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Stimulated Brillouin scattering experiments in the ionospheric plasma using a single electromagnetic pump wave have previously been observed to generate an electromagnetic sideband wave, emitted by the plasma, together with an ion- acoustic wave. Here we report results of a controlled, pump and probe beat-wave driven Brillouin scattering experiment, in which an ion-acoustic wave generated by the beating of electromagnetic pump and probe waves, results in electromagnetic sideband waves that are recorded on the ground. The experiment used the EISCAT facility in northern Norway, which has several high power electromagnetic wave transmitters and receivers in the radio frequency range. An electromagnetic pump consisting of large amplitude radio waves with ordinary (O) or extraordinary (X) mode polarization was injected into the overhead ionosphere, along with a less powerful probe wave, and radio sideband emissions observed on the ground clearly show stimulated Brillouin emissions at frequencies agreeing with, and changing with, the pump and probe frequencies. The experiment was simulated using a numerical full-scale model which clearly supports the interpretation of the experimental results. Such controlled beat-wave experiments demonstrate a way of remotely investigating the ionospheric plasma parameters.

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BACKGROUND: Combined administration of intravenous (iv) and intraperitoneal (ip) (iv/ip) chemotherapy is an effective adjuvant treatment option after primary debulking surgery (PDS) for advanced ovarian cancer (OC). Increased toxicityand patient burden limit its use in daily practice. OBJECTIVE: To assess toxicity and survival outcomes of iv/ip chemotherapy in daily practice in the Netherlands. METHODS: This retrospective cohort study included 81 women who underwent at least an optimal PDS for FIGO stage III OC followed by iv/ip chemotherapy according to the Armstrong regimen, in four hospitals in the Netherlands between January 2007 and May 2016. We collected information on surgical procedure, abdominal port implantation, toxicity, and recurrence-free and overall survival. RESULTS: All participants underwent PDS, of whom 60 (74%) had their ip catheter implanted during PDS. Most frequently reported all grade toxicity was haematological n = 44 (54%). Forty-four patients (54%) completed all six cycles of iv/ip chemotherapy. The most frequent causes of discontinuation of iv/ip administration were renal dysfunction (12/37 = 32%) and catheter problems (7/37 = 19%). Median recurrence-free survival and overall survival were 24 months (range 0 - 108) and 80 months (range 4-115), respectively. Surgical outcome, completion of more than three courses of treatment and intra-abdominal localisation of recurrent disease were associated with better survival outcomes. CONCLUSION: In daily practice, 54% of patients with advanced OC could complete all scheduled cycles of iv/ ip chemotherapy with acceptable morbidity and toxicity, leading to outcomes comparable with the results of published trials on iv/ip chemotherapy.

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BACKGROUND: The mental status examination (MSE) is part of everyday psychiatric practice. However, it is unknown which items of the MSE are considered important and how the MSE is appreciated in the Netherlands.
AIM: To gain insight in the importance of the MSE, and to investigate which items are used in everyday practice.
METHOD: Dutch psychiatrists and residents filled in a questionnaire, using a 5-point Likert scale, where they rated frequency of use and importance of 24 different items of the Dutch MSE. They also reported which items, in their opinion, should be rated 'always', 'on indication only' or 'never'. Finally, the respondents were asked about their need of education and training in the MSE. The data were collected through an online questionnaire, which was distributed through email and the website of the Dutch psychiatric association.
RESULTS: A total of 402 respondents filled in the questionnaire, of which 60.4% were psychiatrists and 39.6% were residents. The MSE was seen as an essential part of the everyday psychiatric practice. The current format was appreciated strongly. In current practice, 10 items of the MSE were 'always' rated by more than 50% of the respondents. Ten items were rated very rarely, if ever. Respondents thought these items should only be rated on specific indication. There was a need for extra training in the MSE amongst residents and psychiatrists.
CONCLUSION: The Dutch MSE, consisting of 24 items, is strongly appreciated by psychiatrists and residents as an essential part of the psychiatric diagnostic process. In the everyday practice only a part of the items are used frequently.

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BACKGROUND: Health-related quality of life (HRQoL) is an important issue in the rapidly evolving field of adjuvant treatment for stage III melanoma. Dendritic cell vaccination is one of the adjuvant forms of therapy currently investigated. METHODS: We enrolled adults with stage III melanoma to receive adjuvant dendritic cell vaccination after a complete radical lymph node dissection. HRQoL assessment was one of the secondary endpoints of this trial and investigated with the EORTC-QLQ-C30 questionnaire at baseline and week 26. RESULTS: Fifteen patients with a median age of 50 years were included in the study, with twelve evaluable patients on study at time of the second questionnaire. Global health status and role functioning improved clinically relevant with a mean difference of 15 (p = 0.010) and 26 points (p = 0.005), respectively. DISCUSSION: Despite the small number of patients, we found a clinically relevant improved global health status. Besides, compared to the other investigated therapies, toxicity of dendritic cell vaccination is low, which supports our finding. CONCLUSION: This is the first description of HRQoL in melanoma patients receiving dendritic cell vaccination. We show the expected improvement in global health status after surgical treatment of stage III melanoma. Thus, adjuvant dendritic cell vaccination does not seem to hamper this improvement, as shown in our small explorative study.

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Langmuir cavitons have been artificially produced in Earth's ionosphere, but evidence of naturally occurring cavitation has been elusive. By measuring and modeling the spectra of electrostatic plasma modes, we show that natural cavitating, or strong, Langmuir turbulence does occur in the ionosphere, via a process in which a beam of auroral electrons drives Langmuir waves, which in turn produce cascading Langmuir and ion-acoustic excitations and cavitating Langmuir turbulence. The data presented here are the first direct evidence of cavitating Langmuir turbulence occurring naturally in any space or astrophysical plasma.

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AIM: After implantation of a sacral nerve modulation (SNM) device for faecal incontinence (FI), patients are subjected to a rigid follow-up schedule. If symptoms recur, it may be necessary to reprogramme the stimulation parameters of the device. The aims of this study was to assess the need for reprogramming in patients with an SNM implant for FI. METHOD: All patients who received a permanent SNM implant for FI from January 2000 to February 2008 were included in this study. Patients were subjected to a rigid follow-up schedule at 1, 3, 6 and 12 months, and yearly thereafter. Stimulator settings of the SNM device and changes made at every visit were collected and added to the database, and the number of patients in whom the stimulation parameter settings needed reprogramming was determined. RESULTS: A total of 155 patients (11 men) were analysed. The mean age (± standard deviation) of the patients was 57.7 ± 11.9 years. Median follow-up was 28.1 (range: 1.0-93.6) months. The mean voltage increased significantly from 1.8 V at 1 month to 2.0 V at 3 months. Thirty-nine (25.2%) patients required no reprogramming of their SNM implant during any of their follow-up visits; however, 51 (32.9%) patients required reprogramming at 1-25% of their visits, 42 (27.1%) patients at 26-50% of their visits, 14 (9.0%) patients at 51-75% of their visits and nine (5.8%) patients at 76-100% of their visits. CONCLUSION: Physicians and patients need to be aware of the fact that reprogramming of the SNM stimulator needs to be carried out at least once during follow-up in the majority of patients. Trained physicians or specialist nurses are imperative to ensure effective follow-up and appropriate SNM reprogramming.

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BACKGROUND AND AIMS: This study aims to evaluate the therapeutic effect of retrograde colonic irrigation in patients with faecal incontinence after a low anterior resection for a rectal carcinoma. MATERIALS AND METHODS: Patients with a previous low anterior resection, who were selected for treatment with retrograde colonic irrigation for faecal incontinence between 2005 and 2008, were included in the study. The data from the patients were gathered by chart research and an interview by phone. RESULTS: Thirty patients were included in the study. Three patients died and one patient was not able to answer questions due to a cognitive disorder. The data of the remaining 26 patients were analysed. Five patients had already stopped with the retrograde colonic irrigation treatment due to side effects. Twelve of the 21 patients (57.46%) who still performed RCI became completely (pseudo)continent, three patients (14.2%) were incontinent for flatus and six patients (29.4%) were still incontinent for liquid stool. Five patients stopped with the retrograde colonic irrigation treatment due to side-effects. CONCLUSION: Retrograde colonic irrigation is an effective method to treat patients with faecal incontinence after a low anterior resection for rectal carcinoma. Retrograde colonic irrigation is not invasive and has only mild side effects.

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Optical emissions and incoherent scatter radar data obtained during high-frequency electromagnetic pumping of the ionospheric plasma from the ground give data on electron energization in an energy range from 2 to 100 eV. Optical emissions at 4278 A from N2+ that require electrons with energies above the 18 eV ionization energy give the first images ever of pump-induced ionization of the thermosphere. The intensity at 4278 A is asymmetric around the ionospheric electron gyroharmonic, being stronger above the gyroresonance. This contrasts with emissions at 6300 A from O(1D) and of electron temperature enhancements, which have minima at the gyroharmonic but have no apparent asymmetry. This direct evidence of pump-induced ionization contradicts previous indirect evidence, which indicated that ionization is most efficiently produced when the pump frequency was below the gyroharmonic.

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Maternal ratings on internalizing (INT) and externalizing (EXT) behaviors were collected in a large, population-based longitudinal sample. The numbers of participating twin pairs at ages 3, 7, 10, and 12 were 5,602, 5,115, 2,956, and 1,481, respectively. Stability in both behaviors was accounted for by genetic and shared environmental influences. The genetic contribution to stability (INT: 43%; EXT: 60%) resulted from the fact that a subset of genes expressed at an earlier age was still active at the next time point. A common set of shared environmental factors operated at all ages (INT: 47%; EXT: 34%). The modest contribution of nonshared environmental factors (INT: 10%; EXT: 6%) could not be captured by a simple model. Significant age-specific influences were found for all components, indicating that genetic and environmental factors also contributed to changes in problem behavior.

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BACKGROUND: Twin studies of childhood behavior problems support the conclusion that individual differences in impulsivity, hyperactivity, and inattention are largely due to genetic influences. Non-genetic variation is due to environmental influences that are unique to the individual, and possibly to rater contrast effects. In the present longitudinal twin study, we report on the size of genetic and environmental effects on individual differences in attention problems at ages 3, 7, 10 and 12 years. METHODS: Mothers were asked to complete the CBCL for their twin offspring when the children were 3 (n = 11,938), 7 (n = 10,657), 10 (n = 6,192), and 12 years old (n = 3,124). We focus on the Overactivity (OA) scale in the Child Behavior Checklist (CBCL/2-3), and on the Attention Problem (AP) scale of the CBCL/4-18. The data were analyzed using longitudinal structural equation modeling. RESULTS: Broad heritability of OA and AP is estimated at nearly 75%, at each age. A contrast effect was observed at age 3 only. The results revealed less stability of OA at age 3 to AP at age 7 (r = .40), compared to the stability from AP at age 7 and beyond (r = .70). Genetic effects explained between 76% and 92% of the covariance between OA and AP. CONCLUSIONS: OA and AP are highly heritable at all ages in both genders. The same set of genes appears to be expressed in boys and girls. The size of genetic and environmental contributions remains the same across the ages studied. Stability in OA and AP is accounted for by genetic influences. Children who do not display OA or AP at a given age are unlikely to develop these problems at a subsequent age.

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Aggression in humans is associated with substantial morbidity and mortality. In this study we report on the aggressive behavior syndrome (AGG) in young children as defined by the Child Behavior Checklist (CBCL) and the Teacher Report Form (TRF). We assessed aggression in a large sample of Dutch twins at ages 3, 7, and 10 years. The purpose of this study was three-fold. First, we determined the number of children who are "clinically deviant" on the AGG scale. Second, we assessed the genetic and environmental contributions to AGG for the maternal, paternal, and teacher ratings at each age, for boys and girls. Third, we explored issues of rater bias by analyzing parental and teacher data simultaneously. CBCL data were available from mothers on 6436 three-year-old, 5451 seven-year-old, and 2972 ten-year-old twin pairs and CBCL data from fathers on 4207 three-year-old, 4269 seven-year-old, and 2295 ten-year-old twin pairs. Teacher report data from the TRF were collected for 1036 seven-year-old and 903 ten-year-old twin pairs from the Netherlands Twin Registry. Structural equation modeling was employed to obtain genetic and environmental estimates at each age. Analyses were conducted separately by age and informant, as well as simultaneously, for all informants. Differences in raw scores across gender were found, with boys being rated as more aggressive than girls by all informants. Mothers reported more symptoms than fathers, who reported more symptoms than teachers. Evidence for moderate to high genetic influence (51%-72%) was seen for AGG by all three informants at all ages with only small sex differences in heritability estimates. Best fitting models for AGG by parent reports also included a small contribution of common environment. The largest sex differences in heritabilities were seen at age 10. Contributions of common (13%-27%) and unique (16%-31%) environment were small to moderate. There was some evidence of genetic dominance by teacher report for 10-year-old girls.

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The differentiation hypothesis in cognitive development states that cognitive abilities become progressively more independent as children grow older. Studies of phenotypic development in children have generally failed to produce convincing support for this hypothesis. The aim of the present study is to investigate the issue of differentiation at the genetic and environmental level. Six psychometric measures assessing verbal and nonverbal cognitive abilities were administered to 209 Dutch twin pairs at ages 5, 7, and 10 years. Longitudinal results provided little evidence for the differentiation hypothesis. Stability in subtest performance is due mainly to genetic influences. The shared environment contribution to phenotypic stability is small. The unique environment contributes to age-specific variance only.

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Aggressive Behavior (AGG) and Rule-Breaking Behavior (RB) are two of the eight CBCL syndromes. The phenotypic correlation between AGG and RB ranges from.48 to.76, and varies depending on the rater and the sex of the child. Prevalence of AGG and RB (i.e., T > or = 67) is in the range of 6%-7% in both boys and girls. Fifty percent to 60% of the children who are deviant on AGG are also deviant on RB and vice versa. Why so many children show problem behavior in the clinical range for both syndromes is unclear. This co-occurrence could be due to genetic factors influencing both traits, to environmental factors influencing both traits, or to both. The purpose of this study is to use a genetically informative sample to estimate genetic and environmental influences on AGG and RB and to investigate the etiology of the co-occurrence of both behaviors. We do this using multiple informants to take into account underlying sources of parental agreement and disagreement in ratings of their offspring. To this end, mother and father ratings of AGG and RB were collected by using the Child Behavior Checklist in a large sample of 12-year-old twins. Parental agreement is represented by an interparent correlation in the range of .53-.76, depending on phenotype (AGG or RB) and sex of the child. Genetic influences account for 79% and 69% of the individual differences in RB and AGG behavior (defined as AGG and RB on which both parents do agree) in boys. In girls 56% and 72% of the variance in RB and AGG are accounted for by genetic factors. Shared environmental influences are significant for RB in girls only, explaining 23% of the total variance. Eighty percent of the covariance between AGG and RB, similarly assessed by both parents, can be explained by genetic influences. So, co-occurrence in AGG and RB is mainly caused by a common set of genes. Parental disagreement seems to be a combination of so-called rater bias and of parental specific views.

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Sibling interaction effects are suggested by a difference in phenotypic variance between monozygotic (MZ) twins and dizygotic (DZ) twins, and a pattern of twin correlations that is inconsistent with additive genetic influences. Notably, negative sibling interaction will result in MZ correlations which are more than twice as high as DZ correlations, a pattern also seen in the presence of genetic dominance. Negative sibling interaction effects have been reported in most genetic studies on Attention Deficit Hyperactivity Disorder (ADHD) and related phenotypes, while the presence of genetic dominance is not always considered in these studies. In the present paper the statistical power to detect both negative sibling interaction effects and genetic dominance is explored. Power calculations are presented for univariate models including sources of variation due to additive genetic influences, unique environmental influences, dominant genetic influences and a negative sibling interaction (i.e., contrast effect) between phenotypes of twins. Parameter values for heritability and contrast effects are chosen in accordance with published behavior genetic studies on ADHD and associated phenotypes. Results show that when both genetic dominance and contrast effects are truly present and using a classical twin design, genetic dominance is more likely to go undetected than the contrast effect. Failure to detect the presence of genetic dominance consequently gives rise to slightly biased estimates of additive genetic effects, unique environmental effects, and the contrast effect. Contrast effects are more easily detected in the absence of genetic dominance. If the significance of the contrast effect is evaluated while also including genetic dominance, small contrast effects are likely to go undetected, resulting in a relatively large bias in estimates of the other parameters. Alternative genetic designs, such as adding pairs of unrelated siblings reared together to a classical twin design, or adding non-twin siblings to twin pairs, greatly enhances the statistical power to detect contrast effects as well as the power to distinguish between genetic dominance and contrast effects.

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Multiple twin studies of attention problems (AP) from the Child Behavior Checklist or ADHD from the DSM criteria have reported on the genetic and environmental influences on these behaviors. The majority of these have studied AP and ADHD symptoms in twin samples combined across wide age spans, combined rater information and both genders. Thus, it is possible that the results are complicated by developmental, informant, and gender differences. The purpose of this study was to assess for the genetic and environmental contributions to overactive behavior (a syndrome highly related to AP in 7-, 10-, and 12-years olds) in 3-years olds (3,671 twin pairs), and attention problems in 7- (3,373 twin pairs), 10- (2,485 twin pairs), and 12-years olds (1,305 twin pairs) while controlling for developmental, gender and rater contrast contributions. Using a cross-sectional twin design, contributions from genetic additive, genetic dominance, unique environmental and rater contrast effects were estimated for CBCL maternal reports. We found that genetic influences on overactive behavior and attention problems are high across an age span that covers pre-school and elementary school age. Although girls display less problem behavior compared to boys, heritability estimates were found equal for both genders at each age. Environmental experiences that are unique to the individual accounted for the remaining influence. At the age of 3 years, a rater contrast effect was detected. We hypothesize that the contrast effect represents a maternal rater bias effect that is dependent on the age of the twins. The implications of these findings are discussed with reference to the clinical setting and in the context of future research.

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Measures of intelligence were collected in 209 twin pairs at 5, 7, 10, and 12 years of age, as part of a longitudinal project on intelligence, brain function, and behavioral problems. Intelligence was measured at 5, 7, and 10 years of age with the RAKIT, a well-known Dutch intelligence test, consisting of 6 subscales. At 12 years of age, the complete WISC-R was administered (12 subscales). Both intelligence tests resulted in a measure of full-scale IQ (FSIQ). Participation rate is around 93% at age 12. Correlation coefficients over time are high: (r(5-7) = .65; r(5-10) = .65; r(5-12) = .64; r(7-10) = .72; r(7-12) = .69 and r(10-12) = .78). Genetic analyses show significant heritabilities at all ages, with the expected increase of genetic influences and decrease of shared environmental influences over the years. Genetic influences seem to be the main driving force behind continuity in general cognitive ability, represented by a common factor influencing FSIQ at all ages. Shared environmental influences are responsible for stability as well as change in the development of cognitive abilities, represented by a common factor influencing FSIQ at all ages and age-specific influences, respectively.

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This study reports on zygosity determination in twins of childhood age. Parents responded to questionnaire items dealing with twin similarity in physical characteristics and frequency of mistaking one twin for another by parents, relatives and strangers. The accuracy of zygosity diagnosis was evaluated across twins aged 6, 8, and 10 and across parents. In addition, it was examined whether the use of multiple raters and the use of longitudinal data lead to an improvement of zygosity assignment. Complete data on zygosity questions and on genetic markers or blood profiles were available for 618 twin pairs at the age of 6 years. The method used was predictive discriminant analyses. Agreement between zygosity assigned by the replies to the questions and zygosity determined by DNA markers/blood typing was around 93%. The accuracy of assignment remained constant across age and parents. Analyses of data provided by both parents and collected over multiple ages did not result in better prediction of zygosity. Details on the discriminant function are provided.

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The genetic and environmental factor structures of intellectual abilities in 5-year-old Dutch twins were examined. Six subtests of the RAKIT, a Dutch intelligence test, were administered to 209 twin pairs. The subtests were categorized as either verbal or nonverbal. The genetic covariance structure displayed a two-common factor structure including specific factors to account for subtest residual variance. The correlation between the genetic Verbal and genetic Nonverbal factors did not differ significantly from zero. The shared environmental influence displayed a single-common factor structure. Unique environmental influences did not contribute to the covariance between subtests and were specific in origin. Estimates of heritability of the subtests ranged from 15% to 56%. Shared environmental influences were significantly present, but were modest in magnitude. The phenotypic data was best described by an oblique two-factor model. This model was not mirrored in the factor structures found for either the genetic or environmental covariances.

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