Detection of gluten in duplicate portions to determine gluten intake of coeliac disease patients on a gluten-free diet.

This study determined the gluten content of foods and meals consumed by coeliac disease (CD) patients who adhere to a gluten-free diet, and to estimate the total daily intake of gluten of these patients. CD patients fulfilling defined inclusion criteria were preselected and approached for participation in the study. Duplicate portions (DP) of foods and mixed dishes were collected from the CD patients for evaluating complete daily food intake during two individual days. Also, for these days, written food records were completed by the participants. From each DP, a laboratory sample was prepared and analysed for its gluten concentration and total daily gluten intake was calculated. Each individual's total daily intakes of energy and macronutrients were calculated using the Dutch food composition database. In total, twenty-seven CD patients participated, seven males and twenty females, aged between 21 and 64 years. In thirty-two (6 %) of 499 food samples collected in total, more than 3 mg/kg gluten was present. In four of these thirty-two samples, the gluten concentration was above the European legal limit of 20 mg/kg and three of the four samples had a gluten-free label. The maximal gluten intake was 3·3 mg gluten/d. The gluten tolerance for sensitive CD patients (>0·75 mg/d) was exceeded on at least six out of fifty-four study days. To also protect these sensitive CD patients, legal thresholds should be re-evaluated and the detection limit of analytical methods for gluten analysis lowered.

IRC +10 216 in 3-D: morphology of a TP-AGB star envelope.

During their late pulsating phase, AGB stars expel most of their mass in the form of massive dusty envelopes, an event that largely controls the composition of interstellar matter. The envelopes, however, are distant and opaque to visible and NIR radiation: their structure remains poorly known and the mass-loss process poorly understood. Millimeter-wave interferometry, which combines the advantages of longer wavelength, high angular resolution and very high spectral resolution is the optimal investigative tool for this purpose. Mm waves pass through dust with almost no attenuation. Their spectrum is rich in molecular lines and hosts the fundamental lines of the ubiquitous CO molecule, allowing a tomographic reconstruction of the envelope structure. The circumstellar envelope IRC +10 216 and its central star, the C-rich TP-AGB star closest to the Sun, are the best objects for such an investigation. Two years ago, we reported the first detailed study of the CO(2-1) line emission in that envelope, made with the IRAM 30-m telescope. It revealed a series of dense gas shells, expanding at a uniform radial velocity. The limited resolution of the telescope (HPBW 11″) did not allow us to resolve the shell structure. We now report much higher angular resolution observations of CO(2-1), CO(1-0), CN(2-1) and C4H(24-23) made with the SMA, PdB and ALMA interferometers (with synthesized half-power beamwidths of 3″, 1″ and 0.3″, respectively). Although the envelope appears much more intricate at high resolution than with an 11″ beam, its prevailing structure remains a pattern of thin, nearly concentric shells. The average separation between the brightest CO shells is 16″ in the outer envelope, where it appears remarkably constant. Closer to the star (< 40″), the shell pattern is denser and less regular, showing intermediary arcs. Outside the small (r < 0.3″) dust formation zone, the gas appears to expand radially at a constant velocity, 14.5 km s-1, with small turbulent motions. Based on that property, we have reconstructed the 3-D structure of the outer envelope and have derived the gas temperature and density radial profiles in the inner (r < 25″) envelope. The shell-intershell density contrast is found to be typically 3. The over-dense shells have spherical or slightly oblate shapes and typically extend over a few steradians, implying isotropic mass loss. The regular spacing of shells in the outer envelope supports the model of a binary star system with a period of 700 years and a near face-on elliptical orbit. The companion fly-by triggers enhanced episodes of mass loss near periastron. The densification of the shell pattern observed in the central part of the envelope suggests a more complex scenario for the last few thousand years.

A new era of thoracic oncology? Ex-vivo stereotactic ablative radiosurgery within Ex-vivo Lung Treatment System as a hybrid therapy for unresectable locally advanced pulmonary malignancies.

The concept of oligometastases is the medical rationale for a local treatment of a limited number of metastatic tumor manifestations. Patients with pulmonary oligometastases are candidates for surgery or radiotherapy, however there are a number of technical issues that limit treatment. Technical issues relating to radiotherapy include organs at risk of irradiation, chest wall toxicity and decreased precision of tumor targeting because of breathing movements. Technical issues relating to surgery include loss of lung parenchyma and unresectability. We propose the hypothesis that ex-vivo radiosurgery as new hybrid technique in thoracic oncology has the capability to overcome these technical issues and will expand the medical spectrum in thoracic oncology. The proposed - highly complex - technique consists of surgical lung explantation, followed by stereotactic radiotherapy during ex-vivo perfusion followed by surgical re-implantation.

Inhalative steroids as an individual treatment in symptomatic lung cancer patients with radiation pneumonitis grade II after radiotherapy - a single-centre experience.

PURPOSE: To assess efficacy of our single-centre experience with inhalative steroids (IS) in lung cancer patients with symptomatic radiation pneumonitis (RP) grade II. MATERIAL AND METHODS: Between 05/09 and 07/10, 24 patients (female, n = 8; male, n = 16) with lung cancer (non-small cell lung carcinoma [NSCLC]: n = 19; small cell lung cancer [SCLC]: n = 3; unknown histology: n = 2) and good performance status (ECOG ≤1) received definitive radiotherapy to the primary tumour site and involved lymph nodes with concurrent chemotherapy (n = 18), sequential chemotherapy (n = 2) or radiation only (n = 4) and developed symptomatic RP grade II during follow-up. No patient presented with oxygen requiring RP grade III. The mean age at diagnosis was 66 years (range: 50-82 years). Nine patients suffered from chronic obstructive pulmonary disease (COPD) before treatment, and 18 patients had a smoking history (median pack years: 48). The mean lung dose was 15.5 Gy (range: 3.0-23.1 Gy). All patients were treated with IS. If a patient's clinical symptoms did not significantly improve within two weeks of IS therapy initiation, their treatment was switched to oral prednisolone. RESULTS: All 24 patients were initially treated with a high dose IS (budesonide 800 µg 1-0-1) for 14 days. Of the patients, 18 showed a significant improvement of clinical symptoms and 6 patients did not show significant improvement of clinical symptoms and were classified as non-responders to IS. Their treatment was switched to oral steroids after two weeks (starting with oral prednisolone, 0.5 mg/kg bodyweight; at least 50 mg per day). All of these patients responded to the prednisolone. None of non-responders presented with increased symptoms of RP and required oxygen and / or hospitalization (RP grade III). The median follow-up after IS treatment initiation was 18 months (range: 4-66 months). The median duration of IS treatment and prednisolone treatment was 8.2 months (range: 3.0-48.3 months) and 11.4 months (range: 5.0-44.0 months), respectively. Of the 18 IS treatment responders, 2 (11.1 %) patients with pre-existing grade 2 COPD still required IS (400 µg twice a day) 45.0 and 48.3 months after radiotherapy, respectively. For the remaining 16 responders (88.9 %), IS therapy was stopped after 7.7 months (range: 3.0-18.2 months). None of the patients treated with IS developed any specific IS-related side effects such as oral candidiasis. CONCLUSION: This single-centre experience shows that high-dose IS is an individual treatment option for radiation-induced pneumonitis grade II in patients with a good performance status.

Immunochemical Detection Methods for Gluten in Food Products: Where Do We Go from Here?

Accurate and reliable quantification methods for gluten in food are necessary to ensure proper product labeling and thus safeguard the gluten sensitive consumer against exposure. Immunochemical detection is the method of choice, as it is sensitive, rapid and relatively easy to use. Although a wide range of detection kits are commercially available, there are still many difficulties in gluten detection that have not yet been overcome. This review gives an overview of the currently commercially available immunochemical detection methods, and discusses the problems that still exist in gluten detection in food. The largest problems are encountered in the extraction of gluten from food matrices, the choice of epitopes targeted by the detection method, and the use of a standardized reference material. By comparing the available techniques with the unmet needs in gluten detection, the possible benefit of a new multiplex immunoassay is investigated. This detection method would allow for the detection and quantification of multiple harmful gluten peptides at once and would, therefore, be a logical advancement in gluten detection in food.

Effects of shade and feeding zilpaterol hydrochloride to finishing steers on performance, carcass quality, heat stress, mobility, and body temperature.

Steers ( = 480; 22% with black hides and 78% with red hides) were used to study the effects of shade and feeding zilpaterol hydrochloride (ZH) on performance, carcass quality, heat stress, mobility, and body temperature (BT). A randomized block design with a 2 × 2 factorial treatment arrangement was used with 4 replicates per treatment. Factors included housing type (open or shaded pens) and the feeding of ZH (0 or 8.33 mg/kg DM) the last 21 d on feed with a 3-d withdrawal. Cattle were blocked by BW into a heavy or light block and randomly assigned to pen within each block. Rumen boluses to record BT were inserted before ZH feeding. Respiration rate and panting scores were recorded daily during the ZH feeding period. Mobility scores were collected at various time points from before ZH feeding through harvest. Interactions between ZH and housing type were not significant ( > 0.26) for animal performance, carcass characteristics, and respiration or panting score. No differences ( > 0.44) were observed for DMI, ADG, or G:F on a live basis due to ZH; however, cattle fed in open pens tended ( = 0.08) to have a greater ADG than cattle in shaded pens. Cattle fed ZH had 14 kg heavier carcasses with larger LM area ( < 0.01) than control cattle. Respiration rates for cattle fed ZH were greater ( = 0.05) with no differences ( = 0.88) due to housing. Time affected ( < 0.01) mobility scores, with observations on the morning of harvest at the abattoir being the worst for all groups of cattle. An interaction ( < 0.01) was observed between ZH and housing type for BT. Cattle fed ZH, in both shaded and open pens, had lower ( < 0.05) average, maximum, and area under the curve BT than control cattle fed in the same housing type. However, the observed reduction in BT due to ZH was greater for cattle fed ZH in open pens than for cattle fed ZH in shaded pens. From these results, we conclude that ZH improved HCW with little impact on heat stress or mobility, suggesting that animal welfare was not affected by feeding ZH for 21 d at the end of the feeding period.

Inter-laboratory validation study of two immunochemical methods for detection of processed ruminant proteins.

In order to facilitate safe re-introduction of non-ruminant processed animal proteins (PAPs) in aqua feed, two immunoassays have been tested in an interlaboratory study for their capability to detect ruminant PAPs processed under European conditions. The sensitivity of the MELISA-TEK assay was improved by applying a specific extraction kit. Six approved blank pork and poultry samples were adulterated to produce 15 samples spiked at 0.5%, 1.0% and 2.0% with ruminant material, sterilised at either 133 °C or 137 °C. Fourteen participants investigated the 6 blanks and 15 spiked samples, making 21 samples for the final test. For both assays specificity and sensitivity were at 97% or higher. Concordance and accordance were higher than 95% with one exception. The results indicate that both assays provided correct results at 0.5% and higher for the detecting ruminant PAPs (sterilised at 133 °C) in non-ruminant PAPs. Given the 2% upper limit of ruminant PAPs in non-ruminant PAPs for avoiding an increase in BSE incidents, these methods are fit for monitoring non-ruminant PAPs intended for aqua feed.

The visual analogue thermometer and the graphic numeric rating scale: a comparison of self-report instruments for pain measurement in adults with burns.

To evaluate the adequacy of pain management in burn care, pain measurement is essential. The visual analogue thermometer (VAT) and graphic numeric rating scale (GNRS) are frequently used self-report instruments for burn pain. To legitimise their interchangeable use in research and practice, we aimed to compare self-reports obtained by the VAT and GNRS, the ability of the scales to differentiate background from procedural pain, and to compare potential cutpoints. Adults with acute burns (N=319) participated in the study (67% male, mean age 40.3 years (SD 16), mean TBSA 9.9% (SD 10.4). Correlation coefficients between VAT and GNRS were 0.64 and 0.55 for, respectively, morning and afternoon background pain and 0.51 for procedural pain (p<0.01). VAT scores were lower than GNRS scores for all pain types (p<0.01). Both scales could differentiate background from procedural pain: procedural pain was higher (p<0.01). The standardized response mean was moderate (0.518 for VAT and 0.571 for GNRS). Self-reported thresholds for 'unacceptable pain' by GNRS were higher than by VAT (p<0.001). ROC analyses showed that the highest sensitivity was reached for pain score 2 for both scales. The results suggest that the instruments cannot be used interchangeably without taking their differences into account.

Postoperative periclavicular radiotherapy in breast cancer patients with 1-3 positive axillary lymph nodes. Outcome and morbidity.

PURPOSE: The goal of this work was to examine the possible influence of periclavicular irradiation on outcome of breast cancer patients with 1-3 positive lymph nodes with special emphasis on late toxicity rates. PATIENTS AND METHODS: Between 1997 and 2000, 235 breast cancer patients (T1-2, 1-3 involved lymph nodes) were treated at our department following breast conservative surgery: 139 patients (59.1%) had one, 62 patients (26.4%) two, and 34 patients (14.5%) three positive lymph nodes. Extracapsular spread (ECS) was described in 72 patients (30.6%). There were 67 patients (28.5%) who received additional radiotherapy to the ipsilateral periclavicular lymph nodes (PCLNI), while 168 patients did not (noPCLNI). Patients were re-examined or contacted by phone with regard to treatment-related late effects. RESULTS: After a median follow-up of 78 months (range 7-107 months), 22 patients (9.4%) developed local, 9 (3.8%) axillary, 4 periclavicular (1.7%), and 41 distant failure (17.4%). The actuarial 8-year locoregional recurrence-free (LRRFS), disease-free (DFS), and overall survival rates (OS) were 83%, 67%, and 74%, respectively. Survival data for the PCLNI vs. noPCLNI group were 72% vs. 89% (p = 0.3), 56% vs. 73% (p = 0.4), and 86% vs. 70% (p = 0.3), respectively. No higher toxicity rates were reported in the PCLNI group compared to the noPCLNI group. CONCLUSION: We could not demonstrate any difference in outcome in breast cancer patients with 1-3 positive axillary lymph node metastases with or without periclavicular lymph node irradiation. In addition, patients with PCLNI did not complain about higher rates of late toxicities. However, patients with ECS, which may predict for locoregional failure, may benefit from adjuvant periclavicular irradiation.

Evaluation of variation in the phosphoinositide-3-kinase catalytic subunit alpha oncogene and breast cancer risk.

BACKGROUND: Somatic mutations in phosphoinositide-3-kinase catalytic subunit alpha (PIK3CA) are frequent in breast tumours and have been associated with oestrogen receptor (ER) expression, human epidermal growth factor receptor-2 overexpression, lymph node metastasis and poor survival. The goal of this study was to evaluate the association between inherited variation in this oncogene and risk of breast cancer. METHODS: A single-nucleotide polymorphism from the PIK3CA locus that was associated with breast cancer in a study of Caucasian breast cancer cases and controls from the Mayo Clinic (MCBCS) was genotyped in 5436 cases and 5280 controls from the Cancer Genetic Markers of Susceptibility (CGEMS) study and in 30 949 cases and 29 788 controls from the Breast Cancer Association Consortium (BCAC). RESULTS: Rs1607237 was significantly associated with a decreased risk of breast cancer in MCBCS, CGEMS and all studies of white Europeans combined (odds ratio (OR)=0.97, 95% confidence interval (CI) 0.95-0.99, P=4.6 × 10(-3)), but did not reach significance in the BCAC replication study alone (OR=0.98, 95% CI 0.96-1.01, P=0.139). CONCLUSION: Common germline variation in PIK3CA does not have a strong influence on the risk of breast cancer.

An extremely luminous panchromatic outburst from the nucleus of a distant galaxy.

Variable x-ray and γ-ray emission is characteristic of the most extreme physical processes in the universe. We present multiwavelength observations of a unique γ-ray-selected transient detected by the Swift satellite, accompanied by bright emission across the electromagnetic spectrum, and whose properties are unlike any previously observed source. We pinpoint the event to the center of a small, star-forming galaxy at redshift z = 0.3534. Its high-energy emission has lasted much longer than any γ-ray burst, whereas its peak luminosity was ∼100 times higher than bright active galactic nuclei. The association of the outburst with the center of its host galaxy suggests that this phenomenon has its origin in a rare mechanism involving the massive black hole in the nucleus of that galaxy.

Spectroscopic confirmation of a galaxy at redshift z = 8.6.

Galaxies had their most significant impact on the Universe when they assembled their first generations of stars. Energetic photons emitted by young, massive stars in primeval galaxies ionized the intergalactic medium surrounding their host galaxies, cleared sightlines along which the light of the young galaxies could escape, and fundamentally altered the physical state of the intergalactic gas in the Universe continuously until the present day. Observations of the cosmic microwave background, and of galaxies and quasars at the highest redshifts, suggest that the Universe was reionized through a complex process that was completed about a billion years after the Big Bang, by redshift z ≈ 6. Detecting ionizing Lyman-α photons from increasingly distant galaxies places important constraints on the timing, location and nature of the sources responsible for reionization. Here we report the detection of Lyα photons emitted less than 600 million years after the Big Bang. UDFy-38135539 (ref. 5) is at a redshift of z = 8.5549 ± 0.0002, which is greater than those of the previously known most distant objects, at z = 8.2 (refs 6 and 7) and z = 6.96 (ref. 8). We find that this single source is unlikely to provide enough photons to ionize the volume necessary for the emission line to escape, requiring a significant contribution from other, probably fainter galaxies nearby.

Re-irradiation of head and neck cancer-impact of total dose on outcome.

AIM: To evaluate the outcome of re-irradiation and to define favourable pre-treatment characteristics. PATIENTS AND METHODS: seventy-five patients with locally recurrent head and neck cancer were treated with re-irradiation, either postoperatively or as definitive treatment, with and without chemotherapy. Mean time period between first and second series of irradiation was 19 months. Mean overall dose of re-irradiation was 46 Gy. Median follow-up was 8.7 months. RESULTS: Overall survival, loco-regional disease-free survival and metastasis-free survival after two years were 23%, 24% and 77%, respectively. Higher overall doses of re-irradiation gave a statistically significant better outcome with regard to overall survival (p=0.018). CONCLUSION: For patients with locally recurrent head and neck cancer, re-irradiation is a feasible therapeutic option. The total dose at re-irradiation improves overall survival. Therefore, re-irradiation with curative intent should only be applied if a sufficient total dose of ≥46 Gy can be given.

A gamma-ray burst at a redshift of z approximately 8.2.

Long-duration gamma-ray bursts (GRBs) are thought to result from the explosions of certain massive stars, and some are bright enough that they should be observable out to redshifts of z > 20 using current technology. Hitherto, the highest redshift measured for any object was z = 6.96, for a Lyman-alpha emitting galaxy. Here we report that GRB 090423 lies at a redshift of z approximately 8.2, implying that massive stars were being produced and dying as GRBs approximately 630 Myr after the Big Bang. The burst also pinpoints the location of its host galaxy.

Flares from a candidate Galactic magnetar suggest a missing link to dim isolated neutron stars.

Magnetars are young neutron stars with very strong magnetic fields of the order of 10(14)-10(15) G. They are detected in our Galaxy either as soft gamma-ray repeaters or anomalous X-ray pulsars. Soft gamma-ray repeaters are a rare type of gamma-ray transient sources that are occasionally detected as bursters in the high-energy sky. No optical counterpart to the gamma-ray flares or the quiescent source has yet been identified. Here we report multi-wavelength observations of a puzzling source, SWIFT J195509+261406. We detected more than 40 flaring episodes in the optical band over a time span of three days, and a faint infrared flare 11 days later, after which the source returned to quiescence. Our radio observations confirm a Galactic nature and establish a lower distance limit of approximately 3.7 kpc. We suggest that SWIFT J195509+261406 could be an isolated magnetar whose bursting activity has been detected at optical wavelengths, and for which the long-term X-ray emission is short-lived. In this case, a new manifestation of magnetar activity has been recorded and we can consider SWIFT J195509+261406 to be a link between the 'persistent' soft gamma-ray repeaters/anomalous X-ray pulsars and dim isolated neutron stars.

Broadband observations of the naked-eye gamma-ray burst GRB 080319B.

Long-duration gamma-ray bursts (GRBs) release copious amounts of energy across the entire electromagnetic spectrum, and so provide a window into the process of black hole formation from the collapse of massive stars. Previous early optical observations of even the most exceptional GRBs (990123 and 030329) lacked both the temporal resolution to probe the optical flash in detail and the accuracy needed to trace the transition from the prompt emission within the outflow to external shocks caused by interaction with the progenitor environment. Here we report observations of the extraordinarily bright prompt optical and gamma-ray emission of GRB 080319B that provide diagnostics within seconds of its formation, followed by broadband observations of the afterglow decay that continued for weeks. We show that the prompt emission stems from a single physical region, implying an extremely relativistic outflow that propagates within the narrow inner core of a two-component jet.