Molecular mechanics force fields from ab initio calculations

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/87595/2/224_1.pd

Internet as a source of medicines information (MI) among frequent internet users

Background: The internet is widely and increasingly used to search for health information. Previous studies have focused mainly on health information on the internet and not specifically on medicines information (MI). Objectives: The aim of this study was to explore the internet as a source of MI compared to other sources of MI; to identify those who use the internet as a source of MI; and to describe patterns of use of the internet as a source of MI. Methods: A cross-sectional design employed a web-based questionnaire posted by patients' and other organizations as well as pharmacies on their websites during six weeks in the beginning of 2014. Logistic regression analysis was used to assess associations of background variables to the use of different MI sources. Results: The most frequently used MI sources among respondents (n = 2489) were package leaflets (90%), pharmacists (83%), physicians (72%), and the internet (68%). According to a multivariate analysis, internet use for MI was associated with female gender, age <65 years, higher education, daily use of the internet, and continuous use of vitamins or herbals. MI was most commonly searched from a Finnish health portal (56%) and websites of pharmacies (41%). Of the respondents, nearly half (43%) used search engines to find information from the internet. The names of the medicinal product, symptom or disease were the most commonly used search terms. Conclusions: Well-educated, young women tend to search MI on the internet. Health care professionals should discuss reliable MI websites and tools that can help patients evaluate the reliability of information.Peer reviewe

Fermi polarons in two dimensions

We theoretically analyze inverse radiofrequency (rf) spectroscopy experiments in two-component Fermi gases. We consider a small number of impurity atoms interacting strongly with a bath of majority atoms. In two-dimensional geometries we find that the main features of the rf spectrum correspond to an attractive polaron and a metastable repulsive polaron. Our results suggest that the attractive polaron has been observed in a recent experiment [Phys. Rev. Lett. 106, 105301 (2011)].Comment: 6 pages, 7 figure

Perusterveydenhuollon ja erikoissairaanhoidon puheterapeuttien työhyvinvointi:työtyytyväisyys, työperäinen stressi ja työn laatu

Tiivistelmä. Tämän pro gradu -tutkielman tarkoituksena oli selvittää perusterveydenhuollossa ja erikoissairaanhoidossa työskentelevien puheterapeuttien työhyvinvointia. Työhyvinvointia tutkittiin työtyytyväisyyden, työperäisen stressin ja työn laatuun liittyvien tekijöiden näkökulmasta. Lisäksi näissä organisaatioissa työskentelevien puheterapeuttien kokemuksia vertailtiin keskenään. Tutkimus toteutettiin Webropol-kyselynä, johon vastasi 304 puheterapeuttia. Vastaajista perusterveydenhuollossa työskenteli 229 ja erikoissairaanhoidossa 75. Tutkimusta varten kehitettiin kyselylomake, joka koostui yhteensä 52 kysymyksestä ja väittämästä. Kysely jaettiin kolmeen osa-alueeseen, joista ensimmäisessä kysyttiin vastaajien taustatekijöitä. Toisessa osassa kartoitettiin työn laatuun liittyviä tekijöitä ja viimeinen osa käsitteli työtyytyväisyyttä ja työperäisen stressin kokemista. Tulokset osoittivat, että puheterapeutit ovat melko tyytyväisiä työhönsä, vaikka stressiäkin koetaan. Työtyytyväisyyden ja taustatekijöiden välillä ei ollut tilastollisesti merkitseviä yhteyksiä. Taustatekijöistä työperäisen stressiin oli tilastollisesti erittäin merkitsevästi yhteydessä ylitöiden tekeminen. Lisäksi stressin ja työorganisaation väliltä löytyi yhteys. Suuntaa-antavia yhteyksiä löytyi jonkin verran sekä työtyytyväisyyden että stressin osalta. Suurin osa työn laatuun liittyvistä tekijöistä oli yhteydessä työtyytyväisyyteen ja työperäiseen stressiin. Työn laatuun liittyvät tekijät myös selittivät työtyytyväisyyttä ja stressiä. Työtyytyväisyyden osalta perusterveydenhuollon ja erikoissairaanhoidon puheterapeuttien välillä oli ero tyytyväisyydessä työympäristöön. Perusterveydenhuollon puheterapeutit olivat erikoissairaanhoidon puheterapeutteja tyytyväisempiä työympäristöönsä. Työperäisen stressin osalta ryhmät erosivat tilastollisesti merkitsevästi toisistaan. Perusterveydenhuollon puheterapeutit kokivat stressiä enemmän. Ryhmien välisiä eroja löytyi myös muutaman työn laatuun liittyvän tekijän kohdalla. Esimerkiksi arviointi- ja kuntoutusjaksojen riittävä pituus sekä jonossa olevien asiakkaiden vaikutus työskentelylle erotteli ryhmiä. Tämän työn tulokset ovat samansuuntaisia kuin aiemmissa tutkimuksissa, mutta myös eroavaisuuksia oli havaittavissa esimerkiksi taustatekijöiden kohdalla. Työn laatuun liittyvien tekijöiden kautta saatiin erilaista näkökulmaa työhyvinvoinnin tutkimiseen. Tutkimus toi tärkeää tietoa puheterapeuttien työhyvinvoinnista, koska aihetta ei ole tutkittu riittävästi. Tutkimuksen suhteellisen suuren vastaajamäärän vuoksi tuloksia voidaan pitää luotettavina ja yleistettävinä ainakin työtyytyväisyyden ja työperäisen stressin osalta. Tutkimuksen avulla voidaan myös kehittää puheterapeuttien työhyvinvointia, jotta tyytyväisyys työhön säilyisi ja toisaalta työperäisen stressin määrä pysyisi kohtuullisena. Työhyvinvointitutkimus tukee paitsi puheterapeuttien työskentelyä ja työssä jaksamista, myös laadukkaiden puheterapiapalveluiden tarjoamista

Introducing untargeted data-independent acquisition for metaproteomics of complex microbial samples

Mass spectrometry-based metaproteomics is a relatively new field of research that enables the characterization of the functionality of microbiota. Recently, we demonstrated the applicability of data-independent acquisition (DIA) mass spectrometry to the analysis of complex metaproteomic samples. This allowed us to circumvent many of the drawbacks of the previously used data-dependent acquisition (DDA) mass spectrometry, mainly the limited reproducibility when analyzing samples with complex microbial composition. However, the DDA-assisted DIA approach still required additional DDA data on the samples to assist the analysis. Here, we introduce, for the first time, an untargeted DIA metaproteomics tool that does not require any DDA data, but instead generates a pseudospectral library directly from the DIA data. This reduces the amount of required mass spectrometry data to a single DIA run per sample. The new DIA-only metaproteomics approach is implemented as a new open-source software package named glaDIAtor, including a modern web-based graphical user interface to facilitate wide use of the tool by the community.</p

Effect of Inhaled Xenon on Cerebral White Matter Damage in Comatose Survivors of Out-of-Hospital Cardiac Arrest: A Randomized Clinical Trial

IMPORTANCE: Evidence from preclinical models indicates that xenon gas can prevent the development of cerebral damage after acute global hypoxic-ischemic brain injury but, thus far, these putative neuroprotective properties have not been reported in human studies. OBJECTIVE: To determine the effect of inhaled xenon on ischemic white matter damage assessed with magnetic resonance imaging (MRI). DESIGN, SETTING, AND PARTICIPANTS: A randomized single-blind phase 2 clinical drug trial conducted between August 2009 and March 2015 at 2 multipurpose intensive care units in Finland. One hundred ten comatose patients (aged 24-76 years) who had experienced out-of-hospital cardiac arrest were randomized. INTERVENTIONS: Patients were randomly assigned to receive either inhaled xenon combined with hypothermia (33°C) for 24 hours (n = 55 in the xenon group) or hypothermia treatment alone (n = 55 in the control group). MAIN OUTCOMES AND MEASURES: The primary end point was cerebral white matter damage as evaluated by fractional anisotropy from diffusion tensor MRI scheduled to be performed between 36 and 52 hours after cardiac arrest. Secondary end points included neurological outcome assessed using the modified Rankin Scale (score 0 [no symptoms] through 6 [death]) and mortality at 6 months. RESULTS: Among the 110 randomized patients (mean age, 61.5 years; 80 men [72.7%]), all completed the study. There were MRI data from 97 patients (88.2%) a median of 53 hours (interquartile range [IQR], 47-64 hours) after cardiac arrest. The mean global fractional anisotropy values were 0.433 (SD, 0.028) in the xenon group and 0.419 (SD, 0.033) in the control group. The age-, sex-, and site-adjusted mean global fractional anisotropy value was 3.8% higher (95% CI, 1.1%-6.4%) in the xenon group (adjusted mean difference, 0.016 [95% CI, 0.005-0.027], P = .006). At 6 months, 75 patients (68.2%) were alive. Secondary end points at 6 months did not reveal statistically significant differences between the groups. In ordinal analysis of the modified Rankin Scale, the median (IQR) value was 1 (1-6) in the xenon group and 1 (0-6) in the control group (median difference, 0 [95% CI, 0-0]; P = .68). The 6-month mortality rate was 27.3% (15/55) in the xenon group and 34.5% (19/55) in the control group (adjusted hazard ratio, 0.49 [95% CI, 0.23-1.01]; P = .053). CONCLUSIONS AND RELEVANCE: Among comatose survivors of out-of-hospital cardiac arrest, inhaled xenon combined with hypothermia compared with hypothermia alone resulted in less white matter damage as measured by fractional anisotropy of diffusion tensor MRI. However, there was no statistically significant difference in neurological outcomes or mortality at 6 months. These preliminary findings require further evaluation in an adequately powered clinical trial designed to assess clinical outcomes associated with inhaled xenon among survivors of out-of-hospital cardiac arrest. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00879892

Gut microbiota composition is associated with temperament traits in infants

Background: One of the key behavioral phenotypes in infancy are different temperament traits, and certain early life temperament traits have been shown to precede later mental health problems. Differences in the gut microbiota composition (GMC) have been suggested to link with neurodevelopment. For example, toddler temperament traits have been found to associate with differences in GMC; however, studies in infants are lacking although infancy is a rapid period of neurodevelopment as well as GM development. Thus, we aimed to investigate association between infant GMC and temperament. Methods: The study population (n = 301, 53% boys) was drawn from the FinnBrain Birth Cohort Study. Stool samples were collected from the 2.5-month-old infants and sequenced with 16S Illumina MiSeq platform. GMC taxonomic composition (at Genus and OTU level), observed sample clusters, diversity and richness were investigated in relation to the maternal reports of Infant Behavior Questionnaire -Revised (IBQ-R) at the age of 6 months. Results: Three sample clusters (Bifidobacterium/Enterobacteriaceae, Bacteroides, V. Dispar) based on GMC were identified, of which Bifidobacterium/Enterobacteriaceae–cluster presented with higher scores on the IBQ-R main dimension regulation and its subscale duration of orienting compared to Bacteroides-cluster. The clusters associated with temperament in a sex-dependent manner. The IBQ-R main dimension surgency (positive emotionality) was associated positively both with genus Bifidobacterium and Streptococcus. Alpha diversity had a negative association with negative emotionality and fear reactivity. Conclusion This is the first study demonstrating associations, but not causal connections, between GMC and temperament in young infants in a prospective design

A multifrequency analysis of radio variability of blazars

We have carried out a multifrequency analysis of the radio variability of blazars, exploiting the data obtained during the extensive monitoring programs carried out at the University of Michigan Radio Astronomy Observatory (UMRAO, at 4.8, 8, and 14.5 GHz) and at the Metsahovi Radio Observatory (22 and 37 GHz). Two different techniques detect, in the Metsahovi light curves, evidences of periodicity at both frequencies for 5 sources (0224+671, 0945+408, 1226+023, 2200+420, and 2251+158). For the last three sources consistent periods are found also at the three UMRAO frequencies and the Scargle (1982) method yields an extremely low false-alarm probability. On the other hand, the 22 and 37 GHz periodicities of 0224+671 and 0945+408 (which were less extensively monitored at Metsahovi and for which we get a significant false-alarm probability) are not confirmed by the UMRAO database, where some indications of ill-defined periods about a factor of two longer are retrieved. We have also investigated the variability index, the structure function, and the distribution of intensity variations of the most extensively monitored sources. We find a statistically significant difference in the distribution of the variability index for BL Lac objects compared to flat-spectrum radio quasars (FSRQs), in the sense that the former objects are more variable. For both populations the variability index steadily increases with increasing frequency. The distribution of intensity variations also broadens with increasing frequency, and approaches a log-normal shape at the highest frequencies. We find that variability enhances by 20-30% the high frequency counts of extragalactic radio-sources at bright flux densities, such as those of the WMAP and Planck surveys.Comment: A&A accepted. 12 pages, 16 figure

Head-to-head comparison of plasma p-tau181, p-tau231 and glial fibrillary acidic protein in clinically unimpaired elderly with three levels of APOE4-related risk for Alzheimer's disease

Plasma phosphorylated tau (p-tau) and glial fibrillary acidic protein (GFAP) both reflect early changes in Alzheimer's disease (AD) pathology. Here, we compared the biomarker levels and their association with regional β-amyloid (Aβ) pathology and cognitive performance head-to-head in clinically unimpaired elderly (n = 88) at three levels of APOE4-related genetic risk for sporadic AD (APOE4/4 n = 19, APOE3/4 n = 32 or non-carriers n = 37). Concentrations of plasma p-tau181, p-tau231 and GFAP were measured using Single molecule array (Simoa), regional Aβ deposition with 11C-PiB positron emission tomography (PET), and cognitive performance with a preclinical composite. Significant differences in plasma p-tau181 and p-tau231, but not plasma GFAP concentrations were present between the APOE4 gene doses, explained solely by brain Aβ load. All plasma biomarkers correlated positively with Aβ PET in the total study population. This correlation was driven by APOE3/3 carriers for plasma p-tau markers and APOE4/4 carriers for plasma GFAP. Voxel-wise associations with amyloid-PET revealed different spatial patterns for plasma p-tau markers and plasma GFAP. Only higher plasma GFAP correlated with lower cognitive scores. Our observations suggest that plasma p-tau and plasma GFAP are both early AD markers reflecting different Aβ-related processes

PhosPiR: an automated phosphoproteomic pipeline in R

Large-scale phosphoproteome profiling using mass spectrometry (MS) provides functional insight that is crucial for disease biology and drug discovery. However, extracting biological understanding from these data is an arduous task requiring multiple analysis platforms that are not adapted for automated high-dimensional data analysis. Here, we introduce an integrated pipeline that combines several R packages to extract high-level biological understanding from large-scale phosphoproteomic data by seamless integration with existing databases and knowledge resources. In a single run, PhosPiR provides data clean-up, fast data overview, multiple statistical testing, differential expression analysis, phosphosite annotation and translation across species, multilevel enrichment analyses, proteome-wide kinase activity and substrate mapping and network hub analysis. Data output includes graphical formats such as heatmap, box-, volcano- and circos-plots. This resource is designed to assist proteome-wide data mining of pathophysiological mechanism without a need for programming knowledge.</p