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- Faries, B., et al.
(författare)
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Completion dissection or observation for sentinel-node metastasis in melanoma
- 2017
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Ingår i: New England Journal of Medicine. - 0028-4793. ; 376:23, s. 2211-2222
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND Sentinel-lymph-node biopsy is associated with increased melanoma-specific survival (i.e., survival until death from melanoma) among patients with node-positive intermediatethickness melanomas (1.2 to 3.5 mm). The value of completion lymph-node dissection for patients with sentinel-node metastases is not clear. METHODS In an international trial, we randomly assigned patients with sentinel-node metastases detected by means of standard pathological assessment or a multimarker molecular assay to immediate completion lymph-node dissection (dissection group) or nodal observation with ultrasonography (observation group). The primary end point was melanoma-specific survival. Secondary end points included disease-free survival and the cumulative rate of nonsentinel-node metastasis. RESULTS Immediate completion lymph-node dissection was not associated with increased melanomaspecific survival among 1934 patients with data that could be evaluated in an intention-Totreat analysis or among 1755 patients in the per-protocol analysis. In the per-protocol analysis, the mean (-SE) 3-year rate of melanoma-specific survival was similar in the dissection group and the observation group (86-1.3% and 86-1.2%, respectively; P = 0.42 by the logrank test) at a median follow-up of 43 months. The rate of disease-free survival was slightly higher in the dissection group than in the observation group (68-1.7% and 63-1.7%, respectively; P = 0.05 by the log-rank test) at 3 years, based on an increased rate of disease control in the regional nodes at 3 years (92-1.0% vs. 77-1.5%; P<0.001 by the log-rank test); these results must be interpreted with caution. Nonsentinel-node metastases, identified in 11.5% of the patients in the dissection group, were a strong, independent prognostic factor for recurrence (hazard ratio, 1.78; P = 0.005). Lymphedema was observed in 24.1% of the patients in the dissection group and in 6.3% of those in the observation group. CONCLUSIONS Immediate completion lymph-node dissection increased the rate of regional disease control and provided prognostic information but did not increase melanoma-specific survival among patients with melanoma and sentinel-node metastases.
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- Rees, CA, et al.
(författare)
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Derivation and validation of a novel risk assessment tool to identify children aged 2-59 months at risk of hospitalised pneumonia-related mortality in 20 countries
- 2022
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Ingår i: BMJ global health. - : BMJ. - 2059-7908. ; 7:4
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Tidskriftsartikel (refereegranskat)abstract
- Existing risk assessment tools to identify children at risk of hospitalised pneumonia-related mortality have shown suboptimal discriminatory value during external validation. Our objective was to derive and validate a novel risk assessment tool to identify children aged 2–59 months at risk of hospitalised pneumonia-related mortality across various settings.MethodsWe used primary, baseline, patient-level data from 11 studies, including children evaluated for pneumonia in 20 low-income and middle-income countries. Patients with complete data were included in a logistic regression model to assess the association of candidate variables with the outcome hospitalised pneumonia-related mortality. Adjusted log coefficients were calculated for each candidate variable and assigned weighted points to derive the Pneumonia Research Partnership to Assess WHO Recommendations (PREPARE) risk assessment tool. We used bootstrapped selection with 200 repetitions to internally validate the PREPARE risk assessment tool.ResultsA total of 27 388 children were included in the analysis (mean age 14.0 months, pneumonia-related case fatality ratio 3.1%). The PREPARE risk assessment tool included patient age, sex, weight-for-age z-score, body temperature, respiratory rate, unconsciousness or decreased level of consciousness, convulsions, cyanosis and hypoxaemia at baseline. The PREPARE risk assessment tool had good discriminatory value when internally validated (area under the curve 0.83, 95% CI 0.81 to 0.84).ConclusionsThe PREPARE risk assessment tool had good discriminatory ability for identifying children at risk of hospitalised pneumonia-related mortality in a large, geographically diverse dataset. After external validation, this tool may be implemented in various settings to identify children at risk of hospitalised pneumonia-related mortality.
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- Mai, Xiao-Mei, et al.
(författare)
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Symptoms to pollen and fruits early in life and allergic disease at 4 years of age
- 2008
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Ingår i: Allergy. European Journal of Allergy and Clinical Immunology. - : Wiley. - 0105-4538 .- 1398-9995. ; 63:11, s. 1499-504
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The predictive value of reported early symptoms to pollen or fruits on later allergic disease is unclear. Our aim is to evaluate if symptoms to pollen and/or to fruits early in life are associated with allergic disease and sensitization to pollen at 4 years. METHODS: The study included 3619 children from the Barn (Children), Allergy, Milieu, Stockholm, Epidemiology project (BAMSE) birth cohort. Reported symptoms of wheeze, sneeze or rash to birch, grass or weed, symptoms (vomiting, diarrhea, rash, facial edema, sneeze, or wheeze) to fruits including tree-nuts at 1 or 2 years of age, and definitions of asthma, rhinitis and eczema at 4 years were derived from questionnaire data. Sensitization to pollen allergens was defined as allergen-specific IgE-antibodies to any pollen (birch/timothy/mugwort) > or =0.35 kU(A)/l. RESULTS: At 1 or 2 years of age, 6% of the children were reported to have pollen-related symptoms, 6% had symptoms to fruits, and 1.4% to both pollen and fruits. Children with symptoms to both pollen and fruits at 1 or 2 years of age had an increased risk for sensitization to any pollen allergen at age 4 (OR(adj) = 4.4, 95% CI = 2.1-9.2). This group of children also had a substantially elevated risk for developing any allergic disease (asthma, rhinitis, or eczema) at 4 years irrespective of sensitization to pollen (OR(adj) = 8.6, 95% CI = 4.5-16.4). CONCLUSIONS: The prevalence of reported symptoms to pollen and fruits is very low in early childhood. However, children with early symptoms to both pollen and fruits appear to have a markedly elevated risk for allergic disease.
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- Taylor, Rachael M., et al.
(författare)
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Diet quality and cardiovascular outcomes : A systematic review and meta-analysis of cohort studies
- 2024
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Ingår i: Nutrition & Dietetics. - : Wiley-Blackwell Publishing Inc.. - 1446-6368 .- 1747-0080.
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Tidskriftsartikel (refereegranskat)abstract
- AimsTo evaluate relationships between diet quality and cardiovascular outcomes.MethodsSix databases were searched for studies published between January 2007 and October 2021. Eligible studies included cohort studies that assessed the relationship between a priori diet quality and cardiovascular disease mortality and morbidity in adults. The Academy of Nutrition and Dietetics Checklist was used to assess the risk of bias. Study characteristics and outcomes were extracted from eligible studies using standardised processes. Data were summarised using risk ratios for cardiovascular disease incidence and mortality with difference compared for highest versus lowest diet quality synthesised in meta-analyses using a random effects model.ResultsOf the 4780 studies identified, 159 studies (n = 6 272 676 adults) were included. Meta-analyses identified a significantly lower cardiovascular disease incidence (n = 42 studies, relative risk 0.83, 95% CI 0.82–0.84, p < 0.001) and mortality risk (n = 49 studies, relative risk 0.83, 95% CI 0.82–0.84, p < 0.001) among those with highest versus lowest diet quality. In sensitivity analyses of a high number of pooled studies (≥13 studies) the Mediterranean style diet patterns and adherence to the heart healthy diet guidelines were significantly associated with a risk reduction of 15% and 14% for cardiovascular disease incidence and 17% and 20% for cardiovascular disease mortality respectively (p < 0.05).ConclusionsHigher diet quality is associated with lower incidence and risk of mortality for cardiovascular disease however, significant study heterogeneity was identified for these relationships.
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- Gil, Natali, et al.
(författare)
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Heparanase Is Essential for the Development of Diabetic Nephropathy in Mice
- 2012
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 61:1, s. 208-216
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Tidskriftsartikel (refereegranskat)abstract
- Diabetic nephropathy (DN) is the major life-threatening complication of diabetes. Abnormal permselectivity of glomerular basement membrane (GBM) plays an important role in DN pathogenesis. Heparanase is the predominant enzyme that degrades heparan sulfate (HS), the main polysaccharide of the GBM. Loss of GBM HS in diabetic kidney was associated with increased glomerular expression of heparanase; however, the causal involvement of heparanase in the pathogenesis of DN has not been demonstrated. We report for the first time the essential involvement of heparanase in DN. With the use of Hpse-KO mice, we found that deletion of the heparanase gene protects diabetic mice from DN. Furthermore, by investigating the molecular mechanism underlying induction of the enzyme in DN, we found that transcription factor early growth response 1 (Egr1) is responsible for activation of heparanase promoter under diabetic conditions. The specific heparanase inhibitor SST0001 markedly decreased the extent of albuminuria and renal damage in mouse models of DN. Our results collectively underscore the crucial role of heparanase in the pathogenesis of DN and its potential as a highly relevant target for interventions in patients with DN.
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- Hoffmann, Henry, et al.
(författare)
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Self-aware computing in the Angstrom processor
- 2012
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Ingår i: Proceedings of the 49th Annual Design Automation Conference. - New York, NY, USA : ACM. - 9781450311991 ; , s. 259-264
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Konferensbidrag (refereegranskat)abstract
- Addressing the challenges of extreme scale computing re- quires holistic design of new programming models and sys- tems that support those models. This paper discusses the Angstrom processor, which is designed to support a new Self-aware Computing (SEEC) model. In SEEC, applications explicitly state goals, while other systems components provide actions that the SEEC runtime system can use to meet those goals. Angstrom supports this model by ex- posing sensors and adaptations that traditionally would be managed independently by hardware. This exposure allows SEEC to coordinate hardware actions with actions specified by other parts of the system, and allows the SEEC runtime system to meet application goals while reducing costs (e.g., power consumption).
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