Patients' perspectives on radiation in health care.

As radiation therapy is needed by approximately 50% of patients with cancer there needs to be ongoing research to ensure that radiation therapy targets the tumour effectively and minimises potential side effects. Major advances in radiation therapy, due to improvements in engineering and computing, have made it more precise, reducing side effects and improving cancer control. Patients need to be informed of its risks, both short and long term, to enable them to be active participants in their cancer treatment path.

Seeing is believing: The effect of prison-based insight-days on student nurses' perceptions of undertaking practice placements within a prison healthcare environment.

Prisoners' access to healthcare should mirror that of the general public, but is adversely affected by challenges in recruiting nurses to work in custodial settings, potentially impacting on prisoner well-being. To address this issue prison-based insight-days have been developed jointly by one university and prison to positively influence students' views of undertaking placements in custodial settings because nurses are known to subsequently seek employment in areas where they have had positive student placements. A phenomenological investigation explored student nurses' lived experiences of prison-based insight-days. Questionnaires and interviews were used to gather qualitative data about students' feelings both prior to and following the insight-day (n = 17). All data was thematically analysed resulting in four themes: pre-placement curiosity, escalating admission anxiety, calming down inside and post-placement decision making. The empirical findings showed that first-hand exposure to prisoners, and to the realities of a working prison, were crucial factors in dispelling stereotypes and addressing negative preconceptions of prison healthcare environments, as students could find prison placements unexpectedly appealing. Drawing on the findings, this paper recommends that facilitating prison insight-days within custodial settings may be one way to encourage students to undertake prison placements.

Correlations Between the Thermosphere's Semiannual Density Variations and Infrared Emissions Measured With the SABER Instrument.

This paper presents measurements of the amplitudes and timings of the combined, annual, and semiannual variations of thermospheric neutral density, and a comparison of these density variations with measurements of the infrared emissions from carbon dioxide and nitric oxide in the thermosphere. The density values were obtained from measurements of the atmospheric drag experienced by the Challenging Minisatellite Payload, Gravity Recovery and Climate Experiment A, Gravity field and Ocean Circulation Explorer, and three Swarm satellites, while the optical emissions were measured with the Sounding of the Atmosphere using Broadband Emission Radiometry (SABER) instrument on the Thermosphere Ionosphere Mesosphere Energetics and Dynamics satellite. These data span a time period of 16 years. A database containing global average densities that were derived from the orbits of about 5,000 objects (Emmert, 2009, https://doi.org/10.1029/2009JA014102, 2015b, https://doi.org/10.1002/2015JA021047) was employed for calibrating these density data. A comparison with the NRLMSISE-00 model was used to derive measurements of how much the density changes over time due to these seasonal variations. It is found that the seasonal density oscillations have significant variations in amplitude and timing. In order to test the practicality of using optical emissions as a monitoring tool, the SABER data were fit to the measured variations. Even the most simple fit that used only filtered carbon dioxide emissions had good correlations with the measured oscillations. However, the density oscillations were also well predicted by a simple Fourier series, contrary to original expectations. Nevertheless, measurements of the optical emissions from the thermosphere are expected to have a role in future understanding and prediction of the semiannual variations.

Thermospheric Nitric Oxide Response to Shock-led Storms.

We present a multi-year superposed epoch study of the Sounding of the Atmosphere using Broadband Emission Radiometry nitric oxide (NO) emission data. NO is a trace constituent in the thermosphere that acts as cooling agent via infrared (IR) emissions. The NO cooling competes with storm time thermospheric heating resulting in a thermostat effect. Our study of nearly 200 events reveals that shock-led interplanetary coronal mass ejections (ICMEs) are prone to early and excessive thermospheric NO production and IR emissions. Excess NO emissions can arrest thermospheric expansion by cooling the thermosphere during intense storms. The strongest events curtail the interval of neutral density increase and produce a phenomenon known as thermospheric 'overcooling'. We use Defense Meteorological Satellite Program particle precipitation data to show that interplanetary shocks and their ICME drivers can more than double the fluxes of precipitating particles that are known to trigger the production of thermospheric NO. Coincident increases in Joule heating likely amplify the effect. In turn, NO emissions more than double. We discuss the roles and features of shock/sheath structures that allow the thermosphere to temper the effects of extreme storm time energy input and explore the implication these structures may have on mesospheric NO. Shock-driven thermospheric NO IR cooling likely plays an important role in satellite drag forecasting challenges during extreme events.

High correlations between temperature and nitric oxide in the thermosphere.

Obtaining accurate predictions of the neutral density in the thermosphere has been a long-standing problem. During geomagnetic storms the auroral heating in the polar ionospheres quickly raises the temperature of the thermosphere, resulting in higher neutral densities that exert a greater drag force on objects in low Earth orbit. Rapid increases and decreases in the temperature and density may occur within a couple days. A key parameter in the thermosphere is the total amount of nitric oxide (NO). The production of NO is accelerated by the auroral heating, and since NO is an efficient radiator of thermal energy, higher concentrations of this molecule accelerate the rate at which the thermosphere cools. This paper describes an improved technique that calculates changes in the global temperature of the thermosphere. Starting from an empirical model of the Poynting flux into the ionosphere, a set of differential equations derives the minimum, global value of the exospheric temperature, which can be used in a neutral density model to calculate the global values. The relative variations in NO content are used to obtain more accurate cooling rates. Comparisons with the global rate of NO emissions that are measured with the Sounding of the Atmosphere using Broadband Emission Radiometry instrument show that there is very good agreement with the predicted values. The NO emissions correlate highly with the total auroral heating that has been integrated over time. We also show that the NO emissions are highly correlated with thermospheric temperature, as well as indices of solar extreme ultraviolet radiation.

In vitro electrical conductivity of seizing and non-seizing mouse brain slices at 10 kHz.

The electrical conductivity of small samples of mouse cortex (in vitro) has been measured at 10 kHz through the four-electrode method of van der Pauw. Brain slices from three mice were prepared under seizing and non-seizing conditions by changing the concentration of magnesium in the artificial cerebrospinal fluid used to maintain the tissue. These slices provided 121 square samples of cortical tissue; the conductivity of these samples was measured with an Agilent E4980A four-point impedance monitor. Of these, 73 samples were considered acceptable on the grounds of having good electrical contact between electrodes and tissue excluding outlier measurements. Results show that there is a significant difference (p = 0.03) in the conductivities of the samples under the two conditions. The seizing and non-seizing samples have mean conductivities of 0.33 and 0.36 S m(-1), respectively; however, these quantitative values should be used with caution as they are both subject to similar systematic uncertainties due to non-ideal temperature conditions and non-ideal placement of electrodes. We hypothesize that the difference between them, which is more robust to uncertainty, is due to the changing gap junction connectivity during seizures.

Simulating the influence of vernalization, photoperiod and optimum temperature on wheat developmental rates.

BACKGROUND AND AIMS: Accurately representing development is essential for applying crop simulations to investigate the effects of climate, genotypes or crop management. Development in wheat (Triticum aestivum, T. durum) is primarily driven by temperature, but affected by vernalization and photoperiod, and is often simulated by reducing thermal-time accumulation using vernalization or photoperiod factors or limiting accumulation when a lower optimum temperature (T(optl)) is exceeded. In this study T(optl) and methods for representing effects of vernalization and photoperiod on anthesis were examined using a range of planting dates and genotypes. METHODS: An examination was made of T(optl) values of 15, 20, 25 and 50 degrees C, and either the most limiting or the multiplicative value of the vernalization and photoperiod development rate factors for simulating anthesis. Field data were from replicated trials at Ludhiana, Punjab, India with July through to December planting dates and seven cultivars varying in vernalization response. KEY RESULTS: Simulations of anthesis were similar for T(optl) values of 20, 25 and 50 degrees C, but a T(optl) of 15 degrees C resulted in a consistent bias towards predicting anthesis late for early planting dates. Results for T(optl) above 15 degrees C may have occurred because mean temperatures rarely exceeded 20 degrees C before anthesis for many planting dates. For cultivars having a strong vernalization response, anthesis was more accurately simulated when vernalization and photoperiod factors were multiplied rather than using the most limiting of the two factors. CONCLUSIONS: Setting T(optl) to a high value (30 degrees C) and multiplying the vernalization and photoperiod factors resulted in accurately simulating anthesis for a wide range of planting dates and genotypes. However, for environments where average temperatures exceed 20 degrees C for much of the pre-anthesis period, a lower T(optl) (23 degrees C) might be appropriate. These results highlight the value of testing a model over a wide range of environments.

Biplot Analysis of Diallel Data.

Diallel crosses have been used in genetic research to determine the inheritance of important traits among a set of genotypes and to identify superior parents for hybrid or cultivar development. Conventional diallel analysis is limited to partitioning the total variation of the data into general combining ability (GCA) of each genotype and specific combining ability (SCA) of each cross. In this paper we formulate a biplot approach for graphical diallel analysis. The biplot is constructed by the first two principal components (PCs) derived from subjecting the tester-centered diallel data to singular value decomposition. It displays the most important entry by tester patterns of the data and allows the following information to be extracted visually: (i) GCA of each genotype; (ii) SCA of each genotype; (iii) groups of parents with similar genetics; and (iv) superior hybrids. In addition, the biplot allows hypotheses to be formulated concerning the genetics of the genotypes. Three published diallel data sets of wheat (Triticum aestivum L.) and maize (Zea mays L.) were used to demonstrate the biplot approach and detailed procedures were provided for constructing and interpreting a biplot.

Antibodies to the major linear neutralizing domains of cytomegalovirus glycoprotein B among natural seropositives and CMV subunit vaccine recipients.

The gB protein (gpUL55) of human cytomegalovirus (CMV) contains C-terminal (AD-1) and N-terminal (AD-2) linear immunodominant neutralizing domains. To measure antibodies to these epitopes, a modified protein (delta-gB) lacking heavily glycosylated intervening regions, the transmembrane domain, and the cytoplasmic domain, was expressed in recombinant baculovirus-infected cells. Eighty-six percent of 600 naturally CMV-seropositive individuals and 93% of 121 gB vaccine recipients had antibodies to delta-gB as detected by enzyme-linked immunosorbent assay (ELISA). The antibody level in vaccinees (median optical density [OD] = 1.73) exceeded that in natural seropositives (median OD = 0.94; p < .0001). Eleven percent of 95 natural seropositives and 7% of 120 gB vaccinees lacked A-gB antibodies but had neutralizing activity. Among subjects with delta-gB antibody, there were weak correlations between antibody level and neutralizing titer. These data suggest that antibodies to linear neutralizing gB domains are highly prevalent in naturally-infected individuals and regularly develop in gB vaccinees. However, for some individuals, discontinuous and/or linear epitopes not represented on delta-gB may be more important in the generation of neutralizing responses.

Dextran sulfate inhibits IFN-gamma-induced Jak-Stat pathway in human vascular endothelial cells.

Human vascular endothelial cells can be induced by IFN-gamma to express class II MHC proteins. Previously, dextran sulfate was shown to selectively inhibit expression of class II MHC by preventing transcription of the gene encoding CIITA, a transactivator protein required for IFN-gamma-inducible expression of class II genes. In this study we characterized the effects of dextran sulfate on the intracellular events occurring prior to CIITA activation. Immunoprecipitation and Western blot analyses indicated that IFN-gamma-induced phosphorylation of Stat1 and Jak2 was blocked by dextran sulfate. In addition, electron micrographs showing the large accumulation of dextran sulfate particles in the cytoplasms of endothelial cells demonstrated that Stat and Jak proteins may directly interact with dextran sulfate. Binding of radiolabeled IFN-gamma to cells indicated that dextran sulfate may also modulate IFN-gamma interactions with the cell surface. Thus, dextran sulfate is capable of interfering with the IFN-gamma-induced expression of class II MHC genes at multiple sites.

Reliability of the Washington University Road Test. A performance-based assessment for drivers with dementia of the Alzheimer type.

OBJECTIVE: To assess the reliability and stability of a standardized road test for healthy aging people and those with dementia of the Alzheimer type (DAT). DESIGN: A prospective study involving patients with DAT and age-matched healthy controls in which subjects' driving performance was evaluated by several raters in an initial and a follow-up road test. SETTING: Urban medical school and urban highways and streets. SUBJECTS: A convenience sample of 58 controls, 36 subjects with very mild DAT, and 29 subjects with mild DAT. RESULTS: Analysis of road test ability of controls (2 subjects [3%] failed the test), very mild DAT subjects (7 subjects [19%] failed), and mild DAT subjects (12 subjects [41%] failed) disclosed a significant association between driving performance and dementia status (chi 2[4] = 20.65 [N = 123]; P < .001; Kendall tau-b = 0.306). Interrater reliability for assessment of driving performance ranged from kappa = 0.85 to 0.96. One-month test-retest stability on the road test was 0.76 (quantitative scoring) and 0.53 (clinical judgment). CONCLUSIONS: Dementia adversely affects driving performance even in its mild stages, although some persons with DAT seem to drive safely for some time after disease onset. A traffic-interactive, performance-based road test that examines cognitive behaviors provides an accurate and reliable functional assessment of driving ability.

Environmental cueing may effect performance on a road test for drivers with dementia of the Alzheimer type.

This paper examines the impact of environmental cueing on a road test for persons with dementia of the Alzheimer type (DAT). In an earlier study, we demonstrated the reliability and stability of the Washington University Road Test in a sample of 58 healthy elderly controls and 65 subjects with DAT. We found that dementia adversely affects driving performance even in its mild stages. Here were elaborate on the results of a follow-up road test conducted 1 month after the baseline test (n = 63) explore possible reasons why the stability of the follow-up road test was lower than expected. We conclude that environmental cueing may affect performance on a road test in DAT.

Processing of human cytomegalovirus glycoprotein B in recombinant adenovirus-infected cells.

Intracellular processing of human cytomegalovirus (HCMV) glycoprotein B (gB; gpUL55) expressed by a recombinant adenovirus (Ad-gB) was studied in human A549 cells as processing events could affect immunogenicity when such viruses are used as live-recombinant vaccines. Cleavage of [35S]methionine-labelled gp13O into gp93 and gp55 reached a maximum after a 3 h chase. Cleavage was completely inhibited by brefeldin A, suggesting that processing normally occurs as a late Golgi or post-Golgi event. Uncleaved gp 130 remained completely sensitive to endo-beta-N-acetylglucosaminidase H (Endo-H) in untreated cells following long chase periods, indicating high-mannose oligosaccharides at all of the 18 N-linked glycosylation sites (Asn-X-Ser/Thr) and retention in the endoplasmic reticulum. Endo-H analysis of gp55 from swainsonine-treated and untreated cells was consistent with glycosylation at all three potential sites, with two oligosaccharides remaining sensitive to Endo-H and one being processed to Endo-H resistance. The heavily glycosylated N-terminal gp93 subunit was not detected by [35S]methionine-labelling but was easily detected along with gp55 after labelling with [3H]mannose. No cleavage of gp 130 was observed in analogous pulse-chase radiolabelling of Ad-gB-infected human fibroblasts, even though these cells are permissive for HCMV replication and can process the native gB molecule. Processing of gB in recombinant adenovirus-infected A549 cells was generally similar to that previously reported for native gB in HCMV-infected fibroblasts.

IFN-gamma-induced MHC class II gene expression is suppressed in endothelial cells by dextran sulfate.

IFN-gamma-activated endothelial cells actively participate in initiating immune responses by interacting with immunocompetent cells via class II MHC proteins. In this study, dextran sulfate, a synthetic heparin analogue, was shown to selectively inhibit IFN-gamma-induced surface expression of HLA-DR molecules by human umbilical cord vascular endothelial cells, but not other cytokine-induced molecules such as ELAM-1 or ICAM-1. Inhibition occurred regardless of whether dextran sulfate was added 24 h before, at the same time as, or 24 h after IFN-gamma stimulation of cells. In addition, both high (500 kDa) and low (5 kDa) molecular mass dextran sulfate molecules were able to block class II expression, whereas treating cells with naturally occurring polysulfated glycosaminoglycans such as heparin, heparan, and chondroitin sulfate did not produce any suppressive effects. Radiolabeling of cells with [35S]methionine followed by radioimmunoprecipitation using anti-HLA-DR alpha mAb demonstrated that biosynthesis of class II proteins was specifically blocked. RT-PCR and Southern blotting were utilized to examine transcription of the HLA-DR alpha gene and demonstrated an absence of HLA-DR alpha mRNA from dextran sulfate-treated and IFN-gamma-induced cells. Dextran sulfate also prevented transcription of the gene encoding CIITA, a transactivator protein required for IFN-gamma-inducible expression of class II genes. Thus, dextran sulfate apparently inhibited this step or an earlier one in the intracellular signaling pathway for IFN-gamma in human endothelial cells, subsequent to IFN-gamma binding to its cell surface receptor.

Review of the visual system in Parkinson's disease.

In an era when the prevalence of Parkinson's disease (PD) is increasing because our population is aging, eye care professionals need to become aware of the visual changes experienced by PD patients. This paper reviews the visual pathophysiology of PD and the results of the lack of dopamine on the retina and visual cortex. It also discusses the impact of PD on the oculomotor system and the visual sensory pathways with the consequent effects on reading, balance, and driving abilities of PD patients. Further research on the visual system and PD may provide improved means for early diagnostic testing as well as the possibility of vision rehabilitation for treatment of visual performance impairments.

Cleavable signal peptides are rarely found in bacterial cytoplasmic membrane proteins (review).

Most proteins destined for secretion are synthesized with amino-terminal extensions, known as signal peptides, which play a vital role in their translocation across the membrane bordering the cytoplasm. Following translocation across the eukaryotic endoplasmic reticulum (ER) membrane or the bacterial cytoplasmic membrane, signal peptides are proteolytically removed from the preproteins. The process of membrane protein assembly can be likened to that of protein export in that it involves the translocation of portions of proteins across membranes. Moreover, the topological similarities between eukaryotic ER and plasma membrane proteins and bacterial cytoplasmic membrane proteins suggest that the mechanisms of membrane protein assembly may, like those of protein export, share fundamental similarities in eukaryotic and bacterial cells. However, whilst many of the ER and plasma membrane proteins of higher eukaryotes are synthesized with cleavable signal peptides, the same is true of only very few bacterial cytoplasmic membrane proteins. This fact is not widely appreciated, probably because certain exceptional (signal peptide-containing) bacterial membrane proteins, such as the major coat protein of bacteriophage M13, have been the subject of extensive investigations. In this review we highlight this anomaly and discuss it within the general context of membrane protein topology.

Assembly of eukaryotic class III (N-out, C-in) membrane proteins into the Escherichia coli cytoplasmic membrane.

Class III membrane proteins lack cleavable signal peptides but adopt an N-out, C-in topology with respect to their native membranes. We have analysed the fate of two eukaryotic class III plasma membrane proteins, human erythrocyte glycophorin C and influenza A virus M2 protein, in Escherichia coli. The N-terminal domains of both proteins were efficiently localised to the extracytoplasmic side of the bacterial cytoplasmic membrane. When beta-lactamase was fused to the C-terminus of glycophorin C it was localised to the cytoplasm, and protease treatment of spheroplasts caused a reduction in size of the fusion protein consistent with glycophorin C adopting its native topology in E. coli.

Evaluation and retraining programs for older drivers.

Although many individuals who have had strokes or other physical problems assume that they can no longer drive, they are often unaware of retraining programs. In addition to formal courses supported by sponsoring agencies, such as the AAA, there are also programs run by occupational therapists. This article addresses issues relevant to the role of occupational therapists in evaluation and retraining of older drivers and describes several cases as examples. To better inform the public about driver retraining programs for the elderly and the disabled population, the American Occupational Therapy Association has published a pamphlet entitled Able Driving Is Safe Driving that provides information on how driving skills may be affected by age or illness. This publication also will provide examples of adaptive driving equipment usage and driver training. AOTA hopes this pamphlet will inform older adults of their options in maintaining independent community mobility. Research is needed to find out if older adults have relinquished driving because of a physical disability that may have been treatable with rehabilitation. Also, there needs to be a comparison study of classroom driving instruction to actual skill performance so that older adults and insurance companies are investing in programs that will demonstrate the outcome of improved driving performance.

Protection against a lethal influenza virus challenge by immunization with a haemagglutinin-expressing plasmid DNA.

Direct DNA inoculations have been used to demonstrate that in vivo transfections can be used to elicit protective immune responses. The direct inoculation of an H7 haemagglutinin-expressing DNA protected chickens against lethal challenge with an H7N7 influenza virus. Three-week-old chickens were vaccinated by inoculating 100 micrograms of plasma DNA by each of three routes (intravenous, intraperitoneal and subcutaneous). One month later, chickens were boosted with 100 micrograms of DNA by each of the three routes. At 1-2 weeks postboost, chickens were challenged via the nares with 100 lethal doses of an H7N7 virus. Low to undetectable levels of H7-specific antibodies were present postvaccination and boost. High titres of H7-specific antibodies appeared within 1 week of challenge. In a series of four experiments, 50% (28/56) of the DNA-vaccinated and < 2% (1/67) of the control chickens survived the challenge. This exceptionally simple method of immunization holds high promise for the development of subunit vaccines.