Korneales Crosslinking bei Keratokonus, klinischer Vergleich des beschleunigten zum konventionellen Dresdner

Das korneale Crosslinking ist mittlerweile ein seit mehr als einem Jahrzehnt etabliertes Verfahren zur Behandlung von kornealen Ektasien, insbesondere des Keratokonus. Versuche, die Interventionszeit zu reduzieren, führten zu Modifikationen des ursprünglich von Wollensak et al. [51] entwickelten Protokolls. Auch wenn heutzutage die beschleunigten Behandlungsprotokolle an mehreren Kliniken angewandt werden, gibt es wenige Studien zum Vergleich der Protokolle untereinander. Diese Studie beinhaltet 413 Augen von 316 Patienten mit progressivem Keratokonus, die eine Crosslinking Behandlung im Zeitraum von 1. Januar 2009 bis 30. Dezember 2014 in der Augenklinik der LMU - München erhielten. Die Behandlung erfolgte entweder mit dem konventionellen Dresdner - Protokoll (Gruppe A - Strahlungsenergie: 3mW / cm², Bestrahlungsdauer: 30 min) oder mit dem beschleunigten Protokoll (Gruppe B - Strahlungsenergie: 9 mW / cm², Bestrahlungsdauer: 10 min). Mit dem konventionellen (Gruppe A) wurden 131 Augen von 101 Patienten und mit dem beschleunigten Protokoll (Gruppe B) 282 Augen von 215 Patienten behandelt. UCVA (Fernvisus ohne Korrektur) und CDVA (Fernvisus mit Korrektur) sowie die Tomographiedaten (Pentacam HR®) wurden während eines postoperativen Beobachtungszeitraumes von 36 Monaten zwischen den Gruppen verglichen. UCVA und CDVA stiegen in beiden Gruppen ohne statistische Signifikanz zwischen den beiden Gruppen nach 36 Monaten (p = 0.081 und p = 0.344). Der maximale Keratometriewert der kornealen Vorderfläche (KMAX) ergab in beiden Gruppen eine statistisch signifikante Besserung (p = 0.04, p = 0.01) ohne signifikante Differenz zwischen den Gruppen (p = 0.113). Die Keratokonus - Indices (ISV, IVA, KI) besserten sich unabhängig vom Behandlungsprotokoll ohne statistisch signifikante Differenz zwischen den Gruppen (p = 0.21, p = 0.316, p = 0.107). Die Hornhautdicke (PACHM) zeigte in Gruppe A eine weitere Abnahme um 9 μm (p = 0.014) und blieb in Gruppe B stabil (p = 0.063) mit statistisch signifikanter Differenz zwischen den Gruppen nach 36 Monaten (p = 0.032). Zusammenfassend zeigt diese Studie, dass das beschleunigte Crosslinking - Protokoll ähnliche Ergebnisse wie das konventionelle Dresdner - Protokoll bezüglich der Keratometriewerte, der Keratokonus - Indices und der Visusentwicklung erzielt. Gleichzeitig offenbaren unsere Ergebnisse eine Überlegenheit des beschleunigten Protokolls in Bezug auf die geringere korneale Ausdünnung nach der Operation. Dieser Vorteil, zusammen mit der Zeitersparnis bei Anwendung des Protokolls sind überzeugende Argumente für dessen Verwendung.Corneal crosslinking is an established method for more than a decade for the treatment of corneal ectasias, especially keratoconus. Attempts to reduce the intervention time led to modifications of the protocol originally developed by Wollensak et al.[51]. Although many ophthalmic operation centers today use accelerated treatment protocols, there are few studies comparing the protocols with one another. 413 eyes of 316 patients with progressive keratoconus who received a crosslinking treatment in the period from 01/01/2009 to 30/12/2014 in the eye clinic of the Ludwig Maximilian University of Munich were included in this study. The treatment was conducted either with the conventional Dresden protocol (group A - radiation energy: 3mW / cm², radiation time: 30 min) or with the accelerated protocol (group B - radiation energy: 9mW / cm², radiation time: 10 min). 131 eyes of 101 patients were treated with the conventional protocol (group A) and 282 eyes of 215 patients with the accelerated protocol (group B). UCVA (uncorrected distance visual acuity) and CDVA (corrected distance visual acuity) as well as tomography data (Pentacam HR®) were compared between the groups during a postoperative observation period of 36 months. UCVA and CDVA increased in both groups without statistical significance between the two groups after 36 months (p = 0.081 and p = 0.344, respectively). The maximum keratometry value of the anterior corneal surface (KMAX) showed statistically significant improvement in both groups (p = 0.04, p = 0.01) with no significant difference between groups (p = 0.113). Keratoconus indices (ISV, IVA, KI) improved regardless of treatment protocol with no statistically significant difference between groups (p = 0.21, p = 0.316, p = 0.107). The thinnest corneal thickness (PACHM) showed a further decrease of 9 μm in group A (p = 0.014) and remained stable in group B (p = 0.063) with a statistically significant difference between groups after 36 months (p = 0.032). In conclusion, our study demonstrates that the accelerated crosslinking protocol yields comparable outcomes to the conventional Dresden protocol regarding keratometry values, keratoconus indices, and visual acuity. Furthermore, our findings highlight the superiority of the accelerated protocol in terms of reduced corneal thinning post-surgery. This advantage, combined with the time-saving aspect of this protocol, provides a compelling rationale for its adoption

Replicated microcellular aluminium structures for thermal management

Open-pore aluminium foams are of interest in thermal management of power electronics due to their large specific surface area, low weight and relatively high thermal conductivity. The replication process is a low-cost and simple foam manufacturing method that offers many opportunities for the investigation of the influence exerted by the microstructure (porosity, pore size) and geometry or their combination in the performance of metal foams in heat-exchange applications. In this study, we explored replicated aluminium foams as a part of an integrated heat sink manufactured in one step that seamlessly combines metal and ceramic phases. Replicated aluminium foams were manufactured and tested first under natural and then under forced convection. A dedicated test apparatus was built to test these samples under both natural and forced convection, using the guarding ring technique. In the case of natural convection, the aluminium foams had different pore sizes (125-180 µm, 400-450 µm and 5 mm), porosities (78 to 86%) and geometry (disk, cylinder and finned structures). In all cases, replicated aluminium foams were found to dissipate the same amount of heat as their bulk aluminium (alloy) equivalents. The thermal heat exchange performance of replicated microcellular aluminium was also measured under forced convection. The test rig was modified to measure the pressure drop and volumetric air flow in a cylindrically symmetric jet impingement configuration. Foams of different pore size (125-180, 400-450 and 900-1300 µm), porosity (between 75 and 85 %), height (1 and 2.8 cm) and infiltrated at various pressures (between 2.7 and 70 bars) were manufactured for thermal testing, all having a hollow central channel, through which air is injected at a range of flow rates. The results show that within the covered parameter range foams of higher porosities, larger pore sizes and lower infiltration pressures dissipate more heat at lower cost in terms of pumping power. Shorter heights also dissipate more heat for a given volumetric flow but do so at the cost of an increased pressure drop and hence greater pumping power expenditure. A numerical model, developed and written by Dr. D. Ingram, using the finite-volumes technique, was employed to elucidate how the various parameters influence the heat transfer. The model solves the Darcy-Forchheimer formulation of fluid flow in porous media, which is then coupled to a convective/conductive heat transfer model of the same structure. These simulations were used to perform parametric studies on the influence of height and pore size with regard to the thermal behaviour of replicated foams. Furthermore, the model was benchmarked against the experimental results; overall, despite some discrepancies with measured temperature profiles, the model captures data trends well, and provides insight on the physical phenomena that underlie the experimental data and observations. In particular, the presence and influence of recirculating air flow along the inner portion of the heat exchanger structures was identified. Finally, we successfully fabricated the proposed integrated multimaterial structure and tested it under forced convection, using the same conditions as the replicated aluminium foams. Results demonstrate that this type of structures can be effectively used to cool power electronics

THE ENVIRONMENTAL IMPACT ON THE MATURATION OF MGE-DERIVED CORTICAL INTERNEURONS

Οι διάμεσοι νευρώνες που εκκρίνουν τον νευροδιαβιβαστή γ-αμινοβουτιρικό οξύ (GABA) είναι η μια από τις δυο κύριες ομάδες νευρώνων του φλοιού των θηλαστικών. Προέρχονται από τρεις περιοχές του αναπτυσσόμενου εμβρυικού τελεγκέφαλου- την έσω και οπίσθια γαγγλιακή περιοχή (MGE, CGE) και την προ-οπτική περιοχή (POA). Περίπου το 70% όλων των διάμεσων νευρώνων του φλοιού παράγονται στην MGE και περιλαμβάνουν δυο κύριους τύπους, οι οποίοι χαρακτηρίζονται από την έκφραση συγκεκριμένων μοριακών δεικτών. Ο πρώτος τύπος περιλαμβάνει τους διάμεσους νευρώνες που εκφράζουν την πρωτεΐνη δέσμευσης ασβεστίου παρβαλβουμίνη (PV) και αυτούς που εκφράζουν το νευροπεπτιδίο σωματοστατίνη (SST). Η περιοχή προέλευσής τους καθορίζει τον τύπο των διάμεσων νευρώνων που θα δημιουργηθούν, με βάση την έκφραση των μοριακών δεικτών που εκφράζουν, αλλά τα τελικά μορφολογικά, μοριακά και ηλεκτροφυσιολογικά τους χαρακτηριστικά διαμορφώνονται αργότερα στο μικροπεριβάλλον του φλοιού. Το πώς το μικροπεριβάλλον του φλοιού επηρεάζει την ωρίμανση των διάμεσων νευρώνων έχει ήδη υπάρξει αντικείμενο μελέτης, ωστόσο έχει επικεντρωθεί σε πρώιμα αναπτυξιακά στάδια. Σκοπός της παρούσας ερευνητικής εργασίας είναι να εξετάσει το πώς το μικροπεριβάλλον του φλοιού επηρεάζει την ωρίμανση των διάμεσων νευρώνων που προέρχονται από την MGE σε μεταγενέστερα στάδια της ζωής του οργανισμού. Για να μελετηθεί η επιρροή του μικροπεριβάλλοντος του φλοιού στην ωρίμανση των PV+ και SST+ διάμεσων νευρώνων, χρησιμοποιήθηκαν δύο προσεγγίσεις: στην πρώτη περίπτωση, επηρεάσαμε τα επίπεδα της εισερχόμενης αισθητηριακής πληροφορίας στον πρωτοταγή αισθητικό φλοιό του ποντικού in vivo, ενώ στην δεύτερη, επηρεάσαμε τα ενδοφλοιικά επίπεδα ηλεκτρικής δραστηριότητας, με τη χρήση κατάλληλων ιών συνδυαστικά με μεθόδους χημειο-γενετικής, in vivo. Τα αποτελέσματά μας έδειξαν ότι ούτε η αύξηση ούτε η μείωση των επιπέδων αισθητηριακής δραστηριότητας, ούτε τα μειωμένα επίπεδα ενδο-φλοιικής δραστηριότητας επηρεάζουν την πυκνότητα ή την κατανομή των PV+ και SST+ διάμεσων νευρώνων στις διάφορες στοιβάδες του φλοιού. Αντίθετα, παρατηρήσαμε μια μικρή, αλλά στατιστικά σημαντική αύξηση στην πυκνότητα των PV+ διάμεσων νευρώνων, όταν αυξήσαμε τα επίπεδα ηλεκτρικής δραστηριότητας με μεθόδους χημειο-γενετικής εντός του φλοιού.GABAergic cortical interneurons (cIN) are one of the two main classes of cortical neurons and arise from three proliferating regions of the embryonic basal telencephalon-the medial and caudal ganglionic eminences (MGE, CGE) and the preoptic area (POA). Around 70% of all cINs are born in the MGE and include two main types, which are defined by the expression of the calcium-binding protein parvalbumin (PV) and the neuropeptide somatostatin (SST). The place of origin restricts IN fates into major classes, but their distinct mature identity is defined later, within their cortical environment. Only a few studies examine how the cortical environment affects the maturation of MGE-derived cINs, during early postnatal stages. To address this, we assessed how cortical activity levels affect the density and the layer acquisition of PV+ and SST+ cINs, by using two different approaches: In the first one we manipulated sensory input in vivo, in the mouse somatosensory barrel cortex and in the second one, we manipulated intra-cortical activity levels by employing an in vivo virus-based approach in combination with chemogenetics. Our results indicate that neither increased/decreased sensory input, nor decreased intra-cortical activity levels affected the density or the cortical distribution of PV+ and SST+ cINs. On the other hand, we observed a small but statistically significant increase in the density of PV+ cINs, in the presence of increased intra-cortical activity levels

Differences in corneal clinical findings after standard and accelerated cross-linking in patients with progressive keratoconus

Background: The purpose of this study was to identify differences in clinical corneal findings after standard and accelerated epithelial off cross-linking (CXL) during a long-term follow-up. Methods: Two hundred forty-one patients (184 male) were included in this monocentric, retrospective, non-randomized and unmasked study. One hundred forty-eight eyes were treated with the accelerated protocol and 138 with the standard protocol with epithelial off CXL, if diagnosed with keratoconus and a progression in Kmax of more than one dioptre during the preceding 6 months, plus a minimal pachymetry measurement of 400 mu m in keratometry (Pentacam, Oculus GmbH, Wetzlar, Germany). Exclusion criteria were previous surgery, other corneal conditions or age above 50 years. Follow-up time was 36 months with clinical examination and keratometry at every visit. Outcome measures were the observed rate of corneal changes, differences between treatment groups and correlation with keratometry measurements. Results: In patients with accelerated CXL, significantly more clear corneas were seen at three (p = 0.015) and six (p = 0.002) months after surgery than following the standard protocol. The rate of clear corneas dropped from 52.2% pre-operation (OP) to a minimum of 19.3% after 6 months in the standard protocol group compared with 50.7% clear corneas pre-OP and a minimum of 40.8% in the accelerated group. In the standard protocol group, more striae were found 3 months after intervention than in the accelerated group (p = 0.05). Conclusions: In patients with accelerated CXL, fewer morphological corneal changes were observed than after conventional CXL. However, rarely, corneal changes persisted for a long time