Swedish Families Research Articles

Incorporation of Detailed Family History from the Swedish Family Cancer Database into the PCPT Risk Calculator

A detailed family history provides an inexpensive alternative to genetic profiling for individual risk assessment. We updated the PCPT Risk Calculator to include detailed family histories. The study included 55,168 prostate cancer cases and 638,218 controls from the Swedish Family Cancer Database who were 55 years old or older in 1999 and had at least 1 male first-degree relative 40 years old or older and 1 female first-degree relative 30 years old or older. Likelihood ratios, calculated as the ratio of risk of observing a specific family history pattern in a prostate cancer case compared to a control, were used to update the PCPT Risk Calculator. Having at least 1 relative with prostate cancer increased the risk of prostate cancer. The likelihood ratio was 1.63 for 1 first-degree relative 60 years old or older at diagnosis (10.1% of cancer cases vs 6.2% of controls), 2.47 if the relative was younger than 60 years (1.5% vs 0.6%), 3.46 for 2 or more relatives 60 years old or older (1.2% vs 0.3%) and 5.68 for 2 or more relatives younger than 60 years (0.05% vs 0.009%). Among men with no diagnosed first-degree relatives the likelihood ratio was 1.09 for 1 or more second-degree relatives diagnosed with prostate cancer (12.7% vs 11.7%). Additional first-degree relatives with breast cancer, or first-degree or second-degree relatives with prostate cancer compounded these risks. A detailed family history is an independent predictor of prostate cancer compared to commonly used risk factors. It should be incorporated into decision making for biopsy. Compared with other costly biomarkers it is inexpensive and universally available.

Parental feeding practices and associations with child weight status. Swedish validation of the Child Feeding Questionnaire finds parents of 4-year-olds less restrictive

The Child Feeding Questionnaire (CFQ) assesses parental feeding attitudes, beliefs and practices concerned with child feeding and obesity proneness. The questionnaire has been developed in the U.S., and validation studies in other countries are limited. The aim of this study was to examine the psychometric properties of the CFQ in Sweden and the associations between parenting practices and children's weight status. Based on records from the Swedish population register, all mothers of 4-year-olds (n = 3007) from the third largest city in Sweden, Malmö, were contacted by mail. Those who returned the CFQ together with a background questionnaire (n = 876) received the CFQ again to enable test-retest evaluation; 564 mothers completed the CFQ twice. We used confirmatory factor analysis to test whether the original 7-factor model was supported. Good fit (CFI = 0.94, TLI = 0.95, RMSEA = 0.04, SRMR = 0.05) was obtained after minor modifications such as dropping 2 items on restriction and adding 3 error covariances. The internal reliability and the 2-week test-retest reliability were good. The scores on restriction were the lowest ever reported. When the influence of parenting practices on child BMI (dependent variable) was examined in a structural equation model (SEM), child BMI had a positive association with restriction and a negative association with pressure to eat. Restriction was positively influenced by concern about child weight. The second SEM treated parenting practices as dependent variables. Parental foreign origin and child BMI had direct effects on restriction, while pressure to eat was also influenced by parental education. While the results of the study support the usefulness of the CFQ in Sweden, carefully designed cross-cultural comparisons are needed to explain why the levels of restrictive feeding in Swedish families are the lowest reported.

Impaired metabolic control and socio-demographic status in immigrant children at onset of Type1 diabetes.

The aim of the present study was to compare clinical and socio-demographic conditions at the onset of Type1 diabetes in children born to immigrant families and children born to Swedish families, and to assess whether those conditions had an impact on metabolic status. This was an observational nationwide population-based matched cohort study on prospectively recorded registry data of all children with diabetes in Sweden and their families during 2000-2010. Out of a total of 13415 children from the Swedish Childhood Diabetes Registry (SWEDIABKIDS), 879 children born to immigrant parents were collected. To these we added 2627 children with Swedish-born parents, matched for gender, age and year of onset of Type1 diabetes. The proportion of low capillary pH (<7.30) at onset was higher in the immigrant cohort [25.8% vs. 16.4% in the Swedish cohort (P<0.001)]. HbA1c was also higher [95mmol/mol (10.8%) vs. 88mmol/mol (10.2%), respectively (P<0.001)]. In a logistic regression model with low pH as the dependent variable, we were unable to reveal any significant association to socio-demographic factors, but the odds ratio for HbA1c was 0.983 (95%CI 0.976-0.991) and for plasma glucose was 0.953 (95%CI 0.933-0.973). Children born to immigrant parents have lower capillary pH and higher HbA1c at diabetes onset. Immigrant families harbour lower socio-demographic living conditions, but this fact does not seem to influence the inferior metabolic condition at diabetes onset.

Stability and change in sustainability of daily routines and social networks in families of children with profound intellectual and multiple disabilities.

Children with profound intellectual and multiple disabilities (PIMD) demand intense family accommodations from birth and onwards. This study used an exploratory and qualitative study design to investigate stability and change in sustainability of daily routines and social networks of Swedish families of children with PIMD. Eight families participated over two years in eco-cultural family interviews and social networks interviews collected at home visits. Data were analyzed descriptively and by manifest contents analysis. Results showed variations in sustainability of daily routines over time across families. The sustainability was linked to fathers' involvement, couples' connectedness and emotional support. Stability and change of social networks were characterized by low overlap between the child and family networks, the children's communicative dependency and low density of able communication partners. The results indicate that patterns of stability and change were linked both to family resources and child characteristics.

Response to the commentary of Segrot et al on the Swedish SFP trial.

The commentary of Segrot et al on the Swedish Strengthening Families Program (SFP) trial is important. The spread of evidence-based practice has resulted in an increased interest in empirically supported interventions (ESIs) and a growing number of controlled trials of imported and culturally adapted interventions. Evidence from selected case examples of replication trials of family-based US Blueprints model and promising programs appears mixed.1 We are beginning to learn from these successes and failures that features of both ESIs and the research designs used to test them may contribute to outcomes, that is, whether transport from one cultural context to another is successful in terms of program implementation and observed outcomes. To understand the contradictory results from studies of imported ESIs, at least four explanations are available. The first has …

Phenotyping age‐sependent changes in the 5xFAD Alzheimer’s Disease Model mice (LB556)

5XFAD transgenic (Tg) mice express 5 human familial Alzheimer’s Disease (AD) gene mutations ‐ Amyloid Precursor Protein mutations from the Swedish, Florida and London families, along with 2 mutations in presenilin‐1. Their early onset brain pathology, accelerated Aβ42 amyloid deposition, age‐dependent neurodegeneration and cognitive decline, make these mice an attractive translatable AD model.We used behavioral, biochemical and electrophysiological analyses to track age‐dependent changes in 5XFAD mice, compared with their age‐matched wild‐type mice. With sensitive NanoPro Western, 3 month old 5XFAD mice showed a significant increase of p‐T181‐Tau in the cerebral spinal fluid. Their hippocampal ELISA Aβ40 and 42 levels increased progressively from 2,3,6 months. Under confocal microscopy, the secondary and tertiary dendritic spine counts in Golgi‐stained 9 month prefrontal and hippocampal pyramidal neurons showed a significant loss. Hippocampal slice electrophysiology using the multielectrode MED64 system is used to assess synaptic plasticity, i.e. long‐term potentiation.Using the Laboras vibration‐sensitive platforms, we discovered that there was a significant dark phase hyperactivity and bi‐directional circling that resembled striatal degeneration, and hyperlocomotion at 9, 12, but not 2 month, matching the chronic EEG recordings of a significant reduction in NREM and REM sleep at 9 month. The onset of cognitive decline started at 4 months (working memory, Y‐maze spontaneous alteration), 5 month (episodic memory, Novel Object Recognition), and 6 month (spatial memory, Morris Water Maze). Sub‐chronic treatment in 4 months old 5XFAD mice by: a) Donepezil + Memantine (2 weeks), or b) Traditional Chinese herbal formula (1 month), led to a significantly improvement in Y‐maze spontaneous alternation performance.Findings from these studies guide us to select the right ages of 5XFAD mice to test for pharmacological changes in AD biomarkers and behaviors in AD research.

Autosomal dominant brachyolmia in a large Swedish family: Phenotypic spectrum and natural course

Autosomal dominant brachyolmia (Type 3, OMIM #113500) belongs to a group of skeletal dysplasias caused by mutations in the transient receptor potential cation channel, subfamily V, member 4 (TRPV4) gene, encoding a Ca++-permeable, non-selective cation channel. The disorder is characterized by disproportionate short stature with short trunk, scoliosis and platyspondyly. The phenotypic variability and long-term natural course remain inadequately characterized. The purpose of this study was to describe a large Swedish family with brachyolmia type 3 due to a heterozygous TRPV4 mutation c.1847G>A (p.R616Q) in 11 individuals. The mutation has previously been detected in another family with autosomal dominant brachyolmia [Rock et al., 2008]. Review of hospital records and patient assessments indicated that clinical symptoms of brachyolmia became evident by school age with chronic pain in the spine and hips; radiographic changes were evident earlier. Growth was not affected during early childhood but deteriorated with age in some patients due to increasing spinal involvement. Affected individuals had a wide range of subjective symptoms with chronic pain in the extremities and the spine, and paresthesias. Our findings indicate that autosomal dominant brachyolmia may be associated with significant long-term morbidity, as seen in this family.

Gendered Resource Access and Utilisation in Swedish Family Farming

Gendered relations in resource access and farming are two important intersecting themes of gender studies in a northern rural context. However, conventional analysis and perceptions of the economy conceal the contribution of women within families, in businesses and in the labor market. This article demonstrate the significance of capital to farming women’s engagement with agriculture using a Swedish case study, based on descriptive analyses of data from the Federation of Swedish Farmers. To disclose the embodiment of family farming, gendered control of land, business activities and farm incomes is analyzed. On this empirical basis, we argue for reconstitution of farm-related entrepreneurial research, rural development policies and rural gender studies from a new material feminist approach. Access to resources, typically land, together with social forces and embodied experiences constitute the basis of strategic focus and agency. We demonstrate that acknowledgement of access to resources in the research process and in the understanding of social relations, resistance and situated knowledge are essential.

Erratum: Intra-Hippocampal Transplantation of Neural Precursor Cells with Transgenic Over-Expression of IL-1 Receptor Antagonist Rescues Memory and Neurogenesis Impairments in an Alzheimer’s Disease Model

Correction to: Neuropsychopharmacology advance online publication, 11 September 2013; doi:10.1038/npp.2013.208 In this article, the first sentence after the ‘Subjects’ subheading in the MATERIALS AND METHODS section (top of the right column on page 2) should be replaced by ‘Subjects were Tg(HuAPP695, K670N-M671L)2576 (Tg2576) mice (Hsiao et al, 1996), carrying a double mutation that was found in a large Swedish family with early-onset AD, as well as their littermate controls.

Genotype-phenotype analysis in inherited prion disease with eight octapeptide repeat insertional mutation

A minority of inherited prion diseases (IPD) are caused by four to 12 extra octapeptide repeat insertions (OPRI) in the prion protein gene (PRNP). Only four families affected by IPD with 8-OPRI have been reported, one of them was a three-generation Swedish kindred in which four of seven affected subjects had chorea which was initially attributed to Huntington’s disease (HD). Following the exclusion of HD, this phenotype was labeled Huntington disease-like 1 (HDL1). Here, we provide an update on the Swedish 8-OPRI family, describe the clinical features of one of its affected members with video-recordings, compare the four 8-OPRI families and study the effect of PRNP polymorphic codon 129 and gender on phenotype. Surprisingly, the Swedish kindred displayed the longest survival of all of the 8-OPRI families with a mean of 15.1 years from onset of symptoms. Subjects with PRNP polymorphic codon 129M in the mutated allele had significantly earlier age of onset, longer survival and earlier age of death than 129V subjects. Homozygous 129MM had earlier age of onset than 129VV. Females had a significantly earlier age of onset and earlier age of death than males. Up to 50% of variability in age of onset was conferred by the combined effect of PRNP polymorphic codon 129 and gender. An inverse correlation between early age of onset and long survival was found for this mutation.

Family business and business history: An example of comparative research

This paper deals with one of the pillars of contemporary business history – the use of cross-national comparisons. Besides the longitudinal, the comparative perspective is a crucial dimension of business and economic history research. During the last decades several attempts have been made to illustrate the process of development and structuring of national markets and corporations both currently and in a historical perspective, through the use of a comparative method. This paper aims to point out the possibilities and problems with this approach. It especially highlights the role of institutional factors and changes as important determinants for national development and as obstacles for good comparative exercises. It also discusses the role of functional and coherent definitions in comparative research and the problems connected with data collection and analysis. The main research question is how cross-national comparisons can help us develop business history research further. A comparison between family firms in Italy and Sweden shows that the development of family business in these two countries exhibited extensive similarities during the early decades of the twentieth century. However after World War II the two countries became more diversified in terms of their industrial structure. While Swedish family firms became an important part of national big business, Italian family businesses developed into smaller and more flexible organisations. Thus, today in Sweden several family-owned and controlled firms are among the largest in the country, particularly in capital- and technology-intensive industries. Italian family firms, even if present among the largest in the country, are largely in industries other than high tech, and show a degree of organisational sophistication inferior to their Swedish counterparts. This paper discusses the driving forces behind this development, showing how the explicit use of the comparative, longitudinal approach can highlight the patterns of convergence and divergence across national business models.

Proper Food and a Tight Budget

Much attention has been devoted in recent years to issues of food and health in childhood. Being a parent today implies exposure to multiple discourses concerning food and health and how best to bring up one's child. In this study, parents from German and Swedish families with low socio-economic status took part in qualitative studies to examine issues of food in relation to health. The findings suggest that eating habits are influenced by a number of factors. In everyday food consumption, the ideal of proper, healthy food is challenged by time and financial restrains and by individual tastes. A comparison of confectionery versus fruit reveals that the consumption of these eatables is connected to different social contexts and to different sets of values. While there is a tendency to categorize certain groups as less responsible and more problematic, we argue that for the successful development of a health program it is crucial to start by considering structural factors and social inequality and then to take advantage of people's own resources, and work for the active participation of those involved.

Hertiginnan, hovet och staden i det gustavianska Stockholm

&lt;p&gt;The Duchess, the Court, and the City in Gustavian Stockholm&lt;/p&gt;&lt;p&gt;&lt;br /&gt;This article analyses the everyday urban sociability and the staging of politics of the Swedish duchess Hedwig Elizabeth Charlotte in the years around 1790. The cultural and social life of the Gustavian court has been the focus of much scholarly attention. However, the main aim of these studies has been to examine court life as a reflection of Gustavus III&amp;rsquo;s personality and political ambitions. This article, however, integrates Gustavian court sociability in a broader European pattern by focusing on the monarch&amp;rsquo;s sister-in-law. It aims to give a detailed account of social practice through a vast selection of the Duchess&amp;rsquo;s personal remains: her political journal and letters, informal notes to friends, and household accounts showing the sums she spent on charity. It also takes into account royal theatre box subscription lists as a way to identify the composition of the theatre audience. The claim of this article is that the Swedish royal family maintained their authority through their daily urban presence, such as their walks in the public gardens and main streets of Stockholm, their attendance at weekly balls at the Stock Exchange (B&amp;ouml;rshuset), or their visits to the royal theatres. Through a carefully ritualized sociability, the court preserved their social exclusivity in their urban encounters.&lt;/p&gt;

P.16.13 Myopathy with typical OPMD morphology without association with the PABPN1 gene locus

Oculopharyngeal muscular dystrophy (OPMD) is an adult-onset disease characterized by progressive ptosis of the eyelids and dysphagia. Intranuclear inclusions of tubulofilamentous (INIs) in skeletal muscle constitute a pathological hallmark for this disease. The filaments are up to 250 nm in length and have external diameter of 8.5 nm and an internal diameter of 3 nm. The only causative mutation described to date is a triplet repeat expansion consisting of 2–7 additional base triplets in a repeat sequence in exon 1 of the polyadenine binding protein nuclear 1 (PABPN1) gene localized on chromosome 14q11.2. This results in an increase in length of a polyalanine tract in the PABPN1 protein from 10 to 12–17 residues. We describe the clinical, histopathological and genetically findings in three individuals from a Swedish family, with a dominantly inherited adult-onset myopathy characterized by ptosis and dysphagia. Muscle histopathological features included rimmed vacuoles and nuclei containing inclusions of unique 8.5 nm filaments and insoluble PABPN1 protein. The PABPN1 gene was excluded as the disease causative gene in this family both by direct DNA sequencing of the gene together with high density single nucleotide polymorphism (SNP) arrays covering the entire genome excluding the locus harbouring the PABPN1 gene.

A Possible Mechanism behind Autoimmune Disorders Discovered By Genome-Wide Linkage and Association Analysis in Celiac Disease

Celiac disease is a common autoimmune disorder characterized by an intestinal inflammation triggered by gluten, a storage protein found in wheat, rye and barley. Similar to other autoimmune diseases such as type 1 diabetes, psoriasis and rheumatoid arthritis, celiac disease is the result of an immune response to self-antigens leading to tissue destruction and production of autoantibodies. Common diseases like celiac disease have a complex pattern of inheritance with inputs from both environmental as well as additive and non-additive genetic factors. In the past few years, Genome Wide Association Studies (GWAS) have been successful in finding genetic risk variants behind many common diseases and traits. To complement and add to the previous findings, we performed a GWAS including 206 trios from 97 nuclear Swedish and Norwegian families affected with celiac disease. By stratifying for HLA-DQ, we identified a new genome-wide significant risk locus covering the DUSP10 gene. To further investigate the associations from the GWAS we performed pathway analyses and two-locus interaction analyses. These analyses showed an over-representation of genes involved in type 2 diabetes and identified a set of candidate mechanisms and genes of which some were selected for mRNA expression analysis using small intestinal biopsies from 98 patients. Several genes were expressed differently in the small intestinal mucosa from patients with celiac autoimmunity compared to intestinal mucosa from control patients. From top-scoring regions we identified susceptibility genes in several categories: 1) polarity and epithelial cell functionality; 2) intestinal smooth muscle; 3) growth and energy homeostasis, including proline and glutamine metabolism; and finally 4) innate and adaptive immune system. These genes and pathways, including specific functions of DUSP10, together reveal a new potential biological mechanism that could influence the genesis of celiac disease, and possibly also other chronic disorders with an inflammatory component.

Pioneer in Team-Based Care Explains How Psychiatrists Can Get Involved

Pioneer in Team-Based Care Explains How Psychiatrists Can Get Involved

Different Stages of White Matter Changes in the Original HDLS Family Revealed by Advanced MRI Techniques

The temporal evolution of white matter (WM) changes on MR examinations in hereditary diffuse leukoencephalopathy with spheroids (HDLS) is largely unknown. Our purpose was to investigate the evolution of these WM changes with diffusion weighted/tensor imaging (DWI/DTI) and MR Spectroscopy (MRS). A newly diagnosed patient with HDLS from the original Swedish family was followed prospectively with 5 MRI as well as DWI/DTI and MRS examinations during 16 months. The DTI eigenvalues demonstrated changes that suggested early myelin and axonal disturbances in the normal appearing WM (NAWM). DWI/DTI showed a rim of decreased diffusion progressively expanding through the WM from the initial frontal periventricular zones, and indicated complete destruction of axons and myelin in the area behind the front. MRS findings were suggestive of axonal destruction in the NAWM. We describe HDLS changes in three temporal stages of development corresponding to lesions outside, in the vicinity of, and behind a characteristic rim centrifugally progressing from the ventricular horns. The axonal disturbances indicated by MRS changes in the NAWM support a primary axonal degeneration, as proposed in the original HDLS report, rather than axonal degeneration secondary to demyelination. These findings could help in differential diagnosis of HDLS.

Congenital dyserythropoietic anemia type III (CDA III) is caused by a mutation in kinesin family member, KIF23

AbstractHaplotype analysis and targeted next-generation resequencing allowed us to identify a mutation in the KIF23 gene and to show its association with an autosomal dominant form of congenital dyserythropoietic anemia type III (CDA III). The region at 15q23 where CDA III was mapped in a large Swedish family was targeted by array-based sequence capture in a female diagnosed with CDA III and her healthy sister. Prioritization of all detected sequence changes revealed 10 variants unique for the CDA III patient. Among those variants, a novel mutation c.2747C>G (p.P916R) was found in KIF23, which encodes mitotic kinesin-like protein 1 (MKLP1). This variant segregates with CDA III in the Swedish and American families but was not found in 356 control individuals. RNA expression of the 2 known splice isoforms of KIF23 as well as a novel one lacking the exons 17 and 18 was detected in a broad range of human tissues. RNA interference–based knock-down and rescue experiments demonstrated that the p.P916R mutation causes cytokinesis failure in HeLa cells, consistent with appearance of large multinucleated erythroblasts in CDA III patients. We conclude that CDA III is caused by a mutation in KIF23/MKLP1, a conserved mitotic kinesin crucial for cytokinesis.

Best vitelliform macular dystrophy in a Swedish family: genetic analysis and a seven‐year follow‐up of photodynamic treatment of a young boy with choroidal neovascularization

To determine the mutation in a Swedish family with Best disease (vitelliform macular dystrophy; VMD) and to investigate the short- and long-term effects of photodynamic treatment (PDT) on subretinal neovascularization in a young boy. The five members of three generations of a family with VMD underwent a thorough ophthalmological examination, including best-corrected visual acuity (VA), visual field, colour vision, biomicroscopy of the posterior segment (dilated), fundus photography and electro-oculography (EOG). For the proband, an eleven-year-old boy, his father and grandfather, dark adaptation test, angiography and electroretinography (ERG) were also performed. After PCR amplification, the genotype was determined by cleavage with restriction enzyme, specific for the W93C allele. Four family members had an abnormal EOG response. All showed the W93C mutation in the VMD2 gene. Visual acuity ranged from 20/20 to 20/250. The fundus manifestations varied from minor pigmentary changes over egg yolk-like lesions to chorioretinal atrophy, and fluorescein angiography showed corresponding pathology. In the proband, VA decreased during follow-up from 0.5 (20/40) to 0.08 (20/250) due to a subfoveal neovascularization with haemorrhage, and PDT with visudyne was begun. The haemorrhage resolved within 2 months, and after three treatments, VA had increased to 0.25 (20/80). One year later, acuity had improved to 0.5 (20/40), and this result was stable throughout the 7 years of the follow-up. The mutation was determined to be W93C, the most common mutation in VMD in Sweden. In an eleven-year-old boy with subretinal neovascularization, PDT seemed to be beneficial also in a long-term follow-up.

Fetal and Maternal Genes’ Influence on Gestational Age in a Quantitative Genetic Analysis of 244,000 Swedish Births

Although there is increasing evidence that genetic factors influence gestational age, it is unclear to what extent this is due to fetal and/or maternal genes. In this study, we apply a novel analytical model to estimate genetic and environmental contributions to pregnancy history records obtained from 165,952 Swedish families consisting of offspring of twins, full siblings, and half-siblings (1987-2008). Results indicated that fetal genetic factors explained 13.1% (95% confidence interval (CI): 6.8, 19.4) of the variation in gestational age at delivery, while maternal genetic factors accounted for 20.6% (95% CI: 18.1, 23.2). The largest contribution to differences in the timing of birth were environmental factors, of which 10.1% (95% CI: 7.0, 13.2) was due to factors shared by births of the same mother, and 56.2% (95% CI: 53.0, 59.4) was pregnancy specific. Similar models fit to the same data dichotomized at clinically meaningful thresholds (e.g., preterm birth) resulted in less stable parameter estimates, but the collective results supported a model of homogeneous genetic and environmental effects across the range of gestational age. Since environmental factors explained most differences in the timing of birth, genetic studies may benefit from understanding the specific effect of fetal and maternal genes in the context of these yet-unidentified factors.