The effect of ionic strength on the kinetic stability of NADH oxidase in a bubble column

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Moreel klimaat van scholen voor voortgezet onderwijs: De perceptie van de leerlingen

Wetensch. publicatieFaculteit der Sociale Wetenschappe

A highly magnified candidate for a young galaxy seen when the Universe was 500 Myrs old

The early Universe at redshift z\sim6-11 marks the reionization of the intergalactic medium, following the formation of the first generation of stars. However, those young galaxies at a cosmic age of \lesssim 500 million years (Myr, at z \gtrsim 10) remain largely unexplored as they are at or beyond the sensitivity limits of current large telescopes. Gravitational lensing by galaxy clusters enables the detection of high-redshift galaxies that are fainter than what otherwise could be found in the deepest images of the sky. We report the discovery of an object found in the multi-band observations of the cluster MACS1149+22 that has a high probability of being a gravitationally magnified object from the early universe. The object is firmly detected (12 sigma) in the two reddest bands of HST/WFC3, and not detected below 1.2 {\mu}m, matching the characteristics of z\sim9 objects. We derive a robust photometric redshift of z = 9.6 \pm 0.2, corresponding to a cosmic age of 490 \pm 15Myr (i.e., 3.6% of the age of the Universe). The large number of bands used to derive the redshift estimate make it one of the most accurate estimates ever obtained for such a distant object. The significant magnification by cluster lensing (a factor of \sim15) allows us to analyze the object's ultra-violet and optical luminosity in its rest-frame, thus enabling us to constrain on its stellar mass, star-formation rate and age. If the galaxy is indeed at such a large redshift, then its age is less than 200 Myr (at the 95% confidence level), implying a formation redshift of zf \lesssim 14. The object is the first z>9 candidate that is bright enough for detailed spectroscopic studies with JWST, demonstrating the unique potential of galaxy cluster fields for finding highly magnified, intrinsically faint galaxies at the highest redshifts.Comment: Submitted to the Nature Journal. 39 Pages, 13 figure

Distinguishing Asthma Phenotypes Using Machine Learning Approaches.

Asthma is not a single disease, but an umbrella term for a number of distinct diseases, each of which are caused by a distinct underlying pathophysiological mechanism. These discrete disease entities are often labelled as asthma endotypes. The discovery of different asthma subtypes has moved from subjective approaches in which putative phenotypes are assigned by experts to data-driven ones which incorporate machine learning. This review focuses on the methodological developments of one such machine learning technique-latent class analysis-and how it has contributed to distinguishing asthma and wheezing subtypes in childhood. It also gives a clinical perspective, presenting the findings of studies from the past 5 years that used this approach. The identification of true asthma endotypes may be a crucial step towards understanding their distinct pathophysiological mechanisms, which could ultimately lead to more precise prevention strategies, identification of novel therapeutic targets and the development of effective personalized therapies

Safety of a new extensively hydrolysed formula in children with cow's milk protein allergy: a double blind crossover study

BACKGROUND: Formulae for infants with cow's milk protein allergy (CMA) should be based on extensively hydrolysed protein. 'Extensively' however is not strictly defined. Differences in molecular weight and peptide chain length may affect its clinical outcome. We studied the safety of a new extensively hydrolysed casein based formula (Frisolac Allergycare(®): FAC) for children with IgE mediated CMA. METHODS: Thirty children, aged 1.5 – 14.8 years old (median 4.9 years) with persistent CMA were enrolled in this double-blind reference product (Nutramigen(®): NUT) controlled crossover study. All had positive skin prick tests (SPT) and IgE mediated allergy, showing immediate reactions after ingestion of small amounts of milk. Twenty-five children also had positive radio allergen sorbent tests (RAST) to cow's milk. Formulae provided consisted of 80% elementary formula in combination with 20% reference or test product. Crossover periods lasted for two weeks. From both products molecular weight (MALDI-TOF method and HPLC) and peptide chain length distribution (adapted Edman degradation) were determined. RESULTS: Maximum molecular weights of NUT and FAC are 2.1 and 2.56 kDa, respectively. The contribution of free amino acids and small peptides <0.5 kDa is 46% for FAC and 53% for NUT. About 50% of the protein fraction of both products consists of peptides longer than four amino acids. Three children did not complete the study. The other children all tolerated FAC very well; no adverse reactions were reported. CONCLUSIONS: The new extensively hydrolysed casein-based formula (FAC) can safely be used in children with IgE mediated cow's milk allergy

Clinical practice. Diagnosis and treatment of cow’s milk allergy

Introduction Cow's milk allergy (CMA) is thought to affect 2-3% of infants. The signs and symptoms are nonspecific and may be difficult to objectify, and as the diagnosis requires cow's milk elimination followed by challenge, often, children are considered cow's milk allergic without proven diagnosis. Diagnosis Because of the consequences, a correct diagnosis of CMA is pivotal. Open challenges tend to overestimate the number of children with CMA. The only reliable way to diagnose CMA is by double-blind, placebo-controlled challenge (DBPCFC). Therapy At present, the only proven treatment consists of elimination of cow's milk protein from the child's diet and the introduction of formulas based on extensively hydrolysed whey protein or casein; amino acid-based formula is rarely indicated. The majority of children will regain tolerance to cow's milk within the first 5 years of life. Conclusions Open challenges can be used to reject CMA, but for adequate diagnosis, DBPCFC is mandatory. In most children, CMA can be adequately treated with extensively hydrolysed whey protein or casein formulas

Clinical practice: Breastfeeding and the prevention of allergy

The increase in allergic disease prevalence has led to heightened interest in the factors determining allergy risk, fuelled by the hope that by influencing these factors one could reduce the prevalence of allergic conditions. The most important modifiable risk factors for allergy are maternal smoking behaviour and the type of feeding. A smoke-free environment for the child (to be), exclusive breastfeeding for 4–6 months and the postponement of supplementary feeding (solids) until 4 months of age are the main measures considered effective. There is no place for restricted diets during pregnancy or lactation. Although meta-analyses suggest that hypoallergenic formula after weaning from breastfeeding grants protection against the development of allergic disease, the evidence is limited and weak. Moreover, all current feeding measures aiming at allergy prevention fail to show effects on allergic manifestations later in life, such as asthma. In conclusion, the allergy preventive effect of dietary interventions in infancy is limited. Counselling of future parents on allergy prevention should pay attention to these limitations

Current state and future of pediatric allergology in Europe: A road map

The history of pediatric allergology (PA) in Europe is relatively youthful, dating back to 1984, when a small group of pediatricians founded the European Working Group on Pediatric Allergy and Immunology—later giving rise to ESPACI (European Society on Pediatric Allergology and Clinical Immunology). In 1990, the first dedicated journal, Pediatric Allergy and Immunology (PAI), was founded. There are striking differences across Europe, and even within European countries, in relation to the training pathways for doctors seeing children with allergic disease(s). In 2016, the EAACIClemens von Pirquet Foundation (CvP) organized and sponsored a workshop with the European Academy of Allergy and Clinical Immunology (EAACI) Pediatric Section. This collaboration focussed on the future of PA and specifically on education, research, and networking/ advocacy. The delegates representing many countries across Europe have endorsed the concept that optimal care of children with allergic diseases is delivered by pediatricians who have received dedicated training in allergy, or allergists who have received dedicated training in pediatrics. In order to meet the needs of children and families with allergic disease(s), the pediatric allergist is highly encouraged to develop several networks. Our challenge is to reinforce a clear strategic approach to scientific excellence to across our member base and to ensure and enhance the relevance of European pediatric research in allergy. With research opportunities in basic, translational, clinical, and epidemiologic trials, more trainees and trained specialists are needed and it is an exciting time to be a pediatric allergologist

Randomised controlled trial of food elimination diet based on IgG antibodies for the prevention of migraine like headaches

<p>Abstract</p> <p>Background</p> <p>Research suggests that food intolerance may be a precipitating factor for migraine like headaches.</p> <p>Aim</p> <p>To evaluate the effectiveness of the ELISA (Enzyme Linked Immuno-Sorbent Assay) Test and subsequent dietary elimination advice for the prevention of migraine like headaches.</p> <p>Design</p> <p>Randomised controlled trial.</p> <p>Setting</p> <p>Community based volunteers in the UK.</p> <p>Participants</p> <p>Volunteers who met the inclusion criteria for migraine like headaches and had one or more food intolerance were included in the study. Participants received either a true diet (n = 84) or a sham diet (n = 83) sheet. Participants were advised to remove the intolerant foods from their diet for 12 weeks.</p> <p>Main outcome measures</p> <p>Number of headache days over a 12 week period (item A MIDAS questionnaire). Other measures includes the total MIDAS score and total HIT-6 score.</p> <p>Results</p> <p>The results indicated a small decrease in the number of migraine like headaches over 12 weeks, although this difference was not statistically significant (IRR 1.15 95% CI 0.94 to 1.41, p = 0.18). At the 4 week assessment, use of the ELISA test with subsequent diet elimination advice significantly reduced the number of migraine like headaches (IRR 1.23 95%CI 1.01 to 1.50, p = 0.04). The disability and impact on daily life of migraines were not significantly different between the true and sham diet groups.</p> <p>Conclusions</p> <p>Use of the ELISA test with subsequent diet elimination advice did not reduce the disability or impact on daily life of migraine like headaches or the number of migraine like headaches at 12 weeks but it did significantly reduce the number of migraine like headaches at 4 weeks.</p> <p>Trial registration number</p> <p>ISRCTN: <a href="http://www.controlled-trials.com/ISRTCN89559672">ISRTCN89559672</a></p

Impact of non-axillary sentinel node biopsy on staging and treatment of breast cancer patients

The purpose of this study was to evaluate the occurrence of lymphatic drainage to non-axillary sentinel nodes and to determine the implications of this phenomenon. A total of 549 breast cancer patients underwent lymphoscintigraphy after intratumoural injection of 99mTc-nanocolloid. The sentinel node was intraoperatively identified with the aid of intratumoural administered patent blue dye and a gamma-ray detection probe. Histopathological examination of sentinel nodes included step-sectioning at six levels and immunohistochemical staining. A sentinel node outside level I or II of the axilla was found in 149 patients (27%): internal mammary sentinel nodes in 86 patients, other non-axillary sentinel nodes in 44 and both internal mammary and other non-axillary sentinel nodes in nineteen patients. The intra-operative identification rate was 80%. Internal mammary metastases were found in seventeen patients and metastases in other non-axillary sentinel nodes in ten patients. Staging improved in 13% of patients with non-axillary sentinel lymph nodes and their treatment strategy was changed in 17%. A small proportion of clinically node negative breast cancer patients can be staged more precisely by biopsy of sentinel nodes outside level I and II of the axilla, resulting in additional decision criteria for postoperative regional or systemic therapy