Scintillation characteristics of the EJ-299-02H scintillator.

A study of the dead layer thickness and quenching factor of a plastic scintillator for use in ultracold neutron (UCN) experiments is described. Alpha spectroscopy was used to determine the thickness of a thin surface dead layer to be 630 ± 110 nm. The relative light outputs from the decay of 241Am and Compton scattering of electrons were used to extract Birks' law coefficient, yielding a kB value of 0.087 ± 0.003 mm/MeV, consistent with some previous reports for other polystyrene-based scintillators. The results from these measurements are incorporated into the simulation to show that an energy threshold of (∼9 keV) can be achieved for the UCNProBe experiment. This low threshold enables high beta particle detection efficiency and the indirect measurement of UCN. The ability to make the scintillator deuterated, accompanied by its relatively thin dead layer, gives rise to unique applications in a wide range of UCN experiments, where it can be used to trap UCN and detect charged particles in situ.

Measurement of Electron-Neutrino Charged-Current Cross Sections on

Using an 185-kg NaI[Tl] array, COHERENT has measured the inclusive electron-neutrino charged-current cross section on ^{127}I with pion decay-at-rest neutrinos produced by the Spallation Neutron Source at Oak Ridge National Laboratory. Iodine is one the heaviest targets for which low-energy (≤50 MeV) inelastic neutrino-nucleus processes have been measured, and this is the first measurement of its inclusive cross section. After a five-year detector exposure, COHERENT reports a flux-averaged cross section for electron neutrinos of 9.2_{-1.8}^{+2.1}×10^{-40} cm^{2}. This corresponds to a value that is ∼41% lower than predicted using the MARLEY event generator with a measured Gamow-Teller strength distribution. In addition, the observed visible spectrum from charged-current scattering on ^{127}I has been measured between 10 and 55 MeV, and the exclusive zero-neutron and one-or-more-neutron emission cross sections are measured to be 5.2_{-3.1}^{+3.4}×10^{-40} and 2.2_{-0.5}^{+0.4}×10^{-40} cm^{2}, respectively.

Ultracold neutron properties of the Eljen-299-02D deuterated scintillator.

In this paper, we report studies of the Fermi potential and loss per bounce of ultracold neutrons (UCNs) on a deuterated scintillator (Eljen-299-02D). These UCN properties of the scintillator enable its use in a wide variety of applications in fundamental neutron research.

A packaged intervention to improve viral load monitoring within a deeply rural health district of South Africa.

BACKGROUND: The KwaZulu-Natal (KZN) province of South Africa has the highest prevalence of HIV infection in the world. Viral load (VL) testing is a crucial tool for clinical and programmatic monitoring. Within uMkhanyakude district, VL suppression rates were 91% among patients with VL data; however, VL performance rates averaged only 38·7%. The objective of this study was to determine if enhanced clinic processes and community outreach could improve VL monitoring within this district. METHODS: A packaged intervention was implemented at three rural clinics in the setting of the KZN HIV AIDS Drug Resistance Surveillance Study. This included file hygiene, outreach, a VL register and documentation revisions. Chart audits were used to assess fidelity. Outcome measures included percentage VL performed and suppressed. Each rural clinic was matched with a peri-urban clinic for comparison before and after the start of each phase of the intervention. Monthly sample proportions were modelled using quasi-likelihood regression methods for over-dispersed binomial data. RESULTS: Mkuze and Jozini clinics increased VL performance overall from 33·9% and 35·3% to 75·8% and 72·4%, respectively which was significantly greater than the increases in the comparison clinics (RR 1·86 and 1·68, p < 0·01). VL suppression rates similarly increased overall by 39·3% and 36·2% (RR 1·84 and 1·70, p < 0·01). The Chart Intervention phase showed significant increases in fidelity 16 months after implementation. CONCLUSIONS: The packaged intervention improved VL performance and suppression rates overall but was significant in Mkuze and Jozini. Larger sustained efforts will be needed to have a similar impact throughout the province.

Comparative analyses of published cost effectiveness models highlight critical considerations which are useful to inform development of new models.

Background: Comparative analyses of published cost effectiveness models provide useful insights into critical issues to inform the development of new cost effectiveness models in the same disease area.Objective: The purpose of this study was to describe a comparative analysis of cost-effectiveness models and highlight the importance of such work in informing development of new models. This research uses genotypic antiretroviral resistance testing after first line treatment failure for Human Immunodeficiency Virus (HIV) as an example.Method: A literature search was performed, and published cost effectiveness models were selected according to predetermined eligibility criteria. A comprehensive comparative analysis was undertaken for all aspects of the models.Results: Five published models were compared, and several critical issues were identified for consideration when developing a new model. These include the comparator, time horizon and scope of the model. In addition, the composite effect of drug resistance prevalence, antiretroviral therapy efficacy, test performance and the proportion of patients switching to second-line ART potentially have a measurable effect on model results. When considering CD4 count and viral load, dichotomizing patients according to higher cost and lower quality of life (AIDS) versus lower cost and higher quality of life (non-AIDS) status will potentially capture differences between resistance testing and other strategies, which could be confirmed by cross-validation/convergent validation. A quality adjusted life year is an essential outcome which should be explicitly explored in probabilistic sensitivity analysis, where possible.Conclusions: Using an example of GART for HIV, this study demonstrates comparative analysis of previously published cost effectiveness models yields critical information which can be used to inform the structure and specifications of new models.

Long, intrinsic horizontal axons radiating through and beyond rat barrel cortex have spatial distributions similar to horizontal spreads of activity evoked by whisker stimulation.

Stimulation of a single whisker evokes a peak of activity that is centered over the associated barrel in rat primary somatosensory cortex, and yet the evoked local field potential and the intrinsic signal optical imaging response spread symmetrically away from this barrel for over 3.5 mm to cross cytoarchitectonic borders into other "unimodal" sensory cortical areas. To determine whether long horizontal axons have the spatial distribution necessary to underlie this activity spread, we injected adeno-associated viral vectors into barrel cortex and characterized labeled axons extending from the injection site in transverse sections of flattened cortex. Combined qualitative and quantitative analyses revealed labeled axons radiating diffusely in all directions for over 3.5 mm from supragranular injection sites, with density declining over distance. The projection pattern was similar at four different cortical depths, including infragranular laminae. Infragranular vector injections produced patterns similar to the supragranular injections. Long horizontal axons were detected both using a vector with a permissive cytomegalovirus promoter to label all neuronal subtypes and using a calcium/calmodulin-dependent protein kinase II α vector to restrict labeling to excitatory cortical pyramidal neurons. Individual axons were successfully reconstructed from series of supragranular sections, indicating that they traversed gray matter only. Reconstructed axons extended from the injection site, left the barrel field, branched, and sometimes crossed into other sensory cortices identified by cytochrome oxidase staining. Thus, radiations of long horizontal axons indeed have the spatial characteristics necessary to explain horizontal activity spreads. These axons may contribute to multimodal cortical responses and various forms of cortical neural plasticity.

Lung deposition and pharmacokinetics of nebulized cyclosporine in lung transplant patients.

BACKGROUND: Inhaled cyclosporine (CsA) is being investigated as a prophylaxis for lung transplant rejection. Lung deposition and systemic exposure of nebulized CsA in lung transplant patients was evaluated as part of the Phase 3 cyclosporine inhalation solution (CIS) trial (CYCLIST). METHODS: Ten patients received 300 mg of CIS (62.5 mg/mL CsA in propylene glycol) admixed with 148 MBq of Tc-DTPA (technetium-99m bound to diethylenetriaminepentaacetic acid) administered using a Sidestream(®) disposable jet nebulizer. Deposition was assessed using a dual-headed gamma camera. Blood samples were collected over a 24-hr time period after aerosol dosing and analyzed for CsA levels. A pharmacokinetic analysis of the resulting blood concentration versus time profiles was performed. RESULTS: The average total deposited dose was 53.7 ± 12.7 mg. Average pulmonary dose was 31.8 ± 16.3 mg, and stomach dose averaged 15.5 ± 11.1 mg. Device performance was consistent, with breathing maneuvers influencing dose variation. Predose coaching with five of 10 patients reduced stomach deposition (22.6 ± 11.2 vs. 8.3 ± 5.2 mg; p=0.03). Blood concentrations declined quickly from a maximum of 372 ± 140 ng/mL to 15.3 ± 9.7 ng/mL at 24 hr post dose. Levels of AUC(0-24) [area under the concentration vs. time curve from 0 to 24 hr] averaged 1,493 ± 746 ng hr/mL. On a three times per week dose regimen, this represents <5% of the weekly systemic exposure of twice per day oral administration. CONCLUSIONS: Substantial doses of CsA can be delivered to the lungs of lung transplant patients by inhaled aerosol. Systemic levels are small relative to typical oral CsA administration.

Copy number variation in pediatric multiple sclerosis.

BACKGROUND: Pediatric onset multiple sclerosis (MS) accounts for 2-4% of all MS. It is unknown whether the disease shares the same underlying pathophysiology found in adult patients or an extreme early onset phenotype triggered by distinct biological mechanisms. It has been hypothesized that copy number variations (CNVs) may result in extreme early onset diseases because CNVs can have major effects on many genes in large genomic regions. OBJECTIVES AND METHODS: The objective of the current research was to identify CNVs, with a specific focus on de novo CNVs, potentially causing early onset MS by competitively hybridizing 30 white non-Hispanic pediatric MS patients with each of their parents via comparative genomic hybridization (CGH) analysis on the Agilent 1M CGH array. RESULTS AND DISCUSSION: We identified 10 CNVs not overlapping with any CNV regions currently reported in the Database of Genomic Variants (DGV). Fifty-five putatively de novo CNVs were also identified: all but one common in the DGV. We found the single rare CNV was a private variation harboring the SACS gene. SACS mutations cause autosomal-recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) disease. Additional clinical review revealed that the patient with the SACS gene CNV shared some features of both MS and ARSACS. CONCLUSIONS: This is the first reported study analyzing pediatric MS CNVs. While not yielding causal variation in our initial pediatric dataset, our approach confirmed diagnosis of an ARSACS-like disease in addition to MS in the affected individual, which led to a more complete understanding of the patient's disease course and prognosis.

Multilevel analysis of the Be Active Eat Well intervention: environmental and behavioural influences on reductions in child obesity risk.

BACKGROUND: The Be Active Eat Well (BAEW) community-based child obesity prevention intervention was successful in modestly reducing unhealthy weight gain in primary school children using a multi-strategy and multi-setting approach. OBJECTIVE: To (1) examine the relationship between changes in obesity-related individual, household and school factors and changes in standardised child body mass index (zBMI), and (2) determine if the BAEW intervention moderated these effects. METHODS: The longitudinal relationships between changes in individual, household and school variables and changes in zBMI were explored using multilevel modelling, with measurement time (baseline and follow-up) at level 1, individual (behaviours, n = 1812) at level 2 and households (n = 1318) and schools (n = 18) as higher levels (environments). The effect of the intervention was tested while controlling for child age, gender and maternal education level. RESULTS: This study confirmed that the BAEW intervention lowered child zBMI compared with the comparison group (-0.085 units, P = 0.03). The variation between household environments was found to be a large contributor to the percentage of unexplained change in child zBMI (59%), compared with contributions from the individual (23%) and school levels (1%). Across both groups, screen time (P = 0.03), sweet drink consumption (P = 0.03) and lack of household rules for television (TV) viewing (P = 0.05) were associated with increased zBMI, whereas there was a non-significant association with the frequency the TV was on during evening meals (P = 0.07). The moderating effect of the intervention was only evident for the relationship between the frequency of TV on during meals and zBMI, however, this effect was modest (P = 0.04). CONCLUSIONS: The development of childhood obesity involves multi-factorial and multi-level influences, some of which are amenable to change. Obesity prevention strategies should not only target individual behaviours but also the household environment and family practices. Although zBMI changes were modest, these findings are encouraging as small reductions can have population level impacts on childhood obesity levels.

Multiple sclerosis susceptibility alleles in African Americans.

Multiple sclerosis (MS) is an autoimmune demyelinating disease characterized by complex genetics and multifaceted gene-environment interactions. Compared to whites, African Americans have a lower risk for developing MS, but African Americans with MS have a greater risk of disability. These differences between African Americans and whites may represent differences in genetic susceptibility and/or environmental factors. SNPs from 12 candidate genes have recently been identified and validated with MS risk in white populations. We performed a replication study using 918 cases and 656 unrelated controls to test whether these candidate genes are also associated with MS risk in African Americans. CD6, CLEC16a, EVI5, GPC5, and TYK2 contained SNPs that are associated with MS risk in the African American data set. EVI5 showed the strongest association outside the major histocompatibility complex (rs10735781, OR=1.233, 95% CI=1.06-1.43, P-value=0.006). In addition, RGS1 seems to affect age of onset whereas TNFRSF1A seems to be associated with disease progression. None of the tested variants showed results that were statistically inconsistent with the effects established in whites. The results are consistent with shared disease genetic mechanisms among individuals of European and African ancestry.

Selective cervical nerve root blockade: prospective study of immediate and longer term complications.

BACKGROUND AND PURPOSE: Selective cervical nerve root blockade (SCNRB) is a useful procedure for evaluating and treating patients with cervical radiculopathy. Reports of complications related to injections within the cervical nerve root foramen have raised serious doubts regarding the safety of this procedure. This study was performed to prospectively evaluate the safety of fluoroscopically guided outpatient diagnostic and therapeutic SCNRB. MATERIALS AND METHODS: Eight hundred two consecutive fluoroscopically guided diagnostic and/or therapeutic SCNRBs in 659 patients were performed during a 14-month period (November 2006-December 2007) at affiliated outpatient imaging centers. Each examination was performed by 1 of 8 experienced procedural radiologists by using an anterior oblique approach, with the needle position confirmed with radiographic contrast before injection of an admixture of local anesthetic and steroid. All patients were assessed immediately and at 30 minutes following the procedure. Additionally, 460 patients were called by telephone 30 days following the procedure. All complications were recorded. RESULTS: Of the 802 attempted procedures, 799 were successfully completed. Three procedures were aborted due to anxiety, challenging body habitus, or persistent venous opacification observed during contrast injection and despite needle repositioning. There were no serious complications, such as stroke, spinal cord insult, permanent nerve root deficit, infection, or significant hematoma. There were 33 minor complications occurring within 30 minutes of the procedure; the most common was vasovagal symptoms. Three hundred forty-five patients were successfully contacted by telephone at 30 days postinjection, 9 of whom reported increased or new pain symptoms. CONCLUSIONS: With our technique, fluoroscopically guided SCNRB is a safe outpatient procedure with a low immediate and delayed complication rate.

Variability in the preoperative management of infants with hypoplastic left heart syndrome.

Infants with hypoplastic left heart syndrome (HLHS) commonly undergo initial surgical palliation during the first week of life. Few data exist on optimal preoperative management strategies; therefore, the management of these infants prior to surgery is anecdotal and variable. To more fully define this variability in preoperative care of infants with HLHS, a survey was designed to describe current preoperative management practices in the infant with HLHS. The questionnaire explored management styles as well as preoperative monitoring techniques and characteristics of the respondent's health care institution. The responses were compiled and are reported. A striking lack of consistency in preoperative management techniques for infants with HLHS is apparent. The impact of these preoperative strategies is unknown. Despite challenges in anatomic and hemodynamic variability at presentation, a prospective randomized controlled trial comparing ventilatory management techniques, enteral feeding strategies, and the utility of various monitoring tools on short- and long-term outcome is needed.

Selective cervical nerve root blockade: experience with a safe and reliable technique using an anterolateral approach for needle placement.

BACKGROUND AND PURPOSE: [corrected] Our aim was to evaluate the safety and clinical utility of a fluoroscopically guided anterolateral oblique approach technique for outpatient diagnostic and therapeutic selective cervical nerve root blockade (SCNRB). MATERIALS AND METHODS: During a 13-year period (1994 through February 2007), 4612 patients underwent fluoroscopically guided diagnostic and/or therapeutic extraforaminal SCNRB by using an anterior oblique approach at affiliated outpatient imaging centers. Each procedure was performed by 1 of 6 procedural radiologists, all highly experienced in and actively performing spinal injections on a full-time basis in clinical practice. All of the proceduralists were thoroughly experienced with lumbar injections before endeavoring to perform SCNRBs. Nonionic contrast was injected in nearly all patients (except isolated patients with contrast allergy), and a minimum of 2 projection filming procedures were performed to document the accuracy of needle placement and contrast dispersal before the injection of therapeutic substances. All clinically significant complications beyond skin discoloration and temporary exacerbation of symptoms were recorded. RESULTS: There were no serious neurologic complications, such as stroke, spinal cord insult, or permanent nerve root deficit. One life-threatening anaphylactic reaction occurred and was attributed to the injected materials and not the specific procedure itself. Another patient had a 3- to 4-minute grand mal seizure, from which he fully recovered within 30 minutes. There were no infections. CONCLUSION: The technique we describe for fluoroscopically guided SCNRB is a useful and safe outpatient procedure when performed by skilled and experienced proceduralists.

Diskography: infectious complications from a series of 12,634 cases.

BACKGROUND AND PURPOSE: Diskography is commonly performed to investigate pain of suspected diskogenic origin. Although uncommon, diskitis is a feared complication of this procedure. We reviewed the incidence of diskitis and other infectious complications following diskography in a large busy outpatient practice and discuss technical aspects that may contribute to infection prevention. METHODS: We reviewed the electronic records of all diskograms obtained at our institution during a 12.25-year period, looking for all cases of procedure-related infection. All diskograms had been obtained by skilled and experienced procedural radiologists in dedicated spine-injection suites with specialized technical staff. RESULTS: There were 12,634 examinations performed on 10,663 patients for a total of 37,135 disk levels. Of the disk levels, 5981 were cervical; 3083, thoracic; and 28,071, lumbar. Two cases of confirmed lumbar diskitis and no cases of either cervical or thoracic diskitis were seen in our series. No other infectious complications were found. The incidence of diskitis was 0.016% per examination and 0.0054% per disk level. CONCLUSION: In skilled and experienced hands using proper technique, diskography is a safe outpatient procedure with an extremely low incidence of diskitis and other procedure-related infections.

Neonate with vein of Galen malformation and heart failure: serial changes in plasma B-type natriuretic peptide following endovascular embolization.

We report a neonate with vein of Galen malformation (VGM) who developed congestive heart failure (CHF) early after birth. Serial changes in plasma B-type natriuretic peptide (BNP) following an endovascular embolization procedure for VGM were mirrored in his clinical CHF status. The plasma BNP level markedly increased to 1800 pg/ml (normal, <100 pg/ml) in accordance with the severity of CHF. It rapidly decreased to 356 pg/ml during the first week after endovascular embolization for VGM. In the following 3 weeks there was an unexpected upward trend in plasma BNP despite echocardiography revealing normal biventricular function. After additional evaluation and treatment for CHF, BNP decreased again and the patient's clinical status concurrently improved. The patient was discharged with a normal BNP level. Monitoring serial plasma BNP provides valuable information regarding the need for additional evaluation or treatment of newborns with CHF and may be used to document improvement.

Aerosol cyclosporin therapy in lung transplant recipients with bronchiolitis obliterans.

The majority of patients who develop bronchiolitis obliterans, after lung transplantation, die within 2-3 yrs after onset since treatment with conventional immunosuppression is typically ineffective. A case/control study was conducted in lung transplant recipients with biopsy-documented bronchiolitis obliterans to determine whether aerosol cyclosporin use contributed to increased survival. The cases comprised 39 transplant recipients who received open-label aerosol cyclosporin treatment in addition to conventional immunosuppression. The controls were transplant recipients treated with conventional immunosuppression alone. There were 51 controls from the University of Pittsburgh Medical Center and 100 from a large multicentric database (Novartis Lung Transplant Database). Forced expiratory volume in one second expressed as a percentage of the predicted value was an independent predictor of survival in all patients with bronchiolitis obliterans. Cox proportional-hazards analysis revealed a survival advantage for aerosol cyclosporin cases compared to the Pittsburgh control group. A survival advantage was also seen when comparing study cases to multicentric controls. Aerosol cyclosporin, given with conventional immunosuppression to lung transplant recipients with bronchiolitis obliterans, provides a survival advantage over conventional therapy alone.

Diagnostic properties of transbronchial biopsy in lung transplant recipients who require mechanical ventilation.

INTRODUCTION: Bronchoscopy with transbronchial biopsy (TBBx) and bronchoalveolar lavage is useful and safe for diagnosing acute rejection and infection in lung transplant recipients. However, its role is less well defined in determining the etiology of allograft dysfunction in the setting of respiratory failure necessitating mechanical ventilation. METHODS: We retrospectively identified 41 mechanically ventilated patients with respiratory failure in whom 42 TBBx were followed within a 10 day period by surgical lung biopsy (SLBx) to determine the sensitivity, specificity, and positive and negative predictive values of TBBx compared with SLBx. RESULTS: The sensitivity, specificity, and positive and negative predictive values of TBBx for all episodes of acute rejection and for significant episodes of acute cellular rejection were 53.3% and 36.0%; 91.7% and 94.1%; 94.1% and 90.0%; 44.0% and 50.0%, respectively. A significantly higher histologic grade was noted on SLBx compared with TBBx specimens obtained within a 10-day period (2.39 +/- 1.02 vs 0.97 +/- 0.11, p

Perceptual correlates of neural representations evoked by odorant enantiomers.

Spatial activation patterns within the olfactory bulb are believed to contribute to the neural representation of odorants. In this study, we attempted to predict the perceptions of odorants from their evoked patterns of neural activity in the olfactory bulb. We first describe the glomerular activation patterns evoked by pairs of odorant enantiomers based on the uptake of [(14)C]2-deoxyglucose in the olfactory bulb glomerular layer. Using a standardized data matrix enabling the systematic comparison of these spatial odorant representations, we hypothesized that the degree of similarity among these representations would predict their perceptual similarity. The two enantiomers of carvone evoked overlapping but significantly distinct regions of glomerular activity; however, the activity patterns evoked by the enantiomers of limonene and of terpinen-4-ol were not statistically different from one another. Commensurate with these data, rats spontaneously discriminated between the enantiomers of carvone, but not between the enantiomers of limonene or terpinen-4-ol, in an olfactory habituation task designed to probe differences in olfactory perception.

A fatigue clinic in a comprehensive cancer center: design and experiences.

Cancer-related fatigue is now the most prevalent symptom of cancer, occurring in 60-90% of patients. Fatigue has been identified by cancer patients as a factor influencing functionality and quality of life. Our objectives in developing a fatigue specialty clinic at The University of Texas M. D. Anderson Cancer Center were to improve our patients' quality of life by decreasing fatigue; educate health care providers, patients, and patients' families about cancer-related fatigue; develop an appropriate clinical and diagnostic evaluation for this symptom; correlate objective measures of fatigue with its clinical evaluation; and develop innovative treatment plans for cancer-related fatigue. This article describes the general clinic design and operations and the preliminary analysis of the first 40 patients evaluated in the fatigue clinic.