Stabilization of Ge-rich defect complexes originating from E centers in Si1- xGex:P

Thermal evolution of vacancy complexes was studied in P-doped ([P]=10 exp 18 cm exp −3) proton irradiated Si1−xGex with Ge contents of 10%, 20%, and 30% in the range of 250–350 °C using positron annihilation spectroscopy. The radiation damage recovers in the course of anneals but the final state differs from that in as-grown samples indicating the presence of small Ge clusters in the samples, contrary to the initially random Ge distribution. The activation energy for the annealing process was estimated to be 1.4±0.3 eV and attributed to the dissociation energy of the vacancy-phosphorus-germanium (V-P-Ge) complex.Peer reviewe

Stronger prejudices are associated with decreased model-based control

Background: Prejudices against minorities can be understood as habitually negative evaluations that are kept in spite of evidence to the contrary. Therefore, individuals with strong prejudices might be dominated by habitual or "automatic" reactions at the expense of more controlled reactions. Computational theories suggest individual differences in the balance between habitual/model-free and deliberative/model-based decision-making. Methods: 127 subjects performed the two Step task and completed the blatant and subtle prejudice scale. Results: By using analyses of choices and reaction times in combination with computational modeling, subjects with stronger blatant prejudices showed a shift away from model-based control. There was no association between these decision-making processes and subtle prejudices. Conclusion: These results support the idea that blatant prejudices toward minorities are related to a relative dominance of habitual decision-making. This finding has important implications for developing interventions that target to change prejudices across societies

Model-Based and Model-Free Control Predicts Alcohol Consumption Developmental Trajectory in Young Adults: A 3-Year Prospective Study.

BACKGROUND: A shift from goal-directed toward habitual control has been associated with alcohol dependence. Whether such a shift predisposes to risky drinking is not yet clear. We investigated how goal-directed and habitual control at age 18 predict alcohol use trajectories over the course of 3 years. METHODS: Goal-directed and habitual control, as informed by model-based (MB) and model-free (MF) learning, were assessed with a two-step sequential decision-making task during functional magnetic resonance imaging in 146 healthy 18-year-old men. Three-year alcohol use developmental trajectories were based on either a consumption score from the self-reported Alcohol Use Disorders Identification Test (assessed every 6 months) or an interview-based binge drinking score (grams of alcohol/occasion; assessed every year). We applied a latent growth curve model to examine how MB and MF control predicted the drinking trajectory. RESULTS: Drinking behavior was best characterized by a linear trajectory. MB behavioral control was negatively associated with the development of the binge drinking score; MF reward prediction error blood oxygen level-dependent signals in the ventromedial prefrontal cortex and the ventral striatum predicted a higher starting point and steeper increase of the Alcohol Use Disorders Identification Test consumption score over time, respectively. CONCLUSIONS: We found that MB behavioral control was associated with the binge drinking trajectory, while the MF reward prediction error signal was closely linked to the consumption score development. These findings support the idea that unbalanced MB and MF control might be an important individual vulnerability in predisposing to risky drinking behavior

BMI is positively associated with accelerated epigenetic aging in twin pairs discordant for body mass index

Background Obesity is a heritable complex phenotype that can increase the risk of age-related outcomes. Biological age can be estimated from DNA methylation (DNAm) using various "epigenetic clocks." Previous work suggests individuals with elevated weight also display accelerated aging, but results vary by epigenetic clock and population. Here, we utilize the new epigenetic clock GrimAge, which closely correlates with mortality. Objectives We aimed to assess the cross-sectional association of body mass index (BMI) with age acceleration in twins to limit confounding by genetics and shared environment. Methods and results Participants were from the Finnish Twin Cohort (FTC; n = 1424), including monozygotic (MZ) and dizygotic (DZ) twin pairs, and DNAm was measured using the Illumina 450K array. Multivariate linear mixed effects models including MZ and DZ twins showed an accelerated epigenetic age of 1.02 months (p-value = 6.1 x 10(-12)) per one-unit BMI increase. Additionally, heavier twins in a BMI-discordant MZ twin pair (Delta BMI >3 kg/m(2)) had an epigenetic age 5.2 months older than their lighter cotwin (p-value = 0.0074). We also found a positive association between log (homeostatic model assessment of insulin resistance) and age acceleration, confirmed by a meta-analysis of the FTC and two other Finnish cohorts (overall effect = 0.45 years, p-value = 4.1 x 10(-25)) from adjusted models. Conclusion We identified significant associations of BMI and insulin resistance with age acceleration based on GrimAge, which were not due to genetic effects on BMI and aging. Overall, these results support a role of BMI in aging, potentially in part due to the effects of insulin resistance.Peer reviewe

Ibrutinib, lenalidomide, and rituximab in relapsed or refractory mantle cell lymphoma (PHILEMON) : a multicentre, open-label, single-arm, phase 2 trial

Background Regimens based on ibrutinib alone and lenalidomide and rituximab in combination show high activity in patients with relapsed or refractory mantle cell lymphoma. We hypothesised that the combination of all three drugs would improve efficacy compared with previously published data on either regimen alone. Methods In this multicentre, open-label, single-arm, phase 2 trial, we enrolled patients aged 18 years or older with relapsed or refractory mantle cell lymphoma who had previously been treated with at least one rituximab-containing regimen, an Eastern Cooperative Oncology Group performance status score of 0-3, and at least one site of measurable disease, and who met criteria for several laboratory-assessed parameters. Treatment was divided into an induction phase of 12 cycles of 28 days with all three drugs and a maintenance phase with ibrutinib and rituximab only (cycle duration 56 days), given until disease progression or unacceptable toxicity. In the induction phase, patients received intravenous (375 mg/m(2)) or subcutaneous (1400 mg) rituximab once a week during cycle 1 and then once every 8 weeks. Oral ibrutinib (560 mg once a day) was given to patients every day in the cycle, whereas oral lenalidomide (15 mg once a day) was given on days 1-21. The primary endpoint was overall response assessed in the intention-totreat population according to Lugano criteria. Safety analysis included all patients who received the treatment, irrespective of eligibility or duration of treatment. The trial is ongoing, but is no longer accruing patients, and is registered with ClinicalTrials. gov, number NCT02460276. Findings Between April 30, 2015, and June 1, 2016, we enrolled 50 patients with relapsed or refractory mantle cell lymphoma at ten centres in Sweden, Finland, Norway, and Denmark. At a median follow-up of 17.8 months (IQR 14.7-20.9), 38 (76%, 95% CI 63-86) patients had an overall response, including 28 (56%, 42-69) patients who had a complete response and ten (20%, 11-33) who had a partial response. The most common grade 3-4 adverse events were neutropenia (in 19 [38%] of 50 patients), infections (in 11 [22%] patients), and cutaneous toxicity (in seven [14%] patients). There were three treatment-related deaths during the study, two due to sepsis and one due to embolic stroke. Interpretation Our results provide preliminary evidence that the triplet combination of ibrutinib, lenalidomide, and rituximab is an active regimen in patients with relapsed or refractory mantle cell lymphoma, and should be evaluated in a prospective randomised controlled trial.Peer reviewe

Toisiolaki - lääketieteellisen tutkimuksen mahdollistaja vai tukahduttaja?

Vertaisarvioitu.Lähtökohdat : Suomessa tuli 1.5.2019 voimaan niin sanottu toisiolaki eli Laki sosiaali- ja terveys¬tietojen toissijaisesta käytöstä. Kyselytutkimuksemme tarkoitus oli selvittää kliinikkotutkijoiden kokemuksia toisiolain vaikutuksista ja käytännön toteutuksesta. Menetelmät : Suomalaisia kliinikkotutkijoita pyydettiin arvioimaan Webropol-alustalla toisiolain aiheuttamia aikataulumuutoksia, talousvaikutuksia, tutkimusyhteistyössä tapahtuneita muutoksia, mahdollisia esteitä ja hyötyjä lain voimaantuloon liittyen sekä muita lain aiheuttamia positiivisia ja negatiivisia vaikutuksia. Tulokset : Vastaajista (n = 430) 64,4 % raportoi, että tutkimustoiminnan kustannukset ovat nousseet toisiolain mukana. Vastaajista 38,4–45,6 % oli jättänyt tutkimusprojekteja käynnistämättä joko lupahakemuksen hinnan tai etäkäyttöympäristön kustannusten sekä sen käyttövaatimuksen vuoksi. Päätelmät :Tutkimuksemme perusteella on syytä epäillä, että toisiolain soveltaminen vaikuttaa heikentävästi julkaisujen määrään ja laatuun ja heikentää Suomen kilpailukykyä etenkin tutkija¬lähtöisessä tutkimuksessa. Toisiolain seuraukset kohdistuvat erityisesti suomalaisiin potilaisiin, heidän hoitonsa laatuun sekä hoidon tasavertaisuuteen.Peer reviewe

Toisiolaki - lääketieteellisen tutkimuksen mahdollistaja vai tukahduttaja?

Lähtökohdat : Suomessa tuli 1.5.2019 voimaan niin sanottu toisiolaki eli Laki sosiaali- ja terveys­tietojen toissijaisesta käytöstä. Kyselytutkimuksemme tarkoitus oli selvittää kliinikkotutkijoiden kokemuksia toisiolain vaikutuksista ja käytännön toteutuksesta. Menetelmät : Suomalaisia kliinikkotutkijoita pyydettiin arvioimaan Webropol-alustalla toisiolain aiheuttamia aikataulumuutoksia, talousvaikutuksia, tutkimusyhteistyössä tapahtuneita muutoksia, mahdollisia esteitä ja hyötyjä lain voimaantuloon liittyen sekä muita lain aiheuttamia positiivisia ja negatiivisia vaikutuksia. Tulokset : Vastaajista (n = 430) 64,4 % raportoi, että tutkimustoiminnan kustannukset ovat nousseet toisiolain mukana. Vastaajista 38,4–45,6 % oli jättänyt tutkimusprojekteja käynnistämättä joko lupahakemuksen hinnan tai etäkäyttöympäristön kustannusten sekä sen käyttövaatimuksen vuoksi. Päätelmät :Tutkimuksemme perusteella on syytä epäillä, että toisiolain soveltaminen vaikuttaa heikentävästi julkaisujen määrään ja laatuun ja heikentää Suomen kilpailukykyä etenkin tutkija­lähtöisessä tutkimuksessa. Toisiolain seuraukset kohdistuvat erityisesti suomalaisiin potilaisiin, heidän hoitonsa laatuun sekä hoidon tasavertaisuuteen.publishedVersionPeer reviewe

BMI is positively associated with accelerated epigenetic aging in twin pairs discordant for body mass index

Background Obesity is a heritable complex phenotype that can increase the risk of age-related outcomes. Biological age can be estimated from DNA methylation (DNAm) using various "epigenetic clocks." Previous work suggests individuals with elevated weight also display accelerated aging, but results vary by epigenetic clock and population. Here, we utilize the new epigenetic clock GrimAge, which closely correlates with mortality. Objectives We aimed to assess the cross-sectional association of body mass index (BMI) with age acceleration in twins to limit confounding by genetics and shared environment. Methods and results Participants were from the Finnish Twin Cohort (FTC; n = 1424), including monozygotic (MZ) and dizygotic (DZ) twin pairs, and DNAm was measured using the Illumina 450K array. Multivariate linear mixed effects models including MZ and DZ twins showed an accelerated epigenetic age of 1.02 months (p-value = 6.1 x 10(-12)) per one-unit BMI increase. Additionally, heavier twins in a BMI-discordant MZ twin pair (Delta BMI >3 kg/m(2)) had an epigenetic age 5.2 months older than their lighter cotwin (p-value = 0.0074). We also found a positive association between log (homeostatic model assessment of insulin resistance) and age acceleration, confirmed by a meta-analysis of the FTC and two other Finnish cohorts (overall effect = 0.45 years, p-value = 4.1 x 10(-25)) from adjusted models. Conclusion We identified significant associations of BMI and insulin resistance with age acceleration based on GrimAge, which were not due to genetic effects on BMI and aging. Overall, these results support a role of BMI in aging, potentially in part due to the effects of insulin resistance.</p

New national and regional biological records for Finland 11. Contributions to Bryophyta and Marchantiophyta 10

Ten species of mosses (Bryophyta: Entosthodon obtusus, Entosthodon ulvinenii, Eurhynchiastrum diversifolium, Hedwigia emodica, Hedwigia mollis, Hygrohypnum styriacum, Plagiothecium rossicum, Polytrichum perigoniale, Tortella alpicola and Ulota intermedia) are presented as new for Finland. Cephalozia lacinulata, previously considered to be regionally extinct from Finland, is reported to being found again. New records in biogeographical provinces for 67 species of mosses and 34 species of liverworts are listed. Finally, 6 occurrences in provinces are removed due to misidentifications or missing specimens