Characterisation of SiPM Photon Emission in the Dark.

In this paper, we report on the photon emission of Silicon Photomultipliers (SiPMs) from avalanche pulses generated in dark conditions, with the main objective of better understanding the associated systematics for next-generation, large area, SiPM-based physics experiments. A new apparatus for spectral and imaging analysis was developed at TRIUMF and used to measure the light emitted by the two SiPMs considered as photo-sensor candidates for the nEXO neutrinoless double-beta decay experiment: one Fondazione Bruno Kessler (FBK) VUV-HD Low Field (LF) Low After Pulse (Low AP) (VUV-HD3) SiPM and one Hamamatsu Photonics K.K. (HPK) VUV4 Multi-Pixel Photon Counter (MPPC). Spectral measurements of their light emissions were taken with varying over-voltage in the wavelength range of 450-1020 nm. For the FBK VUV-HD3, at an over-voltage of 12.1±1.0 V, we measured a secondary photon yield (number of photons (γ) emitted per charge carrier (e-)) of (4.04±0.02)×10-6γ/e-. The emission spectrum of the FBK VUV-HD3 contains an interference pattern consistent with thin-film interference. Additionally, emission microscopy images (EMMIs) of the FBK VUV-HD3 show a small number of highly localized regions with increased light intensity (hotspots) randomly distributed over the SiPM surface area. For the HPK VUV4 MPPC, at an over-voltage of 10.7±1.0 V, we measured a secondary photon yield of (8.71±0.04)×10-6γ/e-. In contrast to the FBK VUV-HD3, the emission spectra of the HPK VUV4 did not show an interference pattern-likely due to a thinner surface coating. The EMMIs of the HPK VUV4 also revealed a larger number of hotspots compared to the FBK VUV-HD3, especially in one of the corners of the device. The photon yield reported in this paper may be limited if compared with the one reported in previous studies due to the measurement wavelength range, which is only up to 1020 nm.

The clinical outcome and microbiological profile of bone-anchored hearing systems (BAHS) with different abutment topographies: a prospective pilot study.

PURPOSE: In this prospective clinical pilot study, abutments with different topologies (machined versus polished) were compared with respect to the clinical outcome and the microbiological profile. Furthermore, three different sampling methods (retrieval of abutment, collection of peri-abutment exudate using paper-points, and a small peri-abutment soft-tissue biopsy) were evaluated for the identification and quantification of colonising bacteria. METHODS: Twelve patients, seven with machined abutment and five with polished abutment, were included in the analysis. Three different sampling procedures were employed for the identification and quantification of colonising bacteria from baseline up to 12 months, using quantitative culturing. Clinical outcome measures (Holgers score, hygiene, pain, numbness and implant stability) were investigated. RESULTS: The clinical parameters, and total viable bacteria per abutment or in tissue biopsies did not differ significantly between the polished and machined abutments. The total CFU/mm2 abutment and CFU/peri-abutment fluid space of anaerobes, aerobes and staphylococci were significantly higher for the polished abutment. Anaerobic bacteria were detected in the tissue biopsies before BAHS implantation. Anaerobes and Staphylococcus spp. were detected in all three compartments after BAHS installation. For most patients (10/12), the same staphylococcal species were found in at least two of the three compartments at the same time-point. The common skin coloniser Staphylococcus epidermidis was identified in all patients but one (11/12), whereas the pathogen Staphylococcus aureus was isolated in five of the patients. Several associations between clinical and microbiological parameters were found. CONCLUSIONS: There was no difference in the clinical outcome with the use of polished versus machined abutment at 3 and 12 months after implantation. The present pilot trial largely confirmed a suitable study design, sampling and analytical methodology to determine the effects of modified BAHS abutment properties. LEVEL OF EVIDENCE: 2. Controlled prospective comparative study.

Etv2/ER71 induces vascular mesoderm from Flk1+PDGFRα+ primitive mesoderm.

Etv2 (Ets Variant 2) has been shown to be an indispensable gene for the development of hematopoietic cells (HPCs)/endothelial cells (ECs). However, how Etv2 specifies the mesoderm-generating HPCs/ECs remains incompletely understood. In embryonic stem cell (ESC) differentiation culture and Etv2-null embryos, we show that Etv2 is dispensable for generating primitive Flk-1(+)/PDGFRα(+) mesoderm but is required for the progression of Flk-1(+)/PDGFRα(+) cells into vascular/hematopoietic mesoderm. Etv2-null ESCs and embryonic cells were arrested as Flk-1(+)/PDGFRα(+) and failed to generate Flk-1(+)/PDGFRα(-) mesoderm. Flk-1(+)/Etv2(+) early embryonic cells showed significantly higher hemato-endothelial potential than the Flk-1(+)/Etv2(-) population, suggesting that Etv2 specifies a hemato-endothelial subset of Flk-1(+) mesoderm. Critical hemato-endothelial genes were severely down-regulated in Etv2-null Flk-1(+) cells. Among those genes Scl, Fli1, and GATA2 were expressed simultaneously with Etv2 in early embryos and seemed to be critical targets. Etv2 reexpression in Etv2-null cells restored the development of CD41(+), CD45(+), and VE-cadherin(+) cells. Expression of Scl or Fli1 alone could also restore HPCs/ECs in the Etv2-null background, indicating that these 2 genes are critical downstream targets. Furthermore, VEGF induced Etv2 potently and rapidly in Flk-1(+) mesoderm. We propose that Flk-1(+)/PDGFRα(+) primitive mesoderm is committed into Flk-1(+)/PDGFRα(-) vascular mesoderm through Etv2 and that up-regulation of Etv2 by VEGF promotes this commitment.

Minimally invasive surgery as a new clinical standard for bone anchored hearing implants-real-world data from 10 years of follow-up and 228 surgeries.

Purpose: To explore the clinical practice development of different surgical techniques when installing bone-anchored hearing implants and their associated trends in outcomes. Design: Retrospective study of 228 bone-anchored hearing implants in 200 patients, performed over a 10-year period between 2012 and 2022 in a referral hospital. Method: Real-world data of demography, etiology, surgical setup, complications, and audiological outcomes were collected. Eligibility criteria from clinical practice were applied. Results: The minimally invasive technique is associated with shorter surgery duration, 20 vs. 44 min as compared to a linear incision technique. The minimally invasive technique was also associated with a lower occurrence of complications when compared to linear incision techniques (intraoperative; 1.8% vs. 4.9%, postoperative; 49% vs. 66%). Most differences were seen in complications relating to skin and wound healing. Conclusion: Adoption of a minimally invasive surgical technique for the installations of bone-anchored hearing implants can reduce surgical complexity without compromising safety aspects or clinical benefits.

Long-term osseointegration of laser-ablated hearing implants in sheep cranial bone.

Osseointegration, the ability for an implant to be anchored in bone tissue with direct bone-implant contact and allowing for continuous adaptive remodelling, is clinically used in different reconstructive fields, such as dentistry, orthopedics and otology. The latter uses a bone conducting sound processor connected to a skin-penetrating abutment that is mounted on a titanium implant placed in the temporal bone, thereby acting as a path for transmission of the vibrations generated by the sound processor. The success of the treatment relies on bone healing and osseointegration, which could be improved by surface modifications. The aim of this study was to evaluate the long-term osseointegration in a sheep skull model and compare a laser-ablated implant surface with a machined implant. Commercially available 4 mm titanium implants, either with a machined (Wide Ponto) or a laser-ablated surface (Ponto BHX, Oticon Medical, Sweden), were used in the current study. The surfaces were evaluated by scanning electron microscopy. The implantation was performed with a full soft tissue flap and the osteotomy was prepared using the MIPS drill kit (Oticon Medical, Sweden) prior to installation of the implants in the frontal bone of eight female sheep. After five months, biopsies including the implant and surrounding bone tissue obtained, processed and analysed using histology, histomorphometry, scanning electron microscopy and Raman spectroscopy. The animals healed well, without signs of adverse events. Histomorphometry showed a large amount of bone tissue around both implant types, with 75% of the threaded area occupied by bone for both implant types. A large amount of bone-implant contact was observed for both implant types, with 67%-71% of the surface covered by bone. Both implant types were surrounded by mature remodelled lamellar bone with high mineral content, corroborating the histological observations. The current results show that the laser-ablated surface induces healing similar to the well-known clinically used machined surface in ovine cranial bone. In conclusion, the present long-term experimental results indicate that a laser-ablated implant performs equally well as a clinically used implant with a machined surface. This, together with previously reported, improved early biomechanical anchorage, suggests future, safe and efficient clinical potential.

Cytokine expression profile in the bone-anchored hearing system: 12-week results from a prospective randomized, controlled study.

OBJECTIVE: To study the effect of implanting the percutaneous bone-anchored hearing system (BAHS) itself and inflammation of the peri-abutment skin warrant clarification. In this study, we aimed to acquire further insight into the immune responses related to BAHS surgery and peri-implant skin inflammation. MATERIALS AND METHODS: During surgery and 12 weeks post-implantation, skin biopsies were obtained. If applicable, additional biopsies were taken during cases of inflammation. The mRNA expression of IL-1ß, IL-6, IL-8, TNFα, IL-17, IL-10, TGF-ß, MIP-1α, MMP-9, TIMP-1, COL1α1, VEGF-A, FGF-2 TLR-2, and TLR-4 was quantified using qRT-PCR. RESULTS: Thirty-five patients agreed to the surgery and 12-week biopsy. Twenty-two patients had mRNA of sufficient quality for analysis. Ten were fitted with a BAHS using the minimally invasive Ponto surgery technique. Twelve were fitted with a BAHS using the linear incision technique with soft-tissue preservation. Five biopsies were obtained during episodes of inflammation. The post-implantation mRNA expression of IL-1ß (P = .002), IL-8 (P = .003), MMP9 (P = .005), TIMP-1 (P = .002), and COL1α1 (P < .001) was significantly up-regulated. IL-6 (P = .009) and FGF-2 (P = .004) mRNA expression was significantly down-regulated after implantation. Within patients, no difference between post-implantation mRNA expression (at 12 weeks) and when inflammation was observed. Between patients, the expression of IL-1ß (P = .015) and IL-17 (P = .02) was higher during cases of inflammation compared with patients who had no inflammation at 12-week follow-up. CONCLUSIONS: As part of a randomized, prospective, clinical trial, the present study reports the molecular profile of selected cytokines in the soft tissue around BAHS. Within the limit of this study, the results showed that 12 weeks after BAHS implantation the gene expression of some inflammatory cytokines (IL-8 and IL-1ß) is still relatively high compared with the baseline, steady-state, expression. The up-regulation of anabolic (COL1α1) and tissue-remodeling (MMP-9 and TIMP1) genes indicates an ongoing remodeling process after 12 weeks of implantation. The results suggest that IL-1ß, IL-17, and TNF-α may be interesting markers associated with inflammation.

The Use of Cone Beam Computed Tomography in Assessing the Insertion of Bone Conduction Hearing Implants.

OBJECTIVE: This study aimed to compare postoperative cone beam CT (CBCT) imaging to implant stability quotient (ISQ) measurement and direct caliper measurements as a suitable technique to assess bone conduction hearing implant (BCHI) seating and insertion depth. METHODS: In vitro, BCHIs were completely (n = 9) and partially inserted (n = 9) in bone blocks of different densities and subsequently scanned. Scans were processed using 3DSlicer 4.3.1 and Mathematica 10.3. ISQ measurements were obtained for all BCHIs mounted with different abutment lengths (9, 12, and 14 mm). CBCT imaging was performed for patients with a clinical indication. RESULTS: In vitro, 95% prediction intervals for partially inserted and completely inserted BCHIs were determined. ISQ values significantly decreased with partial insertion, low-density artificial bone, and longer abutment lengths. Evaluation of in vitro and in vivo 3D models allowed for assessment of insertion depth and inclination. CONCLUSION: CBCT imaging allows to study implant seating and insertion depth after BCHI surgery. This can be useful when visual confirmation is limited. It is possible to distinguish a partial BCHI insertion from a complete insertion in artificial bone blocks. This technique could prove to be a valuable research tool. In vitro, ISQ values for Ponto BCHIs relate to abutment length, insertion depth, and artificial bone density.