Differenzierung von Methicillin-sensiblem und Methicillin-resistentem Staphylococcus aureus anhand flüchtiger organischer Verbindungen mittels Multikapillarsäulen-Ionenmobilitätsspektrometrie und elektronischer Nase „Cyranose 320“

Hintergrund: Staphylococcus aureus besiedelt als Kommensale 20 – 40 % der Bevölkerung und gehört zu den häufigsten Verursachern nosokomialer Infektionen. Bereits frühzeitig sind multiresistente Stämme entstanden, welche in Methicillin-sensible Stämme (MSSA) und Methicillin-resistente Stämme (MRSA) eingeteilt werden. Auch gegen Reserveantibiotika entwickeln sich zunehmend Resistenzen. S. aureus ist für eine erhöhte Morbidität und Mortalität sowie für eine verlängerte Hospitalisationszeit inklusive Isolationsmaßnahmen und damit einhergehender Kosten verantwortlich. Die mikrobiologische Diagnostik mittels Erregerkultivierung stellt den Goldstandard zum Keimnachweis und zur Bestimmung von Resistenzen dar, ist jedoch zeitaufwendig und teuer. Die PCR-basierte Diagnostik ist zwar schneller, jedoch wirtschaftlich nicht effizient. Ein frühzeitiger Keimnachweis durch Screening-Untersuchungen mit darauffolgender Isolation oder Dekolonisierung kann zu einer Reduktion der Keimübertragung und folglich der Morbidität, Mortalität und der assoziierten Kosten führen. Somit besteht die Notwendigkeit für kosten- und zeiteffektive Methoden zur Erkennung von MSSA und MRSA mit hoher diagnostischer Wertigkeit. Ziel: In der vorliegenden Arbeit sollte festgestellt werden, ob sich MRSA und MSSA anhand der Analyse volatiler organischer Verbindungen (volatile organic compounds, VOC), welche durch Stoffwechselprozesse von Organismen exprimiert werden, mittels Multikapillarsäulen-Ionenmobilitätsspektrometrie (MCC-IMS) sowie der elektronischen Nase Cyranose 320 aus dem Nährmedium Brain Heart Infusion Broth (BHI) identifizieren und voneinander differenzieren lassen. Methoden: Es wurden aus routinemäßig entnommenen Screening-Abstrichen je 20 Proben mit MRSA und MSSA ins Flüssignährmedium BHI übertragen und auf eine Konzentration von 108 KBE/ml verdünnt. Aus jeder Probe wurden 500 μl für die Messungen entnommen. Mit dem MCC-IMS wurden mittels Headspace-Messungen je 20 MRSA- und MSSA- Proben und analog dazu 27 Proben des nicht bebrüteten Flüssignährmediums BHI analysiert. Vor jeder Probenmessung erfolgte eine Leermessung der Laborflasche zur Referenz und zur Elimination von Störfaktoren. Die aus den Messungen resultierenden Peaks wurden visualisiert und statistisch analysiert und ermöglichten im Anschluss durch Zuordnung spezifischer Peaks zu den jeweiligen Proben eine Differenzierung der Gruppen. Durch Abgleich mit einer bestehenden Datenbank konnten die Peaks entsprechenden organischen Substanzen zugeordnet werden. Mit der Cyranose 320 wurde der Headspace von je 20 MRSA- und MSSA-Proben und von 20 Proben nicht bebrüteter BHI analysiert. Jede Probe wurde 5-mal hintereinander gemessen, um ein Machine-Learning zu gewährleisten. Im Anschluss erfolgten eine lineare Diskriminanzanalyse und die Berechnung der Mahalanobis-Distanz zur Differenzierung der Gruppen. Eine Leave-One-Out Kreuzvalidierung wurde zur Bestimmung des Kreuzvalidierungswerts durchgeführt. Die Gruppen konnten durch eine Mustererkennung voneinander unterschieden werden. Ergebnisse: Mittels MCC-IMS konnten in der Gegenüberstellung der Gruppen MRSA und BHI 19 hochsignifikante Peaks (p [ 0.001) nachgewiesen werden, welche eine Unterscheidung mit einer Sensitivität und Spezifität von jeweils ] 90 % bis 99.9 % ermöglichen. MSSA konnte aus dem Nährmedium BHI anhand 20 hochsignifikanter Peaks mit einer Sensitivität von 92.6 % bis 96.3 % und einer Spezifität von 90 % bis 99.9 % differenziert werden. MRSA und MSSA konnten anhand 11 hochsignifikanter Peaks mit einer Sensitivität und Spezifität von jeweils 90 % bis 99.9% voneinander differenziert werden. Zwei Peaks waren ausreichend, um anhand eines Entscheidungsbaums in zwei Schritten eine Trennung aller Gruppen zu gewährleisten. Die Cyranose 320 konnte die Gruppen MRSA und BHI mit einer Sensitivität von 96 % und einer Spezifität von 94 % voneinander abgrenzen. Eine Differenzierung von MSSA und BHI konnte mit einer Sensitivität von 81 % und einer Spezifität von 75 % erreicht werden. MRSA und MSSA konnten mit einer Sensitivität von 100 % und einer Spezifität von 91 % voneinander unterschieden werden. Schlussfolgerung: Eine Unterscheidung der Bakterien MRSA und MSSA aus dem Flüssignährmedium BHI und insbesondere eine Differenzierung der Keime voneinander ist mittels MCC-IMS sowie Cyranose 320 mit hoher Sensitivität und Spezifität möglich. Es bedarf weiterer, prospektiver Studien im klinischen Setting, um die Ergebnisse zu verifizieren und somit eine potenzielle zeit- und kostensparende Alternative zur konventionellen Diagnostik zu ermöglichen

TRAJECTORIES OF DSM-IV SYMPTOMS OF ADHD, ODD AND ADHD+ODD IN MIDDLE CHILDHOOD: EXAMINING THE CO-VARIATION OF ADHD AND ODD SYMPTOMS AND THEIR DIFFERENTIAL PREDICTORS AND OUTCOMES

Although the importance of investigating the developmental course of problem behavior has been emphasized in the developmental psychopathology literature, few studies have examined both ADHD and ODD symptoms longitudinally to ascertain developmental changes in symptom patterns or their co-occurrence across time. Furthermore, few studies control for comorbid symptoms, making it unclear whether ADHD, ODD or their combination drive the reported associations with early risk factors and later negative outcomes. Consequently, the current study aimed to (1) explicate longitudinal patterns of DSM-IV defined ADHD and ODD symptoms and their co-occurrence across middle childhood (ages 9 to 12) using a person-centered, semi-parametric group-based modeling approach (Nagin, 1999); (2) examine the associations of trajectories of ADHD, ODD and ADHD+ODD symptoms with possible early risk factors, children's executive functioning and maternal parenting at 54 months; and (3) investigate whether academic and social outcomes at age 12 varied as a function of symptom trajectories. Prospective data were collected from birth through sixth grade from a community sample of 1081 children participating in the NICHD Study of Early Child Care and Youth Development (SECCYD). Five longitudinal patterns of ADHD symptoms were identified: very low, low, increasing, decreasing, and high stable symptom trajectories. Only three trajectories of ODD symptoms were identified: very low, low, and high stable symptom groups. The dual symptom trajectory model did not converge making it impossible to explore dual symptom trajectories. Differential associations with early risk factors and later outcomes were found after controlling for comorbid disruptive symptoms. Preschool measures of children's executive functioning predicted later levels of ADHD symptoms, but not ODD symptoms. Maternal sensitivity predicted later ODD and ADHD symptoms and harsh maternal control predicted ADHD symptoms. Later academic performance was associated with ADHD symptoms after controlling for ODD symptoms, but not with ODD symptoms alone. Finally, both ADHD and ODD symptoms were significantly associated with mother- and teacher-reported social skills. These results underscore the importance of early cognitive skills in predicting elevated ADHD symptoms and of early relationship quality in predicting symptoms of both ADHD and ODD; implications for intervention are discussed

UNDERSTANDING AND PREDICTING THE EARLY COURSE OF SYMPTOMS OF ATTENTION DEFICIT HYPERACTIVITY DISORDER

Using data from the NICHD Study of Early Child Care, we examined whether: 1) attention deficit hyperactivity disorder (ADHD) symptoms remain stable from preschool (54 months) through early school age (1st grade); 2) preschool behavioral inhibition moderates the relationship between preschool and first grade ADHD symptomatology; and 3) deficits in behavioral inhibition at preschool age mediate the relationship between ADHD symptomatology assessed at preschool and first grade. Modest stability in ADHD symptoms from 54 months to 1st grade was found. Two out of three measures of inhibition predicted later teacher ratings uniquely. However, no evidence of moderation or mediation was found. Results are discussed in terms of executive and motivational facets of inhibition that may be related to early signs of ADHD

Management of abdominal pseudotumours in haemophilia: a systematic review

AIM: Haemophilic pseudotumours are complications in patients with haemophilia A or B and result from locally repetitive bleeding, mainly in the musculoskeletal system. Abdominal haemophilic pseudotumours are exceptionally rare but may cause severe complications. This systematic review aimed to evaluate therapy strategies for symptomatic abdominal haemophilic pseudotumours. METHODS: We systematically searched three databases (Medline [PubMed], Web of Science and EMBASE) for publications published between 1995 and 2023. Two reviewers independently selected the studies, extracted data and performed a quality assessment using the JBI critical appraisal checklist. RESULTS: From a total of 1199 articles, 39 articles describing 41 cases were included for final analysis. Conservative or interventional treatment was performed in 12 cases. In eight cases, a step-up to surgical therapy after interventional treatment was indicated. Primary surgical therapy was performed in 21 cases. Failure to cure was documented in 50% (n = 6) of patients treated in the first group, with a mortality rate of 16.6% (n = 2). Interventional therapy with a step-up to surgery showed no morbidity or mortality. Primary surgical resection documented favourable results in 66.6% (n = 14), with failure to cure in 9.5% (n = 2) and a mortality rate of 14.3% (n = 3). CONCLUSION: Primary surgical resection can be a first-line therapy for symptomatic, abdominal haemophilic pseudotumours, whereas preoperative embolisation could be used as a bridging therapy before surgery, especially in emergency settings. Diagnostic biopsy and percutaneous drainage should be avoided to prevent complications

Evaluation of Proclarix in the diagnostic work‐up of prostate cancer

Objectives: The use of multiparametric magnetic resonance imaging (mpMRI) has been widely adopted in the diagnostic work‐up for suspicious prostate cancer (PCa) and is recommended in most current guidelines. However, mpMRI lesions are often indeterminate and/or turn out to be false‐positive on prostate biopsy. The aim of this work was to evaluate Proclarix, a biomarker test for the detection of relevant PCa, regarding its diagnostic value in all men before biopsy and in men with indeterminate lesions on mpMRI (PI‐RADS 3) during work‐up for PCa. Materials and Methods: Men undergoing mpMRI‐targeted and systematic biopsy of the prostate were prospectively enrolled. The Proclarix test was evaluated for the detection accuracy of clinically significant PCa (csPCa) defined as Grade Group ≥ 2 and its association to mpMRI results. Further, Proclarix's performance was also tested when adapted to prostate volume (Proclarix density) and performance compared to PSA density (PSAD). Results: A total of 150 men with a median age of 65 years and median PSA of 5.8 ng/mL were included in this study. CsPCa was diagnosed in 65 (43%) men. Proclarix was significantly associated with csPCa and higher PI‐RADS score (p < 0.001). At the pre‐defined cut‐off of 10%, Proclarix's sensitivity for csPCa was 94%, specificity 19%, negative predictive value 80% and positive predictive value 47%. Proclarix density showed the highest AUC for the detection of csPCa of 0.77 (95%CI: 0.69–0.85) compared to PSA, PSAD and Proclarix alone. Proclarix was able to identify all six csPCa in men with PI‐RADS 3 lesions (n = 28), whereas PSAD missed two out of six. At optimized cut‐offs, Proclarix density outperformed PSAD by potentially avoiding 41% of unnecessary biopsies. Conclusion: Proclarix demonstrates high sensitivity in detecting csPCa but may still result in unnecessary biopsies. However, Proclarix density was able to outperform PSAD and Proclarix and was found to be useful in men with PI‐RADS 3 findings by safely avoiding unnecessary biopsies without missing csPCa

The Cult Statues of the Pantheon

This article reconsiders the possible statuary of the Pantheon in Rome, both in its original Augustan form and in its later phases. It argues that the so-called ‘Algiers Relief’ has wrongly been connected with the Temple of Mars Ultor and is in fact evidence of the association of the Divus Julius with Mars and Venus in the Pantheon of Agrippa, a juxtaposition which reflects the direction of Augustan ideology in the 20s b.c. and the building's celestial purpose. This triple statue group became the focus of the later Pantheon, and its importance is highlighted by the hierarchized system of architectural ornament of the present building

Cautious Resilience: The Impact of the Global Financial Crisis on Latin American and Caribbean Microfinance Institutions

Funded by MIF, CAF and Calmeadow, this MicroRate report provides a snapshot of how the impact of the global financial crisis evolved during the last quarter of 2008. The study combines data and interviews from 52 microfinance institutions (MFIs) and 23 microfinance investment vehicles (MIVs). The report concludes that microfinance will be more affected by this economic cycle than in the past because MFIs are today more tightly integrated into the global economy. The report also includes a synopsis of potential roles for microfinance stakeholders and actions to be taken in 2009

Arbeiten aus dem Hirnanatomischen Institut in Zürich / Über Seelenblindheit

Wilhelm Frh. von Stauffenber

Cautious Resilience: The Impact of the Global Financial Crisis on Latin American and Caribbean Microfinance Institutions

Funded by MIF, CAF and Calmeadow, this MicroRate report provides a snapshot of how the impact of the global financial crisis evolved during the last quarter of 2008. The study combines data and interviews from 52 microfinance institutions (MFIs) and 23 microfinance investment vehicles (MIVs). The report concludes that microfinance will be more affected by this economic cycle than in the past because MFIs are today more tightly integrated into the global economy. The report also includes a synopsis of potential roles for microfinance stakeholders and actions to be taken in 2009.Microbusinesses & Microfinance