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Anniina Heikkilä,1 Lasse Lehtonen,2 Jari Haukka,3 Satu Havulinna,4 Kristiina Junttila5 1HUS Nursing Administrative Group, Helsinki University Hospital and University of Helsinki, Helsinki, Finland; 2HUS Diagnostic Center, Helsinki University Hospital and University of Helsinki, Helsinki, Finland; 3Clinicum/Department of Public Health, University of Helsinki, Helsinki, Finland; 4Department of Public Health and Welfare, Finnish Institute for Health and Welfare, Helsinki, Finland; 5Nursing Research Center, Helsinki University Hospital and University of Helsinki, Helsinki, FinlandCorrespondence: Anniina Heikkil&#x00E4HUS Nursing Administrative Group, Helsinki University Hospital and University of Helsinki, P.O. Box 705, Helsinki, FI-00029, FinlandTel +358415437870Email anniina.heikkila@hus.fiPurpose: The purpose of this study was to evaluate the validity and reliability of the Peninsula Health Fall Risk Assessment Tool (PHFRAT) in acute care in various medical specialties. The assessment has not been previously studied in acute care.Methods: The cross-sectional study was conducted in a large acute care hospital system. The retrospective medical data were used to explore the validity of the PHFRAT. The data consisted of all adult inpatients (≥ 18 age) evaluated by the PHFRAT during 2014– 2016 (n = 22,700). The Poisson regression, logistic regression, sensitivity, specificity, and the area under the ROC curve were evaluated. The data for the reliability study were collected in 2016 in twelve units by evaluating the patients (n = 359) twice using the PHFRAT. The prospective data were analyzed using Fleiss’ Kappa, and the content validity index was also counted.Results: In the somatic data, the change in the risk level from low risk to high risk increases the probability of falls by a factor of 2.8 (p< 0.01). When the cut-off point was 9, sensitivity and specificity were 72% and 59%, respectively, and the area under the ROC curve was 0.67 (p< 0.01). Validity varied by medical specialties. In the validity analysis, it was not possible to calculate the statistical significance from the psychiatry data. The inter-rater reliability was 0.68 (p< 0.01).Conclusion: This study shows that the PHFRAT proved to be moderately suitable for detecting the risk of falling for adult patients admitted to somatic units in acute care. The reliability of the PHFRAT was moderate. The results indicate the need to study the PHFRAT more broadly in psychiatric care as well as some specialties in somatic care.Keywords: falls, fall risk assessment, PHFRAT, acute care

OBJECTIVE: To assess whether treating patients with a presymptomatic patent ductus arteriosus (PDA), based on early routine echocardiography, performed regardless of clinical signs, improved outcomes. STUDY DESIGN: This multicenter, survey-linked retrospective cohort study used an institutional-level questionnaire and individual patient-level data and included infants of

To assess associations between 5 min Apgar score and mortality and severe neurological injury (SNI) and to report test characteristics in preterm neonates.

Objective To determine if postnatal transfer or birth in a non-tertiary hospital is associated with adverse outcomes. Design Observational cohort study with propensity score matching. Setting National health service neonatal care in England; population data held in the National Neonatal Research Database. Participants Extremely preterm infants born at less than 28 gestational weeks between 2008 and 2015 (n=17 577) grouped based on birth hospital and transfer within 48 hours of birth: upward transfer (non-tertiary to tertiary hospital, n=2158), non-tertiary care (born in non-tertiary hospital; not transferred, n=2668), and controls (born in tertiary hospital; not transferred, n=10 866). Infants were matched on propensity scores and predefined background variables to form subgroups with near identical distributions of confounders. Infants transferred between tertiary hospitals (horizontal transfer) were separately matched to controls in a 1:5 ratio. Main outcome measures Death, severe brain injury, and survival without severe brain injury. Results 2181 infants, 727 from each group (upward transfer, non-tertiary care, and control) were well matched. Compared with controls, infants in the upward transfer group had no significant difference in the odds of death before discharge (odds ratio 1.22, 95% confidence interval 0.92 to 1.61) but significantly higher odds of severe brain injury (2.32, 1.78 to 3.06; number needed to treat (NNT) 8) and significantly lower odds of survival without severe brain injury (0.60, 0.47 to 0.76; NNT 9). Compared with controls, infants in the non-tertiary care group had significantly higher odds of death (1.34, 1.02 to 1.77; NNT 20) but no significant difference in the odds of severe brain injury (0.95, 0.70 to 1.30) or survival without severe brain injury (0.82, 0.64 to 1.05). Compared with infants in the upward transfer group, infants in the non-tertiary care group had no significant difference in death before discharge (1.10, 0.84 to 1.44) but significantly lower odds of severe brain injury (0.41, 0.31 to 0.53; NNT 8) and significantly higher odds of survival without severe brain injury (1.37, 1.09 to 1.73; NNT 14). No significant differences were found in outcomes between the horizontal transfer group (n=305) and controls (n=1525). Conclusions In extremely preterm infants, birth in a non-tertiary hospital and transfer within 48 hours are associated with poor outcomes when compared with birth in a tertiary setting. We recommend perinatal services promote pathways that facilitate delivery of extremely preterm infants in tertiary hospitals in preference to postnatal transfer.

To compare length of stay (LOS) in neonatal care for extremely preterm babies admitted to networks participating in the International Network for Evaluating Outcomes of Neonates (iNeo).

Collaboration and cooperation of clinicians and neonatal units at regional, national, and international levels are key features of many networks or systems that aim to improve neonatal outcomes. Network performance is typically assessed by comparing individual, unit-level outcomes. In this paper, we provide insight into another dimension, i.e., inter-center outcome variation in 10 national/regional neonatal collaborations from 11 high-income countries. We illustrate the use of coefficients of variation for evaluation of mortality and a composite outcome of mortality, severe neurological injury, treated retinopathy of prematurity, and bronchopulmonary dysplasia, as a measure of inter-center variation. These inter-center variation estimates could help to identify areas of opportunities and challenges for each country/region; they also provide "macro"-level evaluations that can be useful for clinicians, administrators, managers and policy makers.

Tiivistelmä. Tarkastelen kandidaatintutkielmassani positiivisen psykologian erilaisia onnellisuus- ja hyvinvointiteorioita sekä niiden pohjalta keinoja, joiden avulla yksilö voi lisätä omaa onnellisuuttaan. Onnellisuus on ajankohtainen aihe, sillä lähes kaikki pyrkivät elämässään onnellisuuteen. Tutkimuskysymykseni ovat: "Minkälaisia onnellisuusteorioita psykologiassa on? Miten onnellisuusteoriat mallintavat onnellisuuden ja hyvinvoinnin lisäämistä? Ja millä tavoin yksilö voi lisätä omaa onnellisuuttaan?". Ensin määrittelen positiivisen psykologian, onnellisuuden ja hyvinvoinnin käsitteet. Tämän jälkeen lähden tarkastelemaan onnellisuuden eri teorioita. Etenen tutkielmassani tarkastelemalla positiivisen psykologian tutkimuksia sekä näkökulmia onnellisuudesta. Tämän pohjalta käsittelen kysymystä, minkälaisin keinoin yksilö voi lisätä omaa onnellisuuttaan. Käytän tutkielmassani tutkimusmetodina kirjallisuuskatsausta. Onnellisuus on positiivisen psykologian yksi suurimmista tutkimuskohteista. Onnellisuuden käsitteelle on silti hankala antaa yhtä tiettyä määritelmää, sillä onnellisuuteen liittyy monenlaisia näkökulmia ja mielipiteitä riippuen ihmisistä ja kulttuureista. Tutkimuksessani onkin tarkoitus saada selvyyttä erilaisiin käsityksiin onnellisuudesta ja sen pohjalta määritellä paremmin, kuinka onnellisuutta pystyy lisäämään. Tuloksista tulee ilmi, että onnellisuuteen vaikuttavat monenlaiset tekijät. Kaksoistutkimusten perusteella on kehitelty teoria, jonka myötä ajatellaan geenien vaikuttavan onnellisuuteen 50 prosenttia, tietoinen toiminta 40 prosenttia ja olosuhteet vain 10 prosenttia. Tutkielman tuloksissa korostuu ihmissuhteiden tärkeys sekä yksilön oma voima vaikuttaa omaan onnellisuuteensa. Yksilö voi edistää omaa onnellisuuttaan monen eri keinoin. Tärkeimpinä nostetaan esille muun muassa ihmissuhteisiin panostaminen, kiitollisuuden ja optimismin vaaliminen sekä tavoitteiden asettaminen.

Background Very preterm infants are at high risk of death or severe morbidity. The objective was to determine the significance of severe congenital heart defects (CHDs) for these risks. Methods and Results This cohort study included infants from 10 countries born from 2007-2015 at 24 to 31 weeks' gestation with birth weights

To evaluate the proportion of neonatal intensive care units with facilities supporting parental presence in their infants' rooms throughout the 24-hour day (ie, infant-parent rooms) in high-income countries and to analyze the association of this with outcomes of extremely preterm infants.

We surveyed care practices for critically ill very preterm infants admitted to neonatal intensive care units (NICUs) in the International Network for Evaluating Outcomes in Neonates (iNeo) to identify differences relevant to outcome comparisons.

Neonates born very preterm (before 32 weeks’ gestational age), are a significant public health concern because of their high-risk of mortality and life-long disability. In addition, caring for very preterm neonates can be expensive, both during their initial hospitalization and their long-term cost of permanent impairments. To address these issues, national and regional neonatal networks around the world collect and analyse data from their constituents to identify trends in outcomes, and conduct benchmarking, audit and research. Improving neonatal outcomes and reducing health care costs is a global problem that can be addressed using collaborative approaches to assess practice variation between countries, conduct research and implement evidence-based practices. The International Network for Evaluating Outcomes (iNeo) of neonates was established in 2013 with the goal of improving outcomes for very preterm neonates through international collaboration and comparisons. To date, 10 national or regional population-based neonatal networks/datasets participate in iNeo collaboration. The initiative now includes data on >200,000 very preterm neonates and has conducted important epidemiological studies evaluating outcomes, variations and trends. The collaboration has also surveyed >320 neonatal units worldwide to learn about variations in practices, healthcare service delivery, and physical, environmental and manpower related factors and support services for parents. The iNeo collaboration serves as a strong international platform for Neonatal-Perinatal health services research that facilitates international data sharing, capacity building, and global efforts to improve very preterm neonate care.

The availability of and variability in healthcare professionals in neonatal units in different countries has not been well characterized. Our objective was to identify variations in the healthcare professionals for preterm neonates in 10 national or regional neonatal networks participating in the International Network for Evaluating Outcomes (iNeo) of neonates.

Neonates born very preterm (before 32 weeks' gestational age), are a significant public health concern because of their high-risk of mortality and life-long disability. In addition, caring for very preterm neonates can be expensive, both during their initial hospitalization and their long-term cost of permanent impairments. To address these issues, national and regional neonatal networks around the world collect and analyse data from their constituents to identify trends in outcomes, and conduct benchmarking, audit and research. Improving neonatal outcomes and reducing health care costs is a global problem that can be addressed using collaborative approaches to assess practice variation between countries, conduct research and implement evidence-based practices. The International Network for Evaluating Outcomes (iNeo) of neonates was established in 2013 with the goal of improving outcomes for very preterm neonates through international collaboration and comparisons. To date, 10 national or regional population-based neonatal networks/datasets participate in iNeo collaboration. The initiative now includes data on >200,000 very preterm neonates and has conducted important epidemiological studies evaluating outcomes, variations and trends. The collaboration has also surveyed >320 neonatal units worldwide to learn about variations in practices, healthcare service delivery, and physical, environmental and manpower related factors and support services for parents. The iNeo collaboration serves as a strong international platform for Neonatal-Perinatal health services research that facilitates international data sharing, capacity building, and global efforts to improve very preterm neonate care.

To compare necrotising enterocolitis (NEC) prevention practices and NEC associated factors between units from eight countries of the International Network for Evaluation of Outcomes of Neonates, and to assess their association with surgical NEC rates.

To evaluate outcome trends of neonates born very preterm in 11 high-income countries participating in the International Network for Evaluating Outcomes of neonates.

Objective To evaluate outcome trends of neonates born very preterm in 11 high-income countries participating in the International Network for Evaluating Outcomes of neonates. Study design In a retrospective cohort study, we included 154 233 neonates admitted to 529 neonatal units between January 1, 2007, and December 31, 2015, at 24(0/7) to 31(6/7) weeks of gestational age and birth weight

Objectives: To assess factors contributing to patient injuries in operative rhinology. Design: Data of the accepted patient injury claims involving operative rhinology, between the years 2001 and 2011, were obtained from the Finnish Patient Insurance Centre registry. Two senior otolaryngologists analysed and evaluated the injury mechanisms. Main outcome measures: Analysis and classification of factors contributing to patient injuries. Results: During the ten-year study period, there were 67 patient injuries in operative rhinology, comprising 36% of all patient injuries in otorhinolaryngologic surgery. The majority (78%) of patients were treated in university or central hospitals and almost all (90%) by fully trained otolaryngology specialists. The factors contributing to the injuries were errors in surgical technique, like lesions to the orbit, skull base and meninges, and adjacent nerves, as well as mistakes with removable packings left in situ. Nearly half of the patients had undergone endoscopic sinus surgery. One patient died because of bleeding from the intracranial artery. Fourteen patients (21%) needed a re-operation due to the injury. Conclusions: Patient injuries in rhinology were caused by typical complications of common operations performed by otorhinolaryngology specialists. The increased volume of endoscopic sinus surgery was evident also in patient injuries.

Background: There are significant international variations in chronic lung disease rates among very preterm infants yet there is little data on international variations in respiratory strategies. Objective: To evaluate practice variations in the respiratory management of extremely preterm infants born at

Background: Rates of retinopathy of prematurity (ROP) and ROP treatment vary between neonatal intensive care units (NICUs). Neonatal care practices, including oxygen saturation (SpO(2)) targets and criteria for the screening and treatment of ROP, are potential contributing factors to the variations. Objectives: To survey variations in SpO(2) targets in 2015 (and whether there had been recent changes) and criteria for ROP screening and treatment across the networks of the International Network for Evaluating Outcomes in Neonates (iNeo). Methods: Online prepiloted questionnaires on treatment practices for preterm infants were sent to the directors of 390 NICUs in 10 collaborating iNeo networks. Nine questions were asked and the results were summarized and compared. Results: Overall, 329/390 (84%) NICUs responded, and a majority (60%) recently made changes in upper and lower SpO(2) target limits, with the median set higher than previously by 2-3% in 8 of 10 networks. After the changes, fewer NICUs (15 vs. 28%) set an upper SpO(2) target limit >95% and fewer (3 vs. 5%) a lower limit

Objective To compare the rates of retinopathy of prematurity (ROP) and treatment of ROP by laser or intravitreal anti-vascular endothelial growth factor among preterm neonates from high-income countries participating in the International Network for Evaluating Outcomes (iNeo) of neonates. Methods A retrospective cohort study was conducted on extremely preterm infants weighing

The use of different definitions for bronchopulmonary dysplasia (BPD) has been an ongoing challenge. We searched papers published in English from 2010 and 2015 reporting BPD as an outcome, together with studies that compared BPD definitions between 1978 and 2015. We found that the incidence of BPD ranged from 6% to 57%, depending on the definition chosen, and that studies that investigated correlations with long-term pulmonary and/or neurosensory outcomes reported moderate-to-low predictive values regardless of the BPD criteria. Conclusion: A comprehensive and evidence-based definition for BPD needs to be developed for benchmarking and prognostic use.

© 2017, Springer-Verlag Wien.We present the results of experiments on dynamic nuclear polarization and relaxation of 75As in silicon crystals. Experiments are performed in strong magnetic fields of 4.6 T and temperatures below 1 K. At these conditions donor electron spins are fully polarized, and the allowed and forbidden electron spin resonance transitions are well resolved. We demonstrate effective nuclear polarization of 75As nuclei via the Overhauser effect on the time scale of several hundred seconds. Excitation of the forbidden transitions leads to a polarization through the solid effect. The relaxation rate of donor nuclei has strong temperature dependence characteristic of Orbach process.

Early neonatal death (ENND), defined as the death of a newborn between zero and seven days after birth, represents 73% of all postnatal deaths worldwide. Despite a 50% reduction in childhood mortality, reduction of ENND has significantly lagged behind other Millennium Developmental Goal achievements and is a growing contributor to overall mortality in children aged

We present an experimental study of electron spin waves in atomic hydrogen gas compressed to high densities of $\sim 5 \times 10^{18}$ cm$^{-3}$ at temperatures ranging from 0.26 to 0.6 K in strong magnetic field of 4.6 T. Hydrogen gas is in a quantum regime when the thermal de Broglie wavelength is much larger than the s-wave scattering length. In this regime the identical particle effects play major role in atomic collisions and lead to the Identical Spin Rotation effect (ISR). We observed a variety of spin wave modes caused by this effect with strong dependence on the magnetic potential caused by variations of the polarizing magnetic field. We demonstrate confinement of the ISR modes in the magnetic potential and manipulate their properties by changing the spatial profile of magnetic field. We have found that at a high enough density of H gas the magnons accumulate in their ground state in the magnetic trap and exhibit long coherence, which has a profound effect on the electron spin resonance spectra. Such macroscopic accumulation of the ground state occurs at a certain critical density of hydrogen gas, where the chemical potential of the magnons becomes equal to the energy of their ground state in the trapping potential., 16 pages, 15 figures

Kandidaatintyö tehtiin toimeksiantona Outokummun Tornion tehtaiden Neutralointi- ja regenerointilaitokselle tarkoituksena selvittää jatkuvatoimisen öljyä vedessä ympäristömittausjärjestelmän soveltuvuutta Neutralointi- ja regenerointilaitoksen rasvanpoistoprosessissa puhdistetun veden laadun tarkkailuun. Laitteiston soveltuvuuden arvioimiseksi järjestettiin neljän viikon koejakso, jonka tarkoituksena oli osoittaa, että se pystyy havaitsemaan poikkeamat veden laadussa. Tavoitteena oli myös arvioida laitteiston teknistä sopivuutta ja huollon tarvetta. Tässä työssä seurattiin neljän viikon koejaksoa ja mittauksen luotettavuuden arvioimiseksi koejakson ajan puhdistetusta vedestä otettiin manuaalisesti tutkimusnäytteitä, joiden tuloksia verrattiin automaattisen mittauksen tuloksiin. Ennen koejakson alkua puhdistetun veden laatua valvottiin kaksi kertaa viikossa otetuilla manuaalisilla näytteillä, jolloin prosessin häiriötilanteisiin ei ollut mahdollista reagoida välittömästi. Jatkuvatoimisen öljyä vedessä-mittauksen avulla öljy- ja rasvapitoisuuksia nostaviin prosessihäiriöihin pystyttäisiin puuttumaan heti niiden ilmetessä, ja öljy- ja rasvakuormitus vähenisi ja pitoisuudet pysyisivät Outokummun Tornion tehtaiden sisäisen rajaarvon alapuolella. Laitteisto osoittautui koejakson aikana toimintavarmaksi ja huollon tarve oli kohtalaisen vähäinen. Koejakson aikana ei tapahtunut merkittäviä prosessihäiriöitä, mutta laitteisto reagoi pienempiin poikkeamiin koejakson aikana. Laitteisto vaikutti sopivan Outokummun Tornion tehtaiden tarpeita vastaavaksi. Manuaalisesti kerättyjen tutkimusnäytteiden ja automaattimittausten tulosten välillä havaittiin pieniä eroavaisuuksia, mutta kokonaisuutena vastaavuus oli hyvä. Koejakson perusteella Outokumpu päätti hankkia laitteiston käyttöönsä.

© 2015, Springer Science+Business Media New York.We report on the measurements of electrons trapped in solid molecular films of H (Formula presented.) , HD, and D (Formula presented.). A narrow ESR line associated with the trapped electrons was detected with (Formula presented.) , which turned out to be shifted by (Formula presented.) 0.3 G from the free electron resonance. Comparison is made with earlier measurements where a similar line has been seen. In addition, for a (Formula presented.) mixture, after raising the temperature above 1 K, we observe a strong line at the location of the electron cyclotron resonance. The line amplitude is dependent on temperature and has an activation energy of 26 K. We believe that at elevated temperatures, electrons diffuse from the bulk of the film to the surface.

© 2016 the Owner Societies.We report on a study of the exchange tunneling reaction D + HD → D2 + H in a pure solid HD matrix and in a D2 matrix with a 0.23% HD admixture at temperatures between 130 mK and 1.5 K. We found that the exchange reaction rates, kexHD ∼ 3 × 10-27 cm3 s-1 in the pure HD matrix, and kexD2 = 9(4) × 10-28 cm3 s-1 in the D2 matrix, are nearly independent of temperature within this range. This confirms the quantum tunnelling nature of these reactions, and their ability to proceed at temperatures down to absolute zero. Based on these observations we concluded that exchange tunneling reaction H + H2 → H2 + H should also proceed in a H2 matrix at the lowest temperatures. On the other hand, the recombination of H atoms in solid H2 and D atoms in solid D2 is substantially suppressed at the lowest temperatures as a result of a decreased probability of resonant tunneling of atoms when they approach each other.

We present the results of experiments on dynamic nuclear polarization and relaxation of 75As in silicon crystals. Experiments are performed in strong magnetic fields of 4.6 T and temperatures below 1 K. At these conditions donor electron spins are fully polarized, and the allowed and forbidden ESR transitions are well resolved. We demonstrate effective nuclear polarization of 75As nuclei via the Overhauser effect on the time scale of several hundred seconds. Excitation of the forbidden transitions leads to a polarization through the solid effect. The relaxation rate of donor nuclei has strong temperature dependence characteristic of Orbach process., Comment: 9 pages, 7 figures

We report on a study of the exchange tunneling reaction D+HD$\rightarrow$D$_{2}$+H in a pure solid HD matrix and in a D$_{2}$ matrix with 0.23$\%$ HD admixture at temperatures between 130$\,$mK and 1.5$\,$K. We found that the exchange reaction rates, $k_{exHD}\sim3\times10^{-27}$cm$^{3}$s$^{-1}$ in the pure HD matrix, and $k_{exD_{2}}=9(4)\times10^{-28}$cm$^{-3}$ in the D$_{2}$ matrix are nearly independent of temperature within this range. This confirms quantum tunnelling nature of these reactions, and their ability to proceed at temperatures down to absolute zero. Based on these observations we concluded that exchange tunneling reaction H+H$_{2}\rightarrow$H$_{2}$+H should also proceed in a H$_{2}$ matrix at the lowest temperatures. On contrary, the recombination of H atoms in solid H$_{2}$ and D atoms in solid D$_{2}$ is substantially suppressed at the lowest temperatures as a result of increasing of violation for resonance tunneling of atoms when they approach each other.

© 2015 American Physical Society. We demonstrate an efficient control of Si29 nuclear spins for specific lattice sites near P31 donors in silicon at temperatures below 1 K and in a high magnetic field of 4.6 T. Excitation of the forbidden electron-nuclear transitions leads to a pattern of well-resolved holes and peaks in the electron spin resonance (ESR) lines of P31. The pattern originates from dynamic polarization (DNP) of the Si29 nuclear spins near the donors via the solid effect. DNP of Si29 is demonstrated also with the Overhauser effect where the allowed ESR transitions are excited. In this case mostly the remote Si29 nuclei having weak interaction with the donors are polarized, which results in a single hole and a sharp peak pair in the ESR spectrum. Our work shows that the solid effect can be used for initialization of Si29 nuclear spin qubits near the donors.

© 2014 American Physical Society. Efficient manipulation of nuclear spins is important for utilizing them as qubits for quantum computing. In this work we report record high polarizations of 31P and Si29 nuclear spins in P-doped silicon in a strong magnetic field (4.6 T) and at temperatures below 1 K. We reached 31P nuclear polarization values exceeding 98% after 20 min of pumping the high-field electron spin resonance (ESR) line with a very small microwave power of 0.4 μW. We evaluate that the ratio of the hyperfine-state populations increases by three orders of magnitude after 2 hours of pumping, and an extremely pure nuclear spin state can be created, with less than 0.01 ppb impurities. A negative dynamic nuclear polarization has been observed by pumping the low-field ESR line of 31P followed by the flip-flip cross relaxation, the transition which is fully forbidden for isolated donors. We estimate that while pumping the ESR transitions of 31P also the nuclei of Si29 get polarized, and polarization exceeding 60% has been obtained. We performed measurements of relaxation rates of flip-flop and flip-flip transitions which turned out to be nearly temperature independent. Temperature dependence of the 31P nuclear relaxation was studied down to 0.75 K, below which the relaxation time became too long to be measured. We found that the polarization evolution under pumping and during relaxation deviates substantially from a simple exponential function of time. We suggest that the nonexponential polarization dynamics of 31P donors is mediated by the orientation of Si29 nuclei, which affect the transition probabilities of the forbidden cross-relaxation processes.

We demonstrate that the dynamic nuclear polarization (DNP) of phosphorus donors in silicon can be very effective in a magnetic field of 4.6 T and at temperatures below 1 K. The DNP occurs due to the Overhauser effect following a cross relaxation via the forbidden flip-flop or flip-flip transitions. Nuclear polarization values $P>0.98$ were reached after 20 min of pumping with 0.4 $��$W of microwave power. We evaluated that the ratio of hyperfine state populations increased by three orders of magnitude after 2 hours of pumping, and an extremely pure nuclear spin system containing $

We demonstrate an efficient control of $^{29}$Si nuclear spin orientation for specific lattice sites near $^{31}$P donors in silicon crystals at temperatures below 1 K and in high magnetic field of 4.6 T. Excitation of the forbidden electron-nuclear transitions leads to a pattern of narrow holes and peaks in the ESR lines of $^{31}$P. The pattern originates from dynamic polarization the $^{29}$Si nuclear spins near the donors via the solid effect. This method can be used for initialization of qubits based on $^{29}$Si nuclear spins in the all-silicon quantum computer. In comparison, polarization of $^{29}$Si performed by pumping the allowed ESR transitions, did not create any patterns. Instead, a single narrow spectral hole was burnt in the ESR line. The difference is explained by a rapid spin diffusion during the microwave pumping of the allowed transitions.

Levosimendan is a new calcium sensitizer, acting calcium-dependently on cardiac troponin C. In the present study pharmacokinetic-pharmacodynamic interrelations of levosimendan were assessed.Ten healthy subjects (22-27 years) were given single doses of 2 mg of levosimendan in 4 different formulations: intravenous (i.v.), conventional tablet (CT), conventional capsule (CC), and slow-release tablet (SR) on different days. Systolic time intervals and impedance cardiography were recorded up to 4 hours post drug. Plasma concentrations of levosimendan and its metabolite OR-1855 were analyzed using HPLC. Hysteresis loops were constructed by connecting the effect-concentration points in time order. In addition, pharmacokinetic-pharmacodynamic modelling was performed with the i.v. data.The i.v. administration, giving a maximal levosimendan concentration of 180 ng x ml(-1), increased heart rate by 8 beats min(-1) and cardiac output by 18%. It shortened heart rate corrected electromechanical systole QS2i by 23 ms, indicating a fairly strong positive inotropic effect. The conventional oral formulations (giving maximal drug concentrations of about 70-80 ng x ml(-1)) increased heart rate by 4-5 beats min(-1) and cardiac output by 5-8%, while QS2i shortened by 9-13 ms. The SR formulation resulted in low drug concentrations and generally weaker effects than the other formulations. The bioavailability of CT and CC was 83 and 87%, while that of SR was only 31%. QS2i showed counter-clockwise hysteresis after all formulations (p0.01). The mean equilibration half-time (ln(2)/k(e0)) after i.v. administration was 9.6 min. Only after SR, OR-1855 was detected in appreciable amounts in plasma, the highest value being 2.2 ng x ml(-1) which occurred 24 hours after drug intake.In conclusion, the pharmacokinetic-dynamic behavior of the inotropy index QS2i indicates an equilibration delay of levosimendan, which most probably reflects the time the drug requires to distribute from plasma to its cardiac site of action. The deviant kinetic-dynamic profile of the oral slow-release formulation suggests a different absorption pattern of levosimendan from this formulation.

To study the changes in immune system during aging and their effects on patient survival, immune functions of 18 very old (92-107 years) hospital patients were tested. After three years follow-up, the survival of patients and the correlation of immune capacity to lifetime were determined. In the very old patients, the frequency of T lymphocytes was significantly lower than in young adults. This decrease was attributed more to the CD8-positive than to CD4-positive cell subset, leading to generally high CD4/CD8 ratios. The mitogenic responses to phytohemagglutinin (PHA) and concanavalin A (Con A), but not pokeweed mitogen (PWM), were decreased significantly in cultures with isolated lymphocytes, while in whole blood cultures the responses to PHA and PWM but not to Con A were reduced. In very advanced age, there was a significant decrease in the number of B cells, and the ability to produce IgM in vitro was decreased. During the follow-up time, 15 out of the 18 patients died. However, their lifetime was not in correlation with any single immune parameter.

Transplantation of allogeneic bursal cells into cyclophosphamide-treated, immunodeficient chickens is a useful experimental model for analyzing the mechanisms of transplantation tolerance, especially because transplanted bursal cells do not produce graft-versus-host disease. In this study we have determined B-lymphoid chimerism in various lymphoid organs after transplantation of allogeneic bursal stem cells or postbursal cells, and used a variety of tests to determine presence of immunological tolerance. Transplanted bursal stem cells induced a state of stable chimerism that could easily be detected in peripheral blood and other lymphoid organs. Chimerism induced by postbursal cells was low in peripheral blood, but clearly observable in other lymphoid organs, especially in spleen and thymus. Both bursal and postbursal cells induced specific unresponsiveness to donor-line alloantigens. Bursal cell recipients accepted donor line skin grafts--and their graft-versus-host reactivity, as assayed by embryonal splenomegaly, and mixed lymphocyte reactivity against donor line alloantigens were significantly decreased. Despite differences in chimerism, a strong transplantation tolerance was readily induced with bursal stem cells and with postbursal cells.

Chickens surgically bursectomized in ovo (Bx) at 60 hr of embryonic development offer a unique model to study selectively the influence of the bursa of Fabricius on thymus-dependent immune functions because the lymphoid cells of these animals develop in the total absence of the bursal microenvironment. The Bx chickens have been shown to be unable to respond to antigenic stimulation by specific antibody production. In the present study, we have characterized different aspects of T-cell-mediated immunity in Bx chickens. Our results indicate the existence of a normal, functional T cell system in these animals. Peripheral blood leukocytes from Bx chickens were able to induce normal graft-versus-host reaction and mixed lymphocyte reaction. The capacity of peripheral blood T cells from Bx animals to produce interleukin-2 was indistinguishable from that of their normal counterparts, suggesting normal function of T helper cells. We demonstrate that peripheral blood leukocytes from Bx birds have normal in vitro proliferative responses to nonspecific T cell mitogens, concanavalin A, and phytohemagglutinin, and to a specific antigen, keyhole limpet hemocyanin. The inability of the Bx chickens to respond to specific antigens is therefore restricted to B cells and to production of specific antibodies. Our findings indicate that the bursa of Fabricius is not necessary for the development of thymus-dependent immune functions and support the suggestion that the specific function of the bursa is the creation of antibody diversity.

B cells from bursa of Fabricius of newly hatched chickens are able to reconstitute the B cell compartment of chemically bursectomized chickens. The resulting B cell chimerism can be detected with monoclonal antibodies against donor B cell alloantigen. Chimeric chickens accept donor-type skin grafts and are unresponsive to donor major histocompatibility complex (MHC) antigens in graft-vs.-host splenomegaly assay and mixed lymphocyte reaction. To study the capability of B cells to induce tolerance to selected MHC antigens, we transplanted class I or total MHC-incompatible bursa cells into cyclophosphamide-treated recipients. The recipients of class I or total MHC-incompatible bursa cells were equally tolerant of donor-MHC antigens. To further analyze the mechanisms of tolerance to class I antigens vs. total MHC, spleen cells from tolerant chickens were transferred to irradiated, histocompatible secondary hosts. The secondary recipients were also unresponsive to bursa cell donor-strain MHC antigens. However, if the chimeric B cells were depleted before the spleen cell transfer, the transfer of tolerance to total MHC was severely inhibited. Instead, most recipients of B cell-depleted spleen cells tolerant of class I antigens were still tolerant of bursa cell donor MHC. Our results indicate differences in the transferability of tolerance to class I antigens vs. entire MHC, although in primary recipients of bursa cells the tolerance is similar. These data suggest that a mechanism that is not dependent on the presence of donor cell chimerism contributes to the maintenance of tolerance to donor class I antigens. The transfer of tolerance to total MHC disparity requires the presence of chimeric cells indicating that donor alloantigen expression is needed for induction of tolerance in the secondary hosts.

Transplantation tolerance was induced in cyclophosphamide-treated, B-cell-depleted chickens by transfer of allogeneic bursal cells. To study the presence of specific suppressor cells in tolerant birds, mitomycin-C-treated peripheral blood lymphocytes (PBL) from tolerant recipients were cocultured in mixed lymphocyte cultures of normal syngeneic responder and allogeneic stimulator cells. No evidence of suppression was detected, since responses in cultures with tolerant cocultured cells were on the same level as the mixed lymphocyte reaction (MLR) of normal responders without cocultured cells. However, responses in cultures with normal cocultured cells were significantly higher. If cocultured cells were not treated with mitomycin C, responses to tolerizing alloantigen were equally high in cultures with tolerant cocultured cells as in cultures with normal cocultured cells. Likewise, when lymphocytes from tolerant chickens were mixed with normal syngeneic cells in graft-versus-host (GVH) splenomegaly assay, no suppression was detected, but the GVH reaction was even stronger than the reaction induced by the mixture of cells from two normal chickens. Furthermore, administration of chicken T cell growth factor (TCGF) into the cultures enhanced considerably the MLR of tolerant cells against the tolerizing alloantigen, but not against syngeneic or third-party stimulator cells. These results indicate that the transplantation tolerance in B-cell-chimeric chickens is due to lack of alloantigen-specific helper cells. When exogenous help is offered to tolerant cells either by normal syngeneic cells or by exogenous TCGF, the reactivity of tolerant cells against the tolerogen is reestablished.

Ontogeny of alloreactivity in the chicken thymus and spleen was studied in mixed lymphocyte cultures. Mixed lymphocyte reaction (MLR) to total major histocompatibility complex (MHC) (B-complex in chicken) disparity was first detected in the thymus of 16-day-old embryo and regularly detectable from the 18th embryonal day on. Small strain-specific differences in the strength and appearance of the response were, however, observed. MLR to class I MHC (B-F) antigen disparity was not detectable before hatching. Exogenous interleukin-2-containing supernatant added to the cultures had only a minor effect on MLR of embryonal thymocytes. In the spleen, MLR was first detectable in some strain combinations on day 3 and regularly found on the 7th day posthatching, indicating colonization of peripheral lymphoid organs by thymus-derived mature T cells. Our results show the association of phenotypic and functional maturation of chicken T cells. The ontogeny of alloreactivity can now be compared to the appearance of T cell receptor (TCR), CD4, and CD8-bearing cells in the thymus and peripheral lymphoid organs.

ObjectivesTo develop research priorities on the consequences of very preterm (VPT) birth for the RECAP Preterm platform which brings together data from 23 European VPT birth cohorts.Design and settingThis study used a two-round modified Delphi consensus process. Round 1 was based on 28 research themes related to childhood outcomes (ResultsOf 71 individuals contacted, 64 (90%) participated as panel members comprising obstetricians, neonatologists, nurses, general and specialist paediatricians, psychologists, physiotherapists, parents, adults born preterm, policy makers and epidemiologists from 17 countries. All 28 initial themes were ranked in the top 10 by at least six panel members. Highest ranking themes were: education (73% of panel members' top 10 choices); care and outcomes of extremely preterm births, including ethical decisions (63%); growth and nutrition (60%); emotional well-being and social inclusion (55%); parental stress (55%) and impact of social circumstances on outcomes (52%). Highest ranking themes were robust across panel members classified by background. 15 new themes had at least 6 top 10 endorsements in round 2.ConclusionsThis study elicited a broad range of research priorities on the consequences of VPT birth, with good consensus on highest ranks between stakeholder groups. Several highly ranked themes focused on the socioemotional needs of children and parents, which have been less studied.

This cross-linguistic study investigated whether the native language has any influence on lexical composition among Italian ( N = 125) and Finnish ( N = 116) very preterm (born at