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- Rayner, C, et al.
(författare)
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A genome-wide association meta-analysis of prognostic outcomes following cognitive behavioural therapy in individuals with anxiety and depressive disorders
- 2019
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Ingår i: Translational psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 9:1, s. 150-
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Tidskriftsartikel (refereegranskat)abstract
- Major depressive disorder and the anxiety disorders are highly prevalent, disabling and moderately heritable. Depression and anxiety are also highly comorbid and have a strong genetic correlation (rg ≈ 1). Cognitive behavioural therapy is a leading evidence-based treatment but has variable outcomes. Currently, there are no strong predictors of outcome. Therapygenetics research aims to identify genetic predictors of prognosis following therapy. We performed genome-wide association meta-analyses of symptoms following cognitive behavioural therapy in adults with anxiety disorders (n = 972), adults with major depressive disorder (n = 832) and children with anxiety disorders (n = 920; meta-analysis n = 2724). We estimated the variance in therapy outcomes that could be explained by common genetic variants (h2SNP) and polygenic scoring was used to examine genetic associations between therapy outcomes and psychopathology, personality and learning. No single nucleotide polymorphisms were strongly associated with treatment outcomes. No significant estimate of h2SNP could be obtained, suggesting the heritability of therapy outcome is smaller than our analysis was powered to detect. Polygenic scoring failed to detect genetic overlap between therapy outcome and psychopathology, personality or learning. This study is the largest therapygenetics study to date. Results are consistent with previous, similarly powered genome-wide association studies of complex traits.
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- Wells, Jerry M., et al.
(författare)
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Homeostasis of the Gut Barrier and Potential Biomarkers
- 2017
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Ingår i: American Journal of Physiology - Gastrointestinal and Liver Physiology. - Bethesda, USA : American Physiological Society. - 0193-1857 .- 1522-1547. ; 312:3, s. G171-G193
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Tidskriftsartikel (refereegranskat)abstract
- The gut barrier plays a crucial role by spatially compartmentalizing bacteria to the lumen through the production of secreted mucus and is fortified by the production of sIgA and antimicrobial peptides and proteins. With exception of sIgA the expression of these protective barrier factors is largely controlled by innate immune recognition of microbial molecular ligands. Several specialized adaptations and checkpoints are operating in the mucosa to scale the immune response according to the threat and prevent overreaction to the trillions of symbionts inhabiting the human intestine. A healthy microbiota plays a key role influencing epithelial barrier functions. However, perturbation of gut barrier homeostasis can lead to increased inflammatory signaling, increased epithelial permeability and dysbiosis of the microbiota, which are recognized to play a role in the pathophysiology of gastrointestinal disorders. Additionally, the gut-brain signaling may be affected by prolonged mucosal immune activation, leading to increased afferent sensory signaling and abdominal symptoms. In turn, neuronal mechanisms can affect the intestinal barrier partly by activation of the HPA-axis and both mast cell-dependent as well as mast cell- independent mechanisms. Several biomarkers have been used to measure gut permeability and loss of barrier integrity in patients but there remains a need to explore their use in assessing impact of nutritional factors on gut barrier function. Future studies should aim to establish normal ranges of the available biomarkers and their predictive value for gut health in human cohorts.
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- Abdulaziz, Mohammed, et al.
(författare)
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Improving Receiver Close-In Blocker Tolerance by Baseband Gm-C Notch Filtering
- 2019
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Ingår i: IEEE Transactions on Circuits and Systems I: Regular Papers. - 1549-8328. ; 66:3, s. 885-896
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Tidskriftsartikel (refereegranskat)abstract
- This paper presents a receiver front end with improved blocker handling implemented in a 65-nm CMOS technology. Since close-in blockers are challenging to reject at RF, the receiver features a baseband (BB) notch filter, which effectively sinks close-in blocker current directly from the output of an LNTA and passive mixer structure. The notch-filter frequency can be tuned to match the blocker offset frequency, and the measurements indicate a significant improvement in the overall front-end interference robustness, while sensitivity remains unaffected. To optimize notch performance, the BB impedance is analyzed in detail. The front-end RF range is 750 MHz-3 GHz with an RF channel bandwidth of 20 MHz corresponding to 10-MHz BB bandwidth. The notch frequency is programmable from 16, which is less than one octave from the channel edge, up to 160 MHz. The gain-compression improvement is upto 9 dB, while IIP2 can be increased by more than 26 dB without calibration and IIP3 is 1 dBm. The current overhead for the notch function is between 7.5 and 30 mA, but it only exists under strong blocker conditions as the notch filter can be switched off if strong blockers are absent. The total front-end current consumption excluding the notch filter varies with LO frequency from 31 to 44 mA from a 1.2-V supply.
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