| 1. |
- Zamora, Juan Carlos, et al.
(författare)
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Considerations and consequences of allowing DNA sequence data as types of fungal taxa
- 2018
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Ingår i: IMA Fungus. - : INT MYCOLOGICAL ASSOC. - 2210-6340 .- 2210-6359. ; 9:1, s. 167-185
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Tidskriftsartikel (refereegranskat)abstract
- Nomenclatural type definitions are one of the most important concepts in biological nomenclature. Being physical objects that can be re-studied by other researchers, types permanently link taxonomy (an artificial agreement to classify biological diversity) with nomenclature (an artificial agreement to name biological diversity). Two proposals to amend the International Code of Nomenclature for algae, fungi, and plants (ICN), allowing DNA sequences alone (of any region and extent) to serve as types of taxon names for voucherless fungi (mainly putative taxa from environmental DNA sequences), have been submitted to be voted on at the 11th International Mycological Congress (Puerto Rico, July 2018). We consider various genetic processes affecting the distribution of alleles among taxa and find that alleles may not consistently and uniquely represent the species within which they are contained. Should the proposals be accepted, the meaning of nomenclatural types would change in a fundamental way from physical objects as sources of data to the data themselves. Such changes are conducive to irreproducible science, the potential typification on artefactual data, and massive creation of names with low information content, ultimately causing nomenclatural instability and unnecessary work for future researchers that would stall future explorations of fungal diversity. We conclude that the acceptance of DNA sequences alone as types of names of taxa, under the terms used in the current proposals, is unnecessary and would not solve the problem of naming putative taxa known only from DNA sequences in a scientifically defensible way. As an alternative, we highlight the use of formulas for naming putative taxa (candidate taxa) that do not require any modification of the ICN.
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| 2. |
- Jordan, Stanley C, et al.
(författare)
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IgG Endopeptidase in Highly Sensitized Patients Undergoing Transplantation.
- 2017
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Ingår i: New England Journal of Medicine. - : Massachusetts Medical Society. - 0028-4793 .- 1533-4406. ; 377:5, s. 442-453
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Donor-specific antibodies create an immunologic barrier to transplantation. Current therapies to modify donor-specific antibodies are limited and ineffective in the most highly HLA-sensitized patients. The IgG-degrading enzyme derived from Streptococcus pyogenes (IdeS), an endopeptidase, cleaves human IgG into F(ab')2 and Fc fragments inhibiting complement-dependent cytotoxicity and antibody-dependent cellular cytotoxicity, which suggests that IdeS might be useful for desensitization. We report on the combined experience of two independently performed open-label, phase 1-2 trials (conducted in Sweden and the United States) that assessed the efficacy of IdeS with regard to desensitization and transplantation of a kidney from an HLA-incompatible donor.METHODS: We administered IdeS to 25 highly HLA-sensitized patients (11 patients in Uppsala or Stockholm, Sweden, and 14 in Los Angeles) before the transplantation of a kidney from an HLA-incompatible donor. Frequent monitoring for adverse events, outcomes, donor-specific antibodies, and renal function was performed, as were renal biopsies. Immunosuppression after transplantation consisted of tacrolimus, mycophenolate mofetil, and glucocorticoids. Patients in the U.S. study also received intravenous immune globulin and rituximab after transplantation to prevent antibody rebound.RESULTS: Recipients in the U.S. study had a significantly longer cold ischemia time (the time elapsed between procurement of the organ and transplantation), a significantly higher rate of delayed graft function, and significantly higher levels of class I donor-specific antibodies than those in the Swedish study. A total of 38 serious adverse events occurred in 15 patients (5 events were adjudicated as being possibly related to IdeS). At transplantation, total IgG and HLA antibodies were eliminated. A total of 24 of 25 patients had perfusion of allografts after transplantation. Antibody-mediated rejection occurred in 10 patients (7 patients in the U.S. study and 3 in the Swedish study) at 2 weeks to 5 months after transplantation; all these patients had a response to treatment. One graft loss, mediated by non-HLA IgM and IgA antibodies, occurred.CONCLUSIONS: IdeS reduced or eliminated donor-specific antibodies and permitted HLA-incompatible transplantation in 24 of 25 patients. (Funded by Hansa Medical; ClinicalTrials.gov numbers, NCT02224820 , NCT02426684 , and NCT02475551 .).
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| 3. |
- Larsson, Susanna C, et al.
(författare)
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Alcohol consumption and risk of heart failure : Meta-analysis of 13 prospective studies
- 2018
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Ingår i: Clinical Nutrition. - : Elsevier BV. - 0261-5614 .- 1532-1983. ; 37:4, s. 1247-1251
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND & AIMS: Controversy exists on the association between alcohol consumption and risk of heart failure (HF). We carried out a meta-analysis to summarize available prospective data on alcohol consumption and HF.METHODS: We searched PubMed for relevant studies published until January 1, 2017. Relative risk (RR) estimates from individual studies were pooled in a random-effects meta-analysis.RESULTS: A total of 13 prospective studies, with 13,738 HF cases and 355,804 participants, were included in the meta-analysis. Light alcohol drinking (0.1-7 drinks/week) was inversely associated with risk of HF (RR, 0.86; 95% confidence interval, 0.81-0.90). There was no statistically significant association between moderate (7.1-14 drinks/week), high (14.1-28 drinks/week), or heavy (>28 drinks/week) alcohol consumption and HF risk. Former drinking was associated with an increased risk of HF compared with never or occasional drinking (RR, 1.22; 95% confidence interval, 1.11-1.33).CONCLUSIONS: This meta-analysis found that light alcohol drinking was associated with a lower risk of HF. Former drinking was associated with a higher risk of HF.
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| 4. |
- Larsson, Susanna C, et al.
(författare)
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Contrasting association between alcohol consumption and risk of myocardial infarction and heart failure : Two prospective cohorts.
- 2017
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Ingår i: International Journal of Cardiology. - : Elsevier BV. - 0167-5273 .- 1874-1754. ; 231, s. 207-210
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The potential cardioprotective effect of light-to-moderate alcohol consumption is disputed, and the association between heavy drinking and heart failure (HF) risk is unclear. We examined the association between alcohol consumption and risk of myocardial infarction (MI) and HF in two prospective cohorts.METHODS: We analyzed data from the Cohort of Swedish Men (40,590 men) and the Swedish Mammography Cohort (34,022 women). Participants were free of ischemic heart disease and HF at baseline. MI and HF cases were ascertained by linkage with the Swedish National Patient Register. Cox proportional hazards regression model was used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs).RESULTS: During follow-up (1998-2010), we ascertained 3678 and 1905 cases of MI and HF, respectively, in men and 1500 and 1328 cases of MI and HF, respectively, in women. Alcohol consumption was inversely associated with MI in both men and women (P trend <0.001); compared with light drinkers, the multivariable HRs were 0.70 (95% CI, 0.56-0.87) in men who consumed >28 drinks/week and 0.32 (95% CI, 0.15-0.67) in women who consumed 15-21 drinks/week. Alcohol consumption was not inversely associated with HF risk. However, in men, the risk of HF was higher in never, former, and heavy drinkers (>28 drinks/week; HR=1.45; 95% CI, 1.09-1.93) compared with light drinkers.CONCLUSIONS: Alcohol consumption has divergent associations with MI and HF, with an inverse association observed for MI but not HF. Heavy drinking was associated with an increased HF risk in men.
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| 5. |
- Larsson, Susanna C., et al.
(författare)
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Dietary Approaches to Stop Hypertension Diet and Incidence of Stroke : Results From 2 Prospective Cohorts
- 2016
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Ingår i: Stroke. - 0039-2499 .- 1524-4628. ; 47:4, s. 986-990
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND PURPOSE: High adherence to the Dietary Approaches to Stop Hypertension (DASH) diet is associated with lower risk of hypertension, the major risk factor for stroke. We examined whether adherence to the DASH diet is inversely associated with the incidence of stroke.METHODS: The study population comprised 74 404 men and women (45-83 years of age), without stroke at baseline, from the Cohort of Swedish Men and the Swedish Mammography Cohort. Diet was assessed with a food-frequency questionnaire. A modified DASH diet score was created based on consumption of vegetables, fruits, legumes and nuts, whole grains, low-fat dairy, red meat and processed meat, and sweetened beverages. Stroke cases were identified through linkage to the Swedish National Patient and Cause of Death Registers. Relative risks and 95% confidence intervals were estimated using Cox proportional hazards regression model.RESULTS: During 882 727 person-years (mean, 11.9 years) of follow-up, 3896 ischemic strokes, 560 intracerebral hemorrhages, and 176 subarachnoid hemorrhages were ascertained. The modified DASH diet score was statistically significantly inversely associated with the risk of ischemic stroke (P for trend=0.002), with a multivariable relative risk of 0.86 (95% confidence interval, 0.78-0.94) for the highest versus the lowest quartile of the score. The modified DASH diet score was nonsignificantly inversely associated with intracerebral hemorrhage (corresponding relative risk=0.81; 95% confidence interval, 0.63-1.05) but was not associated with subarachnoid hemorrhage.CONCLUSIONS: These findings indicate that high adherence to the DASH diet is associated with a reduced risk of ischemic stroke.CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifiers: NCT01127698 and NCT01127711 for the Swedish Mammography Cohort and the Cohort of Swedish Men, respectively.
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| 6. |
- Larsson, Susanna C., et al.
(författare)
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Differing association of alcohol consumption with different stroke types : a systematic review and meta-analysis.
- 2016
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Ingår i: BMC Medicine. - : Springer Science and Business Media LLC. - 1741-7015. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Whether light-to-moderate alcohol consumption is protective against stroke, and whether any association differs by stroke type, is controversial. We conducted a meta-analysis to summarize the evidence from prospective studies on alcohol drinking and stroke types.METHODS: Studies were identified by searching PubMed to September 1, 2016, and reference lists of retrieved articles. Additional data from 73,587 Swedish adults in two prospective studies were included. Study-specific results were combined in a random-effects model.RESULTS: The meta-analysis included 27 prospective studies with data on ischemic stroke (25 studies), intracerebral hemorrhage (11 studies), and/or subarachnoid hemorrhage (11 studies). Light and moderate alcohol consumption was associated with a lower risk of ischemic stroke, whereas high and heavy drinking was associated with an increased risk; the overall RRs were 0.90 (95 % CI, 0.85-0.95) for less than 1 drink/day, 0.92 (95 % CI, 0.87-0.97) for 1-2 drinks/day, 1.08 (95 % CI, 1.01-1.15) for more than 2-4 drinks/day, and 1.14 (95 % CI, 1.02-1.28) for more than 4 drinks/day. Light and moderate alcohol drinking was not associated with any hemorrhagic stroke subtype. High alcohol consumption (>2-4 drinks/day) was associated with a non-significant increased risk of both hemorrhagic stroke subtypes, and the relative risk for heavy drinking (>4 drinks/day) were 1.67 (95 % CI, 1.25-2.23) for intracerebral hemorrhage and 1.82 (95 % CI, 1.18-2.82) for subarachnoid hemorrhage.CONCLUSION: Light and moderate alcohol consumption was inversely associated only with ischemic stroke, whereas heavy drinking was associated with increased risk of all stroke types with a stronger association for hemorrhagic strokes.
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| 7. |
- Larsson, Susanna C., et al.
(författare)
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Prognosis of carotid dissecting aneurysms : Results from CADISS and a systematic review
- 2017
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Ingår i: Neurology. - 0028-3878 .- 1526-632X. ; 88:7, s. 646-652
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To determine the natural history of dissecting aneurysm (DA) and whether DA is associated with an increased recurrent stroke risk and whether type of antithrombotic drugs (antiplatelets vs anticoagulants) modifies the persistence or development of DA.METHODS: We included 264 patients with extracranial cervical artery dissection (CAD) from the Cervical Artery Dissection in Stroke Study (CADISS), a multicenter prospective study that compared antiplatelet with anticoagulation therapy. Logistic regression was used to estimate age- and sex-adjusted odds ratios. We conducted a systematic review of published studies assessing the natural history of DA and stroke risk in patients with non-surgically-treated extracranial CAD with DA.RESULTS: In CADISS, DA was present in 24 of 264 patients at baseline. In 36 of 248 patients with follow-up neuroimaging at 3 months, 12 of the 24 baseline DAs persisted, and 24 new DA had developed. There was no association between treatment allocation (antiplatelets vs anticoagulants) and whether DA at baseline persisted at follow-up or whether new DA developed. During 12 months of follow-up, stroke occurred in 1 of 48 patients with DA and in 7 of 216 patients without DA (age- and sex-adjusted odds ratio 0.84; 95% confidence interval 0.10-7.31; p = 0.88). Published studies, mainly retrospective, showed a similarly low risk of stroke and no evidence of an increased stroke rate in patients with DA.CONCLUSIONS: The results of CADISS provide evidence suggesting that DAs may have benign prognosis and therefore medical treatment should be considered.
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| 8. |
- Larsson, Susanna C., et al.
(författare)
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Type 1 and type 2 diabetes mellitus and incidence of seven cardiovascular diseases
- 2018
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Ingår i: International Journal of Cardiology. - : ELSEVIER IRELAND LTD. - 0167-5273 .- 1874-1754. ; 262, s. 66-70
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Tidskriftsartikel (refereegranskat)abstract
- Background: The association between type 1 diabetes mellitus (T1DM) and specific cardiovascular diseases (CVD) is uncertain. Furthermore, data on type 2 diabetes mellitus (T2DM) in relation to risk of aortic valve stenosis, atrial fibrillation, abdominal aortic aneurysm, and intracerebral hemorrhage are scarce and inconclusive. We examined the associations of T1DM and T2DM with incidence of seven CVD outcomes.Methods: This study comprised 71,483 Swedish adults from two population-based prospective cohorts. T1DM and T2DM diagnosis and incident CVD cases were ascertained through linkage with the population-based registers.Results: T1DM was associated with myocardial infarction (hazard ratio [HR] 3.26; 95% confidence interval [CI] 2.47-4.30), heart failure (HR 2.68; 95% CI 1.76-4.09), and ischemic stroke (HR 2.61; 95% CI 1.80-3.79). Increased risk of myocardial infarction, ischemic stroke, and heart failure was also observed in T2DM patients and the magnitude of the associations increased with longer T2DM duration. T2DM was also associated with an increased risk of aortic valve stenosis (HR 1.34; 95% CI 1.05-1.71) and with lower risk of abdominal aortic aneurysm (HR 0.57; 95% CI 0.40-0.82) and intracerebral hemorrhage (HR 0.51; 95% CI 0.30-0.88). Only long-term T2DM(>= 20 years) was associated with an increased risk of atrial fibrillation (HR 1.44; 95% CI 1.02-2.04).Conclusion: T1DM and T2DM are associated with increased risk of major CVD outcomes. Trial registration: The Cohort of Swedish Men and the Swedish Mammography Cohort are registered at clinicaltrials.gov as NCT01127711 and NCT01127698, respectively.
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| 9. |
- Mansouri, Larry, et al.
(författare)
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Functional loss of I kappa B epsilon leads to NF-kappa B deregulation in aggressive chronic lymphocytic leukemia
- 2015
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Ingår i: Journal of Experimental Medicine. - : Rockefeller University Press. - 0022-1007 .- 1540-9538. ; 212:6, s. 833-843
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Tidskriftsartikel (refereegranskat)abstract
- NF-kappa B is constitutively activated in chronic lymphocytic leukemia (CLL); however, the implicated molecular mechanisms remain largely unknown. Thus, we performed targeted deep sequencing of 18 core complex genes within the NF-kappa B pathway in a discovery and validation CLL cohort totaling 315 cases. The most frequently mutated gene was NFKBIE (21/315 cases; 7%), which encodes I kappa B epsilon, a negative regulator of NF-kappa B in normal B cells. Strikingly, 13 of these cases carried an identical 4-bp frameshift deletion, resulting in a truncated protein. Screening of an additional 377 CLL cases revealed that NFKBIE aberrations predominated in poor-prognostic patients and were associated with inferior outcome. Minor subclones and/or clonal evolution were also observed, thus potentially linking this recurrent event to disease progression. Compared with wild-type patients, NFKBIE-deleted cases showed reduced I kappa B epsilon protein levels and decreased p65 inhibition, along with increased phosphorylation and nuclear translocation of p65. Considering the central role of B cell receptor (BcR) signaling in CLL pathobiology, it is notable that I kappa B epsilon loss was enriched in aggressive cases with distinctive stereotyped BcR, likely contributing to their poor prognosis, and leading to an altered response to BcR inhibitors. Because NFKBIE deletions were observed in several other B cell lymphomas, our findings suggest a novel common mechanism of NF-kappa B deregulation during lymphomagenesis.
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| 10. |
- Mansouri, Larry, et al.
(författare)
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Functional loss of IκBε leads to NF-κB deregulation in aggressive chronic lymphocytic leukemia.
- 2015
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Ingår i: Journal of Experimental Medicine. - : Rockefeller University Press. - 1540-9538 .- 0022-1007. ; 212:6, s. 833-843
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Tidskriftsartikel (refereegranskat)abstract
- NF-κB is constitutively activated in chronic lymphocytic leukemia (CLL); however, the implicated molecular mechanisms remain largely unknown. Thus, we performed targeted deep sequencing of 18 core complex genes within the NF-κB pathway in a discovery and validation CLL cohort totaling 315 cases. The most frequently mutated gene was NFKBIE (21/315 cases; 7%), which encodes IκBε, a negative regulator of NF-κB in normal B cells. Strikingly, 13 of these cases carried an identical 4-bp frameshift deletion, resulting in a truncated protein. Screening of an additional 377 CLL cases revealed that NFKBIE aberrations predominated in poor-prognostic patients and were associated with inferior outcome. Minor subclones and/or clonal evolution were also observed, thus potentially linking this recurrent event to disease progression. Compared with wild-type patients, NFKBIE-deleted cases showed reduced IκBε protein levels and decreased p65 inhibition, along with increased phosphorylation and nuclear translocation of p65. Considering the central role of B cell receptor (BcR) signaling in CLL pathobiology, it is notable that IκBε loss was enriched in aggressive cases with distinctive stereotyped BcR, likely contributing to their poor prognosis, and leading to an altered response to BcR inhibitors. Because NFKBIE deletions were observed in several other B cell lymphomas, our findings suggest a novel common mechanism of NF-κB deregulation during lymphomagenesis.
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