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We study the added-worker effect in the Netherlands with large-scale administrative panel data for the period 1999-2015. Conditioning on samples with similar employment histories, we employ differences-in-differences to estimate the effect of a male partner's unemployment shock on the female partner's income. We find a modest added-worker effect of 2-5% of the male partner's income loss, as compared to the much larger compensating effect from social insurance schemes. The added-worker effect largely disappeared at the beginning of the Great Recession, but resurfaced a few years later. Over the years, profits from self-employment have become more important in dealing with unemployment shocks., Competing Interests: Conflict of interestThe authors declare no competing interests., (© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2021.)

Background: Palliative care should be holistic, but spiritual issues are often overlooked. General practitioners and nurses working together in PaTz-groups (palliative home care groups) consider spiritual issues in palliative care to be relevant, but experience barriers in addressing spiritual issues and finding spiritual caregivers. This study evaluates the feasibility and perceived added value of a listening consultation service by spiritual caregivers in primary palliative care., Methods: From December 2018 until September 2019, we piloted a listening consultation service in which spiritual caregivers joined 3 PaTz-groups whose members referred patients or their relatives with spiritual care needs to them. Evaluation occurred through (i) monitoring of the implementation, (ii) in-depth interviews with patients (n = 5) and involved spiritual caregivers (n = 5), (iii) short group interviews in 3 PaTz-groups (17 GPs, 10 nurses and 3 palliative consultants), and (iv) questionnaires filled out by the GP after each referral, and by the spiritual caregiver after each consultation. Data was analysed thematically and descriptively., Results: Consultations mostly took place on appointment at the patients home instead of originally intended walk-in consultation hours. Consultations were most often with relatives (72%), followed by patients and relatives together (17%) and patients (11%). Relatives also had more consecutive consultations (mean 4.1 compared to 2.2 for patients). Consultations were on existential and relational issues, loss, grief and identity were main themes. Start-up of the referrals took more time and effort than expected. In time, several GPs of each PaTz-group referred patients to the spiritual caregiver. In general, consultations and joint PaTz-meetings were experienced as of added value. All patients and relatives as well as several GPs and nurses experienced more attention for and awareness of the spiritual domain. Patients and relatives particularly valued professional support of spiritual caregivers, as well as recognition of grief as an normal aspect of life., Conclusions: If sufficient effort is given to implementation, listening consultation services can be a good method for PaTz-groups to find and cooperate with spiritual caregivers, as well as for integrating spiritual care in primary palliative care. This may strengthen care in the spiritual domain, especially for relatives who are mourning.

Imitation problems are commonly reported in children with an autism spectrum disorder. However, it has not yet been determined whether imitation problems persist into young adulthood. In this study, we investigated imitation skills of 20 intellectually able young adults with autism spectrum disorder relative to 19 age-matched neurotypical adults. For this purpose, we used a bar-transport task, which evokes the application of the end-state comfort principle. Specifically, we examined whether young adults with autism spectrum disorder imitated the means-end structure of a demonstrator's bar-transport action with and without application of the end-state comfort principle (imitation task). In addition, we examined whether participants spontaneously applied the end-state comfort principle during a similar bar-transport task (free execution task). Results revealed that young adults with autism spectrum disorder imitated the means-end structure of observed actions to the same degree as neurotypical adults ( p = 0.428). In contrast, they applied the end-state comfort principle less often during free executed actions ( p = 0.035). Moreover, during these actions, they were slower to place the bar into the penholder ( p = 0.023), which contributed to the reduced efficiency of their performance. Findings suggest that imitation abilities of young adults with autism spectrum disorder are preserved and that observing others' actions might promote more efficient action planning in this population.

This study investigated if decreased cognitive control, reflected in response inhibition and working-memory performance, is an underlying mechanism of risky driving in young novice drivers. Thirty-eight participants aged 17 to 25 years old, with less than 1 year of driving experience, completed a simulated drive that included several risky driving measures. Measures of response inhibition and verbal working memory were negatively associated with the standard deviation of the lateral lane position. Response inhibition, but not working memory, was also negatively related with the detection of, reaction to, and crashes with road hazards. Unexpectedly, increased cognitive control did not always relate to decreased risky driving. Visuospatial working-memory performance related positively with yellow-light running and negatively with the minimal following distance inside the city center. The findings evidence the role of cognitive control in explaining risky driving in young novice drivers. This relationship, however, differed per cognitive function and per driving parameter. Implications for future research and traffic safety interventions are discussed.

Leigh syndrome is an early onset, often fatal progressive neurodegenerative disorder caused by mutations in the mitochondrial or nuclear DNA. Until now, mutations in more than 35 genes have been reported to cause Leigh syndrome, indicating an extreme genetic heterogeneity for this disorder, but still only explaining part of the cases. The possibility of whole exome sequencing enables not only mutation detection in known candidate genes, but also the identification of new genes associated with Leigh syndrome in small families and isolated cases. Exome sequencing was combined with homozygosity mapping to identify the genetic defect in a Moroccan family with fatal Leigh syndrome in early childhood and specific magnetic resonance imaging abnormalities in the brain. We detected a homozygous nonsense mutation (c.20C>A; p.Ser7Ter) in the thiamine transporter SLC19A3. In vivo overexpression of wild-type SLC19A3 showed an increased thiamine uptake, whereas overexpression of mutant SLC19A3 did not, confirming that the mutation results in an absent or non-functional protein. Seventeen additional patients with Leigh syndrome were screened for mutations in SLC19A3 using conventional Sanger sequencing. Two unrelated patients, both from Moroccan origin and one from consanguineous parents, were homozygous for the same p.Ser7Ter mutation. One of these patients showed the same MRI abnormalities as the patients from the first family. Strikingly, patients receiving thiamine had an improved life-expectancy. One patient in the third family deteriorated upon interruption of the thiamine treatment and recovered after reinitiating. Although unrelated, all patients came from the province Al Hoceima in Northern Morocco. Based on the recombination events the mutation was estimated to have occurred 1250-1750 years ago. Our data shows that SLC19A3 is a new candidate for mutation screening in patients with Leigh syndrome, who might benefit from high doses of thiamine and/or biotin. Especially, Moroccan patients with Leigh syndrome should be tested for the c.20C>A founder mutation in SLC19A3.

Background: Mitochondrial disorders are associated with abnormalities of the oxidative phosphorylation (OXPHOS) system and cause significant morbidity and mortality in the population. The extensive clinical and genetic heterogeneity of these disorders due to a broad variety of mutations in several hundreds of candidate genes, encoded by either the mitochondrial DNA (mtDNA) or nuclear DNA (nDNA), impedes a straightforward genetic diagnosis. A new disease gene is presented here, identified in a single Kurdish patient born from consanguineous parents with neonatally fatal Leigh syndrome and complex I deficiency., Methods and Results: Using homozygosity mapping and subsequent positional candidate gene analysis, a total region of 255.8 Mb containing 136 possible mitochondrial genes was identified. A pathogenic mutation was found in the complex I subunit encoding the NDUFA9 gene, changing a highly conserved arginine at position 321 to proline. This is the first disease-causing mutation ever reported for NDUFA9. Complex I activity was restored in fibroblasts of the patient by lentiviral transduction with wild type but not mutant NDUFA9, confirming that the mutation causes the complex I deficiency and related disease., Conclusions: The data show that homozygosity mapping and candidate gene analysis remain an efficient way to detect mutations even in small consanguineous pedigrees with OXPHOS deficiency, especially when the enzyme deficiency in fibroblasts allows appropriate candidate gene selection and functional complementation.

In mechanically ventilated preterm infants, the combination of immaturity, volutrauma, oxidative stress, and inflammatory processes can lead to chronic lung injury. Mitochondrial DNA (mtDNA) is more susceptible to oxidative damage than nuclear DNA. We aimed to investigate the level of mtDNA damage (deletions, mutations and changes in copy number) in bronchoalveolar lavage (BAL) cells from 10 preterm infants (27-30 weeks). A first BAL (BAL1) was done within 24 h of endotracheal intubation and BAL2 was performed 30-103 h thereafter. Deletions were analyzed by long range PCR, point mutations by heteroduplex analysis of the D-loop region, and copy number changes by real-time PCR. Using these methods, no deletions were found in any of the BAL samples. When BAL1 and BAL2 samples were compared no new mutations were found. In contrast, a marked decrease in mtDNA copy number was observed in 5 patients. In conclusion, we found that exposure of preterm infants to short term mechanical ventilation did not lead to detrimental consequences for the mtDNA in the form of mutations or deletions.

Background: Mutations in the DNA polymerase-gamma (POLG) gene are a major cause of clinically heterogeneous mitochondrial diseases, associated with mtDNA depletion and multiple deletions., Objective: To determine the spectrum of POLG mutations in our Dutch patient cohort, to evaluate the pathogenicity of novel mutations, and to establish genotype-phenotype correlations., Results: The authors identified 64 predominantly recessive mutations in 37 patients from a total of 232 patients, consisting of 23 different mutations. The substitution p.A467T was most frequently observed (n = 23), but was as frequent in childhood cases as in adult cases. Five new pathogenic recessive mutations, p.Lys925ArgfsX42, p.R275X, p.G426S, p.A804T and p.R869Q were identified. The known dominant chronic progressive external ophthalmoplegia (CPEO) mutation p.R943H was for the first time associated with premature ovarian failure as well. In 19 patients the authors identified only a single recessive mutation, or a sequence variant with unclear clinical significance. The data substantiate earlier observations that in POLG patients a fatal status epilepticus and liver failure can be triggered by sodium valproate. It is therefore important to exclude POLG mutations before administering this treatment., Conclusion: The clinical features of the patient are the most important features to select putative POLG mutation carriers and not the presence of mtDNA deletions or OXPHOS (oxidative phosphorylation) activity. The authors conclude that POLG mutations are an important cause of heterogeneous mitochondrial pathology and that more accurate genotype-phenotype correlations allow a more rapid genetic diagnosis and improved prognosis for mutation carriers.

Objective: The purpose of the present study was to answer the question whether pain report can be increased and decreased by operant conditioning. We predicted that the conditioned pain effects would remain significant after correction for social desirability and fantasy proneness. Furthermore, we tried to show that the neurophysiologic basis of verbal pain report, defined by pain (event)-related potentials, was affected by the conditioning procedure. Specifically, it was expected that the central recording site N150-P260 pain (event)-related potentials peak-to-peak amplitude would show the largest effect., Methods: There were 4 groups: an up-conditioning group, a down-conditioning group, an at-random conditioning, and no-feedback control group. Healthy patients received 45 calibrated pain stimuli of equal physical intensity and were asked to rate the pain intensity they experienced. Up-conditioning was established by rewarding the subject if pain report increased compared with the previous trial. Down-conditioning of pain report was achieved by rewarding a decrease in the pain score., Results: Results of the subjective pain reports clearly indicated that both forms of conditioning succeeded. Up-conditioning resulted in the highest pain scores and down-conditioning in the lowest scores with the two control groups in between them. Controlling for level of social desirability and fantasy proneness did not negatively influence these results. The N150-P260 pain (event)-related potentials peak-to-peak central recording site component also showed the predicted effect and reached statistical significance., Discussion: We concluded that the subjective report of pain as well as a specific pain-related potentials component can be operantly conditioned.

Background: Post-traumatic amnesia is considered to be the best single indicator of the severity of closed head injury. Usually, it has been estimated retrospectively. For practical reasons this also tends to be the most common clinical method. It has been argued that prospective assessment is more accurate and reliable, but this has never been evaluated empirically in severe head injury., Methods: Post-traumatic amnesia was initially assessed prospectively and later retrospectively by a separate observer in the same patients., Results: The correlation between the two methods was high. In addition, both measures significantly correlated with other measures of severity of brain injury and with measures of outcome., Conclusion: Retrospective measurement of post-traumatic amnesia is a valid method.