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Aim This European multicentric study aimed to prove safety and performance of the Bonebridge BCI 602 in children and adults suffering from either conductive hearing loss (CHL), mixed hearing loss (MHL), or single-sided sensorineural deafness (SSD). Methods 33 patients (13 adults and 10 children with either CHL or MHL and 10 patients with SSD) in three study groups were included. Patients were their own controls (single-subject repeated measures), comparing the unaided or pre-operative to the 3-month post-operative outcomes. Performance was evaluated by sound field thresholds (SF), word recognition scores (WRS) and/or speech reception thresholds in quiet (SRT) and in noise (SNR). Safety was demonstrated with a device-specific surgical questionnaire, adverse event reporting and stable pure-tone measurements. Results The Bonebridge BCI 602 significantly improved SF thresholds (+ 25.5 dB CHL/MHL/SSD), speech intelligibility in WRS (+ 68.0% CHL/MHL) and SRT in quiet (− 16.5 dB C/MHL) and in noise (− 3.51 dB SNR SSD). Air conduction (AC) and bone conduction (BC) thresholds remained stable over time. All adverse events were resolved, with none unanticipated. Mean audio processor wearing times in hours [h] per day for the CHL/MHL group were ~ 13 h for adults, ~ 11 h for paediatrics and ~ 6 h for the SSD group. The average surgical length was 57 min for the CHL/MHL group and 42 min for the SSD group. The versatility of the BCI 602 (reduced drilling depth and ability to bend the transition for optimal placement) allows for treatment of normal, pre-operated and malformed anatomies. All audiological endpoints were reached. Conclusions The Bonebridge BCI 602 significantly improved hearing thresholds and speech understanding. Since implant placement follows the patient’s anatomy instead of the shape of the device and the duration of surgery is shorter than with its predecessor, implantation is easier with the BCI 602. Performance and safety were proven for adults and children as well as for the CHL/MHL and SSD indications 3 months post-operatively.

Approximately 1 in 10 children with hearing loss is affected by auditory neuropathy spectrum disorder (ANSD). People who have ANSD usually have great difficulty understanding speech or communicating. However, it is possible for these patients to have audiograms that may indicate profound hearing loss up to normal hearing. This disorder is prognosed with positive, intact or present otoacoustic emissions (OAE) and/or cochlear microphonics (CM) as well as abnormal or absent auditory brainstem responses (ABR). Treatment methods include conventional hearing aids as well as cochlear implants. Cochlear implants (CI) usually promise better speech understanding for ANSD patients. We performed a systematic literature review aiming to show what improvements can effectively be achieved with cochlear implants in children with ANSD and compare this with our experience with two cases of ANSD implanted at our clinic. The retrospective review of two young CI patients diagnosed with ANSD during infancy demonstrated improvements over time in speech development communicated by their parents.

Purpose This multicentric, retrospective study aimed to analyze the short-term safety and effectiveness of the mCLIP Partial Prosthesis . Methods Patients underwent tympanoplasty with implantation of a mCLIP Partial Prosthesis. Follow-up examination included ear microscopy and pure-tone audiometry to determine the post-operative pure tone average of the frequencies 0.5, 1, 2 and 3 kHz (PTA 4 ). The post-operative PTA 4 air bone gap (ABG) was used to evaluate the audiological outcome. A post-operative minimum and maximum follow-up period was not defined. Thus, the follow-up times of each study center were different, which resulted in different follow-up times for the audiological analysis and for adverse events (AE). Results 72 (66 adults, 6 children) patients were implanted with the mCLIP Partial Prosthesis. 68 (62 adults, 6 children) patients underwent audiological examination; all 72 patients were examined for adverse events. All patients ( N  = 68): 72.1% of the patients showed a PTA 4 ABG of ≤ 20 dB. Individual post-operative bone conduction (BC) PTA 4 thresholds were stable in 67 patients. The mean post-operative follow-up time was 78 ± 46 days. Children ( N  = 6): 5 out of 6 children showed a PTA 4 ABG of ≤ 20 dB. None of the children reported a BC PTA 4 deterioration of > 10 dB HL after the implantation. The mean post-operative follow-up time was 101 ± 45 days. Adverse events (all patients, N = 72): 15 (14 adults, 1 child) patients had AEs (27 AEs and 2 Follow-Ups). The mean post-operative follow-up time was 375 days. Conclusion Clinical data show satisfactory audiological parameters after implantation of the mCLIP Partial Prosthesis. The prosthesis is safe and effective for implantation in children and adults. Trial registration number NCT05565339, 09 September 2022, retrospectively registered.

Biochar and its properties can be significantly altered according to how it is produced, and this has ramifications towards how biochar behaves once added to soil. We produced biochars from corncob and miscanthus straw via different methods (slow pyrolysis, hydrothermal and flash carbonization) and temperatures to assess how carbon cycling and soil microbial communities were affected. Mineralization of biochar, its parent feedstock, and native soil organic matter were monitored using 13C natural abundance during a 1-year lab incubation. Bacterial and fungal community compositions were studied using T-RFLP and ARISA, respectively. We found that persistent biochar-C with a half-life 60 times higher than the parent feedstock can be achieved at pyrolysis temperatures of as low as 370 °C, with no further gains to be made at higher temperatures. Biochar re-applied to soil previously incubated with our highest temperature biochar mineralized faster than when applied to unamended soil. Positive priming of native SOC was observed for all amendments but subsided by the end of the incubation. Fungal and bacterial community composition of the soil-biochar mixture changed increasingly with the application of biochars produced at higher temperatures as compared to unamended soil. Those changes were significantly (P < 0.005) related to biochar properties (mainly pH and O/C) and thus were correlated to pyrolysis temperature. In conclusion, our results suggest that biochar produced at temperatures as low as 370 °C can be utilized to sequester C in soil for more than 100 years while having less impact on soil microbial activities than high-temperature biochars.

The kinesin-3 family member KIF1A has been shown to be important for experience dependent neuroplasticity. In Drosophila , amorphic mutations in the KIF1A homolog unc-104 disrupt the formation of mature boutons. Disease associated KIF1A mutations have been associated with motor and sensory dysfunctions as well as non-syndromic intellectual disability in humans. A hypomorphic mutation in the forkhead-associated domain of Unc-104, unc-104 bris , impairs active zone maturation resulting in an increased fraction of post-synaptic glutamate receptor fields that lack the active zone scaffolding protein Bruchpilot. Here, we show that the unc-104 bris mutation causes defects in synaptic transmission as manifested by reduced amplitude of both evoked and miniature excitatory junctional potentials. Structural defects observed in the postsynaptic compartment of mutant NMJs include reduced glutamate receptor field size, and altered glutamate receptor composition. In addition, we observed marked loss of postsynaptic scaffolding proteins and reduced complexity of the sub-synaptic reticulum, which could be rescued by pre- but not postsynaptic expression of unc-104 . Our results highlight the importance of kinesin-3 based axonal transport in synaptic transmission and provide novel insights into the role of Unc-104 in synapse maturation.

The kinesin-3 family member Unc-104/KIF1A is required for axonal transport of many presynaptic components to synapses, and mutation of this gene results in synaptic dysfunction in mice, flies and worms. Our studies at the Drosophila neuromuscular junction indicate that many synaptic defects in unc-104-null mutants are mediated independently of Unc-104’s transport function, via the Wallenda (Wnd)/DLK MAP kinase axonal damage signaling pathway. Wnd signaling becomes activated when Unc-104’s function is disrupted, and leads to impairment of synaptic structure and function by restraining the expression level of active zone (AZ) and synaptic vesicle (SV) components. This action concomitantly suppresses the buildup of synaptic proteins in neuronal cell bodies, hence may play an adaptive role to stresses that impair axonal transport. Wnd signaling also becomes activated when pre-synaptic proteins are over-expressed, suggesting the existence of a feedback circuit to match synaptic protein levels to the transport capacity of the axon. Each nerve cell, or neuron, has a long nerve fiber – called an axon – that forms specialized sites for information exchange – called synapses – with other cells. Many molecules work at synapses to coordinate the exchange of information. These molecules are largely made in the central part of the neuron – known as the cell body – and are then transported along the axon to the synapses. The transport of these molecules is carried out by proteins known as molecular motors. One molecular motor, called KIF1A in humans and Unc-104 in fruit flies, is thought to be a major transporter of synaptic molecules. Mutations that hinder this molecular motor result in neurons failing to form synapses and, instead, synaptic components accumulate in the cell body. However, it was not clearif Unc-104 does actually carry all of the components needed to assemble synapses along axons, or if it influences synapse formation in another way. Now, Li, Zhang et al. report new evidence that supports the second of these two hypotheses. The experiments made use of fruit flies in which the gene for Unc-104 had been deleted, and revealed that inhibiting enzymes in a specific signaling pathway could reverse the synaptic problems caused by the loss of Unc-104. The signaling pathway, which is conserved between flies and humans, involves an enzyme that is called Wnd in flies and DLK in humans. The Wnd/DLK signaling pathway was previously known to regulate how neurons respond when their axons are damaged (either by growing new axons or dying, depending on the context). Further investigation by Li, Zhang et al. revealed that signaling via the Wnd enzyme becomes triggered whenever the Unc-104 molecular motor is impaired. This activation correlates with the build-up of synaptic proteins in the cell body. Once activated, the pathway then reduces the total amount of synaptic proteins that the cell makes. This reduction matches the neuron’s reduced ability to transport them along the axon, and may help the neuron to adapt when axonal transport is impaired. However, the reduction in synaptic proteins also impaired the exchange of information at the synapses. These findings suggest how DLK could be behind problems with synapses in diseases in which transport along axons is impaired. These diseases include hereditary spastic paraplegia, which has been linked to mutations in human KIF1A, and may also include ALS and Alzheimer’s disease, which have recently been linked to DLK. DLK has received recent attention as a candidate drug target because it contributes to the deterioration of damaged neurons. These new findings further expand that interest by suggesting that inhibiting DLK may help neurons to maintain working synapses, which is more useful than simply preventing damaged neurons from dying.

Mutations in the kinesin-3 family member KIF1A have been associated with hereditary spastic paraplegia (HSP), hereditary and sensory autonomic neuropathy type 2 (HSAN2) and non-syndromic intellectual disability (ID). Both autosomal recessive and autosomal dominant forms of inheritance have been reported. Loss of KIF1A or its homolog unc-104 causes early postnatal or embryonic lethality in mice and Drosophila, respectively. In this study, we use a previously described hypomorphic allele of unc-104, unc-104(bris) , to investigate the impact of partial loss-of-function of kinesin-3 on synapse maturation at the Drosophila neuromuscular junction (NMJ). Unc-104(bris) mutants exhibit structural defects where a subset of synapses at the NMJ lack all investigated active zone (AZ) proteins, suggesting a complete failure in the formation of the cytomatrix at the active zone (CAZ) at these sites. Modulating synaptic Bruchpilot (Brp) levels by ectopic overexpression or RNAi-mediated knockdown suggests that the loss of AZ components such as Ca(2+) channels and Liprin-α is caused by impaired kinesin-3 based transport rather than due to the absence of the key AZ organizer protein, Brp. In addition to defects in CAZ assembly, unc-104(bris) mutants display further defects such as depletion of dense core and synaptic vesicle (SV) markers from the NMJ. Notably, the level of Rab3, which is important for the allocation of AZ proteins to individual release sites, was severely reduced at unc-104(bris) mutant NMJs. Overexpression of Rab3 partially ameliorates synaptic phenotypes of unc-104(bris) larvae, suggesting that lack of presynaptic Rab3 contributes to defects in synapse maturation.

The application of biochar to soils is a promising technique for increasing soil organic C and offsetting GHG emissions. However, large-scale adoption by farmers will likely require the proof of its utility to improve plant growth and soil quality. In this context, we conducted a four-year field experiment between October 2010 to October 2014 on a fertile silty clay loam Albeluvisol in Norway to assess the impact of biochar on soil physical properties, soil microbial biomass, and oat and barley yield. The following treatments were included: Control (soil), miscanthus biochar 8 t C ha1 (BC8), miscanthus straw feedstock 8 t C ha1 (MC8), and miscanthus biochar 25 t C ha1 (BC25). Average volumetric water content at field capacity was significantly higher in BC25 when compared to the control due to changes in BD and total porosity. The biochar amendment had no effect on soil aggregate (2–6 mm) stability, pore size distribution, penetration resistance, soil microbial biomass C and N, and basal respiration. Biochar did not alter crop yields of oat and barley during the four growing seasons. In order to realize biochar’s climate mitigation potential, we suggest future research and development efforts should focus on improving the agronomic utility of biochar in engineered fertilizer and soil amendment products.

Northern peatlands hold large amounts of organic carbon (C) in their soils and are as such important in a climate change context. Blanket bogs, i.e. nutrient-poor peatlands restricted to maritime climates, may be extra vulnerable to global warming since they require a positive water balance to sustain their moss dominated vegetation andCsink functioning. This study presents a 4.5 year record of land– atmosphere carbon dioxide (CO2) exchange from the Andøya blanket bog in northern Norway. Compared with other peatlands, the Andøya peatland exhibited low flux rates, related to the low productivity of the dominating moss and lichen communities and the maritime settings that attenuated seasonal temperature variations. It was observed that under periods of high vapour pressure deficit, net ecosystem exchange was reduced, which was mainly caused by a decrease in gross primary production. However, no persistent effects of dry conditions on theCO2 exchange dynamics were observed, indicating that under present conditions and within the range of observed meteorological conditions the Andøya blanket bog retained its C uptake function. Continued monitoring of these ecosystem types is essential in order to detect possible effects of a changing climate.

Peatlands store substantial amounts of carbon and are vulnerable to climate change. We present a modified version of the Organising Carbon and Hydrology In Dynamic Ecosystems (ORCHIDEE) land surface model for simulating the hydrology, surface energy, and CO2 fluxes of peatlands on daily to annual timescales. The model includes a separate soil tile in each 0.5∘ grid cell, defined from a global peatland map and identified with peat-specific soil hydraulic properties. Runoff from non-peat vegetation within a grid cell containing a fraction of peat is routed to this peat soil tile, which maintains shallow water tables. The water table position separates oxic from anoxic decomposition. The model was evaluated against eddy-covariance (EC) observations from 30 northern peatland sites, with the maximum rate of carboxylation (Vcmax) being optimized at each site. Regarding short-term day-to-day variations, the model performance was good for gross primary production (GPP) (r2= 0.76; Nash–Sutcliffe modeling efficiency, MEF = 0.76) and ecosystem respiration (ER, r2= 0.78, MEF = 0.75), with lesser accuracy for latent heat fluxes (LE, r2= 0.42, MEF = 0.14) and and net ecosystem CO2 exchange (NEE, r2= 0.38, MEF = 0.26). Seasonal variations in GPP, ER, NEE, and energy fluxes on monthly scales showed moderate to high r2 values (0.57–0.86). For spatial across-site gradients of annual mean GPP, ER, NEE, and LE, r2 values of 0.93, 0.89, 0.27, and 0.71 were achieved, respectively. Water table (WT) variation was not well predicted (r2 < 0.1), likely due to the uncertain water input to the peat from surrounding areas. However, the poor performance of WT simulation did not greatly affect predictions of ER and NEE. We found a significant relationship between optimized Vcmax and latitude (temperature), which better reflects the spatial gradients of annual NEE than using an average Vcmax value.