Trustworthiness and metrics in visualizing similarity of gene expression

BACKGROUND: Conventionally, the first step in analyzing the large and high-dimensional data sets measured by microarrays is visual exploration. Dendrograms of hierarchical clustering, self-organizing maps (SOMs), and multidimensional scaling have been used to visualize similarity relationships of data samples. We address two central properties of the methods: (i) Are the visualizations trustworthy, i.e., if two samples are visualized to be similar, are they really similar? (ii) The metric. The measure of similarity determines the result; we propose using a new learning metrics principle to derive a metric from interrelationships among data sets. RESULTS: The trustworthiness of hierarchical clustering, multidimensional scaling, and the self-organizing map were compared in visualizing similarity relationships among gene expression profiles. The self-organizing map was the best except that hierarchical clustering was the most trustworthy for the most similar profiles. Trustworthiness can be further increased by treating separately those genes for which the visualization is least trustworthy. We then proceed to improve the metric. The distance measure between the expression profiles is adjusted to measure differences relevant to functional classes of the genes. The genes for which the new metric is the most different from the usual correlation metric are listed and visualized with one of the visualization methods, the self-organizing map, computed in the new metric. CONCLUSIONS: The conjecture from the methodological results is that the self-organizing map can be recommended to complement the usual hierarchical clustering for visualizing and exploring gene expression data. Discarding the least trustworthy samples and improving the metric still improves it

National Early Warning Score 2 (NEWS2) and 3-Level Triage Scale as Risk Predictors in Frail Older Adults in the Emergency Department

Background The aim of the emergency department (ED) triage is to recognize critically ill patients and to allocate resources. No strong evidence for accuracy of the current triage instruments, especially for the older adults, exists. We evaluated the National Early Warning Score 2 (NEWS2) and a 3-level triage assessment as risk predictors for frail older adults visiting the ED. Methods This prospective, observational study was performed in a Finnish ED. The data were collected in a six-month period and included were >= 75-year-old residents with Clinical Frailty Scale score of at least four. We analyzed the predictive values of NEWS2 and the three-level triage scale for 30-day mortality, hospital admission, high dependency unit (HDU) and intensive care unit (ICU) admissions, a count of 72-h and 30-day revisits, and ED length-of-stay (LOS). Results A total of 1711 ED visits were included. Median for age, CFS, LOS and NEWS2 were 85 years, 6 points, 6.2 h and 1 point, respectively. 30-day mortality was 96/1711. At triage, 69, 356 and 1278 of patients were assessed as red, yellow and green, respectively. There were 1103 admissions, of them 31 to an HDU facility, none to ICU. With NEWS2 and triage score, AUCs for 30-day mortality prediction were 0.70 (0.64-0.76) and 0.62 (0.56-0.68); for hospital admission prediction 0.62 (0.60-0.65) and 0.55 (0.52-0.56), and for HDU admission 0.72 (0.61-0.83) and 0.80 (0.70-0.90), respectively. The NEWS2 divided into risk groups of low, medium and high did not predict the ED LOS (p = 0.095). There was a difference in ED LOS between the red/yellow and as red/green patient groups (p <0.001) but not between the yellow/green groups (p = 0.59). There were 48 and 351 revisits within 72 h and 30 days, respectively. With NEWS2 AUCs for 72-h and 30-day revisit prediction were 0.48 (95% CI 0.40-0.56) and 0.47 (0.44-0.51), respectively; with triage score 0.48 (0.40-0.56) and 0.49 (0.46-0.52), respectively. Conclusions The NEWS2 and a local 3-level triage scale are statistically significant, but poor in accuracy, in predicting 30-day mortality, and HDU admission but not ED LOS or revisit rates for frail older adults. NEWS2 also seems to predict hospital admission.Peer reviewe

Sääntelyyn perustuvat rahapelihaittojen ehkäisytoimet ja niiden soveltuvuus Suomen rahapelijärjestelmään : Tutkimustietoon ja asiantuntija-arvioihin perustuva selvitys 1.6.2017

Sosiaali- ja terveysministeriö antoi 16.2.2017 Terveyden ja hyvinvoinnin laitoksen (THL) rahapeli- ja päihdeasiantuntijoista muodostetulle työryhmälle toimeksiannon selvittää tutkimusnäytön valossa vaikuttavimpia rahapelihaittojen ehkäisytoimia, sekä niiden soveltuvuutta Suomeen. Työryhmä esittää tutkimusnäytön ja asiantuntijatiedon pohjalta kuutta vaikuttavaksi katsomaansa sääntelytoimenpidettä rahapelihaittojen ehkäisemiseksi Suomessa. Esitettävät toimenpiteet ovat: rahapelejä tarjoavien toimipisteiden maantieteellisen keskittymisen ja sijaintipaikkojen rajoittaminen, pelipisteiden määrän rajoittaminen (erityisesti rahapeliautomaattien osalta), pelaamisen rajoittaminen anniskelupaikoissa, pakollinen pelaajan tunnistautuminen, pakolliset pelaajan itse asettamat rajat pelikulutukselle, sekä pelaajan itselleen hakema pelikielto. Työryhmä pitää vaikuttavuuden kannalta tärkeänä toimenpiteiden huolellista toimeenpanoa ja vaikutusten arviointia

Sääntelyyn perustuvat rahapelihaittojen ehkäisytoimet ja niiden soveltuvuus Suomen rahapelijärjestelmään : Tutkimustietoon ja asiantuntija-arvioihin perustuva selvitys 1.6.2017

Sosiaali- ja terveysministeriö antoi 16.2.2017 Terveyden ja hyvinvoinnin laitoksen (THL) rahapeli- ja päihdeasiantuntijoista muodostetulle työryhmälle toimeksiannon selvittää tutkimusnäytön valossa vaikuttavimpia rahapelihaittojen ehkäisytoimia, sekä niiden soveltuvuutta Suomeen. Työryhmä esittää tutkimusnäytön ja asiantuntijatiedon pohjalta kuutta vaikuttavaksi katsomaansa sääntelytoimenpidettä rahapelihaittojen ehkäisemiseksi Suomessa. Esitettävät toimenpiteet ovat: rahapelejä tarjoavien toimipisteiden maantieteellisen keskittymisen ja sijaintipaikkojen rajoittaminen, pelipisteiden määrän rajoittaminen (erityisesti rahapeliautomaattien osalta), pelaamisen rajoittaminen anniskelupaikoissa, pakollinen pelaajan tunnistautuminen, pakolliset pelaajan itse asettamat rajat pelikulutukselle, sekä pelaajan itselleen hakema pelikielto. Työryhmä pitää vaikuttavuuden kannalta tärkeänä toimenpiteiden huolellista toimeenpanoa ja vaikutusten arviointia

Treating gambling disorder with as needed administration of intranasal naloxone: A pilot study to evaluate acceptability, feasibility and outcomes

Background and aim There is growing interest in the use of medication-assisted treatments for gambling disorder (GD). Opioid receptor antagonists are hypothesised to blunt the craving associated with gambling. This study was designed to assess the feasibility of using an intranasal naloxone spray to treat GD.Design An 8-week, open-label, uncontrolled pilot study.Setting A single study site in the capital region of Finland.Subjects Twenty problem gamblers (nine men) were randomised into two groups. Group A (n=10) took one dose into one nostril (2 mg naloxone), as needed, with a maximum of 4 doses/day (max. 8 mg/day). Group B (n=10) took one dose into each nostril (4 mg naloxone) as needed, with a maximum of 4 doses/day (max. 16 mg/day).Intervention Naloxone hydrochloride nasal spray.Measures Acceptability and feasibility of the intervention were assessed. Use of study medication, adverse events, gambling frequency and gambling expenditure were recorded in a mobile diary. Problem gambling: South Oaks Gambling Screen (SOGS), depressive symptoms: Beck Depression Inventory (BDI) and alcohol use: Alcohol Use Disorders Identification Test were recorded.Results Study completion rate was 90%. Acceptability and feasibility scores were high. Group B used intranasal naloxone more frequently than group A, and consequently used more naloxone. No serious adverse events were reported. The postintervention SOGS scores were lower (median=4 (IQR=3.75) versus preintervention scores (median=12 (IQR=4.75)). Depressive symptoms were reduced during the trial (preintervention BDI median=9, IQR=9 vs postintervention BDI median=6, IQR=6).Conclusions The acceptability and feasibility of using intranasal naloxone were high, and no serious adverse events were reported. Preliminary results suggest mixed results in terms of gambling behaviour (ie, reduced frequency but not expenditure) and decreased depressive symptoms.</div

Sääntelyyn perustuvat rahapelihaittojen ehkäisytoimet ja niiden soveltuvuus Suomen rahapelijärjestelmään

Sosiaali- ja terveysministeriö antoi 16.2.2017 Terveyden ja hyvinvoinnin laitoksen (THL) rahapeli- ja päihdeasiantuntijoista muodostetulle työryhmälle toimeksiannon selvittää tutkimusnäytön valossa vaikuttavimpia rahapelihaittojen ehkäisytoimia, sekä niiden soveltuvuutta Suomeen. Työryhmä esittää tutkimusnäytön ja asiantuntijatiedon pohjalta kuutta vaikuttavaksi katsomaansa sääntelytoimenpidettä rahapelihaittojen ehkäisemiseksi Suomessa. Esitettävät toimenpiteet ovat: rahapelejä tarjoavien toimipisteiden maantieteellisen keskittymisen ja sijaintipaikkojen rajoittaminen, pelipisteiden määrän rajoittaminen (erityisesti rahapeliautomaattien osalta), pelaamisen rajoittaminen anniskelupaikoissa, pakollinen pelaajan tunnistautuminen, pakolliset pelaajan itse asettamat rajat pelikulutukselle, sekä pelaajan itselleen hakema pelikielto. Työryhmä pitää vaikuttavuuden kannalta tärkeänä toimenpiteiden huolellista toimeenpanoa ja vaikutusten arviointia

Molecular detection and phylogenetic analysis of Borrelia miyamotoi strains from ticks collected in the capital region of Finland

Borrelia miyamotoi is an emerging pathogen that shares high similarity with relapsing fever Borrelia, but has an atypical clinical presentation. Within the framework of tick-borne disease surveillance in Finland, human serum samples suspected for tick-borne encephalitis (n=974) and questing ticks (n=739) were collected from the capital region in Finland to determine the prevalence of B. miyamotoi. All tested human samples were negative and 5 (0.68 %) Ixodes ricinus ticks were positive for B. miyamotoi. Partial sequencing of the flagellin (flaB) gene of 3 positive samples and 27 B. miyamotoi-positive tick samples obtained from previous studies across Finland were amplified, sequenced, and included in the phylogenetic analysis.The phylogenetic tree revealed that most B. miyamotoi strains isolated from ticks in Finland share high similarity with other European strains, including strains related to human infection. Possible disease transmission may occur during exposure to tick bites. A single strain collected from an I. persulcatus tick in Pajujärvi grouped with an outlier of B. miyamotoi strains isolated from Russia and Far East Asian countries. Further studies should investigate the pathogen’s role in human infection in Finland.Another important finding is the occurrence of I. persulcatus ticks (8%) collected by crowdsourcing from the coastal southern part of Finland. This suggests a regular introduction and a possible wide expansion of this tick species in the country. This could be associated with transmission of new pathogens.</p

Recent establishment of tick-borne encephalitis foci with distinct viral lineages in the Helsinki area, Finland

Number of tick-borne encephalitis (TBE) cases has increased and new foci have emerged in Finland during the last decade. We evaluated risk for locally acquired TBE in the capital region inhabited by 1.2 million people. We screened ticks and small mammals from probable places of TBE virus (TBEV) transmission and places without reported circulation. The TBEV positive samples were sequenced and subjected to phylogenetic analysis. Within the study period 2007-2017, there was a clear increase of both all TBE cases and locally acquired cases in the Helsinki area. The surveillance of ticks and small mammals for TBEV confirmed four distinct TBEV foci in the Helsinki area. All detected TBEV strains were of the European subtype. TBEV genome sequences indicated that distinct TBEV lineages circulate in each focus. Molecular clock analysis suggested that the virus lineages were introduced to these foci decades ago. In conclusion, TBE has emerged in the mainland of Helsinki area during the last decade, with at least four distinct virus lineages independently introduced into the region previously. Although the overall annual TBE incidence is below the threshold for recommending general vaccinations, the situation requires further surveillance to detect and prevent possible further emergence of local TBE clusters.Peer reviewe