| 1. |
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| 2. |
- Beral, V, et al.
(författare)
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Alcohol, tobacco and breast cancer - collaborative reanalysis of individual data from 53 epidemiological studies, including 58515 women with breast cancer and 95067 women without the disease
- 2002
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Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 1532-1827 .- 0007-0920. ; 87, s. 1234-45
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Tidskriftsartikel (refereegranskat)abstract
- Alcohol and tobacco consumption are closely correlated and published results on their association with breast cancer have not always allowed adequately for confounding between these exposures. Over 80% of the relevant information worldwide on alcohol and tobacco consumption and breast cancer were collated, checked and analysed centrally. Analyses included 58515 women with invasive breast cancer and 95067 controls from 53 studies. Relative risks of breast cancer were estimated, after stratifying by study, age, parity and, where appropriate, women's age when their first child was born and consumption of alcohol and tobacco. The average consumption of alcohol reported by controls from developed countries was 6.0 g per day, i.e. about half a unit/drink of alcohol per day, and was greater in ever-smokers than never-smokers, (8.4 g per day and 5.0 g per day, respectively). Compared with women who reported drinking no alcohol, the relative risk of breast cancer was 1.32 (1.19 - 1.45, P < 0.00001) for an intake of 35 - 44 g per day alcohol, and 1.46 (1.33 - 1.61, P < 0.00001) for greater than or equal to 45 g per day alcohol. The relative risk of breast cancer increased by 7.1% (95% CI 5.5-8.7%; P<0.00001) for each additional 10 g per day intake of alcohol, i.e. for each extra unit or drink of alcohol consumed on a daily basis. This increase was the same in ever-smokers and never-smokers (7.1 % per 10 g per day, P < 0.00001, in each group). By contrast, the relationship between smoking and breast cancer was substantially confounded by the effect of alcohol. When analyses were restricted to 22 255 women with breast cancer and 40 832 controls who reported drinking no alcohol, smoking was not associated with breast cancer (compared to never-smokers, relative risk for ever-smokers= 1.03, 95% CI 0.98 - 1.07, and for current smokers=0.99, 0.92 - 1.05). The results for alcohol and for tobacco did not vary substantially across studies, study designs, or according to 15 personal characteristics of the women; nor were the findings materially confounded by any of these factors. If the observed relationship for alcohol is causal, these results suggest that about 4% of the breast cancers in developed countries are attributable to alcohol. In developing countries, where alcohol consumption among controls averaged only 0.4 g per day, alcohol would have a negligible effect on the incidence of breast cancer. In conclusion, smoking has little or no independent effect on the risk of developing breast cancer; the effect of alcohol on breast cancer needs to be interpreted in the context of its beneficial effects, in moderation, on cardiovascular disease and its harmful effects on cirrhosis and cancers of the mouth, larynx, oesophagus and liver. (C) 2002 Cancer Research UK.
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| 3. |
- Horwich, A, et al.
(författare)
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EAU–ESMO consensus statements on the management of advanced and variant bladder cancer - an international collaborative multi-stakeholder effort : under the auspices of the EAU and ESMO Guidelines Committees
- 2019
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Ingår i: Annals of Oncology. - : Oxford University Press. - 0923-7534 .- 1569-8041. ; 30:11, s. 1697-1727
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Although guidelines exist for advanced and variant bladder cancer management, evidence is limited/conflicting in some areas and the optimal approach remains controversial.OBJECTIVE: To bring together a large multidisciplinary group of experts to develop consensus statements on controversial topics in bladder cancer management.DESIGN: A steering committee compiled proposed statements regarding advanced and variant bladder cancer management which were assessed by 113 experts in a Delphi survey. Statements not reaching consensus were reviewed; those prioritised were revised by a panel of 45 experts before voting during a consensus conference.SETTING: Online Delphi survey and consensus conference.PARTICIPANTS: The European Association of Urology (EAU), the European Society for Medical Oncology (ESMO), experts in bladder cancer management.OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Statements were ranked by experts according to their level of agreement: 1-3 (disagree), 4-6 (equivocal), 7-9 (agree). A priori (level 1) consensus was defined as ≥70% agreement and ≤15% disagreement, or vice versa. In the Delphi survey, a second analysis was restricted to stakeholder group(s) considered to have adequate expertise relating to each statement (to achieve level 2 consensus).RESULTS AND LIMITATIONS: Overall, 116 statements were included in the Delphi survey. Of these, 33 (28%) statements achieved level 1 consensus and 49 (42%) statements achieved level 1 or 2 consensus. At the consensus conference, 22 of 27 (81%) statements achieved consensus. These consensus statements provide further guidance across a broad range of topics, including the management of variant histologies, the role/limitations of prognostic biomarkers in clinical decision making, bladder preservation strategies, modern radiotherapy techniques, the management of oligometastatic disease and the evolving role of checkpoint inhibitor therapy in metastatic disease.CONCLUSIONS: These consensus statements provide further guidance on controversial topics in advanced and variant bladder cancer management until a time where further evidence is available to guide our approach.
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| 4. |
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| 5. |
- Helbig, K. L., et al.
(författare)
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De Novo Pathogenic Variants in CACNA1E Cause Developmental and Epileptic Encephalopathy with Contractures, Macrocephaly, and Dyskinesias
- 2018
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Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 103:5, s. 666-678
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Tidskriftsartikel (refereegranskat)abstract
- Developmental and epileptic encephalopathies (DEEs) are severe neurodevelopmental disorders often beginning in infancy or early childhood that are characterized by intractable seizures, abundant epileptiform activity on EEG, and developmental impairment or regression. CACNA1E is highly expressed in the central nervous system and encodes the alpha(1)-subunit of the voltage-gated Ca(V)2.3 channel, which conducts high voltage-activated R-type calcium currents that initiate synaptic transmission. Using next-generation sequencing techniques, we identified de novo CACNA1E variants in 30 individuals with DEE, characterized by refractory infantile-onset seizures, severe hypotonia, and profound developmental impairment, often with congenital contractures, macrocephaly, hyperkinetic movement disorders, and early death. Most of the 14, partially recurring, variants cluster within the cytoplasmic ends of all four S6 segments, which form the presumed Ca(V)2.3 channel activation gate. Functional analysis of several S6 variants revealed consistent gain-of-function effects comprising facilitated voltage-dependent activation and slowed inactivation. Another variant located in the domain II S4-S5 linker results in facilitated activation and increased current density. Five participants achieved seizure freedom on the anti-epileptic drug topiramate, which blocks R-type calcium channels. We establish pathogenic variants in CACNA1E as a cause of DEEs and suggest facilitated R-type calcium currents as a disease mechanism for human epilepsy and developmental disorders.
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| 6. |
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| 7. |
- Jin, S. C., et al.
(författare)
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Mutations disrupting neuritogenesis genes confer risk for cerebral palsy
- 2020
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 52:10
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Tidskriftsartikel (refereegranskat)abstract
- Whole-exome sequencing of 250 parent-offspring trios identifies an enrichment of rare damaging de novo mutations in individuals with cerebral palsy and implicates genetically mediated dysregulation of early neuronal connectivity in the etiology of this disorder. In addition to commonly associated environmental factors, genomic factors may cause cerebral palsy. We performed whole-exome sequencing of 250 parent-offspring trios, and observed enrichment of damaging de novo mutations in cerebral palsy cases. Eight genes had multiple damaging de novo mutations; of these, two (TUBA1AandCTNNB1) met genome-wide significance. We identified two novel monogenic etiologies,FBXO31andRHOB, and showed that theRHOBmutation enhances active-state Rho effector binding while theFBXO31mutation diminishes cyclin D levels. Candidate cerebral palsy risk genes overlapped with neurodevelopmental disorder genes. Network analyses identified enrichment of Rho GTPase, extracellular matrix, focal adhesion and cytoskeleton pathways. Cerebral palsy risk genes in enriched pathways were shown to regulate neuromotor function in aDrosophilareverse genetics screen. We estimate that 14% of cases could be attributed to an excess of damaging de novo or recessive variants. These findings provide evidence for genetically mediated dysregulation of early neuronal connectivity in cerebral palsy.
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| 8. |
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| 9. |
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| 10. |
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| 11. |
- Abrahamsen, E. Povl, et al.
(författare)
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ANTARCTICA AND THE SOUTHERN OCEAN
- 2020
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Ingår i: BULLETIN OF THE AMERICAN METEOROLOGICAL SOCIETY. - 0003-0007 .- 1520-0477. ; 101:8
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Tidskriftsartikel (refereegranskat)
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| 12. |
- Bekema, Hendrika J., et al.
(författare)
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Systematic Review of Adrenalectomy and Lymph Node Dissection in Locally Advanced Renal Cell Carcinoma
- 2013
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Ingår i: European Urology. - : Elsevier. - 0302-2838 .- 1873-7560. ; 64:5, s. 799-810
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Forskningsöversikt (refereegranskat)abstract
- Context: Controversy remains over whether adrenalectomy and lymph node dissection (LND) should be performed concomitantly with radical nephrectomy (RN) for locally advanced renal cell carcinoma (RCC) cT3-T4N0M0. Objective: To systematically review all relevant literature comparing oncologic, perioperative, and quality-of-life (QoL) outcomes for locally advanced RCC managed with RN with or without concomitant adrenalectomy or LND.Evidence acquisition: Relevant databases were searched up to August 2012. Randomised controlled trials (RCTs) and comparative studies were included. Outcome measures were overall survival, QoL, and perioperative adverse effects. Risks of bias (RoB) were assessed using Cochrane RoB tools. Quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation approach.Evidence synthesis: A total of 3658 abstracts and 252 full-text articles were screened. Eight studies met the inclusion criteria: six LNDs (one RCT and five nonrandomised studies [NRSs]) and two adrenalectomies (two NRSs). RoB was high across the evidence base, and the quality of evidence from outcomes ranged from moderate to very low. Meta-analyses were not undertaken because of diverse study designs and data heterogeneity. There was no significant difference in survival between the groups, even though 5-yr overall survival appears better for the RN plus LND group compared with the no-LND group in one randomised study. There was no evidence of a difference in adverse events between the RN plus LND and no-LND groups. No studies reported QoL outcomes. There was no evidence of an oncologic difference between the RN with adrenalectomy and RN without adrenalectomy groups. No studies reported adverse events or QoL outcomes.Conclusions: There is insufficient evidence to draw any conclusions on oncologic outcomes for patients having concomitant LND or ipsilateral adrenalectomy compared with patients having RN alone for cT3-T4N0M0 RCC. The quality of evidence is generally low and the results potentially biased. Further research in adequately powered trials is needed to answer these questions.
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| 13. |
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| 14. |
- Knipp, D.J., et al.
(författare)
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Ionospheric Convection Response to Slow, Strong Variations in a Northward Interplanetary Magnetic Field: A Case Study for January 14, 1988
- 1993
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Ingår i: Journal of Geophysical Research. - 0148-0227 .- 2156-2202. ; 98, s. 19273-19292
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Tidskriftsartikel (refereegranskat)abstract
- We analyze ionospheric convection patterns over the polar regions during the passage of an interplanetary magnetic cloud on January 14, 1988, when the interplanetary magnetic field (IMF) rotated slowly in direction and had a large amplitude. Using the assimilative mapping of ionospheric electrodynamics (AMIE) procedure, we combine simultaneous observations of ionospheric drifts and magnetic perturbations from many different instruments into consistent patterns of high-latitude electrodynamics, focusing on the period of northward IMF. By combining satellite data with ground-based observations, we have generated one of the most comprehensive data sets yet assembled and used it to produce convection maps for both hemispheres. We present evidence that a lobe convection cell was embedded within normal merging convection during a period when the IMF B(y) and B(z) components were large and positive. As the IMF became predominantly northward, a strong reversed convection pattern (afternoon-to-morning potential drop of around 100 kV) appeared in the southern (summer) polar cap, while convection in the northern (winter) hemisphere became weak and disordered with a dawn-to-dusk potential drop of the order of 30 kV. These patterns persisted for about 3 hours, until the IMF rotated significantly toward the west. We interpret this behavior in terms of a recently proposed merging model for northward IMF under solstice conditions, for which lobe field lines from the hemisphere tilted toward the Sun (summer hemisphere) drape over the dayside magnetosphere, producing reverse convection in the summer hemisphere and impeding direct contact between the solar wind and field lines connected to the winter polar cap. The positive IMF B(x) component present at this time could have contributed to the observed hemispheric asymmetry. Reverse convection in the summer hemisphere broke down rapidly after the ratio \textbackslashB(y)/B(z)\textbackslash exceeded unity, while convection in the winter hemisphere strengthened. A dominant dawn-to-dusk potential drop was established in both hemispheres when the magnitude of B(y) exceeded that of B(z), with potential drops of the order of 100 kV, even while B(z) remained northward. The later transition to southward B(z) produced a gradual intensification of the convection, but a greater qualitative change occurred at the transition through \textbackslashB(y)/B(z)\textbackslash = 1 than at the transition through B(z) = 0. The various convection patterns we derive under northward IMF conditions illustrate all possibilities previously discussed in the literature: nearly single-cell and multicell, distorted and symmetric, ordered and unordered, and sunward and antisunward.
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| 15. |
- MacLennan, Steven, et al.
(författare)
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Systematic Review of Oncological Outcomes Following Surgical Management of Localised Renal Cancer
- 2012
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Ingår i: European Urology. - : Elsevier BV. - 0302-2838 .- 1873-7560. ; 61:5, s. 972-993
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Forskningsöversikt (refereegranskat)abstract
- Context: Renal cell carcinoma (RCC) accounts for 2-3% of adult malignancies. There remain uncertainties over the oncological outcomes for the surgical management of localised RCC. Objective: Systematically review relevant literature comparing oncological outcomes of surgical management of localised RCC (T1-2N0M0). Evidence acquisition: Relevant databases including Medline, Embase, and the Cochrane Library were searched up to October 2010, and an updated scoping search was performed up to January 2012. Randomised controlled trials (RCTs) or quasi-RCTs, prospective observational studies with controls, retrospective matched-pair studies, and comparative studies from well-defined registries/databases were included. The main outcomes were overall survival, cancer-specific survival, recurrence, and metastases. The Cochrane risk of bias tool was used to assess RCTs, and an extended version was used to assess nonrandomised studies (NRSs). The quality of evidence was assessed using Grading of Recommendations Assessment, Development, and Evaluation (GRADE). Evidence synthesis: A total of 4580 abstracts and 389 full-text articles were assessed. Thirty-four studies met the inclusion criteria (6 RCTs and 28 NRSs). Meta-analyses were planned but were deemed inappropriate due to data heterogeneity. There were high risks of bias and low-quality evidence across the evidence base. Open radical nephrectomy and open partial nephrectomy showed similar cancer-specific and overall survival, but when both open and laparoscopic approaches are considered together, the evidence showed improved survival for partial nephrectomy for tumours <= 4 cm. The overall evidence suggests either equivalent or better survival with partial nephrectomy. Laparoscopic radical nephrectomy offered equivalent survival to open radical nephrectomy, and all laparoscopic approaches achieved equivalent survival. Open and laparoscopic partial nephrectomy achieved equivalent survival. The issue of ipsilateral adrenalectomy or complete lymph node dissection with radical nephrectomy or partial nephrectomy remains unresolved. Conclusions: The evidence base suggests localised RCCs are best managed by nephron-sparing surgery where technically feasible. However, the current evidence base has significant limitations due to studies of low methodological quality marked by high risks of bias. (C) 2012 European Association of Urology. Published by Elsevier B. V. All rights reserved.
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| 16. |
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| 17. |
- Witjes, J. Alfred, et al.
(författare)
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EAU-ESMO Consensus Statements on the Management of Advanced and Variant Bladder Cancer – An International Collaborative Multistakeholder Effort : Under the Auspices of the EAU-ESMO Guidelines Committees
- 2020
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Ingår i: European Urology. - : Elsevier. - 0302-2838 .- 1873-7560. ; 77:2, s. 223-250
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Although guidelines exist for advanced and variant bladder cancer management, evidence is limited/conflicting in some areas and the optimal approach remains controversial.OBJECTIVE: To bring together a large multidisciplinary group of experts to develop consensus statements on controversial topics in bladder cancer management.DESIGN: A steering committee compiled proposed statements regarding advanced and variant bladder cancer management which were assessed by 113 experts in a Delphi survey. Statements not reaching consensus were reviewed; those prioritised were revised by a panel of 45 experts prior to voting during a consensus conference.SETTING: Online Delphi survey and consensus conference.PARTICIPANTS: The European Association of Urology (EAU), the European Society for Medical Oncology (ESMO), experts in bladder cancer management.OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Statements were ranked by experts according to their level of agreement: 1-3 (disagree), 4-6 (equivocal), and 7-9 (agree). A priori (level 1) consensus was defined as ≥70% agreement and ≤15% disagreement, or vice versa. In the Delphi survey, a second analysis was restricted to stakeholder group(s) considered to have adequate expertise relating to each statement (to achieve level 2 consensus).RESULTS AND LIMITATIONS: Overall, 116 statements were included in the Delphi survey. Of these statements, 33 (28%) achieved level 1 consensus and 49 (42%) achieved level 1 or 2 consensus. At the consensus conference, 22 of 27 (81%) statements achieved consensus. These consensus statements provide further guidance across a broad range of topics, including the management of variant histologies, the role/limitations of prognostic biomarkers in clinical decision making, bladder preservation strategies, modern radiotherapy techniques, the management of oligometastatic disease, and the evolving role of checkpoint inhibitor therapy in metastatic disease.CONCLUSIONS: These consensus statements provide further guidance on controversial topics in advanced and variant bladder cancer management until a time when further evidence is available to guide our approach.PATIENT SUMMARY: This report summarises findings from an international, multistakeholder project organised by the EAU and ESMO. In this project, a steering committee identified areas of bladder cancer management where there is currently no good-quality evidence to guide treatment decisions. From this, they developed a series of proposed statements, 71 of which achieved consensus by a large group of experts in the field of bladder cancer. It is anticipated that these statements will provide further guidance to health care professionals and could help improve patient outcomes until a time when good-quality evidence is available.
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| 18. |
- Zhu, C. H., et al.
(författare)
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Topological Ferroelectric Bistability in a Polarization-Modulated Orthogonal Smectic Liquid Crystal
- 2012
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Ingår i: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 1520-5126 .- 0002-7863. ; 134:23, s. 9681-9687
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Tidskriftsartikel (refereegranskat)abstract
- We report a bent-core liquid crystal (LC) compound exhibiting two fluid smectic phases in which two-dimensional, polar, orthorhombic layers order into three-dimensional ferroelectric states. The lower-temperature phase has a uniform polarization field which responds in an analog fashion to applied electric field. The higher-temperature phase is a new smectic state with periodic undulation of the polarization, structurally modulated layers, and a bistable response to applied electric field which originates in the periodically splay-modulated bulk of the LC rather than by surface stabilization at the cell boundaries.
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| 19. |
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| 20. |
- Shen, Y., et al.
(författare)
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Field alignment of bent-core smectic liquid crystals for analog optical phase modulation
- 2015
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Ingår i: Applied Physics Letters. - : AIP Publishing. - 0003-6951 .- 1077-3118. ; 106:19
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Tidskriftsartikel (refereegranskat)abstract
- A general method for aligning bent-core smectic liquid crystal materials is described. Alternating electric fields between interdigitated electrodes patterned on one cell surface create torques on the liquid crystal that result in uniform "bookshelf" orientation of the smectic layers. The aligned cell can then be driven in the conventional way by applying an electric field between all of the stripe electrodes connected together and a monolithic electrode on the other cell surface. Fast, analog, optical phase-only modulation is demonstrated in a device containing a polar, bent-core SmAPF material aligned using this technique.
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| 21. |
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