Eosinophilic granulomatosis with polyangiitis (Churg-Strauss) (EGPA) Consensus Task Force recommendations for evaluation and management.

OBJECTIVE: To develop disease-specific recommendations for the diagnosis and management of eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome) (EGPA). METHODS: The EGPA Consensus Task Force experts comprised 8 pulmonologists, 6 internists, 4 rheumatologists, 3 nephrologists, 1 pathologist and 1 allergist from 5 European countries and the USA. Using a modified Delphi process, a list of 40 questions was elaborated by 2 members and sent to all participants prior to the meeting. Concurrently, an extensive literature search was undertaken with publications assigned with a level of evidence according to accepted criteria. Drafts of the recommendations were circulated for review to all members until final consensus was reached. RESULTS: Twenty-two recommendations concerning the diagnosis, initial evaluation, treatment and monitoring of EGPA patients were established. The relevant published information on EGPA, antineutrophil-cytoplasm antibody-associated vasculitides, hypereosinophilic syndromes and eosinophilic asthma supporting these recommendations was also reviewed. DISCUSSION: These recommendations aim to give physicians tools for effective and individual management of EGPA patients, and to provide guidance for further targeted research.

Endobronchial valves in severe emphysematous patients: CT evaluation of lung fissures completeness, treatment radiological response and quantitative emphysema analysis

OBJECTIVE: To evaluate lung fissures completeness, post-treatment radiological response and quantitative CT analysis (QCTA) in a population of severe emphysematous patients submitted to endobronchial valves (EBV) implantation. MATERIALS AND METHODS: Multi-detectors CT exams of 29 patients were studied, using thin-section low dose protocol without contrast. Two radiologists retrospectively reviewed all images in consensus; fissures completeness was estimated in 5% increments and post-EBV radiological response (target lobe atelectasis/volume loss) was evaluated. QCTA was performed in pre and post-treatment scans using a fully automated software. RESULTS: CT response was present in 16/29 patients. In the negative CT response group, all 13 patients presented incomplete fissures, and mean oblique fissures completeness was 72.8%, against 88.3% in the other group. QCTA most significant results showed a reduced post-treatment total lung volume (LV) (mean 542 ml), reduced EBV-submitted LV (700 ml) and reduced emphysema volume (331.4 ml) in the positive response group, which also showed improved functional tests. CONCLUSION: EBV benefit is most likely in patients who have complete interlobar fissures and develop lobar atelectasis. In patients with no radiological response we observed a higher prevalence of incomplete fissures and a greater degree of incompleteness. The fully automated QCTA detected the post-treatment alterations, especially in the treated lung analysis.

Identifying strategies for mitigating the global warming impact of the EU-25 economy using a multi-objective input-output approach

Global warming mitigation has recently become a priority worldwide. A large body of literature dealing with energy related problems has focused on reducing greenhouse gases emissions at an engineering scale. In contrast, the minimization of climate change at a wider macroeconomic level has so far received much less attention. We investigate here the issue of how to mitigate global warming by performing changes in an economy. To this end, we make use of a systematic tool that combines three methods: linear programming, environmentally extended input output models, and life cycle assessment principles. The problem of identifying key economic sectors that contribute significantly to global warming is posed in mathematical terms as a bi criteria linear program that seeks to optimize simultaneously the total economic output and the total life cycle CO2 emissions. We have applied this approach to the European Union economy, finding that significant reductions in global warming potential can be attained by regulating specific economic sectors. Our tool is intended to aid policymakers in the design of more effective public policies for achieving the environmental and economic targets sought.

Balancing effluent quality, economic cost and greenhouse gas emissions during the evaluation of (plant-wide) control/operational strategies in WWTPs

The objective of this paper was to show the potential additional insight that result from adding greenhouse gas (GHG) emissions to plant performance evaluation criteria, such as effluent quality (EQI) and operational cost (OCI) indices, when evaluating (plant-wide) control/operational strategies in wastewater treatment plants (WWTPs). The proposed GHG evaluation is based on a set of comprehensive dynamic models that estimate the most significant potential on-site and off-site sources of CO2, CH4 and N2O. The study calculates and discusses the changes in EQI, OCI and the emission of GHGs as a consequence of varying the following four process variables: (i) the set point of aeration control in the activated sludge section; (ii) the removal efficiency of total suspended solids (TSS) in the primary clarifier; (iii) the temperature in the anaerobic digester; and (iv) the control of the flow of anaerobic digester supernatants coming from sludge treatment. Based upon the assumptions built into the model structures, simulation results highlight the potential undesirable effects of increased GHG production when carrying out local energy optimization of the aeration system in the activated sludge section and energy recovery from the AD. Although off-site CO2 emissions may decrease, the effect is counterbalanced by increased N2O emissions, especially since N2O has a 300-fold stronger greenhouse effect than CO2. The reported results emphasize the importance and usefulness of using multiple evaluation criteria to compare and evaluate (plant-wide) control strategies in a WWTP for more informed operational decision making

Dual inhibitors of beta-amyloid aggregation and acetylcholinesterase as multi-target anti-Alzheimer drug candidates

Notwithstanding the functional role that the aggregates of some amyloidogenic proteins can play in different organisms, protein aggregation plays a pivotal role in the pathogenesis of a large number of human diseases. One of such diseases is Alzheimer"s disease (AD), where the overproduction and aggregation of the β-amyloid peptide (Aβ) are regarded as early critical factors. Another protein that seems to occupy a prominent position within the complex pathological network of AD is the enzyme acetylcholinesterase (AChE), with classical and non-classical activities involved at the late (cholinergic deficit) and early (Aβ aggregation) phases of the disease. Dual inhibitors of Aβ aggregation and AChE are thus emerging as promising multi-target agents with potential to efficiently modify the natural course of AD. In the initial phases of the drug discovery process of such compounds, in vitro evaluation of the inhibition of Aβ aggregation is rather troublesome, as it is very sensitive to experimental assay conditions, and requires expensive synthetic Aβ peptides, which makes cost-prohibitive the screening of large compound libraries. Herein, we review recently developed multi-target anti-Alzheimer compounds that exhibit both Aβ aggregation and AChE inhibitory activities, and, in some cases also additional valuable activities such as BACE-1 inhibition or antioxidant properties. We also discuss the development of simplified in vivo methods for the rapid, simple, reliable, unexpensive, and high-throughput amenable screening of Aβ aggregation inhibitors that rely on the overexpression of Aβ42 alone or fused with reporter proteins in Escherichia coli.

Maritime Safety in the Gulf of Finland. Review on Policy Instruments

Suomenlahden lisääntynyt meriliikenne on herättänyt huolta meriliikenteen turvallisuuden tasosta, ja erityisesti Venäjän öljyviennin kasvu on lisännyt öljyonnettomuuden todennäköisyyttä Suomenlahdella. Erilaiset kansainväliset, alueelliset ja kansalliset ohjauskeinot pyrkivät vähentämään merionnettomuuden riskiä ja meriliikenteen muita haittavaikutuksia. Tämä raportti käsittelee meriturvallisuuden yhteiskunnallisia ohjauskeinoja: ohjauskeinoja yleisellä tasolla, meriturvallisuuden keskeisimpiä säätelijöitä, meriturvallisuuden ohjauskeinoja ja meriturvallisuuspolitiikan tulevaisuuden näkymiä, ohjauskeinojen tehokkuutta ja nykyisen meriturvallisuuden ohjausjärjestelmän heikkouksia. Raportti on kirjallisuuskatsaus meriturvallisuuden yhteiskunnalliseen sääntelyn rakenteeseen ja tilaan erityisesti Suomenlahden meriliikenteen näkökulmasta. Raportti on osa tutkimusprojektia ”SAFGOF - Suomenlahden meriliikenteen kasvunäkymät 2007 - 2015 ja kasvun vaikutukset ympäristölle ja kuljetusketjujen toimintaan” ja sen työpakettia 6 ”Keskeisimmät riskit ja yhteiskunnalliset vaikutuskeinot”. Yhteiskunnalliset ohjauskeinot voidaan ryhmitellä hallinnollisiin, taloudellisiin ja tietoohjaukseen perustuviin ohjauskeinoihin. Meriturvallisuuden edistämisessä käytetään kaikkia näitä, mutta hallinnolliset ohjauskeinot ovat tärkeimmässä asemassa. Merenkulun kansainvälisen luonteen vuoksi meriturvallisuuden sääntely tapahtuu pääosin kansainvälisellä tasolla YK:n ja erityisesti Kansainvälisen merenkulkujärjestön (IMO) toimesta. Lisäksi myös Euroopan Unionilla on omaa meriturvallisuuteen liittyvää sääntelyä ja on myös olemassa muita alueellisia meriturvallisuuden edistämiseen liittyviä elimiä kuten HELCOM. Joitakin meriturvallisuuden osa-alueita säädellään myös kansallisella tasolla. Hallinnolliset meriturvallisuuden ohjauskeinot sisältävät aluksen rakenteisiin ja varustukseen, alusten kunnon valvontaan, merimiehiin ja merityön tekemiseen sekä navigointiin liittyviä ohjauskeinoja. Taloudellisiin ohjauskeinoihin kuuluvat esimerkiksi väylä- ja satamamaksut, merivakuutukset, P&I klubit, vastuullisuus- ja korvauskysymykset sekä taloudelliset kannustimet. Taloudellisten ohjauskeinojen käyttö meriturvallisuuden edistämiseen on melko vähäistä verrattuna hallinnollisten ohjauskeinojen käyttöön, mutta niitä voitaisiin varmasti käyttää enemmänkin. Ongelmana taloudellisten ohjauskeinojen käytössä on se, että ne kuuluvat pitkälti kansallisen sääntelyn piiriin, joten alueellisten tai kansainvälisten intressien edistäminen taloudellisilla ohjauskeinoilla voi olla hankalaa. Tieto-ohjaus perustuu toimijoiden vapaaehtoisuuteen ja yleisen tiedotuksen lisäksi tieto-ohjaukseen sisältyy esimerkiksi vapaaehtoinen koulutus, sertifiointi tai meriturvallisuuden edistämiseen tähtäävät palkinnot. Poliittisella tasolla meriliikenteen aiheuttamat turvallisuusriskit Suomenlahdella on otettu vakavasti ja paljon työtä tehdään eri tahoilla riskien minimoimiseksi. Uutta sääntelyä on odotettavissa etenkin liittyen meriliikenteen ympäristövaikutuksiin ja meriliikenteen ohjaukseen kuten meriliikenteen sähköisiin seurantajärjestelmiin. Myös inhimilliseen tekijän merkitykseen meriturvallisuuden kehittämisessä on kiinnitetty lisääntyvissä määrin huomiota, mutta inhimilliseen tekijän osalta tehokkaiden ohjauskeinojen kehittäminen näyttää olevan haasteellista. Yleisimmin lääkkeeksi esitetään koulutuksen kehittämistä. Kirjallisuudessa esitettyjen kriteereiden mukaan tehokkaiden ohjauskeinojen tulisi täyttää seuraavat vaatimukset: 1) tarkoituksenmukaisuus – ohjauskeinojen täytyy olla sopivia asetetun tavoitteen saavuttamiseen, 2) taloudellinen tehokkuus – ohjauskeinon hyödyt vs. kustannukset tulisi olla tasapainossa, 3) hyväksyttävyys – ohjauskeinon täytyy olla hyväksyttävä asianosaisten ja myös laajemman yhteiskunnan näkökulmasta katsottuna, 4) toimeenpano – ohjauskeinon toimeenpanon pitää olla mahdollista ja sen noudattamista täytyy pystyä valvomaan, 5) lateraaliset vaikutukset – hyvällä ohjauskeinolla on positiivisia seurannaisvaikutuksia muutoinkin kuin vain ohjauskeinon ensisijaisten tavoitteiden saavuttaminen, 6) kannustin ja uuden luominen – hyvä ohjauskeino kannustaa kokeilemaan uusia ratkaisuja ja kehittämään toimintaa. Meriturvallisuutta koskevaa sääntelyä on paljon ja yleisesti ottaen merionnettomuuksien lukumäärä on ollut laskeva viime vuosikymmenien aikana. Suuri osa sääntelystä on ollut tehokasta ja parantanut turvallisuuden tasoa maailman merillä. Silti merionnettomuuksia ja muita vaarallisia tapahtumia sattuu edelleen. Nykyistä sääntelyjärjestelmää voidaan kritisoida monen asian suhteen. Kansainvälisen sääntelyn aikaansaaminen ei ole helppoa: prosessi on yleensä hidas ja tuloksena voi olla kompromissien kompromissi. Kansainvälinen sääntely on yleensä reaktiivista eli ongelmakohtiin puututaan vasta kun jokin onnettomuus tapahtuu sen sijaan että se olisi proaktiivista ja pyrkisi puuttumaan ongelmakohtiin jo ennen kuin jotain tapahtuu. IMO:n työskentely perustuu kansallisvaltioiden osallistumiseen ja sääntelyn toimeenpano tapahtuu lippuvaltioiden toimesta. Kansallisvaltiot ajavat IMO:ssa pääasiallisesti omia intressejään ja sääntelyn toimeenpanossa on suuria eroja lippuvaltioiden välillä. IMO:n kyvyttömyys puuttua havaittuihin ongelmiin nopeasti ja ottaa sääntelyssä huomioon paikallisia olosuhteita on johtanut siihen, että esimerkiksi Euroopan Unioni on alkanut itse säädellä meriturvallisuutta ja että on olemassa sellaisia alueellisia erityisjärjestelyjä kuin PSSA (particularly sensitive sea area – erityisen herkkä merialue). Merenkulkualalla toimii monenlaisia yrityksiä: toisaalta yrityksiä, jotka pyrkivät toimimaan turvallisesti ja kehittämään turvallisuutta vielä korkeammalle tasolle, ja toisaalta yrityksiä, jotka toimivat niin halvalla kuin mahdollista, eivät välitä turvallisuusseikoista, ja joilla usein on monimutkaiset ja epämääräiset omistusolosuhteet ja joita vahingon sattuessa on vaikea saada vastuuseen. Ongelma on, että kansainvälisellä merenkulkualalla kaikkien yritysten on toimittava samoilla markkinoilla. Vastuuttomien yritysten toiminnan mahdollistavat laivaajat ja muut alan toimijat, jotka suostuvat tekemään yhteistyötä niiden kanssa. Välinpitämätön suhtautuminen turvallisuuteen johtuu osaksi myös merenkulun vanhoillisesta turvallisuuskulttuurista. Verrattaessa meriturvallisuuden sääntelyjärjestelmää kokonaisuutena tehokkaiden ohjauskeinoihin kriteereihin, voidaan todeta, että monien kriteerien osalta nykyistä järjestelmää voidaan pitää tehokkaana ja onnistuneena. Suurimmat ongelmat lienevät sääntelyn toimeenpanossa ja ohjauskeinojen kustannustehokkuudessa. Lippuvaltioiden toimeenpanoon perustuva järjestelmä ei toimi toivotulla tavalla, josta mukavuuslippujen olemassa olo on selvin merkki. Ohjauskeinojen, sekä yksittäisten ohjauskeinojen että vertailtaessa eri ohjauskeinoja keskenään, kustannustehokkuutta on usein vaikea arvioida, minkä seurauksena ohjauskeinojen kustannustehokkuudesta ei ole saatavissa luotettavaa tietoa ja tuloksena voi olla, että ohjauskeino on käytännössä pienen riskin eliminoimista korkealla kustannuksella. Kansainvälisen tason meriturvallisuus- (ja merenkulku-) politiikan menettelytavoiksi on ehdotettu myös muita vaihtoehtoja kuin nykyinen järjestelmä, esimerkiksi monitasoista tai polysentristä hallintojärjestelmää. Monitasoisella hallintojärjestelmällä tarkoitetaan järjestelmää, jossa keskushallinto on hajautettu sekä vertikaalisesti alueellisille tasoille että horisontaalisesti ei-valtiollisille toimijoille. Polysentrinen hallintojärjestelmä menee vielä askeleen pidemmälle. Polysentrinen hallintojärjestelmä on hallintotapa, jonka puitteissa kaikentyyppiset toimijat, sekä yksityiset että julkiset, voivat osallistua hallintoon, siis esimerkiksi hallitukset, edunvalvontajärjestöt, kaupalliset yritykset jne. Kansainvälinen lainsäädäntö määrittelee yleiset tasot, mutta konkreettiset toimenpiteet voidaan päättää paikallisella tasolla eri toimijoiden välisessä yhteistyössä. Tämän tyyppisissä hallintojärjestelmissä merenkulkualan todellinen, kansainvälinen mutta toisaalta paikallinen, toimintaympäristö tulisi otetuksi paremmin huomioon kuin järjestelmässä, joka perustuu kansallisvaltioiden keskenään yhteistyössä tekemään sääntelyyn. Tällainen muutos meriturvallisuuden hallinnassa vaatisi kuitenkin suurta periaatteellista suunnanmuutosta, jollaisen toteutumista ei voi pitää kovin todennäköisenä ainakaan lyhyellä tähtäimellä.

Training system for conceptual design and evaluation for wastewater treatment

Rising population, rapid urbanisation and growing industrialisation have severely stressed water quality and its availability in Malawi. In addition, financial and institutional problems and the expanding agro industry have aggravated this problem. The situation is worsened by depleting water resources and pollution from untreated sewage and industrial effluent. The increasing scarcity of clean water calls for the need for appropriate management of available water resources. There is also demand for a training system for conceptual design and evaluation for wastewater treatment in order to build the capacity for technical service providers and environmental practitioners in the country. It is predicted that Malawi will face a water stress situation by 2025. In the city of Blantyre, this situation is aggravated by the serious pollution threat from the grossly inadequate sewage treatment capacity. This capacity is only 23.5% of the wastewater being generated presently. In addition, limited or non-existent industrial effluent treatment has contributed to the severe water quality degradation. This situation poses a threat to the ecologically fragile and sensitive receiving water courses within the city. This water is used for domestic purposes further downstream. This manuscript outlines the legal and policy framework for wastewater treatment in Malawi. The manuscript also evaluates the existing wastewater treatment systems in Blantyre. This evaluation aims at determining if the effluent levels at the municipal plants conform to existing standards and guidelines and other associated policy and regulatory frameworks. The raw material at all the three municipal plants is sewage. The typical wastewater parameters are Biochemical Oxygen Demand (BOD5), Chemical Oxygen Demand (COD), and Total Suspended Solids (TSS). The treatment target is BOD5, COD, and TSS reduction. Typical wastewater parameters at the wastewater treatment plant at MDW&S textile and garments factory are BOD5 and COD. The treatment target is to reduce BOD5 and COD. The manuscript further evaluates a design approach of the three municipal wastewater treatment plants in the city and the wastewater treatment plant at Mapeto David Whitehead & Sons (MDW&S) textile and garments factory. This evaluation utilises case-based design and case-based reasoning principles in the ED-WAVE tool to determine if there is potential for the tool in Blantyre. The manuscript finally evaluates the technology selection process for appropriate wastewater treatment systems for the city of Blantyre. The criteria for selection of appropriate wastewater treatment systems are discussed. Decision support tools and the decision tree making process for technology selection are also discussed. Based on the treatment targets and design criteria at the eight cases evaluated in this manuscript in reference to similar cases in the ED-WAVE tool, this work confirms the practical use of case-based design and case-based reasoning principles in the ED-WAVE tool in the design and evaluation of wastewater treatment 6 systems in sub-Sahara Africa, using Blantyre, Malawi, as the case study area. After encountering a new situation, already collected decision scenarios (cases) are invoked and modified in order to arrive at a particular design alternative. What is necessary, however, is to appropriately modify the case arrived at through the Case Study Manager in order to come up with a design appropriate to the local situation taking into account technical, socio-economic and environmental aspects. This work provides a training system for conceptual design and evaluation for wastewater treatment.

Fraud detection in the banking sector : a multi-agent approach

Fraud is an increasing phenomenon as shown in many surveys carried out by leading international consulting companies in the last years. Despite the evolution of electronic payments and hacking techniques there is still a strong human component in fraud schemes. Conflict of interest in particular is the main contributing factor to the success of internal fraud. In such cases anomaly detection tools are not always the best instruments, since the fraud schemes are based on faking documents in a context dominated by lack of controls, and the perpetrators are those ones who should control possible irregularities. In the banking sector audit team experts can count only on their experience, whistle blowing and the reports sent by their inspectors. The Fraud Interactive Decision Expert System (FIDES), which is the core of this research, is a multi-agent system built to support auditors in evaluating suspicious behaviours and to speed up the evaluation process in order to detect or prevent fraud schemes. The system combines Think-map, Delphi method and Attack trees and it has been built around audit team experts and their needs. The output of FIDES is an attack tree, a tree-based diagram to ”systematically categorize the different ways in which a system can be attacked”. Once the attack tree is built, auditors can choose the path they perceive as more suitable and decide whether or not to start the investigation. The system is meant for use in the future to retrieve old cases in order to match them with new ones and find similarities. The retrieving features of the system will be useful to simplify the risk management phase, since similar countermeasures adopted for past cases might be useful for present ones. Even though FIDES has been built with the banking sector in mind, it can be applied in all those organisations, like insurance companies or public organizations, where anti-fraud activity is based on a central anti-fraud unit and a reporting system.

Evaluation of outpatient discharge in patients with cutaneous melanoma

OBJECTIVE: to evaluate discharge in a group of patients with cutaneous melanoma according to recently established criteria. METHODS: we conducted an observational, cross-sectional study with 32 patients at the Hospital Universitário Clementino Fraga Filho (HUCFF) / Universidade Federal do Rio de Janeiro (UFRJ), between 1995 and 2013, in the following stages: IA (17 cases, 53.12%), IB (4 cases, 12.5%), IIA (3 cases, 9.37%), IIC (1 case, 3.12%), IIIB (1 case, 3.12%), IIIC (3 cases, 9.37%), melanomas in situ (2 cases, 6.25%), Tx (1 case, 3.12%). RESULTS: the follow-up time varied from one to 20 years (stage IA), five to 15 years (stage IB), six to 17 years (stage IIA), 20 years (stage IIC), 23 years (stage IIIB) and 14 to 18 years (stage IIIC). One melanoma in situ (subungueal) was discharged in the fourth year of follow-up and the other was promptly discharged. The Tx melanoma was followed for 12 years. We observed no relapses or recurrences in the period. CONCLUSION: although a controversial issue, it was possible to endorse the discharge of the patients since our follow-up time had already exceeded the one recommended by the other authors.

Evaluation of common mental disorders in women with polycystic ovary syndrome and its relationship with body mass index

PURPOSE: To evaluate the prevalence of common mental disorders in women diagnosed with polycystic ovary syndrome as compared with paired controls without this syndrome. METHODS: Cross-sectional study with a Control Group examining women between the ages of 18 and 30 who did not use antidepressants and who sought the Gynecology Service of the researched sites. For every woman diagnosed with the polycystic ovary syndrome, another with the same age, educational status and presence or absence of sexual partners was sought without this diagnosis. In total, 166 patients agreed to participate, consisting of 95 diagnosed with polycystic ovary syndrome and 71 in the Control Group. The diagnosis of polycystic ovary syndrome was made by the presence of two from three criteria: oligomenorrhea or amenorrhea, clinical or biochemical hyperandrogenism and polycystic ovaries on transvaginal ultrasound, following exclusion of patients with Cushing's syndrome, congenital adrenal hyperplasia, and androgen-secreting tumors. Weight and height were measured to calculate the body mass index. The Self-Reporting Questionnaire, which evaluated 20 items, was used as an indicator of common mental disorders. A χ² analysis stratified by the category of body mass index was used to compare the prevalence of common mental disorders, between the groups of women with and without the polycystic ovary syndrome. RESULTS: There were no significant differences in age, education, presence of sexual partners, ethnicity, socioeconomic status, use of psychiatric medication, and search for consultation in mental health between the studied groups. The prevalence of obese women with indications of common mental disorders was significantly higher in women with polycystic ovary syndrome than in the Control Group. In the group with healthy body mass index, the incidence of common mental disorders was statistically significant different between women with polycystic ovary syndrome and normal controls (p=0.008). CONCLUSIONS: Women with diagnosis of this disease have an almost three-fold increased likelihood of common mental disorders as compared with those without polycystic ovary syndrome. Although obesity is often observed in polycystic ovary syndrome, even women with a healthy body mass index have an increased risk of psychiatric comorbidity.

Anatomical and functional characteristics of the pelvic floor in nulliparous women submitted to three-dimensional endovaginal ultrasonography: case control study and evaluation of interobserver agreement

PURPOSE: To determine anatomical and functional pelvic floor measurements performed with three-dimensional (3-D) endovaginal ultrasonography in asymptomatic nulliparous women without dysfunctions detected in previous dynamic 3-D anorectal ultrasonography (echo defecography) and to demonstrate the interobserver reliability of these measurements. METHODS: Asymptomatic nulliparous volunteers were submitted to echo defecography to identify dynamic dysfunctions, including anatomical (rectocele, intussusceptions, entero/sigmoidocele and perineal descent) and functional changes (non-relaxation or paradoxical contraction of the puborectalis muscle) in the posterior compartment and assessed with regard to the biometric index of levator hiatus, pubovisceral muscle thickness, urethral length, anorectal angle, anorectal junction position and bladder neck position with the 3-D endovaginal ultrasonography. All measurements were compared at rest and during the Valsalva maneuver, and perineal and bladder neck descent was determined. The level of interobserver agreement was evaluated for all measurements. RESULTS: A total of 34 volunteers were assessed by echo defecography and by 3-D endovaginal ultrasonography. Out of these, 20 subjects met the inclusion criteria. The 14 excluded subjects were found to have posterior dynamic dysfunctions. During the Valsalva maneuver, the hiatal area was significantly larger, the urethra was significantly shorter and the anorectal angle was greater. Measurements at rest and during the Valsalva maneuver differed significantly with regard to anorectal junction and bladder neck position. The mean values for normal perineal descent and bladder neck descent were 0.6 cm and 0.5 cm above the symphysis pubis, respectively. The intraclass correlation coefficient ranged from 0.62-0.93. CONCLUSIONS: Functional biometric indexes, normal perineal descent and bladder neck descent values were determined for young asymptomatic nulliparous women with the 3-D endovaginal ultrasonography. The method was found to be reliable to measure pelvic floor structures at rest and during Valsalva, and might therefore be suitable for identifying dysfunctions in symptomatic patients.

Development of porous glass-fiber reinforced composite for bone implants. Evaluation of antimicrobial effect and implant fixation

Cranial bone reconstructions are necessary for correcting large skull bone defects due to trauma, tumors, infections and craniotomies. Traditional synthetic implant materials include solid or mesh titanium, various plastics and ceramics. Recently, biostable glass-fiber reinforced composites (FRC), which are based on bifunctional methacrylate resin, were introduced as novel implant solution. FRCs were originally developed and clinically used in dental applications. As a result of further in vitro and in vivo testing, these composites were also approved for clinical use in cranial surgery. To date, reconstructions of large bone defects were performed in 35 patients. This thesis is dedicated to the development of a novel FRC-based implant for cranial reconstructions. The proposed multi-component implant consists of three main parts: (i) porous FRC structure; (ii) bioactive glass granules embedded between FRC layers and (iii) a silver-polysaccharide nanocomposite coating. The porosity of the FRC structure should allow bone ingrowth. Bioactive glass as an osteopromotive material is expected to stimulate the formation of new bone. The polysaccharide coating is expected to prevent bacterial colonization of the implant. The FRC implants developed in this study are based on the porous network of randomly-oriented E-glass fibers bound together by non-resorbable photopolymerizable methacrylate resin. These structures had a total porosity of 10–70 volume %, of which > 70% were open pores. The pore sizes > 100 μm were in the biologically-relevant range (50-400 μm), which is essential for vascularization and bone ingrowth. Bone ingrowth into these structures was simulated by imbedding of porous FRC specimens in gypsum. Results of push-out tests indicated the increase in the shear strength and fracture toughness of the interface with the increase in the total porosity of FRC specimens. The osteopromotive effect of bioactive glass is based on its dissolution in the physiological environment. Here, calcium and phosphate ions, released from the glass, precipitated on the glass surface and its proximity (the FRC) and formed bone-like apatite. The biomineralization of the FRC structure, due to the bioactive glass reactions, was studied in Simulated Body Fluid (SBF) in static and dynamic conditions. An antimicrobial, non-cytotoxic polysaccharide coating, containing silver nanoparticles, was obtained through strong electrostatic interactions with the surface of FRC. In in vitro conditions the lactose-modified chitosan (chitlac) coating showed no signs of degradation within seven days of exposure to lysozyme or one day to hydrogen peroxide (H2O2). The antimicrobial efficacy of the coating was tested against Staphylococcus aureus and Pseudomonas aeruginosa. The contact-active coating had an excellent short time antimicrobial effect. The coating neither affected the initial adhesion of microorganisms to the implant surface nor the biofilm formation after 24 h and 72 h of incubation. Silver ions released to the aqueous environment led to a reduction of bacterial growth in the culture medium.

Advanced analysis and design methods for preparative chromatographic separation processes

Preparative liquid chromatography is one of the most selective separation techniques in the fine chemical, pharmaceutical, and food industries. Several process concepts have been developed and applied for improving the performance of classical batch chromatography. The most powerful approaches include various single-column recycling schemes, counter-current and cross-current multi-column setups, and hybrid processes where chromatography is coupled with other unit operations such as crystallization, chemical reactor, and/or solvent removal unit. To fully utilize the potential of stand-alone and integrated chromatographic processes, efficient methods for selecting the best process alternative as well as optimal operating conditions are needed. In this thesis, a unified method is developed for analysis and design of the following singlecolumn fixed bed processes and corresponding cross-current schemes: (1) batch chromatography, (2) batch chromatography with an integrated solvent removal unit, (3) mixed-recycle steady state recycling chromatography (SSR), and (4) mixed-recycle steady state recycling chromatography with solvent removal from fresh feed, recycle fraction, or column feed (SSR–SR). The method is based on the equilibrium theory of chromatography with an assumption of negligible mass transfer resistance and axial dispersion. The design criteria are given in general, dimensionless form that is formally analogous to that applied widely in the so called triangle theory of counter-current multi-column chromatography. Analytical design equations are derived for binary systems that follow competitive Langmuir adsorption isotherm model. For this purpose, the existing analytic solution of the ideal model of chromatography for binary Langmuir mixtures is completed by deriving missing explicit equations for the height and location of the pure first component shock in the case of a small feed pulse. It is thus shown that the entire chromatographic cycle at the column outlet can be expressed in closed-form. The developed design method allows predicting the feasible range of operating parameters that lead to desired product purities. It can be applied for the calculation of first estimates of optimal operating conditions, the analysis of process robustness, and the early-stage evaluation of different process alternatives. The design method is utilized to analyse the possibility to enhance the performance of conventional SSR chromatography by integrating it with a solvent removal unit. It is shown that the amount of fresh feed processed during a chromatographic cycle and thus the productivity of SSR process can be improved by removing solvent. The maximum solvent removal capacity depends on the location of the solvent removal unit and the physical solvent removal constraints, such as solubility, viscosity, and/or osmotic pressure limits. Usually, the most flexible option is to remove solvent from the column feed. Applicability of the equilibrium design for real, non-ideal separation problems is evaluated by means of numerical simulations. Due to assumption of infinite column efficiency, the developed design method is most applicable for high performance systems where thermodynamic effects are predominant, while significant deviations are observed under highly non-ideal conditions. The findings based on the equilibrium theory are applied to develop a shortcut approach for the design of chromatographic separation processes under strongly non-ideal conditions with significant dispersive effects. The method is based on a simple procedure applied to a single conventional chromatogram. Applicability of the approach for the design of batch and counter-current simulated moving bed processes is evaluated with case studies. It is shown that the shortcut approach works the better the higher the column efficiency and the lower the purity constraints are.

Developing usability evaluation heuristics for augmented reality applications

There is no generic usability heuristics for Augmented Reality (AR) applications, thus, the aim of this thesis was to develop one. The development of the heuristics was carried out in phases. Based on a literature review, a preliminary version of the heuristics was developed, which was evaluated by four experts. As a result, six evaluation criteria were formed: 1) interaction methods and controls, 2) presentation of virtual objects, 3) relationship between virtual objects and real world, 4) information related to virtual objects, 5) suitability for the usage context and 6) physical comfort of use. The heuristics should be used with Nielsen's (1995) generic usability evaluation heuristics. The heuristics are not ready to be used as such, since it must still be tested in practice.

Translation into Brazilian Portuguese, cultural adaptation and evaluation of the reliability of the Disabilities of the Arm, Shoulder and Hand Questionnaire

The objective of the present study was to translate, adapt and validate a Brazilian Portuguese version of the Disabilities of the Arm, Shoulder and Hand (DASH) Questionnaire. The study was carried out in two steps. The first was to translate the DASH into Portuguese and to perform cultural adaptation and the second involved the determination of the reliability and validity of the DASH for the Brazilian population. For this purpose, 65 rheumatoid arthritis patients of either sex (according to the classification criteria of the American College of Rheumatology), ranging in age from 18 to 60 years and presenting no other diseases involving the upper limbs, were interviewed. The patients were selected consecutively at the rheumatology outpatient clinic of UNIFESP. The following results were obtained: in the first step (translation and cultural adaptation), all patients answered the questions. In the second step, Spearman's correlation coefficients for interobserver evaluation ranged from 0.762 to 0.995, values considered to be highly reliable. In addition, intraclass correlation coefficients ranged from 0.97 to 0.99, also highly reliable values. Spearman's correlation coefficients and the intraclass correlation coefficients obtained during intra-observer evaluation ranged from 0.731 to 0.937 and from 0.90 to 0.96, respectively, being highly reliable values. The Ritchie Index showed a weak correlation with Brazilian DASH scores, while the visual analog scale of pain showed a good correlation with DASH score. We conclude that the Portuguese version of the DASH is a reliable instrument.