Genen - wat willen we ermee? 21 wetenschappers over de consequenties van genomics

Even voelden we ons almachtig, toen in 2000 het hele menselijk genoom was ontrafeld. Genetica werd uitgebreid tot ‘genomics’. Niet alleen konden we allerlei eigenschappen aan onze genen gaan toeschrijven; we zouden ook mooie eigenschappen kunnen gaan maken en ziektes juist uitschakelen. Erfelijkheidsonderzoek kun je nu voor een paar honderd euro laten doen - de vraag is wat je aan de gegevens hebt. Ondertussen weten we wel veel meer van erfelijke verbanden van aandoeningen, maar met die kennis kunnen we ze nog steeds niet zomaar genezen. Het ‘genomics’-onderzoek is zó fundamenteel, de verwachtingen waren zó hooggespannen, dat er ethici bij werden gehaald om na te denken over de mogelijk verstrekkende gevolgen van dit onderzoek. Maar de ethici draaien het liever om en vragen: welk wetenschappelijk onderzoek hebben we nodig voor de grote problemen waar we nog steeds mee zitten? In dit boek spreken 21 wetenschappers zich uit over onderwerpen die met genomics samenhangen. Over hoe ingewikkeld het (menselijk) leven in elkaar zit; over de zin en onzin om heel lang en gezond te willen leven; over het belang en het gevaar van hoog-technologisch onderzoek voor ons aller welzijn; over de algemene toegankelijkheid en toepasbaarheid van wetenschappelijke kennis; etc. De geïnterviewden waarschuwen voor te hoge verwachtingen; voor te ingrijpende maatregelen rond het gebruik van genomics; voor het stellen van verkeerde prioriteiten; en ze stellen voor om daar meer, en opener, met elkaar over te praten

Educational paper: Imaging child abuse: the bare bones

Fractures are reported to be the second most common findings in child abuse, after skin lesions such as bruises and contusions. This makes careful interpretation of childhood fractures in relation to the provided clinical history important. In this literature review, we address imaging techniques and the prevailing protocols as well as fractures, frequently seen in child abuse, and the differential diagnosis of these fractures. The use of a standardised protocol in radiological imaging is stressed, as adherence to the international guidelines has been consistently poor. As fractures are a relatively common finding in childhood and interpretation is sometimes difficult, involvement of a paediatric radiologist is important if not essential. Adherence to international guidelines necessitates review by experts and is therefore mandatory. As in all clinical differential diagnoses, liaison between paediatricians and paediatric radiologists in order to obtain additional clinical information or even better having joint review of radiological studies will improve diagnostic accuracy. It is fundamental to keep in mind that the diagnosis of child abuse can never be solely based on radiological imaging but always on a combination of clinical, investigative and social findings. The quality and interpretation, preferably by a paediatric radiologist, of radiographs is essential in reaching a correct diagnosis in cases of suspected child abuse

Human renal and systemic hemodynamic, natriuretic, and neurohumoral responses to different doses of L-NAME

Experimental evidence indicates that the renal circulation is more sensitive to the effects of nitric oxide (NO) synthesis inhibition than other vascular beds. To explore whether in men the NO-mediated vasodilator tone is greater in the renal than in the systemic circulation, the effects of three different intravenous infusions of NG-nitro-L-arginine methyl ester (L-NAME; 1, 5, and 25 microg. kg-1. min-1 for 30 min) or placebo on mean arterial pressure (MAP), systemic vascular resistance (SVR), renal blood flow (RBF), renal vascular resistance (RVR), glomerular filtration rate (GFR), and fractional sodium and lithium excretion (FENa and FELi) were studied in 12 healthy subjects, each receiving randomly two of the four treatments on two different occasions. MAP was measured continuously by means of the Finapres device, and stroke volume was calculated by a model flow method. GFR and RBF were estimated from the clearances of radiolabeled thalamate and hippuran. Systemic and renal hemodynamics were followed for 2 h after start of infusions. During placebo, renal and systemic hemodynamics and FENa and FELi remained stable. With the low and intermediate L-NAME doses, maximal increments in SVR and RVR were similar: 20.4 +/- 19.6 and 23.5 +/- 16.0%, respectively, with the low dose and 31.4 +/- 26.7 and 31.2 +/- 14.4%, respectively, with the intermediate dose (means +/- SD). With the high L-NAME dose, the increment in RVR was greater than the increment in SVR. Despite a decrease in RBF, FENa and FELi did not change with the low L-NAME dose, but they decreased by 31.2 +/- 11.0 and 20.2 +/- 6.3%, respectively, with the intermediate dose and by 70.8 +/- 8.1 and 31.5 +/- 15.9% with the high L-NAME dose, respectively. It is concluded that in men the renal circulation is not more sensitive to the effects of NO synthesis inhibition than the systemic circulation and that the threshold for NO synthesis inhibition to produce antinatriuresis is higher than the threshold level to cause renal vasoconstriction

Isotopic Resolution of Fission Fragments from 238U+12C Transfer and Fusion Reactions

Expérience GANILInternational audienceRecent results from an experiment at GANIL, performed to investigate the main properties of fission-fragment yields and energy distributions in different fissioning nuclei as a function of the excitation energy, in a neutron-rich region of actinides, are presented. Transfer reactions in inverse kinematics between a 238U beam and a 12C target produced different actinides, within a range of excitation energy below 30 MeV. These fissioning nuclei are identified by detecting the target-like recoil, and their kinetic and excitation energy are determined from the reconstruction of the transfer reaction. The large-acceptance spectrometer VAMOS was used to identify the mass, atomic number and charge state of the fission fragments in flight. As a result, the characteristics of the fission-fragment isotopic distributions of a variety of neutron-rich actinides are observed for the first time over the complete range of fission fragments

Evaluation of a psychoeducational intervention for adolescents with inflammatory bowel disease

OBJECTIVES: Inflammatory bowel disease (IBD), comprising Crohn's disease, ulcerative colitis, and indeterminate colitis, often has its onset in adolescence. The aim of this study was to evaluate whether a psychoeducational group intervention (aiming to enhance information seeking and giving about the disease, relaxation, social competence, and positive thinking) can strengthen the coping efforts of adolescents with IBD and have a positive effect on their Health-Related Quality of Life (HRQoL). METHODS: Adolescent IBD patients from the Emma Children's Hospital AMC and adolescent members of the Crohn and Ulcerative Colitis Association in The Netherlands, were invited to participate in The intervention study. Using reliable and valid self-report instruments the adolescent's coping styles, feelings of competence, and HRQoL were assessed before and 6-8 months after the intervention. The parents were asked to fill in the Child Behavior Check List. Linear regression analyses were performed to test whether group participation was predictive of the outcome measures while correcting for the first measurement occasion and sex. RESULTS AND CONCLUSION: Forty patients responded positively to invitation to the intervention. Eighteen adolescents, however, lived too far away to attend and served as a control group. Twenty-two children were enrolled and attended in groups of four to six children in six group sessions, supervised by two psychologists. The intervention seemed to have a positive effect on: coping (predictive control, P<0.01), feelings of competence (global self-worth, P<0.05 and physical appearance, P<0.01), and HRQoL (body image, P<0.05). These results give good reason to continue this intervention study with a larger population. © 2009 Lippincott Williams & Wilkins, Inc

Out-of-hours care in western countries: assessment of different organizational models

Contains fulltext : 81655.pdf (publisher's version ) (Open Access)BACKGROUND: Internationally, different organizational models are used for providing out-of-hours care. The aim of this study was to assess prevailing models in order to identify their potential strengths and weaknesses. METHODS: An international web-based survey was done in 2007 in a sample of purposefully selected key informants from 25 western countries. The questions concerned prevailing organizational models for out-of-hours care, the most dominant model in each country, perceived weaknesses, and national plans for changes in out-of-hours care. RESULTS: A total of 71 key informants from 25 countries provided answers. In most countries several different models existed alongside each other. The Accident and Emergency department was the organizational model most frequently used. Perceived weaknesses of this model concerned the coordination and continuity of care, its efficiency and accessibility. In about a third of the countries, the rota group was the most dominant organizational model for out-of-hours care. A perceived weakness of this model was lowered job satisfaction of physicians. The GP cooperative existed in a majority of the participating countries; no weaknesses were mentioned with respect to this model. Most of the countries had plans to change the out-of-hours care, mainly toward large scale organizations. CONCLUSION: GP cooperatives combine size of scale advantages with organizational features of strong primary care, such as high accessibility, continuity and coordination of care. While specific patients require other organizational models, the co-existence of different organizational models for out-of-hours care in a country may be less efficient for health systems

Involvement of (pro)renin receptor in the glomerular filtration barrier

(Pro)renin receptor-bound prorenin not only causes the generation of angiotensin II via the nonproteolytic activation of prorenin, it also activates the receptor’s own intracellular signaling pathways independent of the generated angiotensin II. Within the kidneys, the (pro)renin receptor is not only present in the glomerular mesangium, it is also abundant in podocytes, which play an important role in the maintenance of the glomerular filtration barrier. Recent in vivo studies have demonstrated that the overexpression of the (pro)renin receptor to a degree similar to that observed in hypertensive rat kidneys leads to slowly progressive nephropathy with proteinuria. In addition, the handle region peptide, which acts as a decoy peptide and competitively inhibits the binding of prorenin to the receptor, is more beneficial than an angiotensin-converting enzyme inhibitor with regard to alleviating proteinuria and glomerulosclerosis in experimental animal models of diabetes and essential hypertension. Thus, the (pro)renin receptor may be upregulated in podocytes under hypertensive conditions and may contribute to the breakdown of the glomerular filtration barrier

Lifetime measurements of N ≃ 20 phosphorus isotopes using the AGATA γ-ray tracking spectrometer

International audienceLifetimes of excited states of the phosphorus isotopes 1533,34,35,36P have been measured by using the differential recoil-distance method. The isotopes of phosphorus were populated in binary grazing reactions initiated by a beam of S36 ions of energy 225 MeV incident on a thin Pb208 target mounted in the Cologne plunger apparatus. The combination of the PRISMA magnetic spectrometer and an early implementation of the AGATA γ-ray tracking array was used to detect γ rays in coincidence with projectile-like nuclear species. Lifetime measurements of populated states were made within the range from about 1 to 100 ps. The number of states for which lifetime measurements were possible was limited by statistics. For P33, lifetime limits were determined for the first 3/2+ and 5/2+ states at 1431 and 1848 keV, respectively; the results are compared with previous published lifetime values. The lifetime of the first 2+ state of P34 at 429 keV was determined and compared with earlier measurements. For P35, the states for which lifetimes, or lifetime limits, were determined were those at 2386, 3860, 4101, and 4493 keV, with Jπ values of 3/2+, 5/2+, 7/21−, and 7/22−, respectively. There have been no previous published lifetimes for states in this nucleus. A lifetime was measured for the stretched π(1f7/2)⊗ν(1f7/2)Jπ=(7+) state of P36 at 5212 keV and a lifetime limit was established for the stretched π(1d3/2)⊗ν(1f7/2)Jπ=(5−) state at 2030 keV. There are no previously published lifetimes for states of P36. Measured lifetime values were compared with the results of state-of-the-art shell-model calculations based on the PSDPF effective interaction. In addition, measured branching ratios, published mixing ratios, and electromagnetic transition rates, where available, have been compared with shell-model values. In general, there is good agreement between experiment and the shell model; however there is evidence that the shell-model values of the M1 transition rates for the 3/21+→1/2+ (ground state) and 5/21+→3/21+ transitions in P33 underestimate the experimental values by a factor between 5 and 10. In P35 there are some disagreements between experimental and shell-model values of branching ratios for the first and second excited 7/2− states. In particular, there is a serious disagreement for the decay characteristics of the second 7/2− state at 4493 keV, for which the shell-model counterpart lies at 4754 keV. In this case, the shell-model competing electromagnetic decay branches are dominated by E1 and M1 transitions