| 1. |
- Szatmari, Peter, et al.
(författare)
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Mapping autism risk loci using genetic linkage and chromosomal rearrangements.
- 2007
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 39:3, s. 319-328
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Tidskriftsartikel (refereegranskat)abstract
- Autism spectrum disorders (ASDs) are common, heritable neurodevelopmental conditions. The genetic architecture of ASDs is complex, requiring large samples to overcome heterogeneity. Here we broaden coverage and sample size relative to other studies of ASDs by using Affymetrix 10K SNP arrays and 1,168 families with at least two affected individuals, performing the largest linkage scan to date while also analyzing copy number variation in these families. Linkage and copy number variation analyses implicate chromosome 11p12-p13 and neurexins, respectively, among other candidate loci. Neurexins team with previously implicated neuroligins for glutamatergic synaptogenesis, highlighting glutamate-related genes as promising candidates for contributing to ASDs.
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| 2. |
- Bartlett, Jonathan W, et al.
(författare)
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Determining cut-points for Alzheimer's disease biomarkers: statistical issues, methods and challenges.
- 2012
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Ingår i: Biomarkers in medicine. - : Future Medicine Ltd. - 1752-0371 .- 1752-0363. ; 6:4, s. 391-400
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Tidskriftsartikel (refereegranskat)abstract
- New proposed criteria for the clinical diagnosis of Alzheimer's disease increasingly incorporate biomarkers, most of which are normally measured on a continuous scale. Operationalizing such criteria thus requires continuous biomarkers to be dichotomized, which in turns requires the selection of a cut-point at which to dichotomize. In this article, we review the statistical principles underlying the choice of cut-points, describe some of the most commonly adopted statistical approaches used to estimate cut-points, highlight potential pitfalls in some of the approaches and characterize in what sense the estimated cut-point from each approach is optimal. We also emphasize that how a cut-point is selected must be made in reference to how the resulting dichotomized biomarker is to be used, and in particular what actions will follow from a positive or negative test result.
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| 3. |
- Skillbäck, Tobias, et al.
(författare)
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CSF neurofilament light differs in neurodegenerative diseases and predicts severity and survival.
- 2014
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Ingår i: Neurology. - 1526-632X .- 0028-3878. ; 83:21, s. 1945-53
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Tidskriftsartikel (refereegranskat)abstract
- We hypothesized that CSF neurofilament light (NFL) levels would be elevated in dementias with subcortical involvement, including vascular dementia (VaD), but less elevated in dementias primarily affecting gray matter structures, such as Alzheimer disease (AD), and that elevated CSF NFL would correlate with disease severity and shorter survival time irrespective of clinical diagnosis.
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| 4. |
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| 5. |
- Gonzalez-Ericsson, Paula, et al.
(författare)
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The path to a better biomarker: application of a risk management framework for the implementation of PD‐L1 and TILs as immuno‐oncology biomarkers into breast cancer clinical trials and daily practice
- 2020
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Ingår i: Journal of Pathology. - : Wiley. - 1096-9896 .- 0022-3417. ; 250:5, s. 667-684
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Forskningsöversikt (refereegranskat)abstract
- Immune checkpoint inhibitor therapies targeting PD‐1/PD‐L1 are now the standard of care in oncology across several hematologic and solid tumor types, including triple negative breast cancer (TNBC). Patients with metastatic or locally advanced TNBC with PD‐L1 expression on immune cells occupying ≥1% of tumor area demonstrated survival benefit with the addition of atezolizumab to nab‐paclitaxel. However, concerns regarding variability between immunohistochemical PD‐L1 assay performance and inter‐reader reproducibility have been raised. High tumor‐infiltrating lymphocytes (TILs) have also been associated with response to PD‐1/PD‐L1 inhibitors in patients with breast cancer (BC). TILs can be easily assessed on hematoxylin and eosin–stained slides and have shown reliable inter‐reader reproducibility. As an established prognostic factor in early stage TNBC, TILs are soon anticipated to be reported in daily practice in many pathology laboratories worldwide. Because TILs and PD‐L1 are parts of an immunological spectrum in BC, we propose the systematic implementation of combined PD‐L1 and TIL analyses as a more comprehensive immuno‐oncological biomarker for patient selection for PD‐1/PD‐L1 inhibition‐based therapy in patients with BC. Although practical and regulatory considerations differ by jurisdiction, the pathology community has the responsibility to patients to implement assays that lead to optimal patient selection. We propose herewith a risk‐management framework that may help mitigate the risks of suboptimal patient selection for immuno‐therapeutic approaches in clinical trials and daily practice based on combined TILs/PD‐L1 assessment in BC.
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| 6. |
- Khanolkar, Amal, et al.
(författare)
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Socioeconomic and early-life factors and risk of being overweight or obese in children of Swedish- and foreign-born parents
- 2013
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Ingår i: Pediatric Research. - : Springer Science and Business Media LLC. - 0031-3998 .- 1530-0447. ; 74:3, s. 356-363
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Ethnic minorities/immigrants have differential health as compared with natives. The epidemic in child overweight/obesity (OW/OB) in Sweden is leveling oft but lower socioeconomic groups and immigrants/ethnic minorities may not have benefited equally from this trend. We investigated whether nonethnic Swedish children are at increased risk for being OW/OB and whether these associations are mediated by parental socioeconomic position (SEP) and/or early-life factors such as birth weight, maternal smoking, BMI, and breastfeeding. METHODS: Data on 10,628 singleton children (51% boys, mean age: 4.8 y, born during the period 2000-2004) residing in Uppsala were analyzed. OW/OB was computed using the International Obesity Task Force's sex- and age-specific cutoffs. The mother's nativity was used as proxy for ethnicity. Logistic regression was used to analyze ethnicity-OW/OB associations. RESULTS: Children of North African, Iranian, South American, and Turkish ethnicity had increased odds for being overweight/obese as compared with children of Swedish ethnicity (adjusted odds ratio (OR): 2.60 (95% confidence interval (CI): 1.57-4.27), 1.67 (1.03-2.72), 3.00 (1.86-4.80), and 2.90 (1.73-4.88), respectively). Finnish children had decreased odds for being overweight/obese (adjusted OR: 0.53 (0.32-0.90)). CONCLUSION: Ethnic differences in a child's risk for OW/OB exist in Sweden that cannot be explained by SEP or maternal or birth factors. As OW/OB often tracks into adulthood, more effective public health policies that intervene at an early age are needed.
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| 7. |
- Markmann, James F., et al.
(författare)
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Executive Summary of IPITA-TTS Opinion Leaders Report on the Future of beta-Cell Replacement
- 2016
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Ingår i: Transplantation. - 0041-1337 .- 1534-6080. ; 100:7, s. E25-E31
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Forskningsöversikt (refereegranskat)abstract
- The International Pancreas and Islet Transplant Association (IPITA), in conjunction with the Transplantation Society (TTS), convened a workshop to consider the future of pancreas and islet transplantation in the context of potential competing technologies that are under development, including the artificial pancreas, transplantation tolerance, xenotransplantation, encapsulation, stem cell derived beta cells, beta cell proliferation, and endogenous regeneration. Separate workgroups for each topic and then the collective group reviewed the state of the art, hurdles to application, and proposed research agenda for each therapy that would allow widespread application. Herein we present the executive summary of this workshop that focuses on obstacles to application and the research agenda to overcome them; the full length article with detailed background for each topic is published as an online supplement to Transplantation.
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