38 research outputs found
Uncovering the heterogeneity and temporal complexity of neurodegenerative diseases with Subtype and Stage Inference
The heterogeneity of neurodegenerative diseases is a key confound to disease understanding and treatment development, as study cohorts typically include multiple phenotypes on distinct disease trajectories. Here we introduce a machine-learning technique\u2014Subtype and Stage Inference (SuStaIn)\u2014able to uncover data-driven disease phenotypes with distinct temporal progression patterns, from widely available cross-sectional patient studies. Results from imaging studies in two neurodegenerative diseases reveal subgroups and their distinct trajectories of regional neurodegeneration. In genetic frontotemporal dementia, SuStaIn identifies genotypes from imaging alone, validating its ability to identify subtypes; further the technique reveals within-genotype heterogeneity. In Alzheimer\u2019s disease, SuStaIn uncovers three subtypes, uniquely characterising their temporal complexity. SuStaIn provides fine-grained patient stratification, which substantially enhances the ability to predict conversion between diagnostic categories over standard models that ignore subtype (p = 7.18
7 10 124 ) or temporal stage (p = 3.96
7 10 125 ). SuStaIn offers new promise for enabling disease subtype discovery and precision medicine
Accelarated immune ageing is associated with COVID-19 disease severity
Background
The striking increase in COVID-19 severity in older adults provides a clear example of immunesenescence, the age-related remodelling of the immune system. To better characterise the association between convalescent immunesenescence and acute disease severity, we determined the immune phenotype of COVID-19 survivors and non-infected controls.
Results
We performed detailed immune phenotyping of peripheral blood mononuclear cells isolated from 103 COVID-19 survivors 3–5 months post recovery who were classified as having had severe (n = 56; age 53.12 ± 11.30 years), moderate (n = 32; age 52.28 ± 11.43 years) or mild (n = 15; age 49.67 ± 7.30 years) disease and compared with age and sex-matched healthy adults (n = 59; age 50.49 ± 10.68 years). We assessed a broad range of immune cell phenotypes to generate a composite score, IMM-AGE, to determine the degree of immune senescence. We found increased immunesenescence features in severe COVID-19 survivors compared to controls including: a reduced frequency and number of naïve CD4 and CD8 T cells (p < 0.0001); increased frequency of EMRA CD4 (p < 0.003) and CD8 T cells (p < 0.001); a higher frequency (p < 0.0001) and absolute numbers (p < 0.001) of CD28−ve CD57+ve senescent CD4 and CD8 T cells; higher frequency (p < 0.003) and absolute numbers (p < 0.02) of PD-1 expressing exhausted CD8 T cells; a two-fold increase in Th17 polarisation (p < 0.0001); higher frequency of memory B cells (p < 0.001) and increased frequency (p < 0.0001) and numbers (p < 0.001) of CD57+ve senescent NK cells. As a result, the IMM-AGE score was significantly higher in severe COVID-19 survivors than in controls (p < 0.001). Few differences were seen for those with moderate disease and none for mild disease. Regression analysis revealed the only pre-existing variable influencing the IMM-AGE score was South Asian ethnicity (
= 0.174, p = 0.043), with a major influence being disease severity (
= 0.188, p = 0.01).
Conclusions
Our analyses reveal a state of enhanced immune ageing in survivors of severe COVID-19 and suggest this could be related to SARS-Cov-2 infection. Our data support the rationale for trials of anti-immune ageing interventions for improving clinical outcomes in these patients with severe disease
Prediction of Turbulence Generated Random Vibrational Response of Turbomachinery Blading
Are sequence family variants useful for identifying deletions in the human Y chromosome [lettet
Comparison of ureteroscopy (URS) complementary treatment after extracorporeal shock wave lithotripsy failure with primary URS lithotripsy with holmium laser treatment for proximal ureteral stones larger than10mm
Abstract Background To compare ureteroscopy (URS) complementary treatment following extracorporeal shock wave lithotripsy (SWL) failure with primary URS lithotripsy for proximal ureteral stones > 10 mm, and try to find out acceptable number of SWL sessions followed by safe URS. Methods This was a retrospective study following approval from Medical Ethics Committee of People's Hospital of Chongqing Banan District. Patients (n = 340) who received URS in our hospital for stones > 10 mm from Jan 2015 to June 2020 were divided into two groups according to their previous SWL history. Group 1 consisted of 160 patients that underwent unsuccessful SWL before URS. Group 2 encompassed 180 patients without SWL before URS. Patient’s operative outcomes were compared. A logistic regression and receiver operator characteristics (ROC) were used to identify the acceptable number of SWL sessions prior to URS, regarding the intra-operative complications of URS. Results The group 1 required more surgery time (41.38 ± 11.39 min vs. 36.43 ± 13.36 min, p = 0.01). At the same time, more intra-operative (68.1% VS 22.8%, p 0.05). The median (25–75%) of SWL sessions before URS was 2 (1–3) in group 1. According to the results of logistic regression analysis, patients suffered more SWL failure have an increased risk of complications during URS (OR = 1.995, 95% CI: 1.636–2.434). ROC showed that the optimal number of SWL session followed by URS were 0.5, with a sensitivity of 67.7% and specificity of 71.5%. Intra-operative complication rates of URS treatment were higher in patients who suffered > 1 SWL failure (72.6% vs 57.4%, p = 0.047). Conclusion There was no acceptable number of SWL sessions that could be followed by URS with fewer intra-operative complications. Patients who underwent previous SWL were likely to suffer more intra-operative complications, the average operating time, hospitalization time, and needing further treatment, during URS treatment for proximal ureteral stones larger than 10 mm
AZFc deletions and spermatogenic failure: A population-based survey of 20,000 y chromosomes
10.1016/j.ajhg.2012.09.003American Journal of Human Genetics915890-896AJHG