Hearing impairment amongst people with Osteogenesis Imperfecta in Germany.

INTRODUCTION: Hearing impairment concerns a relevant percentage of individuals with Osteogenesis Imperfecta (OI). When looking at the current literature, the percentage of affected individuals with OI varies greatly from 32 to 58% of patients having mild OI and 21% to 27% of patients having moderate to severe OI. Little is known about the German population with OI. METHOD: The goal of this study was to detect how many patients with OI, who visited the annual meeting of the German Association for Osteogenesis Imperfecta in 2023, proved to have a hearing impairment. In this prospective, cross-sectional study, each included individual obtained ear microscopy, audiometry, stapedius reflexes, tympanometry, and OAEs. Furthermore, each patient was asked a set of questions concerning the medical history. RESULTS: Of the included patients, 33% had hearing impairment. A significant difference was found for the mean air-bone gap (ABG) as well as the hearing threshold of the right ears. The difference was found between OI type III and IV (p = 0.0127) for the mean ABG and OI type I and IV (p = 0.0138) as well as III and IV (p = 0.0281) for the hearing threshold. Spearman's rank correlation showed a high correlation between age and hearing threshold. Of the patients between 40 and 50 years old, 56% had hearing loss. CONCLUSION: Hearing loss in individuals with OI is still a relevant problem, especially age-related in OI type I. Audiometry should be performed at least when individuals experience subjective hearing loss. The implementation of a screening starting at 40 years should be discussed and studied.

Simultaneous closure of a perilymphatic fistula and placement of cochlear implant in a case of complex inner ear malformation.

Key Clinical Message: In young infants, under the age of one-year, cochlear malformation with profound hearing loss complicated by a perilymphatic fistula (PLF), presents a serious clinical challenge, warranting immediate audiological and surgical intervention. Timely PLF detection and closure, along with an early CI can significantly improve the prognosis of such patients and helps them in achieving their maximum hearing and developmental potential, in the long term. Abstract: Inner ear malformation (IEM) with incomplete partition and cystic cochlea is mostly accompanied by profound hearing loss. It gets further complicated with other malformations such as a perilymphatic fistula (PLF). This case concerns an 8-month-old child cochlear malformation and profound hearing loss. Surgical intervention identified a PLF at the stapedial footplate, which was successfully closed. The surgery also included the placement of a cochlear implant (CI) in the right ear, via the round window. The left ear was equipped with hearing aids, with persistent hearing thresholds at 70-80 db. At the age of 6 years, the child showed a good hearing outcome with the CI, with only moderate speech delay. Cochlear malformation accompanied by a perilymphatic leakage warrants immediate surgical closure of the PLF, to minimize the risk of bacterial meningitis. Wherever possible, the feasibility of a CI should be explored in such cases and a CI should be placed for treatment of hearing loss. Audiological and speech outcomes may vary with the use of the CI, especially in cases of IEM. However, an early CI coupled with timely PLF detection and closure can help children with profound hearing loss, in achieving their maximum hearing and developmental potential, in the long run.

Elementary Observations: Building Blocks of Physical Information Gain.

In this paper, we are concerned with the process of experimental information gain. Building on previous work, we show that this is a discontinuous process in which the initiating quantum-mechanical matter-instrument interactions are being turned into macroscopically observable events (EOs). In the course of time, such EOs evolve into spatio-temporal patterns of EOs, which allow conceivable alternatives of physical explanation to be distinguished. Focusing on the specific case of photon detection, we show that during their lifetimes, EOs proceed through the four phases of initiation, detection, erasure and reset. Once generated, the observational value of EOs can be measured in units of the Planck quantum of physical action h=4.136×10-15eVs. Once terminated, each unit of entropy of size kB=8.617×10-5eV/K, which had been created in the instrument during the observational phase, needs to be removed from the instrument to ready it for a new round of photon detection. This withdrawal of entropy takes place at an energetic cost of at least two units of the Landauer minimum energy bound of ELa=ln⁡2kBTD for each unit of entropy of size kB.

Ice sheet-free West Antarctica during peak early Oligocene glaciation.

One of Earth's most fundamental climate shifts, the greenhouse-icehouse transition 34 million years ago, initiated Antarctic ice sheet buildup, influencing global climate until today. However, the extent of the ice sheet during the Early Oligocene Glacial Maximum (~33.7 to 33.2 million years ago) that immediately followed this transition-a critical knowledge gap for assessing feedbacks between permanently glaciated areas and early Cenozoic global climate reorganization-is uncertain. In this work, we present shallow-marine drilling data constraining earliest Oligocene environmental conditions on West Antarctica's Pacific margin-a key region for understanding Antarctic ice sheet evolution. These data indicate a cool-temperate environment with mild ocean and air temperatures that prevented West Antarctic Ice Sheet formation. Climate-ice sheet modeling corroborates a highly asymmetric Antarctic ice sheet, thereby revealing its differential regional response to past and future climatic change.

Events as Elements of Physical Observation: Experimental Evidence.

It is argued that all physical knowledge ultimately stems from observation and that the simplest possible observation is that an event has happened at a certain space-time location X→=x→,t. Considering historic experiments, which have been groundbreaking in the evolution of our modern ideas of matter on the atomic, nuclear, and elementary particle scales, it is shown that such experiments produce as outputs streams of macroscopically observable events which accumulate in the course of time into spatio-temporal patterns of events whose forms allow decisions to be taken concerning conceivable alternatives of explanation. Working towards elucidating the physical and informational characteristics of those elementary observations, we show that these represent hugely amplified images of the initiating micro-events and that the resulting macro-images have a cognitive value of 1 bit and a physical value of Wobs=Eobsτobs≫h. In this latter equation, Eobs stands for the energy spent in turning the initiating micro-events into macroscopically observable events, τobs for the lifetimes during which the generated events remain macroscopically observable, and h for Planck's constant. The relative value Gobs=Wobs/h finally represents a measure of amplification that was gained in the observation process.

Microstructural alterations of major thalamic nuclei in the chronic pediatric spinal cord injured population.

Background: The brain undergoes reorganization following spinal cord injury (SCI), but little is known about how the thalamus is affected in pediatric SCIs. Purpose: To characterize microstructural alterations in the thalamus after SCI with diffusion tensor imaging (DTI) metrics. Methods: 18 pediatric participants with chronic SCI (8-20 years) were stratified using the American Spinal Injury Association Impairment Scale (AIS) into groups: A, B, and C/D. DTI of the brain used a 3 T Siemens Verio MRI using the parameters: 20 directions, number of averages = 3, b = 1000 s/mm2, voxel size = 1.8 mm × 1.8 mm, slice thickness = 5 mm, TE = 95 ms, TR = 4300 ms, 30 slices, FOV = 230 × 230 mm2, matrix = 128 × 128, acquisition time = 4:45 min. Diffusion data was processed to generate DTI metrics FA, MD, AD, and RD. Data analysis: DTI metrics were acquired by superimposing the AAL3 thalamic atlas onto participant diffusion images registered to MNI152 space. We utilized a multiple Mann-Whitney U-test to compare between AIS groups, considering values of p ≤ 0.05 as significant. Results: FA, AD, RD, and MD significantly differed in thalamic nuclei between AIS groups A vs B and B vs C/D. Significant nuclei include the right ventral anterior, left intralaminar, bilateral lateral pulvinar, and right lateral geniculate. Conclusion: Our findings suggest the presence of microstructural alterations based on SCI severity in pediatric patients. These results are encouraging and warrant further study.

Pathogenic missense variation in PABPC1L/EPAB causes female infertility due to oocyte maturation arrest at the germinal vesicle stage.

Women undergoing controlled ovarian hyperstimulation prior to in vitro fertilization (IVF) are treated using various protocols to induce multiple follicular growths. Complete failure of all oocytes to mature during IVF cycles is rare; however, it is a known cause of primary female infertility. Recently, pathogenic variations in a few genes have been identified in women with oocyte maturation defects; however, the underlying genetic causes remain largely unknown.This study included a Turkish family comprising three sisters with recurring oocyte maturation arrest at the germinal vesicle stage after multiple ovarian stimulations. Exome sequencing revealed a homozygous missense variant (c.1037C>T, p.Ala346Val) in the EPAB gene (also known as PABPC1L) in all three affected sisters, which was either absent or heterozygous in the unaffected family members. Functional experiments confirming the pathogenicity of the variant were performed by transfecting HEK293T cells and demonstrated the instability and increased rate of proteolysis of the mutated PABPC1L/EPAB protein. The identified variant, located in the well-conserved fourth RNA recognition motif (RRM4), in silico 3D modelling suggested changes in the physical properties of the pathogenic variant of PABPC1L/EPAB. Our findings validate PABPC1L/EPAB as an essential genetic contributor to the oocyte maturation process in humans and have direct implications for the genetic counselling of patients and their family members.

Corrigendum: Echocardiography and extravascular lung water during 3 weeks of exposure to high altitude in otherwise healthy asthmatics.

[This corrects the article DOI: 10.3389/fphys.2023.1214887.].

Echocardiography and extravascular lung water during 3 weeks of exposure to high altitude in otherwise healthy asthmatics.

Background: Asthma rehabilitation at high altitude is common. Little is known about the acute and subacute cardiopulmonary acclimatization to high altitude in middle-aged asthmatics without other comorbidities. Methods: In this prospective study in lowlander subjects with mostly mild asthma who revealed an asthma control questionnaire score >0.75 and participated in a three-week rehabilitation program, we assessed systolic pulmonary artery pressure (sPAP), cardiac function, and extravascular lung water (EVLW) at 760 m (baseline) by Doppler-echocardiography and on the second (acute) and last day (subacute) at a high altitude clinic in Kyrgyzstan (3100 m). Results: The study included 22 patients (eight male) with a mean age of 44.3 ± 12.4 years, body mass index of 25.8 ± 4.7 kg/m2, a forced expiratory volume in 1 s of 92% ± 19% predicted (post-bronchodilator), and partially uncontrolled asthma. sPAP increased from 21.8 mmHg by mean difference by 7.5 [95% confidence interval 3.9 to 10.5] mmHg (p < 0.001) during acute exposure and by 4.8 [1.0 to 8.6] mmHg (p = 0.014) during subacute exposure. The right-ventricular-to-pulmonary-artery coupling expressed by TAPSE/sPAP decreased from 1.1 by -0.2 [-0.3 to -0.1] mm/mmHg (p < 0.001) during acute exposure and by -0.2 [-0.3 to -0.1] mm/mmHg (p = 0.002) during subacute exposure, accordingly. EVLW significantly increased from baseline (1.3 ± 1.8) to acute hypoxia (5.5 ± 3.5, p < 0.001) but showed no difference after 3 weeks (2.0 ± 1.8). Conclusion: In otherwise healthy asthmatics, acute exposure to hypoxia at high altitude increases pulmonary artery pressure (PAP) and EVLW. During subacute exposure, PAP remains increased, but EVLW returns to baseline values, suggesting compensatory mechanisms that contribute to EVLW homeostasis during acclimatization.

Space hardware for concrete sample production on ISS "MASON concrete mixer".

Advances in space flight technology will enable the construction of Moon or even Mars bases in the not-too-distant future. Thus, materials will be needed that are suitable for building in microgravity environments. One idea is to use concrete, the most used construction material on Earth, for these challenging tasks. The hardening and the properties of concrete under the boundary conditions prevailing on Earth are well understood, but there is only limited research on concrete produced in microgravity. Hence, a research project called MASON was established, which aims to mix and harden concrete on the ISS and to investigate the properties of the specimens made in microgravity extensively. Since a defined geometry of the specimens would be favorable for these investigations, a special hardware was developed, called the MASON Concrete Mixer (MCM), which allows the production of concrete specimens fulfilling the requirements on the geometry as well as the safety requirements. Subsequently, the development, design, tests, and qualification of the MCM as well as its usage are presented.

Measurement of the α-Particle Monopole Transition Form Factor Challenges Theory: A Low-Energy Puzzle for Nuclear Forces?

We perform a systematic study of the α-particle excitation from its ground state 0_{1}^{+} to the 0_{2}^{+} resonance. The so-called monopole transition form factor is investigated via an electron scattering experiment in a broad Q^{2} range (from 0.5 to 5.0 fm^{-2}). The precision of the new data dramatically supersedes that of older sets of data, each covering only a portion of the Q^{2} range. The new data allow the determination of two coefficients in a low-momentum expansion, leading to a new puzzle. By confronting experiment to state-of-the-art theoretical calculations, we observe that modern nuclear forces, including those derived within chiral effective field theory that are well tested on a variety of observables, fail to reproduce the excitation of the α particle.

Cost of exome analysis in patients with intellectual disability: a micro-costing study in a French setting.

BACKGROUND: With the development of next generation sequencing technologies in France, exome sequencing (ES) has recently emerged as an opportunity to improve the diagnosis rate of patients presenting an intellectual disability (ID). To help French policy makers determine an adequate tariff for ES, we aimed to assess the unit cost per ES diagnostic test for ID from the preparation of the pre-analytical step until the report writing step and to identify its main cost drivers. METHODS: A micro-costing bottom-up approach was conducted for the year 2018 in a French setting as part of the DISSEQ study, a cost-effectiveness study funded by the Ministry of Health and performed in collaboration with the GAD (Génétique des Anomalies du Développement), a genetic team from the Dijon University Hospital, and a public sequencing platform, the Centre National de Recherche en Génomique Humaine (CNRGH). The analysis was conducted from the point of view of these two ES stakeholders. All of the resources (labor, equipment, disposables and reagents, reusable material) required to analyze blood samples were identified, collected and valued. Several sensitivity analyses were performed. RESULTS: The unit nominal cost per ES diagnostic test for ID was estimated to be €2,019.39. Labor represented 50.7% of the total cost. The analytical step (from the preparation of libraries to the analysis of sequences) represented 88% of the total cost. Sensitivity analyses suggested that a simultaneous price decrease of 20% for the capture kit and 50% for the sequencing support kit led to an estimation of €1,769 per ES diagnostic test for ID. CONCLUSION: This is the first estimation of ES cost to be done in the French setting of ID diagnosis. The estimation is especially influenced by the price of equipment kits, but more generally by the organization of the centers involved in the different steps of the analysis and the time period in which the study was conducted. This information can now be used to define an adequate tariff and assess the efficiency of ES. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT03287206 on September 19, 2017.

Fully Automatic Method for Reliable Spinal Cord Compartment Segmentation in Multiple Sclerosis.

BACKGROUND AND PURPOSE: Fully automatic quantification methods of spinal cord compartments are needed to study pathologic changes of the spinal cord GM and WM in MS in vivo. We propose a novel method for automatic spinal cord compartment segmentation (SCORE) in patients with MS. MATERIALS AND METHODS: The cervical spinal cords of 24 patients with MS and 24 sex- and age-matched healthy controls were scanned on a 3T MR imaging system, including an averaged magnetization inversion recovery acquisition sequence. Three experienced raters manually segmented the spinal cord GM and WM, anterior and posterior horns, gray commissure, and MS lesions. Subsequently, manual segmentations were used to train neural segmentation networks of spinal cord compartments with multidimensional gated recurrent units in a 3-fold cross-validation fashion. Total intracranial volumes were quantified using FreeSurfer. RESULTS: The intra- and intersession reproducibility of SCORE was high in all spinal cord compartments (eg, mean relative SD of GM and WM: ≤ 3.50% and ≤1.47%, respectively) and was better than manual segmentations (all P < .001). The accuracy of SCORE compared with manual segmentations was excellent, both in healthy controls and in patients with MS (Dice similarity coefficients of GM and WM: ≥ 0.84 and ≥0.92, respectively). Patients with MS had lower total WM areas (P < .05), and total anterior horn areas (P < .01 respectively), as measured with SCORE. CONCLUSIONS: We demonstrate a novel, reliable quantification method for spinal cord tissue segmentation in healthy controls and patients with MS and other neurologic disorders affecting the spinal cord. Patients with MS have reduced areas in specific spinal cord tissue compartments, which may be used as MS biomarkers.

Effect of 5 weeks of oral acetazolamide on patients with pulmonary vascular disease: A randomized, double-blind, cross-over trial.

BACKGROUND: The carbonic anhydrase inhibitor acetazolamide stimulates ventilation through metabolic acidosis mediated by renal bicarbonate excretion. In animal models, acetazolamide attenuates acute hypoxia-induced pulmonary hypertension (PH), but its efficacy in treating patients with PH due to pulmonary vascular disease (PVD) is unknown. METHODS: 28 PVD patients (15 pulmonary arterial hypertension, 13 distal chronic thromboembolic PH), 13 women, mean±SD age 61.6±15.0 years stable on PVD medications, were randomised in a double-blind crossover protocol to 5 weeks acetazolamide (250mg b.i.d) or placebo separated by a ≥2 week washout period. Primary endpoint was the change in 6-minute walk distance (6MWD) at 5 weeks. Additional endpoints included safety, tolerability, WHO functional class, quality of life, arterial blood gases, and hemodynamics (by echocardiography). RESULTS: Acetazolamide had no effect on 6MWD compared to placebo (treatment effect: mean change [95%CI] -18 [-40 to 4]m, p=0.102) but increased arterial blood oxygenation through hyperventilation induced by metabolic acidosis. Other measures including pulmonary hemodynamics were unchanged. No severe adverse effects occurred, side effects that occurred significantly more frequently with acetazolamide vs. placebo were change in taste (22/0%), paraesthesia (37/4%) and mild dyspnea (26/4%). CONCLUSIONS: In patients with PVD, acetazolamide did not change 6MWD compared to placebo despite improved blood oxygenation. Some patients reported a tolerable increase in dyspnoea during acetazolamide treatment, related to hyperventilation, induced by the mild drug-induced metabolic acidosis. Our findings do not support the use of acetazolamide to improve exercise in patients with PVD at this dosing. GOV IDENTIFIER: NCT02755298.

Magnetic and electronic properties unveil polaron formation in Eu[Formula: see text]In[Formula: see text]Sb[Formula: see text].

The intermetallic compound Eu[Formula: see text]In[Formula: see text]Sb[Formula: see text], an antiferromagnetic material with nonsymmorphic crystalline structure, is investigated by magnetic, electronic transport and specific heat measurements. Being a Zintl phase, insulating behavior is expected. Our thermodynamic and magnetotransport measurements along different crystallographic directions strongly indicate polaron formation well above the magnetic ordering temperatures. Pronounced anisotropies of the magnetic and transport properties even above the magnetic ordering temperature are observed despite the Eu[Formula: see text] configuration which testify to complex and competing magnetic interactions between these ions and give rise to intricate phase diagrams discussed in detail. Our results provide a comprehensive framework for further detailed study of this multifaceted compound with possible nontrivial topology.

Evaluation of auditory pathway excitability using a pre-operative trans-tympanic electrically evoked auditory brainstem response under local anesthesia in cochlear implant candidates.

OBJECTIVE: Subjective promontory stimulation is used to evaluate cochlear implant (CI) candidacy, but the test reliability is low. Electrically evoked auditory brainstem response (EABR) can verify the function of the auditory system objectively. This study's procedure uses a trans-tympanic rounded bent-tip electrode to perform pre-operative EABR under local anaesthesia (LA-TT-EABR) using MED-EL Software and Hardware. This study aimed to determine usability and effectiveness for CI candidates. DESIGN: We hypothesised that LA-TT-EABR waveforms of good quality would be related to successful hearing outcomes. We assumed that the duration of hearing loss/deafness was a confounding factor to study outcomes. STUDY SAMPLE: 19 borderline CI candidates. RESULTS: Positive LA-TT-EABR results were confirmed in 14 patients. LA-TT-EABR's mean latency was 2.05 ± 0.31 ms (eII/eIII) and 4.24 ± 0.39 ms (eIV/eV). Latencies weren't statistically different from intra-operative EABR elicited by basal CI contacts. All positive LA-TT-EABR patients benefitted from CI and speech performance improved one year after implantation. One patient with negative LA-TT-EABR was cochlear-implanted and had no hearing sensation. CONCLUSIONS: LA-TT-EABR is a tool in the frame of pre-operative objective testing the auditory pathway. It seems useful for clinical testing CI candidacy. Based on this study's outcomes, LA-TT-EABR should be recommended for uncertain CI candidates.

Identification of newborns at risk of early-onset neonatal infection: New French guidelines and practices at Nantes University Hospital.

New French guidelines in 2017 aimed to improve the identification of newborns at risk of early-onset neonatal infection (EONI). Identification is based on perinatal risk factors, management of perinatal antibiotic prophylaxis, and standardized clinical assessment. We conducted a retrospective cross-study at the University Hospital of Nantes. The main objective was to assess implementation of the French guidelines. Of 1240 births included, 40% (501) required perinatal antibiotic prophylaxis (adequate in 67.3%) and 306 (24.7%) needed a standardized clinical assessment (performed in 69.2%). Only two newborns (0.16%) included in the study received neonatal antibiotic therapy. On the basis of the assessment conducted in our maternity ward, implementation of the recommendations seems to be effective.

Engineering of dense arrays of Vertical Si1-xGexnanostructures.

Vertical nanostructure technologies are becoming more important for the down scaling of nanoelectronic devices such as logic transistors or memories. Such devices require dense vertical nanostructured channel arrays (VNCA) that can be fabricated through a top-down approach based on group IV materials. We present progresses on the top-down fabrication of highly anisotropic and ultra-dense Si1-xGex(x= 0, 0.2, 0.5) VNCAs. Dense nanowire and nanosheet patterns were optimized through high resolution lithography and transferred onto Si1-xGexsubstrates by anisotropic reactive ion etching with a fluorine chemistry. The right gas mixtures for a given Ge content resulted in perfectly vertical and dense arrays. Finally we fabricated oxide shell/SiGe core heterostructures by dry- and wet-thermal oxidation and evaluated their applicability for nanostructure size engineering, as already established for silicon nanowires. The impact of the nanostructured shape (wire or sheet), size and Ge content on the oxide growth were investigated and analysed in detail through transmission electron microscopy.

Using fluorescent promoter-reporters to study sugar utilization control in Bifidobacterium longum NCC 2705.

Bifidobacteria are amongst the first bacteria to colonize the human gastro-intestinal system and have been proposed to play a crucial role in the development of the infant gut since their absence is correlated to the development of diseases later in life. Bifidobacteria have the capacity to metabolize a diverse range of (complex) carbohydrates, reflecting their adaptation to the lower gastro-intestinal tract. Detailed understanding of carbohydrate metabolism regulation in this genus is of prime importance and availability of additional genetic tools easing such studies would be beneficial. To develop a fluorescent protein-based reporter system that can be used in B. longum NCC 2705, we first selected the most promising fluorescent protein out of the seven we tested (i.e., mCherry). This reporter protein was then used to study the carbohydrate mediated activation of PBl1518 and PBl1694, two promoters respectively predicted to be controlled by the transcriptional factors AraQ and AraU, previously suggested to regulate arabinose utilization and proposed to also act as global transcriptional regulators in bifidobacteria. We confirmed that in B. longum NCC 2705 the AraQ controlled promoter (PBl1518) is induced strongly by arabinose and established that the AraU controlled promoter (PBl1694) was mostly induced by the hexoses galactose and fructose. Combining the mCherry reporter system with flow cytometry, we established that NCC 2705 is able to co-metabolize arabinose and glucose while galactose was only consumed after glucose exhaustion, thus illustrating the complexity of different carbohydrate consumption patterns and their specific regulation in this strain.