The Effect of Switching Ranibizumab to Aflibercept in Refractory Cases of Macular Edema Secondary to Ischemic Central Vein Occlusion.

Background: Macular edema resulting from central retinal vein occlusion is effectively treated with anti-vascular endothelial growth factor injections. However, some patients need monthly retreatment and still show frequent recurrences. The purpose of this study was to evaluate the visual and anatomic outcomes of refractory macular edema resulting from ischemic central retinal vein occlusion in patients switched from ranibizumab to aflibercept intravitreal injections. Patients and Methods: We describe a retrospective series of patients followed in the Medical Retina Unit of the Jules Gonin Eye Hospital for macular edema due to ischemic central retinal vein occlusion, refractory to monthly retreatment with ranibizumab, and changed to aflibercept. Refractory macular edema was defined as persistence of any fluid at each visit one month after last injection during at least 6 months. All patients had to have undergone pan-retinal laser scan. Results: Six patients were identified, one of whom had a very short-term follow-up (excluded from statistics). Mean age was 57 ± 12 years. The mean changes in visual acuity and central macular thickness from baseline to switch were + 20.6 ± 20.3 ETDRS letters and - 316.4 ± 276.6 µm, respectively. The additional changes from before to after the switch were + 9.2 ± 9.5 ETDRS letters and - 248.0 ± 248.7 µm, respectively. The injection intervals could often be lengthened after the switch. Conclusions: Intravitreal aflibercept seems to be a promising alternative treatment for macular edema refractory to ranibizumab in ischemic central retinal vein occlusion.

Prevalence and diversity of Chlamydiales in Swiss ruminant farms.

Chlamydia and Chlamydia-related bacteria are known to infect various organisms and may cause a wide range of diseases, especially in ruminants. To gain insight into the prevalence of these bacteria in the ruminant environment, we applied a pan-Chlamydiales PCR followed by sequencing to 72 ruminant environmental samples from water, feed bunks and floors. Chlamydiales from four family-level lineages were detected indicating a high biodiversity of Chlamydiales in ruminant farms. Parachlamydiaceae were detected in all three types of environmental samples and was the most abundant family-level taxon (60%). In contrast, only one bacterium from each of the following family-level lineages was identified: Chlamydiaceae, Criblamydiaceae and Simkaniaceae. The observed high prevalence of Parachlamydiaceae in water samples may suggest water as the main source of contamination for ruminants as well as their environment due to spoilage. The absence of reported infections in the investigated ruminant farms might indicate that either detected Chlamydiales are of reduced pathogenicity or infective doses have not been reached.

Aportació al coneixement de l"herbari Trèmols de l"Institut Botànic de Barcelona.

The herbarium BC-Trèmols was created during the second half of the 19th century by the Catalan chemist and botanist Frederic Trèmols Borrell. Between 1930 and 1960, the technician Antoni Marcos carried out a thorough review. The current collection consists of approximately 9000 specimen sheets; is made up of 58 volumes reordered by Marcos,two volumes with the original structure, four boxes of Hieracium and 85 boxes with additional material. Up to now 22 volumes and four boxes of Hieracium have been computerized (3695 specimens); we made an inventory at genus level of all volumes, and we computerized the original catalogue of the herbarium and the existing taxonomical fiches. We have also developed a preliminary inventory of the contents of the extra boxes. The analysis of these 3695 herbarium specimens clearly shows that it mainly consists of samples obtained by exchange (67.1%) especially within the Société Helvétique pour l"Échange des Plantes and the Societat Botànica Barcelonesa. Among the materials studied we found two specimens regarded as interesting from a taxonomical and/or nomenclatural point of view (isotypes of Silene holzmanii Heldr. ex Boiss. and of Arenaria minutiflora Loscos). Therefore, the main interest of the herbarium lies in the diversity of the geographical provenance of plants, which makes of this collection one of the first"pan-European herbaria" in Catalonia.

Database Marketing from the Customer Relationship ManagementPerspective

Tietokantamarkkinointi voi olla vain apuväline markkinointitoimenpiteiden suorittamisessa, mutta se voidaan toisaalta nähdä myös olennaisena osana asiakassuhdehallintaa. Tietokantamarkkinointi asiakassuhdehallinnan näkökulmasta tähtää asiakastyytyväisyyteen ja asiakasuskollisuuteen, sekä asiakassuhteen tuottavuuteen ja kannattavuuteen, mikä voidaan saavuttaa tehokkaan tiedonhallinnan avulla. Tämä mahdollistaa räätälöityjen toimenpiteiden suorittamisen ja tehostaa kohdentamista ja segmentointia, myös asiakkaiden tuottavuuden perusteella. Normatiivinen case-tutkimus, joka tehtiin Alankomaissa Eurooppalaisessa tietotekniikan lisäarvoa tuottavassa jälleenmyyntikanavassa osoittaa, että tietokantamarkkinointi etenkin asiakas- suhdehallinnan näkökulmasta olisi sopiva keino lisätä asiakastyytyväisyyttä ja –tuottavuutta. Se myös tehostaisi sisäisiä tietovirtoja ja markkinointitoimenpiteitä, kuten esimerkiksi markkinointiviestintää, kampanjanhallintaa ja myyntiprosesseja yritysten välisessä kaupankäynnissä.

Liikeidean kehittäminen case; videoneuvotteluna toteutettava opetus

Tutkielman aihealue kuuluu liikeidean kehittämisen kenttään. Tutkielmassa on teoreettinen ja empiirinen osa. Teoreettisen viitekehyksen alussa käsitellään tietoyhteiskuntaa eri näkökulmista käsin. Lisäksi on käsitelty videoneuvotteluna toteutettua opetusta ja videoneuvottelutekniikkaa sekä pohdittu etäopetuskäsitteen suhdetta videoneuvotteluvälitteiseen opetukseen. Koska tutkielmassa on innovatiivinen ote, on lähdeaineiston avulla käsitelty myös innovaatioita. Liikeidean kehittämisen tueksi on selvennetty toiminta-ajatuksen ja liikeidean käsitteitä. Empiirinen osa rakentuu kyselytutkimuksen tulosten esittelyn sekä liikeidean kehittämisen ympärille. Empiirisen osan päätavoite on kehittää liikeideaa yritykselle, joka välittäisi erityisasiantuntijatason opetusta videoneuvottelujärjestelmien kautta. Liikeidean kehittämisen tueksi ja sen testaamiseksi on suoritettu sähköpostin avulla kyselytutkimus valitussa asiakaskohderyhmässä. Kyselytutkimuksen perusteella videoneuvottelujärjestelmien kautta välitettävälle erityisasiantuntemukselle on kysyntää. Videoneuvotteluna toteutettavaan opetukseen on mahdollista rakentaa moniulotteisesti asiakkaiden arvostamaa lisäarvoa. Liikeidean toteutuksen onnistumisen kannalta kriittisen tärkeitä tekijöitä ovat oikean asiakaskohderyhmän valitseminen, koulutussuunnittelu sekä markkinoinnin onnistuminen Erittäin kriittinen tekijä on erityisasiantuntijoiden "sisäänosto".

Comment on 'The Molecular Evolutionary Patterns of the Insulin/FOXO Signaling Pathway'

Letter to the Editor on Wang M, Wang Q, Wang Z, Zhang X, Pan Y. The molecular evolutionary patterns of the insulin/FOXO signaling pathway

New Algorithm for Managing Childhood Illness Using Mobile Technology (ALMANACH): A Controlled Non-Inferiority Study on Clinical Outcome and Antibiotic Use in Tanzania.

INTRODUCTION: The decline of malaria and scale-up of rapid diagnostic tests calls for a revision of IMCI. A new algorithm (ALMANACH) running on mobile technology was developed based on the latest evidence. The objective was to ensure that ALMANACH was safe, while keeping a low rate of antibiotic prescription. METHODS: Consecutive children aged 2-59 months with acute illness were managed using ALMANACH (2 intervention facilities), or standard practice (2 control facilities) in Tanzania. Primary outcomes were proportion of children cured at day 7 and who received antibiotics on day 0. RESULTS: 130/842 (15∙4%) in ALMANACH and 241/623 (38∙7%) in control arm were diagnosed with an infection in need for antibiotic, while 3∙8% and 9∙6% had malaria. 815/838 (97∙3%;96∙1-98.4%) were cured at D7 using ALMANACH versus 573/623 (92∙0%;89∙8-94∙1%) using standard practice (p<0∙001). Of 23 children not cured at D7 using ALMANACH, 44% had skin problems, 30% pneumonia, 26% upper respiratory infection and 13% likely viral infection at D0. Secondary hospitalization occurred for one child using ALMANACH and one who eventually died using standard practice. At D0, antibiotics were prescribed to 15∙4% (12∙9-17∙9%) using ALMANACH versus 84∙3% (81∙4-87∙1%) using standard practice (p<0∙001). 2∙3% (1∙3-3.3) versus 3∙2% (1∙8-4∙6%) received an antibiotic secondarily. CONCLUSION: Management of children using ALMANACH improve clinical outcome and reduce antibiotic prescription by 80%. This was achieved through more accurate diagnoses and hence better identification of children in need of antibiotic treatment or not. The building on mobile technology allows easy access and rapid update of the decision chart. TRIAL REGISTRATION: Pan African Clinical Trials Registry PACTR201011000262218.

Socially anxious and confident men interact with a forward virtual woman: an experiment study

Male volunteers entered an immersive virtual reality that depicted a party, where they were approached by a lone virtual woman who initiated a conversation. The goal was to study how socially anxious and socially confident men would react to this event. Interest focused on whether the socially anxious participants would exhibit sustained anxiety during the conversation or whether this would diminish over time, and differ from the responses of the more socially confident men.

Diverse Routes from School, via Higher Education, to Employment. A Comparison of Nine European Countries

The central theme for this study is graduate employment and employability in European-wide discussion. In this study, the complex relationships between higher education and the world of work are explored from the vantage point of how individuals make use of the higher education system in their transition from education to employment. The variation among individual transition processes in nine European countries is analysed with the help of a comparable graduate survey. Countries in this study are Italy, Spain, France, Austria, Germany, the Netherlands, the United Kingdom, Finland, and Norway. The data used for the study is commonly known as the “CHEERS” or “Careers after Higher Education, A European Research Survey.” The data was collected in 1999. The study discusses the possibilities and limitations the higher education system has in supporting the initial education-to-work transitions of youth. The study also addresses problems with comparing national higher education systems in terms of enrolment and graduate employability. A central purpose for this study is to reflect on concerns about the prolongation of individual transitions with a framework that simultaneously considers both the graduate employability and the duration of the education-to-work transition process. The key concept for this study is the standard student/graduate; synonym concepts are the traditional and the conventional student/graduate. Standard graduates are relatively young individuals who are performing their initial transition from education to working-life and who complete the degree-earning process within the stipulated time frame. In all nine countries, standard graduates make up a considerable share of the student flow, passing from higher education to the labour markets. The share of standard graduates is by far the largest in France, where they comprise the overwhelming mass. The proportion of the standard graduates is the lowest in Italy, Finland, and Austria where approximately one in four graduates completed the process of higher education within the stipulated time frame. Of the nine countries compared, employability of the whole graduate population is the greatest in Norway, the UK, Finland, and the Netherlands. Compared with employability of the whole graduate population, variation among the countries is considerably reduced when reviewing the employability of only the standard graduates. Thereby, even though the ranking among countries remains largely unchanged, the variations among them are smaller when the duration of degree earning process is standardized. The study also discusses other ideal types of student careers (or transition processes) besides the standard student/graduate. Results of regression analyses indicate that that at the pan-European level analysis, the graduate labour markets are not heavily segmented in terms of the type of the individual transition process. When considering within-country differences between the graduates, the field of studies is clearly a more powerful explanatory variable than the type of the transition process. There are, nevertheless, clear indications that, irrespective of the country, chances of finding a high status job are, on the average, highest amongst those who graduate within the stipulated duration of the degree program and who thereby have experienced the standard student career, whereas, participating in working life while studying protects against unemployment after finishing one’s degree.

Stepwise emergence of azole, echinocandin and amphotericin B multidrug resistance in vivo in Candida albicans orchestrated by multiple genetic alterations.

OBJECTIVES: The objective of this study was to characterize the underlying molecular mechanisms in consecutive clinical Candida albicans isolates from a single patient displaying stepwise-acquired multidrug resistance. METHODS: Nine clinical isolates (P-1 to P-9) were susceptibility tested by EUCAST EDef 7.2 and Etest. P-4, P-5, P-7, P-8 and P-9 were available for further studies. Relatedness was evaluated by MLST. Additional genes were analysed by sequencing (including FKS1, ERG11, ERG2 and TAC1) and gene expression by quantitative PCR (CDR1, CDR2 and ERG11). UV-spectrophotometry and GC-MS were used for sterol analyses. In vivo virulence was determined in the insect model Galleria mellonella and evaluated by log-rank Mantel-Cox tests. RESULTS: P-1 + P-2 were susceptible, P-3 + P-4 fluconazole resistant, P-5 pan-azole resistant, P-6 + P-7 pan-azole and echinocandin resistant and P-8 + P-9 MDR. MLST supported genetic relatedness among clinical isolates. P-4 harboured four changes in Erg11 (E266D, G307S, G450E and V488I), increased expression of ERG11 and CDR2 and a change in Tac1 (R688Q). P-5, P-7, P-8 and P-9 had an additional change in Erg11 (A61E), increased expression of CDR1, CDR2 and ERG11 (except for P-7) and a different amino acid change in Tac1 (R673L). Echinocandin-resistant isolates harboured the Fks1 S645P alteration. Polyene-resistant P-8 + P-9 lacked ergosterol and harboured a frameshift mutation in ERG2 (F105SfsX23). Virulence was attenuated (but equivalent) in the clinical isolates, but higher than in the azole- and echinocandin-resistant unrelated control strain. CONCLUSIONS: C. albicans demonstrates a diverse capacity to adapt to antifungal exposure. Potentially novel resistance-inducing mutations in TAC1, ERG11 and ERG2 require independent validation.

The High Prevalence and Diversity of Chlamydiales DNA within Ixodes ricinus Ticks Suggest a Role for Ticks as Reservoirs and Vectors of Chlamydia-Related Bacteria.

The Chlamydiales order is composed of nine families of strictly intracellular bacteria. Among them, Chlamydia trachomatis, C. pneumoniae, and C. psittaci are established human pathogens, whereas Waddlia chondrophila and Parachlamydia acanthamoebae have emerged as new pathogens in humans. However, despite their medical importance, their biodiversity and ecology remain to be studied. Even if arthropods and, particularly, ticks are well known to be vectors of numerous infectious agents such as viruses and bacteria, virtually nothing is known about ticks and chlamydia. This study investigated the prevalence of Chlamydiae in ticks. Specifically, 62,889 Ixodes ricinus ticks, consolidated into 8,534 pools, were sampled in 172 collection sites throughout Switzerland and were investigated using pan-Chlamydiales quantitative PCR (qPCR) for the presence of Chlamydiales DNA. Among the pools, 543 (6.4%) gave positive results and the estimated prevalence in individual ticks was 0.89%. Among those pools with positive results, we obtained 16S rRNA sequences for 359 samples, allowing classification of Chlamydiales DNA at the family level. A high level of biodiversity was observed, since six of the nine families belonging to the Chlamydiales order were detected. Those most common were Parachlamydiaceae (33.1%) and Rhabdochlamydiaceae (29.2%). "Unclassified Chlamydiales" (31.8%) were also often detected. Thanks to the huge amount of Chlamydiales DNA recovered from ticks, this report opens up new perspectives on further work focusing on whole-genome sequencing to increase our knowledge about Chlamydiales biodiversity. This report of an epidemiological study also demonstrates the presence of Chlamydia-related bacteria within Ixodes ricinus ticks and suggests a role for ticks in the transmission of and as a reservoir for these emerging pathogenic Chlamydia-related bacteria.

Combined deletion of cathepsin protease family members reveals compensatory mechanisms in cancer.

Proteases are important for regulating multiple tumorigenic processes, including angiogenesis, tumor growth, and invasion. Elevated protease expression is associated with poor patient prognosis across numerous tumor types. Several multigene protease families have been implicated in cancer, including cysteine cathepsins. However, whether individual family members have unique roles or are functionally redundant remains poorly understood. Here we demonstrate stage-dependent effects of simultaneously deleting cathepsin B (CtsB) and CtsS in a murine pancreatic neuroendocrine tumor model. Early in tumorigenesis, the double knockout results in an additive reduction in angiogenic switching, whereas at late stages, several tumorigenic phenotypes are unexpectedly restored to wild-type levels. We identified CtsZ, which is predominantly supplied by tumor-associated macrophages, as the compensatory protease that regulates the acquired tumor-promoting functions of lesions deficient in both CtsB and CtsS. Thus, deletion of multiple cathepsins can lead to stage-dependent, compensatory mechanisms in the tumor microenvironment, which has potential implications for the clinical consideration of selective versus pan-family cathepsin inhibitors in cancer.

Establishing International Blood Pressure References Among Nonoverweight Children and Adolescents Aged 6 to 17 Years.

BACKGROUND: Several distributions of country-specific blood pressure (BP) percentiles by sex, age, and height for children and adolescents have been established worldwide. However, there are no globally unified BP references for defining elevated BP in children and adolescents, which limits international comparisons of the prevalence of pediatric elevated BP. We aimed to establish international BP references for children and adolescents by using 7 nationally representative data sets (China, India, Iran, Korea, Poland, Tunisia, and the United States). METHODS AND RESULTS: Data on BP for 52 636 nonoverweight children and adolescents aged 6 to 19 years were obtained from 7 large nationally representative cross-sectional surveys in China, India, Iran, Korea, Poland, Tunisia, and the United States. BP values were obtained with certified mercury sphygmomanometers in all 7 countries by using standard procedures for BP measurement. Smoothed BP percentiles (50th, 90th, 95th, and 99th) by age and height were estimated by using the Generalized Additive Model for Location Scale and Shape model. BP values were similar between males and females until the age of 13 years and were higher in males than females thereafter. In comparison with the BP levels of the 90th and 95th percentiles of the US Fourth Report at median height, systolic BP of the corresponding percentiles of these international references was lower, whereas diastolic BP was similar. CONCLUSIONS: These international BP references will be a useful tool for international comparison of the prevalence of elevated BP in children and adolescents and may help to identify hypertensive youths in diverse populations.