The role of targeted viral load testing in diagnosing virological failure in children on antiretroviral therapy with immunological failure

Objectives  To determine the improvement in positive predictive value of immunological failure criteria for identifying virological failure in HIV-infected children on antiretroviral therapy (ART) when a single targeted viral load measurement is performed in children identified as having immunological failure. Methods  Analysis of data from children (<16 years at ART initiation) at South African ART sites at which CD4 count/per cent and HIV-RNA monitoring are performed 6-monthly. Immunological failure was defined according to both WHO 2010 and United States Department of Health and Human Services (DHHS) 2008 criteria. Confirmed virological failure was defined as HIV-RNA >5000 copies/ml on two consecutive occasions <365 days apart in a child on ART for ≥18 months. Results  Among 2798 children on ART for ≥18 months [median (IQR) age 50 (21-84) months at ART initiation], the cumulative probability of confirmed virological failure by 42 months on ART was 6.3%. Using targeted viral load after meeting DHHS immunological failure criteria rather than DHHS immunological failure criteria alone increased positive predictive value from 28% to 82%. Targeted viral load improved the positive predictive value of WHO 2010 criteria for identifying confirmed virological failure from 49% to 82%. Conclusion  The addition of a single viral load measurement in children identified as failing immunologically will prevent most switches to second-line treatment in virologically suppressed children.

Horizontal ridge augmentation using autogenous block grafts and the guided bone regeneration technique with collagen membranes: a clinical study with 42 patients

OBJECTIVE: To analyze the clinical outcome of horizontal ridge augmentation using autogenous block grafts covered with an organic bovine bone mineral (ABBM) and a bioabsorbable collagen membrane. MATERIAL AND METHODS: In 42 patients with severe horizontal bone atrophy, a staged approach was chosen for implant placement following horizontal ridge augmentation. A block graft was harvested from the symphysis or retromolar area, and secured to the recipient site with fixation screws. The width of the ridge was measured before and after horizontal ridge augmentation. The block graft was subsequently covered with ABBM and a collagen membrane. Following a tension-free primary wound closure and a mean healing period of 5.8 months, the sites were re-entered, and the crest width was re-assessed prior to implant placement. RESULTS: Fifty-eight sites were augmented, including 41 sites located in the anterior maxilla. The mean initial crest width measured 3.06 mm. At re-entry, the mean width of the ridge was 7.66 mm, with a calculated mean gain of horizontal bone thickness of 4.6 mm (range 2-7 mm). Only minor surface resorption of 0.36 mm was observed from augmentation to re-entry. CONCLUSIONS: The presented technique of ridge augmentation using autogenous block grafts with ABBM filler and collagen membrane coverage demonstrated successful horizontal ridge augmentation with high predictability. The surgical method has been further simplified by using a resorbable membrane. The hydrophilic membrane was easy to apply, and did not cause wound infection in the rare instance of membrane exposure.

Distribution of intracellular and secreted surfactant during postnatal rat lung development

Pulmonary surfactant prevents alveolar collapse via reduction of surface tension. In contrast to human neonates, rats are born with saccular lungs. Therefore, rat lungs serve as a model for investigation of the surfactant system during postnatal alveolar formation. We hypothesized that this process is associated with characteristic structural and biochemical surfactant alterations. We aimed to discriminate changes related to alveolarization from those being either invariable or follow continuous patterns of postnatal changes. Secreted active (mainly tubular myelin (tm)) and inactive (unilamellar vesicles (ulv)) surfactant subtypes as well as intracellular surfactant (lamellar bodies (lb)) in type II pneumocytes (PNII) were quantified before (day (d) 1), during (d 7), at the end of alveolarization (d 14), and after completion of lung maturation (d 42) using electron microscopic methods supplemented by biochemical analyses (phospholipid quantification, immunoblotting for SP-A). Immunoelectron microscopy determined the localization of surfactant protein A (SP-A). (1) At d 1 secreted surfactant was increased relative to d 7-42 and then decreased significantly. (2) Air spaces of neonatal lungs comprised lower fractions of tm and increased ulv, which correlated with low SP-A concentrations in lung lavage fluid (LLF) and increased respiratory rates, respectively. (3) Alveolarization (d 7-14) was associated with decreasing PNII size although volume and sizes of Lb continuously increased. (4) The volume fractions of Lb correlated well with the pool sizes of phospholipids in lavaged lungs. Our study emphasizes differential patterns of developmental changes of the surfactant system relative to postnatal alveolarization.

Antiretroviral therapy in resource-limited settings 1996 to 2006: patient characteristics, treatment regimens and monitoring in sub-Saharan Africa, Asia and Latin America

OBJECTIVES: To describe temporal trends in baseline clinical characteristics, initial treatment regimens and monitoring of patients starting antiretroviral therapy (ART) in resource-limited settings. METHODS: We analysed data from 17 ART programmes in 12 countries in sub-Saharan Africa, South America and Asia. Patients aged 16 years or older with documented date of start of highly active ART (HAART) were included. Data were analysed by calculating medians, interquartile ranges (IQR) and percentages by regions and time periods. Not all centres provided data for 2006 and 2005 and 2006 were therefore combined. RESULTS: A total of 36,715 patients who started ART 1996-2006 were included in the analysis. Patient numbers increased substantially in sub-Saharan Africa and Asia, and the number of initial regimens declined, to four and five, respectively, in 2005-2006. In South America 20 regimes were used in 2005-2006. A combination of 3TC/D4T/NVP was used for 56% of African patients and 42% of Asian patients; AZT/3TC/EFV was used in 33% of patients in South America. The median baseline CD4 count increased in recent years, to 122 cells/microl (IQR 53-194) in 2005-2006 in Africa, 134 cells/microl (IQR 72-191) in Asia, and 197 cells/microl (IQR 61-277) in South America, but 77%, 78% and 51%, respectively, started with <200 cells/microl in 2005-2006. In all regions baseline CD4 cell counts were higher in women than men: differences were 22cells/microl in Africa, 65 cells/microl in Asia and 10 cells/microl in South America. In 2005-2006 a viral load at 6 months was available in 21% of patients Africa, 8% of Asian patients and 73% of patients in South America. Corresponding figures for 6-month CD4 cell counts were 74%, 77% and 81%. CONCLUSIONS: The public health approach to providing ART proposed by the World Health Organization has been implemented in sub-Saharan Africa and Asia. Although CD4 cell counts at the start of ART have increased in recent years, most patients continue to start with counts well below the recommended threshold. Particular attention should be paid to more timely initiation of ART in HIV-infected men.

Laser-Sintern. Die Schluesseltechnologie des e-Manufacturing TM

e-Manufacturing™, das ist die schnelle, flexible und kostengünstige Fertigung von Produkten, Formen/Werkzeugen oder Modellen direkt aus elektronischen Daten. e-Manufacturing™ schließt Rapid Prototyping, Rapid Tooling oder Rapid Manufacturing ein, geht aber zugleich weit über den Gedanken der schnellen Verfügbarkeit hinaus. Zwar wird auch in Zukunft die schnelle Produktentwicklung eine immer wichtigere Rolle spielen, bei der e-Manufacturing™ für ein verkürztes Time to Market sorgt, Entwicklungskosten verringert und zur Risikominimierung beiträgt. Darüber hinaus entstehen aber auch neue Geschäftsmodelle, da Kleinserienproduktion, steigende Variantenvielfalt und eine individualisierte Produktion (Mass Customization) plötzlich möglich und wirtschaftlich sind und sich neue Logistikkonzepte wie (Spare) parts on demand entwickeln. Die neue Konstruktionsfreiheit des Laser-Sinterns ermöglicht neue Produktkonzepte. Minimale Einschränkungen durch das Fertigungsverfahren erlauben funktionelle Integration und die Fertigung des „Unmöglichen“, da kreisförmige und lineare Werkzeugbewegungen das Produktdesign nicht mehr beeinflussen bzw. limitieren. Auch die Fertigungskonzepte unterliegen einem Wandel und werden deutlich flexibler. Werkzeuglose Produktion, losgrößenangepasste Fertigung und dezentrale Fertigung on demand sind die Schlagworte der Zukunft. Der vorliegende Beitrag zeigt Beispiele für den erfolgreichen kommerziellen Einsatz von Laser-Sintern in allen Phasen des Produktlebenszyklus. Der Schwerpunkt liegt dabei auf der direkten Herstellung von Funktionsteilen in der Serienfertigung. Die entscheidenden Faktoren für eine erfolgreiche Einführung und Anwendung von e-Manufacturing™ werden diskutiert. Der Beitrag zeigt auf, wie die neuesten technologischen Innovationen im Laser-Sintern, speziell zur Produktivitätssteigerung, das Spektrum der Anwendungsfelder erweitern, in denen dieses Fertigungsverfahren kostengünstige Lösungen bietet.

42'195 Meter ins Rampenlicht - Standortmarketing durch Marathonevents in Schweizer Städten

Mit der Durchführung von Sportevents werden vielfältige Hoffnungen verbunden. Unter anderem können Events Informationen über eine Destination transportieren und dadurch das zukünftige Verhalten von relevanten Zielgruppen wie Touristen oder Investoren beeinflussen. Die vorliegende Studie untersucht anhand von drei Marathonevents die Wechselwirkung zwischen Event und Destination sowie die Strategien zur Optimierung der positiven Effekte. Dabei zeigt sich, dass die Passung der Eventthematik zu den Destinationsschwerpunkten sowie der frühzeitige Einbezug aller relevanten Stake Holder Schlüsselrollen spielen. Alle drei betrachteten Marathonevents nehmen im Standortmarketing der jeweiligen Destination keine zentrale Rolle ein, sondern leisten in moderatem Umfang einen Beitrag zum Destination Branding.