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Abstract The Rey Auditory Verbal Learning Test (RAVLT) is a commonly used tool for evaluating verbal learning and memory in neuropsychological assessments. In recent years, we developed a Virtual Reality (VR) adaptation of the RAVLT (VR-RVLT), aiming for increased ecological validity compared to the traditional pen and paper gold standard (GS-RAVLT). Following validation in healthy cohorts, the VR-RAVLT was validated with thirty individuals with Parkinson's Disease (PD) that completed both the GS-RAVLT and the VR- RAVLT. Validity of the VR-RAVLT was evaluated by assessing its construct and discriminant validity, and test–retest reliability, in comparison to the GS-RAVLT. Results of the PD participants were compared to those of 46 previously recruited healthy participants with comparable age and level of education. Main outcome measures derived from the remembered items on the test lists, exhibited significant and comparable correlations between VR-RAVLT and GS-RAVLT, both among healthy participants and PD participants. Likewise, serial position effects were similar for both formats amog the PD participants. Additionally, both formats showed similar discriminatory ability between healthy controls and PD participants, as well as comparable test–retest reliability measures. Taken together, the results suggest that the VR-based RAVLT is equally effective in measuring verbal memory capabilities in individuals with PD as compared to the GS-RAVLT. Certain results indicate that the virtual reality version has the capability to encompass additional factors that might impact memory performance, thereby suggesting an enhanced ecological validity.

Abstract Parkinson’s Disease (PD)-typical declines in gait coordination are possibly explained by weakness in bilateral cortical and muscular connectivity. Here, we seek to determine whether this weakness and consequent decline in gait coordination is affected by dopamine levels. To this end, we compare cortico-cortical, cortico-muscular, and intermuscular connectivity and gait outcomes between body sides in people with PD under ON and OFF medication states, and in older adults. In our study, participants walked back and forth along a 12 m corridor. Gait events (heel strikes and toe-offs) and electrical cortical and muscular activities were measured and used to compute cortico-cortical, cortico-muscular, and intermuscular connectivity (i.e., coherences in the alpha, beta, and gamma bands), as well as features characterizing gait performance (e.g., the step-timing coordination, length, and speed). We observe that people with PD, mainly during the OFF medication, walk with reduced step-timing coordination. Additionally, our results suggest that dopamine intake in PD increases the overall cortico-muscular connectivity during the stance and swing phases of gait. We thus conclude that dopamine corrects defective feedback caused by impaired sensory-information processing and sensory-motor integration, thus increasing cortico-muscular coherences in the alpha bands and improving gait.

Abstract Movement deterioration is the hallmark of Parkinson’s disease (PD), characterized by levodopa-induced motor-fluctuations (i.e., symptoms’ variability related to the medication cycle) in advanced stages. However, motor symptoms are typically too sporadically and/or subjectively assessed, ultimately preventing the effective monitoring of their progression, and thus leading to suboptimal treatment/therapeutic choices. Smartwatches (SW) enable a quantitative-oriented approach to motor-symptoms evaluation, namely home-based monitoring (HBM) using an embedded inertial measurement unit. Studies validated such approach against in-clinic evaluations. In this work, we aimed at delineating personalized motor-fluctuations’ profiles, thus capturing individual differences. 21 advanced PD patients with motor fluctuations were monitored for 2 weeks using a SW and a smartphone-dedicated app (Intel Pharma Analytics Platform). The SW continuously collected passive data (tremor, dyskinesia, level of activity using dedicated algorithms) and active data, i.e., time-up-and-go, finger tapping, hand tremor and hand rotation carried out daily, once in OFF and once in ON levodopa periods. We observed overall high compliance with the protocol. Furthermore, we observed striking differences among the individual patterns of symptoms’ levodopa-related variations across the HBM, allowing to divide our participants among four data-driven, motor-fluctuations’ profiles. This highlights the potential of HBM using SW technology for revolutionizing clinical practices.

Coordinated movement of four limbs is a hallmark of healthy locomotion. No measures exist to quantify four-limb coordination. This study aimed to investigate temporal four-limb coordination and proposed a new metric for quantifying the inter-limb phase of rhythmic locomotion-related movements. Kinetic data of arm and leg movements generated during walking (self-selected speed) from healthy adults were used to extract the phases (φ) between all possible limb pairings. The φ series were used to calculate each pair’s Phase Coordination Index (PCI). The PCI quantifies the accuracy and consistency of generating anti-phased rhythmic movements (lower PCI values mean better coordination). We also calculated the Quadruple-PCI (Q-PCI) by combining all φ values of all limb pairs. We found a significant correlation between the PCI values of all limb pairings and the Q-PCI (pairs involving arms: Pearson’s R > 0.79, p < 0.001; leg–leg: Pearson’s R = 0.3, p < 0.01). The PCI values that involve arms (median values between 6.5% and 8.3%) were significantly higher than the leg–leg PCI (median values between 3.8% and 4.1%), and the Q-PCI (median values between 8.3% and 9.7%) was significantly higher than all other PCI values. We also found a negative correlation between the arm swing amplitude and the PCI values (Spearman’s Rho of different limb pairings ranging from −0.25 to −0.5, p < 0.05), suggesting that higher arm swing amplitude leads to better coordination. Four-limb coordination analysis is a novel method for comprehensive assessment of gait coordination, which is often compromised among persons with disabilities.

Abstract Daily life activities often involve decision-based reaching movements in different contexts and circumstances. These activities span a wide array of cognitive load types we face while executing motor functions. Here we use a virtual reality-based neurocognitive testing platform to assess cognitive-induced changes in motor behavior as reflected by modulations in head-hand coordination. Our paradigm is based on the Color Trails Test (CTT), which is designed to assess two types of cognitive functions: Trails A—sustained visual attention (SVA), and Trails B—divided attention (DA). The virtual reality CTT adaptation (VR-CTT) requires execution of large multi-directional hand movements and head rotations. We employed a cross-correlation analysis on hand and head kinematics data collected from 122 healthy participants (ages: 20–90 years; divided as follows: young, middle-aged, and older adults) who completed the VR-CTT. The level of spatial coherence of head-hand movements was found to be high (R ≥ 0.76) in both Trails A and B, in all age groups. However, assessing head-hand phase shifts revealed longer time lags (i.e., in which head leads hand) in Trails B versus Trails A, in all age groups. We conclude that allocating cognitive resources to DA task reduces head-hand synchrony as compared to SVA conditions.

Abstract Background Interventions using split belt treadmills (SBTM) aim to improve gait symmetry (GA) in Parkinson's disease (PD). Comparative effects in conjugated SBTM conditions were not studied systematically despite potentially affecting intervention outcomes. We compared gait adaptation effects instigated by SBTM walking with respect to the type (increased\decreased speed) and the side (more/less affected) of the manipulated belt in PD. Methods Eight individuals with PD performed four trials of SBTM walking, each consisted of baseline tied belt configuration, followed by split belt setting – either WS or BS belt's speed increased or decreased by 50% from baseline, and final tied belt configuration. Based on the disease's motor symptoms, a 'worst' side (WS) and a 'best' side (BS) were defined for each participant. Results SB initial change in GA was significant regardless of condition (p ≤ 0.02). This change was however more pronounced for BS-decrease compared with its matching condition WS-increase (p = 0.016). Similarly, the same was observed for WS-decrease compared to BS-increase (p = 0.013). Upon returning to tied belt condition, both BS-decrease and WS-increased resulted in a significant change in GA (p = 0.04). Upper limb asymmetry followed a similar trend of GA reversal, although non-significant. Conclusions Stronger effects on GA were obtained by decreasing the BS belt’s speed of the best side, rather than increasing the speed of the worst side. Albeit a small sample size, which limits the generalisability of these results, we propose that future clinical studies would benefit from considering such methodological planning of SBTM intervention, for maximising of intervention outcomes. Larger samples may reveal arm swinging asymmetries alterations to match SBTM adaptation patterns. Finally, further research is warranted to study post-adaption effects in order to define optimal adaptation schemes to maximise the therapeutic effect of SBTM based interventions.

Freezing of Gait (FOG) is among the most debilitating symptoms of Parkinson’s Disease (PD), characterized by a sudden inability to generate effective stepping. In preparation for the development of a real-time FOG prediction and intervention device, this work presents a novel FOG prediction algorithm based on detection of altered interlimb coordination of the legs, as measured using two inertial movement sensors and analyzed using a wavelet coherence algorithm. Methods: Fourteen participants with PD (in OFF state) were asked to walk in challenging conditions (e.g. with turning, dual-task walking, etc.) while wearing inertial motion sensors (waist, 2 shanks) and being videotaped. Occasionally, participants were asked to voluntarily stop (VOL). FOG and VOL events were identified by trained researchers based on videos. Wavelet analysis was performed on shank sagittal velocity signals and a synchronization loss threshold (SLT) was defined and compared between FOG and VOL. A proof-of-concept analysis was performed for a subset of the data to obtain preliminary classification characteristics of the novel measure. Results: 128 FOG and 42 VOL episodes were analyzed. SLT occurred earlier for FOG (MED = 1.81 sec prior to stop, IQR = 1.57) than for VOL events (MED = 0.22 sec, IQR = 0.76) (Z =−4.3, p < 0.001, ES = 1.15). These time differences were not related with measures of disease severity. Preliminary results demonstrate sensitivity of 98%, specificity of 42% (mostly due to ‘turns’ detection) and balanced accuracy of 70% for SLT-based prediction, with good differentiation between FOG and VOL. Conclusions: Wavelet analysis provides a relatively simple, promising approach for prediction of FOG in people with PD.

The notion that young healthy adults can substantially improve in activities that are part of their daily routine is often overlooked because it is assumed that such activities have come to be fully mastered. We followed, in young healthy adults, the effects of repeated executions of the Timed-Up-and-Go (TUG) task, a clinical test that assesses the ability to execute motor activities relevant to daily function-rising from a seated position, walking, turning and returning to a seated position. The participants (N = 15) performed 18 consecutive trials of the TUG in one session, and were retested on the following day and a week later. The participants were video recorded and wore inertial measurement units. Task execution times improved robustly; performance was well fitted by a power function, with large gains at the beginning of the session and nearing plateau in later trials, as one would expect in the learning of a novel task. Moreover, these gains were well retained overnight and a week later, with further gains accruing in the subsequent test-sessions. Significant intra-session and inter-session changes occurred in step kinematics as well; some aspects underwent inter-sessions recalibrations, but other aspects showed delayed inter-session changes, suggesting post-practice memory consolidation processes. Even common everyday tasks can be improved upon by practice; a small number of consecutive task repetitions can trigger lasting gains in young healthy individuals performing highly practiced routine tasks. This new learning in highly familiar tasks proceeded in a time-course characteristic of the acquisition of novel 'how to' (procedural) knowledge.

Abstract Background Adherence to direct oral anticoagulants (DOACs) remains a concern among non‐valvular atrial fibrillation (AF) patients. We aimed to assess patterns of adherence with DOACs and examine their association with ischemic stroke and systemic embolism (SE). Methods This retrospective cohort study includes all adult members of Clalit Health Services, the largest healthcare provider in Israel, with newly diagnosed non‐valvular AF between January 2014 and March 2019, who initiated DOACs within 90 days of AF diagnosis and used DOACs exclusively. Adherence was assessed using the proportion of days covered (PDC) over the first year of treatment, and high adherence was defined as PDC ≥80%. Regression models were used to identify predictors of high adherence to DOACs and to examine the association between adherence and stroke or SE. Results Overall 15,255 patients were included in this study. The proportion of highly adherent (PDC ≥80%) DOACs users was around 75% and decreased slightly over the years. On multivariable analyses, the likelihood of high adherence to DOACs increased with age and across higher socioeconomic classes, and was more likely among females, Jews, statins users, and patients with CHA2DS2‐VASc score ≥2. Risk of stroke and SE was lower among highly adherent DOACs users; adjusted HR 0.56 (95% CI, 0.45–0.71), compared to users with PDC

The study aimed to investigate the neural changes that differentiate Parkinson’s disease patients with freezing of gait and age-matched controls, using ambulatory electroencephalography event-related features. Compared to controls, definite freezers exhibited significantly less alpha desynchronization at the motor cortex about 300 ms before and after the start of overground walking and decreased low-beta desynchronization about 300 ms before and about 300 and 700 ms after walking onset. The late slope of motor potentials also differed in the sensory and motor areas between groups of controls, definite, and probable freezers. This difference was found both in preparation and during the execution of normal walking. The average frontal peak of motor potential was also found to be largely reduced in the definite freezers compared with the probable freezers and controls. These findings provide valuable insights into the underlying structures that are affected in patients with freezing of gait, which could be used to tailor drug development and personalize drug care for disease subtypes. In addition, the study’s findings can help in the evaluation and validation of nonpharmacological therapies for patients with Parkinson’s disease.

ObjectiveUterine size is one of the essential factors determining the feasibility of a minimally invasive gynecologic surgery approach. A traditional electromechanical morcellator is a well-known tool but not without flaws. We aim to assess feasibility and safety of a novel intrauterine power morcellation device for uterine size reduction to overcome these limitations during hysterectomy.MethodsThis single-arm, observational study was conducted in a single tertiary care medical center from April 2022 to July 2022. Feasibility and safety of a novel intrauterine morcellation device for uterine size reduction was tested in ten post-hysterectomy uteri (Ex-vivo).Measurements and main resultsTen uteri were examined in this trial. No major complications occurred during the procedure. All ten (10) uteri were successfully reduced in size (size reduction range was between 9% to 54%). The average resection time using the Heracure Device was 4.3 minutes (range: 1min- 10min). Mean uterus weight reduction was 21%, with a mean circumference reduction of 25%. No leakage was observed from the outer surface of the uterus/serosa after the saline injection post-procedure examination.ConclusionIn this novel experiment, we verified the feasibility and safety of the Heracure device for vaginal intra-uterine morcellation for uterine size reduction. This technique could enable rapid and easy removal of the uterus through the vaginal orifice.Clinical trial registrationName of the registry: ClinicalTrials.gov; Number Identifier: NCT05332132.

ObjectiveTranslations and adaptations of traditional neuropsychological tests to virtual reality (VR) technology bear the potential to increase their ecological validity since the technology enables simulating everyday life conditions in a controlled manner. The current paper describes our translation of a commonly used neuropsychological test to VR, the Rey Auditory Verbal Learning Test (RAVLT). For this aim, we developed a VR adaptation of the RAVLT (VR-RAVLT) Which is based on a conversation with a secretary in a virtual office using a fully immersive VR system. To validate the VR-RAVLT, we tested its construct validity, its age-related discriminant validity and its test-retest validity in reference to the original gold standard RAVLT (GS-RAVLT).MethodSeventy-eight participants from different age groups performed the GS-RAVLT and the VR-RAVLT tests in a counterbalanced order in addition to other neuropsychological tests. Construct validity was validated using Pearson’s correlations coefficients and serial position effects; discriminant validity was validated using receiver operating characteristic area under the curve values and test-retest reliability was validated using intraclass correlation coefficients.ResultsComparing both RAVLTs’ format results indicates that the VR-RAVLT has comparable construct, discriminant and test–retest validities.Conclusionthe novel VR-RAVLT and the GS-RAVLT share similar psychometric properties suggesting that the two tests measure the same cognitive construct. This is an indication of the feasibility of adapting the RAVLT to the VR environment. Future developments will employ this approach for clinical diagnosis and treatment.

Asher et al analyzed synchronization networks of electroencephalography brain waves from three Parkinson’s disease (PD) patient groups with different freezing of gait (FoG) severity using tools based on network science and non-linear dynamics. Their findings suggest that there is a potential relationship between PD/FoG severity and overall EEG synchronization and their approach could be used to help gain further insight into the pathophysiology leading to FoG.

Abstract Background Falls commonly occur due to losses of balance associated with vertical body movements (e.g. reacting to uneven ground, street curbs). Research, however, has focused on horizontal perturbations, such as forward and backward translations of the standing surface. This study describes and compares muscle activation patterns following vertical and horizontal perturbations during standing and walking, and investigates the role of vision during standing postural responses. Methods Fourteen healthy participants (ten males; 27±4 years-old) responded to downward, upward, forward, and backward perturbations while standing and walking in a virtual reality (VR) facility containing a moveable platform with an embedded treadmill; participants were also exposed to visual perturbations in which only the virtual scenery moved. We collected bilateral surface electromyography (EMG) signals from 8 muscles (tibialis anterior, rectus femoris, rectus abdominis, external oblique, gastrocnemius, biceps femoris, paraspinals, deltoids). Parameters included onset latency, duration of activation, and activation magnitude. Standing perturbations comprised dynamic-camera (congruent), static-camera (incongruent) and eyes-closed sensory conditions. ANOVAs were used to compare the effects of perturbation direction and sensory condition across muscles. Results Vertical perturbations induced longer onset latencies and shorter durations of activation with lower activation magnitudes in comparison to horizontal perturbations (p

Abstract Background Neuropsychological tests of executive function have limited real-world predictive and functional relevance. An emerging solution for this limitation is to adapt the tests for implementation in virtual reality (VR). We thus developed two VR-based versions of the classic Color-Trails Test (CTT), a well-validated pencil-and-paper executive function test assessing sustained (Trails A) and divided (Trails B) attention—one for a large-scale VR system (DOME-CTT) and the other for a portable head-mount display VR system (HMD-CTT). We then evaluated construct validity, test–retest reliability, and age-related discriminant validity of the VR-based versions and explored effects on motor function. Methods Healthy adults (n = 147) in three age groups (young: n = 50; middle-aged: n = 80; older: n = 17) participated. All participants were administered the original CTT, some completing the DOME-CTT (14 young, 29 middle-aged) and the rest completing the HMD-CTT. Primary outcomes were Trails A and B completion times (tA, tB). Spatiotemporal characteristics of upper-limb reaching movements during VR test performance were reconstructed from motion capture data. Statistics included correlations and repeated measures analysis of variance. Results Construct validity was substantiated by moderate correlations between the’gold standard’ pencil-and-paper CTT and the VR adaptations (DOME-CTT: tA 0.58, tB 0.71; HMD-CTT: tA 0.62, tB 0.69). VR versions showed relatively high test–retest reliability (intraclass correlation; VR: tA 0.60–0.75, tB 0.59–0.89; original: tA 0.75–0.85, tB 0.77–0.80) and discriminant validity (area under the curve; VR: tA 0.70–0.92, tB 0.71–0.92; original: tA 0.73–0.95, tB 0.77–0.95). VR completion times were longer than for the original pencil-and-paper test; completion times were longer with advanced age. Compared with Trails A, Trails B target-to-target VR hand trajectories were characterized by delayed, more erratic acceleration and deceleration, consistent with the greater executive function demands of divided vs. sustained attention; acceleration onset later for older participants. Conclusions The present study demonstrates the feasibility and validity of converting a neuropsychological test from two-dimensional pencil-and-paper to three-dimensional VR-based format while preserving core neuropsychological task features. Findings on the spatiotemporal morphology of motor planning/execution during the cognitive tasks may lead to multimodal analysis methods that enrich the ecological validity of VR-based neuropsychological testing, representing a novel paradigm for studying cognitive-motor interactions.

Objectives Patients with haematological malignancies receiving immunosuppressive therapy are at highest risk of invasive pneumococcal disease. Our goal was to investigate whether vaccination of haematological patients with pneumococcal 13-valent conjugated vaccine (PCV13) prior to therapy initiation is associated with decreased hospital admissions due to pneumonia or sepsis within 12 months.Design and setting A longitudinal retrospective cohort study was conducted at the haematology unit of Carmel Medical Center, Israel.Participants Information on adult patients (>18 years) who were diagnosed between 1 January 2009 and 30 December 2019 with haematological malignancies and received immunosuppressive therapy was retrieved from the electronic health records. Patients with haematological malignancies who received the PCV13 vaccination during or after initiation of the immunosuppressive therapy were excluded from the study.Outcome measures A multivariate logistic regression model was performed to determine whether PCV13 vaccination is associated with fewer hospital admissions due to pneumonia or sepsis.Results The cohort included 616 patients, of which 418 (67%) patients were not vaccinated and 198 (33%) were vaccinated. Within 12 months, 15.1% (n=63) of non-vaccinated patients compared with only 7.1% (n=14) of the vaccinated patients were hospitalised due to pneumonia or sepsis. The logistic regression analysis demonstrated that receiving PCV13 vaccination is associated with 45% (OR=0.45, 95% CI: 0.246 to 0.839, p=0.012) reduced odds of being hospitalised due to pneumonia or sepsis in patients with haematological malignancies receiving immunosuppressive therapy.Conclusion This is the first observational study to demonstrate the association between PCV13 vaccination and hospital admissions in patients with haematological malignancies receiving immunosuppressive therapy. Patients receiving PCV13 vaccination before immunosuppressive therapy initiation had significantly reduced odds of hospitalisation due to pneumonia or sepsis compared with non-PCV13-vaccinated patients.

Introduction Several studies have shown an association between panic disorder (PD) and reduced balance abilities, mainly based on functional balance scales. This pilot study aims to demonstrate the feasibility of studying balance abilities of persons with PD (PwPD) using computerized static and, for the first time, dynamic balance measurements in order to characterize balance control strategies employed by PwPD. Methods Twelve PwPD and 11 healthy controls were recruited. PD diagnosis was confirmed using the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM‐IV), and the severity of symptoms was evaluated using the Hamilton Anxiety Scale (HAM‐A), PD Severity Scales (PDSS), and Panic and Agoraphobia Scale (PAS). Balance was clinically assessed using the Activities‐Specific Balance Confidence (ABC) scale and physically by the Mini‐Balance Evaluation Systems Test (Mini‐BESTest). Dizziness was evaluated using the Dizziness Handicap Inventory (DHI) scale. Postural control was evaluated statically by measuring body sway and dynamically by measuring body responses to rapid unexpected physical perturbations. Results PwPD had higher scores on the HAM‐A (17.6 ± 10.3 vs. 3.0 ± 2.9; p

Gait is a complex mechanism relying on integration of several sensory inputs such as vestibular, proprioceptive, and visual cues to maintain stability while walking. Often humans adapt their gait to changes in surface inclinations, and this is typically achieved by modulating walking speed according to the inclination in order to counteract the gravitational forces, either uphill (exertion effect) or downhill (braking effect). The contribution of vision to these speed modulations is not fully understood. Here we assessed gait speed effects by parametrically manipulating the discrepancy between virtual visual inclination and the actual surface inclination (aka visual incongruence). Fifteen healthy participants walked in a large-scale virtual reality (VR) system on a self-paced treadmill synchronized with projected visual scenes. During walking they were randomly exposed to varying degrees of physical-visual incongruence inclinations (e.g., treadmill leveled & visual scene uphill) in a wide range of inclinations (−15° to +15°). We observed an approximately linear relation between the relative change in gait speed and the anticipated gravitational forces associated with the virtual inclinations. Mean relative gait speed increase of ~7%, ~11%, and ~17% were measured for virtual inclinations of +5°, +10°, and +15°, respectively (anticipated decelerating forces were proportional to sin[5°], sin[10°], sin[15°]). The same pattern was seen for downhill virtual inclinations with relative gait speed modulations of ~-10%, ~-16%, and ~-24% for inclinations of −5°, −10°, and −15°, respectively (in anticipation of accelerating forces). Furthermore, we observed that the magnitude of speed modulation following virtual inclination at ±10° was associated with subjective visual verticality misperception. In conclusion, visual cues modulate gait speed when surface inclinations change proportional to the anticipated effect of the gravitational force associated the inclinations. Our results emphasize the contribution of vision to locomotion in a dynamic environment and may enhance personalized rehabilitation strategies for gait speed modulations in neurological patients with gait impairments.

Background: Fear of flying (FoF) is a phobia with 10–40% prevalence in the industrialized world. FoF is accompanied by severe economic, social, vocational, and emotional consequences. In recent years, virtual reality (VR)-based exposure therapy (VRET) for FoF has been introduced. Positive long-term efficacy of FoF-VRET has been reported by several studies, which, however, were limited by relatively small, non-representative samples and a lack of comparative pre/post functional efficacy outcome measures. Our objective was to evaluate the efficacy of a VRET treatment utilizing a large-scale VR system, experienced by a representative sample of self-referred individuals.Methods: We conducted a retrospective survey. Of 274 individuals who received the treatment (over a period of 3 years), 209 met inclusion/criteria, and 98 agreed to participate. We mainly collected information regarding flight activity before and after treatment relying on evidence such as boarding passes and flight tickets. The primary outcome measures were (1) number of flights per month (FpM) and (2) number of flight hours per month (FHpM). For each participant, these outcomes were computed for the post-treatment period (≥6 months after FoF-VRET) and the corresponding pre-treatment period.Results: FpM (mean ± SD) increased from 0.04 ± 0.06 to 0.16 ± 14 flights (p < 0.0001). FHpM rose from 0.19 ± 0.35 to 0.79 ± 0.87 h per month (p < 0.0001).Conclusion: These results are indicative of FoF-VRET treatment efficacy. Future studies should evaluate long-term maintenance of the treatment effect and thus identify the optimal frequency for delivery of periodic booster treatments.

While it is known that heritage speakers diverge from the homeland baseline, there is still no consensus on the mechanisms triggering this divergence. We investigate the impact of two potential factors shaping adult heritage language (HL) grammars: (1) cross-linguistic influence (CLI), originally proposed for second language acquisition (SLA), and (2) background factors associated with input. To assess the role of CLI and input we compared two groups of adult heritage speakers of Russian (n = 66) with two typologically distinct societal languages (SLs), Hebrew and American English. Their production was evaluated for three morphosyntactic phenomena: adjective-noun agreement, accusative case morphology, and numerical phrases. Using self-rating and baseline vocabulary tasks as proficiency measures, we conducted controlled experiments to assess mastery of the target phenomena. Our results show that, while CLI is the main mechanism behind HL grammar maintenance, increased input and proficiency can modulate performance in the absence of grammatical similarities between the HL and SL. An analysis of non-target responses revealed systematic patterns, including reliance on default, or unmarked, forms in both groups, in line with previous research. These findings contribute to the literature on the mechanisms of HL grammar formation and maintenance.

Abstract Background Measurement of factor VII (FVII) activity does not enable prediction of bleeding tendency in individuals with inherited FVII deficiency. Objective To characterize the molecular and functional features of FVII in a family with FVII deficiency and correlate them with the bleeding tendency. Patients/Methods We studied 7 family members with very low FVII activity using prothrombin time (PT), activated factor VII (FVIIa), FVII activity level, and thrombin generation. The factor 7 gene was sequenced and the mutation was analyzed by prediction software. Results The proband has very low FVII activity (0%–4%), with PT ranging between 5% to 18% depending on the tissue factor (TF) origin. Direct sequencing demonstrated a single homozygous nucleotide substitution G > A in exon 6, predicting a novel missense mutation Cys164Tyr. Three members of the family were found to be heterozygous carriers of this mutation. One of them was a compound heterozygote, carrying both the Cys164Tyr and Ala244Val mutation (linked to Arg353Gln polymorphism). Her FVII activity and antigen levels were 3%–7% and 8%, respectively. The other heterozygous carriers demonstrated FVII activity of 41%–54%, FVII antigen of 46%–66%, and FVIIa activity of 30%. FVIIa was undetectable in the homozygous and compound heterozygous subjects. Thrombin generation was normal in the presence of calcium, but no response to TF addition was observed in the homozygous proband, and a reduced response was observed in the compound heterozygous subject. Conclusion The patient homozygous for the “Carmel” mutation has mild clinical manifestations despite very low FVII activity, which correlates with thrombin generation results.