Development, implementation, and evaluation of the Apollo model of pediatric rehabilitation service delivery

This article presents the experience of a rehabilitation program that un- dertook the challenge to reorganize its services to address accessibility issues and im- prove service quality. The context in which the reorganization process occurred, along with the relevant literature justifying the need for a new service delivery model, and an historical perspective on the planning; implementation; and evaluation phases of the process are described. In the planning phase, the constitution of the working committee, the data collected, and the information found in the literature are presented. Apollo, the new service delivery model, is then described along with each of its components (e.g., community, group, and individual interventions). Actions and lessons learnt during the implementation of each component are presented. We hope by sharing our experiences that we can help others make informed decisions about service reorganization to im- prove the quality of services provided to children with disabilities, their families, and their communities.

Evaluation of dynamic pass-through of carbon prices into electricity prices – a cointegrated VECM analysis

This paper addresses the impact of the CO2 opportunity cost on the wholesale electricity price in the context of the Iberian electricity market (MIBEL), namely on the Portuguese system, for the period corresponding to the Phase II of the European Union Emission Trading Scheme (EU ETS). In the econometric analysis a vector error correction model (VECM) is specified to estimate both long–run equilibrium relations and short–run interactions between the electricity price and the fuel (natural gas and coal) and carbon prices. The model is estimated using daily spot market prices and the four commodities prices are jointly modelled as endogenous variables. Moreover, a set of exogenous variables is incorporated in order to account for the electricity demand conditions (temperature) and the electricity generation mix (quantity of electricity traded according the technology used). The outcomes for the Portuguese electricity system suggest that the dynamic pass–through of carbon prices into electricity prices is strongly significant and a long–run elasticity was estimated (equilibrium relation) that is aligned with studies that have been conducted for other markets.

Enantiomeric fraction evaluation of pharmaceuticals in environmentalmatrices by liquid chromatography-tandem mass spectrometry

The interest for environmental fate assessment of chiral pharmaceuticals is increasing and enantioselective analytical methods are mandatory. This study presents an enantioselective analytical method for the quantification of seven pairs of enantiomers of pharmaceuticals and a pair of a metabolite. The selected chiral pharmaceuticals belong to three different therapeutic classes, namely selective serotonin reuptake inhibitors (venlafaxine, fluoxetine and its metabolite norfluoxetine), beta-blockers (alprenolol, bisoprolol, metoprolol, propranolol) and a beta2-adrenergic agonist (salbutamol). The analytical method was based on solid phase extraction followed by liquid chromatography tandem mass spectrometry with a triple quadrupole analyser. Briefly, Oasis® MCX cartridges were used to preconcentrate 250 mL of water samples and the reconstituted extracts were analysed with a Chirobiotic™ V under reversed mode. The effluent of a laboratory-scale aerobic granular sludge sequencing batch reactor (AGS-SBR) was used to validate the method. Linearity (r2 > 0.99), selectivity and sensitivity were achieved in the range of 20–400 ng L−1 for all enantiomers, except for norfluoxetine enantiomers which range covered 30–400 ng L−1. The method detection limits were between 0.65 and 11.5 ng L−1 and the method quantification limits were between 1.98 and 19.7 ng L−1. The identity of all enantiomers was confirmed using two MS/MS transitions and its ion ratios, according to European Commission Decision 2002/657/EC. This method was successfully applied to evaluate effluents of wastewater treatment plants (WWTP) in Portugal. Venlafaxine and fluoxetine were quantified as non-racemic mixtures (enantiomeric fraction ≠ 0.5). The enantioselective validated method was able to monitor chiral pharmaceuticals in WWTP effluents and has potential to assess the enantioselective biodegradation in bioreactors. Further application in environmental matrices as surface and estuarine waters can be exploited.

Evaluation of antihypertensive drugs in patients with obstructive sleep apnea and in rats submitted to chronic intermittent hypoxia

RESUMO: A hipertensão arterial (HA) é uma patologia altamente prevalente, embora claramente subdiagnosticada, em doentes com síndrome de apneia obstrutiva do sono (SAOS). Estas duas patologias apresentam uma estreita relação e a monitorização ambulatória da pressão arterial (MAPA), por um período de 24 horas, parece ser o método mais preciso para o diagnóstico de hipertensão em doentes com SAOS. No entanto, esta ferramenta de diagnóstico para além de ser dispendiosa e envolver um número acrescido de meios técnicos e humanos, é mais morosa e, por conseguinte, não é utilizada por rotina no contexto do diagnóstico da SAOS. Por outro lado, apesar da aplicação de pressão positiva contínua nas vias aéreas (CPAP – Continous Positive Airway Pressure) ser considerada a terapêutica de eleição para os doentes com SAOS, o seu efeito no abaixamento da pressão arterial (PA) parece ser modesto, exigindo, por conseguinte, a implementação concomitante de terapêutica anti-hipertensora. Acontece que são escassos os dados relativos aos regimes de fármacos anti-hipertensores utilizados em doentes com SAOS e, acresce ainda que, as guidelines terapêuticas para o tratamento farmacológico da HA, neste grupo particular de doentes, permanecem, até ao momento, inexistentes. A utilização de modelos animais de hipóxia crónica intermitente (CIH), que mimetizam a HA observada em doentes com SAOS, revela-se extremamente importante, uma vez que se torna imperativo identificar fármacos que promovam um controle adequado da PA neste grupo de doentes. No entanto, estudos concebidos com o intuito de investigar o efeito anti-hipertensor dos fármacos neste modelo animal revelam-se insuficientes e, por outro lado, os escassos estudos que testaram fármacos anti-hipertensores neste modelo não foram desenhados para responder a questões de natureza farmacológica. Acresce ainda que se torna imprescindível garantir a escolha de um método para administração destes fármacos que seja não invasivo e que minimize o stress do animal. Embora a gavagem seja uma técnica indiscutivelmente eficaz e amplamente utilizada para a administração diária de fármacos a animais de laboratório, ela compreende uma sequência de procedimentos geradores de stress para os animais e, que podem por conseguinte, constituir um viés na interpretação dos resultados obtidos. O objectivo global da presente investigação translacional foi contribuir para a identificação de fármacos anti-hipertensores mais efectivos para o tratamento da HT nos indivíduos com SAOS e investigar mecanismos subjacentes aos efeitos sistémicos associadas à SAOS bem como a sua modulação por fármacos anti-hipertensores. Os objectivos específicos foram: em primeiro lugar,encontrar novos critérios, baseados nas medidas antropométricas, que permitam a identificação de doentes com suspeita de SAOS, que erroneamente se auto-classifiquem como nãohipertensos, e desta forma promover um uso mais criterioso do MAPA; em segundo lugar, investigar a existência de uma hipotética associação entre os esquemas de fármacos antihipertensores e o controle da PA (antes e após a adaptação de CPAP) em doentes com SAOS em terceiro lugar, avaliar a eficácia do carvedilol (CVD), um fármaco bloqueador β-adrenérgico não selectivo com actividade antagonista α1 intrínseca e propriedades anti-oxidantes num modelo animal de hipertensão induzida pela CIH; em quarto lugar, explorar os efeitos da CIH sobre o perfil farmacocinético do CVD; e, em quinto lugar, investigar um método alternativo à gavagem para a administração crónica de fármacos anti-hipertensores a animais de laboratório. Com este intuito, na primeira fase deste projecto, fizemos uso de uma amostra com um número apreciável de doentes com SAOS (n=369), que acorreram, pela primeira vez, à consulta de Patologia do Sono do CHLN e que foram submetidos a um estudo polissonográfico do sono, à MAPA e que preencheram um questionário que contemplava a obtenção de informação relativa ao perfil da medicação anti-hipertensora em curso. Numa segunda fase, utilizámos um modelo experimental de HT no rato induzida por um paradigma de CIH. Do nosso trabalho resultaram os seguintes resultados principais: em primeiro lugar, o índice de massa corporal (IMC) e o perímetro do pescoço (PP) foram identificados como preditores independentes de “auto-classificação errónea” da HA em doentes com suspeita de SAOS; em segundo lugar, não encontramos qualquer associação com significado estatístico entre os vários esquemas de fármacos anti-hipertensores bem como o número de fármacos incluídos nesse esquemas, e o controle da PA (antes e depois da adaptação do CPAP); em terceiro lugar, apesar das doses de 10, 30 e 50 mg/kg de carvedilol terem promovido uma redução significativa da frequência cardíaca, não foi observado qualquer decréscimo na PA no nosso modelo animal; em quarto lugar, as razões S/(R+S) dos enantiómeros do CVD nos animais expostos à CIH e a condições de normóxia revelaram-se diferentes; e, em quinto lugar, a administração oral voluntária mostrou ser um método eficaz para a administração diária controlada de fármacos anti-hipertensores e que é independente da manipulação e contenção do animal. Em conclusão, os resultados obtidos através do estudo clínico revelaram que o controle da PA, antes e após a adaptação do CPAP, em doentes com SAOS é independente, quer do esquema de fármacos anti-hipertensores, quer do número de fármacos incluídos num determinado esquema. Os nossos resultados salientam ainda a falta de validade da chamada self-reported hypertension e sugerem que em todos os doentes com suspeita de SAOS, com HA não diagnosticada e com um IMC e um PP acima de 27 kg/m2 e 39 cm, respectivamente, a confirmação do diagnóstico de HA deverá ser realizada através da MAPA, ao invés de outros métodos que com maior frequência são utilizados com este propósito. Os resultados obtidos no modelo animal de HA induzida pela CIH sugerem que o bloqueio do sistema nervoso simpático, juntamente com os supostos efeitos pleiotrópicos do CVD, não parece ser a estratégia mais adequada para reverter este tipo particular de hipertensão e indicam que as alterações farmacocinéticas induzidas pela CIH no ratio S/(R+S) não justificam a falta de eficácia anti-hipertensora do CVD observada neste modelo animal. Por último, os resultados do presente trabalho suportam ainda a viabilidade da utilização da administração oral voluntária, em alternativa à gavagem, para a administração crónica de uma dose fixa de fármacos anti-hipertensores.---------------------------- ABSTRACT: Hypertension (HT) is a highly prevalent condition, although under diagnosed, in patients with obstructive sleep apnea (OSA). These conditions are closely related and 24-hour ambulatory blood pressure monitoring (ABPM) seems to be the most accurate measurement for diagnosing hypertension in OSA. However, this diagnostic tool is expensive and time-consuming and, therefore, not routinely used. On the other hand, although continuous positive airway pressure (CPAP) is considered the gold standard treatment for symptomatic OSA, its lowering effect on blood pressure (BP) seems to be modest and, therefore, concomitant antihypertensive therapy is still required. Data on antihypertensive drug regimens in patients with OSA are scarce and specific therapeutic guidelines for the pharmacological treatment of hypertension in these patients remain absent. The use of animal models of CIH, which mimic the HT observed in patients with OSA, is extremely important since it is imperative to identify preferred compounds for an adequate BP control in this group of patients. However, studies aimed at investigating the antihypertensive effect of antihypertensive drugs in this animal model are insufficient, and most reports on CIH animal models in which drugs have been tested were not designed to respond to pharmacological issues. Moreover, when testing antihypertensive drugs (AHDs) it becomes crucial to ensure the selection of a non-invasive and stress-free method for drug delivery. Although gavage is effective and a widely performed technique for daily dosing in laboratory rodents, it comprises a sequence of potentially stressful procedures for laboratory animals that may constitute bias for the experimental results. The overall goal of the present translational research was to contribute to identify more effective AHDs for the treatment of hypertension in patients with OSA and investigate underlying mechanisms of systemic effects associated with OSA, as well as its modulation by AHDs. The specific aims were: first, to find new predictors based on anthropometric measures to identify patients that misclassify themselves as non-hypertensive, and thereby promote the selective use of ABPM; second, to investigate a hypothetical association between ongoing antihypertensive regimens and BP control rates in patients with OSA, before and after CPAP adaptation; third, to determine, in a rat model of CIH-induced hypertension, the efficacy of carvedilol (CVD), a nonselective beta-blocker with intrinsic anti-α1-adrenergic activity and antioxidant properties; fourth, to explore the effects of CIH on the pharmacokinetics profile of CVD and fifth, to investigate an alternative method to gavage, for chronic administration of AHDs to laboratory rats. For that, in the first phase of this project, we used a sizeable sample of patients with OSA (n=369), that attended a first visit at Centro Hospitalar Lisboa Norte, EPE Sleep Unit, and underwent overnight polysomnography, 24-h ABPM and filled a questionnaire that included ongoing antihypertensive medication profile registration. In the second phase, a rat experimental model of HT induced by a paradigm of CIH that simulates OSA was used. The main findings of this work were: first, body mass index (BMI) and neck circumference (NC) were identified as independent predictors of hypertension misclassification in patients suspected of OSA; second, in patients with OSA, BP control is independent of both the antihypertensive regimen and the number of antihypertensive drugs, either before or after CPAP adaptation; third, although the doses of 10, 30 and 50 mg/Kg of CVD promoted a significant reduction in heart rate, no decrease in mean arterial pressure was observed; fourth, the S/(R+S) ratios of CVD enantiomers, between rats exposed to CIH and normoxic conditions, were different and fifth, voluntary ingestion proved to be an effective method for a controlled daily dose administration, with a define timetable, that is independent of handling and restraint procedures. In conclusion, the clinical study showed that BP control in OSA patients is independent of both the antihypertensive regimen and the number of antihypertensive drugs. Additionally, our results highlight the lack of validity of self-reported hypertension and suggest that all patients suspected of OSA with undiagnosed hypertension and with a BMI and NC above 27 Kg/m2 and 39 cm should be screened for hypertension, through ABPM. The results attained in the rat model of HT related to CIH suggest that the blockade of the sympathetic nervous system together with the putative pleiotropic effects of carvedilol is not able to revert hypertension induced by CIH and point out that the pharmacokinetic changes induced by CIH on S/(R+S) ratio are not apparently responsible for the lack of efficacy of carvedilol in reversing this particular type of hypertension. Finally, the results here presented support the use of voluntary oral administration as a viable alternative to gavage for chronic administration of a fixed dose of AHDs.

Evaluation de la douleur chez les personnes cérébrolésées non-communicantes aux soins intensifs

La douleur est fréquente en milieu de soins intensifs et sa gestion est l'une des missions des infirmières. Son évaluation est une prémisse indispensable à son soulagement. Cependant lorsque le patient est incapable de signaler sa douleur, les infirmières doivent se baser sur des signes externes pour l'évaluer. Les guides de bonne pratique recommandent chez les personnes non communicantes l'usage d'un instrument validé pour la population donnée et basé sur l'observation des comportements. A l'heure actuelle, les instruments d'évaluation de la douleur disponibles ne sont que partiellement adaptés aux personnes cérébrolésées dans la mesure où ces personnes présentent des comportements qui leur sont spécifiques. C'est pourquoi, cette étude vise à identifier, décrire et valider des indicateurs, et des descripteurs, de la douleur chez les personnes cérébrolésées. Un devis d'étude mixte multiphase avec une dominante quantitative a été choisi pour cette étude. Une première phase consistait à identifier des indicateurs et des descripteurs de la douleur chez les personnes cérébrolésées non communicantes aux soins intensifs en combinant trois sources de données : une revue intégrative des écrits, une démarche consultative utilisant la technique du groupe nominal auprès de 18 cliniciens expérimentés (6 médecins et 12 infirmières) et les résultats d'une étude pilote observationnelle réalisée auprès de 10 traumatisés crâniens. Les résultats ont permis d'identifier 6 indicateurs et 47 descripteurs comportementaux, vocaux et physiologiques susceptibles d'être inclus dans un instrument d'évaluation de la douleur destiné aux personnes cérébrolésées non- communicantes aux soins intensifs. Une deuxième phase séquentielle vérifiait les propriétés psychométriques des indicateurs et des descripteurs préalablement identifiés. La validation de contenu a été testée auprès de 10 experts cliniques et 4 experts scientifiques à l'aide d'un questionnaire structuré qui cherchait à évaluer la pertinence et la clarté/compréhensibilité de chaque descripteur. Cette démarche a permis de sélectionner 33 des 47 descripteurs et valider 6 indicateurs. Dans un deuxième temps, les propriétés psychométriques de ces indicateurs et descripteurs ont été étudiés au repos, lors de stimulation non nociceptive et lors d'une stimulation nociceptive (la latéralisation du patient) auprès de 116 personnes cérébrolésées aux soins intensifs hospitalisées dans deux centres hospitaliers universitaires. Les résultats montrent d'importantes variations dans les descripteurs observés lors de stimulation nociceptive probablement dues à l'hétérogénéité des patients au niveau de leur état de conscience. Dix descripteurs ont été éliminés, car leur fréquence lors de la stimulation nociceptive était inférieure à 5% ou leur fiabilité insuffisante. Les descripteurs physiologiques ont tous été supprimés en raison de leur faible variabilité et d'une fiabilité inter juge problématique. Les résultats montrent que la validité concomitante, c'est-à-dire la corrélation entre l'auto- évaluation du patient et les mesures réalisées avec les descripteurs, est satisfaisante lors de stimulation nociceptive {rs=0,527, p=0,003, n=30). Par contre la validité convergente, qui vérifiait l'association entre l'évaluation de la douleur par l'infirmière en charge du patient et les mesures réalisés avec les descripteurs, ainsi que la validité divergente, qui vérifiait si les indicateurs discriminent entre la stimulation nociceptive et le repos, mettent en évidence des résultats variables en fonction de l'état de conscience des patients. Ces résultats soulignent la nécessité d'étudier les descripteurs de la douleur chez des patients cérébrolésés en fonction du niveau de conscience et de considérer l'hétérogénéité de cette population dans la conception d'un instrument d'évaluation de la douleur pour les personnes cérébrolésées non communicantes aux soins intensifs. - Pain is frequent in the intensive care unit (ICU) and its management is a major issue for nurses. The assessment of pain is a prerequisite for appropriate pain management. However, pain assessment is difficult when patients are unable to communicate about their experience and nurses have to base their evaluation on external signs. Clinical practice guidelines highlight the need to use behavioral scales that have been validated for nonverbal patients. Current behavioral pain tools for ICU patients unable to communicate may not be appropriate for nonverbal brain-injured ICU patients, as they demonstrate specific responses to pain. This study aimed to identify, describe and validate pain indicators and descriptors in brain-injured ICU patients. A mixed multiphase method design with a quantitative dominant was chosen for this study. The first phase aimed to identify indicators and descriptors of pain for nonverbal brain- injured ICU patients using data from three sources: an integrative literature review, a consultation using the nominal group technique with 18 experienced clinicians (12 nurses and 6 physicians) and the results of an observational pilot study with 10 traumatic brain injured patients. The results of this first phase identified 6 indicators and 47 behavioral, vocal and physiological descriptors of pain that could be included in a pain assessment tool for this population. The sequential phase two tested the psychometric properties of the list of previously identified indicators and descriptors. Content validity was tested with 10 clinical and 4 scientific experts for pertinence and comprehensibility using a structured questionnaire. This process resulted in 33 descriptors to be selected out of 47 previously identified, and six validated indicators. Then, the psychometric properties of the descriptors and indicators were tested at rest, during non nociceptive stimulation and nociceptive stimulation (turning) in a sample of 116 brain-injured ICLI patients who were hospitalized in two university centers. Results showed important variations in the descriptors observed during the nociceptive stimulation, probably due to the heterogeneity of patients' level of consciousness. Ten descriptors were excluded, as they were observed less than 5% of the time or their reliability was insufficient. All physiologic descriptors were deleted as they showed little variability and inter observer reliability was lacking. Concomitant validity, testing the association between patients' self report of pain and measures performed using the descriptors, was acceptable during nociceptive stimulation (rs=0,527, p=0,003, n=30). However, convergent validity ( testing for an association between the nurses' pain assessment and measures done with descriptors) and divergent validity (testing for the ability of the indicators to discriminate between rest and a nociceptive stimulation) varied according to the level of consciousness These results highlight the need to study pain descriptors in brain-injured patients with different level of consciousness and to take into account the heterogeneity of this population forthe conception of a pain assessment tool for nonverbal brain-injured ICU patients.

Safety and immunogenicity of the M72/AS01 candidate tuberculosis vaccine in HIV-infected adults on combination antiretroviral therapy: a phase I/II, randomized trial.

OBJECTIVE: Tuberculosis (TB) is highly prevalent among HIV-infected people, including those receiving combination antiretroviral therapy (cART), necessitating a well tolerated and efficacious TB vaccine for these populations. We evaluated the safety and immunogenicity of the candidate TB vaccine M72/AS01 in adults with well controlled HIV infection on cART. DESIGN: A randomized, observer-blind, controlled trial (NCT00707967). METHODS: HIV-infected adults on cART in Switzerland were randomized 3 : 1 : 1 to receive two doses, 1 month apart, of M72/AS01, AS01 or 0.9% physiological saline (N = 22, N = 8 and N = 7, respectively) and were followed up to 6 months postdose 2 (D210). Individuals with CD4⁺ cell counts below 200 cells/μl were excluded. Adverse events (AEs) including HIV-specific and laboratory safety parameters were recorded. Cell-mediated (ICS) and humoral (ELISA) responses were evaluated before vaccination, 1 month after each dose (D30, D60) and D210. RESULTS: Thirty-seven individuals [interquartile range (IQR) CD4⁺ cell counts at screening: 438-872 cells/μl; undetectable HIV-1 viremia] were enrolled; 73% of individuals reported previous BCG vaccination, 97.3% tested negative for the QuantiFERON-TB assay. For M72/AS01 recipients, no vaccine-related serious AEs or cART-regimen adjustments were recorded, and there were no clinically relevant effects on laboratory safety parameters, HIV-1 viral loads or CD4⁺ cell counts. M72/AS01 was immunogenic, inducing persistent and polyfunctional M72-specific CD4⁺ T-cell responses [medians 0.70% (IQR 0.37-1.07) at D60] and 0.42% (0.24-0.61) at D210, predominantly CD40L⁺IL-2⁺TNF-α⁺, CD40L⁺IL-2⁺ and CD40L⁺IL-2⁺TNF-α⁺IFN-γ⁺]. All M72/AS01 vaccines were seropositive for anti-M72 IgG after second vaccination until study end. CONCLUSION: M72/AS01 was clinically well tolerated and immunogenic in this population, supporting further clinical evaluation in HIV-infected individuals in TB-endemic settings.

Evaluation du dispositif d'urgences sociales EMUS

Le concept EMUS (équipe mobile d'urgences sociales) trouve son origine dans la réunion consacrée à l'urgence sociale qui s'est tenue en fin d'année 2009 et dans le rapport sur la création de l'équipe mobile d'urgence établi en été 2010 à la suite de cette réunion. Le Département de la santé et de l'action sociale (DSAS) a mandaté l'IUMSP pour effectuer une évaluation accompagnante du projet dans sa phase pilote pour: Accompagner le projet par des bilans intermédiaires dans le but d'effectuer des ajustements du projet ; Mesurer l'impact du projet ; Évaluer le dispositif en place ; Évaluer le fonctionnement du dispositif ; Évaluer ses interventions. Les résultats de cette évaluation sont présentés dans le présent rapport. Des résultats intermédiaires (quantitatifs et qualitatifs) ont également été présentés au comité de pilotage de l'évaluation sous forme orale (présentations PowerPoint suivies d'une discussion), et cela à deux reprises (septembre 2012 et juin 2013). Une synthèse de ces résultats intermédiaires peut être consultée à l'annexe 8.1

Evaluation of a new serological test for the detection of anti-Coxiella and anti-Rickettsia antibodies.

Coxiella burnetii and members of the genus Rickettsia are obligate intracellular bacteria. Since cultivation of these organisms requires dedicated techniques, their diagnosis usually relies on serological or molecular biology methods. Immunofluorescence is considered the gold standard to detect antibody-reactivity towards these organisms. Here, we assessed the performance of a new automated epifluorescence immunoassay (InoDiag) to detect IgM and IgG against C. burnetii, Rickettsia typhi and Rickettsia conorii. Samples were tested with the InoDiag assay. A total of 213 sera were tested, of which 63 samples from Q fever, 20 from spotted fever rickettsiosis, 6 from murine typhus and 124 controls. InoDiag results were compared to micro-immunofluorescence. For acute Q fever, the sensitivity of phase 2 IgG was only of 30% with a cutoff of 1 arbitrary unit (AU). In patients with acute Q fever with positive IF IgM, sensitivity reached 83% with the same cutoff. Sensitivity for chronic Q fever was 100% whereas sensitivity for past Q fever was 65%. Sensitivity for spotted Mediterranean fever and murine typhus were 91% and 100%, respectively. Both assays exhibited a good specificity in control groups, ranging from 79% in sera from patients with unrelated diseases or EBV positivity to 100% in sera from healthy patients. In conclusion, the InoDiag assay exhibits an excellent performance for the diagnosis of chronic Q fever but a very low IgG sensitivity for acute Q fever likely due to low reactivity of phase 2 antigens present on the glass slide. This defect is partially compensated by the detection of IgM. Because it exhibits a good negative predictive value, the InoDiag assay is valuable to rule out a chronic Q fever. For the diagnosis of rickettsial diseases, the sensitivity of the InoDiag method is similar to conventional immunofluorescence.

Set-up and evaluation of a mid-infrared reflectometer and investigation of the optical properties of doped tin telluride

A system comprised of a Bomem interferometer and a LT3-110 Heli-Tran cryostat was set up to measure the reflectance of materials in the mid-infrared spectral region. Several tests were conducted to ensure the consistency and reliability of the system. Silicon and Chromium, two materials with well known optical properties were measured to test the accuracy of the system, and the results were found to be in good agreement with the literature. Reflectance measurements on pure SnTe and several Pb and Mn-doped alloys were carried out. These materials were chosen because they exhibit a strong plasma edge in the mid infrared region. The optical conductivity and several related optical parameters were calculated from the measured reflectance. Very low temperature measurements were carried out in the far-infrared on Sn9SMn2Te, and the results are indicative of a spin glass phase at 0.8 K. Resistivity measurements were made at room temperature. The resistivity values were found, as expected, to decrease with increasing carrier concentration and to increase with increasing manganese concentration.

Laser Induced Photoacoustic Technique for the Detection of Phase Transitions in Liquid Crystals

In this paper we report the use of a laser induced phoroacoustic technique for the detection of multiple phase transitions in heptyl-oxy-cyanobiphenyl (70CB) and octyl-oxy-cyanobiphenyl (80CB) liquid crystals. The observed photoacoustic signal amplitude profile carries clear signatures of two tirst order transitions in 70CB and two tirst order and a second order transitions in 80CB. Analysis of the experimental data using Rosencwaig-Gersho theory shows that the sudden decrease in the photoacoustic (PA) signal amplitude during phase transitions is due to a sharp increase in the heat capacity of the samples near the transition temperatures.

Post Environmental Evaluation of the Rajjaprabha Dam in Thailand

This thesis Entitled Post-Environmental Evaluation of The Rajjaprabha Dam In Thailand. This post evaluation of environmental consequences of Rajjaprabha dam IS conducted ten years after its commencement. The Rajjaprabha dam project was planned and implemented as a multipurpose project, mainly for hydropower production, flood protection, fisheries, recreation and irrigation. The project includes the dam and reservoir with a 240 MW hydropower plant located about 90 km upstream from Surat Thani province, and irrigation systems covering the coastal plain in Surat Thani. The upstream storage reservoir (with about 5,639 mcm storage) and the hydropower plant had already been implemented. The first phase of irrigation system covers an area of 23,100 hectares. The second phase is envisaged to cover about 50,000 hectares. This study was conducted with the following objectives: (I) to assess all existing environmental resources and their values with the help of input-output analysis (2) to findout the beneficial impacts of the project (3) to evaluate the actual positive effects vis-a-vis the estimated effects before the project was implemented and (4) to identify all significant changes in relatives to the impacts previously assessed. The study area includes the Phum Duang river basin of about 4,668 km2 (placed on the areas that are upstream and downstream to the damsite), The duration of study is limited to 10 years after the dam has become operational i.e. from 1987-1997. The results of the study reveal that there is no significant changes in climatic and ground water resources, with respect to the study area inspte of the fact that the physical and chemical properties of the soil have slightly changed. Sedimentation in the reservoir does not have much effect on the function of the dam.

Weiterentwicklung der schulpraktischen Lehrerbildung durch Kooperation der Ersten und Zweiten Phase am Beispiel der Region Nordhessen

Die Kooperation zwischen den beiden Phasen der Lehrerbildung an Universität und Studienseminar und die Qualitätsssteigerung der schulpraktischen Ausbildung werden nicht nur im Hessischen Lehrerbildungsgesetz als eine der Möglichkeiten gesehen, die Ausbildungsqualität angehender Lehrer zu verbessern. Um die Bedingungen für die Intensivierung der Kooperation zwischen den beiden Phasen bestimmen zu können werden in einer Expertenbefragung (Studie 1) die Haltung und Erwartung von Vertretern der universitären Lehrerbildung, des Referendariats und der Bildungsadministration erhoben. Dabei werden die Schulpraktischen Studien als Beispiele für eine phasenübergreifende Kooperation herausgestellt. Die Untersuchung zeigt aber nicht nur geeignete Möglichkeit der Zusammenarbeit auf. Es werden auch Ursachen erforscht, welche Gründe die Kooperation hemmen oder behindern, wie etwa gegenseitige Vorbehalte, fehlende Verbindlichkeit oder institutionalisiertes Ungleichgewicht zwischen den beiden Phasen. Seit der Kritik u. a. von Terhart (2000) an der mangelnden Abstimmung zwischen Erster und Zweiter Phase der Lehrerbildung und der Klage von Oelkers (2000) über den fehlenden Nachweis, wie wirksam die Lehrerbildung ist, sind in den letzten Jahren Studien über die Erste und Zweite Phase der Lehrerbildung entstanden. In die Darstellung des Stand der Forschung zur schulpraktischen Lehrerausbildung werden zwei groß angelegte Untersuchungen (MT21 und COACTIV) einbezogen, deren Ergebnisse die Diskussion um die Wirksamkeit der (Mathematik-) Lehrerbildung und der Bedeutung des (mathematik-)fachdidaktischen Wissens in den letzten Jahren entscheidend geprägt haben. Darüber hinaus werden die Forschungen des Deutschen Instituts für internationale Bildungsforschung (DIPF) zum Referendariat und von Schubarth zur Lehrerausbildung in der Ersten und Zweiten Phase dargestellt. Zu den schulpraktischen Studien werden einschlägige Untersuchungen angeführt (wie die von Hascher oder von Bodensohn u.a.), die ergänzt bzw. kontrastiert werden durch die Ergebnisse kleinerer Evaluationen. Schließlich werden Studien zur Rolle der Mentoren herangezogen, die sich mit den Unterrichtsnachbesprechungen im Rahmen der Schulpraktika oder mit dem Mentorieren auseinandersetzen. In die Ergebnisse der Studie 1 (s.o.) und in den Forschungsstand lassen sich Kooperationsformen zwischen der Ersten und Zweiten Phase der Lehrerbildung einbetten, die in der schulpraktischen Ausbildung verwirklicht werden können. Mit dem Kooperationspraktikum haben Vertreter der Ersten und der Zweiten Phase der Lehrerausbildung gemeinsame eine Form gefunden, wie ohne strukturelle Veränderung und bei möglichst geringem zusätzlichen Aufwand im bestehenden Ausbildungsrahmen eine fünfwöchige Lernpartnerschaft zwischen Referendaren und Studierenden unter Verantwortung eines gemeinsamen Mentors realisiert werden kann. Die Evaluation dieses Kooperationspraktikums (Studie 2) zeigt, dass die Lernpartner diese Art der Zusammenarbeit positiv empfinden. Es werden aber auch Probleme aufgezeigt, die verdeutlichen, mit welchen Schwierigkeiten die Forderung nach phasenübergreifender Kooperation in der konkreten Umsetzung verbunden sein kann. Um die Befunde aus der Evaluation zum Kooperationspraktikum auch wegen der relativ kleinen Stichprobe richtig einordnen zu können, werden sie mit den relevanten Forschungsergebnissen in Verbindung gebracht. Idealisierende Vorstellungen von Kooperation zwischen Erster und Zweiter Phase sind allerdings fehl am Platz. Die Hoffnung auf einen bruchlosen Übergang unterschätzt auch die Anforderungen an den Rollenwechsel vom Studierenden zum Referendaren. Um ein Kooperation durch Lernpartnerschaften im Rahmen eines Kooperationspraktikums zu verwirklichen, sind Gelingens¬bedingungen zu berücksichtigen, zu denen sowohl Rahmenbedingungen als auch die Möglichkeiten zur Institutionalisierung gehören. Beide Ausbildungsphasen haben zwar als gemeinsames Ziel, Lehrer für die Schule zu qualifizieren und sie verbindet zudem der schulpraktische Ausbildungsteil, der in den Schulen stattfindet. Dieser Ausbildungsteil hat aber je nach Phase eine andere Bedeutung und unterscheidet sich zudem nicht nur nach Aufwand und Anspruch, sondern vor allem aufgrund der institutionellen Rolle seiner Akteure. Das Kooperationspraktikum berücksichtigt diese Unterschiedlichkeit und zeigt trotzdem einen Weg auf, gegenseitigen von der Zusammenarbeit zu profitieren. Von daher kann das Kooperationspraktikum einen Beitrag zur Weiterentwicklung der phasenübergreifenden Zusammenarbeit leisten und die Erkenntnisse könnten bei der Konzeption eines Praxissemesters gewinnbringend eingebracht werden.

Synthesis and evaluation of cyclic cationic peptides as antimicrobial agents for use in plant protection

Aquesta tesi doctoral se centra en l'estudi de l'aplicació de pèptids antimicrobians en la lluita contra agents patògens de cultius de plantes d'interès econòmic.L'estratègia sintètica s'ha portat a terme utilitzant metodologies convencionals de síntesi de pèptids en fase sòlida com l'estratègia tridimensional ortogonal Fmoc/tBut/Allyl. Ha calgut fer la recerca de les condicions òptimes per a l'eliminació del grup Allyl i la ciclació. D'entre els pèptids cíclics de 4-10 aminoacids sintetitzats, el decapèptid c(Lys-Leu-Lys-Leu-Lys-Phe-Lys-Lys-Leu-Gln) ha resultat ésser el més efectiu i s'ha pres com a base per al disseny d'una quimioteca de 56 pèptids. Dels resultats obtinguts s'ha sintetitzat una segona quimioteca basada en l'estructura general c(X1-X2-X3-X4-Lys-Phe-Lys-Lys-Leu-Gln) determinada com la que posseix el millor perfil d'activitat. Els pèptids més efectius obtinguts constituixen els primers exemples de pèptids cíclics actius contra E. amylovora i poden ser considerats com a bons candidats pel desenvolupament d'agents antimicrobians efectius en protecció vegetal.

Evaluation of forest snow processes models (SnowMIP2)

Thirty‐three snowpack models of varying complexity and purpose were evaluated across a wide range of hydrometeorological and forest canopy conditions at five Northern Hemisphere locations, for up to two winter snow seasons. Modeled estimates of snow water equivalent (SWE) or depth were compared to observations at forest and open sites at each location. Precipitation phase and duration of above‐freezing air temperatures are shown to be major influences on divergence and convergence of modeled estimates of the subcanopy snowpack. When models are considered collectively at all locations, comparisons with observations show that it is harder to model SWE at forested sites than open sites. There is no universal “best” model for all sites or locations, but comparison of the consistency of individual model performances relative to one another at different sites shows that there is less consistency at forest sites than open sites, and even less consistency between forest and open sites in the same year. A good performance by a model at a forest site is therefore unlikely to mean a good model performance by the same model at an open site (and vice versa). Calibration of models at forest sites provides lower errors than uncalibrated models at three out of four locations. However, benefits of calibration do not translate to subsequent years, and benefits gained by models calibrated for forest snow processes are not translated to open conditions.

Initial results from Phase 2 of the international urban energy balance model comparison

Urban land surface schemes have been developed to model the distinct features of the urban surface and the associated energy exchange processes. These models have been developed for a range of purposes and make different assumptions related to the inclusion and representation of the relevant processes. Here, the first results of Phase 2 from an international comparison project to evaluate 32 urban land surface schemes are presented. This is the first large-scale systematic evaluation of these models. In four stages, participants were given increasingly detailed information about an urban site for which urban fluxes were directly observed. At each stage, each group returned their models' calculated surface energy balance fluxes. Wide variations are evident in the performance of the models for individual fluxes. No individual model performs best for all fluxes. Providing additional information about the surface generally results in better performance. However, there is clear evidence that poor choice of parameter values can cause a large drop in performance for models that otherwise perform well. As many models do not perform well across all fluxes, there is need for caution in their application, and users should be aware of the implications for applications and decision making.