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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Optical analysis of glutamate spread in the neuropil.

Fast synaptic communication uses diffusible transmitters whose spread is limited by uptake mechanisms. However, on the submicron-scale, the distance between two synapses, the extent of glutamate spread has so far remained difficult to measure. Here, we show that quantal glutamate release from individual hippocampal synapses activates extracellular iGluSnFr molecules at a distance of >1.5 µm. 2P-glutamate uncaging near spines further showed that alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-Rs and N-methyl-D-aspartate (NMDA)-Rs respond to distant uncaging spots at approximately 800 and 2000 nm, respectively, when releasing the amount of glutamate contained in approximately five synaptic vesicles. The uncaging-induced remote activation of AMPA-Rs was facilitated by blocking glutamate transporters but only modestly decreased by elevating the recording temperature. When mimicking release from neighboring synapses by three simultaneous uncaging spots in the microenvironment of a spine, AMPA-R-mediated responses increased supra-additively. Interfering with extracellular glutamate diffusion through a glutamate scavenger system weakly reduced field synaptic responses but not the quantal amplitude. Together, our data suggest that the neuropil is more permissive to short-range spread of transmitter than suggested by theory, that multivesicular release could regularly coactivate nearest neighbor synapses and that on this scale glutamate buffering by transporters primarily limits the spread of transmitter and allows for cooperative glutamate signaling in extracellular microdomains.

Father newborn skin-to-skin wheelchair transfer from delivery room to neonatal care unit: Possible change in practices.

OBJECTIVE: To evaluate the transfer of newborns from the delivery room to the neonatal care unit with their fathers on wheelchairs in terms of the safety of the procedure and paternal anxiety. METHODS: A prospective observational single-center before-and-after pilot study was conducted from February to May 2018 at the University Maternity Hospital of Nantes. Safe transfer was judged on the basis of episodes of hypothermia or hypoglycemia. Paternal anxiety was assessed with the State-Trait Anxiety Inventory (STAI) scale after newborn transfer. RESULTS: Overall, 70 preterm newborns were enrolled, 44 were carried in wheelchairs in the father's arms (target group) and 26 were transferred in an incubator (control group). After adjusting for gestational age and birthweight, there were no statistically significantly differences between the target and the control group in the rates of hypothermia (43.9% vs 30.8%, p = 0,59) and hypoglycemia (9.52% vs 19.23%, p = 0,19). The STAI scale score was not significantly different between groups after incubator transfer or wheelchair transfer, at 35 ± 8.2 and 38 ± 10.2, respectively (p = 0.07). CONCLUSION: Transferring a newborn to the neonatal care unit via wheelchair with the father is a safe alternative to incubator transfer.

Demonstrating the processes and outcomes of a rural Community Mental Health Rehabilitation Service: A realist evaluation.

BACKGROUND: As part of significant mental health reform, the Community Mental Health Rehabilitation Service (CMHRS) was implemented in rural South Australia. The CMHRS is a 10-bed mental health residential program offering rehabilitative mental health support to rural residents. AIM: To analyse the CMHRS service delivery model and its impact on recovery outcomes for consumers. METHODS: A mixed method, realist evaluation approach was utilised. A purposive sample of CMHRS staff (n = 6) and consumers (n = 8) were recruited. Consumer recovery was measured using the RAS-DS (on admission and discharge). Participants' perspectives of the service were gained via one staff focus group (n = 6) and individual semi-structured interviews (consumers n = 6; staff n = 2). Pre-post RAS-DS scores were analysed using paired t-tests/Wilcoxon paired-signed rank test, with qualitative data analysed thematically. RESULTS: Significant positive increases in RAS-DS total scores were observed at discharge, supported by the qualitative themes of (re)building relationships and social connections and recovering health and wellbeing. Contextual factors (e.g. staffing) and program mechanisms (e.g. scheduling) impacting on service implementation were identified. CONCLUSION: Maintaining a rehabilitation recovery-focused approach, balanced with an appropriately trained multi-disciplinary team, are vital for maximising positive consumer outcomes. SIGNIFICANCE: This realist evaluation identifies critical factors impacting rural mental health rehabilitation service delivery.

COVID-19 in children at Strasbourg University Hospital: A retrospective study of the first 2months of the epidemic.

CONTEXT: The emergence and rapid spread of coronavirus disease 2019 (COVID-19) have shaken the planet, both in terms of health and economical aspects, constituting a real challenge for the scientific community. PROBLEM: At the time of the arrival of the epidemic in France, there were limited data regarding how COVID-19 could affect children. A lesser severity compared with adults was described, but knowledge concerning clinical forms and screening strategies was missing. METHODOLOGY: In this retrospective and non-interventional epidemiological study, we aimed to describe the epidemiology and the clinical features of COVID-19 pediatric disease in the first university hospital affected by the epidemic in France. We included all underage patients who tested positive for SARS-CoV-2 by polymerase chain reaction (PCR) assays on nasopharyngeal smears performed between February 25, 2020 and April 30, 2020. RESULTS: The presence of fever and respiratory signs was frequent (>50%), as was the presence of general or digestive signs, but patients were also frequently asymptomatic, making the discovery of a positive smear fortuitous. There were no deaths in our cohort. CONCLUSION: No patient with a serious form of COVID-19 was treated in the pediatrics departments of Strasbourg University Hospital during the first 2 months of the epidemic. Diagnostic strategies have evolved over the course of the epidemic, ranging from exploring relevant symptoms to systematic screening.