Systems, methods, and apparatus of a low conductance silicon micro-leak for mass spectrometer inlet

Systems, methods and apparatus are provided through which in some embodiments a mass spectrometer micro-leak includes a number of channels fabricated by semiconductor processing tools and that includes a number of inlet holes that provide access to the channels

Systems, Methods, and Apparatus of a Low Conductance Silicon Micro-Leak for Mass Spectrometer Inlet

Systems, methods and apparatus are provided through which in some embodiments a mass spectrometer micro-leak includes a number of channels fabricated by semiconductor processing tools and that includes a number of inlet holes that provide access to the channels

Local industrial pollution induces astrocyte cytoskeleton rearrangement in the dice snake brain: GFAP as a biomarker

The present study was designed to evaluate the responsiveness of modulation of glial fibrillary acidic protein (GFAP) content and its fragmentation in the snake brain as a biomarker of local industrial pollution of aquatic ecosystems. Despite GFAP being a well known cytoskeleton marker of astrocytes’ reactivity in the brain of vertebrates, its expression in the snake brain remains insufficiently described. The GFAP expression and its fragmentation were detected using the immunoblot method in the snake brain. ROS level was determined with dichlorofluorescein diacetate fluorescence. The content of the glial fibrillary acidic protein (GFAP) of filament (cytoskeleton) and soluble (cytosol) fractions in the brain of dice snake Natrix tessellata from three ecosystems with different rates of industrial pollution were studied (two polluted and one clean control site). Characteristic increase in GFAP fragmentation was noted for the snakes from both the researched polluted sites. Significant increase in the content of the GFAP cleaved polypeptide fragments induced by industrial pollution exposure was confirmed in the snakes’ brains. Meaningful GFAP fragmentation was determined in snake brain astrocytes as an increase in cleaved fragments of 47–35 kDa molecular weight for both soluble and cytoskeletal GFAP fractions. We found significant abnormality in the ratio of the GFAP soluble fraction to the cytoskeletal one in contaminant-exposed dice snakes. It should testify to significant metabolic disturbance in nerve cells of the dice snakes. Furthermore, growth of reactive oxygen species level as the main cause of oxidative stress was determined in brains of the snakes exposed to environmental toxicity. Thus, astrocyte cytoskeleton disorders are associated with pollutant-induced redox imbalance in the snake brain. Despite the limited data on glial cell biology in the reptilian brain, the observed results prove that snake astrocytes can respond to the environmental toxicity using typical astroglial response. The presented results evidence that monitoring of molecular characteristics of glial cytoskeleton in dice snakes could be used as reliable biomarker of neurotoxicity and adverse effects of industrial pollution. Further studies are required to elucidate the role of astrocyte cytoskeleton in the response against neurotoxic contaminants

Correlation between Interleukin-4 and Interleukin-6 and auto antibodies in Systemic Lupus Erythematosus.

Background: There is a general acceptance which illustrated that auto antibodies act as a central immunological disturbance in most of the auto immune diseases, among these auto immune diseaselies the SLE Patients and Methods: Thirty five patients with SLE were compared to twenty age and sex matched, control subjects and studied for the presence of auto antibodies, plus IL-4 and IL-6 using Elisa method and immune fluorescent method (for ANA only) Results: Data showed that IL-6 detectable levels were statistically significant in patients with positive anti ds-DNA, but not significant statistically in ANA positive patients although it was detected in 24 (70.6%) of positive ANA patients, while there was no statistically significant correlation between IL- 4 detectable level and autoantibodies production. Conclusion: There is apparently a positive correlation between IL-6 and anti ds DNA production in lupus patients

Galileo Probe Mass Spectrometer experiment

The Galileo Probe Mass Spectrometer (GPMS) is a Probe instrument designed to measure the chemical and isotopic composition including vertical variations of the constituents in the atmosphere of Jupiter. The measurement will be performed by in situ sampling of the ambient atmosphere in the pressure range from approximately 150 mbar to 20 bar. In addition batch sampling will be performed for noble gas composition measurement and isotopic ratio determination and for sensitivity enhancement of non-reactive trace gases.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/43775/1/11214_2004_Article_BF00216852.pd

The abundances of constituents of Titan's atmosphere from the GCMS instrument on the Huygens probe

Saturn's largest moon, Titan, remains an enigma, explored only by remote sensing from Earth, and by the Voyager and Cassini spacecraft. The most puzzling aspects include the origin of the molecular nitrogen and methane in its atmosphere, and the mechanism(s) by which methane is maintained in the face of rapid destruction by photolysis. The Huygens probe, launched from the Cassini spacecraft, has made the first direct observations of the satellite's surface and lower atmosphere. Here we report direct atmospheric measurements from the Gas Chromatograph Mass Spectrometer (GCMS), including altitude profiles of the constituents, isotopic ratios and trace species ( including organic compounds). The primary constituents were confirmed to be nitrogen and methane. Noble gases other than argon were not detected. The argon includes primordial Ar-36, and the radiogenic isotope Ar-40, providing an important constraint on the outgassing history of Titan. Trace organic species, including cyanogen and ethane, were found in surface measurements.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62703/1/nature04122.pd

A Repurposing Programme Evaluating Repurposing Transdermal Oestradiol Patches for the Treatment of Prostate Cancer Within the PATCH and STAMPEDE Trials: Current Results and Adapting Trial Design

AIMS: Androgen deprivation therapy (ADT), usually achieved with luteinising hormone releasing hormone analogues (LHRHa), is central to prostate cancer management. LHRHa reduce both testosterone and oestrogen and are associated with significant long-term toxicity. Previous use of oral oestrogens as ADT was curtailed because of cardiovascular toxicity. Transdermal oestrogen (tE2) patches are a potential alternative ADT, supressing testosterone without the associated oestrogen-depletion toxicities (osteoporosis, hot flushes, metabolic abnormalities) and avoiding cardiovascular toxicity, and we here describe their evaluation in men with prostate cancer. MATERIALS AND METHODS: The PATCH (NCT00303784) adaptive trials programme (incorporating recruitment through the STAMPEDE [NCT00268476] platform) is evaluating the safety and efficacy of tE2 patches as ADT for men with prostate cancer. An initial randomised (LHRHa versus tE2) phase II study (n = 251) with cardiovascular toxicity as the primary outcome measure has expanded into a phase III evaluation. Those with locally advanced (M0) or metastatic (M1) prostate cancer are eligible. To reflect changes in both management and prognosis, the PATCH programme is now evaluating these cohorts separately. RESULTS: to date: Recruitment is complete, with 1362 and 1128 in the M0 and M1 cohorts, respectively. Rates of androgen suppression with tE2 were equivalent to LHRHa, with improved metabolic parameters, quality of life and bone health indices (mean absolute change in lumbar spine bone mineral density of -3.0% for LHRHa and +7.9% for tE2 with an estimated difference between arms of 9.3% (95% confidence interval 5.3-13.4). Importantly, rates of cardiovascular events were not significantly different between the two arms and the time to first cardiovascular event did not differ between treatment groups (hazard ratio 1.11, 95% confidence interval 0.80-1.53; P = 0.54). Oncological outcomes are awaited. FUTURE: Efficacy results for the M0 cohort (primary outcome measure metastases-free survival) are expected in the final quarter of 2023. For M1 patients (primary outcome measure - overall survival), analysis using restricted mean survival time is being explored. Allied translational work on longitudinal samples is underway

Dose escalation improves therapeutic outcome: post hoc analysis of data from a 12-week, multicentre, double-blind, parallel-group trial of trospium chloride in patients with urinary urge incontinence

<p>Abstract</p> <p>Background</p> <p>Flexible dosing of anticholinergics used for overactive bladder (OAB) treatment is a useful strategy in clinical practice for achieving a maximum effective and maximum tolerated level of therapeutic benefit. In this post hoc analysis we evaluated the efficacy and tolerability of trospium chloride treatment for urinary urge incontinence (UUI) with focus on flexible dosing.</p> <p>Methods</p> <p>The data came from a 12-week, randomised, double-blind, phase IIIb study in which 1658 patients with urinary frequency plus urge incontinence received trospium chloride 15 mg TID (n = 828) or 2.5 mg oxybutynin hydrochloride TID (n = 830). After four weeks, daily doses were doubled and not readjusted in 29.2% (242/828) of patients in the trospium group, and in 23.3% (193/830) in the oxybuytnin group, until the end of treatment. We assessed the absolute reduction in weekly UUI episodes and the change in intensity of dry mouth, recorded in patients' micturition diaries. Adverse events were also evaluated. Statistics were descriptive.</p> <p>Results</p> <p>Dose escalation of either trospium or oxybutynin increased reduction in UUI episodes in the population studied. At study end, there were no relevant differences between the "dose adjustment" subgroups and the respective "no dose adjustment" subgroups (trospium: <it>P </it>= 0.249; oxybutynin: <it>P </it>= 0.349). After dose escalation, worsening of dry mouth was higher in both dose adjusted subgroups compared to the respective "no dose adjustment" subgroups (<it>P </it>< 0.001). Worsening of dry mouth was lower in the trospium groups than in the oxybutynin groups (<it>P </it>< 0.001). Adverse events were increased in the dose adjusted subgroups.</p> <p>Conclusions</p> <p>Flexible dosing of trospium was proven to be as effective, but better tolerated as the officially approved adjusted dose of oxybutynin.</p> <p>Trial registration (parent study)</p> <p>The study was registered with the German Federal Institute for Drugs and Medical Devices (BfArM, Berlin, Germany), registration number 4022383, as required at the time point of planning this study.</p

Estimating the future global dose demand for measles–rubella microarray patches

BackgroundProgress toward measles and rubella (MR) elimination has stagnated as countries are unable to reach the required 95% vaccine coverage. Microarray patches (MAPs) are anticipated to offer significant programmatic advantages to needle and syringe (N/S) presentation and increase MR vaccination coverage. A demand forecast analysis of the programmatic doses required (PDR) could accelerate MR-MAP development by informing the size and return of the investment required to manufacture MAPs.MethodsUnconstrained global MR-MAP demand for 2030–2040 was estimated for three scenarios, for groups of countries with similar characteristics (archetypes), and four types of uses of MR-MAPs (use cases). The base scenario 1 assumed that MR-MAPs would replace a share of MR doses delivered by N/S, and that MAPs can reach a proportion of previously unimmunised populations. Scenario 2 assumed that MR-MAPs would be piloted in selected countries in each region of the World Health Organization (WHO); and scenario 3 explored introduction of MR-MAPs earlier in countries with the lowest measles vaccine coverage and highest MR disease burden. We conducted sensitivity analyses to measure the impact of data uncertainty.ResultsFor the base scenario (1), the estimated global PDR for MR-MAPs was forecasted at 30 million doses in 2030 and increased to 220 million doses by 2040. Compared to scenario 1, scenario 2 resulted in an overall decrease in PDR of 18%, and scenario 3 resulted in a 21% increase in PDR between 2030 and 2040. Sensitivity analyses revealed that assumptions around the anticipated reach or coverage of MR-MAPs, particularly in the hard-to-reach and MOV populations, and the market penetration of MR-MAPs significantly impacted the estimated PDR.ConclusionsSignificant demand is expected for MR-MAPs between 2030 and 2040, however, efforts are required to address remaining data quality, uncertainties and gaps that underpin the assumptions in this analysis

Primary leptomeningeal plasmablastic lymphoma

Lymphomas that develop in human immunodeficiency virus (HIV) infected patients are predominantly aggressive B-cells lymphomas. The most common HIV-associated lymphomas include Burkitt lymphoma, diffuse large B-cell lymphoma (that often involves the CNS), primary effusion lymphoma, and plasmablastic lymphoma (PBL). Of these, PBL is relatively uncommon and displays a distinct affinity for presentation in the oral cavity. In this manuscript we report a previously undescribed primary leptomeningeal form of PBL in a patient with acquired immunodeficiency syndrome. A 40-year-old HIV positive man presented with acute onset confusion, emesis, and altered mental status. Lumbar puncture showed numerous nucleated cells with atypical plasmocyte predominance. CSF flowcytometry showed kappa restriction with CD8 and CD38 positivity and negative lymphocyte markers, while the MRI showed diffuse leptomeningeal enhancement. As the extensive systemic work-up failed to reveal any disease outside the brain, an en bloc diagnostic brain and meningeal biopsy was performed. The biopsy specimen showed sheets of plasmacytoid cells with one or more large nuclei, prominent nuclear chromatin, scattered mitoses, and abundant cytoplasm, highly suggestive of plasmablastic lymphoma. HIV-associated malignancies have protean and often confusing presentations, which pose diagnostic difficulties posed to the practicing neurological-surgeons. Even in cases where an infectious cause is suspected for the meningeal enhancement, neoplastic involvement should be considered, and cytology and flow-cytometry should be routinely ordered on the CSF samples