916 resultados para reference frames
Resumo:
BACKGROUND: Niemann-Pick type C (NP-C) is a rare progressive neurodegenerative lipid storage disorder with heterogeneous clinical presentation and challenging diagnostic procedures. Recently oxysterols have been reported to be specific biomarkers for NP-C but knowledge on the intra-individual variation and on reference intervals in children and adolescents are lacking. METHODS: We established a LC-MS/MS assay to measure Cholestane-3β, 5α, 6β-triol (C-triol) and 7-Ketocholesterol (7-KC) following Steglich esterification. To assess reference intervals and intra-individual variation we determined oxysterols in 148 children and adolescents from 0 to 18 years and repeat measurements in 19 of them. RESULTS: The reported method is linear (r>0.99), sensitive (detection limit of 0.03 ng/mL [0.07 nM] for C-triol, and 0.54 ng/mL [1.35 nM] for 7-KC) and precise, with an intra-day imprecision of 4.8% and 4.1%, and an inter-day imprecision of 7.0% and 11.0% for C-triol (28 ng/ml, 67 nM) and 7-KC (32 ng/ml, 80 nM), respectively. Recoveries for 7-KC and C-triol range between 93% and 107%. The upper reference limit obtained for C-triol is 40.4 ng/mL (95% CI: 26.4-61.7 ng/mL, 96.0 nM, 95% CI: 62.8-146.7 nM) and 75.0 ng/mL for 7-KC (95% CI: 55.5-102.5 ng/mL, 187.2 nM, 95% CI: 138.53-255.8 nM), with no age or gender dependency. Both oxysterols have a broad intra-individual variation of 46%±23% for C-triol and 52%±29% for 7-KC. Nevertheless, all Niemann-Pick patients showed increased C-triol levels including Niemann-Pick type A and B patients. CONCLUSIONS: The LC-MS/MS assay is a robust assay to quantify C-triol and 7-KC in plasma with well documented reference intervals in children and adolescents to screen for NP-C in the pediatric population. In addition our results suggest that especially the C-triol is a biomarker for all three Niemann-Pick diseases.
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This paper describes an evaluation framework that allows a standardized and quantitative comparison of IVUS lumen and media segmentation algorithms. This framework has been introduced at the MICCAI 2011 Computing and Visualization for (Intra)Vascular Imaging (CVII) workshop, comparing the results of eight teams that participated. We describe the available data-base comprising of multi-center, multi-vendor and multi-frequency IVUS datasets, their acquisition, the creation of the reference standard and the evaluation measures. The approaches address segmentation of the lumen, the media, or both borders; semi- or fully-automatic operation; and 2-D vs. 3-D methodology. Three performance measures for quantitative analysis have been proposed. The results of the evaluation indicate that segmentation of the vessel lumen and media is possible with an accuracy that is comparable to manual annotation when semi-automatic methods are used, as well as encouraging results can be obtained also in case of fully-automatic segmentation. The analysis performed in this paper also highlights the challenges in IVUS segmentation that remains to be solved.
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We empirically contribute to the debate on business education in building on a decision frame perspective of decision making in corporate responsibility settings. Business schools have been accused to teach amoral theories, leading their students to behave less morally and engendering corporate responsibility scandals. Research has also pointed toward self-selection: business students would differ from non-business students before entering business school. We examine the role of socioeconomic status, core self-evaluations in this regard. Further, we investigate the belief in a free market as a distal influence triggering a business frame, and moral intensity as a proximal influence triggering a moral frame on responsible decision making by business and non-business students. Cross-sectional data obtained from 566 students on two decision making scenarios mostly supported our hypotheses. Socioeconomic status but not core self-evaluations explain the belief in a free market, and had indirect effects on the likelihood to make a less responsible decision. Importantly, the relationship between business studies and the belief in a free market remained significant after accounting for these variables. Our study thus contributes to the socialization and self-selection arguments. We discuss theoretical and practical implications for research on decision frames and for business education, respectively.
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Tutkimuksen tavoitteena oli tuottaa tietoa siitä, mitä maahanmuuttajia koskevat erityiskysymykset suomalaisessa lastensuojelun sosiaalityössä ovat ja miten näitä kysymyksiä lastensuojelussa käsitellään. Teoreettismetodologisena viitekehyksenä on sosiaalinen konstruktionismi. Etnisten suhteiden tutkimusperinteessä työ paikantuu keskusteluun, jossa kulttuuri ja etnisyys nähdään sosiaalisesti rakentuvina ja muuntuvina. Analyysissä sovelletaan diskurssianalyyttistä metodologiaa. Tutkimus rakentuu yhteenveto-osiosta ja neljästä artikkelista. Maahanmuuttajasosiaalityötä ja lastensuojelua tarkastellaan sosiaalityöntekijöiden, muiden ammattilaisten ja asiakkaiden kielenkäytön kautta. Aineisto koostuu 11 lastensuojelun asiakaskeskustelusta ja niiden jälkeen keskustelun osapuolille tehdyistä haastatteluista, joita on yhteensä 35. Tutkimuksessa analysoidaan seuraavia kysymyksiä: Miten sosiaalityöntekijät tulkitsevat maahanmuuttajasosiaalityön erityisyyttä oman ammatillisen tehtävänsä näkökulmasta? Minkälaisia ominaisuuksia sosiaalityöntekijät rakentavat maahanmuuttaja-asiakkaille? Miten lastensuojelun keskusteluissa puhutaan monikulttuurisuuteen liittyvistä teemoista, kuten erilaisuudesta ja samanlaisuudesta sekä kulttuuri- ja rasismikysymyksistä? Miten maahanmuuttajalasten ja -nuorten osallisuus lastensuojelun asiakaskeskusteluissa rakentuu aikuisten ja lasten itsensä tuottamana? Mitä ja miten maahanmuuttajalapset ja -nuoret puhuvat kokemuksistaan lastensuojelussa ja suomalaisessa yhteiskunnassa? Maahanmuuttajien erityiskysymyksiä ovat kieleen, kulttuuriin ja valtayhteiskunnan toimintaan liittyvät ymmärtämisvaikeudet, kokemukset arkipäivän rasismista sekä perheen ja yhteisön merkittävä, osin ristiriitainen rooli. Lapsilla ja nuorilla kulttuuri on muuntuvaa ja jatkuvien neuvottelujen kohteena. Aineiston lastensuojelutilanteiden taustalla on usein kouluympäristöön liittyviä vaikeuksia. Haastatteluissa lapset kertovat kokemuksistaan ja toimijuudestaan perheeseen, yhteisöön ja kouluun paikantuvissa tilanteissa. Asiakaskeskusteluissa lasten puhuja-asema on usein heikko, jos aikuiset eivät aktiivisesti vahvista sitä. Jotkut lapset ottavat itse vahvan puhuja-aseman. Asiakaskeskusteluissa maahanmuuttajien erityiskysymyksistä puhutaan harvoin eksplisiittisesti. Haastatteluissa sosiaalityöntekijät enemmän tai vähemmän tietoisesti paikantavat maahanmuuttajasosiaalityötä vieraannuttavaan, sopeuttavaan, tasa-arvoistavaan, kulttuuritietoiseen, rasismitietoiseen ja osallistavaan kehykseen. Kehykset nostavat sosiaalityön tavoitteista, menetelmistä ja asiakkaasta keskeisiksi erilaisia asioita. Tulkinnat ovat muuntuvia, vaikka osoittavat myös tiettyä säännönmukaisuutta. Kulttuuri on keskeinen käsite erilaisuuden ja samanlaisuuden ymmärtämiseksi. Sekä työntekijät että asiakkaat perustelevat toivottavia elämäntapoja "omalla kulttuurillaan" ja selittävät ongelmia ”erilaisella kulttuurilla”. Kulttuurin käsitettä voidaan myös käyttää työvälineenä asiakaskeskusteluissa avattaessa asiakkaan omaa näkökulmaa korostavaa dialogia. Perheen ja kulttuurisen yhteisön merkitys on tärkeää arvioida lapsen ja nuoren hyvinvoinnin ja kulttuurisen identiteetin kehittymisen näkökulmasta. Sosiaalityöntekijöillä on merkittävä välittäjän rooli yhtäältä valtayhteiskunnan ja maahanmuuttaja-asiakkaiden, toisaalta vanhempien, yhteisöjen sekä lasten ja nuorten välillä. Lastensuojelussa haasteena on arkipäivän rasismin tiedostaminen sekä siihen pureutuvien työmenetelmien kehittäminen.
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Leukemiaa sairastavien lasten kuumeiset infektiot, erityisesti respiratoriset virusinfektiot Tausta: Hengitysteiden virusinfektiot ovat lasten tavallisimpia sairauksia. Infektiota aiheuttava virus voidaan uusilla menetelmillä löytää lähes kaikissa tapauksissa. Leukemiaa sairastavilla lapsilla on perustaudin ja leukemian hoitojen takia tavallista suurempi infektioalttius, ja kuumeilu on tavallista leukemiahoidon aikana. Suurin osa syöpähoidon aikaisten kuumejaksojen syistä jää kuitenkin selvittämättä. Tavoitteet: Prospektiivisen 5 vuotta kestäneen monikeskustutkimuksen tavoitteena oli etsiä uusimmilla mikrobiologisilla menetelmillä leukemiaa sairastavien lasten kuumeen syy. Tätä varten tutkittiin 16 virusta virusviljelyllä, antigeeniosoituksella ja nukleiinihappo-osoituksella. Näytteitä otettiin nenästä, ulosteesta, virtsasta ja verestä. Lisäksi tutkittiin MxA-proteiinin kykyä osoittaa virusinfektio syöpälapsella. Tulokset: Tutkimuksen aikana analysoitiin 138 kuumejaksoa 51 leukemialapsella. Kokonaisseuranta-aika oli 1.5 vuotta/lapsi. Kuumejaksojen ilmaantuvuus oli 2.1 jaksoa potilasta kohden suhteutettuna vuoden riskiaikaan. Hengistysteiden virusinfektio voitiin osoittaa 82 kuumejaksossa (59%). Kaksi tai useampi virus löydettiin 12 %:ssa kuumejaksoista. Tavallisimmat virukset olivat rhinovirus (22 %), respiratory syncytial virus eli RS-virus (11 %), human herpes virus 6 (7 %), human bocavirus (5 %), sytomegalovirus (5 %), parainfluenssavirukset (5 %) ja influenssa A -virus (4 %). Kahdelle potilaalle kehittyi pneumonia, muilla oireet olivat lievät. Veriviljely oli positiivinen 19 kuumejaksossa (14 %), ja puolessa tapauksista löydettiin samanaikaisesti respiratorinen virus. MxA proteini ilmeni veren lymfosyyteissä useimmilla virusinfektioon sairastuneilla syöpälapsilla. Päätelmät: Kuumeiset respiratoriset virusinfektiot ovat tavallisia leukemiaa sairastavilla lapsilla. Infektion oireet ovat tavallisesti vähäiset, mutta pienelle osalle voi kehittyä veriviljelypositiivinen sepsis tai pneumonia. Kuumeen syy jäi selvittämättä vain harvoissa tapauksissa.
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Aims: The aims were to create clinically feasible reference intervals for thyroidstimulating hormone (TSH) and free thyroxine (FT4) and to analyze associations between thyroid function and self-rated health, neuropsychiatric symptoms, depression and dementia in the elderly. The second aim was also to establish reference intervals for sex hormones and to analyze associations between sex hormone levels and self-rated health, symptoms, depression and dementia in elderly men. Subjects and methods: The study population comprised 1252 subjects aged 65 years or over, living in the municipality of Lieto, south-western Finland. Self-rated health, life satisfaction, symptoms, depression, and dementia were assessed with specific questions, clinical examination and tools such as the Zung Self-report Depression Scale and the Mini-Mental State Examination. Independent variables were dichotomized, and associations of these variables with TSH, FT4 or sex hormone levels were assessed. Levels of TSH and FT4 in thyroid disease–free women and women treated with thyroxine were also compared. Results: Elevated concentrations of thyroid peroxidase antibodies (TPOAb) or thyroglobulin antibodies (TgAb) were found to have a marked effect on the upper reference limit for TSH among women, who were thyroid antibody positive more higher than suggested in several recent guidelines. After age adjustment, there were no associations between TSH levels and self-rated health, life satisfaction, or most neuropsychiatric symptoms in the thyroid disease-free population. Although women with thyroxine treatment for primary hypothyroidism had far higher TSH levels than thyroid disease-free women, there were no differences between thyroid-disease free women and women with stable thyroxine treatment regarding self-rated health, life satisfaction or symptoms. Age had a significant positive association with luteinizing hormone (LH), follicle 2 practice, one range in men aged 65 years or over can be used for T, E2 and FSH measured with the AutoDelfia method, but two separate reference intervals should be used for fT, LH and SHBG. After adjustment for age, higher levels of T and fT were associated with better self-rated health (SRH) in the reference population. After adjustment for age and body mass index (BMI), there were no associations between sex hormone concentrations and self-rated health, life satisfaction or most symptoms in concentration. Conclusion: Age-specific reference intervals were derived for thyroid function and sex hormones based on comprehensive data from a community-dwelling population with a high participation rate. The results do not support the need to decrease the upper reference limit for TSH or to lower the optimal TSH target in levothyroxine treatment in older adults, as recommended in recent guidelines. Older age or being overweight symptoms among elderly men. The associations of single symptoms with T levels were inconsistent among elderly men, although the association of low T level with diagnosed depression might be clinically significant.
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The formation of reference groups comprises an important procedure in chemical provenance studies of archaeological pottery. Material from ancient kilns is thought to be especially suitable for reference groups, as it comprises a definite unit of past production. Pottery from the Late Minoan IA kiln excavated at Kommos, Crete was analysed in order to produce a reference group in this important area of Minoan ceramic production. The samples were characterized by a combination of techniques providing information on the chemistry, mineralogy and microstructure of the ceramic body. Initially, the study was unable to establish, in a straightforward manner, a chemical reference group. Different ceramic pastes and a range of selective alterations and contaminations, affected by variable firing temperatures and burial environment, were shown to be responsible for the compositional variability. Procedures are described to compensate for such alterations and the perturbations in the data that they produce.
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Tämä tutkimus perustuu prosessijohtamiseen ja tilaus-toimitusprosessin suorituskyvyn mittaamiseen. Tutkimusongelmaa lähestytään toiminta-analyyttisen ja konstruktiivisen tutkimusotteen avulla. Toiminta-analyyttinen tutkimusote vaatii tutkimusongelmaan liittyvään teoriaan perehtymistä ja suosituksia toimenpiteistä. Tämän vuoksi tutkimuksessa on syvennytty aikaisempiin suorituskykyä sekä prosessijohtamista koskeviin teorioihin ja tutkimusraportteihin, jotta löydettäisiin case-yrityksen näkökulmasta vastauksia esitettyihin tutkimuskysymyksiin. Tutkimuksen tarkoituksena on analysoida case-yrityksen tilaus-toimitusprosessin johtamista ja prosessin suorituskykyyn vaikuttavia tekijöitä. Tavoitteena on löytää sellaisia suorituskyvyn osa-alueita, joiden mittaaminen tuottaa helpoiten ja nopeasti tietoa päätöksenteon tueksi sekä tilaus-toimituksen johtamista varten. Toisena tavoitteena on selvittää, millaisilla mittareilla yrityksen suorituskykyä voidaan mitata. Tutkimuksessa hyödynnetään toiminta-analyyttistä ja konstruktiivista tutkimusotetta sekä otteisiin liittyviä eri tutkimusmenetelmiä. Tutkimuksen lähestymistapa perustuu pk-yrityksen lähtökohtiin. Koska työssä tarkastellaan suorituskykyä sisäisen suorituskyvyn näkökulmasta, työssä esitellään sisäisen suorituskyvyn eri osa-alueita. Kansainvälisen tutkimuksen mukaan pk-yritykselle tärkeitä sisäisen suorituskyvyn osa-alueita ovat aika, joustavuus, laatu, talous, asiakastyytyväisyys sekä henkilöstön osaaminen ja innovatiivisuus. Tässä tutkimuksessa edellä mainitut suorituskyvyn osa-alueet todennettiin tärkeiksi, kun analysoitiin case-yrityksen tilaus-toimituksen kriittisiä menestystekijöitä. Tutkimustyön tuloksena rakennettiin yksinkertainen ja helppokäyttöinen mittaristo sekä analysointimenetelmä, jonka avulla on mahdollista seurata tilaus-toimitusprosessin suorituskykyä. Mittaristo rakennettiin SAKE-suorituskyvyn analysointijärjestelmän pohjalle.
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CONTEXT: Complex steroid disorders such as P450 oxidoreductase deficiency or apparent cortisone reductase deficiency may be recognized by steroid profiling using chromatographic mass spectrometric methods. These methods are highly specific and sensitive, and provide a complete spectrum of steroid metabolites in a single measurement of one sample which makes them superior to immunoassays. The steroid metabolome during the fetal-neonatal transition is characterized by (a) the metabolites of the fetal-placental unit at birth, (b) the fetal adrenal androgens until its involution 3-6 months postnatally, and (c) the steroid metabolites produced by the developing endocrine organs. All these developmental events change the steroid metabolome in an age- and sex-dependent manner during the first year of life. OBJECTIVE: The aim of this study was to provide normative values for the urinary steroid metabolome of healthy newborns at short time intervals in the first year of life. METHODS: We conducted a prospective, longitudinal study to measure 67 urinary steroid metabolites in 21 male and 22 female term healthy newborn infants at 13 time-points from week 1 to week 49 of life. Urine samples were collected from newborn infants before discharge from hospital and from healthy infants at home. Steroid metabolites were measured by gas chromatography-mass spectrometry (GC-MS) and steroid concentrations corrected for urinary creatinine excretion were calculated. RESULTS: 61 steroids showed age and 15 steroids sex specificity. Highest urinary steroid concentrations were found in both sexes for progesterone derivatives, in particular 20α-DH-5α-DH-progesterone, and for highly polar 6α-hydroxylated glucocorticoids. The steroids peaked at week 3 and decreased by ∼80% at week 25 in both sexes. The decline of progestins, androgens and estrogens was more pronounced than of glucocorticoids whereas the excretion of corticosterone and its metabolites and of mineralocorticoids remained constant during the first year of life. CONCLUSION: The urinary steroid profile changes dramatically during the first year of life and correlates with the physiologic developmental changes during the fetal-neonatal transition. Thus detailed normative data during this time period permit the use of steroid profiling as a powerful diagnostic tool.
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Mammalian gene expression displays widespread circadian oscillations. Rhythmic transcription underlies the core clock mechanism, but it cannot explain numerous observations made at the level of protein rhythmicity. We have used ribosome profiling in mouse liver to measure the translation of mRNAs into protein around the clock and at high temporal and nucleotide resolution. We discovered, transcriptome-wide, extensive rhythms in ribosome occupancy and identified a core set of approximately 150 mRNAs subject to particularly robust daily changes in translation efficiency. Cycling proteins produced from nonoscillating transcripts revealed thus-far-unknown rhythmic regulation associated with specific pathways (notably in iron metabolism, through the rhythmic translation of transcripts containing iron responsive elements), and indicated feedback to the rhythmic transcriptome through novel rhythmic transcription factors. Moreover, estimates of relative levels of core clock protein biosynthesis that we deduced from the data explained known features of the circadian clock better than did mRNA expression alone. Finally, we identified uORF translation as a novel regulatory mechanism within the clock circuitry. Consistent with the occurrence of translated uORFs in several core clock transcripts, loss-of-function of Denr, a known regulator of reinitiation after uORF usage and of ribosome recycling, led to circadian period shortening in cells. In summary, our data offer a framework for understanding the dynamics of translational regulation, circadian gene expression, and metabolic control in a solid mammalian organ.
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Adolescence is an important time for acquiring high peak bone mass. Physical activity is known to be beneficial to bone development. The effect of estrogen-progestin contraceptives (EPC) is still controversial. Altogether 142 (52 gymnasts, 46 runners, and 42 controls) adolescent women participated in this study, which is based on two 7-year (n =142), one 6-year (n =140) and one 4-year (n =122) follow-ups. Information on physical activity, menstrual history, sexual maturation, nutrition, living habits and health status was obtained through questionnaires and interviews. The bone mineral density (BMD) and content (BMC) of lumbar spine (LS) and femoral neck (FN) were measured by dual- energy X-ray absoptiometry. Calcaneal sonographic measurements were also made. The physical activity of the athletes participating in this study decreased after 3-year follow-up. High-impact exercise was beneficial to bones. LS and FN BMC was higher in gymnasts than in controls during the follow-up. Reduction in physical activity had negative effects on bone mass. LS and FN BMC increased less in the group having reduced their physical activity more than 50%, compared with those continuing at the previous level (1.69 g, p=0.021; 0.14 g, p=0.015, respectively). The amount of physical activity was the only significant parameter accounting for the calcaneal sonography measurements at 6-year follow-up (11.3%) and reduced activity level was associated with lower sonographic values. Long-term low-dose EPC use seemed to prevent normal bone mass acquisition. There was a significant trend towards a smaller increase in LS and FN BMC among long-term EPC users. In conclusion, this study confirms that high-impact exercise is beneficial to bones and that the benefits are partly maintained even after a clear reduction in training level at least for 4 years. Continued exercise is needed to retain all acquired benefits. The bone mass gained and maintained can possibly be maximized in adolescence by implementing high-impact exercise for youngsters. The peak bone mass of the young women participating in the study may be reached before the age of 20. Use of low-dose EPCs seems to suppress normal bone mass acquisition.
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The brain integrates multiple sensory inputs, including somatosensory and visual inputs, to produce a representation of the body. Spinal cord injury (SCI) interrupts the communication between brain and body and the effects of this deafferentation on body representation are poorly understood. We investigated whether the relative weight of somatosensory and visual frames of reference for body representation is altered in individuals with incomplete or complete SCI (affecting lower limbs' somatosensation), with respect to controls. To study the influence of afferent somatosensory information on body representation, participants verbally judged the laterality of rotated images of feet, hands, and whole-bodies (mental rotation task) in two different postures (participants' body parts were hidden from view). We found that (i) complete SCI disrupts the influence of postural changes on the representation of the deafferented body parts (feet, but not hands) and (ii) regardless of posture, whole-body representation progressively deteriorates proportionally to SCI completeness. These results demonstrate that the cortical representation of the body is dynamic, responsive, and adaptable to contingent conditions, in that the role of somatosensation is altered and partially compensated with a change in the relative weight of somatosensory versus visual bodily representations.