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Hypothalamic hamartomas are benign lesions associated with drug resistant epilepsy. Surgical treatment has become an increasingly utilised approach with promising results. This study aims to evaluate seizure outcome and complications after surgery in a population-based series of patients with intractable epilepsy and hypothalamic hamartoma. All patients with hypothalamic hamartoma treated with epilepsy surgery in Sweden since 1995 with at least two years of follow-up were included. Preoperative, two-, five- and ten-year prospective longitudinal data were collected from The Swedish National Epilepsy Surgery Register. Data included seizure types and frequency, duration of epilepsy, clinical characteristics, neurological deficits, cognitive level and complications. In a subgroup from Gothenburg, we also analysed data not included in the register such as classification of hamartomas, surgical procedures and gelastic seizures. Eighteen patients were operated on during the period 1995–2020. The median age at epilepsy onset was 6 months and age at surgery 13 years. Four were seizure free and another four had ≥75% reduction in seizure frequency at the two-year follow-up. Two of the 13 patients with a long-term follow-up (five or ten years) were seizure-free and four had ≥75% reduction in seizure frequency. Three had an increased seizure frequency. No major complications were seen. Five had minor complications. In the Gothenburg subgroup all had open pterional disconnection or intraventricular endoscopic disconnection. Six of 12 were free from gelastic seizures at the two-year follow-up and six of eight at the long-term follow-up. This study supports surgical treatment of hypothalamic hamartomas as a safe method with a low risk of permanent complications. The seizure reduction seems to be persistent over time. • Surgical treatment of hypothalamic hamartomas can be safe and without major complications. • Surgical treatment led to a substantial reduction in seizure frequency in most patients. • Reduction in seizure frequency seems to be persistent over time. [ABSTRACT FROM AUTHOR]

Sweden's Animal Welfare Act of 1988 stated that regulations and directives within the law should be in favor of animals' wellbeing, protect them against unnecessary harm, allow them to express their natural behavior, and prevent behavioral disorders. However, ethological studies present several welfare problems found in animals held legally in factory farming settings. By using one of Sweden's most commonly slaughtered animals—the pig—this paper scrutinizes how politicians consider different interests while debating animal living conditions in factory farms. The results demonstrate an overall absence of discussions addressing welfare problems in Swedish pig farming. When such welfare issues are addressed, they are often overlooked in favor of interests that cannot directly be associated with animal welfare. Political claims of having the best animal welfare legislation in the world are used when arguing for decreasing as well as enhancing the living conditions. [ABSTRACT FROM AUTHOR]

In an age where e-commerce can provide a huge variety of different products online, customers still face the issue of the last mile challenge. The purpose of this paper is to find out if the last-mile delivery of products is efficient and explore the possible improvement to this service. This research shows that home delivery is the preferred method of last-mile delivery. A significant gap was disclosed between the available options for delivery on e-commerce websites and consumer preferences of last-mile delivery. Time of delivery and accuracy are the greatest barriers in the delivery chain. The research also shows that there is a lack of home delivery services provided in the market. The research is limited by the usage of non-probability sampling and equal distribution of respondents of all ages. The research identifies a clear gap between customers' demands in the last mile and the firms' offerings. [ABSTRACT FROM AUTHOR]

Denmark and Sweden have an annual cultivation of straw-producing crops on about 16,000 and 11,000 km 2 respectively. However, the actual use of straw for energy differs considerably: 1.35 Tg y −1 in Denmark and 0.11 Tg y −1 in Sweden. The main objective of this study was to investigate why the use of straw for energy is much larger in Denmark than in Sweden. Differences and commonalities in the conditions for the production and use of straw were reviewed. It was shown that both countries have used a large number of governmental support programmes, as well as monetary instruments (e.g. CO 2 -taxes), to promote the use of bioenergy in general. In contrast to Denmark, however, there have been no specific governmental incentives in Sweden directed at increasing the use of straw for energy. One reason may be the vast and relatively low-cost resources of forest biomass in relation to the available resources of straw. The price of competing fuels such as wood chips and wood pellets has generally been 5–15% higher in Denmark than in Sweden. More in depth regional analyses for eastern Denmark and Scania in south Sweden showed that straw production costs are somewhat lower in eastern Denmark as a result of shorter transport distances, earlier ripening of straw-producing crops and better weather conditions during harvest. At present, expert knowledge and the existence of a mature industry favour the large-scale production and use of straw in Denmark. [ABSTRACT FROM AUTHOR]

Background: Reports on outcome after multilobar resection (MLR) are scarce and most are retrospective single-centre studies or case studies with few patients. The aim of this study is to present seizure and complication outcomes 2 years after MLR in a prospective population-based series. Method: The Swedish National Epilepsy Surgery Registry (SNESUR) provides prospective population-based data on outcome and complications after epilepsy surgery. For this study, we have analysed data on seizure outcome and complications after MLR from the SNESUR between 1990 and 2013. Results: Fifty-seven patients underwent MLR; 40/57 surgeries were performed between 1990 and 2000. Sixteen operations were classified as partial hemispherotomy. Resections were right-sided in 33 (58 %) patients. Mean age was 17.3 years (range, 0.3-63.4 years) and mean duration of epilepsy before surgery was 11.0 years (range, 0.2-37 years). Preoperative neurological deficits were seen in 19 patients (33.3 %). Learning disability (LD) was seen in 18 patients (31.6 %), six had severe LD (IQ <50). Seizure outcome after 2 years was available for 53 patients. Thirteen (24.5 %) were seizure-free and 12 (22.6 %) had >75 % seizure frequency reduction. Three (5.3 %) patients suffered major complications: infarction of the middle cerebral artery, epidural abscess and hemiparesis. Minor complications were seen in ten patients. There was no mortality. Conclusions: This prospective, population-based study provides data on seizure outcome and complications after MLR. In selected patients MLR can be considered, but expectations for seizure freedom should not be too high and patients and parents should be counselled appropriately. [ABSTRACT FROM AUTHOR]

Background: Magnetic resonance diffusion tensor imaging (MR-DTI) is used increasingly to detect diffuse axonal injury (DAI) after traumatic brain injury (TBI). Primary objective: The primary objective was to investigate the changes in the diffusion properties of the corpus callosum in the acute phase and 6 months after TBI and to examine the correlation between DTI parameters and clinical outcome. Research design: Longitudinal prospective study. Methods and procedures: MR-DTI was performed in eight patients with suspected DAI within 11 days and at 6 months post-injury. Six controls were also examined. Fractional anisotropy (FA), trace and parallel and perpendicular diffusivity of the corpus callosum were analysed. The main outcome was the extended Glasgow Outcome Scale score, assessed at 6 months. Main outcomes and results: A significant reduction in FA in the corpus callosum was seen in the acute phase in patients compared with the healthy controls. There was no significant change in the parallel or perpendicular eigenvalues or trace. At 6 months, a significant reduction in FA and a significant increase in trace and perpendicular eigenvalues were noticed compared with controls. Conclusions: The diffusion properties of the corpus callosum correlated with clinical outcome in this longitudinal investigation. [ABSTRACT FROM AUTHOR]

Purpose — The aim of this paper is to investigate cross-cultural variations in the demographics of consumers using self-service technologies (SSTs). Design/methodology/approach — Questionnaires were randomly distributed to individuals in Sweden and Estonia to analyze their SST usage and demographic characteristics. Sweden and Estonia were chosen because of their cultural differences — Sweden represents an established Western European market, whereas Estonia, a former Soviet republic, is considered an emerging market. Findings — Data analysis revealed that the demographics of Swedish and Estonian SST users are quite different. Swedish users are demographically heterogeneous, whereas Estonian users can be segmented according to age, gender, education, and income. Research limitations/implications — A larger study conducted in several cultures would add to our knowledge of a culture's influence on an individual's SST usage. Practical implications — As this study shows, business models used in Western markets may not be applicable to emerging markets because of cultural differences. Therefore, it is important that Western firms intending to expand into emerging markets must become aware of cultural differences. Originality/value — Because the world economy is becoming increasingly cross-cultural, it is imperative to conduct international consumer research to further the understanding of SST usage from a global perspective. This paper provides a thorough examination of which, if any, demographical segments of consumers use SSTs and if the demographics of users vary amongst different cultures. [ABSTRACT FROM AUTHOR]

Production of rape methyl ester (RME) can be carried out with different systems solutions, in which the choice of system is usually related to the scale of the production. The purpose of this study was to analyse whether the use of a small-scale RME production system reduced the environmental load in comparison to a medium- and a large-scale system. To fulfil this purpose, a limited LCA, including air-emissions and energy requirements, was carried out for the three plant sizes. For small plants and physical allocation, the global warming potential was 40.3 g CO2-eq/MJfuel, the acidification potential 236 mg SO2-eq/MJfuel, the eutrophication potential 39.1 mg PO43−-eq/MJfuel, the photochemical oxidant creation potential 3.29 mg C2H4-eq/MJfuel and the energy requirement 295 kJ/MJfuel. It was shown that the differences in environmental impact and energy requirement between small-, medium- and large-scale systems were small or even negligible. The higher oil extraction efficiency and the more efficient use of machinery and buildings in the large-scale system were, to a certain degree, outweighed by the longer transport distances. The dominating production step was the cultivation, in which production of fertilisers, soil emissions and tractive power made major contributions to the environmental load. The results were, however, largely dependent on the method used for allocation of the environmental burden between the RME and the by-products meal and glycerine. This indicates that when different biofuels or production strategies are to be compared, it is important that the results are calculated with the same allocation strategies and system limitations. [Copyright &y& Elsevier]

The operation of power-to-X systems requires measures to control the cost and sustainability of electricity purchased from spot markets. This study investigated different bidding strategies for the day-ahead market with a special focus on Sweden. A price independent order (PIO) strategy was developed assisted by forecasting electricity prices with an artificial neural network. For comparison, a price dependent order (PDO) with fixed bid price was used. The bidding strategies were used to simulate H 2 production with both alkaline and proton exchange membrane electrolysers in different years and technological scenarios. Results showed that using PIO to control H 2 production helped to avoid the purchase of expensive and carbon intense electricity during peak loads, but it also reduced the total number of operating hours compared to PDO. For this reason, under optimal conditions for both bidding strategies, PDO resulted in an average of 10.9% lower levelised cost of H 2 , and more attractive cash flows and net present values than PIO. Nevertheless, PIO showed to be a useful strategy to control costs in years with unexpected hourly price behaviour such as 2018. Furthermore, PIO could be successfully demonstrated in a practical case study to fulfil the on-demand requirement of an industrial captive customer. Image 1 • Two bidding strategies to purchase power in a day-ahead scheme were assessed. • Electricity prices at Nord Pool were forecasted with an artificial neural network. • Without price forecasting the PtX system resulted in higher profitability. • Forecasting reduced purchase of expensive power as well as number of run hours. • Proton exchange membrane will outperform alkaline electrolysis no later than 2025. [ABSTRACT FROM AUTHOR]

Background: Spinocerebellar ataxia 4 (SCA4), characterized in 1996, features adult-onset ataxia, polyneuropathy, and linkage to chromosome 16q22.1; its underlying mutation has remained elusive., Objective: To explore the radiological and neuropathological abnormalities in the entire neuroaxis in SCA4 and search for its mutation., Methods: Three Swedish families with undiagnosed ataxia went through clinical, neurophysiological, and neuroimaging tests, including PET studies and genetic investigations. In four cases, neuropathological assessments of the neuroaxis were performed. Genetic testing included short read whole genome sequencing, short tandem repeat analysis with ExpansionHunter de novo, and long read sequencing., Results: Novel features for SCA4 include dysautonomia, motor neuron affection, and abnormal eye movements. We found evidence of anticipation; neuroimaging demonstrated atrophy in the cerebellum, brainstem, and spinal cord. [ 18 F]FDG-PET demonstrated brain hypometabolism and [ 11 C]Flumazenil-PET reduced binding in several brain lobes, insula, thalamus, hypothalamus, and cerebellum. Moderate to severe loss of Purkinje cells in the cerebellum and of motor neurons in the anterior horns of the spinal cord along with pronounced degeneration of posterior tracts was also found. Intranuclear, mainly neuronal, inclusions positive for p62 and ubiquitin were sparse but widespread in the CNS. This finding prompted assessment for nucleotide expansions. A polyglycine stretch encoding GGC expansions in the last exon of the zink finger homeobox 3 gene was identified segregating with disease and not found in 1000 controls., Conclusions: SCA4 is a neurodegenerative disease caused by a novel GGC expansion in the coding region of ZFHX3, and its spectrum is expanded to include dysautonomia and neuromuscular manifestations., (© 2024 The Author(s). Journal of Internal Medicine published by John Wiley & Sons Ltd on behalf of Association for Publication of The Journal of Internal Medicine.)

Introduction: Brain calcifications are frequent findings on imaging. In a small proportion of cases, these calcifications are associated with pathogenic gene variants, hence termed primary familial brain calcification (PFBC). The clinical penetrance is incomplete and phenotypic variability is substantial. This paper aims to characterize a Swedish PFBC cohort including 25 patients: 20 from seven families and five sporadic cases., Methods: Longitudinal clinical assessment and CT imaging were conducted, abnormalities were assessed using the total calcification score (TCS). Genetic analyses, including a panel of six known PFBC genes, were performed in all index and sporadic cases. Additionally, three patients carrying a novel pathogenic copy number variant in SLC20A2 had their cerebrospinal fluid phosphate (CSF-Pi) levels measured., Results: Among the 25 patients, the majority (76%) displayed varying symptoms during the initial assessment including motor (60%), psychiatric (40%), and/or cognitive abnormalities (24%). Clinical progression was observed in most patients (78.6%), but there was no significant difference in calcification between the first and second scans, with mean scores of 27.3 and 32.8, respectively. In three families and two sporadic cases, pathogenic genetic variants were identified, including a novel finding, in the SLC20A2 gene. In the three tested patients, the CSF-Pi levels were normal., Conclusions: This report demonstrates the variable expressivity seen in PFBC and includes a novel pathogenic variant in the SLC20A2 gene. In four families and three sporadic cases, no pathogenic variants were found, suggesting that new PFBC genes remain to be discovered., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest relevant to this work., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

The majority of rare diseases are genetic, and regardless of advanced high-throughput genomics-based investigations, 60% of patients remain undiagnosed. A major factor limiting our ability to identify disease-causing alterations is a poor understanding of the morbid and normal human genome. A major genomic contributor of which function and distribution remain largely unstudied are the transposable elements (TE), which constitute 50% of our genome. Here we aim to resolve this knowledge gap and increase the diagnostic yield of rare disease patients investigated with clinical genome sequencing. To this end we characterized TE insertions in 1000 Swedish individuals from the SweGen dataset and 2504 individuals from the 1000 Genomes Project (1KGP), creating seven population-specific TE insertion databases. Of note, 66% of TE insertions in SweGen were present at >1% in the 1KGP databases, proving that most insertions are common across populations. Focusing on the rare TE insertions, we show that even though ~0.7% of those insertions affect protein coding genes, they rarely affect known disease casing genes (<0.1%). Finally, we applied a TE insertion identification workflow on two clinical cases where disease causing TE insertions were suspected and could verify the presence of pathogenic TE insertions in both. Altogether we demonstrate the importance of TE insertion detection and highlight possible clinical implications in rare disease diagnostics., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Bilgrav Saether et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: We report the findings from 4437 individuals (3219 patients and 1218 relatives) who have been analyzed by whole genome sequencing (WGS) at the Genomic Medicine Center Karolinska-Rare Diseases (GMCK-RD) since mid-2015. GMCK-RD represents a long-term collaborative initiative between Karolinska University Hospital and Science for Life Laboratory to establish advanced, genomics-based diagnostics in the Stockholm healthcare setting., Methods: Our analysis covers detection and interpretation of SNVs, INDELs, uniparental disomy, CNVs, balanced structural variants, and short tandem repeat expansions. Visualization of results for clinical interpretation is carried out in Scout-a custom-developed decision support system. Results from both singleton (84%) and trio/family (16%) analyses are reported. Variant interpretation is done by 15 expert teams at the hospital involving staff from three clinics. For patients with complex phenotypes, data is shared between the teams., Results: Overall, 40% of the patients received a molecular diagnosis ranging from 19 to 54% for specific disease groups. There was heterogeneity regarding causative genes (n = 754) with some of the most common ones being COL2A1 (n = 12; skeletal dysplasia), SCN1A (n = 8; epilepsy), and TNFRSF13B (n = 4; inborn errors of immunity). Some causative variants were recurrent, including previously known founder mutations, some novel mutations, and recurrent de novo mutations. Overall, GMCK-RD has resulted in a large number of patients receiving specific molecular diagnoses. Furthermore, negative cases have been included in research studies that have resulted in the discovery of 17 published, novel disease-causing genes. To facilitate the discovery of new disease genes, GMCK-RD has joined international data sharing initiatives, including ClinVar, UDNI, Beacon, and MatchMaker Exchange., Conclusions: Clinical WGS at GMCK-RD has provided molecular diagnoses to over 1200 individuals with a broad range of rare diseases. Consolidation and spread of this clinical-academic partnership will enable large-scale national collaboration.

Background: Analysis of cell-free tumour DNA, a liquid biopsy, is a promising biomarker for cancer. We have performed a proof-of principle study to test the applicability in the clinical setting, analysing copy number alterations (CNAs) in plasma and tumour tissue from 44 patients with gastro-oesophageal cancer., Methods: DNA was isolated from blood plasma and a tissue sample from each patient. Array-CGH was applied to the tissue DNA. The cell-free plasma DNA was sequenced by low-coverage whole-genome sequencing using a clinical pipeline for non-invasive prenatal testing. WISECONDOR and ichorCNA, two bioinformatic tools, were used to process the output data and were compared to each other., Results: Cancer-associated CNAs could be seen in 59% (26/44) of the tissue biopsies. In the plasma samples, a targeted approach analysing 61 regions of special interest in gastro-oesophageal cancer detected cancer-associated CNAs with a z-score >5 in 11 patients. Broadening the analysis to a whole-genome view, 17/44 patients (39%) had cancer-associated CNAs using WISECONDOR and 13 (30%) using ichorCNA. Of the 26 patients with tissue-verified cancer-associated CNAs, 14 (54%) had corresponding CNAs in plasma. Potentially clinically actionable amplifications overlapping the genes VEGFA, EGFR and FGFR2 were detected in the plasma from three patients., Conclusions: We conclude that low-coverage whole-genome sequencing without prior knowledge of the tumour alterations could become a useful tool for cell-free tumour DNA analysis of total CNAs in plasma from patients with gastro-oesophageal cancer., Competing Interests: The authors have declared that no competing interests exist.

Novel sequences (NSs), not present in the human reference genome, are abundant and remain largely unexplored. Here, we utilize de novo assembly to study NS in 1,000 Swedish individuals first sequenced as part of the SweGen project revealing a total of 46 Mb in 61,044 distinct contigs of sequences not present in GRCh38. The contigs were aligned to recently published catalogs of Icelandic and Pan-African NSs, as well as the chimpanzee genome, revealing a great diversity of shared sequences. Analyzing the positioning of NS across the chimpanzee genome, we find that 2,807 NS align confidently within 143 chimpanzee orthologs of human genes. Aligning the whole genome sequencing data to the chimpanzee genome, we discover ancestral NS common throughout the Swedish population. The NSs were searched for repeats and repeat elements: revealing a majority of repetitive sequence (56%), and enrichment of simple repeats (28%) and satellites (15%). Lastly, we align the unmappable reads of a subset of the thousand genomes data to our collection of NS, as well as the previously published Pan-African NS: revealing that both the Swedish and Pan-African NS are widespread, and that the Swedish NSs are largely a subset of the Pan-African NS. Overall, these results highlight the importance of creating a more diverse reference genome and illustrate that significant amounts of the NS may be of ancestral origin., (© The Author(s) 2019. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.)

Background: The bladder exstrophy-epispadias complex (BEEC) is a congenital malformation of the bladder and urethra. The underlying causes of this malformation are still largely unknown; however, aside from environment, genetics is thought to play an essential role. The recurrent 22q11.2 microduplication is the most persistently detected genetic aberration found in BEEC cases., Methods: We performed array comparative genomic hybridization (array-CGH) analysis of 76 Swedish BEEC patients. Statistical analysis was performed on current dataset pooled with previously published data on the 22q11.2 microduplication in BEEC patients. We performed massive parallel sequencing (MPS) of the 22q11.2 region in 20 BEEC patients without the 22q11.2 microduplication followed by functional studies., Results: We identified three additional cases with the 22q11.2 microduplication. Pooling data from this study with previously published reports showed a statistically significant enrichment of the 22q11.2 microduplication in BEEC patients (2.61% in cases vs. 0.08% in controls; OR = 32.6; p = 8.7 × 10 -4 ). MPS of the 22q11.2 region in 20 BEEC patients without the 22q11.2 microduplication identified a novel variant in LZTR1 (p.Ser698Phe) in one patient. Functional evaluation of the LZTR1 p.Ser698Phe variant in live NIH 3T3 cells showed that the concentration and cytoplasmic mobility differ between the Lztr1 wt and Lztr1 mut , indicating a potential functional effect of the LZTR1 mut ., Conclusion: Our study further emphasizes the involvement of the 22q11.2 region in BEEC development and highlights LZTR1 as a candidate gene underlying the urogenital malformation., (© 2019 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.)

The incidence of stillbirth in Sweden has essentially remained constant since the 1980's, and despite thorough investigation, many cases remain unexplained. It has been suggested that a proportion of stillbirth cases is caused by heart disease, mainly channelopathies. The aim of this study was to analyze DNA from 290 stillbirth cases without chromosomal abnormalities for pathogenic single nucleotide variants (SNVs) in 70 genes associated with cardiac channelopathies and cardiomyopathies. The HaloPlex Target Enrichment System (Agilent Technologies) was utilized to prepare sequencing libraries which were sequenced on the Illumina NextSeq platform. We found that 12.1% of the 290 investigated stillbirth cases had one (n = 31) or two (n = 4) variants with evidence supporting pathogenicity, i.e. loss-of-function variants (nonsense, frameshift, splice site substitutions), evidence from functional studies, or previous identification of the variants in affected individuals. Regarding identified putative pathogenic variants in genes associated with channelopathies, the prevalence was significantly higher in the stillbirth cohort (n = 23, 7.93%) than the corresponding prevalence of the same variants in the non-Finnish European population of the Exome Aggregation Consortium (2.70%, p<0.001) and SweGen, (2.30%, p<0.001). Our results give further support to the hypothesis that cardiac channelopathies might contribute to stillbirth. Screening for pathogenic SNVs in genes associated with heart disease might be a valuable complement for stillbirth cases where today's conventional investigation does not reveal the underlying cause of fetal demise., Competing Interests: The authors have declared that no competing interests exist.

Object: In this study, the authors' goal was to compare head circumference in hydrocephalic children during the first 4 years of ventriculoperitoneal (VP) shunt treatment with data on healthy children and to investigate predictors of skull growth in children with a VP shunt., Methods: Children from western Sweden treated for hydrocephalus with an initial VP shunt insertion performed between 2001 and 2006 who were younger than 12 months of age at the time of surgery were included. Children with major brain malformations, craniofacial syndromes, large cysts, and tumors were excluded. Head circumference, weight, and height at 9 defined ages up to 4 years were obtained and compared with data from a reference population of 3650 healthy children using the standard deviation score (SDS). Predictors (length, weight, etiology of hydrocephalus, valve type, number of revisions, valve setting, number of adjustments, and time of first surgery) for head circumference SDS and changes in head circumference SDS from shunt insertion at 1 year to last measurement were analyzed using bivariate and multiple linear regression analysis., Results: Fifty children were included. The mean SDSs for head circumference in shunt-treated compared with healthy children were 1.95 ± 2.50 at shunt insertion (p < 0.001, n = 44), 0.38 ± 1.97 at 1 year (p = 0.27, n = 33), -0.96 ± 2.05 at 2 years (p = 0.046, n = 21), -1.39 ± 2.25 at 3 years (p = 0.026, n = 16), and 0.63 ± 3.34 at 4 years (p = 0.73, n = 4). Significant predictors for low head circumference SDS at 1 year of age were low weight (p = 0.002) and short height (p = 0.022) and at last measurement low weight (p < 0.0001), short height (p = 0.002), and 1-4 shunt revisions (p = 0.034). A significant predictor for change in head circumference SDS from shunt insertion to 1 year of age was the number of shunt valve revisions (p = 0.04) and at last measurement an etiology of intraventricular hemorrhage (p = 0.0058)., Conclusions: Shunt-treated children have smaller head circumferences at 2 and 3 years of age than healthy children. Low weight, short height, etiology of intraventricular hemorrhage, and frequent shunt valve revisions are predictors for decreased head circumference. Prospective, randomized studies comparing skull growth using fixed and adjustable pressure-regulated shunt valves and flow-regulated valves are needed.

Replication of reported associations is crucial to the investigation of complex disease. More than 100 SNPs have previously been reported as associated with allergic rhinitis (AR), but few of these have been replicated successfully. To investigate the general reproducibility of reported AR-associations in candidate gene studies, one Swedish (352 AR-cases, 709 controls) and one Singapore Chinese population (948 AR-cases, 580 controls) were analyzed using 49 AR-associated SNPs. The overall pattern of P-values indicated that very few of the investigated SNPs were associated with AR. Given published odds ratios (ORs) most SNPs showed high power to detect an association, but no correlations were found between the ORs of the two study populations or with published ORs. None of the association signals were in common to the two genome-wide association studies published in AR, indicating that the associations represent false positives or have much lower effect-sizes than reported.

Background: The Toll-like receptor proteins are important in host defense and initiation of the innate and adaptive immune responses. A number of studies have identified associations between genetic variation in the Toll-like receptor genes and allergic disorders such as asthma and allergic rhinitis. The present study aim to search for genetic variation associated with allergic rhinitis in the Toll-like receptor genes., Methods: A first association analysis genotyped 73 SNPs in 182 cases and 378 controls from a Swedish population. Based on these results an additional 24 SNPs were analyzed in one Swedish population with 352 cases and 709 controls and one Chinese population with 948 cases and 580 controls., Results: The first association analysis identified 4 allergic rhinitis-associated SNPs in the TLR7-TLR8 gene region. Subsequent analysis of 24 SNPs from this region identified 7 and 5 significant SNPs from the Swedish and Chinese populations, respectively. The corresponding risk-associated haplotypes are significant after Bonferroni correction and are the most common haplotypes in both populations. The associations are primarily detected in females in the Swedish population, whereas it is seen in males in the Chinese population. Further independent support for the involvement of this region in allergic rhinitis was obtained from quantitative skin prick test data generated in both populations., Conclusions: Haplotypes in the TLR7-TLR8 gene region were associated with allergic rhinitis in one Swedish and one Chinese population. Since this region has earlier been associated with asthma and allergic rhinitis in a Danish linkage study this speaks strongly in favour of this region being truly involved in the development of this disease.