| 71. |
- Dunlop, Malcolm G, et al.
(författare)
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Cumulative impact of 10 common genetic variants on colorectal cancer risk in 42,333 individuals from eight populations
- 2012
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Ingår i: Gut. - Stockholm : Karolinska Institutet, Dept of Molecular Medicine and Surgery. - 1468-3288 .- 0017-5749.
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Colorectal cancer (CRC) has a substantial heritable component. Common genetic variation has been shown to contribute to CRC risk. A study was conducted in a large multi-population study to assess the feasibility of CRC risk prediction using common genetic variant data combined with other risk factors. A risk prediction model was built and applied to the Scottish population using available data. DESIGN: Nine populations of European descent were studied to develop and validate CRC risk prediction models. Binary logistic regression was used to assess the combined effect of age, gender, family history (FH) and genotypes at 10 susceptibility loci that individually only modestly influence CRC risk. Risk models were generated from case-control data incorporating genotypes alone (n=39 266) and in combination with gender, age and FH (n=11 324). Model discriminatory performance was assessed using 10-fold internal cross-validation and externally using 4187 independent samples. The 10-year absolute risk was estimated by modelling genotype and FH with age- and gender-specific population risks. RESULTS: The median number of risk alleles was greater in cases than controls (10 vs 9, p<2.2×10(-16)), confirmed in external validation sets (Sweden p=1.2×10(-6), Finland p=2×10(-5)). The mean per-allele increase in risk was 9% (OR 1.09; 95% CI 1.05 to 1.13). Discriminative performance was poor across the risk spectrum (area under curve for genotypes alone 0.57; area under curve for genotype/age/gender/FH 0.59). However, modelling genotype data, FH, age and gender with Scottish population data shows the practicalities of identifying a subgroup with >5% predicted 10-year absolute risk. CONCLUSION: Genotype data provide additional information that complements age, gender and FH as risk factors, but individualised genetic risk prediction is not currently feasible. Nonetheless, the modelling exercise suggests public health potential since it is possible to stratify the population into CRC risk categories, thereby informing targeted prevention and surveillance.
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| 72. |
- Dunnett, Kirsty, et al.
(författare)
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Assessing first-year undergraduate physics students' laboratory practices : seeking to encourage research behaviours
- 2019
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Ingår i: European journal of physics. - : IOP Publishing. - 0143-0807 .- 1361-6404. ; 40:1
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Tidskriftsartikel (refereegranskat)abstract
- Encouraging positive inquiry-focused behaviours within the constraints of a physics teaching laboratory environment can be challenging. Here, we report on an implementation, the 'working grade' ( w-grade), designed to directly assess aspects of students' laboratory practice with the aim of encouraging first-year undergraduate students to look beyond the concept of a correct outcome' to a physics experiment. The w-grade is composed of the five aspects of group work, querying, exploration, attitude and progress which are each marked on a 0, 1, 2, 3 scale. The initial implementation is presented in full as well as a second, simpler variant. The w-grade emphasises and directly rewards inquiry behaviours and students were much more willing to explore the experiments than in previous years.
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| 73. |
- Ghezzi, Angelo, et al.
(författare)
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Rituximab in patients with pediatric multiple sclerosis and other demyelinating disorders of the CNS : Practical considerations
- 2021
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Ingår i: Multiple Sclerosis Journal. - : Sage Publications. - 1352-4585 .- 1477-0970. ; 27:12, s. 1814-1822
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Tidskriftsartikel (refereegranskat)abstract
- Anti-CD20 therapies have established efficacy in the treatment of immune-mediated neurological and non-neurological diseases. Rituximab, one of the first B-cell-directed therapies, is relatively inexpensive compared to newer anti-CD20 molecules, is available in many countries, and has been used off-label in pediatric patients with neuroimmune conditions. The objective of this paper is to describe the experience with rituximab in pediatric multiple sclerosis and other inflammatory immune-mediated disorders of the central nervous system (CNS), and to define a protocol for its use in clinical practice, in particular addressing doses, interval of administration, duration of treatment, and tests to perform at baseline and during follow-up.
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| 74. |
- Gorman, D. M., et al.
(författare)
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The effect of bariatric surgery on diabetic retinopathy: Good, bad, or both?
- 2016
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Ingår i: Diabetes and Metabolism Journal. - : Korean Diabetes Association. - 2233-6079 .- 2233-6087. ; 40:5, s. 354-364
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Tidskriftsartikel (refereegranskat)abstract
- Bariatric surgery, initially intended as a weight-loss procedure, is superior to standard lifestyle intervention and pharmacological therapy for type 2 diabetes in obese individuals. Intensive medical management of hyperglycemia is associated with improved microvascular outcomes. Whether or not the reduction in hyperglycemia observed after bariatric surgery translates to improved microvascular outcomes is yet to be determined. There is substantial heterogeneity in the data relating to the impact of bariatric surgery on diabetic retinopathy (DR), the most common microvascular complication of diabetes. This review aims to collate the recent data on retinal outcomes after bariatric surgery. This comprehensive evaluation revealed that the majority of DR cases remain stable after surgery. However, risk of progression of pre-existing DR and the development of new DR is not eliminated by surgery. Instances of regression of DR are also noted. Potential risk factors for deterioration include severity of DR at the time of surgery and the magnitude of glycated hemoglobin reduction. Concerns also exist over the detrimental effects of postprandial hypoglycemia after surgery. In vivo studies evaluating the chronology of DR development and the impact of bariatric surgery could provide clarity on the situation. For now, however, the effect of bariatric surgery on DR remains inconclusive. © 2016 Korean Diabetes Association.
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| 75. |
- Gorman, Lucy M., et al.
(författare)
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The venoms of the lesser (Echiichthys vipera) and greater (Trachinus draco) weever fish– A review
- 2020
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Ingår i: Toxicon: X. - : Elsevier BV. - 2590-1710. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- In comparison with other animal venoms, fish venoms remain relatively understudied. This is especially true for that of the lesser Echiichthys vipera and greater weever fish Trachinus draco which, apart from the isolation of their unique venom cytolysins, trachinine and dracotoxin, respectively, remain relatively uncharacterised. Envenomation reports mainly include mild symptoms consisting of nociception and inflammation. However, like most fish venoms, if the venom becomes systemic it causes cardiorespiratory and blood pressure changes. Although T. draco venom has not been studied since the 1990's, recent studies on E. vipera venom have discovered novel cytotoxic components on human cancer cells, but due to the scarcity of research on the molecular make-up of the venom, the molecule(s) causing this cytotoxicity remains unknown. This review analyses past studies on E. vipera and T. draco venom, the methods used in the, the venom constituents characterised, the reported symptoms of envenomation and compares these findings with those from other venomous Scorpaeniformes.
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| 76. |
- Hombach-Klonisch, Sabine, et al.
(författare)
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Glioblastoma and chemoresistance to alkylating agents: Involvement of apoptosis, autophagy, and unfolded protein response
- 2018
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Ingår i: Pharmacology and Therapeutics. - : PERGAMON-ELSEVIER SCIENCE LTD. - 0163-7258 .- 1879-016X. ; 184, s. 13-41
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Forskningsöversikt (refereegranskat)abstract
- Despite advances in neurosurgical techniques and radio-/chemotherapy, the treatment of brain tumors remains a challenge. This is particularly true for the most frequent and fatal adult brain tumor, glioblastoma (GB). Upon diagnosis, the average survival time of GB patients remains only approximately 15 months. The alkylating drug temozolomide (TMZ) is routinely used in brain tumor patients and induces apoptosis, autophagy and unfolded protein response (UPR). Here, we review these cellular mechanisms and their contributions to TMZ chemoresistance in brain tumors, with a particular emphasis on TMZ chemoresistance in glioma stem cells and GB.
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| 77. |
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| 78. |
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| 79. |
- Liseau, René, 1949, et al.
(författare)
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ALMA's view of the nearest neighbors to the Sun: The submm/mm SEDs of the α Centauri binary and a new source
- 2016
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 594, s. A109-
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Tidskriftsartikel (refereegranskat)abstract
- Context. The precise mechanisms that provide the nonradiative energy for heating the chromosphere and corona of the Sun and other stars are at the focus of intense contemporary research. Aims. Observations at submm and mm wavelengths are particularly useful to obtain information about the run of the temperature in the upper atmosphere of Sun-like stars. We used the Atacama Large Millimeter/submillimeter Array (ALMA) to study the chromospheric emission of the α Centauri binary system in all six available frequency bands during Cycle 2 in 2014-2015. Methods. Since ALMA is an interferometer, the multitelescope array is particularly suited for the observation of point sources. With its large collecting area, the sensitivity is high enough to allow the observation of nearby main-sequence stars at submm/mm wavelengths for the first time. The comparison of the observed spectral energy distributions with theoretical model computations provides the chromospheric structure in terms of temperature and density above the stellar photosphere and the quantitative understanding of the primary emission processes. Results. Both stars in the α Centauri binary system were detected and resolved at all ALMA frequencies. For both α Cen A and B, the existence and location of the temperature minima, first detected from space with Herschel, are well reproduced by the theoretical models of this paper. The temperature minimum for α Cen B is lower than for A and occurs at a lower height in the atmosphere, but for both stars, Tmin/Teff is consistently lower than what is derived from optical and UV data. In addition, and as a completely different matter, a third point source was detected in Band 8 (405 GHz, 740 αm) in 2015. With only one epoch and only one detection, we are left with little information regarding that object's nature, but we conjecture that it might be a distant solar system object. Conclusions. The submm/mm emission of the α Cen stars is indeed very well reproduced by modified chromospheric models of the quiet Sun. This most likely means that the nonradiative heating mechanisms of the upper atmosphere that are at work in the Sun are also operating in other solar-type stars.
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| 80. |
- Ljungman, L., et al.
(författare)
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Sexual Dysfunction and Reproductive Concerns in Young Men Diagnosed With Testicular Cancer : An Observational Study
- 2019
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Ingår i: Journal of Sexual Medicine. - : Elsevier. - 1743-6095 .- 1743-6109. ; 16:7, s. 1049-1059
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: The survival rates for testicular cancer are excellent; still, there is a lack of knowledge regarding important survivorship issues, such as sexual dysfunction and reproductive concerns.AIM: The aim of this study was to investigate the prevalence and predictors of sexual dysfunction and reproductive concerns and the potential association between these issues in young men ∼2 years after a diagnosis of testicular cancer.METHODS: Data were collected from 111 men (response rate = 50%) diagnosed with testicular cancer at age 16-39. Patients were identified via the Swedish National Quality Registry for Testicular Cancer and approached with a survey, including standardized measures of sexual function, reproductive concerns, body image, and health-related quality of life. The survey was sent to participants approximately 2 years after their cancer diagnosis. Clinical variables were collected from the registry. Predictors were identified by multivariable linear regression analyses.MAIN OUTCOME MEASURES: The main outcomes were sexual function, assessed with the Patient-Reported Outcomes Measurement Information System Sexual Function and Satisfaction measure version 2.0, and reproductive concerns, assessed with the Reproductive Concerns After Cancer scale.RESULTS: Sexual dysfunction was reported by 26% of men, and a high level of reproductive concerns was reported by 28%. Lower satisfaction with sex life was associated with older age (β = -0.41), negative body image (β = -0.42), not having a partner (β = 4.8), and dissatisfaction with sex life before cancer (β = 8.31). Negative body image was associated with reproductive concerns in the dimensions of fertility potential (β = 0.06), partner disclosure (β = 0.08), and child's health (β = 0.07), whereas having had fertility preservation predicted higher levels of concerns with regard to personal health (β = 0.52) and achieving pregnancy (β = 0.53). Clinical variables did not predict either sexual function or reproductive concerns.CLINICAL IMPLICATIONS: Our results show that the majority of young men diagnosed with testicular cancer do not report sexual dysfunction or reproductive concerns 2 years after diagnosis. A sizeable minority, however, does report dysfunction or reproductive concerns, which should be recognized in the follow-up care of this population.STRENGTHS & LIMITATIONS: A strength of the study is the use of high-quality registry data and validated instruments. The lack of Swedish norms for sexual function and reproductive concerns is a possible limitation.CONCLUSION: A subgroup of young men treated for testicular cancer report sexual dysfunction or reproductive concerns approximately 2 years after diagnosis. Factors associated with these issues seem to mainly be psychological, rather than medical, nature. Ljungman L, Eriksson LE, Flynn KE, et al. Sexual Dysfunction and Reproductive Concerns in Young Men Diagnosed With Testicular Cancer: An Observational Study. J Sex Med 2019;16:1049-1059.
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