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| 3. |
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| 4. |
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| 5. |
- Fugl-Meyer, Axel R, et al.
(author)
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Prevalence data in Europe
- 2005
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In: Women's Sexual Function and Dysfunction. - : Taylor & Francis. ; , s. 34-41
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Book chapter (other academic/artistic)
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| 6. |
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| 7. |
- Fugl-Meyer, Axel, et al.
(author)
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Sexualrehabilitation
- 1999
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In: Neuro Rehabilitation. - : Blackwell Wissenschats-Verlag, Berlin. ; , s. 370-
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Book chapter (other academic/artistic)
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| 8. |
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| 11. |
- Fugl-Meyer, Kerstin S., et al.
(author)
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Standard Operating Procedures for Female Genital Sexual Pain
- 2013
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In: Journal of Sexual Medicine. - : Oxford University Press (OUP). - 1743-6095 .- 1743-6109. ; 10:1, s. 83-93
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Journal article (peer-reviewed)abstract
- Introduction. Female genital sexual pain (GSP) is a common, distressing complaint in women of all ages that is underrecognized and undertreated. Definitions and terminology for female GSP are currently being debated. While some authors have suggested that GSP is not per se a sexual dysfunction, but rather a localized genial pain syndrome, others adhere to using clearly sexually related terms such as dyspareunia and vaginismus. Aim. The aims of this brief review are to present definitions of the different types of female GSP. Their etiology, incidence, prevalence, and comorbidity with somatic and psychological disorders are highlighted, and different somatic and psychological assessment and treatment modalities are discussed. Methods. The Standard Operating Procedures (SOP) committee was composed of a chair and five additional experts. No corporate funding or remuneration was received. The authors agreed to survey relevant databases, journal articles and utilize their own clinical experience. Consensus was guided by systematic discussions by e-mail communications. Main Outcome/Results. There is a clear lack of epidemiological data defining female GSP disorders and a lack of evidence supporting therapeutic interventions. However, this international expert group will recommend guidelines for management of female GSP. Conclusions. GSP disorders are complex. It is recommended that their evaluation and treatment are performed through comprehensive somato-psychological multidisciplinary approach. Fugl-Meyer KS, Bohm-Starke N, Damsted Petersen C, Fugl-Meyer A, Parish S, and Giraldi A. Standard operating procedures for female genital sexual pain.
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| 12. |
- Fugl-Meyer, K. S., et al.
(author)
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The effect of tadalafil on psychosocial outcomes in Swedish men with erectile distress : a multicentre, non-randomised, open-label clinical study
- 2006
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In: International journal of clinical practice (Esher). - : Hindawi Limited. - 1368-5031 .- 1742-1241. ; 60:11, s. 1386-1393
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Journal article (peer-reviewed)abstract
- A multicentre, non-randomised, open-label study assessed whether personal distress caused by erectile dysfunction (ED) affected psychosocial outcomes of tadalafil treatment. Eligible Swedish men at least 18 years old reporting >= 3-month history of ED were stratified into two groups (manifest or mild/no distress) based upon a distress question administered at enrolment. Tadalafil 20 mg was taken as needed for 8 weeks. The primary outcome was the difference between the two distress groups in change from baseline in the Psychological and Interpersonal Relationship Scales (PAIRS) spontaneity domain. Secondary outcome measures were PAIRS sexual self-confidence and time concerns domains, Life Satisfaction (LiSat-11) checklist and a Global Assessment of Treatment Response. The study also assessed tolerability. Of 662 men enrolled, 88% had manifest distress and 12% had mild/no distress. Baseline-to-endpoint changes for PAIRS domains were not significantly different between groups. Baseline-to-endpoint changes in LiSat-11 items were not significantly different between groups except for satisfaction with sexual life. Compared with men without ED, below normal baseline satisfaction with partner relationship and family life were normalised at endpoint. Over 90% of men reported improved erection and ability to engage in sexual activity. The most common treatment-emergent adverse events were headache, myalgia, dyspepsia, flushing and back pain. One man discontinued because of myalgia; 630 (95%) completed the study. In conclusion, erectile distress levels vary among patients with ED and distress can affect intra-familiar aspects of life, which may have implications for clinical practise. However, distress does not appear to hinder improvement in both mechanical and psychosocial outcomes of tadalafil treatment.
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| 13. |
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| 14. |
- Kehoe, Laura, et al.
(author)
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Make EU trade with Brazil sustainable
- 2019
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In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 364:6438, s. 341-
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Journal article (other academic/artistic)
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| 15. |
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| 18. |
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| 19. |
- Melin, Roland
(author)
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On life satisfaction and vocational rehabilitation outcome in Sweden
- 2003
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Doctoral thesis (other academic/artistic)abstract
- This dissertation has two parts. Firstly, satisfaction with life as a whole and with 10 life domains (using an instrument termed LiSat-11 with 6-graded scales) is described in a nationally representative sample aged 18-64 years (n: 2,533) and is related to some socio-demographic circumstances. Secondly, vocationally disabled people (n: 109) at an employability institute are prospectively followed in order to determine their life satisfaction and to identify early predictors of vocational rehabilitation outcome.Main results: Gender independently, 70 % of the national sample were satisfied with life as a whole (were happy). The ten domains formed a 4-factor pattern: ”Closeness, Health, Spare time, Provision”. Seven domains were sizeable predictors of overall life satisfaction. In a complex manner socio-demographics were predictive of (gross levels) all LiSat-11 items. Main predictors were perceived health, immigrant status and educational level. Generally, the vocational rehabilitees had low LiSat-11 levels except for the closeness items. They had relatively poor background resources (low “sense of coherence“ level) for successful coping. Whereas a positive rehabilitation outcome was accompanied by increases in several LiSat-11 aspects, only satisfaction with the vocational situation was clearly responsive. Three early predictors of outcome were identified: belief in vocational return, educational level and sense of coherence. In summary: Besides providing reference values for the LiSat-11 instrument, this dissertation demonstrates that different socio-demographic factors influence different areas of concern (domains) in 18- to 64-year-old Swedes. In turn, satisfaction derived from different areas heavily influences level of overall life satisfaction. Moreover, the vocational rehabilitees generally seemed to be predisposed to being poor copers, possibly a major background of low levels of many LiSat-11 aspects. The identified set of predictors of the outcome of vocational rehabilitation emphasizes a need for focusing on psycho-social aspects within vocational rehabilitation.
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| 20. |
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| 21. |
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| 22. |
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| 23. |
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| 24. |
- Viitanen, Matti, et al.
(author)
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Life satisfaction in long-term survivors after stroke
- 1988
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In: Scandinavian Journal of Rehabilitation Medicine. - 0036-5505 .- 1940-2228. ; 20:1, s. 17-24
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Journal article (peer-reviewed)abstract
- Different aspects of the quality of life before and after stroke were registered for 62 communicable, representative long-term (4-6 years) survivors, who reported the global and domain specific life satisfaction that they experienced (7 items, 6 graded-ordinal scales). Reference subjects were 60 healthy individuals in two age cohorts (60-61 years, n = 34; 79-81 years, n = 26) none of whom had been hospitalized during the last seven years prior to the investigation. The main finding is that, after the stroke, at least one aspect of the quality of life had decreased for 61% of them; this concerned global, sexual and leisure satisfaction mainly. Moreover, persisting motor impairment and ADL-disability had a negative effect on several aspects of life satisfaction. As nearly 30% of the non-impaired and the non-disabled interviewees reported decreased global life satisfaction, these changes indicate that they do not cope psychosocially with the stroke as such nor with its sequelae. In contrast, the levels of life satisfaction were similar for the 60-61 and 79-81 year-old interviewees, clinically healthy respondents, indicating stability in the quality of life that they experienced from late middle age into senectitude. For the patients, social integration estimated normatively did not covariate significantly with post-stroke satisfaction derived from social relationships.
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| 25. |
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| 26. |
- Öberg, Katarina, 1963-
(author)
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On Conditions of Swedish Women’s Sexual Well-Being : An Epidemiological Approach
- 2005
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Doctoral thesis (other academic/artistic)abstract
- Objectives: This descriptive epidemiological dissertation aims to identify conditions of Swedish women’s sexual well-being. The focus is on the relationship between their idiosyncratically reported levels, during the last 12 months, of 5 sexual functions/dysfunctions per se and distressing and their socio-psychological situation, including aspects of their sexual history. Levels of sexual functions/dysfunctions are also related to levels of sexual satisfaction and to other aspects of life satisfaction.Methods: Data on a randomized cross-sectional national sample of 1335 women aged 18-74 (59% of target sample) were gathered in 1996 using a combination of structured interviews and questionnaires/checklists. Analyses were performed for the total sample or for sub-samples aged 18-65 years. In 3 of the 4 dissertational articles, trichotomies of a 6-grade scale characterizing level of sexual dysfunctions into No/Mild/Manifest dysfunction were used.Main results: Mild sexual dysfunctions were, generally, much more common than were manifest, and dysfunctional distress was considerably less common than were dysfunctions per se. All dysfunctions, and in particular orgasmic dysfunction, were closely associated with level of sexual well-being. Four factors independently pair-wise linking levels of dysfunctions per se with levels of distressful dysfunction were identified. These were Sexual interest/Desire, Genital function (lubrication and dyspareunia), Orgasm, Vaginismus. Three of these (not vaginismus) were powerful classificators of gross level of sexual well-being. Many of socio-demographic and socio-psychological contextual life-conditions were significantly associated with the different sexual functions/dysfunctions. However, the most prominent contextual variables were satisfaction with partner relationship and partner’s levels of sexual functions.In conclusion, many different socio-psychological aspects must be taken into account to optimize treatment modalities and resources when dealing with women’s sexual dysfunction in order to secure a good level of sexual well-being.
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| 27. |
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| 28. |
- Althof, Stanley E., et al.
(author)
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Sexual Satisfaction in Men with Erectile Dysfunction : Correlates and Potential Predictors
- 2010
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In: The journal of sexual medicine. - : Oxford University Press (OUP). - 1743-6095. ; 7:1, s. 203-215
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Journal article (peer-reviewed)abstract
- Introduction. Sexual satisfaction is an important treatment objective for men with erectile dysfunction (ED). Aims. To evaluate potential associations between International Index of Erectile Function (IIEF) satisfaction at study endpoint and a range of baseline, on-treatment, and endpoint variables. Methods. An exploratory analysis was conducted involving 3,935 subjects with ED randomized to on-demand tadalafil (N = 2,824) or placebo (N = 1,111) in randomized, controlled trials across 28 countries. Patients achieving scores >= 16 on IIEF questions 7, 8, 13, and 14 at study endpoint were operationally defined as satisfied (vs. < 16, not satisfied). Multivariate logistic regression and other analyses were conducted to ascertain correlates and potential predictors of improvements in the IIEF-erectile function domain (IIEF-EF). Main Outcome Measures. Satisfaction on the IIEF at study endpoint, on-treatment improvements in IIEF-EF, and endpoint sexual frequency. Results. Patients who were satisfied with sexual function were on average younger and had less severe ED, a shorter history of the condition, and no history of vascular disorders, hypertension, or diabetes mellitus/insulin use at baseline (P < 0.01 vs. not satisfied for each). Satisfied patients were also more likely to experience a >= 4-point increase on the IIEF-EF domain on treatment (adjusted odds ratio [OR] = 22.4; 95% CI = 17.6-28.5; P < 0.0001) or IIEF-EF >= 26 at endpoint (adjusted OR = 41.0; 95% CI = 33.6-50.2; P < 0.0001). Satisfaction emerged as a strong correlate of a >= 4-point increase in the IIEF-EF on treatment; however, as a correlate of endpoint sexual frequency, baseline sexual frequency was stronger than endpoint satisfaction. Conclusions. Satisfaction is associated with certain baseline, on-treatment, and endpoint variables in ED patients. Further studies are needed to confirm these preliminary findings and explore their meaning for female partners. Althof SE, Buvat J, Gutkin SW, Belger M, Stothard DR, and Fugl-Meyer AR. Sexual satisfaction in men with erectile dysfunction: Correlates and potential predictors. J Sex Med 2010;7:203-215.
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| 29. |
- Amemiya, Chris T., et al.
(author)
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The African coelacanth genome provides insights into tetrapod evolution
- 2013
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 496:7445, s. 311-316
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Journal article (peer-reviewed)abstract
- The discovery of a living coelacanth specimen in 1938 was remarkable, as this lineage of lobe-finned fish was thought to have become extinct 70 million years ago. The modern coelacanth looks remarkably similar to many of its ancient relatives, and its evolutionary proximity to our own fish ancestors provides a glimpse of the fish that first walked on land. Here we report the genome sequence of the African coelacanth, Latimeria chalumnae. Through a phylogenomic analysis, we conclude that the lungfish, and not the coelacanth, is the closest living relative of tetrapods. Coelacanth protein-coding genes are significantly more slowly evolving than those of tetrapods, unlike other genomic features. Analyses of changes in genes and regulatory elements during the vertebrate adaptation to land highlight genes involved in immunity, nitrogen excretion and the development of fins, tail, ear, eye, brain and olfaction. Functional assays of enhancers involved in the fin-to-limb transition and in the emergence of extra-embryonic tissues show the importance of the coelacanth genome as a blueprint for understanding tetrapod evolution.
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| 30. |
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| 31. |
- Axen, Iben, et al.
(author)
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Misinformation, chiropractic, and the COVID-19 pandemic
- 2020
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In: Chiropractic and Manual Therapies. - : BioMed Central (BMC). - 2045-709X. ; 28:1
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Journal article (other academic/artistic)abstract
- Background: In March 2020, the World Health Organization elevated the coronavirus disease (COVID-19) epidemic to a pandemic and called for urgent and aggressive action worldwide. Public health experts have communicated clear and emphatic strategies to prevent the spread of COVID-19. Hygiene rules and social distancing practices have been implemented by entire populations, including 'stay-at-home' orders in many countries. The long-term health and economic consequences of the COVID-19 pandemic are not yet known.Main text: During this time of crisis, some chiropractors made claims on social media that chiropractic treatment can prevent or impact COVID-19. The rationale for these claims is that spinal manipulation can impact the nervous system and thus improve immunity. These beliefs often stem from nineteenth-century chiropractic concepts. We are aware of no clinically relevant scientific evidence to support such statements. We explored the internet and social media to collect examples of misinformation from Europe, North America, Australia and New Zealand regarding the impact of chiropractic treatment on immune function. We discuss the potential harm resulting from these claims and explore the role of chiropractors, teaching institutions, accrediting agencies, and legislative bodies.Conclusions: Members of the chiropractic profession share a collective responsibility to act in the best interests of patients and public health. We hope that all chiropractic stakeholders will view the COVID-19 pandemic as a call to action to eliminate the unethical and potentially dangerous claims made by chiropractors who practise outside the boundaries of scientific evidence.
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| 32. |
- Beal, Jacob, et al.
(author)
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Robust estimation of bacterial cell count from optical density
- 2020
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In: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
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Journal article (peer-reviewed)abstract
- Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data.
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| 33. |
- Bernspång, Birgitta, 1951-
(author)
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Consequences of stroke : aspects of impairments, disabilities and life satisfaction : with special emphasis on perception and on occupational therapy
- 1987
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Doctoral thesis (other academic/artistic)abstract
- Perceptual and motor functions and self-care ability after stroke were assessed within two weeks (n:109; mean age 69±10) and 4-6 years (n:75;70±9) after admission to a non-intensive care stroke unit. Sixty-two of the long-term stroke survivors reported on their life satisfaction (7 items) as experienced (in retrospect) before the stroke and at the time of the investigation. Perceptual functions and actual levels of life satisfaction were registered in 60 clinically healthy subjects aged about 60 or about 80 years.Both early on and late after stroke the 16 items of perceptual function were clearly grouped into two factors, which neatly fitted an ecological perceptual concept. One factor characterized low-order and the other higher-order perception. Impairments of low-order perception occurred for about 10% of the patients, whether investigated early or late after stroke. No one among the reference populations had such impairments. Higher-order perceptual impairments prevailed in 60% early on and in 57% late after stroke and were often more pronounced than those occurring in the reference populations, among whom 35% of the 60 year olds and significantly more - 77% - of the 80 year olds had such impairments. Hence, perceptual impairments are common after stroke, but slight age-dependent reductions should be considered when higher-order perceptual function is assessed and treated after stroke.Together with motor function, which was impaired in 52% of the early and 36% of the late stroke samples, higher-order perceptual function and to a limited extent low-order perception could predict the level of self-care ability in 70% and 62% of the early and late samples, respectively.Whereas levels of global and of domain specific variables of life satisfaction were similar in the two reference populations, the stroke had lead to a reduction in life satisfaction for 61% of the long-term survivors. Reductions were particularly pronounced for global life satisfaction and for satisfaction with leisure and sexuality. Although significantly associated with motor impairment and self-care disability, these reductions could not be attributed only to impairments and disability.The findings are discussed with particular reference to assessment and treatment in occupational therapy.
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| 34. |
- Bernspång, Birgitta, 1951-, et al.
(author)
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Motor and perceptual impairments in acute stroke patients : effects on self-care ability
- 1987
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In: Stroke. - : Lippincott Williams & Wilkins. - 0039-2499 .- 1524-4628. ; 18:6, s. 1081-1086
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Journal article (peer-reviewed)abstract
- The relative importance of motor, perceptual, and some cognitive functions for self-care ability was analyzed in a representative sample of 109 subjects within 2 weeks of acute stroke. Forty-nine patients (45%) were dependent or partly dependent in self-care. Profound motor dysfunction was present in 39%, low-order perceptual deficits in 10%, high-order perceptual deficits in 60%, and disorientation in time and space in 13% of the patients. There was a significant covariation between motor function and self-care ability and between low-order perception and orientation function. Low-order and high-order perception covaried only weakly. Discriminant analyses showed that the actual level of self-care proficiency could be correctly predicted in 70% of the cases by the 4 indexes of motor function, low-order perception, high-order perception, and orientation. The dominating predictor was motor function, and the next highest was high-order perception. When a program for early training is designed with the aim to alleviate long-term self-care disability after stroke, correct assessment of motor and perceptual functions in the individual stroke patient is essential.
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| 35. |
- Bernspång, Birgitta, et al.
(author)
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Perceptual function in the elderly and after stroke
- 1988
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In: Scandinavian Journal of Caring Sciences. - : John Wiley & Sons. - 0283-9318 .- 1471-6712. ; 2:2, s. 75-79
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Journal article (peer-reviewed)abstract
- Perceptual function was assessed in 60 clinically healthy subjects aged about 60 (n=34) and 80 (n=26), and in stroke survivors who were assessed either early (n=109) or four to six years (n=75) after the stroke. Using two indices, one characterising low-order perception and the other higher-order perception, the clinically healthy subjects invariably had no impairment in the low-order index. Slight impairments occurred in 35% of 60-year-old and 77% of 80-year-old healthy subjects. Considerably more pronounced disturbances occurred in the stroke victims, among whom about 60% had impairment or higher-order perceptual function and about 10% had low-order perceptual deficits. Thus as higher-order perception is age dependent, it appears that in rehabilitation of stroke allowance should be made for predictable signs of advancing age.
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| 36. |
- Braasch, Ingo, et al.
(author)
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The spotted gar genome illuminates vertebrate evolution and facilitates human-teleost comparisons
- 2016
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 48:4, s. 427-437
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Journal article (peer-reviewed)abstract
- To connect human biology to fish biomedical models, we sequenced the genome of spotted gar (Lepisosteus oculatus), whose lineage diverged from teleosts before teleost genome duplication (TGD). The slowly evolving gar genome has conserved in content and size many entire chromosomes from bony vertebrate ancestors. Gar bridges teleosts to tetrapods by illuminating the evolution of immunity, mineralization and development (mediated, for example, by Hox, ParaHox and microRNA genes). Numerous conserved noncoding elements (CNEs; often cis regulatory) undetectable in direct human-teleost comparisons become apparent using gar: functional studies uncovered conserved roles for such cryptic CNEs, facilitating annotation of sequences identified in human genome-wide association studies. Transcriptomic analyses showed that the sums of expression domains and expression levels for duplicated teleost genes often approximate the patterns and levels of expression for gar genes, consistent with subfunctionalization. The gar genome provides a resource for understanding evolution after genome duplication, the origin of vertebrate genomes and the function of human regulatory sequences.
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| 37. |
- Brawand, David, et al.
(author)
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The genomic substrate for adaptive radiation in African cichlid fish
- 2014
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 513:7518, s. 375-381
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Journal article (peer-reviewed)abstract
- Cichlid fishes are famous for large, diverse and replicated adaptive radiations in the Great Lakes of East Africa. To understand themolecular mechanisms underlying cichlid phenotypic diversity, we sequenced the genomes and transcriptomes of five lineages of African cichlids: the Nile tilapia (Oreochromis niloticus), an ancestral lineage with low diversity; and four members of the East African lineage: Neolamprologus brichardi/pulcher (older radiation, Lake Tanganyika), Metriaclima zebra (recent radiation, Lake Malawi), Pundamilia nyererei (very recent radiation, Lake Victoria), and Astatotilapia burtoni (riverine species around Lake Tanganyika). We found an excess of gene duplications in the East African lineage compared to tilapia and other teleosts, an abundance of non-coding element divergence, accelerated coding sequence evolution, expression divergence associated with transposable element insertions, and regulation by novel microRNAs. In addition, we analysed sequence data from sixty individuals representing six closely related species from Lake Victoria, and show genome-wide diversifying selection on coding and regulatory variants, some of which were recruited from ancient polymorphisms. We conclude that a number of molecular mechanisms shaped East African cichlid genomes, and that amassing of standing variation during periods of relaxed purifying selection may have been important in facilitating subsequent evolutionary diversification.
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| 38. |
- Brenner, David, et al.
(author)
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Hot-spot KIF5A mutations cause familial ALS
- 2018
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In: Brain. - : Oxford University Press. - 0006-8950 .- 1460-2156. ; 141, s. 688-697
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Journal article (peer-reviewed)abstract
- Heterozygous missense mutations in the N-terminal motor or coiled-coil domains of the kinesin family member 5A (KIF5A) gene cause monogenic spastic paraplegia (HSP10) and Charcot-Marie-Tooth disease type 2 (CMT2). Moreover, heterozygous de novo frame-shift mutations in the C-terminal domain of KIF5A are associated with neonatal intractable myoclonus, a neurodevelopmental syndrome. These findings, together with the observation that many of the disease genes associated with amyotrophic lateral sclerosis disrupt cytoskeletal function and intracellular transport, led us to hypothesize that mutations in KIF5A are also a cause of amyotrophic lateral sclerosis. Using whole exome sequencing followed by rare variant analysis of 426 patients with familial amyotrophic lateral sclerosis and 6137 control subjects, we detected an enrichment of KIF5A splice-site mutations in amyotrophic lateral sclerosis (2/426 compared to 0/6137 in controls; P = 4.2 x 10-3), both located in a hot-spot in the C-terminus of the protein and predicted to affect splicing exon 27. We additionally show co-segregation with amyotrophic lateral sclerosis of two canonical splice-site mutations in two families. Investigation of lymphoblast cell lines from patients with KIF5A splice-site mutations revealed the loss of mutant RNA expression and suggested haploinsufficiency as the most probable underlying molecular mechanism. Furthermore, mRNA sequencing of a rare non-synonymous missense mutation (predicting p. Arg1007Gly) located in the C-terminus of the protein shortly upstream of the splice donor of exon 27 revealed defective KIF5A pre-mRNA splicing in respective patient-derived cell lines owing to abrogation of the donor site. Finally, the non-synonymous single nucleotide variant rs113247976 (minor allele frequency = 1.00% in controls, n = 6137), also located in the C-terminal region [p.(Pro986Leu) in exon 26], was significantly enriched in familial amyotrophic lateral sclerosis patients (minor allele frequency = 3.40%; P = 1.28 x 10-7). Our study demonstrates that mutations located specifically in a C-terminal hotspot of KIF5A can cause a classical amyotrophic lateral sclerosis phenotype, and underline the involvement of intracellular transport processes in amyotrophic lateral sclerosis pathogenesis.
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| 39. |
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| 40. |
- Demir, Selvan, et al.
(author)
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Pursuing the excision of carbon-centred hexanuclear scandium clusters {CSc6} from solid {CSc6}I12Sc
- 2022
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In: Australian journal of chemistry (Print). - : CSIRO Publishing. - 0004-9425 .- 1445-0038. ; 75:9, s. 523-531
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Journal article (peer-reviewed)abstract
- A multi-gram synthetic route to black solid {CSc6}I12Sc (1) was developed which comprises the reaction of scandium triiodide, ScI3, with graphite and scandium metal at 850°C. Compound 1 dissolved in N,N-dimethylacetamide (DMA) to form a red solution. Results derived from 45Sc NMR and EPR spectroscopy indicated that a scandium cluster species exists in this solution along with a complex cation [Sc(DMA)6]3+. From these solutions crystals of [Sc(DMA)6]I3 (2) and a red oily product was isolated. Compound 2 was also prepared independently by dissolving ScI3 in DMA and two polymorphs, orthorhombic 2O and monoclinic 2M were crystallised. {CSc6}I12Sc (1) also dissolved in THF yielding a red solution which contains [ScI6]3− and a scandium cluster species, as analysed by 45Sc NMR and EPR spectroscopy.
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| 41. |
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| 42. |
- Feiner, Nathalie, et al.
(author)
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Asymmetric paralog evolution between the “cryptic” gene Bmp16 and its well-studied sister genes Bmp2 and Bmp4
- 2019
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In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9:1
-
Journal article (peer-reviewed)abstract
- The vertebrate gene repertoire is characterized by “cryptic” genes whose identification has been hampered by their absence from the genomes of well-studied species. One example is the Bmp16 gene, a paralog of the developmental key genes Bmp2 and -4. We focus on the Bmp2/4/16 group of genes to study the evolutionary dynamics following gen(om)e duplications with special emphasis on the poorly studied Bmp16 gene. We reveal the presence of Bmp16 in chondrichthyans in addition to previously reported teleost fishes and reptiles. Using comprehensive, vertebrate-wide gene sampling, our phylogenetic analysis complemented with synteny analyses suggests that Bmp2, -4 and -16 are remnants of a gene quartet that originated during the two rounds of whole-genome duplication (2R-WGD) early in vertebrate evolution. We confirm that Bmp16 genes were lost independently in at least three lineages (mammals, archelosaurs and amphibians) and report that they have elevated rates of sequence evolution. This finding agrees with their more “flexible” deployment during development; while Bmp16 has limited embryonic expression domains in the cloudy catshark, it is broadly expressed in the green anole lizard. Our study illustrates the dynamics of gene family evolution by integrating insights from sequence diversification, gene repertoire changes, and shuffling of expression domains.
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| 43. |
- Feiner, Nathalie, et al.
(author)
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Saltatory Evolution of the Ectodermal Neural Cortex Gene Family at the Vertebrate Origin
- 2013
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In: Genome Biology and Evolution. - : Oxford University Press (OUP). - 1759-6653. ; 5:8, s. 1485-1502
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Journal article (peer-reviewed)abstract
- The ectodermal neural cortex (ENC) gene family, whose members are implicated in neurogenesis, is part of the kelch repeat superfamily. To date, ENC genes have been identified only in osteichthyans, although other kelch repeat-containing genes are prevalent throughout bilaterians. The lack of elaborate molecular phylogenetic analysis with exhaustive taxon sampling has obscured the possible link of the establishment of this gene family with vertebrate novelties. In this study, we identified ENC homologs in diverse vertebrates by means of databasemining and polymerase chain reaction screens. Our analysis revealed that the ENC3 ortholog was lost in the basal eutherian lineage through single-gene deletion and that the triplication between ENC1, -2, and -3 occurred early in vertebrate evolution. Including our original data on the catshark and the zebrafish, our comparison revealed high conservation of thepleiotropic expression pattern of ENC1 and shuffling of expression domains between ENC1, -2, and -3. Compared withmany other gene families including developmental key regulators, the ENC gene family is unique in that conventional molecular phylogenetic inference could identifynoobvious invertebrateortholog. This suggests a composite nature of the vertebrate-specificgene repertoire, consistingnot onlyofdenovogenes introducedat thevertebrateorigin but alsoof long-standinggenes withnoapparent invertebrateorthologs. Some of the latter, including the ENC gene family, may be too rapidly evolving to provide sufficient phylogenetic signals marking orthology to their invertebrate counterparts. Such gene families that experienced saltatory evolution likely remain to be explored and might also have contributed to phenotypic evolution of vertebrates.
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| 44. |
- Franchini, Paolo, et al.
(author)
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Long-term experimental hybridisation results in the evolution of a new sex chromosome in swordtail fish
- 2018
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In: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 9
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Journal article (peer-reviewed)abstract
- The remarkable diversity of sex determination mechanisms known in fish may be fuelled by exceptionally high rates of sex chromosome turnovers or transitions. However, the evolutionary causes and genomic mechanisms underlying this variation and instability are yet to be understood. Here we report on an over 30-year evolutionary experiment in which we tested the genomic consequences of hybridisation and selection between two Xiphophorus fish species with different sex chromosome systems. We find that introgression and imposing selection for pigmentation phenotypes results in the retention of an unexpectedly large maternally derived genomic region. During the hybridisation process, the sex-determining region of the X chromosome from one parental species was translocated to an autosome in the hybrids leading to the evolution of a new sex chromosome. Our results highlight the complexity of factors contributing to patterns observed in hybrid genomes, and we experimentally demonstrate that hybridisation can catalyze rapid evolution of a new sex chromosome.
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| 45. |
- Freischmidt, Axel, et al.
(author)
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Haploinsufficiency of TBK1 causes familial ALS and fronto-temporal dementia
- 2015
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In: Nature Neuroscience. - : Springer Science and Business Media LLC. - 1097-6256 .- 1546-1726. ; 18:5, s. 631-
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Journal article (peer-reviewed)abstract
- Amyotrophic lateral sclerosis (ALS) is a genetically heterogeneous neurodegenerative syndrome hallmarked by adult-onset loss of motor neurons. We performed exome sequencing of 252 familial ALS (fALS) and 827 control individuals. Gene-based rare variant analysis identified an exome-wide significant enrichment of eight loss-of-function (LoF) mutations in TBK1 (encoding TANK-binding kinase 1) in 13 fALS pedigrees. No enrichment of LoF mutations was observed in a targeted mutation screen of 1,010 sporadic ALS and 650 additional control individuals. Linkage analysis in four families gave an aggregate LOD score of 4.6. In vitro experiments confirmed the loss of expression of TBK1 LoF mutant alleles, or loss of interaction of the C-terminal TBK1 coiled-coil domain (CCD2) mutants with the TBK1 adaptor protein optineurin, which has been shown to be involved in ALS pathogenesis. We conclude that haploinsufficiency of TBK1 causes ALS and fronto-temporal dementia.
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| 47. |
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| 48. |
- Fugl-Meyer, Axel R, et al.
(author)
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Aspects of Sexual Satisfaction in Men with Erectile Dysfunction : A factor analytic and logistic regression approach
- 2009
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In: Journal of Sexual Medicine. - : Oxford University Press (OUP). - 1743-6095. ; 6:1, s. 232-242
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Journal article (peer-reviewed)abstract
- Introduction. The International Index of Erectile Function (IIEF), Sexual Encounter Profile (SEP), and Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) assess efficacy of phosphodiesterase type 5 (PDE5) inhibitor treatment of erectile dysfunction (ED). Aims. To determine the degree that multiplicity of satisfaction questions in ED treatment evaluation instruments are congruent, to better understand the concept of sexual "satisfaction,"and to identify factors that correlate with improvement. Methods. Questionnaire data from 4,174 placebo- or tadalafil-treated patients with ED were analyzed. Principal component analysis (PCA) was performed on IIEF and SEP satisfaction questions. Spearman correlation coefficients were determined. Data from 431 of the 4,174 patients who completed EDITS questionnaires were analyzed. Logistic regression was used to investigate improvement of each IIEF satisfaction question. Results. PCA rotated on three factors explained 91% of total variance and separated IIEF Q6 (intercourse frequency) from a SEP and a remaining IIEF factor. All correlations between and among questions were close (ρ = 0.62-0.98; P < 0.0001), except for those with IIEF Q6 (ρ = 0.28-0.34; P < 0.0001). In a sub-sample, PCA of five IIEF, two SEP, and three EDITS questions identified four factors that explained 90% of all variance: EDITS questions, IIEF questions except Q6, SEP questions, and IIEF Q6. Greater improvement in IIEF-EF domain score was consistently and positively associated with satisfaction measures (P < 0.0001). Conclusions. Factor analysis detected close relationships among satisfaction questions in IIEF, SEP, and EDITS instruments, each of which, apart from IIEF Q6 (intercourse frequency), appeared to be an independent measure of satisfaction. Cultural differences may explain different satisfaction correlations with baseline ED severity in different regions. Clinicians may make use of the correlation between intercourse frequency (Q6) and satisfaction when prescribing a PDE5 inhibitor for ED, by explaining that the inhibitor should enable more frequent intercourse.
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