Two-year outcome of an observe-and-plan regimen for neovascular age-related macular degeneration: how to alleviate the clinical burden with maintained functional results.

PurposeThe purpose of this study was to report the 2-year outcome of an individually tailored 'observe-and-plan' treatment regimen for neovascular age-related macular degeneration (nAMD), and to investigate its clinical value in terms of functional outcome. This regimen aimed to reduce the clinical burden (visits) by employing individually fixed injection intervals, based on the predictability of an individual's need for retreatment.MethodsThis prospective case series included 104 patients (115 eyes) with nAMD. Following three loading doses of ranibizumab, the disease recurrence interval was determined in monthly observation visits. Retreatment was applied in a series of three injections with individually fixed intervals (2 weeks shorter than the recurrence interval), combined with periodic adjustment of the intervals. The allowed injection intervals in treatment plans ranged from 1 to 3 months. If there was no recurrence at 3 months, the patient could change to monitoring alone.ResultsMean visual acuity (VA) improved by 8.7, 9.7, and 9.2 letters at months 3, 12, and 24, respectively. The mean number of injections was 7.8 and 5.8 during years 1 and 2, respectively, whereas the mean number of ophthalmic examinations was 4.0 and 2.9, respectively. The mean treatment interval (after the loading doses) was 2.0 months during year 1, and 2.2 months during year 2.ConclusionThe observe-and-plan regimen significantly improved and maintained VA over the course of 2 years. This favourable functional outcome was achieved with fewer clinic visits compared with other regimens. Therefore, this observe-and-plan regimen has the potential to alleviate the clinical burden of nAMD treatment.

Detecting patterns of species diversification in the presence of both rate shifts and mass extinctions.

BACKGROUND: Recent methodological advances allow better examination of speciation and extinction processes and patterns. A major open question is the origin of large discrepancies in species number between groups of the same age. Existing frameworks to model this diversity either focus on changes between lineages, neglecting global effects such as mass extinctions, or focus on changes over time which would affect all lineages. Yet it seems probable that both lineages differences and mass extinctions affect the same groups. RESULTS: Here we used simulations to test the performance of two widely used methods under complex scenarios of diversification. We report good performances, although with a tendency to over-predict events with increasing complexity of the scenario. CONCLUSION: Overall, we find that lineage shifts are better detected than mass extinctions. This work has significance to assess the methods currently used to estimate changes in diversification using phylogenetic trees. Our results also point toward the need to develop new models of diversification to expand our capabilities to analyse realistic and complex evolutionary scenarios.

Kustannusrakenteen simulointi ja optimointi

Primääripakatun tuotteen liiketoiminnallisen arvoketjun kustannusrakenteen tunnistaminen tuo merkittävää lisäarvoa pakkausliiketoiminnan suunnittelua koskevaan päätöksentekoon. Tämän konstruktiivisen tutkimuksen tavoitteena on rakentaa pakkaustuotannon liiketoiminnallisen arvoketjun simulointimalli, jonka avulla voidaan analysoida pakkaustuotannon arvoketjun kustannusrakennetta lähtien pakkausraaka-aineen valmistuksesta ja päättyen kaupan vähittäismyyntiin. Käytettävä tutkimusaineisto koostuu jonoteoriaan ja tuotannonsuunnitteluun liittyvästä kirjallisuudesta, tieteellisistä artikkeleista sekä asiantuntijalausunnoista. Tutkimuksen yhteydessä rakennetun simulointimallin avulla määritettiin erään primääripakatun tuotteen konvertointivaiheen optimaalinen valmistuseräkoko ja liiketoiminnallisen arvoketjun kustannusrakenne. Arvoketjuanalyysissä primääripakatun tuotteen kustannustekijöiksi määritettiin pakkausmateriaali, pakkausvalmistus, pakattava tuote, pakkauksen täyttö ja suljenta sekä pakatun tuotteen jakelulogistiikka ja vähittäismyynti. Arvoketjuanalyysin johtopäätöksenä voidaan todeta, että primääripakatulle esimerkkituotteelle kohdistuvista kustannuksista noin 97 % on brand ownerin ja vähittäismyynnin aiheuttamia ja noin 3 % varsinaisesta tuotteen pakkaamisesta aiheutuvia.

EEG reactivity to pain in comatose patients: Importance of the stimulus type.

INTRODUCTION: Electroencephalogram (EEG) background reactivity is a potentially interesting outcome predictor in comatose patients, especially after cardiac arrest, but recent studies report only fair interrater reliability. Furthermore, there are no definite guidelines for its testing. We therefore investigated the EEG effect of standardized noxious stimuli in comatose patients not reactive to auditory stimuli. METHODS: In this prospective study we applied a protocol using three different painful stimuli (bilateral nipple pinching, pinprick at the nose base, finger-nail compression on each side), grouped in three distinct clusters with an alternated sequence, during EEG recordings in comatose patients. We only analyzed recordings showing any reactivity to pain. Fisher and χ2 tests were used as needed to assess contingency tables. RESULTS: Of 42 studies, 12 did not show any background reactivity, 2 presented SIRPIDs, and 2 had massive artefacts; we thus analyzed 26 EEGs recorded in 17 patients (4 women, 24%). Nipple pinching more frequently induced a change in EEG background activity (p<0.001), with a sensitivity of 97.4% for reactivity. Neither the order of the stimuli in the cluster (p=0.723), nor the cluster order (p=0.901) influenced the results. CONCLUSION: In this pilot study, bilateral, synchronous nipple pinching seems to be the most efficient method to test nociceptive EEG reactivity in comatose patients. This approach may enhance interrater reliability, but deserves confirmation in larger cohorts.

Gestión de la actividad no presencial y autoevaluación de competencias = Management of Student Learning Outside the Classroom and the Self-evaluation of Competences

Psychological Assessment is a core subject of Psychology studies, and of the university degree Human development, at the University of Girona and according to the University regulations, had 12 credits. Until the 2005-06 academic years, the student work conducted outside the classroom consisted of undertaking a psychological assessment that was written and handed in at the end of the course. From this the student obtained a qualification and a review if they applied for it In accordance with the European Credits for Higher Education, this subject was reduced to 9 credits, which is the equivalent of a total of 255 hours of in-class work and outside the classroom. In the 2006-07 academic year we created a guide to manage the student’s experiences outside the classroom, with the objective of encouraging the application of problem solving/critical thinking (Bloom, 1975), in line with the recommendations of the Catalonia Agency for University System Quality (2005). The guide includes: learning objectives, evaluation criterions, a description of activities, work week timetable for the whole course, programmed tutorials to review all steps of the psychological assessment process, and the use of a web-based virtual forum for the transfer of knowledge, analysis and constructive critiques of the assessment done by themselves and their colleagues

The Evolution of the European Regulatory Framework for Electronic Communications

The paper reviews the historical transformation of the European regulatory framework for electronic communications from the era dominated by state-owned enterprises to the presence of regulated competition. In the course of these developments, the vision of the roles of the public and private sectors in electronic communications changed in expected and unexpected ways. While the period is characterized by a shift toward less direct state intervention, the intensity of regulation has increased in many areas. Most recently, in the wake of the financial crisis, new forms of state intervention can be observed, including public investment in communications infrastructure and public-private partnerships. As a result of the reforms, Europe has been able to achieve major successes but it also suffered unanticipated setbacks compared to other regions. The European Union emerged as the global leader in mobile communications during the 1990s and was able to roll-out first-generation broadband access networks more rapidly than many of its peers. Recently, however, Europe as a whole has not performed as well in deploying next-generation networks and advanced mobile communications services. The paper offers a political-economic explanation for these developments and assesses their effects on the performance of the European electronic communications sector and the economy. From this analysis, the European model emerges as a unique institutional arrangement with peculiar advantages and disadvantages. Once these are recognized, sensible next steps to build the strengths while avoiding the weaknesses of the model can be seen more clearly.

The Role of Biomarkers for Starting Antifungals in the Intensive Care Unit

Invasive candidiasis is associated with high mortality rates (35% to 60%), similar to the range reported for septic shock. The most common types include candidemia, frequently observed in immunocompromised patients, and noncandidemic systemic candidiasis, which constitutes the majority of cases in critically ill patients. However, they are difficult to prove and a definite diagnosis usually occurs late in the course of the disease, thus contributing to their bad prognosis. Early empirical treatment improves the prognosis and currently relies on the positive predictive value (PPV) of risk-assessment strategies (colonization index, Candida score, predictive rules) based on combinations of risk factors, but it may have also largely contributed to the overuse of antifungal agents in critically ill patients. In this context, non- culture-based diagnostic methods, including specific and nonspecific biomarkers, may significantly improve the diagnosis of invasive candidiasis. Candida DNA and mannan antigen/antimannan antibodies are of limited interest for the diagnosis of invasive candidiasis as they fail to identify noncandidemic systemic candidiasis, despite early positivity in candidemic patients. The utility of 1,3-beta-D-glucan (b-D-glucan), a panfungal cell wall antigen, has been demonstrated for the diagnosis of fungal infections in immunocompromised patients. Preliminary data suggest that it is also detectable early in critically ill patients developing noncandidemic systemic candidiasis. To take advantage of the high negative predictive value of risk-assessment strategies and the early increase in specific fungal biomarkers in high-risk patients, we propose a practical 2-step approach to improve the selection of patients susceptible to benefit from empirical antifungal treatment.

Progressive multifocal leukoencephalopathy in common variable immunodeficiency: mitigated course under mirtazapine and mefloquine.

Demonstration of survival and outcome of progressive multifocal leukoencephalopathy (PML) in a 56-year-old patient with common variable immunodeficiency, consisting of severe hypogammaglobulinemia and CD4+ T lymphocytopenia, during continuous treatment with mirtazapine (30 mg/day) and mefloquine (250 mg/week) over 23 months. Regular clinical examinations including Rankin scale and Barthel index, nine-hole peg and box and block tests, Berg balance, 10-m walking tests, and Montreal Cognitive Assessment (MoCA) were done. Laboratory diagnostics included complete blood count and JC virus (JCV) concentration in cerebrospinal fluid (CSF). The noncoding control region (NCCR) of JCV, important for neurotropism and neurovirulence, was sequenced. Repetitive MRI investigated the course of brain lesions. JCV was detected in increasing concentrations (peak 2568 copies/ml CSF), and its NCCR was genetically rearranged. Under treatment, the rearrangement changed toward the archetype sequence, and later JCV DNA became undetectable. Total brain lesion volume decreased (8.54 to 3.97 cm(3)) and atrophy increased. Barthel (60 to 100 to 80 points) and Rankin (4 to 2 to 3) scores, gait stability, and box and block (7, 35, 25 pieces) and nine-hole peg (300, 50, 300 s) test performances first improved but subsequently worsened. Cognition and walking speed remained stable. Despite initial rapid deterioration, the patient survived under continuous treatment with mirtazapine and mefloquine even though he belongs to a PML subgroup that is usually fatal within a few months. This course was paralleled by JCV clones with presumably lower replication capability before JCV became undetectable. Neurological deficits were due to PML lesions and progressive brain atrophy.

The new final Clinical Skills examination in human medicine in Switzerland: Essential steps of exam development, implementation and evaluation, and central insights from the perspective of the national Working Group.

OBJECTIVE: Since 2011, the new national final examination in human medicine has been implemented in Switzerland, with a structured clinical-practical part in the OSCE format. From the perspective of the national Working Group, the current article describes the essential steps in the development, implementation and evaluation of the Federal Licensing Examination Clinical Skills (FLE CS) as well as the applied quality assurance measures. Finally, central insights gained from the last years are presented. METHODS: Based on the principles of action research, the FLE CS is in a constant state of further development. On the foundation of systematically documented experiences from previous years, in the Working Group, unresolved questions are discussed and resulting solution approaches are substantiated (planning), implemented in the examination (implementation) and subsequently evaluated (reflection). The presented results are the product of this iterative procedure. RESULTS: The FLE CS is created by experts from all faculties and subject areas in a multistage process. The examination is administered in German and French on a decentralised basis and consists of twelve interdisciplinary stations per candidate. As important quality assurance measures, the national Review Board (content validation) and the meetings of the standardised patient trainers (standardisation) have proven worthwhile. The statistical analyses show good measurement reliability and support the construct validity of the examination. Among the central insights of the past years, it has been established that the consistent implementation of the principles of action research contributes to the successful further development of the examination. CONCLUSION: The centrally coordinated, collaborative-iterative process, incorporating experts from all faculties, makes a fundamental contribution to the quality of the FLE CS. The processes and insights presented here can be useful for others planning a similar undertaking.

Impact of body tilt on the central aortic pressure pulse.

The present work was undertaken to investigate, in young healthy volunteers, the relationships between the forward propagation times of arterial pressure waves and the timing of reflected waves observable on the aortic pulse, in the course of rapid changes in body position. 20 young healthy subjects, 10 men, and 10 women, were examined on a tilt table at two different tilt angles, -10° (Head-down) and + 45° (Head-up). In each position, carotid-femoral (Tcf) and carotid-tibial forward propagation times (Tct) were measured with the Complior device. In each position also, the central aortic pressure pulse was recorded with radial tonometry, using the SphygmoCor device and a generalized transfer function, so as to evaluate the timing of reflected waves reaching the aorta in systole (onset of systolic reflected wave, sT1r) and diastole (mean transit time of diastolic reflected wave, dMTT). The position shift from Head-up to Head-down caused a massive increase in both Tct (women from 130 ± 10 to 185 ± 18 msec P < 0.001, men from 136 ± 9 to 204 ± 18 msec P < 0.001) and dMTT (women from 364 ± 35 to 499 ± 33 msec P < 0.001, men from 406 ± 22 to 553 ± 21 msec P < 0.001). Mixed model regression showed that the changes in Tct and dMTT observed between Head-up and Head-down were tightly coupled (regression coefficient 2.1, 95% confidence interval 1.9-2.3, P < 0.001). These results strongly suggest that the diastolic waves observed on central aortic pulses reconstructed from radial tonometric correspond at least in part to reflections generated in the lower limbs.

Protocol de conservació ex situ del Centre Ictiològic del Parc Natural del Delta de l'Ebre

En aquest Treball de Fi de Grau es pretén establir un protocol per a la conservació ex situ de les espècies que hi ha en el Centre Ictiològic del Parc Natural del Delta de l’Ebre. Les espècies que es troben en el CI són espècies vulnerables o en perill: espinós, samaruc, fartet, rabosa, llopet de riu i tritó palmat. Els objectius d’aquest protocol són: que el CI tingui un protocol propi, aprendre com funciona tot el centre, totes les espècies, com alimentar-les, com manipular-les i com tractar-les durant tot el seu cicle de vida. Un altre objectiu és el de veure si a finals d’any s’obté una alta població de cada espècie, quines són reintroduïdes, les patologies sorgides i els valors dels paràmetres químics de les basses naturals exteriors. El protocol s’elabora a partir de les pràctiques realitzades durant l’estiu del 2013 i els coneixements adquirits, la bibliografia i les dades del CI. Gràcies a això s’ha elaborat el treball. S’ha tractat la conservació ex situ; la problemàtica que sofreixen les espècies; cadascuna d’aquestes espècies; com funciona el CI a nivell de centre i a nivell de personal; les tasques que hi ha diàriament, setmanalment i ocasionalment segons les necessitats de l’estoc; el maneig sanitari; les patologies i com tractar-les; i l’anàlisi genètic. Els resultats obtinguts d’aquest protocol són els resultats numèrics obtinguts de l’any 2013 que són: 1. El gran nombre de cries nascudes de samaruc i fartet, menys de raboseta de riu, poques d’espinós i tritó palmat, i menys de llopet que tot just comença ara en el CI. 2. El total d’uns 5700 individus reitnroduits (samaruc, raboseta de riu i espinós de Girona). 3. La patologia més sorgida és el punt blanc. 4. I els paràmetres químics (amoni, nitrits, nitrats i fòsfor) no són molt elevats. La conclusió final i més important a la que arribo en fer el protocol és la gran importància que té el CI per a conservar aquestes espècies que no es saben apreciar fins que comencen a desparèixer. La existència del CI és més aviat una mesura correctora de tots els impactes que han sofert els habitatges de les espècies tractades i de la introducció d’espècies exòtiques que són una amenaça per les autòctones.

The HIV care cascade in Switzerland: reaching the UNAIDS/WHO targets for patients diagnosed with HIV.

OBJECTIVES: To describe the HIV care cascade for Switzerland in the year 2012. DESIGN/METHODS: Six levels were defined: (i) HIV-infected, (ii) HIV-diagnosed, (iii) linked to care, (iv) retained in care, (v) on antiretroviral treatment (ART), and (vi) with suppressed viral load. We used data from the Swiss HIV Cohort Study (SHCS) complemented by a nationwide survey among SHCS physicians to estimate the number of HIV-patients not registered in the cohort. We also used Swiss ART sales data to estimate the number of patients treated outside the SHCS network. Based on the number of patients retained in care, we inferred the estimates for levels (i) to (iii) from previously published data. RESULTS: We estimate that (i) 15 200 HIV-infected individuals lived in Switzerland in 2012 (margins of uncertainty, 13 400-19 300). Of those, (ii) 12 300 (81%) were diagnosed, (iii) 12 200 (80%) linked, and (iv) 11 900 (79%) retained in care. Broadly based on SHCS network data, (v) 10 800 (71%) patients were receiving ART, and (vi) 10 400 (68%) had suppressed (<200 copies/ml) viral loads. The vast majority (95%) of patients retained in care were followed within the SHCS network, with 76% registered in the cohort. CONCLUSION: Our estimate for HIV-infected individuals in Switzerland is substantially lower than previously reported, halving previous national HIV prevalence estimates to 0.2%. In Switzerland in 2012, 91% of patients in care were receiving ART, and 96% of patients on ART had suppressed viral load, meeting recent UNAIDS/WHO targets.

Bat assemblages in the Nietoperek bat reserve (Western Poland) and their conservation strategies

Międzyrzecz Fortified Front, were Natura 2000 site PLH080003 Nietoperek is situated, was built by the Germans in the 1930s and during the World War II. It is composed of above ground bunkers connected by underground tunnels of ca. 32 km total length. Nietoperek is the eighth largest bats hibernation site in EU. Monthly censuses were carried out from October to April during three consecutive winter seasons (2011/12 – 2013/14) in area covering ca. 30% of the undergrounds. The aims of the study were: (1) to describe changes in numbers of each species in the course of hibernation season, (2) to suggest deadlines for counting particular bat species to obtain maximal numbers and (3) to describe negative impact of tourism on hibernating bats. The results will be useful for restriction of winter tourism in Nietoperek. The total number of bats observed during the study was 37869 individuals of 9 species. Because of difficulties in distinguishing without handling M. mystacinus and M. brandtii were treated as one group. M. myotis constituted from 53% (first season) to 64% (last season) of all hibernating bats. The maximal numbers of individuals were observed in November (first two seasons) and in December (third season). M. daubentonii constituted from 27% (first season) to 21% (last season) and M. nattereri from 10% (first season) to 11% (second season) of all bats. During the three seasons the maximal numbers of M. daubentonii and M. nattereri were observed in November and December respectively. B. barbastellus and P. auritus constituted from 4% (first season) to 2% (last season) of the multi species colony. The maximal numbers of B. barbastellus were observed in January and P. auritus in January (first and second seasons) and in December (third season). Results indicated that the best period for counting maximal numbers of M. myotis and M. daubentonii is November, for M. nattereri is December and for B. barbastellus and P. auritus is January. The study undertaken in the part visited by tourists in winter (total length of 900 m) proved negative effect caused by human disturbance with 23% decline of total bat numbers.

Transcranial Direct Current Stimulation for the Treatment of Chronic Tinnitus: A Randomized Controlled Study.

BACKGROUND: Tinnitus is an often disabling condition for which there is no effective therapy. Current research suggests that tinnitus may develop due to maladaptive plastic changes and altered activity in the auditory and prefrontal cortex. Transcranial direct current stimulation (tDCS) modulates brain activity and has been shown to transiently suppress tinnitus in trials. OBJECTIVE: To investigate the efficacy and safety of tDCS in the treatment of chronic subjective tinnitus. METHODS: In a randomized, parallel, double-blind, sham-controlled study, the efficacy and safety of cathodal tDCS to the auditory cortex with anode over the prefrontal cortex was investigated in five sessions over five consecutive days. Tinnitus was assessed after the last session on day 5, and at follow-up visits 1 and 3 months post stimulation using the Tinnitus Handicap Inventory (THI, primary outcome measure), Subjective Tinnitus Severity Scale, Hospital Anxiety and Depression scale, Visual Analogue Scale, and Clinical Global Impression scale. RESULTS: 42 patients were investigated, 21 received tDCS and 21 sham stimulation. There were no beneficial effects of tDCS on tinnitus as assessed by primary and secondary outcome measures. Effect size assessed with Cohen's d amounted to 0.08 (95% CI: -0.52 to 0.69) at 1 month and 0.18 (95% CI: -0.43 to 0.78) at 3 months for the THI. CONCLUSION: tDCS of the auditory and prefrontal cortices is safe, but does not improve tinnitus. Different tDCS protocols might be beneficial.

Voting advice applications : impact on voting decisions in the 2011 Swiss national elections

In most democracies voting Advice Applications (VAAs) advising citizens which candidate or party they should vote for become more and more popular. It is therefore crucial to know more about the functioning and the effects of such tools. After some general remarks about the spread of these tools and their possible effects gathered so far in various studies, this paper presents the latest results from a research conducted in the course of the 2011 Swiss national elections. They confirm that VAAs can lead to better informed voters and are likely to have a positive impact on electoral turnout. Additionally it can be shown that the Swiss VAA smartvote made voters change their voting intention and that they voted for a different party. This was particularly advantageous for the Green Liberal Party. At the moment, only a minority of voters rely on the voting recommendation by smartvote. This might change dramatically with the introduction of e-voting. Once people can vote electronically, there are hardly any possibilities to prevent voters from transferring their selection of candidates based on the recommendation given by a VAA into the official electronic ballot paper. If this is possible, e-voting will become more popular than postal voting.