ThermoSpots to detect hypothermia in children with severe acute malnutrition

INTRODUCTION: Hypothermia is a risk factor for increased mortality in children with severe acute malnutrition (SAM). Yet frequent temperature measurement remains unfeasible in under-resourced units in developing countries. ThermoSpot is a continuous temperature monitoring sticker designed originally for neonates. When applied to skin, its liquid crystals are designed to turn black with hypothermia and remain green with normothermia.

AIMS: To (i) estimate the diagnostic accuracy of ThermoSpots for detecting WHO-defined hypothermia (core temperature <35.5°C or peripheral temperature <35.0°C) in children with SAM and (ii) determine their acceptability amongst mothers.

METHODS: Children with SAM in a malnutrition unit in Malawi were enrolled during March-July 2010. The sensitivity and specificity of ThermoSpots were calculated by comparing the device colour against 'gold standard' rectal temperatures taken on admission and follow up peripheral temperatures taken until discharge. Guardians completed a questionnaire to assess acceptability.

RESULTS: Hypothermia was uncommon amongst the 162 children enrolled. ThermoSpot successfully detected the one rectal temperature and two peripheral temperatures recorded that met the WHO definition of hypothermia. Overall, 3/846 (0.35%) temperature measurements were in the WHO-defined hypothermia range. Interpreting the brown transition colour (between black and green) as hypothermia improved sensitivities. For milder hypothermia definitions, sensitivities declined (<35.4°C, 50.0%; <35.9°C, 39.2%). Specificity was consistently above 94%. From questionnaires, 40/43 (93%) mothers reported they were 90-100% happy with the device overall. Free-text answers revealed themes of "Skin Rashes", "User-satisfaction" and "Empowerment".

CONCLUSION: Although hypothermia was uncommon in this study, ThermoSpots successfully detected these episodes in malnourished children and were acceptable to mothers. Research in settings where hypothermia is common is needed to determine performance with certainty. Instructing users to act when the device's transition colour appears could improve accuracy. If reliable, ThermoSpots may offer simple, acceptable and continuous temperature measurement for high-burden areas and reduce the workload of over-stretched staff.

Evaluating laser-driven Bremsstrahlung radiation sources for imaging and analysis of nuclear waste packages

A small scale sample nuclear waste package, consisting of a 28 mm diameter uranium penny encased in grout, was imaged by absorption contrast radiography using a single pulse exposure from an X-ray source driven by a high-power laser. The Vulcan laser was used to deliver a focused pulse of photons to a tantalum foil, in order to generate a bright burst of highly penetrating X-rays (with energy >500 keV), with a source size of <0.5 mm. BAS-TR and BAS-SR image plates were used for image capture, alongside a newly developed Thalium doped Caesium Iodide scintillator-based detector coupled to CCD chips. The uranium penny was clearly resolved to sub-mm accuracy over a 30 cm2 scan area from a single shot acquisition. In addition, neutron generation was demonstrated in situ with the X-ray beam, with a single shot, thus demonstrating the potential for multi-modal criticality testing of waste materials. This feasibility study successfully demonstrated non-destructive radiography of encapsulated, high density, nuclear material. With recent developments of high-power laser systems, to 10 Hz operation, a laser-driven multi-modal beamline for waste monitoring applications is envisioned.

Imre Lengyel, Nicola B Quinn, Lajos Csincsik, Craig Ritchie, Ruth E Hogg, Sebastian Crutch, Tunde Peto, Timothy Shakespeare

Investigative Ophthalmology & Visual Science Volume 56 Issue 7 Pages 2795-2795

Further assessment of the complement component 2 and factor B region associated with age-related macular degeneration

PURPOSE. Polymorphic variation in genes involved in regulation of the complement system has been implicated as a major cause of genetic risk, in addition to the LOC387715/HTRA1 locus and other environmental influences. Previous studies have identified polymorphisms in the complement component 2 (CC2) and factor B (CFB) genes, as potential functional variants associated with AMD, in particular CFB R32Q and CC2 rs547154, both of which share strong linkage disequilibrium (LD). METHODS. Data derived from the HapMap Project were used to select 18 haplotype-tagging SNPs across the extended CC2/ CFB region for genotyping, to measure the strength of LD in 318 patients with neovascular AMD and 243 age-matched control subjects to identify additional potential functional variants in addition to those originally reported. RESULTS. Strong LD was measured across this region as far as the superkiller viralicidic activity 2-like gene (SKIV2L). Nine SNPs were identified to be significantly associated with the genetic effect observed at this locus. Of these, a nonsynonymous coding variant SKIV2L R151Q (rs438999; OR, 0.48; 95% confidence interval [CI], 0.31- 0.74; P < 0.001), was in strong LD with CFB R32Q, rs641153 (r2 = 0.95) and may exert a functional effect. When assessed within a logistic regression model measuring the effects of genetic variation at the CFH and LOC387715/HTRA1 loci and smoking, the effect remained significant (OR, 0.38; 95% CI, 0.22- 0.65; P < 0.001). Additional variation identified within this region may also confer a weaker but independent effect and implicate additional genes within the pathogenesis of AMD. CONCLUSIONS. Because of the high level of LD within the extended CC2/CFB region, variation within SKIV2L may exert a functional effect in AMD. Copyright © Association for Research in Vision and Ophthalmology.<br/>

Association of airway cathepsin B and S with inflammation in cystic fibrosis.

Irreversible tissue damage within the cystic fibrosis (CF) lung is mediated by proteolytic enzymes during an inflammatory response. Serine proteinases, in particular neutrophil elastase (NE), have been implicated however, members of the cysteine proteinase family may also be involved. The aim of this study was to determine cathepsin B and S levels in cystic fibrosis (CF) sputum and to assess any relationship to recognized markers of inflammation such as sputum NE, interleukin-8 (IL-8), tumor necrosis factor alpha (TNF-a), urine TNF receptor 1 (TNFr1), plasma IL-6, and serum C-reactive protein (CRP). Proteinase activities were measured in the sputum of 36 clinically stable CF patients using spectrophotometric and fluorogenic assays. Immunoblots were also used to confirm enzyme activity data. All other parameters were measured by ELISA. Patients had a mean age of 27.2 (8.2) years, FEV. of 1.6 (0.79) L and BMI of 20.7 (2.8). Both cathepsin B and S activities were detected in all samples, with mean concentrations of 18.0 (13.5)?µg/ml and 1.6 (0.88)?µg/ml, respectively and were found to correlate not only with each other but with NE, TNF-a and IL-8 (in all cases .?<?0.05). Airway cathepsin B further correlated with circulatory IL-6 and CRP however, no relationship for either cathepsin was observed with urine TNFr1. This data indicates that cathepsin B and S may have important roles in the pathophysiology of CF lung disease and could have potential as markers of inflammation in future studies. Pediatr. Pulmonol. 2010; 45:860–868.

IntCal13 and Marine13 Radiocarbon Age Calibration Curves 0-50,000 Years Cal BP

The IntCal09 and Marine09 radiocarbon calibration curves have been revised utilizing newly available and updated data sets from C measurements on tree rings, plant macrofossils, speleothems, corals, and foraminifera. The calibration curves were derived from the data using the random walk model (RWM) used to generate IntCal09 and Marine09, which has been revised to account for additional uncertainties and error structures. The new curves were ratified at the 21st International Radiocarbon conference in July 2012 and are available as Supplemental Material at www.radiocarbon.org. The database can be accessed at http://intcal.qub.ac.uk/intcal13/.

Association Between Results of a Gene Expression Signature Assay and Recurrence-Free Interval in Patients With Stage II Colon Cancer in Cancer and Leukemia Group B 9581 (Alliance)

PURPOSE: Conventional staging methods are inadequate to identify patients with stage II colon cancer (CC) who are at high risk of recurrence after surgery with curative intent. ColDx is a gene expression, microarray-based assay shown to be independently prognostic for recurrence-free interval (RFI) and overall survival in CC. The objective of this study was to further validate ColDx using formalin-fixed, paraffin-embedded specimens collected as part of the Alliance phase III trial, C9581.

PATIENTS AND METHODS: C9581 evaluated edrecolomab versus observation in patients with stage II CC and reported no survival benefit. Under an initial case-cohort sampling design, a randomly selected subcohort (RS) comprised 514 patients from 901 eligible patients with available tissue. Forty-nine additional patients with recurrence events were included in the analysis. Final analysis comprised 393 patients: 360 RS (58 events) and 33 non-RS events. Risk status was determined for each patient by ColDx. The Self-Prentice method was used to test the association between the resulting ColDx risk score and RFI adjusting for standard prognostic variables.

RESULTS: Fifty-five percent of patients (216 of 393) were classified as high risk. After adjustment for prognostic variables that included mismatch repair (MMR) deficiency, ColDx high-risk patients exhibited significantly worse RFI (multivariable hazard ratio, 2.13; 95% CI, 1.3 to 3.5; P < .01). Age and MMR status were marginally significant. RFI at 5 years for patients classified as high risk was 82% (95% CI, 79% to 85%), compared with 91% (95% CI, 89% to 93%) for patients classified as low risk.

CONCLUSION: ColDx is associated with RFI in the C9581 subsample in the presence of other prognostic factors, including MMR deficiency. ColDx could be incorporated with the traditional clinical markers of risk to refine patient prognosis.