Head motion and Inattention/Hyperactivity share common genetic influences: Implications for fMRI studies of ADHD

Head motion (HM) is a well known confound in analyses of functional MRI (fMRI) data. Neuroimaging researchers therefore typically treat HM as a nuisance covariate in their analyses. Even so, it is possible that HM shares a common genetic influence with the trait of interest. Here we investigate the extent to which this relationship is due to shared genetic factors, using HM extracted from resting-state fMRI and maternal and self report measures of Inattention and Hyperactivity-Impulsivity from the Strengths and Weaknesses of ADHD Symptoms and Normal Behaviour (SWAN) scales. Our sample consisted of healthy young adult twins (N = 627 (63% females) including 95 MZ and 144 DZ twin pairs, mean age 22, who had mother-reported SWAN; N = 725 (58% females) including 101 MZ and 156 DZ pairs, mean age 25, with self reported SWAN). This design enabled us to distinguish genetic from environmental factors in the association between head movement and ADHD scales. HM was moderately correlated with maternal reports of Inattention (r = 0.17, p-value = 7.4E-5) and Hyperactivity-Impulsivity (r = 0.16, p-value = 2.9E-4), and these associations were mainly due to pleiotropic genetic factors with genetic correlations [95% CIs] of rg = 0.24 [0.02, 0.43] and rg = 0.23 [0.07, 0.39]. Correlations between self-reports and HM were not significant, due largely to increased measurement error. These results indicate that treating HM as a nuisance covariate in neuroimaging studies of ADHD will likely reduce power to detect between-group effects, as the implicit assumption of independence between HM and Inattention or Hyperactivity-Impulsivity is not warranted. The implications of this finding are problematic for fMRI studies of ADHD, as failing to apply HM correction is known to increase the likelihood of false positives. We discuss two ways to circumvent this problem: censoring the motion contaminated frames of the RS-fMRI scan or explicitly modeling the relationship between HM and Inattention or Hyperactivity-Impulsivity

Der Prediger vom weißen Berg : Zur Rezeption der besseren Gerechtigkeit aus Mt 5 in Martin Luthers Predigtüberlieferung 1522 1546.

The purpose of this study is to examine the reception of Matthew 5 in Martin Luther s sermons; in other words to investigate how Luther interprets and applies Jesus teaching of the better righteousness and the law in Mt 5. The study applies the reception-historical approach and contributes to the history of effects and the history of interpretation in New Testament exegesis. The study shows that Luther understands the better righteousness of Mt 5 as good works and fulfillment of the law. Luther s interpretation coheres with the intention of the Evangelist, even if Luther s overall concept of righteousness is foreign to Matthew. In Luther s view righteousness is twofold: The greater righteousness of Mt 5 is the second and the actual righteousness (iustitia activa), which follows the first and the foreign righteousness (iustitia passiva). The first righteousness (faith) is for Luther the work of God, while the second righteousness (good works) is co-operation between a Christian and God. In this co-operation the law, as it is taught by Jesus, is not the opposite of the gospel, but the gospel itself in the sense of Christ as an example . The task of the law is to show the dependence of a Christian on God and to help one to love and to serve one s neighbour (brothers as well as enemies) properly. The study underlines a feature in Luther s thinking that has received little attention in Lutheran theology: Luther insists on preaching the law to Christians. In his view Mt 5 is directed to all Christians and particularly to pastors, for whom Jesus here gives an example of how to preach the law. Luther believes similarly to Matthew that Jesus reveals the real meaning of Mosaic Law and confirms its validity for Christians in Mt 5. Like Matthew, Luther insists on the practicability of the commandments of Mt 5 in his view Christians fulfil the law also with joy yet his interpretation of Mt 5 attenuates the radical nature of its commandments. Luther s reception of the individual pericopes of Mt 5 is considerably generative and occasionally contradictory, which is explained by the following factors, among others: Luther receives many ideas from tradition and reads them and his own theological concepts into Matthew s Gospel. He interprets Mt 5 through his understanding of some Old Testament passages as well as Paul. Most of all, Luther s reception of Mt 5 is shaped by his own experience as a preacher, by his relation to his religious enemies, rulers and to the congregation of Wittenberg. Here Luther shares with Matthew the experience of being opposed and concern about the upright living of the believers, which in both cases also explains the polemical tone of the paraenesis.

Eva Stroh Family Collection 1860-2005 Bulk: 1912-1950

The Eva Stroh Family Collection provides material on the lives and family history of members of the Sondheimer and Stroh families. The collection consists of numerous photos and several photo albums, family trees, official documents, correspondence, published articles and clippings and some notes, a notebook documenting cultural activities and some daily calendars.

Rationing in healthcare

Rationing healthcare in some form is inevitable, even in wealthy countries, because resources are scarce and demand for healthcare is always likely to exceed supply. This means that decision-makers must make choices about which health programs and initiatives should receive public funding and which ones should not. These choices are often difficult to make, particularly in Australia, because: - 1 Make explicit rationing based on a national decision-making tool (such as Multi-criteria Decision Analysis) standard process in all jurisdictions. - 2 Develop nationally consistent methods for conducting economic evaluation in health so that good quality evidence on the relative efficiency of various programs and initiatives is generated. - 3 Generate more economic evaluation evidence to inform rationing decisions. - 4 Revise national health performance indicators so that they include true health system efficiency indicators, such as cost-effectiveness. - 5 Apply the Comprehensive Management Framework used to evaluate items on the Medicare Benefits Schedule (MBS) to the Pharmaceutical Benefits Scheme (PBS) and the Prosthesis List to accelerate disinvestment from low-value drugs and prostheses. - 6 Seek agreement among Commonwealth, state and territory governments to work together to undertake work similar to the National Institute for Health and Care Excellence in the United Kingdom and the Canadian Agency for Drugs and Technologies in Health.

What are the 'best buys' in preventing infection following caesarean section?

Caesarean section is the most common surgical procedure performed on women worldwide and infections following caesarean section occur in approximately 10% of Australian women...

The effects of height and BMI on prostate cancer incidence and mortality: A Mendelian randomization study in 20,848 cases and 20,214 controls from the PRACTICAL consortium

Background Epidemiological studies suggest a potential role for obesity and determinants of adult stature in prostate cancer risk and mortality, but the relationships described in the literature are complex. To address uncertainty over the causal nature of previous observational findings, we investigated associations of height- and adiposity-related genetic variants with prostate cancer risk and mortality. Methods We conducted a case–control study based on 20,848 prostate cancers and 20,214 controls of European ancestry from 22 studies in the PRACTICAL consortium. We constructed genetic risk scores that summed each man’s number of height and BMI increasing alleles across multiple single nucleotide polymorphisms robustly associated with each phenotype from published genome-wide association studies. Results The genetic risk scores explained 6.31 and 1.46 % of the variability in height and BMI, respectively. There was only weak evidence that genetic variants previously associated with increased BMI were associated with a lower prostate cancer risk (odds ratio per standard deviation increase in BMI genetic score 0.98; 95 % CI 0.96, 1.00; p = 0.07). Genetic variants associated with increased height were not associated with prostate cancer incidence (OR 0.99; 95 % CI 0.97, 1.01; p = 0.23), but were associated with an increase (OR 1.13; 95 % CI 1.08, 1.20) in prostate cancer mortality among low-grade disease (p heterogeneity, low vs. high grade <0.001). Genetic variants associated with increased BMI were associated with an increase (OR 1.08; 95 % CI 1.03, 1.14) in all-cause mortality among men with low-grade disease (p heterogeneity = 0.03). Conclusions We found little evidence of a substantial effect of genetically elevated height or BMI on prostate cancer risk, suggesting that previously reported observational associations may reflect common environmental determinants of height or BMI and prostate cancer risk. Genetically elevated height and BMI were associated with increased mortality (prostate cancer-specific and all-cause, respectively) in men with low-grade disease, a potentially informative but novel finding that requires replication.

Directional dominance on stature and cognition in diverse human populations

Homozygosity has long been associated with rare, often devastating, Mendelian disorders1, and Darwin was one of the first to recognize that inbreeding reduces evolutionary fitness2. However, the effect of the more distant parental relatedness that is common in modern human populations is less well understood. Genomic data now allow us to investigate the effects of homozygosity on traits of public health importance by observing contiguous homozygous segments (runs of homozygosity), which are inferred to be homozygous along their complete length. Given the low levels of genome-wide homozygosity prevalent in most human populations, information is required on very large numbers of people to provide sufficient power3, 4. Here we use runs of homozygosity to study 16 health-related quantitative traits in 354,224 individuals from 102 cohorts, and find statistically significant associations between summed runs of homozygosity and four complex traits: height, forced expiratory lung volume in one second, general cognitive ability and educational attainment (P < 1 × 10−300, 2.1 × 10−6, 2.5 × 10−10 and 1.8 × 10−10, respectively). In each case, increased homozygosity was associated with decreased trait value, equivalent to the offspring of first cousins being 1.2 cm shorter and having 10 months’ less education. Similar effect sizes were found across four continental groups and populations with different degrees of genome-wide homozygosity, providing evidence that homozygosity, rather than confounding, directly contributes to phenotypic variance. Contrary to earlier reports in substantially smaller samples5, 6, no evidence was seen of an influence of genome-wide homozygosity on blood pressure and low density lipoprotein cholesterol, or ten other cardio-metabolic traits. Since directional dominance is predicted for traits under directional evolutionary selection7, this study provides evidence that increased stature and cognitive function have been positively selected in human evolution, whereas many important risk factors for late-onset complex diseases may not have been.

Targeting neuropilin-1 to inhibit prostate cancer invasion and metastasis

Recent reports provide evidence that the epithelial-to-mesenchymal transition (EMT) plays a key role in prostate cancer (PCa) metastasis and therapy resistance. We have recently identified the cell surface receptor, Neuropilin-1 (NRP1) to be increased during epithelial-mesenchymal transition (EMT) and this study aims to determine whether the inhibition of NRP1 will be a feasible therapeutic strategy for blocking PCa metastasis and therapy resistance.

Metabolomic and proteomic analysis of breast cancer patient samples suggests that glutamate and 12-HETE in combination with CA15-3 may be useful biomarkers reflecting tumour burden

Evaluation of protein and metabolite expression patterns in blood using mass spectrometry and high-throughput antibody-based screening platforms has potential for the discovery of new biomarkers for managing breast cancer patient treatment. Previously identified blood-based breast cancer biomarkers, including cancer antigen 15.3 (CA15-3) are useful in combination with imaging (computed tomography scans, magnetic resonance imaging, X-rays) and physical examination for monitoring tumour burden in advanced breast cancer patients. However, these biomarkers suffer from insufficient levels of accuracy and with new therapies available for the treatment of breast cancer, there is an urgent need for reliable, non-invasive biomarkers that measure tumour burden with high sensitivity and specificity so as to provide early warning of the need to switch to an alternative treatment. The aim of this study was to identify a biomarker signature of tumour burden using cancer and non-cancer (healthy controls/non-malignant breast disease) patient samples. Results demonstrate that combinations of three candidate biomarkers from Glutamate, 12-Hydroxyeicosatetraenoic acid, Beta-hydroxybutyrate, Factor V and Matrix metalloproteinase-1 with CA15-3, an established biomarker for breast cancer, were found to mirror tumour burden, with AUC values ranging from 0.71 to 0.98 when comparing non-malignant breast disease to the different stages of breast cancer. Further validation of these biomarker panels could potentially facilitate the management of breast cancer patients, especially to assess changes in tumour burden in combination with imaging and physical examination.

Aspekte der Melancholietherapie in Martin Luthers Trostbriefen

Pro gradu -tutkielmani tehtävänä on selvittää näkökulmia melankoliaterapiaan Martti Lutherin lohdutuskirjeissä. Lähteinä on ollut neljä lohdutuskirjettä sekä yksi kirje, joka muistuttaa sisällöltään lohdutuskirjettä. Metodina on ollut kirjeiden tyylillis-retorinen analyysi. Aihe on kiinnostava, koska Lutherin kirjeiden ja retoriikan tutkimus on ollut vähäistä verrattuna häntä koskevaan laajaan kansainväliseen tutkimukseen. Työn lähtökohtana on ollut, että yksi kirjallisuuden tärkeimmistä tehtävistä 1500-luvulla oli erilaisten melankolisten sairauksien parantaminen. Kirjallisuuden avulla voitiin torjua hengenvaarallisia melankolisia affekteja kuten epätoivoa, pelkoa, surua ja apatiaa. Lutherin lohdutuskirjeet soveltuvat hyvin melankoliaterapian tutkimiseen, koska ne on kirjoitettu lohtua tarvitseville ihmisille. Työn tutkimuskysymykset ovat: Mitä melankolian hoitokeinoja Luther mainitsee? Missä määrin Lutherin melankoliaterapia on sopusoinnussa 1500-luvulla vallinneiden hoitokäsitysten kanssa? Miten Luther hyödyntää retoriikan ja huumorin keinoja melankoliaterapiassaan? Työn teoriaosassa selvitetään 1500-luvun ihmiskäsitystä sekä teologisesta että lääketieteellisestä näkökulmasta ja esitellään ajalle tyypillisiä humoraaliopin mukaisia melankolian hoitokeinoja. Selvitetään myös retoriikan ja melankoliaterapian suhdetta toisiinsa. Analyysiosassa pääpaino on Lutherin käyttämissä retorisissa keinoissa, mutta siinä hyödynnetään myös teoriaosan havaintoja. Tutkielmassa kirjallisuustieteellinen ja teologinen näkökulma tukevat toisiaan. Kirjallisuustieteellisestä näkökulmasta lohdutuskirjeet on tutkittavissa retoriikan tarjoamien käsitteiden avulla, koska ne on kirjoitettu aikana, jolloin retoriikka oli tärkeä yliopistollinen oppiaine. Tutkielma huomioi myös aiheen teologisen näkökulman, koska ajan kieli on uskonnollisesti värittynyttä ja koska Lutherin melankoliaterapiaan kuuluu vahva hengellinen ulottuvuus. Ihmisen kyky lohduttaa rinnastuu Lutherilla Jumalan kykyyn lohduttaa ihmistä Raamatun sanan kautta. Lutherille Jumala on reetori, jonka työväline on Raamatun pyhä sana. Puhutulla ja kirjoitetulla sanalla on Lutherin melankoliaterapiassa erityisen keskeinen merkitys. Tutkielmani osoittaa, että sekä Lutherin käyttämät retoriset keinot että hänen melankoliaterapiansa ovat suuressa määrin sopusoinnussa 1500-luvun retoriikan ja lääketieteen oppien kanssa. Luther käyttää melankoliaterapiassaan laajasti apuna erilaisia retorisia keinoja kuten toistoa, variaatiota, metaforaa ja esimerkkikertomuksia. Lutherin mainitsemat hoitokeinot kuten esimerkiksi metsästys, ratsastus, syöminen ja juominen, pelien pelaaminen, leikinlasku ja ystävien kanssa seurustelu ovat sopusoinnussa ajan hoitokäsitysten kanssa. Kirjeissä esiintyy myös lääketieteellisestä ja uskonnollisesta näkökulmasta katsottuna kyseenalaisia hoitokeinoja kuten tyhjänpäiväisten juttujen kertominen ja paholaisen kiroileminen. Nämä neuvot ylittävät ajan melankoliaterapiaan kuuluvan kohtuullisuuden säännön, ja ne on ymmärrettävä niiden teologisesta merkityksestä käsin. Lutherille kohtuullisuuden säännön rikkominen on toisinaan sallittua, kun on kysymys vaikeasta paholaisen aiheuttamasta melankoliasta. Kristillinen usko näyttää Lutherille tarjoavan vapauden käyttää tiettyjä hoitokeinoja, joita vielä keskiajalla ei olisi hyväksytty. Toisinaan Luther näkee kirjeen vastaanottajaa kohdanneen vaikeuden Jumalan eikä paholaisen aikaansaannoksena. Tällaisissa tapauksissa melankolia nähdään Jumalan työnä ihmisessä, joka mahdollistaa hengellisen kääntymisen Jumalan, kaiken lohdutuksen Isän puoleen.

Kysymys esineellisyydestä : Georg Lukácsin esineellistymisteoria ja Martin Heideggerin fundamentaaliontologia

Käsilläolevan tutkielman aiheena on esineellistymisen käsite. Sitä tarkastellaan yhtäältä sellaisena kuten se esitetään Georg Lukácsin (1885-1971) teoksessa Historia ja luokkatietoisuus (1923), toisaalta kuten sitä koskeva teoria on luettavissa esiin Martin Heideggerin (1889-1976) läpimurtoteoksesta Oleminen ja aika (1927). Molemmat ajattelijat pyrkivät teoksissaan rakentamaan kokonaisvaltaista tulkintaa länsimaisen ajattelun ja toiminnan taipumuksesta tulkita todellisuus esineellisenä (dinglich), so. eletystä elämästä ja toiminnasta irrallisena olioiden (Dinge) maailmana. Sekä Lukács että Heidegger pyrkivät osoittamaan, että esineellistyneen todellisuuden ontologisena perustana toimii inhimillisen praktisen toiminnan kenttä, josta käsin esineellistävät ja objektivoivat suhtautumistavat todellisuuteen voivat vasta jälkikäteisesti syntyä. Molemmille ajattelijoille esineellisyyden muodostuminen ontologiaa hallitsevaksi tulkinnaksi todellisuuden luonteesta edellyttää myös tietynlaisia sosiaalisen olemisen rakenteita. Tutkielmassa tehdään vertailevaa käsiteanalyysia Lukácsin ja Heideggerin teoreettisten diskurssien välillä. Tavoitteena on rakentaa mahdollisuutta lukea mainittuja filosofeja saman, modernille olemassaololle keskeisen ontologisen sekä eksistentiaalisen ongelman tarkastelijoina. Toisaalta vertaileva lähestymistapa pyrkii myös tuomaan esiin olennaisia ja perustavia eroja Lukácsin marxilaisen ja Heideggerin fundamentaaliontologisen orientaation välillä. Tutkielmassa pyritäänkin osoittamaan, että Heideggerin fundamentaaliontologia ei tarkastele kauppatavaran rakennetta eikä sosiaalisen vaihdon prosesseja marxilaisesta näkökulmasta riittävällä tavalla, kun taas Lukácsin teoreettinen projekti tulee edellyttäneeksi tuottavaan subjektiviteettiin pohjautuvan ontologisen perusasenteen. Tämä ontologinen positio voidaan puolestaan kritisoida hedelmällisesti heideggerilaisesta näkökulmasta. Viime kädessä tutkielma pyrkii avaamaan esineellistymisteorioiden vertailun kautta kysymyksen länsimarxilaisen materialistisen dialektiikan ja Heideggerin fenomenologisen ontologian välisestä suhteesta.