| 1. |
- Brownstein, Catherine A., et al.
(författare)
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An international effort towards developing standards for best practices in analysis, interpretation and reporting of clinical genome sequencing results in the CLARITY Challenge
- 2014
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Ingår i: Genome Biology. - : Springer Science and Business Media LLC. - 1465-6906 .- 1474-760X. ; 15:3, s. R53-
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Tidskriftsartikel (refereegranskat)abstract
- Background: There is tremendous potential for genome sequencing to improve clinical diagnosis and care once it becomes routinely accessible, but this will require formalizing research methods into clinical best practices in the areas of sequence data generation, analysis, interpretation and reporting. The CLARITY Challenge was designed to spur convergence in methods for diagnosing genetic disease starting from clinical case history and genome sequencing data. DNA samples were obtained from three families with heritable genetic disorders and genomic sequence data were donated by sequencing platform vendors. The challenge was to analyze and interpret these data with the goals of identifying disease-causing variants and reporting the findings in a clinically useful format. Participating contestant groups were solicited broadly, and an independent panel of judges evaluated their performance. Results: A total of 30 international groups were engaged. The entries reveal a general convergence of practices on most elements of the analysis and interpretation process. However, even given this commonality of approach, only two groups identified the consensus candidate variants in all disease cases, demonstrating a need for consistent fine-tuning of the generally accepted methods. There was greater diversity of the final clinical report content and in the patient consenting process, demonstrating that these areas require additional exploration and standardization. Conclusions: The CLARITY Challenge provides a comprehensive assessment of current practices for using genome sequencing to diagnose and report genetic diseases. There is remarkable convergence in bioinformatic techniques, but medical interpretation and reporting are areas that require further development by many groups.
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| 2. |
- Cooper, Alan, et al.
(författare)
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A global environmental crisis 42,000 years ago
- 2021
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 371:6531, s. 811-818
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Tidskriftsartikel (refereegranskat)abstract
- Geological archives record multiple reversals of Earth’s magnetic poles, but the global impacts of these events, if any, remain unclear. Uncertain radiocarbon calibration has limited investigation of the potential effects of the last major magnetic inversion, known as the Laschamps Excursion [41 to 42 thousand years ago (ka)]. We use ancient New Zealand kauri trees (Agathis australis) to develop a detailed record of atmospheric radiocarbon levels across the Laschamps Excursion. We precisely characterize the geomagnetic reversal and perform global chemistry-climate modeling and detailed radiocarbon dating of paleoenvironmental records to investigate impacts. We find that geomagnetic field minima ~42 ka, in combination with Grand Solar Minima, caused substantial changes in atmospheric ozone concentration and circulation, driving synchronous global climate shifts that caused major environmental changes, extinction events, and transformations in the archaeological record.
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| 3. |
- Cooper, Alan, et al.
(författare)
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Response to comment on “A global environmental crisis 42,000 years ago”
- 2021
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 374:6570
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Tidskriftsartikel (refereegranskat)abstract
- Our paper about the impacts of the Laschamps Geomagnetic Excursion 42,000 years ago has provoked considerable scientific and public interest, particularly in the so-called Adams Event associated with the initial transition of the magnetic poles. Although we welcome the opportunity to discuss our new ideas, Hawks’ assertions of misrepresentation are especially disappointing given his limited examination of the material.
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| 4. |
- Jung, Christian, et al.
(författare)
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A comparison of very old patients admitted to intensive care unit after acute versus elective surgery or intervention
- 2019
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Ingår i: Journal of critical care. - : W B SAUNDERS CO-ELSEVIER INC. - 0883-9441 .- 1557-8615. ; 52, s. 141-148
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Tidskriftsartikel (refereegranskat)abstract
- Background: We aimed to evaluate differences in outcome between patients admitted to intensive care unit (ICU) after elective versus acute surgery in a multinational cohort of very old patients (80 years; VIP). Predictors of mortality, with special emphasis on frailty, were assessed.Methods: In total, 5063 VIPs were induded in this analysis, 922 were admitted after elective surgery or intervention, 4141 acutely, with 402 after acute surgery. Differences were calculated using Mann-Whitney-U test and Wilcoxon test. Univariate and multivariable logistic regression were used to assess associations with mortality.Results: Compared patients admitted after acute surgery, patients admitted after elective surgery suffered less often from frailty as defined as CFS (28% vs 46%; p < 0.001), evidenced lower SOFA scores (4 +/- 5 vs 7 +/- 7; p < 0.001). Presence of frailty (CFS >4) was associated with significantly increased mortality both in elective surgery patients (7% vs 12%; p = 0.01), in acute surgery (7% vs 12%; p = 0.02).Conclusions: VIPs admitted to ICU after elective surgery evidenced favorable outcome over patients after acute surgery even after correction for relevant confounders. Frailty might be used to guide clinicians in risk stratification in both patients admitted after elective and acute surgery.
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| 6. |
- Shen, Pamela, et al.
(författare)
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Cigarette smoke attenuates the nasal host response to Streptococcus pneumoniae and predisposes to invasive pneumococcal disease in mice.
- 2016
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Ingår i: Infection and Immunity. - 1098-5522. ; 84:5, s. 1536-1547
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Tidskriftsartikel (refereegranskat)abstract
- Streptococcus pneumoniae is a leading cause of invasive bacterial infections, with nasal colonization an important first step for disease. While cigarette smoking is a strong risk factor for invasive pneumococcal disease, underlying mechanisms remain unknown. This is partly due to a lack of clinically relevant animal models investigating nasal pneumococcal colonization in the context of cigarette smoke exposure. We present a model of nasal pneumococcal colonization in cigarette smoke-exposed mice and document, for the first time, that cigarette smoke predisposes to invasive pneumococcal infection and mortality in an animal model. Cigarette smoke increased the risk of bacteraemia and meningitis without prior lung infection. Mechanistically, deficiency in IL-1α or PAFR, an important host receptor thought to bind and facilitate pneumococcal invasiveness, did not rescue cigarette smoke-exposed mice from invasive pneumococcal disease. Importantly, we observed cigarette smoke to attenuate nasal inflammatory mediator expression, particularly that of neutrophil recruiting chemokines, normally elicited by pneumococcal colonization. Smoking cessation during nasal pneumococcal colonization rescued nasal neutrophil recruitment and prevented invasive disease in mice. We propose that cigarette smoke predisposes to invasive pneumococcal disease by suppressing inflammatory processes of the upper respiratory tract. Given that smoking prevalence remain high worldwide, these findings are relevant to the continued efforts to reduce invasive pneumococcal disease burden.
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