Specific language impairment in pre-adolescence, adolescence, and adulthood with special emphasis on health-related quality of life

This clinical study focused on effects of childhood specific language impairment (SLI) on daily functioning in late life. SLI is a neurobiological disorder with genetic predisposition and manifests as poor language production or comprehension or both in a child with age-level non-verbal intelligence and no other known cause for deficient language development. The prevalence rate of around 7% puts it among the most prevalent developmental disorders in childhood. Negative long-term effects, such as problems in learning and behavior, are frequent. In follow-up studies the focus has seldom been on self-perception of daily functioning and participation, which are considered important in the International Classification of Functioning, Disability, and Health (ICF). To investigate the self-perceived aspects of everyday functioning in individuals with childhood receptive SLI compared with age- and gender-matched control populations, the 15D, 16D, and 17D health-related quality of life (HRQoL) questionnaires were applied. These generic questionnaires include 15, 16, and 17 dimensions, respectively, and give both a single index score and a profile with values on each dimension. Information on different life domains (rehabilitation, education, employment etc.) from each age-group was collected with separate questionnaires. The study groups comprised adults, adolescents (12-16 years), and pre-adolescents (8-11 years) who had received a diagnosis of receptive SLI and had been examined, usually before school age, at the Department of Phoniatrics of Helsinki University Central Hospital, where children with language deficits caused by various etiologies are examined and treated by a multidisciplinary team. The adult respondents included 33 subjects with a mean age of 34 years. Measured with 15D, the subjects perceived their HRQoL to be nearly as good as that of their controls, but on the dimensions of speech, usual activities, mental functioning, and distress they were significantly worse off. They significantly more often lived with their parents (19%) or were pensioned (26%) than the adult Finnish population on average. Adults with self-perceived problems in finding words and in remembering instructions, manifestations of persistent language impairment, showed inferior every day functioning to the rest of the study group. Of the adolescents and pre-adolescents, 48 and 51, respectively, responded. The majority in both groups had received special education or extra educational support at school. They all had attended speech therapy at some point; at the time of the study only one adolescent, but every third pre-adolescent still received speech therapy. The 16D score of the adolescent or the 17D score of the pre-adolescents did not differ from that of their controls. The 16D profiles differed on some dimensions; subjects were significantly worse off on the dimension of mental functioning, but better off on the dimension of vitality than controls. Of the 17D dimensions, the study group was significantly worse off on speech, whereas the control group reported significantly more problems in sleeping. Of the childhood performance measures investigated, low verbal intelligence quotient (VIQ), which is often considered to reflect receptive language impairment, was in adults subjects significantly associated with some of the self-perceived problems, such as problems in usual activities and mental functioning. The 15D, 16D, and 17D questionnaires served well in measuring self-perceived HRQoL. Such standardized measures with population values are especially important in confirming with the ICF guidelines. In the future these questionnaires could perhaps be used on a more individual level in follow-up of children in clinics, and even in special schools and classes, to detect those children at greatest risk of negative long-term effects and perhaps diminished well-being regarding daily functioning and participation.

Seeing and hearing speech, sounds, and signs: functional magnetic resonance studies on fluent and dyslexic readers

Speech has both auditory and visual components (heard speech sounds and seen articulatory gestures). During all perception, selective attention facilitates efficient information processing and enables concentration on high-priority stimuli. Auditory and visual sensory systems interact at multiple processing levels during speech perception and, further, the classical motor speech regions seem also to participate in speech perception. Auditory, visual, and motor-articulatory processes may thus work in parallel during speech perception, their use possibly depending on the information available and the individual characteristics of the observer. Because of their subtle speech perception difficulties possibly stemming from disturbances at elemental levels of sensory processing, dyslexic readers may rely more on motor-articulatory speech perception strategies than do fluent readers. This thesis aimed to investigate the neural mechanisms of speech perception and selective attention in fluent and dyslexic readers. We conducted four functional magnetic resonance imaging experiments, during which subjects perceived articulatory gestures, speech sounds, and other auditory and visual stimuli. Gradient echo-planar images depicting blood oxygenation level-dependent contrast were acquired during stimulus presentation to indirectly measure brain hemodynamic activation. Lip-reading activated the primary auditory cortex, and selective attention to visual speech gestures enhanced activity within the left secondary auditory cortex. Attention to non-speech sounds enhanced auditory cortex activity bilaterally; this effect showed modulation by sound presentation rate. A comparison between fluent and dyslexic readers' brain hemodynamic activity during audiovisual speech perception revealed stronger activation of predominantly motor speech areas in dyslexic readers during a contrast test that allowed exploration of the processing of phonetic features extracted from auditory and visual speech. The results show that visual speech perception modulates hemodynamic activity within auditory cortex areas once considered unimodal, and suggest that the left secondary auditory cortex specifically participates in extracting the linguistic content of seen articulatory gestures. They are strong evidence for the importance of attention as a modulator of auditory cortex function during both sound processing and visual speech perception, and point out the nature of attention as an interactive process (influenced by stimulus-driven effects). Further, they suggest heightened reliance on motor-articulatory and visual speech perception strategies among dyslexic readers, possibly compensating for their auditory speech perception difficulties.

Soy supplementation and role of equol production capability in postmenopausal women using tibolone: effects on cardiovascular risk markers

Tibolone, a synthetic steroid, is effective in the treatment of postmenopausal symptoms. Its cardiovascular safety profile has been questioned, because tibolone reduces the levels of high-density lipoprotein (HDL) cholesterol. Soy-derived isoflavones may offer health benefits, particularly as regards lipids and also other cardiovascular disease (CVD) risk factors. The soy-isoflavone metabolite equol is thought to be the key as regards soy-related beneficial effects. We studied the effects of soy supplementation on various CVD risk factors in postmenopausal monkeys and postmenopausal women using tibolone. In addition, the impact of equol production capability was studied. A total of 18 monkeys received casein/lactalbumin (C/L) (placebo), tibolone, soy (a woman s equivalent dose of 138 mg of isoflavones), or soy with tibolone in a randomized order for 14 weeks periods, and there was a 4-week washout (C/L) in between treatments. Postmenopausal women using tibolone (N=110) were screened by means of a one-week soy challenge to find 20 women with equol production capability (4-fold elevation from baseline equol level) and 20 control women, and treated in a randomized cross-over trial with a soy powder (52 g of soy protein containing 112 mg of isoflavones) or placebo for 8 weeks. Before and after the treatments lipids and lipoproteins were assessed in both monkeys and women. In addition, blood pressure, arterial stiffness, endothelial function, sex steroids, sex hormone-binding globulin (SHBG), and vascular inflammation markers were assessed. A 14% increase in plasma low-density lipoprotein (LDL) + very low-density lipoprotein (VLDL) cholesterol was observed in tibolone-treated monkeys vs. placebo. Soy treatment resulted in a 18% decrease in LDL+VLDL cholesterol, and concomitant supplementation with tibolone did not negate the LDL+VLDL cholesterol-lowering effect of soy. A 30% increase in HDL cholesterol was observed in monkeys fed with soy, whereas HDL cholesterol levels were reduced (48%) after tibolone. Interestingly, Soy+Tibolone diet conserved HDL cholesterol levels. Tibolone alone increased the total cholesterol (TC):HDL cholesterol ratio, whereas it was reduced by Soy or Soy+Tibolone. In postmenopausal women using tibolone, reductions in the levels of total cholesterol and LDL cholesterol were seen after soy supplementation compared with placebo, but there was no effect on HDL cholesterol, blood pressure, arterial stiffness or endothelial function. Soy supplementation decreased the levels of estrone in equol producers, and those of testosterone in the entire study population. No changes were seen in the levels of androstenedione, dehydroepiandrosterone sulfate, or SHBG. The levels of vascular cell adhesion molecule-1 increased, and platelet-selectin decreased after soy treatment, whereas C-reactive protein and intercellular adhesion molecule-1 remained unchanged. At baseline and unrelated to soy treatment, equol producers had lower systolic, diastolic and mean arterial pressures, less arterial stiffness and better endothelial function than non-producers. To conclude, soy supplementation reversed the tibolone-induced fall in HDL cholesterol in postmenopausal monkeys, but this effect was not seen in women taking tibolone. Equol production capability was associated with beneficial cardiovascular changes and thus, this characteristic may offer cardiovascular benefits, at least in women using tibolone.

Observations of production and transport of NOx formed by energetic particle precipitation in the polar night atmosphere

This work is focused on the effects of energetic particle precipitation of solar or magnetospheric origin on the polar middle atmosphere. The energetic charged particles have access to the atmosphere in the polar areas, where they are guided by the Earth's magnetic field. The particles penetrate down to 20-100 km altitudes (stratosphere and mesosphere) ionising the ambient air. This ionisation leads to production of odd nitrogen (NOx) and odd hydrogen species, which take part in catalytic ozone destruction. NOx has a very long chemical lifetime during polar night conditions. Therefore NOx produced at high altitudes during polar night can be transported to lower stratospheric altitudes. Particular emphasis in this work is in the use of both space and ground based observations: ozone and NO2 measurements from the GOMOS instrument on board the European Space Agency's Envisat-satellite are used together with subionospheric VLF radio wave observations from ground stations. Combining the two observation techniques enabled detection of NOx enhancements throughout the middle atmosphere, including tracking the descent of NOx enhancements of high altitude origin down to the stratosphere. GOMOS observations of the large Solar Proton Events of October-November 2003 showed the progression of the SPE initiated NOx enhancements through the polar winter. In the upper stratosphere, nighttime NO2 increased by an order of magnitude, and the effect was observed to last for several weeks after the SPEs. Ozone decreases up to 60 % from the pre-SPE values were observed in the upper stratosphere nearly a month after the events. Over several weeks the GOMOS observations showed the gradual descent of the NOx enhancements to lower altitudes. Measurements from years 2002-2006 were used to study polar winter NOx increases and their connection to energetic particle precipitation. NOx enhancements were found to occur in a good correlation with both increased high-energy particle precipitation and increased geomagnetic activity. The average wintertime polar NOx was found to have a nearly linear relationship with the average wintertime geomagnetic activity. The results from this thesis work show how important energetic particle precipitation from outside the atmosphere is as a source of NOx in the middle atmosphere, and thus its importance to the chemical balance of the atmosphere.

Consent Practices and Biomedical Knowledge Production in Tissue Economies

The use of human tissue sample collections has become an important tool in biomedical research. The collection, use and distribution of human tissue samples, which include blood and diagnostic tissue samples, from which DNA can be extracted and analyzed has also become a major bio-political preoccupation, not only in national contexts, but also at the transnational level. The foundation of medical research rests on the relationship between the doctor and the research subject. This relationship is a social one, in that it is based on informed consent, privacy and autonomy, where research subjects are made aware of what they are getting involved in and are then able to make an informed decision as to whether or not to participate. Within the post-genomic era, however, our understanding of what constitutes informed consent, privacy and autonomy is changing in relation to the needs of researchers, but also as a reflection of policy aspirations. This reflects a change in the power relations between the rights of the individual in relation to the interests of science and society. Using the notions of tissue economies and biovalue (Waldby, 2002) this research explores the changing relationship between sources and users of samples in biomedical research by examining the contexts under which human tissue samples and the information that is extracted from them are acquired, circulated and exchanged in Finland. The research examines how individual rights, particularly informed consent, are being configured in relation to the production of scientific knowledge in tissue economies in Finland from the 1990s to the present. The research examines the production of biovalue through the organization of scientific knowledge production by examining the policy context of knowledge production as well as three case studies (Tampere Research Tissue Bank, Hereditary Non-polyposis Colorectal Cancer and the Finnish Genome Information Center) in which tissues are acquired, circulated and exchanged in Finland. The research shows how interpretations of informed consent have become divergent and the elements and processes that have contributed to these differences. This inquiry shows how the relationship between the interests of individuals is re-configured in relation to the interests of science and society. It indicates how the boundary between interpretations of informed consent, on the one hand, and social and scientific interests, on the other, are being re-drawn and that this process is underscored, in part, by the economic, commercial and preventive potential that research using tissue samples are believed to produce. This can be said to fundamentally challenge the western notion that the rights of the individual are absolute and inalienable within biomedical legislation.

Production of psi(2S) Mesons in ppbar Collisions at 1.96 TeV

We have measured the differential cross section for the inclusive production of psi(2S) mesons decaying to mu^{+} mu^{-1} that were produced in prompt or B-decay processes from ppbar collisions at 1.96 TeV. These measurements have been made using a data set from an integrated luminosity of 1.1 fb^{-1} collected by the CDF II detector at Fermilab. For events with transverse momentum p_{T} (psi(2S)) > 2 GeV/c and rapidity |y(psi(2S))| psi(2S)X) Br(psi(2S) -> mu^{+} mu^{-}) to be 3.29 +- 0.04(stat.) +- 0.32(syst.) nb.

Observation of exclusive charmonium production and gamma+gamma to mu+mu- in p+pbar collisions at sqrt{s} = 1.96 TeV

We have observed the reactions p+pbar --> p+X+pbar, with X being a centrally produced J/psi, psi(2S) or chi_c0, and gamma+gamma --> mu+mu-, in proton- antiproton collisions at sqrt{s} = 1.96 TeV using the Run II Collider Detector at Fermilab. The event signature requires two oppositely charged muons, each with pseudorapidity |eta| mu+mu-. Events with a J/psi and an associated photon candidate are consistent with exclusive chi_c0 production through double pomeron exchange. The exclusive vector meson production is as expected for elastic photo- production, gamma+p --> J/psi(psi(2S)) + p, which is observed here for the first time in hadron-hadron collisions. The cross sections ds/dy(y=0) for p + pbar --> p + X + pbar with X = J/psi, psi(2S) orchi_c0 are 3.92+/-0.62 nb, 0.53+/-0.14 nb, and 75+/-14 nb respectively. The cross section for the continuum, with |eta(mu+/-)|

Intonation of Finnish Verbs

A production experiment investigated the tonal shape of Finnish finite verbs in transitive sentences without narrow focus. Traditional descriptions of Finnish stating that non- focused finite verbs do not receive accents were only partly supported. Verbs were found to have a consistently smaller pitch range than words in other word classes, but their pitch contours were neither flat nor explainable by pure interpolation.

Measurement of Particle Production and Inclusive Differential Cross Sections in pbar{p} Collisions at sqrt{s}=1.96 TeV

We report a set of measurements of particle production in inelastic pbar{p} collisions collected with a minimum-bias trigger at the Tevatron Collider with the CDF II experiment. The inclusive charged particle transverse momentum differential cross section is measured, with improved precision, over a range about ten times wider than in previous measurements. The former modeling of the spectrum appears to be incompatible with the high particle momenta observed. The dependence of the charged particle transverse momentum on the event particle multiplicity is analyzed to study the various components of hadron interactions. This is one of the observable variables most poorly reproduced by the available Monte Carlo generators. A first measurement of the event transverse energy sum differential cross section is also reported. A comparison with a Pythia prediction at the hadron level is performed. The inclusive charged particle differential production cross section is fairly well reproduced only in the transverse momentum range available from previous measurements. At higher momentum the agreement is poor. The transverse energy sum is poorly reproduced over the whole spectrum. The dependence of the charged particle transverse momentum on the particle multiplicity needs the introduction of more sophisticated particle production mechanisms, such as multiple parton interactions, in order to be better explained.

Measurement of particle production and inclusive differential cross sections in pp̅ collisions at √s=1.96 TeV

We report a set of measurements of particle production in inelastic pbar{p} collisions collected with a minimum-bias trigger at the Tevatron Collider with the CDF II experiment. The inclusive charged particle transverse momentum differential cross section is measured, with improved precision, over a range about ten times wider than in previous measurements. The former modeling of the spectrum appears to be incompatible with the high particle momenta observed. The dependence of the charged particle transverse momentum on the event particle multiplicity is analyzed to study the various components of hadron interactions. This is one of the observable variables most poorly reproduced by the available Monte Carlo generators. A first measurement of the event transverse energy sum differential cross section is also reported. A comparison with a Pythia prediction at the hadron level is performed. The inclusive charged particle differential production cross section is fairly well reproduced only in the transverse momentum range available from previous measurements. At higher momentum the agreement is poor. The transverse energy sum is poorly reproduced over the whole spectrum. The dependence of the charged particle transverse momentum on the particle multiplicity needs the introduction of more sophisticated particle production mechanisms, such as multiple parton interactions, in order to be better explained.

Search for exclusive Z boson production and observation of high mass ppbar->gammagamma->p+ll+pbar events in ppbar collisions at sqrt(s) = 1.96 TeV

We present a search for exclusive Z boson production in proton-antiproton collisions at sqrt(s) = 1.96 TeV, using the CDF II detector at Fermilab. We observe no exclusive Z->ll candidates and place the first upper limit on the exclusive Z cross section in hadron collisions, sigma(exclu) gammagamma->p+ll+pbar, and measure the cross section for M(ll) > 40 GeV/c2 and |eta(l)|