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The paper describes preparation of $^6$Li-loaded liquid scintillators by methods involving direct dissolution of $^6$Li salts in the commercial diisopropylnaphthalene (DIPN) solvent, without the formation of water-in-oil emulsions. Methods include incorporation of $^6$Li that, unlike previously reported formulations, does not require additions of water or a strong acid such as hydrochloric acid (HCl). Results of the conducted experiments show that dissolution of aromatic and aliphatic $^6$Li salts in DIPN can be easily achieved at 0.1- 0.3% by weight of atomic $^6$Li, using small additions of waterless surfactants, or mild carboxylic acids. An alternative way suggests incorporation of $^6$Li as a part of a surfactant molecule that can be dissolved in DIPN without any solubilizing additions. Proposed methods enable preparation of efficient $^6$Li-loaded liquid scintillators that, at a large scale of 50 cm, exhibit good pulse shape discrimination (PSD) properties combined with up to 107% of light output and up to 115% of the attenuation length measured relative to standard undoped EJ-309 liquid scintillator., Comment: Submitted to Nuclear Instruments and Methods in Physics Research A

Florida is a site of critical inquiry and figures prominently in the US American imaginary. The Sunshine State sets the stage for broader conversations about cultural difference, climate change, and participatory democracy. Contributors to this special issue apply the canonical circuit of culture model to address the interrelated nature of culture and power. They provide methodologically thick, fleshy interpretive analyses that privilege experiential, experimental, and embodied approaches to take seriously Florida cultural politics, people, and popular forms.

Axion Dark Matter eXperiment (ADMX) ultra low noise haloscope technology has enabled the successful completion of two science runs (1A and 1B) that looked for dark matter axions in the $2.66$ to $3.1$ $\mu$eV mass range with Dine-Fischler-Srednicki-Zhitnisky (DFSZ) sensitivity Ref. [1,2]. Therefore, it is the most sensitive axion search experiment to date in this mass range. We discuss the technological advances made in the last several years to achieve this sensitivity, which includes the implementation of components, such as state-of-the-art quantum limited amplifiers and a dilution refrigerator. Furthermore, we demonstrate the use of a frequency tunable Microstrip Superconducting Quantum Interference Device (SQUID) Amplifier (MSA), in Run 1A, and a Josephson Parametric Amplifier (JPA), in Run 1B, along with novel analysis tools that characterize the system noise temperature., Comment: 23 pages, 28 figures

Background: Validated combined symptom-medication scores (CSMSs) are needed to investigate the effects of allergic rhinitis treatments. This study aimed to use real-life data from the MASK-air® app to generate and validate hypothesis- and data-driven CSMSs. Methods: We used MASK-air® data to assess the concurrent validity, test-retest reliability and responsiveness of one hypothesis-driven CSMS (modified CSMS: mCSMS), one mixed hypothesis- and data-driven score (mixed score), and several data-driven CSMSs. The latter were generated with MASK-air® data following cluster analysis and regression models or factor analysis. These CSMSs were compared with scales measuring (i) the impact of rhinitis on work productivity (visual analogue scale [VAS] of work of MASK-air®, and Work Productivity and Activity Impairment: Allergy Specific [WPAI-AS]), (ii) quality-of-life (EQ-5D VAS) and (iii) control of allergic diseases (Control of Allergic Rhinitis and Asthma Test [CARAT]). Results: We assessed 317,176 days of MASK-air® use from 17,780 users aged 16-90 years, in 25 countries. The mCSMS and the factor analyses-based CSMSs displayed poorer validity and responsiveness compared to the remaining CSMSs. The latter displayed moderate-to-strong correlations with the tested comparators, high test-retest reliability and moderate-to-large responsiveness. Among data-driven CSMSs, a better performance was observed for cluster analyses-based CSMSs. High accuracy (capacity of discriminating different levels of rhinitis control) was observed for the latter (AUC-ROC = 0.904) and for the mixed CSMS (AUC-ROC = 0.820). Conclusion: The mixed CSMS and the cluster-based CSMSs presented medium-high validity, reliability and accuracy, rendering them as candidates for primary endpoints in future rhinitis trials. © 2022 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.

BACKGROUND: A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials. \ud \ud \ud METHODS: This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 1010 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674. \ud \ud \ud FINDINGS: Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0-75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4-97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; pinteraction=0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8-80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3-4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation. \ud \ud \ud INTERPRETATION: ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials. \ud \ud \ud FUNDING: UK Research and Innovation, National Institutes for Health Research (NIHR), Coalition for Epidemic Preparedness Innovations, Bill & Melinda Gates Foundation, Lemann Foundation, Rede D'Or, Brava and Telles Foundation, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland's NIHR Clinical Research Network, and AstraZeneca.

In traumatic brain injury (TBI), membranes such as the dura mater, arachnoid mater, and pia mater play a vital role in transmitting motion from the skull to brain tissue. Magnetic resonance elastography (MRE) is an imaging technique developed for noninvasive estimation of soft tissue material parameters. In MRE, dynamic deformation of brain tissue is induced by skull vibrations during magnetic resonance imaging (MRI); however, skull motion and its mode of transmission to the brain remain largely uncharacterized. In this study, displacements of points in the skull, reconstructed using data from an array of MRI-safe accelerometers, were compared to displacements of neighboring material points in brain tissue, estimated from MRE measurements. Comparison of the relative amplitudes, directions, and temporal phases of harmonic motion in the skulls and brains of six human subjects shows that the skull–brain interface significantly attenuates and delays transmission of motion from skull to brain. In contrast, in a cylindrical gelatin “phantom,” displacements of the rigid case (reconstructed from accelerometer data) were transmitted to the gelatin inside (estimated from MRE data) with little attenuation or phase lag. This quantitative characterization of the skull–brain interface will be valuable in the parameterization and validation of computer models of TBI.

Histone deacetylase (HDAC) inhibitors prevent neural cell death in in vivo models of cerebral ischaemia, brain injury and neurodegenerative disease. One mechanism by which HDAC inhibitors may do this is by suppressing the excessive inflammatory response of chronically activated microglia. However, the molecular mechanisms underlying this anti-inflammatory effect and the specific HDAC responsible are not fully understood. Recent data from in vivo rodent studies have shown that inhibition of class I HDACs suppresses neuroinflammation and is neuroprotective. In our study, we have identified that selective HDAC inhibition with inhibitors apicidin, MS-275 or MI-192, or specific knockdown of HDAC1 or 2 using siRNA, suppresses the expression of cytokines interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-α) in BV-2 murine microglia activated with lipopolysaccharide (LPS). Furthermore, we found that in the absence of HDAC1, HDAC2 is up-regulated and these increased levels are compensatory, suggesting that these two HDACs have redundancy in regulating the inflammatory response of microglia. Investigating the possible underlying anti-inflammatory mechanisms suggests an increase in protein expression is not important. Taken together, this study supports the idea that inhibitors selective towards HDAC1 or HDAC2, may be therapeutically useful for targeting neuroinflammation in brain injuries and neurodegenerative disease.

Histone deacetylase (HDAC) inhibitors prevent neural cell death in in vivo models of cerebral ischaemia, brain injury and neurodegenerative disease. One mechanism by which HDAC inhibitors may do this is by suppressing the excessive inflammatory response of chronically activated microglia. However, the molecular mechanisms underlying this anti-inflammatory effect and the specific HDAC responsible are not fully understood. Recent data from in vivo rodent studies has shown that inhibition of class I HDACs suppresses neuroinflammation and is neuroprotective. In our study we have identified that selective HDAC inhibition with inhibitors apicidin, MS-275 or MI-192, or specific knockdown of HDAC1 or 2 using siRNA, suppresses the expression of cytokines interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-α) in BV2 murine microglia activated with lipopolysaccharide (LPS). Furthermore, we found that in the absence of HDAC1, HDAC2 is upregulated and these increased levels are compensatory, suggesting these two HDACs have redundancy in regulating the inflammatory response of microglia. Investigating the possible underlying anti-inflammatory mechanisms suggests an increase in protein expression is not important. Taken together, this study supports the idea that inhibitors selective towards HDAC1 or HDAC2, may be therapeutically useful for targeting neuroinflammation in brain injuries and neurodegenerative disease.Significance StatementThe number of patients suffering a stroke or a neurodegenerative disease, such as Alzheimer’s is increasing These conditions are severely debilitating and are leading causes of mortality, with neural cell death and loss of brain tissue being a major feature. A number of mechanisms contribute to neuronal death, including inflammation in the brain, but we still lack clinical therapies to inhibit this. The work presented here provides further insight into potential molecular therapeutic targets called histone deacetylases (HDACs), which are thought to contribute to neural cell death by promoting inflammation. We show that down regulation of HDAC1 and 2 is sufficient to reduce this inflammatory response. Our findings have clinical relevance because they identify HDAC1 and 2 as promising targets for therapy.

Additional file 1. IPCRG scaling up activities.

The film documentary titled Hip Hop: beyond beats and rhymes captures ongoing conversations among scholars, cultural critics, and hip hop insiders about the state of African Americans by interrogating distinct expressive forms associated with hip hop culture. Durham draws from two scenes to describe her memories as the researched underclass and as the graduate researcher returning to her childhood public housing community to explore the shifting discursive terrain of hip hop as a struggle over meaning waged through class performances. Class is articulated through taste values and notions of respectability. Durham connects the hip hop mantra emphasizing lived, embodied culture with bell hooks' description of a homeplace to recount her researcher/ed self during the Virginia Beach Greekfest race riots and her visit home where she talks about hip hop feminism with a group of African American women from the Norfolk public housing community. By recalling autoethnographic encounters of hip hop at home, Durham calls attention to the politics of class that echoes behind beats and rhymes.

Objectives—(a) To compare the use of high dose intramuscular midazolam with and without intranasal flumazenil in children after suturing. (b) To compare the use of high dose intramuscular midazolam with low dose intramuscular ketamine in children before suturing. Methods—87 children, aged between 1 and 7 years, presenting with simple wounds needing sedation, were studied. Children considered combative (n=47) were given ketamine (2.5 mg/kg intramuscularly). The remaining 40 children were given midazolam (0.4 mg/kg intramuscularly) with and without flumazenil (25 µg/kg, intranasally). Results—The median oxygen saturation was 97% in both midazolam groups. Flumazenil significantly reduced the amount of agitation during recovery (p=0.048) and also the time at which children were ready for discharge (median 55 versus 95 minutes, p value

The microstructural attributes of directionally solidified Ti-48Al-2Cr-2Nb (in at%) produced by the Power Down and Bridgeman techniques at various cooling rates/growth rates are presented. Fully lamellar α 2 -Ti 3 Al+γ-TiAl microstructures with y particles on grain boundaries are present in all conditions. The directionally solidified structure consists of discrete regions of columnar grains either parallel or radial to the growth direction, as well as a region of equiaxed grains. The phase structure and lamellar structure made by the two techniques are examined. Increasing the cooling rate or growth rate decreases the portion of columnar grains parallel to the growth direction and decreases the lamellar interface spacing.

The phase transformations controlling the microstructural evolution during directional solidification (DS) using the Bridgeman process and subsequent cooling are described for a Ti-52Al-2W-0.5Si intermetallic. The DS structure consists mainly of columnar dendrites with various shapes. α-Ti with a dendritic morphology is the primary solidified phase, followed by an incomplete peritectic reaction liquid (L)+α → γ-TiAl. The remaining liquid solidified as y and silicides. During cooling after solidification a dendrites transform into ordered α 2 and y with various morphologies, including near fully lamellar, script α 2 in a y matrix and blocky α 2 in a y matrix. Very fine tungsten-rich precipitates are also observed. The DS alloy is quite brittle. The microstructural evolution and the reason leading to the brittleness of the alloy are discussed.

OBJECTIVE: To compare the use of low dose intramuscular ketamine with high dose intranasal midazolam in children before suturing. METHODS: Altogether 102 children with simple wounds between 1 and 7 years old were allocated to the two study groups. RESULTS: Two children were excluded from the study because of deviation from the agreed protocol. The 50 children in the ketamine group were less likely to cry or need to be restrained during the procedure than those in the midazolam group (p < 0.01). The median oxygen saturation was 97% in both groups. There was no difference in the recovery behaviour and the range of time at which children were ready for discharge, although the median time for the latter was shorter in the midazolam group (75 v 82 minutes). Vomiting occurred in nine of the ketamine and four of the midazolam group. After discharge both groups had an unsteady gait (73% v 71%) which usually resolved within two hours. CONCLUSION: Intranasal midazolam (0.5 mg/kg) effectively sedated the children in that none could remember the suturing. However a significant number still had to be restrained (86% v 14%). Intramuscular ketamine (2.5 mg/kg) produced dissociative anaesthesia in the majority of cases and was the preferred drug of nurse, doctor, and parent.

Harlow et al. (1983) have given a recursive formula which is fundamental for computing the bundle strength distribution under a general class of load sharing rules called monotone load sharing rules. As the bundle size increases, the formula becomes prohibitively complex and, by itself, does not give much insight into the relationship of the assumed load sharing rule to the overall strength distribution. In this paper, an algorithm is given which gives some additional insight into this relationship. Here it is shown how to explicitly compute the bundle strength survival distribution by using a new type of graph called the loading diagram. The graph is parallel in structure and recursive in nature and so would appear to lend itself to large-scale computation. In addition, the graph has an interesting property (which we refer to as the cancellation property) which is related to the asymptotics of the Weibull as a minimum stable law.

Objective: 1) Become aware of the role of intraoperative fluorescence visualization in assessing subclinical changes at surgical margins in patients presenting with severe dysplasia and carcinoma in situ (HGD) or squamous cell carcinoma (SCC). 2) Understand the effectiveness of FV-guided surgery in reducing locoregional recurrence and improving overall survival.Method: A retrospective review was conducted from September 1, 2004, to August 31, 2009, identifying 246 patients (SCC 132; HGD 114) presenting to the BCCA. Surgery was done under FV guidance in 149 patients while 97 were treated conventionally. Outcome measures included pathology-proven local recurrence, regional failure, and death.Results: There was no significant difference between FV and control groups in age, smoking habit, lesion anatomic site, diagnosis, tumor size, and previous cancer history. There were more females in the FV group (51% vs 33%, P = .006). Time to outcome curve was estimated by the Kaplan-Meier method. With an average of 40...

Scalp arteriovenous malformations (AVMs) and sinus pericranii are two rare vascular lesions of the scalp that are part of the differential diagnosis in patients with scalp masses. The necessity of treatment of sinus pericranii, due to its risk of catastrophic hemorrhage or scalp necrosis, makes its diagnosis imperative. There are several theories on the pathogenesis of sinus pericranii with some of them stressing the importance of altered hemodynamic parameters in the affected area. An 8-year-old girl presented with a five centimeter soft, reducible scalp mass that had been present since birth. Clinical and radiographic evaluation revealed a sinus pericranii in association with a scalp AVM. She underwent resection of the sinus pericranii followed by embolization and planned separate en bloc resection of the AVM. During resection of the scalp AVM at a later date, the sinus pericranii was noted to have recurred. Concurrent treatment of all vascular anomalies associated with a sinus pericranii appears to be the key to its complete eradication.

For a century, allergen-specific immunotherapy (SIT) has proven to be an effective treatment for allergic rhinitis, asthma, and insect sting allergy. However, as allergen doses are frequently adapted to the individual patient, there are few data on dose-response relationship in SIT. Allergen products for SIT are being increasingly required to conform to regulatory requirements for human medicines, which include the need to demonstrate dose-dependent effects.This report, produced by a Task Force of the EAACI Immunotherapy Interest Group, evaluates the currently available data on dose-response relationships in SIT and aims to provide recommendations for the design of future studies.Fifteen dose-ranging studies fulfilled the inclusion criteria and twelve reported a dose-response relationship for clinical efficacy. Several studies also reported a dose-response relationship for immunological and safety endpoints. Due to the use of different reference materials and methodologies for the determination of allergen content, variations in study design, and choice of endpoints, no comparisons could be made between studies and, as a consequence, no general dosing recommendations can be made.Despite recently introduced guidelines on the standardization of allergen preparations and study design, the Task Force identified a need for universally accepted standards for the measurement of allergen content in SIT preparations, dosing protocols, and selection of clinical endpoints to enable dose-response effects to be compared across studies.

Much of the ultraviolet-B radiation (UV-B) research on plants has concentrated on vegetative plant parts, and only a small fraction has dealt with the reproductive system. The present study analyzed pollen grains of 34 taxa germinated and grown under two levels of UV-B radiation (187 and 460 mW/m2) or no UV-B (control group). Visible radiation at 260 mmol/m/s was present in all treatments. Taxa included those with binucleate and trinucleate pollen types. We detected differences among species. A significant reduction in pollen germination occurred in only five species. Pollen tubes of50% of the species showed significant reduction in length. Trinucleate pollen types were more likely to exhibit tube length reduction than the binucleate types. Proportionately more monocotyledonous species were sensitive to UV-B treatment than dicotyledonous species, and proportionately more wild species were sensitive than cultivated species and pollen collected from plants growing in the field were somewhat more sensitive than pollen collected from plants grown in the greenhouse. Species in which pollination occurred earlier in the season were more likely to be susceptible to UV-B radiation than those for which anthesis took place later in the season, suggesting a possible adaptation to UV-B radiation.

Summary Practical drillstem-failure prevention seems to be based more on individual knowledge of specific failures than on any standard model. To present a broader approach to drillstem-failure prevention, this paper draws on failure-prediction models, failure-investigation results, drillpipe finite-element analysis, and the API/IADC Drillstring Database to construct a unified approach to failure prevention.

Direct measurements of airborne particle mass concentrations or mass loads are often used to estimate health effects from the inhalation of resuspended contaminated soil. Airborne particle mass concentrations were measured using a personal sampler under a variety of surface-disturbing activities within different depositional environments at both volcanic and nonvolcanic sites near the Sunset Crater volcano in northern Arizona. Focused field investigations were performed at this analog site to improve the understanding of natural and human-induced processes at Yucca Mountain, Nevada. The level of surface-disturbing activity was found to be the most influential factor affecting the measured airborne particle concentrations, which increased over three orders of magnitude relative to ambient conditions. As the surface-disturbing activity level increased, the particle size distribution and the majority of airborne particle mass shifted from particles with aerodynamic diameters less than 10 mum (0.00039 in) to particles with aerodynamic diameters greater than 10 mum (0.00039 in). Under ambient conditions, above average wind speeds tended to increase airborne particle concentrations. In contrast, stronger winds tended to decrease airborne particle concentrations in the breathing zone during light and heavy surface-disturbing conditions. A slight increase in the average airborne particle concentration during ambient conditions was found above older nonvolcanic deposits, which tended to be finer grained than the Sunset Crater tephra deposits. An increased airborne particle concentration was realized when walking on an extremely fine-grained deposit, but the sensitivity of airborne particle concentrations to the resuspendible fraction of near-surface grain mass was not conclusive in the field setting when human activities disturbed the bulk of near-surface material. Although the limited sample size precluded detailed statistical analysis, the differences in airborne particle concentration over 900-y weathered volcanic and nonvolcanic deposits appeared to be potentially significant only under heavy surface disturbances.

In the early 1990s, the Federal Emergency Management Agency (FEMA) and the National Institute of Building Sciences (NIBS) embarked on an initiative to develop a consistent, standardized approach to estimating losses from earthquakes. In 1997, FEMA released the first HAZUS® (Hazards U.S.) model for earthquakes to “provide state, local, and regional officials with the tools necessary to plan and stimulate the efforts to reduce risk from earthquakes and to prepare for emergency response and recovery from an earthquake” (FEMA and NIBS 2003).

Multiband filter radiometers (MBFRs) are extensively used in national networks for UV climate monitoring and information to the public about the potential risk of solar UV exposure. In order to provide an international, uniform expression of the Global UV index measurements, a harmonized calibration scale is needed. In this paper we present the results of the first international intercomparison of MBFRs held in Oslo in 2005. The purposes are to evaluate the UV-index scale of different radiometers and to provide a harmonized UV-index scale based on the radiometers individual directional and absolute spectral response functions. In total 43 MBFR radiometers and 4 high resolution spectroradiometers were assembled, representing UV-monitoring networks operated by institutions in US, Spain, Greece, Poland, Belgium, UK, Austria, Norway, Sweden and Finland. The radiometers are operating worldwide, with stations in the Antarctica and Arctic, North- and South-America, Africa, Europe, Middle-East and Nepal. All sky conditions were realized during the campaign period. The agreement between the users' own processed UVI and the reference is generally very good; within ±5% for 22 out of 26 data sets (75%) and ±10% for 23 out of 26 (88%). Solar zenith dependent discrepancies and drift in the users' UVI scales is seen, but the performance of most radiometers is generally very good. All the objectives planned for the intercomparison were fulfilled and the campaign considered a success.

Some basic assumptions of classical control theory are often unacceptable in analysis of control of and control in ecosystems. Characterization of control in biology indicates that the isolation of control at separable levels of organization and a feedback-type control mechnism are implicit assumptions of control theory. Explicit recognition of hierarchical complexity and congeneric homotaxis (a biological control mechanism) represents progress toward an ecological control theory.

VARSKIN Mod 2 is a DOS-based computer program that calculates the dose to skin from beta and gamma contamination either directly on skin or on material in contact with skin. The default area for calculating the dose is 1 cm 2 . Recently, the U.S. Nuclear Regulatory Commission issued new guidelines for calculating shallow dose equivalent from skin contamination that requires the dose be averaged over 10 cm 2 . VARSKIN Mod 2 was not fully designed to calculate beta or gamma dose estimates averaged over 10 cm 2 , even though the program allows the user to calculate doses averaged over 10 cm 2 . This article explains why VARSKIN Mod 2 overestimates the beta dose when applied to 10 cm 2 areas, describes a manual method for correcting the overestimate, and explains how to perform reasonable gamma dose calculations averaged over 10 cm 2 . The article also describes upgrades underway in Varskin 3.

Rabeprazole is the only proton pump inhibitor that enhances the content of gastric mucin in experimental animals. We have studied, therefore, the effect of rabeprazole on the content of gastric mucin, mucus, and its viscosity in 21 asymptomatic volunteers in a double-blind study. The mucus content during rabeprazole administration significantly increased both in pentagastrin-stimulated (3.36 +/- 0.39 vs 1.50 +/- 0.32 mg/ml, P0.001) and basal (3.31 +/- 0.38 vs 2.28 +/- 0.36 mg/ml, P0.01) conditions. The content of mucin during rabeprazole was 2.6-fold (0.96 +/- 0.08 vs 0.36 +/- 0.06 mg/ml, P0.0001) and 41% (0.82 +/- 0.09 vs 0.58 +/- 0.09 mg/ml, P0.05) higher in stimulated and basal conditions, respectively. The viscosity of gastric juice during rabeprazole administration was also significantly higher both in stimulated (P0.01) and basal (P0.05) conditions. In conclusion, the unique pharmacological property of rabeprazole, significantly augmenting production of gastric mucus and mucin, may translate to additional clinical benefits in protecting the upper alimentary tract mucosa during the acid-related challenge.

A finger-ring dosemeter and reader has been designed that uses OSL readout of α-Al 2 O 3 :C (aluminium oxide). The use of aluminium oxide is important because it allows the sensitive element of the dosemeter to be a very thin layer that reduces the beta and gamma energy dependence to acceptable levels without compromising the required sensitivity for dose measurement. OSL readout allows the ring dosemeter to be interrogated with minimal disassembly. The ring dosemeter consists of three components: aluminium oxide powder for measurement of dose, an aluminium substrate that gives structure to the ring, and an aluminised Mylar cover to prevent the aluminium oxide from exposure to light. The thicknesses of the three components have been optimised for beta response using the Monte Carlo computer code FLUKA. A reader was also designed and developed that allows the dosemeter to be read after removing the Mylar. Future efforts are discussed.

This report presents the results of the first phase of the project entitled ''In-situ, Long-term Monitoring System for Radioactive Contaminants.'' Phase one of this effort included four objectives, each with specific success criteria. The first objective was to produce dosimetry grade fibers and rods of aluminum oxide. The success criterion for this milestone was the production of aluminum oxide rods and fibers that have a minimum measurable dose (MMD) of 100 mrem or less. This milestone was completed and the MMD for the rods was measured to be 1.53 mrem. Based on the MMD, the ability of the sensor to measure {sup 137}Cs, {sup 90}Sr/{sup 90}Y, and {sup 99}Tc was evaluated. It was determined that the sensor can measure the release limit of these radionuclides (50 pCi/cm{sup 3}) in 150 h, 200 h, and 54,000 h, respectively. The monitor is adequate for measuring {sup 137}Cs and {sup 90}Sr/{sup 90}Y but is unsuitable for measuring {sup 99}Tc in soil. The second objective was to construct a prototype sensor (dosimeter and fiber optic channel). There were three success criteria for this milestone: (1) Perform measurements with the sensor for both gamma and beta radiation with a standard deviation of 10% or less; (2) Demonstrate the ability of the sensor to discriminate between gamma and beta radiation; and (3) Obtain similar or relatable results for differing lengths of fiber optic cable. These milestones were met. The sensor was able to measure gamma radiation repeatedly with a standard deviation of 3.15% and beta radiation with a standard deviation of 2.85%. Data is presented that demonstrates that an end cap can be used to discriminate between beta plus gamma radiation using beta radiation from a {sup 90}Sr/{sup 90}Y source, and gamma radiation alone. It is shown that some amount of attenuation occurs in longer fiber optic cables, but it is unclear if the attenuation is due to poor alignment of the dosimeter and the cable. This issue will be investigated further when more dosimeters are available so that the dosimeters can be permanently attached to the longer cables. The third objective was to identify a demonstration site. The success criterion for this milestone was to obtain a written agreement from a DOE site to host the demonstration of the monitor during the third phase. Because of uncertainties in funding of the second and third phases of this effort, a written agreement was not obtained. Instead, verbal agreements were reached with both Hanford and the Nevada Test Site. It is believed that the verbal agreements meet the intent of the objective. The final objective was to prepare the Draft Phase I Topical Report. The success criterion for this milestone was to have the report accepted by NETL. It is anticipated that this objective will be met.

Previous studies suggest that sublingual immunotherapy (SLIT) represents a safer alternative to injection immunotherapy but equivalent efficacy is yet to be confirmed.To evaluate the efficacy and safety of SLIT in grass pollen-induced seasonal rhinoconjunctivitis.A randomized, placebo-controlled trial in 56 adults over 18 months. Outcome measures included diary scores of seasonal symptoms and medication use, overall assessments, conjunctival and intradermal provocation tests and serum antibody measurements. To investigate possible mechanisms, sublingual biopsies were taken for measurement of local T cells, antigen-presenting cells and IL-12 mRNA expression.There were no significant differences between the immunotherapy (IT) and placebo groups for diary symptom scores (P = 0.48) or rescue medication (P = 0.19). The patients' overall assessment of hayfever severity compared with previous years showed a highly significant improvement in favour of the IT group (P0.02). After treatment the late skin response was smaller (P = 0.003) and the ratio of serum allergen-specific IgG4/IgE was higher (P = 0.05) in the IT group. Both of these variables correlated with the clinical response to SLIT. There were no differences between groups in either the sublingual epithelium or lamina propria for numbers of CD3+ cells (epithelium: P = 0.9, lamina propria: P = 0.2), CD1a+ cells (P = 0.3, P = 0.25), CD68+ cells (P = 0.9, P = 1.0) or IL-12 mRNA+ cells (P = 0.6, P = 0.4). Local side-effects were minor and there were no serious treatment-related adverse events.Grass pollen sublingual immunotherapy was well tolerated. Although there was no significant change in diary scores, the improvement in overall assessments, which correlated with inhibition of the late skin response and increases in serum IgG4 : IgE ratio, indicates the need for larger, dose-ranging studies.

To evaluate somatic mitochondrial (mt)DNA mutations in the macula during ageing.Ten 30-microm cryostat sections from the macula (foveal and perifoveal regions) and peripheral retina of 14 donors (aged 14-94 years) were cut for cytochrome c oxidase cytochemistry. The photoreceptor layer was microdissected and DNA extracted for 4977-bp mtDNA (mtDNA(4977)) quantification using PCR. Dual cytochemistry for cytochrome c oxidase and succinate dehydrogenase allowed the detection of cytochrome c oxidase-deficient cones.Findings showed a progressive accumulation of mtDNA(4977) from ages 14 to 94 years. From ages 14 to 60 years there was an increase from 0.006% to 0.25%, and from ages 60 to 94 years there was a steeper increase from 0.25% to 5.39%. Counts of cones in the dual-reacted preparations showed more cytochrome c oxidase-deficient cones in the foveal region than elsewhere.The results show that mitochondrial DNA deletions and cytochrome c oxidase-deficient cones accumulate in the ageing retina, particularly in the foveal region. These defects may contribute to the changes in macular function observed in ageing and age-related maculopathy.

Allergic upper airway diseases such as allergic rhinitis and chronic sinusitis are an increasing problem. Although the pathogenesis remains elusive, an individual's genetic predisposition as well as exposure to the allergen are currently considered factors in their development. Clinical symptoms of sneezing, rhinorrhea, and congestion are primarily a consequence of granulocyte release of chemical mediators such as histamine, prostanoids, and leukotrienes as well as the infiltration of inflammatory cells. Observations subsequent to allergen provocation are comparable to natural exposure and as such much of our understanding of allergic responses is derived from this model. A prominence of CD4(+) T cells and eosinophils, synthesis and release of T(H)2 cytokines, and the coordinate expression of chemokines and adhesion molecules are all characteristic of the allergic response observed in rhinitis and sinusitis. Corticosteroids and immunotherapy target these inflammatory processes and have been observed to successfully reduce and shift the predominantly T(H)2 environment toward T(H)1 cytokine expression. As our understanding of the pathophysiologic features of allergic upper airway disease improves, as well as the relationship between their development and that of lower airway disease, new strategies of diagnosis and treatment will allow for more effective modulation of the allergic process and associated morbidity.

This paper proposes the creation of a corporate sponsored “Lecture from Space” program on board the International Space Station (ISS) with funding coming from a host of new technology and marketing spin-offs. This program would meld existing education initiatives in NASA with new corporate marketing techniques. Astronauts in residence on board the ISS would conduct short ten to fifteen minute live presentations and/or conduct interactive discussions carried out by a teacher in the classroom. This concept is similar to a program already carried out during the Neurolab mission on Shuttle flight STS-90. Building on that concept, the interactive simulcasts would be broadcast over the Internet and linked directly to computers and televisions in classrooms worldwide. In addition to the live broadcasts, educational programs and demonstrations can be recorded in space, and marketed and sold for inclusion in television programs, computer software, and other forms of media. Programs can be distributed directly into...

The association of hindbrain herniation, better known as Chiari malformation, and cystic cavitation of the spinal cord or hydrosyringomyelia has been well described in the literature although there is little consensus regarding its etiology, pathophysiology or optimal treatment.Despite a well-accepted and utilized classification system of both Chiari malformation and hydrosyringomyelia, there remains considerable disagreement regarding the proper management of these patients.This article reviews several popular theories on the etiology and pathophysiology of this disorder, briefly discusses the clinical features and radiologic findings associated with Chiari malformation and hydrosyringomyelia, and reviews basic surgical techniques for decompression of the cranial-cervical junction and treatment of the hydrosyringomyelia.

Although it is widely accepted that clonal genetic alterations are an essential component of tumor progression, little is known of the distribution of such changes in high-risk lesions or how such clones are altered over time. We explored the feasibility of using exfoliative cells collected by scraping the mucosal surface to detect allelic loss in oral lesions of 22 patients (14 squamous cell carcinomas, 2 carcinomas in situ, and 6 dysplasias). The data show that the patterns of allelic loss observed in these samples closely represent those observed in biopsies of the same region. Furthermore, early indications are that this approach can be used to detect recurrent outgrowth of clones of altered cells in patients after therapy.