| 1. |
- Lindström, Sara, et al.
(författare)
-
Genome-wide analyses characterize shared heritability among cancers and identify novel cancer susceptibility regions
- 2023
-
Ingår i: Journal of the National Cancer Institute. - : Oxford University Press. - 0027-8874 .- 1460-2105. ; 115:6, s. 712-732
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The shared inherited genetic contribution to risk of different cancers is not fully known. In this study, we leverage results from 12 cancer genome-wide association studies (GWAS) to quantify pairwise genome-wide genetic correlations across cancers and identify novel cancer susceptibility loci.METHODS: We collected GWAS summary statistics for 12 solid cancers based on 376 759 participants with cancer and 532 864 participants without cancer of European ancestry. The included cancer types were breast, colorectal, endometrial, esophageal, glioma, head and neck, lung, melanoma, ovarian, pancreatic, prostate, and renal cancers. We conducted cross-cancer GWAS and transcriptome-wide association studies to discover novel cancer susceptibility loci. Finally, we assessed the extent of variant-specific pleiotropy among cancers at known and newly identified cancer susceptibility loci.RESULTS: We observed widespread but modest genome-wide genetic correlations across cancers. In cross-cancer GWAS and transcriptome-wide association studies, we identified 15 novel cancer susceptibility loci. Additionally, we identified multiple variants at 77 distinct loci with strong evidence of being associated with at least 2 cancer types by testing for pleiotropy at known cancer susceptibility loci.CONCLUSIONS: Overall, these results suggest that some genetic risk variants are shared among cancers, though much of cancer heritability is cancer-specific and thus tissue-specific. The increase in statistical power associated with larger sample sizes in cross-disease analysis allows for the identification of novel susceptibility regions. Future studies incorporating data on multiple cancer types are likely to identify additional regions associated with the risk of multiple cancer types.
|
|
| 2. |
- Checketts, Matthew, et al.
(författare)
-
Current clinical practice in the screening and diagnosis of spatial neglect post-stroke : findings from a multidisciplinary international survey
- 2021
-
Ingår i: Neuropsychological rehabilitation (Print). - : Routledge. - 0960-2011 .- 1464-0694. ; 31:9, s. 1495-1526
-
Tidskriftsartikel (refereegranskat)abstract
- Spatial neglect has profound implications for quality of life after stroke, yet we lack consensus for screening/diagnosing this heterogeneous syndrome. Our first step in a multi-stage research programme aimed to determine which neglect tests are used (within four categories: cognitive, functional, neurological and neuroimaging/neuromodulation), by which stroke clinicians, in which countries, and whether choice is by professional autonomy or institutional policy. 454 clinicians responded to an online survey: 12 professions (e.g., 39% were occupational therapists) from 33 countries (e.g., 38% from the UK). Multifactorial logistic regression suggested inter-professional differences but fewer differences between countries (Italy was an outlier). Cognitive tests were used by 82% (particularly by psychologists, cancellation and drawing were most popular); 80% used functional assessments (physiotherapists were most likely). 20% (mainly physicians, from Italy) used neuroimaging/ neuromodulation. Professionals largely reported clinical autonomy in their choices. Respondents agreed on the need for a combined approach to screening and further training. This study raises awareness of the translation gap between theory and practice. These findings lay an important foundation to subsequent collaborative action between clinicians, researchers and stroke survivors to reach consensus on screening and diagnostic measures. The immediate next step is a review of the measures' psychometric properties.
|
|
| 3. |
- Itzhaki, Ruth F., et al.
(författare)
-
Microbes and Alzheimer's Disease
- 2016
-
Ingår i: Journal of Alzheimer's Disease. - 1387-2877 .- 1875-8908. ; 51:4, s. 979-984
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- We are researchers and clinicians working on Alzheimer’s disease (AD) or related topics, and we write to express our concern that one particular aspect of the disease has been neglected, even though treatment based on it might slow or arrest AD progression. We refer to the many studies, mainly on humans, implicating specific microbes in the elderly brain, notably herpes simplex virus type 1 (HSV1), Chlamydia pneumoniae, and several types of spirochaete, in the etiology of AD [1–4]. Fungal infection of AD brain [5, 6] has also been described, as well as abnormal microbiota in AD patient blood [7]. The first observations of HSV1 in AD brain were reported almost three decades ago [8]. The ever-increasing number of these studies (now about 100 on HSV1 alone) warrants re-evaluation of the infection and AD concept.AD is associated with neuronal loss and progressive synaptic dysfunction, accompanied by the deposition of amyloid-β (Aβ) peptide, a cleavage product of the amyloid-β protein precursor (AβPP), and abnormal forms of tau protein, markers that have been used as diagnostic criteria for the disease [9, 10]. These constitute the hallmarks of AD, but whether they are causes of AD or consequences is unknown. We suggest that these are indicators of an infectious etiology. In the case of AD, it is often not realized that microbes can cause chronic as well as acute diseases; that some microbes can remain latent in the body with the potential for reactivation, the effects of which might occur years after initial infection; and that people can be infected but not necessarily affected, such that ‘controls’, even if infected, are asymptomatic
|
|
| 4. |
- Itzhaki, Ruth F., et al.
(författare)
-
Microbes and Alzheimer's disease
- 2017
-
Ingår i: Handbook of infection and Alzheimer's disease. - : IOS Press. - 9781614997054 - 9781614997061 ; , s. 3-8
-
Bokkapitel (refereegranskat)
|
|
| 5. |
- Rich, Timothy J., et al.
(författare)
-
An international and multidisciplinary consensus on the labeling of spatial neglect using a modified Delphi method
- 2024
-
Ingår i: Archives of Rehabilitation Research and Clinical Translation. - : Elsevier. - 2590-1095. ; 6:2
-
Tidskriftsartikel (refereegranskat)abstract
- Survivors of neurologic injury (most commonly stroke or traumatic brain injury) frequently experience a disorder in which contralesionally positioned objects or the contralesional features of individual objects are often left unattended or underappreciated. The disorder is known by >200 unique labels in the literature, which potentially causes confusion for patients and their families, complicates literature searches for researchers and clinicians, and promotes a fractionated conceptualization of the disorder. The objective of this Delphi was to determine if consensus (≥75% agreement) could be reached by an international and multidisciplinary panel of researchers and clinicians with expertise on the topic.To accomplish this aim, we used a modified Delphi method in which 66 researchers and/or clinicians with expertise on the topic completed at least 1 of 4 iterative rounds of surveys. Per the Delphi method, panelists were provided with results from each round prior to responding to the survey in the subsequent round with the explicit intention of achieving consensus. The panel ultimately reached consensus that the disorder should be consistently labeled spatial neglect. Based on the consensus reached by our expert panel, we recommend that researchers and clinicians use the label spatial neglect when describing the disorder in general and more specific labels pertaining to subtypes of the disorder when appropriate.
|
|
