From single-molecule to organism-level biophysics

Wuite, G.J.L. [Promotor]Stephens, G.J. [Copromotor

Carotenoid status in man: effects on biomarkers of eye, skin and cardiovascular health

Observational epidemiological studies have consistently shown that a diet rich in carotenoid-containing fruit and vegetables is associated with a reduced risk of chronic diseases. Because intervention studies with hard endpoints are time-consuming and costly, the use of biomarkers could be a promising approach. We studied the relation between serum carotenoid concentrations in a normal physiological range and biomarkers of eye, skin and cardiovascular health.In a cross-sectional study among 376 subjects the associations between serum and adipose tissue lutein and macula pigment (MP) density in the eye were stronger in men than in women. MP density was inversely associated with lens density. Lens density was not related to serum and adipose tissue concentrations of lutein after adjustment for age. A modifying effect was observed on the association between serum carotenoids and minimal erythema dose, a marker of skin sensitivity to UV light. Several carotenoids were inversely associated with markers of inflammation markers and endothelial function.In a 1-year randomized double blind placebo-controlled trial among 341 subjects, the effects of 0, 7, 10 and 17 g/d consumption of sucrose polyesters (SPE) on serum carotenoids and functional biomakers were studied. Lipid standardized carotenoid concentrations decreased by 13-33% in the group consuming 17 g/d SPE in comparison with the control group. Decreases of serum carotenoids in the 10 g/d and 7 g/d SPE groups were less. No negative effects were observed on markers of oxidation, eye health, cardiovascular health, and immune status. In a 4-week randomized single blind placebo-controlled trial among 47 subjects, the effect of 500 g/d fruit and vegetables + 200 mL fruit juice was studied in comparison with 100 g/d fruit and vegetables consumption on serum carotenoids and biomarkers of cardiovascular health. Serum carotenoids increased by 22-128%. Homocysteine concentrations decreased by 11%. No effect was observed on serum lipids, blood pressure and fibrinolysis/coagulation variables.Overall, our studies used biomarkers that are indicative of biological processes currently thought to be important in disease etiology. But the predictive value has not been established. Therefore, our studies cannot be conclusive for disease risk. However, they seem to add proof to the hypothesis that serum carotenoid decreases or increases within normal physiological ranges in periods up to one year, have no or limited impact on biomarkers related to eye, skin and cardiovascular health

Hysteroscopy for treating subfertility associated with suspected major uterine cavity abnormalities

Background : Observational studies suggest higher pregnancy rates after the hysteroscopic removal of endometrial polyps, submucous fibroids, uterine septum or intrauterine adhesions, which are detectable in 10% to 15% of women seeking treatment for subfertility. Objectives : To assess the effects of the hysteroscopic removal of endometrial polyps, submucous fibroids, uterine septum or intrauterine adhesions suspected on ultrasound, hysterosalpingography, diagnostic hysteroscopy or any combination of thesemethods inwomenwith otherwise unexplained subfertility or prior to intrauterine insemination (IUI), in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI). Search methods : We searched theCochraneMenstrualDisorders and Subfertility SpecialisedRegister (8 September 2014), theCochrane Central Register of Controlled Trials (The Cochrane Library 2014, Issue 9), MEDLINE (1950 to 12 October 2014), EMBASE (inception to 12 October 2014), CINAHL (inception to 11 October 2014) and other electronic sources of trials including trial registers, sources of unpublished literature and reference lists. We handsearched the American Society for Reproductive Medicine (ASRM) conference abstracts and proceedings (from January 2013 to October 2014) and we contacted experts in the field. Selection criteria : Randomised comparisons between operative hysteroscopy versus control in women with otherwise unexplained subfertility or undergoing IUI, IVF or ICSI and suspected major uterine cavity abnormalities diagnosed by ultrasonography, saline infusion/ gel instillation sonography, hysterosalpingography, diagnostic hysteroscopy or any combination of these methods. Primary outcomes were live birth and hysteroscopy complications. Secondary outcomes were pregnancy and miscarriage. Data collection and analysis : Two review authors independently assessed studies for inclusion and risk of bias, and extracted data. We contacted study authors for additional information. Main results : We retrieved 12 randomised trials possibly addressing the research questions. Only two studies (309 women) met the inclusion criteria. Neither reported the primary outcomes of live birth or procedure related complications. In women with otherwise unexplained subfertility and submucous fibroids there was no conclusive evidence of a difference between the intervention group treated with hysteroscopic myomectomy and the control group having regular fertility-oriented intercourse during 12 months for the outcome of clinical pregnancy. A large clinical benefit with hysteroscopic myomectomy cannot be excluded: if 21% of women with fibroids achieve a clinical pregnancy having timed intercourse only, the evidence suggests that 39% of women (95% CI 21% to 58%) will achieve a successful outcome following the hysteroscopic removal of the fibroids (odds ratio (OR) 2.44, 95% confidence interval (CI) 0.97 to 6.17, P = 0.06, 94 women, very low quality evidence). There is no evidence of a difference between the comparison groups for the outcome of miscarriage (OR 0.58, 95% CI 0.12 to 2.85, P = 0.50, 30 clinical pregnancies in 94 women, very low quality evidence). The hysteroscopic removal of polyps prior to IUI can increase the chance of a clinical pregnancy compared to simple diagnostic hysteroscopy and polyp biopsy: if 28% of women achieve a clinical pregnancy with a simple diagnostic hysteroscopy, the evidence suggests that 63% of women (95% CI 50% to 76%) will achieve a clinical pregnancy after the hysteroscopic removal of the endometrial polyps (OR 4.41, 95% CI 2.45 to 7.96, P < 0.00001, 204 women, moderate quality evidence). Authors' conclusions : A large benefit with the hysteroscopic removal of submucous fibroids for improving the chance of clinical pregnancy in women with otherwise unexplained subfertility cannot be excluded. The hysteroscopic removal of endometrial polyps suspected on ultrasound in women prior to IUI may increase the clinical pregnancy rate. More randomised studies are needed to substantiate the effectiveness of the hysteroscopic removal of suspected endometrial polyps, submucous fibroids, uterine septum or intrauterine adhesions in women with unexplained subfertility or prior to IUI, IVF or ICSI

Qualification and Flight of a Cutting Edge Sunsensor for Constellation Applications

Satellites for a constellation can be build in a significantly more cost-effective way because the Non-recurring Engineering charges (NRE) can be spread over multiple units. A further significant cost reduction can be achieved if the units and subsystems are optimized for volume production and the units are produced in a continuous production line with a sustainable throughput. Though this optimized production can lead to significant improvement in cost effectiveness, this should in no way impair the reliability of the products. It can be reasoned that the approach implemented by Lens R&D will even increase the reliability of production as it allows for statistical process monitor and control of the product quality. As reliability and cost effectiveness in volume production are core to the Return On Investment (ROI) for constellation owners, these properties have been core design drivers for the BiSon Sunsensors discussed in this paper. After a design change that led to the development of an automated assembly robot, the cutting edge BiSon64-ET and BiSon64-ET-B Sunsensors developed by Lens R&D went through a full ESA qualification program. This means that for the first time ever, a Sunsensor optimized for volume manufacturing has finished a full ESA qualification program. A flight contract has been signed to fly 20 sensors on the two ESA science satellites making up the Proba-3mission. Flight data however already will be received earlier, through a precursor 3U Cubesat mission, flown through the Dutch company Innovative Solutions In Space (ISIS). This paper focusses on the novel manufacturing approach used, the qualification performed and the processes needed to cost effectively produce large quantities of Sunsensors for constellation applications

The alkali-silica reaction: mineralogical and geochemical aspects of some Dutch concretes and Norwegian mylonites

Maarten Broekmans has studied the alkali-silica reaction in two Dutch concretes by means of optical microscopy, geochemical analyses on bulk material and after selective digestion in acid, and with element mapping in polished thin sections. He furthermore characterized the nature of the silica/quartz in the Norwegian mylonites studied previously by Wigum in his PhD-thesis (1995), in the Ohio cherts previously studied by Kneller (1967), and some Dutch cherts by assessing their crystallinity indices following the XRD-method of Murata&Norman (1976). The thesis suggests a simple and straight-forward system to rate concrete damage by assessing and classifying the crack fabric in impregnated full cores under fluorescent illumination. This method does not distinguish between different causes for the observed cracking, but it is quick and does not require expensive instrumentation nor special training. However, identifying the true cause of the cracking is of course essential and can be done as a second stage by thin section petrography. Typically, chert is the main alkali-reactive constituent in Dutch concrete. However, petrographic observations on sand- and siltstone grains in the aggregate indicate that these generate ASR-gel as well, which was not generally accepted in the Netherlands until before recently. The necessary alkali may very well be provided by interstitial clay minerals, and eventually by detrital muscovite on a very local scale with very limited reach. In geological-sedimentary literature, the catalytic effect of sheet silicate minerals (clays, micas) upon the dissolution of quartz is well documented. There is a strong resemblance of the observations made in the ASR-concrete to the features described from sedimentary-diagenetic sandstone compaction, and a similar process is suggested to occur in ASR. This is partly supported by element maps on Na, K, Ca, Si, Fe and S on intact and ASR-cracked chert, and intact and ASR-cracked sandstone. There are marked differences in their alkali-household. The silica involved in an alkali-silica reaction is hardly characterized, often only identified as silica or quartz. However, there are many qualities and/or properties of silica that may or may not affect its solubility, including polymorphism, lattice irregularities (vacancies, dislocations, twinning planes, domain structures), foreign ions and water in the quartz structure, etc, etc. Which of these qualities and/or properties do apply depends on conditions. Thus, merely identifying the alkali-reactive silica as 'quartz' is not good enough, but rises questions about which methods to use for that, and with which criteria? There are few procedures available to determine the quality of the quartz lattice; among those most frequently used is the XRD-method of Murata&Norman (1976), who use relative peak-heights in the quintuplet at 67.74 degrees two-theta in a diffractogram. However, all qualities that do have an effect on the quartz lattice are lumped together, and no further distinction can be made which of these are relevant for that particular sample. Thus, increased (alkali-) solubility cannot be attributed to one single quartz property. This is confirmed in literature, by the great discrepancies reported when the same samples are analyzed by XRD and IR or DTA/TGA. Quartz content of analyzed silica may vary at random from 0% with one method to 100% with another, and may very well be the opposite for another sample. Broekmans found that the samples analyzed (Norwegian mylonites, Ohio cherts, Dutch cherts) span the entire range of crystallinity indices from <1 to 10, but there seems no correlation with available expansion data. Therefore, the applicability of the crystallinity index in its present form to determine the alkali-reactivity potential of quartz is only limited. The thesis contains sixteen full-color plates of graphs, photographic images of impregnated cores, thin section details and element maps, and a numbered reference list with 212 entries

Psychoonkologisches Screening zur Identifikation und Evaluation belasteter Patienten in der ambulanten uroonkologischen Therapie

Die Rolle der Psychoonkologie in der Therapie von onkologischen Patienten gewinnt in den letzten Jahren zunehmend an Bedeutung und ist mittlerweile in den Leitlinien der Onkologie für die meisten Tumorentitäten fest verankert. In Studien konnte die psychische Belastung durch eine Krebserkrankung, die Entwicklung von Distress und die Wirksamkeit einer psychologischen Therapie in solch einer Situation nachgewiesen werden. Die Datenlage zu einzelnen Tumorentitäten, Therapien und dem Behandlungswunsch der Patienten ist für den Bereich der ambulanten Uroonkologie weiterhin lückenhaft. Zur Erfassung einer möglichen Unterversorgung im Rahmen eines ambulanten Therapieregimes bei Prostata-, Nierenzell-, Harnblasen- und Keimzelltumoren wurde am Universitätsklinikum Marburg eine Querschnittsstudie durchgeführt, welche sekundär den Therapiewunsch der Patienten erfasst. Von ursprünglich 95 Patienten konnten beim FBK-10 (cut-off ≥ 15 Punkte) 80 Patienten und beim Distress Thermometer (cut-off ≥ 5 Punkte) 82 Patienten in die Auswertung einbezogen werden. 21,7% / 37 % (FBK-10 / DT) der Patienten mit einem PCA erreichten die cut-off-Werte. Beim NCC waren es 56,8 % / 41,2 %, beim Harnblasenkarzinom 33,3 % / 66,7 % und bei Patienten mit einem Keimzelltumor 28,6 % / 50 %. Die Auswertung erfolgte mittels SPSS nach Alter, Tumorentität, Geschlecht und Therapiewunsch, wobei die Auswertung nach Geschlecht bei einer deutlichen Unterrepräsentation der weiblichen Patientinnen als wenig zielführend zu werten ist. Beide Screeningtools offenbaren eine hohe psychische Belastung der Patienten im ambulanten uroonkologischen Setting, was eine Unterversorgung wahrscheinlich macht. Dem gegenüber steht mit 8,7 % seitens der Patienten (welche dazu Angaben machten) ein sehr geringer Wunsch nach einer psychoonkologischen Betreuung. Gründe für eine ablehnende Einstellung gegenüber einer Therapie können vielfältig sein und reichen von einer Fehleinschätzung bis hin zur Angst vor einer möglichen Stigmatisierung. Der geringe Patientenwunsch bezüglich einer Therapie darf die Screeningergebnisse jedoch nicht verharmlosen. Insgesamt sollte eine Intensivierung der Integration von psychoonkologischen Therapieoptionen in den klinischen Alltag und Verbesserung der Patientenaufklärung bezüglich der Bedeutung dieser Therapie vorangetrieben werden

Hysteroscopy for treating subfertility associated with suspected major uterine cavity abnormalities

Background : Observational studies suggest higher pregnancy rates after the hysteroscopic removal of endometrial polyps, submucous fibroids, uterine septum or intrauterine adhesions, which are present in 10% to 15% of women seeking treatment for subfertility. Objectives : To assess the effects of the hysteroscopic removal of endometrial polyps, submucous fibroids, uterine septum or intrauterine adhesions suspected on ultrasound, hysterosalpingography, diagnostic hysteroscopy or any combination of these methods in women with otherwise unexplained subfertility or prior to intrauterine insemination (IUI), in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI). Search methods : We searched the following databases from their inception to 16 April 2018; The Cochrane Gynaecology and Fertility Group Specialised Register, the Cochrane Central Register of Studies Online,; MEDLINE, Embase, CINAHL, and other electronic sources of trials including trial registers, sources of unpublished literature, and reference lists. We handsearched the American Society for Reproductive Medicine (ASRM) conference abstracts and proceedings (from 1 January 2014 to 12 May 2018) and we contacted experts in the field. Selection criteria : Randomised comparison between operative hysteroscopy versus control for unexplained subfertility associated with suspected major uterine cavity abnormalities. Randomised comparison between operative hysteroscopy versus control for suspected major uterine cavity abnormalities prior to medically assisted reproduction. Primary outcomes were live birth and hysteroscopy complications. Secondary outcomes were pregnancy and miscarriage. Data collection and analysis : Two review authors independently assessed studies for inclusion and risk of bias, and extracted data. We contacted study authors for additional information. Main results : Two studies met the inclusion criteria. 1. Randomised comparison between operative hysteroscopy versus control for unexplained subfertility associated with suspected major uterine cavity abnormalities. In women with otherwise unexplained subfertility and submucous fibroids, we were uncertain whether hysteroscopic myomectomy improved the clinical pregnancy rate compared to expectant management (odds ratio (OR) 2.44, 95% confidence interval (CI) 0.97 to 6.17; P = 0.06, 94 women; very low-quality evidence). We are uncertain whether hysteroscopic myomectomy improves the miscarriage rate compared to expectant management (OR 1.54, 95% CI 0.47 to 5.00; P = 0.47, 94 women; very low-quality evidence). We found no data on live birth or hysteroscopy complication rates. We found no studies in women with endometrial polyps, intrauterine adhesions or uterine septum for this randomised comparison. 2. Randomised comparison between operative hysteroscopy versus control for suspected major uterine cavity abnormalities prior to medically assisted reproduction. The hysteroscopic removal of polyps prior to IUI may have improved the clinical pregnancy rate compared to diagnostic hysteroscopy only: if 28% of women achieved a clinical pregnancy without polyp removal, the evidence suggested that 63% of women (95% CI 45% to 89%) achieved a clinical pregnancy after the hysteroscopic removal of the endometrial polyps (OR 4.41, 95% CI 2.45 to 7.96; P < 0.00001, 204 women; low-quality evidence). We found no data on live birth, hysteroscopy complication or miscarriage rates in women with endometrial polyps prior to IUI. We found no studies in women with submucous fibroids, intrauterine adhesions or uterine septum prior to IUI or in women with all types of suspected uterine cavity abnormalities prior to IVF/ICSI. Authors' conclusions : Uncertainty remains concerning an important benefit with the hysteroscopic removal of submucous fibroids for improving the clinical pregnancy rates in women with otherwise unexplained subfertility. The available low-quality evidence suggests that the hysteroscopic removal of endometrial polyps suspected on ultrasound in women prior to IUI may improve the clinical pregnancy rate compared to simple diagnostic hysteroscopy. More research is needed to measure the effectiveness of the hysteroscopic treatment of suspected major uterine cavity abnormalities in women with unexplained subfertility or prior to IUI, IVF or ICSI