52,232 research outputs found
Lapsuusiällä alkavien epileptisten enkefalopatioiden ja liikehäiriöiden geneettiset syyt ja ilmiasun vaihtelu
No full textAbstractNovel genetic aetiologies for epileptic encephalopathies and movement disorders have been discovered by using next-generation sequencing methods. The phenotypic and genotypic variability in these conditions is very wide.The aim of this study was to discover novel genetic causes and phenotypes of childhood-onset drug-resistant epilepsy and epileptic or developmental encephalopathies that occur separately or together with movement disorders, and familial movement disorders. Furthermore, the use of whole-exome sequencing (WES) as a diagnostic tool in clinical practice was evaluated. Altogether, 12 children with undefined aetiology, who fulfilled the inclusion criteria, were included in the study.GABRG2 gene was identified as a genetic cause of epileptic encephalopathies. Novel GABRG2-associated phenotypes included progressive neurodegeneration, epilepsy in infancy with migrating focal seizures, and autism spectrum disorder. New pathogenic variants, GABRG2 p.P282T and p.S306F, were discovered.The pathogenic NACC1 variant caused focal epilepsy, developmental disability, bilateral cataracts, and dysautonomia. The novel phenotype associated with the NACC1 p.R298W variant included hyperkinetic movement disorder.SAMD9L was found to be the genetic cause for the familial movement disorder. The phenotype associated with the novel SAMD9L p.I891T variant was very variable. Neuroradiological findings included cerebellar atrophy and periventricular white matter changes. After publication of these results, SAMD9L was reported to be one of the most common genetic aetiologies of childhood bone marrow failure and myelodysplastic syndrome.The pathogenic homozygous MTR variant was found to cause early-onset epileptic encephalopathy that occurred together with movement disorder and haematological disturbances. Drug resistant seizures responded to cofactor and vitamin treatments.Whole-exome sequencing for 10 patients with drug-resistant epilepsy or epileptic or developmental encephalopathy provided a genetic diagnosis for two patients (20%).This study confirmed that, for epileptic encephalopathies and movement disorders in which the genetic causes and phenotypes are heterogeneous and sometimes treatable, WES is a useful tool for diagnostics and in the search for novel aetiologies, which might turn out to be more common than expected.Original papersOriginal papers are not included in the electronic version of the dissertation.Komulainen-Ebrahim, J., Schreiber, J. M., Kangas, S. M., Pylkäs, K., Suo-Palosaari, M., Rahikkala, E., … Uusimaa, J. (2019). Novel variants and phenotypes widen the phenotypic spectrum of GABRG2-related disorders. Seizure, 69, 99–104. https://doi.org/10.1016/j.seizure.2019.03.010Self-archived versionKomulainen-Ebrahim, J., Kuismin, O., Kangas, S. M., Kurian, M., Olsén P., & Uusimaa, J. (2019). Novel movement disorder caused by recurrent c.892C>T NACC1 variant. Manuscript in preparation.Tesi, B., Davidsson, J., Voss, M., Rahikkala, E., Holmes, T. D., Chiang, S. C. C., … Bryceson, Y. T. (2017). Gain-of-function SAMD9L mutations cause a syndrome of cytopenia, immunodeficiency, MDS, and neurological symptoms. Blood, 129(16), 2266–2279. https://doi.org/10.1182/blood-2016-10-743302Gorcenco, S., Komulainen-Ebrahim, J., Nordborg, K., Suo-Palosaari, M., Andréasson, S., Krüger, J., … Puschmann, A. (2017). Ataxia-pancytopenia syndrome with SAMD9L mutations. Neurology Genetics, 3(5), e183. https://doi.org/10.1212/nxg.0000000000000183Self-archived versionSaastamoinen, E., Rahikkala, E., Helander, H., Hinttala, R., Risteli, L., Rantala, H., … Komulainen-Ebrahim, J. (2017). Intractable Epilepsy due to MTR Deficiency: Importance of Homocysteine Analysis. Neuropediatrics, 48(6), 467–472. https://doi.org/10.1055/s-0037-1603976TiivistelmäUusien sekvensointimenetelmien käyttöönotto on mahdollistanut epileptisten enkefalopatioiden ja liikehäiriöiden uusien geneettisten syiden löytymisen. Näissä sairausryhmissä geenien ja ilmiasujen vaihtelevuus on suurta.Tutkimuksen tarkoituksena oli löytää uusia geneettisiä syitä ja ilmiasuja lapsuusiällä alkavissa vaikeahoitoisissa epilepsioissa ja epileptisissä tai kehityksellisissä joko itsenäisesti tai yhdessä liikehäiriön kanssa esiintyvissä enkefalopatioissa sekä perheittäin esiintyvissä liikehäiriöissä. Lisäksi selvitettiin eksomisekvensoinnin käyttökelpoisuutta kliinisessä diagnostiikassa näiden potilasryhmien kohdalla. Tutkimukseen osallistui yhteensä 12 sisäänottokriteerit täyttävää lasta, joiden sairauden syy oli jäänyt tuntemattomaksi.GABRG2-geenin mutaatiot aiheuttivat epileptisiä enkefalopatioita, joiden uutena ilmiasuna oli etenevä taudinkuva, johon liittyivät aivojen rappeutuminen, migroiva imeväisiän paikallisalkuinen epilepsia sekä autismikirjon häiriö. Tutkimuksessa löydettiin uusia GABRG2-mutaatioita: p.P282T ja p.S306F.NACC1-geenin mutaatio aiheutti epilepsian, kehitysvammaisuuden, molemminpuolisen kaihin ja autonomisen hermoston toiminnan häiriön. Hyperkineettinen liikehäiriö oli uusi NACC1 p.R298W -mutaatioon liittyvä ilmiasu.SAMD9L-geenin mutaatio aiheutti perheessä esiintyvän liikehäiriön. Neurologinen ja hematologinen ilmiasu olivat hyvin vaihtelevia. Aivojen kuvantamislöydöksiin sisältyi pikkuaivojen rappeutumista ja valkoisen aivoaineen muutoksia aivokammioiden ympärillä. Näiden tutkimustulosten julkaisemisen jälkeen SAMD9L-geenin mutaatioiden on todettu olevan yksi yleisimmistä perinnöllisistä luuytimen vajaatoiminnan ja myelodysplasian syistä.Homotsygoottinen MTR-geenin mutaatio aiheutti varhain alkaneen epileptisen enkefalopatian, liikehäiriön ja hematologisen häiriön. Kofaktori- ja vitamiini hoidot vähensivät epileptisiä kohtauksia, joihin tavanomainen lääkitys ei tehonnut.Geneettiset syyt ja ilmiasut ovat epileptisissä enkefalopatioissa ja liikehäiriöissä hyvin vaihtelevia, ja osaan on olemassa spesifi hoito. Eksomisekvensointi on käyttökelpoinen diagnostiikan ja uusien geneettisten syiden etsimisen apuna. Tässä tutkimuksessa eksomisekvensoinnin avulla kymmenestä potilaasta kahdelle (20 %) saatiin varmistettua geneettinen diagnoosi.OsajulkaisutOsajulkaisut eivät sisälly väitöskirjan elektroniseen versioon.Komulainen-Ebrahim, J., Schreiber, J. M., Kangas, S. M., Pylkäs, K., Suo-Palosaari, M., Rahikkala, E., … Uusimaa, J. (2019). Novel variants and phenotypes widen the phenotypic spectrum of GABRG2-related disorders. Seizure, 69, 99–104. https://doi.org/10.1016/j.seizure.2019.03.010Rinnakkaistallennettu versioKomulainen-Ebrahim, J., Kuismin, O., Kangas, S. M., Kurian, M., Olsén P., & Uusimaa, J. (2019). Novel movement disorder caused by recurrent c.892C>T NACC1 variant. Manuscript in preparation.Tesi, B., Davidsson, J., Voss, M., Rahikkala, E., Holmes, T. D., Chiang, S. C. C., … Bryceson, Y. T. (2017). Gain-of-function SAMD9L mutations cause a syndrome of cytopenia, immunodeficiency, MDS, and neurological symptoms. Blood, 129(16), 2266–2279. https://doi.org/10.1182/blood-2016-10-743302Gorcenco, S., Komulainen-Ebrahim, J., Nordborg, K., Suo-Palosaari, M., Andréasson, S., Krüger, J., … Puschmann, A. (2017). Ataxia-pancytopenia syndrome with SAMD9L mutations. Neurology Genetics, 3(5), e183. https://doi.org/10.1212/nxg.0000000000000183Rinnakkaistallennettu versioSaastamoinen, E., Rahikkala, E., Helander, H., Hinttala, R., Risteli, L., Rantala, H., … Komulainen-Ebrahim, J. (2017). Intractable Epilepsy due to MTR Deficiency: Importance of Homocysteine Analysis. Neuropediatrics, 48(6), 467–472. https://doi.org/10.1055/s-0037-1603976Academic dissertation to be presented with the assent of the Doctoral Training Committee of Health and Biosciences of the University of Oulu for public defence in Auditorium 12 of the Department of Paediatrics, on 10 May 2019, at 12 noonAbstract
Novel genetic aetiologies for epileptic encephalopathies and movement disorders have been discovered by using next-generation sequencing methods. The phenotypic and genotypic variability in these conditions is very wide.
The aim of this study was to discover novel genetic causes and phenotypes of childhood-onset drug-resistant epilepsy and epileptic or developmental encephalopathies that occur separately or together with movement disorders, and familial movement disorders. Furthermore, the use of whole-exome sequencing (WES) as a diagnostic tool in clinical practice was evaluated. Altogether, 12 children with undefined aetiology, who fulfilled the inclusion criteria, were included in the study.
GABRG2 gene was identified as a genetic cause of epileptic encephalopathies. Novel GABRG2-associated phenotypes included progressive neurodegeneration, epilepsy in infancy with migrating focal seizures, and autism spectrum disorder. New pathogenic variants, GABRG2 p.P282T and p.S306F, were discovered.
The pathogenic NACC1 variant caused focal epilepsy, developmental disability, bilateral cataracts, and dysautonomia. The novel phenotype associated with the NACC1 p.R298W variant included hyperkinetic movement disorder.
SAMD9L was found to be the genetic cause for the familial movement disorder. The phenotype associated with the novel SAMD9L p.I891T variant was very variable. Neuroradiological findings included cerebellar atrophy and periventricular white matter changes. After publication of these results, SAMD9L was reported to be one of the most common genetic aetiologies of childhood bone marrow failure and myelodysplastic syndrome.
The pathogenic homozygous MTR variant was found to cause early-onset epileptic encephalopathy that occurred together with movement disorder and haematological disturbances. Drug resistant seizures responded to cofactor and vitamin treatments.
Whole-exome sequencing for 10 patients with drug-resistant epilepsy or epileptic or developmental encephalopathy provided a genetic diagnosis for two patients (20%).
This study confirmed that, for epileptic encephalopathies and movement disorders in which the genetic causes and phenotypes are heterogeneous and sometimes treatable, WES is a useful tool for diagnostics and in the search for novel aetiologies, which might turn out to be more common than expected.Tiivistelmä
Uusien sekvensointimenetelmien käyttöönotto on mahdollistanut epileptisten enkefalopatioiden ja liikehäiriöiden uusien geneettisten syiden löytymisen. Näissä sairausryhmissä geenien ja ilmiasujen vaihtelevuus on suurta.
Tutkimuksen tarkoituksena oli löytää uusia geneettisiä syitä ja ilmiasuja lapsuusiällä alkavissa vaikeahoitoisissa epilepsioissa ja epileptisissä tai kehityksellisissä joko itsenäisesti tai yhdessä liikehäiriön kanssa esiintyvissä enkefalopatioissa sekä perheittäin esiintyvissä liikehäiriöissä. Lisäksi selvitettiin eksomisekvensoinnin käyttökelpoisuutta kliinisessä diagnostiikassa näiden potilasryhmien kohdalla. Tutkimukseen osallistui yhteensä 12 sisäänottokriteerit täyttävää lasta, joiden sairauden syy oli jäänyt tuntemattomaksi.
GABRG2-geenin mutaatiot aiheuttivat epileptisiä enkefalopatioita, joiden uutena ilmiasuna oli etenevä taudinkuva, johon liittyivät aivojen rappeutuminen, migroiva imeväisiän paikallisalkuinen epilepsia sekä autismikirjon häiriö. Tutkimuksessa löydettiin uusia GABRG2-mutaatioita: p.P282T ja p.S306F.
NACC1-geenin mutaatio aiheutti epilepsian, kehitysvammaisuuden, molemminpuolisen kaihin ja autonomisen hermoston toiminnan häiriön. Hyperkineettinen liikehäiriö oli uusi NACC1 p.R298W -mutaatioon liittyvä ilmiasu.
SAMD9L-geenin mutaatio aiheutti perheessä esiintyvän liikehäiriön. Neurologinen ja hematologinen ilmiasu olivat hyvin vaihtelevia. Aivojen kuvantamislöydöksiin sisältyi pikkuaivojen rappeutumista ja valkoisen aivoaineen muutoksia aivokammioiden ympärillä. Näiden tutkimustulosten julkaisemisen jälkeen SAMD9L-geenin mutaatioiden on todettu olevan yksi yleisimmistä perinnöllisistä luuytimen vajaatoiminnan ja myelodysplasian syistä.
Homotsygoottinen MTR-geenin mutaatio aiheutti varhain alkaneen epileptisen enkefalopatian, liikehäiriön ja hematologisen häiriön. Kofaktori- ja vitamiini hoidot vähensivät epileptisiä kohtauksia, joihin tavanomainen lääkitys ei tehonnut.
Geneettiset syyt ja ilmiasut ovat epileptisissä enkefalopatioissa ja liikehäiriöissä hyvin vaihtelevia, ja osaan on olemassa spesifi hoito. Eksomisekvensointi on käyttökelpoinen diagnostiikan ja uusien geneettisten syiden etsimisen apuna. Tässä tutkimuksessa eksomisekvensoinnin avulla kymmenestä potilaasta kahdelle (20 %) saatiin varmistettua geneettinen diagnoosi
Attributes of age-identity
No full textChronological age can be an unsatisfactory method of discriminating between older people. The lay concept of how old people actually feel may be more useful. The aim of the analyses reported in this paper was to investigate indicators of age-identity (or subjective age) among a national random sample of people aged 65 or more years living at home in Britain. Information was initially collected by home interview and a follow-up postal questionnaire 12-18 months later. The age that respondents felt was a more sensitive indicator than chronological age of many indicators of the respondents' health, psychological and social characteristics. Multiple regression analysis showed that baseline health and functional status, and reported changes in these at follow-up, explained 20.4 per cent of the variance in self-perceived age. Adding baseline mental health (anxiety/depression), feelings and fears about ageing at follow-up explained a further 0.8 per cent of the variance, making the total variance explained 21.2 per cent. It is concluded that measures of physical health and functional status and their interactions influenced age-identity. Mental health status and psychological perceptions made a small but significant additional contribution
Accountability in Complex Organizations: World Bank Responses to Civil Society
No full textCivil society actors have been pushing for greater accountability of the World Bank for at least three decades. This paper outlines the range of accountability mechanisms currently in place at the World Bank along four basic levels: (1) staff, (2) project, (3) policy, and (4) board governance. We argue that civil society organizations have been influential in pushing for greater accountability at the project and policy levels, particularly through the establishment and enforcement of social and environmental safeguards and complaint and response mechanisms. But they have been much less successful in changing staff incentives for accountability to affected communities, or in improving board accountability through greater transparency in decision making, more representative vote allocation, or better parliamentary scrutiny. In other words, although civil society efforts have led to some gains in accountability with respect to Bank policies and projects, the deeper structural features of the institution - the incentives staff face and how the institution is governed- remain largely unchanged.
The astrochemical observatory: Computational and theoretical focus on molecular chirality changing torsions around O – O and S – S bonds
No full textThe observation of hydrogen peroxide in the interstellar medium represents a remarkable discovery for the astrochemistry community. The prototypical role that this molecule, arguably the simplest chiral molecule, plays in the evolution of life in biospheres, is related to the chirality change transitions associated with the torsional motions around the O - O and the S - S bonds. In this paper, we present an overview on the state-of-art of possible experiments to demonstrate chiral effects discrimination and computational tools applied to peroxides and persulfides
Equality of Google Scholar with Web of Science Citations: Case of Malaysian Engineering Highly Cited Papers
No full textThis study uses citation analysis from two citation tracking databases, Google Scholar (GS) and ISI Web of Science, in order to test the correlation between them and examine the effect of the number of paper versions on citations. The data were retrieved from the Essential Science Indicators and Google Scholar for 101 highly cited papers from Malaysia in the field of engineering. An equation for estimating the citation in ISI based on Google scholar is offered. The results show a significant and positive relationship between both citation in Google Scholar and ISI Web of Science with the number of versions. This relationship is higher between versions and ISI citations (r = 0.395, p<0.01) than between versions and Google Scholar citations (r = 0.315, p<0.01). Free access to data provided by Google Scholar and the correlation to get ISI citation which is costly, allow more transparency in tenure reviews, funding agency and other science policy, to count citations and analyze scholars’ performance more precisely.Ale Ebrahim, N., Salehi, H., Embi, M. A., Danaee, M., Mohammadjafari, M., Zavvari, A., . . . Shahbazi-Moghadam, M. (2014). Equality of Google Scholar with Web of Science Citations: Case of Malaysian Engineering Highly Cited Papers. Modern Applied Science, 8(5), 63-69. doi: 10.5539/mas.v8n5p6
Incident disability in older adults: prediction models based on two British prospective cohort studies
No full textObjective: to develop and validate a prediction model for incident locomotor disability after 7 years in older adults.Setting: prospective British cohort studies: British Women's Heart and Health Study (BWHHS) for development and the English Longitudinal Study of Ageing (ELSA) for validation.Subjects: community-dwelling older adults.Methods: multivariable logistic regression models after selection of predictors with backward elimination. Model performance was assessed using metrics of discrimination and calibration. Models were internally and externally validated.Results: locomotor disability was reported in BWHHS by 861 of 1,786 (48%) women after 7 years. Age, a history of arthritis and low physical activity levels were the most important predictors of locomotor disability. Models using routine measures as predictors had satisfactory calibration and discrimination (c-index 0.73). Addition of 31 blood markers did not increase the predictive performance. External validation in ELSA showed reduced discrimination (c-index 0.65) and an underestimation of disability risks. A web-based calculator for locomotor disability is available (http://www.sealedenvelope.com/trials/bwhhsmodel/).Conclusions: we developed and externally validated a prediction model for incident locomotor disability in older adults based on routine measures available to general practitioners, patients and public health workers, and showed an adequate discrimination. Addition of blood markers from major biological pathways did not improve the performance of the model. Further replication in additional data sets may lead to further enhancement of the current model
Do perceptions of neighbourhood environment influence health? Baseline findings from a British survey of aging
No full textObjectives: To investigate the relation between perceived neighbourhood environment, social contact and support, and self efficacy, on the health of older people.
Design: British cross sectional population survey of people aged 65 and over.
Participants: 999 people aged 65 plus living at home in Britain.
Results: Regression modelling showed that high self efficacy had a strong independent association with better self rated health status and physical functioning. Indicators of perceived neighbourhood environment that showed strong associations with both good health and functioning were: perceptions of good quality facilities in the area (social/leisure, facilities for people aged 65+, rubbish collection, health services, transport, closeness to shops, somewhere nice to walk), and high levels of neighbourliness (knows/trusts people). Perceptions of problems in the area (noise, crime, air quality, rubbish/litter, traffic, graffiti) were also predictive of poorer health. Measures of social contact and support did not show any independent associations with health or functioning.
Conclusions: The unique value of this paper is in the simultaneous analysis of associations between perceived neighbourhood, social contact and support, self efficacy, and health. The consistent strength of older people?s perceptions of the quality of facilities in their neighbourhoods shows that responsive reinforcement of local infrastructures might have wider health benefits. Also of interest was the strength of self efficacy as a predictor of self rated health and physical functioning. The results have implications for both neighbourhood level interventions and self management programmes in chronic illness
Going Beyond Counting First Authors in Author Co-citation Analysis
No full textThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Improving stroke patients' care: a patient held record is not enough
No full textBackground: Stroke patients' care in hospital tends to be poorly organised, with poor communication and a lack of information being frequent sources of complaint. The purpose of this study was to evaluate whether a patient-held record (PHR) would result in greater patient satisfaction and better care planning for stroke patients.Methods: A time series control (6 months) - intervention (8 months) - control ( 6 months) was used among London teaching hospital general medical and geriatric medicine inpatient wards. All stroke patients admitted to the wards during the intervention phase received a PHR and were instructed in its use. Demographic, stroke severity, social factors and outcomes were collected from all stroke patients during all phases of the study.Results: Of 252 stroke patients aged 46 to 98 years entered into the study, by six months after admission 118 (46.8%) had died. PHR and control group patients were well matched in terms of socio-demographic characteristics and pre-stroke ability. At six months after admission, 119 (97%) patients responded to the questionnaire. Just over half (56%, 13) of intervention group patients recalled receiving a PHR. Of those patients, 59% reported reading the PHR, 27% had lost their PHR, and two-thirds said they had difficulties encouraging staff to write in the PHR. Half felt that possession of the PHR was more trouble than it was worth. PHR group patients were more satisfied with the recovery they had made (79% vs. 59%, p = 0.04), but felt less able to talk to staff about their problems (61% vs. 82%, p = 0.02). PHR group patients reported receiving fewer explanations about their condition (18% vs. 33%, p = 0.12) and treatment (26% vs. 45%, p = 0.07), and were more afraid of asking doctors questions (21% vs. 4%, p = 0.01) than controls. PHR group patients were no better prepared for hospital discharge than control group patients, and both groups were ill-informed about services and benefits that might have helped after discharge from hospital.Conclusions: Stroke patients received poor information and explanations regardless of whether they received a PHR. A PHR did not appear to improve patient satisfaction or discharge planning, and may have reduced opportunities for communication and explanation
Observations of Bºs→ψ(2S)η and Bº(s)→ψ(2S)π+π- decays
No full textFirst observations of the B0s
→ψ(2S)η, B0 →ψ(2S)π
+
π
− and B0s
→ψ(2S)π
+
π
− decays are made
using a dataset corresponding to an integrated luminosity of 1.0 fb−1 collected by the LHCb experiment in
proton–proton collisions at a centre-of-mass energy of
√
s = 7 TeV. The ratios of the branching fractions
of each of the ψ(2S) modes with respect to the corresponding J/ψ decays are
B(B0s
→ψ(2S)η)
÷
B(B0s
→J/ψη)
= 0.83± 0.14 (stat)±0.12 (syst) ±0.02 (B),
;
B(B0→ψ(2S)π
+
π
−
)
÷
B(B0→J/ψπ
+
π
−
)
= 0.56± 0.07 (stat)±0.05 (syst)± 0.01 (B),
;
B(B0s
→ψ(2S)π
+
π
−
)
÷
B(B0s
→J/ψπ
+
π
−
)
= 0.34± 0.04 (stat)±0.03 (syst)± 0.01 (B),
where the third uncertainty corresponds to the uncertainties of the dilepton branching fractions of the J/ψ
and ψ(2S) meson decays
- …
