable indicators of abnormal wear processes. Important differences exist however between elements and the blood fraction under study. Future guidelines must take these differences into account.

Mitochondrial dysfunction in Parkinson's disease.

Parkinson's disease (PD) is a progressive, neurodegenerative condition that has increasingly been linked with mitochondrial dysfunction and inhibition of the electron transport chain. This inhibition leads to the generation of reactive oxygen species and depletion of cellular energy levels, which can consequently cause cellular damage and death mediated by oxidative stress and excitotoxicity. A number of genes that have been shown to have links with inherited forms of PD encode mitochondrial proteins or proteins implicated in mitochondrial dysfunction, supporting the central involvement of mitochondria in PD. This involvement is corroborated by reports that environmental toxins that inhibit the mitochondrial respiratory chain have been shown to be associated with PD. This paper aims to illustrate the considerable body of evidence linking mitochondrial dysfunction with neuronal cell death in the substantia nigra pars compacta (SNpc) of PD patients and to highlight the important need for further research in this area.

Clinical management of casualties exposed to lung damaging agents: a critical review.

There is no specific antidote for the treatment of casualties exposed to chlorine, phosgene, or mustards; therefore, management is largely supportive. Corticosteroid treatment has been given to casualties accidentally exposed to chlorine. Clinical data on efficacy are inconclusive as the numbers given steroids have been small and the indications for administration unclear. There have been no clinical controlled studies. There is a stronger evidence base from animal studies, particularly from porcine and rodent models. Lung injury induced by phosgene and mustard appears to be mediated by glutathione depletion, lipid peroxidation, free radical generation, and subsequent cellular toxicity. There is limited evidence to suggest that repletion of glutathione reduces and/or prevents lung damage by these agents. This may provide an opportunity for therapeutic intervention.

[Idiopathic polypoidal choroidal vasculopathy leading to blindness]. / Forme cécitante de vasculopathie choroïdienne polypoïdale idiopathique.

Idiopathic polypoidal choroidal vasculopathy (IPCV) has recently been recognized as a distinct cause of recurrent subretinal hemorrhages and exudates as well as multiple hemorrhagic retinal pigment epithelium detachments in the macula. IPCV is usually considered to have a good visual prognosis. We report the case of a 44-year-old woman with particularly severe bilateral macular and peripheral IPCV. The patient was followed for 13 years and had final visual acuity of counting fingers in the right eye and 20/400 in the left eye. Patients with IPCV with macular choroidal neovascularization tend to have a poor visual prognosis. This case of IPCV should alert the physician to be particularly attentive to the follow-up of these patients.

Characterization of human villous and extravillous trophoblasts isolated from first trimester placenta.

Trophoblasts of the human placenta differentiate along two pathways to give either extravillous cytotrophoblasts (EVCT) with invasive properties and that are implicated in the implantation process, or villous cytotrophoblasts (VCT) that by cell fusion form multinucleated syncytiotrophoblasts. We report the first isolation and purification of these two cell types from the same chorionic villi of first trimester human placenta. We also studied their differentiation in vitro. Electron microscopy showed that in contrast to VCT, EVCT had no microvilli but contained large fibrinoid inclusions. EVCT cultures required a matrix to invade, and as previously established, VCT cultured on plastic dishes aggregated and fused to form syncytiotrophoblasts. These differentiation processes were characterized by a particular pattern of gene expression as assessed by real-time PCR and confirmed by immunocytochemical analysis of the corresponding proteins. EVCT cultured in vitro expressed high levels of HLA-G, c-erbB2, human placental lactogen, and very little human chorionic gonadotropin. Interestingly, TGFbeta2 was a marker of EVCT in vitro and in situ. These data offer a new tool for cell biologists to study the molecular mechanisms involved in human placental development and its pathology.

Upper aerodigestive tract cancers in former employees at an iron and steel works.

Local concern about numbers of laryngeal cancer cases led to an investigation of the incidence of upper aerodigestive tract (UAT) cancer in an industrial cohort. Males (n = 11 470) who had been directly employed at an iron and steel works in northern England at any time between January 1960 and site closure in September 1983 were followed up for UAT cancers until December 1998. The incidence of UAT and laryngeal cancer was compared to the general population of the region via indirect standardization. Fifty-two members of the cohort developed a UAT cancer during 1960-1998. There were no more UAT cancers than expected [standardized incidence ratio = 97, 95% confidence interval (CI) = 72-127], but slightly more laryngeal cancers than expected (standardized incidence ratio = 118, 95% CI = 78-171), although this estimate was less precise. The lack of complete work histories meant that relationships between cancer incidence and length of service or job categories could not be explored.

[Bilateral optic neuropathy in acute methanol intoxication. A case report]. / Neuropathie optique bilatérale par intoxication aiguë au méthanol. A propos d'un cas.

We report a case of methanol blindness. Ophthalmoscopic examination disclosed swelling in the disc margins extending along the adjacent retinal nerve fiber layer. Although this optic neuropathy is now rare, prompt diagnosis and proper treatment in the acute phase can dramatically improve the prognosis.

Cytogenetic response without changes in peripheral cholinesterase enzymes following exposure to a sheep dip containing diazinon in vivo and in vitro.

Occupational exposure to organophosphorus insecticides (OPs), such as diazinon, may be monitored by the measurement of the activity of peripheral cholinesterase enzymes, including erythrocyte acetylcholinesterase (EAChE) and plasma or serum cholinesterase (plasma or serum ChE). Exposures have also been measured by the analysis of dialkyl phosphate metabolites of OPs in urine. The potential health risks associated with exposure, especially those of a neurological nature, may then be estimated, and appropriate measures to reduce or eliminate exposures can be implemented. There is evidence that some OP pesticides may have in vivo genotoxic effects, suggesting a possible link with cancer with long term or repeated heavy exposures. This paper describes work performed in 17 subjects with a single or two exposures to a sheep dip containing diazinon. Urine samples revealed OP metabolites dimethylphosphate (DMP), dimethylthiophosphate (DMTP), diethylphosphate (DEP) and diethylthiophosphate (DETP) in 37% of subjects at low levels which were not elevated after exposure. EAChE and plasma ChE were also unchanged before and after exposure, and were similar to those measured in unexposed control groups. Sister chromatid exchanges (SCE), a marker of chromosome damage, was significantly elevated in peripheral blood lymphocytes after exposure compared with before. SCE were unchanged in a group of non-occupationally exposed workers. In vitro studies with both authentic diazinon (98%) and diazinon in a sheep dip formulation (45%) showed increased SCE and decreased replicative indices, suggesting toxic and genotoxic effects of diazinon.

Electrophysiological and biochemical effects of single and multiple doses of the organophosphate diazinon in the mouse.

Diazinon is an organophosphorus compound (OP) widely used in pesticides. The relationship between dose of diazinon, inhibition of acetylcholinesterase, and effect on neuromuscular transmission has been studied in a mouse model. Inhibition of acetylcholinesterase activity occurred within 1 h, was maximal by 3 h and remained inhibited for at least 24 h. Blood, brain, diaphragm, and soleus acetylcholinesterase activities were differentially affected by diazinon. Brain and soleus activities were not affected by low doses. Multiple daily dosing of diazinon caused a cumulative decrease in acetylcholinesterase activity, although to a lesser extent in brain and soleus. Diazinon had no effect on the activity of neuropathy target esterase. Plasma and brain levels of diazinon peaked at 15 min after dosing and declined with a half-life of 2.5 h. Metabolic products of diazinon were cleared from the urine within 24 h. Increased miniature end-plate current half decay times occurred in a dose-dependent manner. Single doses of diazinon caused an increase in the jitter (variability of latencies) of evoked action potentials recorded in the diaphragm but did not affect end-plate potential (EPP) jitter. Multiple lower doses of diazinon caused an increase in EPP jitter after 28 days. This effect on nerve function was delayed and occurred when acetylcholinesterase activity had returned to control levels. The results indicate that diazinon produces long-term electrophysiological changes in neurotransmission following repeated dosing in the mouse. This has implications for the current use of diazinon; however, there is a need to further define the mechanism of this effect.

Long-term incidence of reopening of macular holes.

OBJECTIVE: To report the incidence of macular hole reopening after initial successful surgery. DESIGN: A noncomparative retrospective case series. PARTICIPANTS: From a series of 137 consecutive cases of idiopathic macular holes operated on between August 1993 and May 1996, the authors analyzed the charts of 116 cases of successful surgery. SETTING: A single university-based ophthalmology department. INTERVENTION: Pars plana vitrectomy, posterior hyaloid peeling, fluid-air and air-gas exchange with a nonexpansile 17% C2F6 mixture followed by face-down positioning. Eighty-eight patients (64%) received autologous platelets as a biologic adjuvant. The anatomic success rate at the first postoperative month was 116 of 137 (85%). One hundred and six patients (91%) were followed up for more than 2 years. MAIN OUTCOME MEASURE: Macular anatomic status. RESULTS: Mean follow-up was 27 months. Eleven eyes of 11 patients (9.5%) had reopening of the macular hole. The mean period between hole surgery and reopening was 15.4 months (range, 8-29). In 8 of these 11 cases, reopening occurred after cataract extraction. In two cases, an epiretinal membrane was noted. In another case cystoid macular edema was present. The final anatomic success rate with one surgical procedure was 105 of 137 (77%). Eight reopened holes were reoperated on and all were anatomic successes at 1 month. However, four patients experienced a second reopening. CONCLUSIONS: Macular hole reopening occurred in 9.5% of cases (11 of 116). The cause of reopening might have been any anatomic stress such as epiretinal membrane formation or macular edema. However, in most of our reopened cases, no definite cause was evident. Four patients experienced recurrent reopening.