We describe system verification tests and early science results from the pulsar processor (PTUSE) developed for the newly commissioned 64-dish SARAO MeerKAT radio telescope in South Africa. MeerKAT is a high-gain ( ${\sim}2.8\,\mbox{K Jy}^{-1}$ ) low-system temperature ( ${\sim}18\,\mbox{K at }20\,\mbox{cm}$ ) radio array that currently operates at 580–1 670 MHz and can produce tied-array beams suitable for pulsar observations. This paper presents results from the MeerTime Large Survey Project and commissioning tests with PTUSE. Highlights include observations of the double pulsar $\mbox{J}0737{-}3039\mbox{A}$ , pulse profiles from 34 millisecond pulsars (MSPs) from a single 2.5-h observation of the Globular cluster Terzan 5, the rotation measure of Ter5O, a 420-sigma giant pulse from the Large Magellanic Cloud pulsar PSR $\mbox{J}0540{-}6919$ , and nulling identified in the slow pulsar PSR J0633–2015. One of the key design specifications for MeerKAT was absolute timing errors of less than 5 ns using their novel precise time system. Our timing of two bright MSPs confirm that MeerKAT delivers exceptional timing. PSR $\mbox{J}2241{-}5236$ exhibits a jitter limit of $<4\,\mbox{ns h}^{-1}$ whilst timing of PSR $\mbox{J}1909{-}3744$ over almost 11 months yields an rms residual of 66 ns with only 4 min integrations. Our results confirm that the MeerKAT is an exceptional pulsar telescope. The array can be split into four separate sub-arrays to time over 1 000 pulsars per day and the future deployment of S-band (1 750–3 500 MHz) receivers will further enhance its capabilities.

The main objective of this paper is to give an overview of the risks seen in the exploration and production of geothermal energy from the viewpoint of the regulator. The risks are categorised as conventional risks, ultra-deep risks and enhancing factors. These risks are similar to those seen in the oil and gas industry, but the maturity of the geothermal sector in terms of managing such risks is much lower.

Another objective of this paper is to discuss how these risks are managed and mitigated by the sector and the supervisor, State Supervision of Mines (SodM). Portfolio operators developing multiple projects, using skilled employees and embracing continuous improvement are seen as the way forward for the sector to grow safely and sustainably.

This paper concludes that positive developments have started, but a lot of work still needs to be done to ensure safe growth of the geothermal energy sector.

Gaia DR2 was released in April 2018 and contains a photometric catalogue of more than 1 billion sources. This release contains colour information in the form of integrated BP and RP photometry in addition to the latest G-band photometry. The level of uncertainty can be as good as 2 mmag with some residual systematics at the 10 mmag level. The addition of colour information greatly enhances the value of the photometric data for the scientific community. A high level overview of the photometric processing, with a focus on the improvements with respect to Gaia DR1, was given. The definition of the Gaia photometric system, a crucial part of the calibration of the photometry, was also explained. Finally, some of the photometric improvements expected for the next data release were described.

A lacustrine sediment record from the Kangerlussuaq region, West Greenland, has resulted in a pollen, macrofossil, and sediment stratigraphy that encompasses the last 5000 14C yr. Deglaciation of the area and subsequent development of a nearby floodplain occurred before 5000 yr B.P. Since that time eolian sand and silt deposition appear to have been continuous, with a significant increase ca. 1000 14C yr B.P. Pollen analysis shows little change in the character of the vegetation throughout the record. Fluctuations in herb pollen taxa indicate changes in the extent and development of eolian sand sheets. The oldest pollen zone records relatively little pollen accumulation and low taxa diversity. This is followed by a zone of high pollen accumulation, presumably a phase of highest vegetation density, from 4400 to 3400 14C yr B.P. Thereafter, declining pollen accumulation rates reveal a gradual environmental deterioration. Macrofossil analyses record significant limnological changes, with an early eutrophic phase followed by a masotrophic phase and a reversal to more eutrophic conditions in the final phase. The preserved record illustrates the interactions of deglaciation, eolian activity, regional vegetation, and limnological change.

The Gaia Science Alerts project (GSA) aims to augment a precision survey of the Milky Way with a controlled, precision survey of all classes of transient phenomena. While onboard BP/RP spectra from Gaia will ultimately allow us to classify many Gaia Alerts based on Gaia data alone, in the initial phases of the GSA project it is necessary to verify and classify discoveries with ground-based spectroscopic followup. In this article, we describe a subset of the ongoing Gaia Alerts followup programmes, and some of the initial science results from this work.

The prevalence of Chlamydia trachomatis varies between ethnic groups in The Netherlands. It is, however, unknown whether this is associated with specific serogroups. The objective of this study was to determine whether serogroup distribution is associated with ethnic origin in the region of The Hague, The Netherlands. Serogroups of 370 microbiologically confirmed C. trachomatis-positive samples were analysed. The samples were obtained from 247 women and 123 men between January and October 2008, of self-reported Dutch Caucasian, Dutch Antillean, Surinamese, N. African/Turkish or other descent. We observed a difference in serogroup distribution comparing Dutch Caucasian women to Dutch Antillean women (χ2 for distribution P = 0·035). Serogroup C was more common in Dutch Antillean women, whereas serogroup B was less common (P = 0·03). This difference was not observed for Dutch Antillean men. The observed difference in distribution of C. trachomatis serogroups between ethnic groups is relevant for further transmission studies.

Despite the development of consensus-based frameworks to define cancer cachexia, the validity and usefulness of these frameworks are relatively unknown. The aim of the present study was to study the presence of pre-cachexia and cachexia in patients with stage III non-small-cell lung carcinoma (NSCLC) by using a cancer-specific framework and a general framework for cachexia, and to explore the prognostic value of pre-cachexia and cachexia. In forty patients at diagnosis of stage III NSCLC, weight loss, fat-free mass, handgrip strength, anorexia and serum biochemistry, assessed before the first chemotherapy, were used to define ‘cancer cachexia’ or ‘cachexia’. The cancer-specific framework also classified for pre-cachexia and refractory cachexia. Additionally, quality of life was assessed by the European Organisation for Research and Treatment of Cancer – Quality of Life Questionnaire C30. Groups were compared using independent t tests, ANOVA, Kaplan–Meier and Cox survival analyses. Based on the cancer-specific framework, pre-cachexia was present in nine patients (23 %) and cancer cachexia was present in seven patients (18 %). Cancer cachexia was associated with a reduced quality of life (P= 0·03) and shorter survival (hazard ratio (HR) = 2·9; P= 0·04). When using the general framework, cachexia was present in eleven patients (28 %), and was associated with a reduced quality of life (P= 0·08) and shorter survival (HR = 4·4; P= 0·001). In conclusion, pre-cachexia and cachexia are prevalent in this small population of patients at diagnosis of stage III NSCLC. For both frameworks, cachexia appears to be associated with a reduced quality of life and shorter survival. Further studies are warranted to more extensively explore the validity and prognostic value of these new frameworks in cancer patients.

From childhood into adolescence, the child's brain undergoes considerable changes in both structure and function. Twin studies are of great value to explore to what extent genetic and environmental factors explain individual differences in brain development and cognition. In The Netherlands, we initiated a longitudinal study in which twins, their siblings and their parents are assessed at three year intervals. The participants were recruited from The Netherlands Twin Register (NTR) and at baseline consisted of 112 families, with 9-year-old twins and an older sibling. Three years later, 89 families returned for follow-up assessment. Data collection included psychometric IQ tests, a comprehensive neuropsychological testing protocol, and parental and self-ratings of behavioral and emotional problems. Physical maturation was measured through assessment of Tanner stages. Hormonal levels (cortisol, luteinizing hormone, follicle-stimulating hormone, testosterone, and estrogens) were assessed in urine and saliva. Brain scans were acquired using 1.5 Tesla Magnetic Resonance Imaging (MRI), which provided volumetric measures and measures of cortical thickness. Buccal swabs were collected for DNA isolation for future candidate gene and genome-wide analysis studies. This article gives an overview of the study and the main findings. Participants will return for a third assessment when the twins are around 16 years old. Longitudinal twin-sibling studies that map brain development and cognitive function at well-defined ages aid in the understanding of genetic influences on normative brain development.

We studied the short- and long-term effects of classroom separation in twins on behavior problems and academic performance. Short-term effects were studied at age 7 in twins separated at age 5 and long-term effects at age 12 in twins who had been separated or together most of the time at school. Behavior problems were rated by mothers (Child Behavior Checklist at ages 3, 7 and 12) and teachers (Teacher Report Form at ages 7 and 12). Academic achievement was measured at age 12 using a national academic achievement test (CITO). At age 7, twins from separated pairs had more internalizing and externalizing problems than non- separated twins, as rated by both mothers and teachers. Only for the maternal ratings of internalizing problems, however, could these effects be attributed to the separation itself and not to preexisting problems (at age 3) between separated and nonseparated twins. Long-term effects of separation were significant for maternal and teacher ratings of internalizing and externalizing problems, but these effects could be explained by preexisting differences between separated and nonseparated groups. There were no differences in academic achievement between the separated and nonsepa- rated group. These results suggest that the decision to separate twins when they go to school is based in part on the existing behavioral problems of the twins and that, in the long run, separation does not affect problem behavior or academic achievement. The findings were the same for monozygotic and dizygotic twins.

The longitudinal stability of IQ is well-documented as is its increasing heritability with age. In a longitudinal twin study, we addressed the question to what extent heritability and stability differ for full scale (FSIQ), verbal (VIQ), and performance IQ (PIQ) in childhood (age 9–11 years), and early adolescence (age 12–14 years). Genetic and environmental influences and correlations over time were evaluated in an extended twin design, including Dutch twins and their siblings. Intelligence was measured by the Wechsler Intelligence Scale for children — Third version (WISC III). Heritability in childhood was 34% for FSIQ, 37% for VIQ, and 64% for PIQ, and increased up to 65%, 51%, and 72% in early adolescence. The influence of common environment decreased between childhood and early adolescence from explaining 43% of the phenotypic variance for FSIQ to 18% and from 42% for VIQ to 26%. For PIQ common environmental influences did not play a role, either in childhood or in early adolescence. The stability in FSIQ and VIQ across the 3-year interval (rp) was .72 for both measures and was explained by genetic and common environmental correlations across time (FSIQ, rg = .96, rc = 1.0; VIQ, rg =.78, rc = 1.0). Stability of PIQ (rp =.56) was lower and was explained by genetic influences (rg = .90). These results confirm the robust findings of increased heritability of general cognitive abilities during the transition from childhood to adolescence. Interestingly, results for PIQ differ from those for FSIQ and VIQ, in that no significant contribution of environment shared by siblings from the same family was detected.

Accurate assessment of neonatal body composition is essential to studies investigating neonatal nutrition or developmental origins of obesity. Bioelectrical impedance analysis or bioimpedance analysis is inexpensive, non-invasive and portable, and is widely used in adults for the assessment of body composition. There are currently no prediction algorithms using bioimpedance analysis in neonates that have been directly validated against measurements of fat-free mass (FFM). The aim of the study was to evaluate the use of bioimpedance analysis for the estimation of FFM and percentage of body fat over the first 4 months of life in healthy infants born at term, and to compare these with estimations based on anthropometric measurements (weight and length) and with skinfolds. The present study was an observational study in seventy-seven infants. Body fat content of infants was assessed at birth, 6 weeks, 3 and 4·5 months of age by air displacement plethysmography, using the PEA POD body composition system. Bioimpedance analysis was performed at the same time and the data were used to develop and test prediction equations for FFM. The combination of weight+sex+length predicted FFM, with a bias of < 100 g and limits of agreement of 6–13 %. Before 3 months of age, bioimpedance analysis did not improve the prediction of FFM or body fat. At 3 and 4·5 months, the inclusion of impedance in prediction algorithms resulted in small improvements in prediction of FFM, reducing the bias to < 50 g and limits of agreement to < 9 %. Skinfold measurements performed poorly at all ages.

Dutch developments on euthanasia have drawn much attention over the years. Defenders and opponents have been telling very different stories about the practice of euthanasia and the frequency of cases, and the Dutch government has been struggling with the legal and moral problems involved. Concern about the procedures followed by physicians as well as questions on the “real” figures led the government to decide to organize an epidemiological study on the extent and the decision making. The results of the study were published in November 1991 (The End of Life in Medical Practice, 1991). Interpretation of the data may lead to a final settlement of the debate on euthanasia and has inevitably led to a revival of the moral debate of the 1970s. For the moment it has been decided that euthanasia will remain officially illegal under the Penal Code. However, in cases where euthanasia does occur, Attorneys General will continue to check the procedures followed by physicians to ensure no abuses have occurred and to safeguard physicians against prosecution. In this contribution, we discuss the development and intertwinement of legal, medical, and moral aspects of euthanasia in The Netherlands and the effects of the empirical studies of 1991, both on definitions and procedures for medical decisions at the end of life(MDEL)

The development of neonatology and the establishment of neonatal intensive care units has led to a vast array of new medical ethical problems and dilemmas centered around discontinuing treatment or nontreatment decisions. Neonatology has become one of the fields that has made clear that medical success is only rarely nonproblematic. The new technology can be a blessing for some, but it may also become a sad experience to others, with life-long repercussions.

The ethical problems of neonatology transcend national boundaries. Nevertheless, there are differences in approach among various countries. In The Netherlands, the ethical deliberations have been a matter of public debate, but most of the decision making is left to the medical profession; these decisions are considered too harsh for the general public. Recently, two developments have emerged. The Royal Dutch Medical Association (RDMA) and the Dutch Pediatrics Society have published reports with guidelines and ethical reflections. Over the same period of time, cases have been brought to court for legal analysis and the development of case precedence.

Vitamin D is a fat-soluble, seco-steroid hormone. In man, the vitamin D receptor is expressed in almost all tissues, enabling effects in multiple systems of the human body. These effects can be endocrine, paracrine and autocrine. The present review summarises the effects of ageing on the vitamin D endocrine system and on Ca homeostasis. Furthermore, consequences for vitamin D supplementation are discussed.

In this paper we investigate the role of spatial effects in determining the dynamics of a subclass of signalling pathways characterised by their ability to demonstrate oscillatory behaviour. To this end, we formulate a simple spatial model of the p53 network that accounts for both a negative feedback and a transcriptional delay. We show that the formation of protein density patterns can depend on the shape of the cell, position of the nucleus, and the protein diffusion rates. The temporal changes in the total amounts of protein are also subject to spatial influences. The level of DNA damage required to induce sustained oscillations, for instance, depends on the morphology of the cell. The model also provides a new interpretation of experimentally observed undamped oscillations in p53 levels in single cells. Our simulations reveal that alternate sequences of high- and low-amplitude oscillations can occur. We propose that the digital pulses may correspond to snap-shots of our high-amplitude sequences. Shorter waiting-times between subsequent time-lapse fluorescence microscopy images in combination with lower detection thresholds may reveal the irregular high-frequency oscillations suggested by our spatial model.

The ESA space astrometry mission Gaia will measure the positions, parallaxes and proper motions of the 1 billion brightest stars on the sky. Expected accuracies are in the 7–25 μas range down to 15 mag and sub-mas accuracies at the faint limit (20 mag). The astrometric data are complemented by low-resolution spectrophotometric data in the 330–1000 nm wavelength range and, for the brighter stars, radial velocity measurements. The scientific case covers an extremely wide range of topics in galactic and stellar astrophysics, solar system and exoplanet science, as well as the establishment of a very accurate, dense and faint optical reference frame. With a planned launch around 2012 and an (extended) operational lifetime of 6 years, final results are expected around 2021. We give a brief overview of the science goals of Gaia, the overall project organisation, expected performance, and some key technical features and challenges.