Multidimensional Deprivation in Contemporary Switzerland Across Social Groups and Time

We have investigated the phenomenon of deprivation in contemporary Switzerland through the adoption of a multidimensional, dynamic approach. By applying Self Organizing Maps (SOM) to a set of 33 non-monetary indicators from the 2009 wave of the Swiss Household Panel (SHP), we identified 13 prototypical forms (or clusters) of well-being, financial vulnerability, psycho-physiological fragility and deprivation within a topological dimensional space. Then new data from the previous waves (2003 to 2008) were classified by the SOM model, making it possible to estimate the weight of the different clusters in time and reconstruct the dynamics of stability and mobility of individuals within the map. Looking at the transition probabilities between year t and year t+1, we observed that the paths of mobility which catalyze the largest number of observations are those connecting clusters that are adjacent on the topological space.

Orthogonal protecting groups in the synthesis of tryptophanyl-hexahydropyrroloindoles

The synthesis of various polycyclic systems containing a C3a-Ni bond between a hexahydropyrrolo[2,3-b]indole and an indole tryptophan is described here. A series of experiments were performed to determine the best combination of five orthogonal protecting groups and the best reaction conditions for formation of said bond, which is a common feature among many recently discovered marine natural products.

Nikkelin takaisinuutto karboksyylihappoon perustuvasta uuttoreagenssista

Työssä tutkittiin typpihapon soveltuvuutta nikkelin takaisinuuttoon. Tarkoituksena oli selvittää, millä typpihapon konsentraatioilla orgaaninen faasi, joka koostuu Versatic 10 uuttoreagenssista ja alifaattisesta laimentimesta, alkaa nitrautua tai hapettua ja mitkä ovat mahdolliset sivureaktiot. Lisäksi tutkittiin rikkihapon ja eräiden orgaanisten aineiden kontaminaation vaikutusta uuttoliuokseen. Kirjallisuusosassa kartoitetaan mahdollisten nitrautumisreaktioiden mekanismit, sekä kuvataan laimentimen, uuttoreagenssin ja mahdollisten reaktiotuotteiden ominaisuuksia, sekä niiden mahdollisessa muodostumisessa syntyviä riskejä. Orgaanisen faasin kestotesteissä tutkittavia muuttujia olivat typpi- ja rikkihapon konsentraatio, sekoitusaika, lämpötila, avoin tai suljettu astia sekä vieraiden aineiden kontaminaatio. Kontaminaatiota aiheuttavien orgaanisten materiaalien funktionaaliset ryhmät olivat hydroksi-, karbonyyli- ja amiiniryhmät, joiden lisäksi tutkittiin syklisen yhdisteen kontaminaatiota. Analyyseissä käytettiin FT-IR- spektroskopiaa, jolla tutkittiin reagenssin funktionaalisen ryhmän reaktioita ja uusien ryhmien muodostumista, sekä seurattiin selkeytyksessä erottumattomien typpiyhdisteiden määrää ja laatua orgaanisessa faasissa. Uuttofaasin koostumuksen muutosta seurattiin myös mittaamalla leimahduspisteen muutosta.

Fmoc-2-Mercaptobenzothiazole (MBT), for the Introduction of the Fmoc Moiety Free of Side-Reactions

A double side-reaction, consisting in the formation of Fmoc--Ala-OH and Fmoc--Ala-AA-OH, during the preparation of Fmoc protected amino acids (Fmoc-AA-OH) with Fmoc-OSu is discussed. Furthermore, the new Fmoc-2-MBT reagent is proposed for avoiding these side-reactions as well as the formation of the Fmoc-dipeptides (Fmoc-AA-AA-OH) and even tripeptides, which is another important side-reaction when chloroformates such as Fmoc-Cl is used for the protection of the -amino function of the amino acids.

Kaakkoissuomalaisten logistiikkayritysten toimintaedellytykset itäliikenteessä

Venäjän talousromahdus elokuussa 1998 vaikeutti suomalaisten logistiikkayritysten toimintaa, kun kauttakulkuliikenne ja suomalaisten yritysten vienti Venäjälle väheni huomattavasti. Tällöin syntyi uudenlainen kilpailutilanne, jossa ei enää riittänyt kuljetuksia kaikille. Suomalaiset logistiikkayritykset, etenkin kuljetusyritykset jäivät korkeamman kustannustason vuoksi kilpailussa tappiolle. Tämä on johtanut heikoimmassa asemassa olevien yritysten konkursseihin. Tutkimuksen tarkoituksena oli selvittää, miten Venäjän logistiikassa mukana olevat yritykset voivat pysyä mukana kilpailussa. Tutkimus perustuu alueen logistiikkayrityksille ja sidosryhmille tehtyyn kyselyyn ja haastatteluihin. Työn yhteydessä on perehdytty myös aiempiin tutkimuksiin ja selvityksiin. Tutkimuksen perusteella selviytymiskeinoja ovat yhteistyön lisääminen sekä kansainvälisiin että suomalaisiin logistiikkayrityksiin, venäläisten asiakkaiden saaminen ja uusien teknologioiden hyödyntäminen. Pienillä yrityksillä on kaksi mahdollisuutta, pyrkiä osaksi kokonaistoimitusketjua tai -verkostoa tai pyrkiä tarjoamaan erikoispalveluita asiakkaan tarpeiden mukaisesti.

Age and adverse drug reactions from psychopharmacological treatment: data from the AMSP drug surveillance programme in Switzerland.

QUESTION UNDER STUDY: The frequency of severe adverse drug reactions (ADRs) from psychotropic drugs was investigated in hospitalised psychiatric patients in relation to their age. Specifically, the incidence of ADRs in patients up to 60 years was compared to that of patients older than 60 years. METHODS: Prescription rates of psychotropic drugs and reports of severe ADRs were collected in psychiatric hospitals in Switzerland between 2001 and 2010. The data stem from the drug surveillance programme AMSP. RESULTS: A total of 699 patients exhibited severe ADRs: 517 out of 28,282 patients up to 60 years (1.8%); 182 out of 11,446 elderly patients (1.6%, ns). Logistic regression analyses showed a significantly negative relationship between the incidence of ADRs and patients' age in general and in particular for weight gain, extrapyramidal motor system (EPMS) symptoms, increased liver enzymes and galactorrhoea. A significantly negative relationship was observed for age and the dosages of olanzapine, quetiapine, risperidone, valproic acid and lamotrigine. When comparing age groups, frequency of ADRs was lower in general for antipsychotic drugs and anticonvulsants, in particular for valproic acid in the elderly. Weight gain was found to be lower in the elderly for antipsychotic drugs, in particular for olanzapine. For the group of mood-stabilising anticonvulsants (carbamazepine, lamotrigine and valproic acid) the elderly exhibited a lower incidence of reported allergic skin reactions. CONCLUSION: The results suggest that for psychiatric inpatients the incidence of common severe ADRs (e.g., weight gain or EPMS symptoms) arising from psychotropic medication decreases with the age of patients.

The efficiency of indicator groups for the conservation of amphibians in the Brazilian Atlantic Forest

The adequate selection of indicator groups of biodiversity is an important aspect of the systematic conservation planning. However, these assessments differ in the spatial scale, in the methods used and in the groups considered to accomplish this task, which generally produces contradictory results. The quantification of the spatial congruence between species richness and complementarity among different taxonomic groups is a fundamental step to identify potential indicator groups. Using a constructive approach, the main purposes of this study were to evaluate the performance and efficiency of eight potential indicator groups representing amphibian diversity in the Brazilian Atlantic Forest. Data on the geographic range of amphibian species that occur in the Brazilian Atlantic Forest was overlapped to the full geographic extent of the biome, which was divided into a regular equal-area grid. Optimization routines based on the concept of complementarily were applied to verify the performance of each indicator group selected in relation to the representativeness of the amphibians in the Brazilian Atlantic Forest as a whole, which were solved by the algorithm"simulated annealing", through the use of the software MARXAN. Some indicator groups were substantially more effective than others in regards to the representation of the taxonomic groups assessed, which was confirmed by the high significance of data (F = 312.76; p < 0.01). Leiuperidae was considered as the best indicator group among the families analyzed, as it showed a good performance, representing 71% of amphibian species in the Brazilian Atlantic Forest (i.e. 290 species), which may be associated with the diffuse geographic distribution of its species. This study promotes understanding of how the diversity standards of amphibians can be informative for systematic conservation planning on a regional scale.

Switching from tenofovir disoproxil fumarate to tenofovir alafenamide in antiretroviral regimens for virologically suppressed adults with HIV-1 infection: a randomised, active-controlled, multicentre, open-label, phase 3, non-inferiority study.

BACKGROUND: Antiretroviral regimens containing tenofovir disoproxil fumarate have been associated with renal toxicity and reduced bone mineral density. Tenofovir alafenamide is a novel tenofovir prodrug that reduces tenofovir plasma concentrations by 90%, thereby decreasing off-target side-effects. We aimed to assess whether efficacy, safety, and tolerability were non-inferior in patients switched to a regimen containing tenofovir alafenamide versus in those remaining on one containing tenofovir disoproxil fumarate. METHODS: In this randomised, actively controlled, multicentre, open-label, non-inferiority trial, we recruited HIV-1-infected adults from Gilead clinical studies at 168 sites in 19 countries. Patients were virologically suppressed (HIV-1 RNA <50 copies per mL) with an estimated glomerular filtration rate of 50 mL per min or greater, and were taking one of four tenofovir disoproxil fumarate-containing regimens for at least 96 weeks before enrolment. With use of a third-party computer-generated sequence, patients were randomly assigned (2:1) to receive a once-a-day single-tablet containing elvitegravir 150 mg, cobicistat 150 mg, emtricitabine 200 mg, and tenofovir alafenamide 10 mg (tenofovir alafenamide group) or to carry on taking one of four previous tenofovir disoproxil fumarate-containing regimens (tenofovir disoproxil fumarate group) for 96 weeks. Randomisation was stratified by previous treatment regimen in blocks of six. Patients and treating physicians were not masked to the assigned study regimen; outcome assessors were masked until database lock. The primary endpoint was the proportion of patients who received at least one dose of study drug who had undetectable viral load (HIV-1 RNA <50 copies per mL) at week 48. The non-inferiority margin was 12%. This study was registered with ClinicalTrials.gov, number NCT01815736. FINDINGS: Between April 12, 2013 and April 3, 2014, we enrolled 1443 patients. 959 patients were randomly assigned to the tenofovir alafenamide group and 477 to the tenofovir disoproxil fumarate group. Viral suppression at week 48 was noted in 932 (97%) patients assigned to the tenofovir alafenamide group and in 444 (93%) assigned to the tenofovir disoproxil fumarate group (adjusted difference 4·1%, 95% CI 1·6-6·7), with virological failure noted in ten and six patients, respectively. The number of adverse events was similar between the two groups, but study drug-related adverse events were more common in the tenofovir alafenamide group (204 patients [21%] vs 76 [16%]). Hip and spine bone mineral density and glomerular filtration were each significantly improved in patients in the tenofovir alafenamide group compared with those in the tenofovir disoproxil fumarate group. INTERPRETATION: Switching to a tenofovir alafenamide-containing regimen from one containing tenofovir disoproxil fumarate was non-inferior for maintenance of viral suppression and led to improved bone mineral density and renal function. Longer term follow-up is needed to better understand the clinical impact of these changes. FUNDING: Gilead Sciences.

Normal values for pancreatic stone protein in different age groups.

BACKGROUND: Pancreatic stone protein (PSP) has been identified as a promising sepsis marker in adults, children and neonates. However, data on population-based reference values are lacking. This study aimed to establish age-specific reference values for PSP. METHODS: PSP was determined using a specific ELISA. PSP serum concentrations were determined in 372 healthy subjects including 217 neonates, 94 infants and children up to 16 years, and 61 adults. The adjacent categories method was used to determine which age categories had significantly different PSP concentrations. RESULTS: PSP circulating levels were not gender-dependent and ranged from 1.0 to 99.4 ng/ml with a median of 9.2 ng/ml. PSP increased significantly between the age categories, from a median of 2.6 ng/ml in very preterm newborns, to 6.3 ng/ml in term newborns, to 16.1 ng/ml in older children (p < 0.001). PSP levels were higher on postnatal day three compared to levels measured immediately post delivery (p < 0.001). Paired umbilical artery and umbilical vein samples were strongly correlated (p < 0.001). Simultaneously obtained capillary heel-prick versus venous samples showed a good level of agreement for PSP (Rho 0.89, bias 19 %). CONCLUSIONS: This study provides age-specific normal values that may be used to define cut-offs for future trials on PSP. We demonstrate an age-dependent increase of PSP from birth to childhood.

Challenges in the Discovery of Indoleamine 2,3-Dioxygenase 1 (IDO1) Inhibitors.

Since the discovery of indoleamine 2,3-dioxygenase 1 (IDO1) as an attractive target for anticancer therapy in 2003, the search for inhibitors has been intensely pursued both in academia and in pharmaceutical companies. Many novel IDO1 inhibitor scaffolds have been described, and a few potent compounds have entered clinical trials. However, a significant number of the reported compounds contain problematic functional groups, suggesting that enzyme inhibition could be the result of undesirable side reactions instead of selective binding to IDO1. Here, we describe issues in the employed experimental protocols, review and classify reported IDO1 inhibitors, and suggest different approaches for confirming viable inhibitor scaffolds.

Radiothérapie « flash » à très haut débit de dose : un moyen d'augmenter l'indice thérapeutique par minimisation des dommages aux tissus sains [Ultrahigh dose-rate, "flash" irradiation minimizes the side-effects of radiotherapy].

PURPOSE: Pencil beam scanning and filter free techniques may involve dose-rates considerably higher than those used in conventional external-beam radiotherapy. Our purpose was to investigate normal tissue and tumour responses in vivo to short pulses of radiation. MATERIAL AND METHODS: C57BL/6J mice were exposed to bilateral thorax irradiation using pulsed (at least 40Gy/s, flash) or conventional dose-rate irradiation (0.03Gy/s or less) in single dose. Immunohistochemical and histological methods were used to compare early radio-induced apoptosis and the development of lung fibrosis in the two situations. The response of two human (HBCx-12A, HEp-2) tumour xenografts in nude mice and one syngeneic, orthotopic lung carcinoma in C57BL/6J mice (TC-1 Luc+), was monitored in both radiation modes. RESULTS: A 17Gy conventional irradiation induced pulmonary fibrosis and activation of the TGF-beta cascade in 100% of the animals 24-36 weeks post-treatment, as expected, whereas no animal developed complications below 23Gy flash irradiation, and a 30Gy flash irradiation was required to induce the same extent of fibrosis as 17Gy conventional irradiation. Cutaneous lesions were also reduced in severity. Flash irradiation protected vascular and bronchial smooth muscle cells as well as epithelial cells of bronchi against acute apoptosis as shown by analysis of caspase-3 activation and TUNEL staining. In contrast, the antitumour effectiveness of flash irradiation was maintained and not different from that of conventional irradiation. CONCLUSION: Flash irradiation shifted by a large factor the threshold dose required to initiate lung fibrosis without loss of the antitumour efficiency, suggesting that the method might be used to advantage to minimize the complications of radiotherapy.