Molecular Epidemiology and Emergence of Rift Valley Fever

Rift Valley fever (RVF) is a mosquito-borne viral disease which manifested itself during recent epidemics and revealed its significant potential of emergence. Studies on molecular epidemiology undertaken to better understand the factors leading to RVF emergence, have confirmed the mode of circulation of the virus and highlithted probable risks and obstacles for prevention and control. As for several other viral agents, molecular epidemiology is becoming a useful tool in the study of the emergence of RVF as a serious infectious disease.

Group 4: Career development for diverse and underserved populations

Globalization and diverse populations due to migration imply that counselors are expected to deliver career services to populations from a large array of cultural settings. Moreover, individuals belonging to minority or non-dominant groups may be underserved or misserved, thus decreasing their chances of finding employment opportunities through career counseling. To develop specific interventions minority or non-dominant groups, it seems important to understand their strength and weaknesses. These strengths and weaknesses will be presented in terms of risk and resilience factors, such as low future orientation and social support respectively. In the last two decades, several authors have made contributions to adapt and improve career services in order to best meet these minority groups' needs. A review of this literature identified thirteen keys to effective practice. For example, one key is to take responsibility for one's own biases and prejudices. Nonetheless, some underserved groups remain difficult to identify. Comparing some basic national demographic data with data from our counseling centers may be helpful in this context in identifying specific groups and assessing needs. One solution, in order to promote social justice across (all) cultural groups, is to encourage multiculturalism in both career counseling and society as a whole. A more inclusive society would allow each person in a minority or non-dominant group to contribute more effectively to the development and growth of this society.

Induction of CD8 T-cell responses restricted to multiple HLA class I alleles in a cancer patient by immunization with a 20-mer NY-ESO-1f (NY-ESO-1 91-110) peptide.

Immunogenicity of a long 20-mer NY-ESO-1f peptide vaccine was evaluated in a lung cancer patient TK-f01, immunized with the peptide with Picibanil OK-432 and Montanide ISA-51. We showed that internalization of the peptide was necessary to present CD8 T-cell epitopes on APC, contrasting with the direct presentation of the short epitope. CD8 T-cell responses restricted to all five HLA class I alleles were induced in the patient after the peptide vaccination. Clonal analysis showed that B*35:01 and B*52:01-restricted CD8 T-cell responses were the two dominant responses. The minimal epitopes recognized by A*24:02, B*35:01, B*52:01 and C*12:02-restricted CD8 T-cell clones were defined and peptide/HLA tetramers were produced. NY-ESO-1 91-101 on A*24:02, NY-ESO-1 92-102 on B*35:01, NY-ESO-1 96-104 on B*52:01 and NY-ESO-1 96-104 on C*12:02 were new epitopes first defined in this study. Identification of the A*24:02 epitope is highly relevant for studying the Japanese population because of its high expression frequency (60%). High affinity CD8 T-cells recognizing tumor cells naturally expressing the epitopes and matched HLA were induced at a significant level. The findings suggest the usefulness of a long 20-mer NY-ESO-1f peptide harboring multiple CD8 T-cell epitopes as an NY-ESO-1 vaccine. Characterization of CD8 T-cell responses in immunomonitoring using peptide/HLA tetramers revealed that multiple CD8 T-cell responses comprised the dominant response.

Induction of CD8 T-cell responses restricted to multiple HLA class I alleles in a cancer patient by immunization with a 20-mer NY-ESO-1f (NY-ESO-1 91-110) peptide.

Immunogenicity of a long 20-mer NY-ESO-1f peptide vaccine was evaluated in a lung cancer patient TK-f01, immunized with the peptide with Picibanil OK-432 and Montanide ISA-51. We showed that internalization of the peptide was necessary to present CD8 T-cell epitopes on APC, contrasting with the direct presentation of the short epitope. CD8 T-cell responses restricted to all five HLA class I alleles were induced in the patient after the peptide vaccination. Clonal analysis showed that B*35:01 and B*52:01-restricted CD8 T-cell responses were the two dominant responses. The minimal epitopes recognized by A*24:02, B*35:01, B*52:01 and C*12:02-restricted CD8 T-cell clones were defined and peptide/HLA tetramers were produced. NY-ESO-1 91-101 on A*24:02, NY-ESO-1 92-102 on B*35:01, NY-ESO-1 96-104 on B*52:01 and NY-ESO-1 96-104 on C*12:02 were new epitopes first defined in this study. Identification of the A*24:02 epitope is highly relevant for studying the Japanese population because of its high expression frequency (60%). High affinity CD8 T-cells recognizing tumor cells naturally expressing the epitopes and matched HLA were induced at a significant level. The findings suggest the usefulness of a long 20-mer NY-ESO-1f peptide harboring multiple CD8 T-cell epitopes as an NY-ESO-1 vaccine. Characterization of CD8 T-cell responses in immunomonitoring using peptide/HLA tetramers revealed that multiple CD8 T-cell responses comprised the dominant response.

Continent wide response of mountain vegetation to climate change

Climate impact studies have indicated ecological fingerprints of recent global warming across a wide range of habitats. Whereas these studies have shown responses from various local case studies, a coherent large-scale account on temperature-driven changes of biotic communities has been lacking. Here we use 867 vegetation samples above the treeline from 60 summit sites in all major European mountain systems to show that ongoing climate change gradually transforms mountain plant communities. We provide evidence that the more cold-adapted species decline and the more warm-adapted species increase, a process described here as thermophilisation. At the scale of individual mountains this general trend may not be apparent, but at the¦larger, continental scale we observed a significantly higher abundance of thermophilic species in 2008, compared with 2001. Thermophilisation of mountain plant communities mirrors the degree of recent warming and is more pronounced in areas where the temperature increase has been higher. In view of the projected climate change the observed transformation suggests a progressive decline of cold mountain habitats and their biota.

The effect of dose on the antimalarial efficacy of artemether-lumefantrine: a systematic review and pooled analysis of individual patient data.

BACKGROUND: Artemether-lumefantrine is the most widely used artemisinin-based combination therapy for malaria, although treatment failures occur in some regions. We investigated the effect of dosing strategy on efficacy in a pooled analysis from trials done in a wide range of malaria-endemic settings. METHODS: We searched PubMed for clinical trials that enrolled and treated patients with artemether-lumefantrine and were published from 1960 to December, 2012. We merged individual patient data from these trials by use of standardised methods. The primary endpoint was the PCR-adjusted risk of Plasmodium falciparum recrudescence by day 28. Secondary endpoints consisted of the PCR-adjusted risk of P falciparum recurrence by day 42, PCR-unadjusted risk of P falciparum recurrence by day 42, early parasite clearance, and gametocyte carriage. Risk factors for PCR-adjusted recrudescence were identified using Cox's regression model with frailty shared across the study sites. FINDINGS: We included 61 studies done between January, 1998, and December, 2012, and included 14 327 patients in our analyses. The PCR-adjusted therapeutic efficacy was 97·6% (95% CI 97·4-97·9) at day 28 and 96·0% (95·6-96·5) at day 42. After controlling for age and parasitaemia, patients prescribed a higher dose of artemether had a lower risk of having parasitaemia on day 1 (adjusted odds ratio [OR] 0·92, 95% CI 0·86-0·99 for every 1 mg/kg increase in daily artemether dose; p=0·024), but not on day 2 (p=0·69) or day 3 (0·087). In Asia, children weighing 10-15 kg who received a total lumefantrine dose less than 60 mg/kg had the lowest PCR-adjusted efficacy (91·7%, 95% CI 86·5-96·9). In Africa, the risk of treatment failure was greatest in malnourished children aged 1-3 years (PCR-adjusted efficacy 94·3%, 95% CI 92·3-96·3). A higher artemether dose was associated with a lower gametocyte presence within 14 days of treatment (adjusted OR 0·92, 95% CI 0·85-0·99; p=0·037 for every 1 mg/kg increase in total artemether dose). INTERPRETATION: The recommended dose of artemether-lumefantrine provides reliable efficacy in most patients with uncomplicated malaria. However, therapeutic efficacy was lowest in young children from Asia and young underweight children from Africa; a higher dose regimen should be assessed in these groups. FUNDING: Bill & Melinda Gates Foundation.

Proteinuria Increases Plasma Phosphate by Altering Its Tubular Handling.

Proteinuria and hyperphosphatemia are cardiovascular risk factors independent of GFR. We hypothesized that proteinuria induces relative phosphate retention via increased proximal tubule phosphate reabsorption. To test the clinical relevance of this hypothesis, we studied phosphate handling in nephrotic children and patients with CKD. Plasma fibroblast growth factor 23 (FGF-23) concentration, plasma phosphate concentration, and tubular reabsorption of phosphate increased during the proteinuric phase compared with the remission phase in nephrotic children. Cross-sectional analysis of a cohort of 1738 patients with CKD showed that albuminuria≥300 mg/24 hours is predictive of higher phosphate levels, independent of GFR and other confounding factors. Albuminuric patients also displayed higher plasma FGF-23 and parathyroid hormone levels. To understand the molecular mechanisms underlying these observations, we induced glomerular proteinuria in two animal models. Rats with puromycin-aminonucleoside-induced nephrotic proteinuria displayed higher renal protein expression of the sodium-phosphate co-transporter NaPi-IIa, lower renal Klotho protein expression, and decreased phosphorylation of FGF receptor substrate 2α, a major FGF-23 receptor substrate. These findings were confirmed in transgenic mice that develop nephrotic-range proteinuria resulting from podocyte depletion. In vitro, albumin did not directly alter phosphate uptake in cultured proximal tubule OK cells. In conclusion, we show that proteinuria increases plasma phosphate concentration independent of GFR. This effect relies on increased proximal tubule NaPi-IIa expression secondary to decreased FGF-23 biologic activity. Proteinuria induces elevation of both plasma phosphate and FGF-23 concentrations, potentially contributing to cardiovascular disease.

Cartographie et analyse des données disponibles pour estimer le nombre de préservatifs écoulés sur le marché suisse en une année

L'Office fédéral de la santé publique (OFSP) a mandaté la Fédération romande des consommateurs (FRC) et l'Institut universitaire de médecine sociale et préventive (IUMSP) pour réaliser une cartographie du marché des préservatifs et analyser les données disponibles pour estimer le nombre de préservatifs écoulés sur le marché suisse en une année. Les données disponibles identifiées sont les suivantes : 1. Données Verein : l'Association pour le label de qualité des préservatifs possède des données sur le nombre de préservatifs testés chaque année pour l'obtention du label OK. Ces données constituent une estimation du nombre de préservatifs ayant suivi la procédure de certification du label OK. Ces dernières années, des entreprises auraient renoncé à leur collaboration avec l'association pour le label de qualité, ce qui réduit la fiabilité de cette méthode pour suivre l'évolution du marché des préservatifs en Suisse. 2. Données douanes : l'Administration fédérale des douanes établit une statistique du commerce extérieur et met à disposition une base de données qui donne accès aux données statistiques d'importation et d'exportation de préservatifs. Etant donné que cette statistique se base sur les données indiquées par les importateurs et les exportateurs, des erreurs de déclaration peuvent être commises. 3. Données IUMSP : entre 1986 et 2011, l'IUMSP a reçu des producteurs/importateurs des données de mises sur le marché de préservatifs. Ces données, fiables car provenant directement des producteurs/importateurs, ne sont malheureusement plus complètes depuis 2012, en raison d'une difficulté croissante à obtenir de telles informations. 4. Données Nielsen et IMS Health : Nielsen et IMS HEalth sont des entreprises privées qui recensent les données de vente des préservatifs en Suisse réalisées dans les commerces de détail, ainsi que dans les drogueries et pharmacies. Ces données constituent des données de vente réelles obtenues grâce à l'enregistrement des mouvements de la marchandise lors du passage en caisse dans les magasins. La couverture des points de vente est élevée (près de 80% pour les données Nielsen) et stable dans le temps.

Guanylin peptides: cyclic GMP signaling mechanisms

Guanylate cyclases (GC) serve in two different signaling pathways involving cytosolic and membrane enzymes. Membrane GCs are receptors for guanylin and atriopeptin peptides, two families of cGMP-regulating peptides. Three subclasses of guanylin peptides contain one intramolecular disulfide (lymphoguanylin), two disulfides (guanylin and uroguanylin) and three disulfides (E. coli stable toxin, ST). The peptides activate membrane receptor-GCs and regulate intestinal Cl- and HCO3- secretion via cGMP in target enterocytes. Uroguanylin and ST also elicit diuretic and natriuretic responses in the kidney. GC-C is an intestinal receptor-GC for guanylin and uroguanylin, but GC-C may not be involved in renal cGMP pathways. A novel receptor-GC expressed in the opossum kidney (OK-GC) has been identified by molecular cloning. OK-GC cDNAs encode receptor-GCs in renal tubules that are activated by guanylins. Lymphoguanylin is highly expressed in the kidney and heart where it may influence cGMP pathways. Guanylin and uroguanylin are highly expressed in intestinal mucosa to regulate intestinal salt and water transport via paracrine actions on GC-C. Uroguanylin and guanylin are also secreted from intestinal mucosa into plasma where uroguanylin serves as an intestinal natriuretic hormone to influence body Na+ homeostasis by endocrine mechanisms. Thus, guanylin peptides control salt and water transport in the kidney and intestine mediated by cGMP via membrane receptors with intrinsic guanylate cyclase activity.

Jatkokäsittelylupa riksoasiassa

Tutkielman kohteena on oikeudenkäymiskaaren (OK) 25 a luvussa (24.6.2010/650) säännelty jatkokäsittelylupamenettely ja luvan myöntämisen perusteet rikosasioissa. Erityisesti keskitytään oikeudenkäymiskaaren sanotun luvun 11 §:ään ja sitä koskevaan korkeimman oikeuden runsaaseen ratkaisukäytäntöön. Tutkimuskysymyksiä ovat muun muassa: milloin lupa tarvitaan ja milloin se tulee myöntää, niin lainsäädännön nojalla, kuin erityisesti sitä täsmentäneen oikeuskäytännön myötä. Tutkielma pyrkii näin hahmottamaan luvan myöntämiselle muotoutuneita perusteita ja tuomioistuimen harkintamarginaalia. Tutkielman pääpaino on yksittäisten luvanmyöntämisperusteiden tutkimisessa, mutta samalla on mahdollista tarkastella sitä, kuinka aiheena olevan lainsäädännön yleiset tavoitteet ilmenevät jatkokäsittelylupaa koskevassa tähänastisessa oikeuskäytännössä. Tutkimus on pääosin luonteeltaan perinteisen normatiivinen ja lainopillinen eli oikeusdogmaattinen. Se pyrkii voimassa olevan oikeuden tulkintaan ja systematisointiin. Paikoittain aihetta käsitellään myös oikeuspolitiikan keinoin. Erityisesti aihetta pohjustava luku pyrkii hahmottelemaan aiheen taustalla vaikuttavia yhteiskunnallista tavoitteenasettelua ja suunnittelua oikeudellisesta näkökulmasta Tutkielman lähteenä on käytetty oikeusdogmaattisille tutkimuksille tyypillistä aineistoa, kuten lakitekstiä, lainvalmisteluasiakirjoja ja oikeuskirjallisuutta. Lisäksi tutkielmassa on hyödynnetty oikeustapausaineistoa normitulkinnan tukena ja oikeutta luovana elementtinä. Jatkokäsittelyluvan myöntämiseen liittyvä lupakynnys on jäsentynyt ja täsmentynyt korkeimman oikeuden ratkaisukäytännössä. Jatkokäsittelylupamenettelyllä on olennainen merkitys asianosaisten oikeusturvan kannalta. Asianosaisten oikeusturvan toteutumisen kannalta lupajärjestelmän soveltamisalaa tärkeämmässä asemassa on se, miten yksittäisiä jatkokäsittelyluvan myöntämisperusteita sovelletaan.

Tuomioistuinsovittelu vaihtoehtoisena riidanratkaisutapana

Tutkielmassa käsitellään tuomioistuinsovittelua vaihtoehtoisena riidanratkaisutapana. Menettely otettiin käyttöön vuonna 2006, mutta sitä koskeva lainsäädäntö uudistettiin vuonna 2011. Tuomioistuinsovittelusta säädetään laissa riita-asioiden sovittelusta ja sovinnon vahvistamisesta yleisissä tuomioistuimissa (394/2011). Menettelyssä osapuolet etsivät sovinnollista ratkaisua riitaansa sovittelijana toimivan tuomarin johdolla. Tuomioistuinsovittelun säätämisen tavoitteena oli luoda asioiden sopimiselle paremmat edellytykset tuomioistuimissa ja vaihtoehtoinen menettely oikeudenkäynnille. Aihe on ajankohtainen, sillä sovinnollisuudesta tuomioistuimissa on ollut viime vuosina runsaasti keskustelua. Tuomioistuinliitännäinen sovinnon edistäminen riita-asioissa on kuitenkin ollut mahdollista pitkään ennen tuomioistuinsovittelumenettelyn säätämistä. Tuomioistuimilla on velvollisuus riita-asian valmistelussa selvittää sovinnon edellytykset (OK 5:19.4 §) ja dispositiivisissa asioissa tuomioistuimen on pyrittävä saamaan asianosaiset sopimaan asia (OK 5:26 §). Tutkielmassa tarkastellaan sitä, onko tuomioistuinsovittelu tosiasiassa tarpeellinen keino sovinnon edistämiseksi riita-asioissa, kun otetaan huomioon edellä mainitut säännökset. Samoin käsitellään tuomioistuinsovittelun suhdetta siviiliprosessissa tapahtuvaan sovinnon edistämiseen. Tutkielmassa voimassa olevaa lainsäädäntöä arvioimalla selvitetään, onko tuomioistuinsovittelu menetelmänä ja siinä noudatettavat menettelytavat onnistuneita vai voidaanko niitä kritisoida. Keskeisiä lähteitä ovat tuomioistuinsovittelua koskevat lainvalmisteluasiakirjat, erityisesti HE 114/2004 vp. Lain esitöiden lisäksi tutkielmassa hyödynnetään laajasti aiempaa oikeuskirjallisuutta aiheesta. Vaikka tuomioistuinsovittelulle on olemassa oma vahva kannattajakuntansa, sitä käytetään edelleen hyvin vähän. Tämän voidaan katsoa johtuvan muun muassa siitä, että ”riidanratkaisumarkkinoilla” on jo ennestään kattavasti erilaisia yksityisten toimijoiden tarjoamia sovittelupalveluja. Myös perinteisessä siviiliprosessissa toteutettava sovinnon edistäminen on toiminut hyvin, sillä tilastojen mukaan iso osa riita-asioista päättyy sovintoon. Näin ollen voidaan kyseenalaistaa erillisen tuomioistuinsovittelun tarpeellisuus. Vaikka se katsottaisiinkin tarpeelliseksi, tuomioistuinliitännäisen sovinnon edistämisen menettelytapojen yhtenäistämiseksi asiasta olisi perusteltua olla säännökset oikeudenkäymiskaaressa.