Perinatal outcome after selective fetal reduction in monochorionic twin pregnancies: A comparison of techniques over a 20-year period.

OBJECTIVE: To assess the perinatal outcome after fetal reduction in complicated monochorionic (MC) twin pregnancies by comparing different techniques. METHODS: A retrospective cohort study at a national referral center comparing data between four techniques: interstitial laser coagulation, radiofrequency ablation (RFA), fetoscopic laser coagulation (FLC) and bipolar cord coagulation (BCC). The primary outcome was the mortality of the co-twins. Secondary outcomes were preterm pre-labor rupture of membranes (PPROM), gestational age at delivery and neonatal morbidity. RESULTS: 259 MC twin pregnancies underwent selective fetal reduction: 29 IL, 64 RFA, 85 FLC and 81 BCC. The perinatal mortality rate was 29% and fetal demise of the co-twins occurred in 19%. The lowest mortality rate was seen after BCC (17%, p = 0.012). PPROM occurred in 18% patients without significant differences between techniques. The mean gestational age at delivery in liveborn children was 35 weeks and did not differ between techniques. Severe cerebral injury and neonatal morbidity were reported in 4% and 14%, respectively, without significant differences between techniques. CONCLUSIONS: Selective fetal reductions in MC twins are precarious procedures with an increased risk of perinatal mortality of the co-twins. Our results show the lowest mortality rates after BCC. However, high PPROM rates were seen irrespective of the technique.

Measurement of the α-Particle Monopole Transition Form Factor Challenges Theory: A Low-Energy Puzzle for Nuclear Forces?

We perform a systematic study of the α-particle excitation from its ground state 0_{1}^{+} to the 0_{2}^{+} resonance. The so-called monopole transition form factor is investigated via an electron scattering experiment in a broad Q^{2} range (from 0.5 to 5.0 fm^{-2}). The precision of the new data dramatically supersedes that of older sets of data, each covering only a portion of the Q^{2} range. The new data allow the determination of two coefficients in a low-momentum expansion, leading to a new puzzle. By confronting experiment to state-of-the-art theoretical calculations, we observe that modern nuclear forces, including those derived within chiral effective field theory that are well tested on a variety of observables, fail to reproduce the excitation of the α particle.

Bariatric surgery in a patient with cystic fibrosis and diabetes: A case report.

Cystic fibrosis (CF) is incurable and chronic, causing severe multisystemic damage and long-term complications. The most prominent extrapulmonary long-term complication is CF-related diabetes, which is the most reported form of diabetes in individuals with cystic fibrosis. Here we present the first case of an individual with cystic fibrosis who developed type 2 diabetes due to obesity rather than CF-related diabetes. The type 2 diabetes went into remission due to extreme weight loss after gastric bypass surgery. To our knowledge, this case is also the first report describing the effect of bariatric surgery in a patient with CF. This case demonstrates that patients with CF may present with type 2 diabetes instead of CF-related diabetes. Differential diagnosis of these two types of diabetes is essential for optimal treatment and quality of life.

Breakfast partly restores the anti-inflammatory function of high-density lipoproteins from patients with type 2 diabetes mellitus.

Background and aims: High-density lipoproteins (HDL) of patients with type 2 diabetes mellitus (T2DM) have impaired anti-inflammatory activities. The anti-inflammatory activity of HDL has been determined ex vivo after isolation by different methods from blood mostly obtained after overnight fasting. We first determined the effect of the HDL isolation method, and subsequently the effect of food intake on the anti-inflammatory function of HDL from T2DM patients. Methods: Blood was collected from healthy controls and T2DM patients after an overnight fast, and from T2DM patients 3 h after breakfast (n = 17 each). HDL was isolated by a two-step density gradient ultracentrifugation in iodixanol (HDLDGUC2), by sequential salt density flotation (HDLSEQ) or by PEG precipitation (HDLPEG). The anti-inflammatory function of HDL was determined by the reduction of the TNFα-induced expression of VCAM-1 in human coronary artery endothelial cells (HCAEC) and retinal endothelial cells (REC). Results: HDL isolated by the three different methods from healthy controls inhibited TNFα-induced VCAM-1 expression in HCAEC. With apoA-I at 0.7 µM, HDLDGUC2 and HDLSEQ were similarly effective (16% versus 14% reduction; n = 3; p > 0.05) but less effective than HDLPEG (28%, p < 0.05). Since ultracentrifugation removes most of the unbound plasma proteins, we used HDLDGUC2 for further experiments. With apoA-I at 3.2 µM, HDL from fasting healthy controls and T2DM patients reduced TNFα-induced VCAM-1 expression in HCAEC by 58 ± 13% and 51 ± 20%, respectively (p = 0.35), and in REC by 42 ± 13% and 25 ± 18%, respectively (p < 0.05). Compared to preprandial HDL, postprandial HDL from T2DM patients reduced VCAM-1 expression by 56 ± 16% (paired test: p < 0.001) in HCAEC and by 34 ± 13% (paired test: p < 0.05) in REC. Conclusions: The ex vivo anti-inflammatory activity of HDL is affected by the HDL isolation method. Two-step ultracentrifugation in an iodixanol gradient is a suitable method for HDL isolation when testing HDL anti-inflammatory function. The anti-inflammatory activity of HDL from overnight fasted T2DM patients is significantly impaired in REC but not in HCAEC. The anti-inflammatory function of HDL is partly restored by food intake.

First Measurement of the Q

We report on the first Q^{2}-dependent measurement of the beam-normal single spin asymmetry A_{n} in the elastic scattering of 570 MeV vertically polarized electrons off ^{12}C. We cover the Q^{2} range between 0.02 and 0.05 GeV^{2}/c^{2} and determine A_{n} at four different Q^{2} values. The experimental results are compared to a theoretical calculation that relates A_{n} to the imaginary part of the two-photon exchange amplitude. The result emphasizes that the Q^{2} behavior of A_{n} given by the ratio of the Compton to charge form factors cannot be treated independently of the target nucleus.

[Improving care for cleft lip and palate patients: uniform and patient-orientated outcome measures]. / Verbetering van de schisiszorg; uniforme en patiëntgeoriënteerde uitkomstmaten.

The quality of care for patients with cleft lip and palate is extremely variable across the world. Treatment protocols differ and methods of data registration are not uniform. Improving this care by means of comparative research is challenging. The best treatment programmes can be identified by uniformly registering patient-orientated outcomes and comparing the outcomes with those of other treatment centres. That knowledge can be used to improve one's own care. An international team consisting of specialists and cleft lip and palate patients has developed a set of outcome measures that are considered by patients to be most important. This team is coordinated by the International Consortium of Health Outcomes Measurement (ICHOM). The cleft lip and palate outcome set can be used by all centres worldwide in following up on cleft lip and palate patients. In the Erasmus Medical Centre in Rotterdam, the 'Zorgmonitor Schisis' (Care Monitor Cleft Lip and Palate) has been built, an application in which these outcome measures are collected at fixed times. Implementing this set of outcome measures in other cleft lip and palate treatment centres and using the outcomes as (inter)national benchmarks will result in transparency and the improvement of the treatment of cleft lip and palate worldwide.

[Evaluation of referral and intervention patterns at the psychiatric emergency service, Utrecht 2009-2015]. / Knooppunt psychiatrische crisisdienst: evaluatie van patiëntenstromen; samenhang tussen aanmeldreden, aanmelder en crisisbeleid, Utrecht 2009-2015.

BACKGROUND: Emergency psychiatric care in the Netherlands is provided mainly by community mental health services. Although these emergency services vary in their approach per region, they show many similarities: they tend to receive referrals from the same type of agencies and they practice similar techniques of crisis management.
AIM: To identify some of the patterns that appear in the type of psychiatric problems encountered, the type of referral agencies involved and in the intervention strategies practiced by the psychiatric emergency service in Utrecht.
METHOD: We studied the medical records of 938 crisis assessments compiled during five measurement periods between 2009 and 2015. From all these crisis assessments we selected one sample relating to patients coming only from the city of Utrecht - 'model city Utrecht' - and a second sample consisting only of patients referred either by HAP (emergency primary care), the police or a general hospital. Then, by using cross-tabulation and a multinomial logistic regression analyses, we were able to identify associations between the type of referral agency, the type of referral problem and the type of intervention.
RESULTS: Patients referred by the police were more often forcefully admitted (compulsory admission: 27%) than patients referred by general practitioners (6%); most of these patients were then treated as outpatients (83%). Another pattern that emerged, was that confused or aggressive patients were admitted to hospital more frequently than suicidal patients (26%, 29% and 8% respectively).
CONCLUSION: Our study and current trends in the clinical practice operated by the emergency psychiatric services reveal significant correlations between the type of referrals and the type of intervention. However, further research is needed in order to develop the 'best practice' for emergency psychiatric care in the future.

[Hypertension en orthostatic hypotension during use of monoamine oxidase (MAO) inhibitors]. / Hypertensie en orthostatische hypotensie bij gebruik van monoamine-oxidase(MAO)-remmers1.

Monoamine oxidase (mao) inhibitors are antidepressants with potentially severe side-effects. For this reason, the registration of this drug was suspended for some time when safer alternatives became available. However, mao inhibitors can be very effective in cases where depression has proved to be treatment resistant. Consequently, last year tranylcypromine was re-registered for use in the Netherlands. Since mao inhibitors have been used only sporadically in the Netherlands over the last few years, health professionals have only limited knowledge about the side-effects. On the basis of a recent case, we discuss the two most important side-effects of using mao inhibitors, namely hypertension and orthostatic hypotension. We discuss the possible causes and suggest ways on which these two side-effects can be prevented, or treated, should they arise.

MAGNETISM. Imaging and control of ferromagnetism in LaMnO3/SrTiO3 heterostructures.

Oxide heterostructures often exhibit unusual physical properties that are absent in the constituent bulk materials. Here, we report an atomically sharp transition to a ferromagnetic phase when polar antiferromagnetic LaMnO3 (001) films are grown on SrTiO3 substrates. For a thickness of six unit cells or more, the LaMnO3 film abruptly becomes ferromagnetic over its entire area, which is visualized by scanning superconducting quantum interference device microscopy. The transition is explained in terms of electronic reconstruction originating from the polar nature of the LaMnO3 (001) films. Our results demonstrate that functionalities can be engineered in oxide films that are only a few atomic layers thick.

Common variants in PCSK1 influence blood pressure and body mass index.

Proprotein convertase subtilisin/kexin-type 1 (PCSK1) activates precursors pro-opiomelanocortin (POMC), proinsulin and prorenin. We investigated if common variants in the PCSK1 gene influence blood pressure and risk of hypertension. Additionally, we investigated the risk of obesity and type 2 diabetes (T2D). In the Rotterdam Study (RS1), a prospective, population-based cohort (n=5974), four single-nucleotide polymorphisms (rs10515237, rs6232, rs436321 and rs3792747) in PCSK1 were studied. Linear and Cox regression models served to analyze associations between variants and end points. Replication was performed in the Rotterdam Study Plus1 (RSPlus1, n=1895). Rs436321 was significantly associated with systolic and diastolic blood pressure and risk of hypertension (odds ratio (OR): 1.1-1.3; P<0.05 in both populations). Rs6232 was associated with body mass index (BMI) (P=0.007 and P=0.04 in RS1 and RSPlus1, respectively). In RSPlus1, heterozygotes for rs6232 had 1.5 times higher risk of obesity (OR: 1.46; 95% confidence interval: 1.04-2.03; P=0.03). We did not find significant associations of PCSK1 with fasting insulin levels and T2D. We found an association of genetic variation in the PCSK1 gene with blood pressure and hypertension. Furthermore, we replicated the association of PCSK1 with BMI and obesity. No relationship was found between PCSK1 variants and fasting insulin levels and T2D. Our findings suggest that genetic variation in PCSK1 may contribute to, at least, some of these interrelated disorders.

A genetic variant in SLC6A20 is associated with Type 2 diabetes in white-European and Chinese populations.

AIMS: To investigate whether polymorphisms in SLC6A20 are associated with susceptibility to Type 2 diabetes. METHODS: In the Rotterdam Study, a prospective, population-based cohort (n = 5974), 22 tagging polymorphisms with minor allele frequencies>0.05 across SLC6A20 were studied. Replication studies were performed in an independent Dutch case-control study (DiaGene-Rotterdam Study 2 n = 3133), and in a Chinese Han case-control population (n = 2279). A meta-analysis of the results was performed. RESULTS: In the Rotterdam study, the minor alleles of rs13062383, rs10461016 and rs2286489 increased the risk of Type 2 diabetes (hazard ratio 1.37, 95% CI 1.15-1.63, hazard ratio 1.30 95% CI 1.09-1.54 and hazard ratio 1.20, 95% CI 1.07-1.35, respectively). In the DiaGene/Rotterdam Study 2, the A allele of rs13062383 increased the risk of Type 2 diabetes (odds ratio 1.45, 95% CI 1.19-1.76). In the Chinese Han study, the rs13062383 A allele also increased the risk of Type 2 diabetes (odds ratio 1.21, 95% CI 1.03-1.42). Meta-analysis showed a highly significant association of rs13062383 with Type 2 diabetes (odds ratio 1.35, 95% CI 1.21-1.47; P = 3.3 × 10⁻8). CONCLUSIONS: In conclusion, rs13062383 in SLC6A20 increased the susceptibility to Type 2 diabetes in populations with different genetic backgrounds.

Search at the Mainz Microtron for light massive gauge bosons relevant for the muon g-2 anomaly.

A massive, but light, Abelian U(1) gauge boson is a well-motivated possible signature of physics beyond the standard model of particle physics. In this Letter, the search for the signal of such a U(1) gauge boson in electron-positron pair production at the spectrometer setup of the A1 Collaboration at the Mainz Microtron is described. Exclusion limits in the mass range of 40 MeV/c^{2} to 300 MeV/c^{2}, with a sensitivity in the squared mixing parameter of as little as ε^{2}=8×10^{-7} are presented. A large fraction of the parameter space has been excluded where the discrepancy of the measured anomalous magnetic moment of the muon with theory might be explained by an additional U(1) gauge boson.

Enhanced expression of transferrin receptor 1 contributes to oncogenic signalling by sphingosine kinase 1.

Sphingosine kinase 1 (SK1) is a lipid kinase that catalyses the formation of sphingosine-1-phosphate (S1P). Considerable evidence has implicated elevated cellular SK1 in tumour development, progression and disease severity. In particular, SK1 has been shown to enhance cell survival and proliferation and induce neoplastic transformation. Although S1P has been found to have both cell-surface G-protein-coupled receptors and intracellular targets, the specific downstream pathways mediating oncogenic signalling by SK1 remain poorly defined. Here, using a gene expression array approach, we have demonstrated a novel mechanism whereby SK1 regulates cell survival, proliferation and neoplastic transformation through enhancing expression of transferrin receptor 1 (TFR1). We showed that elevated levels of SK1 enhanced total as well as cell-surface TFR1 expression, resulting in increased transferrin uptake into cells. Notably, we also found that SK1 activation and localization to the plasma membrane, which are critical for its oncogenic effects, are necessary for regulation of TFR1 expression specifically through engagement of the S1P G-protein coupled receptor, S1P2. Furthermore, we showed that blocking TFR1 function with a neutralizing antibody inhibits SK1-induced cell proliferation, survival and neoplastic transformation of NIH3T3 fibroblasts. Similar effects were observed following antagonism of S1P2. Together these findings suggest that TFR1 has an important role in SK1-mediated oncogenesis.

Compton scattering for spectroscopic detection of ultra-fast, high flux, broad energy range X-rays.

Compton side-scattering has been used to simultaneously downshift the energy of keV to MeV energy range photons while attenuating their flux to enable single-shot, spectrally resolved, measurements of high flux X-ray sources to be undertaken. To demonstrate the technique a 1 mm thick pixelated cadmium telluride detector has been used to measure spectra of Compton side-scattered radiation from a Cobalt-60 laboratory source and a high flux, high peak brilliance X-ray source of betatron radiation from a laser-plasma wakefield accelerator.

Family-centred care during midface advancement with a rigid external device: what do families need?

Midface advancement with distraction osteogenesis using the rigid external device (RED) is an effective but invasive treatment to correct the hypoplastic midface. This study draws up an inventory of the stressors, needs and coping strategies of families during this treatment, to determine the best conditions for family-centred care. Data were collected by reviewing the patients' files and administering semi-structured interviews. The data were analysed using the software program Atlas.ti and were re-analysed by an independent researcher. Parents and patients were interviewed separately. Fourteen families participated. Four patients had an absolute indication for surgery. All families were eager to have the patient's facial appearance improved. Nevertheless, despite psychological counselling, they experienced stress when confronted with the changed facial appearance. Another stressor was weight loss. Six patients were in a state of acute malnutrition and needed supplementary feeding. We conclude that the best conditions for family-centred care should be aligned to the different phases of treatment. Leading up to surgery it is important to screen families' expectations regarding aesthetic, functional and social outcomes and to assess their capacity to cope with the long treatment and effects of changed facial appearance. Peer contact and psychosocial training to increase self-esteem are tools to enhance co-operation and satisfaction. During the distraction and stabilisation phase, we advise the monitoring of nutritional intake and weight. During all phases of treatment easy accessibility to the team is recommended.

Towards a richer debate on tissue engineering: a consideration on the basis of NEST-ethics.

In their 2007 paper, Swierstra and Rip identify characteristic tropes and patterns of moral argumentation in the debate about the ethics of new and emerging science and technologies (or "NEST-ethics"). Taking their NEST-ethics structure as a starting point, we considered the debate about tissue engineering (TE), and argue what aspects we think ought to be a part of a rich and high-quality debate of TE. The debate surrounding TE seems to be predominantly a debate among experts. When considering the NEST-ethics arguments that deal directly with technology, we can generally conclude that consequentialist arguments are by far the most prominently featured in discussions of TE. In addition, many papers discuss principles, rights and duties relevant to aspects of TE, both in a positive and in a critical sense. Justice arguments are only sporadically made, some "good life" arguments are used, others less so (such as the explicit articulation of perceived limits, or the technology as a technological fix for a social problem). Missing topics in the discussion, at least from the perspective of NEST-ethics, are second "level" arguments-those referring to techno-moral change connected to tissue engineering. Currently, the discussion about tissue engineering mostly focuses on its so-called "hard impacts"-quantifiable risks and benefits of the technology. Its "soft impacts"-effects that cannot easily be quantified, such as changes to experience, habits and perceptions, should receive more attention.

[Prenylation: from bacteria to eukaryotes].

For their protection from host cell immune defense, intracellular eukaryotic parasites developed a variety of mechanisms, including secretion systems III and IV which inject bacterial effectors directly into eukaryotic cells. These effectors may be posttranslational modified by host cell machinery and may function inside the host cell. Recently, to the list of possible posttranslational modifications of bacterial proteins the prenylation was added. In this work we describe current state of the knowledge about the prenylation of eukaryotic and prokaryotic proteins and its inhibitors. The bioinformatics analyses suggest possibility of prenylation for a number of Francisella genus proteins.

Josephson supercurrent through a topological insulator surface state.

The long-sought yet elusive Majorana fermion is predicted to arise from a combination of a superconductor and a topological insulator. An essential step in the hunt for this emergent particle is the unequivocal observation of supercurrent in a topological phase. Here, direct evidence for Josephson supercurrents in superconductor (Nb)-topological insulator (Bi(2)Te(3))-superconductor electron-beam fabricated junctions is provided by the observation of clear Shapiro steps under microwave irradiation, and a Fraunhofer-type dependence of the critical current on magnetic field. Shubnikov-de Haas oscillations in magnetic fields up to 30 T reveal a topologically non-trivial two-dimensional surface state. This surface state is attributed to mediate the ballistic Josephson current despite the fact that the normal state transport is dominated by diffusive bulk conductivity. The lateral Nb-Bi(2)Te(3)-Nb junctions hence provide prospects for the realization of devices supporting Majorana fermions.