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| 2. |
- 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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| 3. |
- Tesi, B., et al.
(författare)
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Targeted high-throughput sequencing for genetic diagnostics of hemophagocytic lymphohistiocytosis
- 2015
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Ingår i: Genome Medicine. - : Springer Science and Business Media LLC. - 1756-994X. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Hemophagocytic lymphohistiocytosis (HLH) is a rapid-onset, potentially fatal hyperinflammatory syndrome. A prompt molecular diagnosis is crucial for appropriate clinical management. Here, we validated and prospectively evaluated a targeted high-throughput sequencing approach for HLH diagnostics. Methods: A high-throughput sequencing strategy of 12 genes linked to HLH was validated in 13 patients with previously identified HLH-associated mutations and prospectively evaluated in 58 HLH patients. Moreover, 2504 healthy individuals from the 1000 Genomes project were analyzed in silico for variants in the same genes. Results: Analyses revealed a mutation detection sensitivity of 97.3 %, an average coverage per gene of 98.0 %, and adequate coverage over 98.6 % of sites previously reported as mutated in these genes. In the prospective cohort, we achieved a diagnosis in 22 out of 58 patients (38 %). Genetically undiagnosed HLH patients had a later age at onset and manifested higher frequencies of known secondary HLH triggers. Rare, putatively pathogenic monoallelic variants were identified in nine patients. However, such monoallelic variants were not enriched compared with healthy individuals. Conclusions: We have established a comprehensive high-throughput platform for genetic screening of patients with HLH. Almost all cases with reduced natural killer cell function received a diagnosis, but the majority of the prospective cases remain genetically unexplained, highlighting genetic heterogeneity and environmental impact within HLH. Moreover, in silico analyses of the genetic variation affecting HLH-related genes in the general population suggest caution with respect to interpreting causality between monoallelic mutations and HLH. A complete understanding of the genetic susceptibility to HLH thus requires further in-depth investigations, including genome sequencing and detailed immunological characterization.
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| 4. |
- Durno, C., et al.
(författare)
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Survival Benefit for Individuals With Constitutional Mismatch Repair Deficiency Undergoing Surveillance
- 2021
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Ingår i: Journal of Clinical Oncology. - : American Society of Clinical Oncology (ASCO). - 0732-183X .- 1527-7755. ; 39:25
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE Constitutional mismatch repair deficiency syndrome (CMMRD) is a lethal cancer predisposition syndrome characterized by early-onset synchronous and metachronous multiorgan tumors. We designed a surveillance protocol for early tumor detection in these individuals. PATIENTS AND METHODS Data were collected from patients with confirmed CMMRD who were registered in the International Replication Repair Deficiency Consortium. Tumor spectrum, efficacy of the surveillance protocol, and malignant transformation of low-grade lesions were examined for the entire cohort. Survival outcomes were analyzed for patients followed prospectively from the time of surveillance implementation. RESULTS A total of 193 malignant tumors in 110 patients were identified. Median age of first cancer diagnosis was 9.2 years (range: 1.7-39.5 years). For patients undergoing surveillance, all GI and other solid tumors, and 75% of brain cancers were detected asymptomatically. By contrast, only 16% of hematologic malignancies were detected asymptomatically (P < .001). Eighty-nine patients were followed prospectively and used for survival analysis. Five-year overall survival (OS) was 90% (95% CI, 78.6 to 100) and 50% (95% CI, 39.2 to 63.7) when cancer was detected asymptomatically and symptomatically, respectively (P = .001). Patient outcome measured by adherence to the surveillance protocol revealed 4-year OS of 79% (95% CI, 54.8 to 90.9) for patients undergoing full surveillance, 55% (95% CI, 28.5 to 74.5) for partial surveillance, and 15% (95% CI, 5.2 to 28.8) for those not under surveillance (P < .0001). Of the 64 low-grade tumors detected, the cumulative likelihood of transformation from low-to high-grade was 81% for GI cancers within 8 years and 100% for gliomas in 6 years. CONCLUSION Surveillance and early cancer detection are associated with improved OS for individuals with CMMRD.
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| 5. |
- Henriksen, J. S., et al.
(författare)
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A pilot study comparing optical coherence tomography, radiography, clinical photography, and polarisation microscopy for studies of hypomineralisation disturbances in enamel
- 2023
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Ingår i: Heliyon. - : Elsevier BV. - 2405-8440. ; 9:2
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Tidskriftsartikel (refereegranskat)abstract
- Aim: To investigate the use of optical coherence tomography (OCT) as a tool to assess general and localised hypomineralisation defects in the enamel. Design and Materials: Ten extracted permanent teeth (four teeth with localised hypomineralisa-tion, four teeth with general hypomineralisation, and two healthy controls) were used in this study. In addition, four participants who underwent OCT served as living controls for the extracted teeth.Methods: The OCT results were compared with clinical photographs, digital radiographs, and polarising microscopy images of tooth sections (considered the gold standard) to determine the method with the most accurate information regarding the extent of enamel disturbances: 1) visibility of enamel disturbance (visible yes/no); if yes, 2) extent of the disturbance in the enamel; and 3) determination of the plausible involvement of the underlying dentin.Results: OCT was more accurate than digital radiography and visual assessment. OCT could provide information about the extent of localised hypomineralised disturbances in the enamel that was comparable to that with polarisation microscopy of the tooth sections.Conclusion: Within the limitations of this pilot study, it can be concluded that OCT is suitable for investigating and evaluating localised hypomineralisation disturbances; however, it is less useful in cases with generalised hypomineralisation of the enamel. In addition, OCT complements radiographic examination of enamel; however, more studies are necessary to elucidate the full extent of the use of OCT in case of hypomineralisation.
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| 6. |
- Meeths, M, et al.
(författare)
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Familial hemophagocytic lymphohistiocytosis type 3 (FHL3) caused by deep intronic mutation and inversion in UNC13D
- 2011
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Ingår i: Blood. - Washington : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 118:22, s. 5783-5793
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Tidskriftsartikel (refereegranskat)abstract
- Familial hemophagocytic lymphohistiocytosis (FHL) is an autosomal recessive, often-fatal hyperinflammatory disorder. Mutations in PRF1, UNC13D, STX11, and STXBP2 are causative of FHL2, 3, 4, and 5, respectively. In a majority of suspected FHL patients from Northern Europe, sequencing of exons and splice sites of such genes required for lymphocyte cytotoxicity revealed no or only monoallelic UNC13D mutations. Here, in 21 patients, we describe 2 pathogenic, noncoding aberrations of UNC13D. The first is a point mutation localized in an evolutionarily conserved region of intron 1. This mutation selectively impairs UNC13D transcription in lymphocytes, abolishing Munc13-4 expression. The second is a 253-kb inversion straddling UNC13D, affecting the 3'-end of the transcript and likewise abolishing Munc13-4 expression. Carriership of the intron 1 mutation was found in patients across Europe, whereas carriership of the inversion was limited to Northern Europe. Notably, the latter aberration represents the first description of an autosomal recessive human disease caused by an inversion. These findings implicate an intronic sequence in cell-type specific expression of Munc13-4 and signify variations outside exons and splice sites as a common cause of FHL3. Based on these data, we propose a strategy for targeted sequencing of evolutionary conserved noncoding regions for the diagnosis of primary immunodeficiencies.
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| 7. |
- Nilsson, H., et al.
(författare)
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Measurements of Transition Probabilities for Complex Ions
- 2003
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Ingår i: Physica Scripta. - : Institute of Physics Publishing (IOPP). - 0031-8949 .- 1402-4896. ; T105:1, s. 61-61
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Tidskriftsartikel (refereegranskat)abstract
- Fourier transform spectroscopy has proven to be a useful tool when measuring wavelengths and branching fractions. The high spectral resolution makes it possible to extend and improve term analyses of complex spectra. We present an overview of our measurements with the Fourier transform spectrometer at Lund Observatory. Much of our work is motivated by astrophysical problems, and we show an application of some of our measurements related to the age determination of the Galaxy.
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| 8. |
- Xu, J. H., et al.
(författare)
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Adaptive and Maladaptive Brain Functional Network Reorganization After Stroke in Hemianopia Patients: An Electroencephalogram-Tracking Study
- 2022
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Ingår i: Brain connectivity. - : Mary Ann Liebert Inc. - 2158-0014 .- 2158-0022. ; 12:8, s. 725-739
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Hemianopia after occipital stroke is believed to be mainly due to local damage at or near the lesion site. However, magnetic resonance imaging studies suggest functional connectivity network (FCN) reorganization also in distant brain regions. Because it is unclear whether reorganization is adaptive or maladaptive, compensating for, or aggravating vision loss, we characterized FCNs electrophysiologically to explore local and global brain plasticity and correlated FCN reorganization with visual performance.Methods: Resting-state electroencephalography (EEG) was recorded in chronic, unilateral stroke patients and healthy age-matched controls (n = 24 each). This study was approved by the local ethics committee. The correlation of oscillating EEG activity was calculated with the imaginary part of coherence between pairs of regions of interest, and FCN graph theory metrics (degree, strength, clustering coefficient) were correlated with stimulus detection and reaction time.Results: Stroke brains showed altered FCNs in the alpha- and low beta-band in numerous occipital, temporal brain structures. On a global level, FCN had a less efficient network organization whereas on the local level node networks were reorganized especially in the intact hemisphere. Here, the occipital network was 58% more rigid (with a more "regular" network structure) whereas the temporal network was 32% more efficient (showing greater "small-worldness"), both of which correlated with worse or better visual processing, respectively.Conclusions: Occipital stroke is associated with both local and global FCN reorganization, but this can be both adaptive and maladaptive. We propose that the more "regular" FCN structure in the intact visual cortex indicates maladaptive plasticity, where less processing efficacy with reduced signal/noise ratio may cause the perceptual deficits in the intact visual field (VF). In contrast, reorganization in intact temporal brain regions is presumably adaptive, possibly supporting enhanced peripheral movement perception. Impact statementThe functional connectivity network (FCN) after occipital stroke changes toward a more "regular" pattern. It is maladaptive in the intact occipital region, possibly leading to creating perceptual deficits causing spatiotemporal visual impairments in the "intact" but crowded visual field. The FCN can also be "adaptive," enabling temporal gyrus structures to compensate for the loss of vision.
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| 9. |
- Bengtsson, Anders K. H., et al.
(författare)
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Applications of eigenvector centrality to small social networks
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- This article investigates conceptual and methodological questions that may arise in applying eigenvector centrality to small social networks such as school classes. The focus on small networks brings out surprising and subtle properties related to the interpretation of the measure. We investigate examples where the weighted adjacency matrix of the underlying social network quantifies inter-individual preferences of whom to work with or play with. We show that mathematical operations such as transposition and symmetrization of the weighted adjacency matrix enhances the power of the measure. It is demonstrated that it is not sufficient to work with the original weight matrix. By working with a symmetrized or a semi-symmetrized or a transposed weight matrix different characteristics of the social interaction are revealed. The method chosen depends on the purpose of the investigation. Identifying isolated or popular individuals in the network are also facilitated using these operations.
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| 10. |
- Chaix, Basile, et al.
(författare)
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Spatial clustering of mental disorders and associated characteristics of the neighbourhood context in Malmo, Sweden, in 2001.
- 2006
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Ingår i: Journal of Epidemiology and Community Health. - : BMJ. - 1470-2738 .- 0143-005X. ; 60:5, s. 427-435
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Tidskriftsartikel (refereegranskat)abstract
- Study objective: Previous research provides preliminary evidence of spatial variations of mental disorders and associations between neighbourhood social context and mental health. This study expands past literature by (1) using spatial techniques, rather than multilevel models, to compare the spatial distributions of two groups of mental disorders (that is, disorders due to psychoactive substance use, and neurotic, stress related, and somatoform disorders); and (2) investigating the independent impact of contextual deprivation and neighbourhood social disorganisation on mental health, while assessing both the magnitude and the spatial scale of these effects. Design: Using different spatial techniques, the study investigated mental disorders due to psychoactive substance use, and neurotic disorders. Participants: All 89285 persons aged 40-69 years residing in Malmo, Sweden, in 2001, geolocated to their place of residence. Main results: The spatial scan statistic identified a large cluster of increased prevalence in a similar location for the two mental disorders in the northern part of Malmo. However, hierarchical geostatistical models showed that the two groups of disorders exhibited a different spatial distribution, in terms of both magnitude and spatial scale. Mental disorders due to substance consumption showed larger neighbourhood variations, and varied in space on a larger scale, than neurotic disorders. After adjustment for individual factors, the risk of substance related disorders increased with neighbourhood deprivation and neighbourhood social disorganisation. The risk of neurotic disorders only increased with contextual deprivation. Measuring contextual factors across continuous space, it was found that these associations operated on a local scale. Conclusions: Taking space into account in the analyses permitted deeper insight into the contextual determinants of mental disorders.
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