Picture description in the assessment of connected speech intelligibility in Parkinson's disease: A pilot study

Introduction: Assessment of intelligibility in dysarthria tends to rely on oral reading of sentences or words. However, self-generated utterances are closer to a clients’ natural speech. This study investigated how transcription of utterances elicited by picture description can be used in the assessment of intelligibility in speakers with Parkinson’s disease. Methods: Speech samples from eleven speakers with Parkinson’s disease and six neurologically healthy persons were audio-recorded. Forty-two naive listeners completed transcriptions of self-generated sentences from a picture description task and orally read sentences from the Swedish Test of Intelligibility, as well as scaled ratings of narrative speech samples. Results: Intelligibility was higher in orally read than self-generated sentences and higher for content words than for the whole sentence in self-generated sentences for most of the speakers, although these within-group differences were not statistically significant at group level. Adding contextual leads for the listeners increased intelligibility in self-generated utterances significantly, but with individual variation. Although correlations between the intelligibility measures were at least moderate or strong, there was a considerable inter- and intra-speaker variability in intelligibility scores between tasks for the speakers with Parkinson’s disease, indicating individual variation of factors that impact intelligibility. Intelligibility scores from neurologically healthy speakers were generally high across tasks with no significant differences between the conditions. Discussion/Conclusion: Within-speaker variability support literature recommendations to use multiple methods and tasks when assessing intelligibility. The inclusion of transcription of self-generated utterances elicited by picture description to the intelligibility assessment has the potential to provide additional information to assessment methods based on oral reading of pre-scripted sentences, and to inform the planning of interventions.

Experimental-analytical approach to assessing mechanosensitive cartilage blood marker kinetics in healthy adults: dose-response relationship and interrelationship of nine candidate markers

Purpose: To determine the suitability of selected blood biomarkers of articular cartilage as mechanosensitive markers and to investigate the dose-response relationship between ambulatory load magnitude and marker kinetics in response to load. Methods: Serum samples were collected from 24 healthy volunteers before and at three time points after a 30-minute walking stress test performed on three test days. In each experimental session, one of three ambulatory loads was applied: 100% body weight (BW); 80%BW; 120%BW. Serum concentrations of COMP, MMP-3, MMP-9, ADAMTS-4, PRG-4, CPII, C2C and IL-6 were assessed using commercial enzyme-linked immunosorbent assays. A two-stage analytical approach was used to determine the suitability of a biomarker by testing the response to the stress test (criterion I) and the dose-response relationship between ambulatory load magnitude and biomarker kinetics (criterion II). Results. COMP, MMP-3 and IL-6 at all three time points after, MMP-9 at 30 and 60 minutes after, and ADAMTS-4 and CPII at immediately after the stress test showed an average response to load or an inter-individual variation in response to load of up to 25% of pre-test levels. The relation to load magnitude on average or an inter-individual variation in this relationship was up to 8% from load level to load level. There was a positive correlation for the slopes of the change-load relationship between COMP and MMP-3, and a negative correlation for the slopes between COMP, MMP-3 and IL-6 with MMP-9, and COMP with IL6. Conclusions: COMP, MMP-3, IL-6, MMP-9, and ADAMTS-4 warrant further investigation in the context of articular cartilage mechanosensitivity and its role in joint degeneration and OA. While COMP seems to be able to reflect a rapid response, MMP-3 seems to reflect a slightly longer lasting, but probably also more distinct response. MMP-3 showed also the strongest association with the magnitude of load.

Exploring dynamic metabolomics data with multiway data analysis: a simulation study

Background Analysis of dynamic metabolomics data holds the promise to improve our understanding of underlying mechanisms in metabolism. For example, it may detect changes in metabolism due to the onset of a disease. Dynamic or time-resolved metabolomics data can be arranged as a three-way array with entries organized according to a subjects mode, a metabolites mode and a time mode. While such time-evolving multiway data sets are increasingly collected, revealing the underlying mechanisms and their dynamics from such data remains challenging. For such data, one of the complexities is the presence of a superposition of several sources of variation: induced variation (due to experimental conditions or inborn errors), individual variation, and measurement error. Multiway data analysis (also known as tensor factorizations) has been successfully used in data mining to find the underlying patterns in multiway data. To explore the performance of multiway data analysis methods in terms of revealing the underlying mechanisms in dynamic metabolomics data, simulated data with known ground truth can be studied. Results We focus on simulated data arising from different dynamic models of increasing complexity, i.e., a simple linear system, a yeast glycolysis model, and a human cholesterol model. We generate data with induced variation as well as individual variation. Systematic experiments are performed to demonstrate the advantages and limitations of multiway data analysis in analyzing such dynamic metabolomics data and their capacity to disentangle the different sources of variations. We choose to use simulations since we want to understand the capability of multiway data analysis methods which is facilitated by knowing the ground truth. Conclusion Our numerical experiments demonstrate that despite the increasing complexity of the studied dynamic metabolic models, tensor factorization methods CANDECOMP/PARAFAC(CP) and Parallel Profiles with Linear Dependences (Paralind) can disentangle the sources of variations and thereby reveal the underlying mechanisms and their dynamics.

Inter-individual Variation in Receptor Expression Influences MERS-CoV Infection and Immune Responses in Airway Epithelia

Middle East respiratory syndrome coronavirus (MERS-CoV) causes respiratory infection in humans, with symptom severity that ranges from asymptomatic to severe pneumonia. Known risk factors for severe MERS include male sex, older age, and the presence of various comorbidities. MERS-CoV gains entry into cells by binding its receptor, dipeptidyl peptidase 4 (DPP4), on the surface of airway epithelia. We hypothesized that expression of this receptor might be an additional determinant of outcomes in different individuals during MERS-CoV infection. To learn more about the role of DPP4 in facilitating MERS-CoV infection and spread, we used ELISA and immunofluorescent staining to characterize DPP4 expression in well-differentiated primary human airway epithelia (HAE). We noted wide inter-individual variation in DPP4 abundance, varying by as much as 1000-fold between HAE donors. This variability appears to influence multiple aspects of MERS-CoV infection and pathogenesis, with greater DPP4 abundance correlating with early, robust virus replication and increased cell sloughing. We also observed increased induction of interferon and some interferon-stimulated genes in response to MERS-CoV infection in epithelia with the greatest DPP4 abundance. Overall, our results indicate that inter-individual differences in DPP4 abundance are one host factor contributing to MERS-CoV replication and host defense responses, and highlight how HAE may serve as a useful model for identifying risk factors associated with heightened susceptibility to serious respiratory pathogens.

Inter- and Intra-Individual Variation in the Behavior of Feed Intake on Nutrient Availability in Early Lactating Dairy Cows

Since energetic deficits in dairy cows can only be reduced at an animal level, the objective of the present study was to determine the extent of variation in intake behavior within and between animals during early lactation, to explore the magnitude of interactions between feed intake, intake behavior and nutrient digestibility, and to identify levers for maximizing feed intake at the individual animal level. Feeding behavior, intake and nutrient digestibility of 28 German Holstein dairy cows, fed TMR with 7.0 MJ NEL, were studied between the 2nd and 15th week after calving. Dry matter intake was assessed daily and nutrient digestibility weekly, with iNDF240 as an intrinsic marker. Results showed high intra- and inter-individual variation in intake behavior parameters with coefficients of variation (CV) up to 0.58 in meal frequency. Nutrient digestibility varied only slightly with CV values up to 0.10 in crude protein. Milk yield, meal frequency, feeding time, feeding rate and meal size had significant positive effects on DMI (p < 0.01). To achieve long-term improvements in feed intake, it is important to optimize feed intake and feeding behavior of individual animals by improving feeding conditions and develop technical tools to identify animals with insufficient feed intake.

The impact of bio-logging on body weight change of the Eurasian beaver

Bio-logging is a common method to collect ecological data on wild animals, but might also induce stress, reduce body condition, and alter behavior. Eurasian beavers (Castor fiber) are a semi-aquatic and nocturnal species that are challenging to observe in the wild. Bio-loggers are hence useful tools to study their behaviour and movements, but this raises concerns of potential negative impacts of tagging. To investigate the potential negative impacts of glue-on tags, we compared body weight change for tagged and untagged Eurasian beavers. We hypothesized that tagged beavers would gain less body weight compared to untagged beavers, and that weight change might be affected by tagging length, tag weight, water temperature and the season of tagging. Daily percentage body weight change in relation to initial body weight during the first capture was compared during 57 tagging periods (18±7 days) and 32 controls periods (64±47 days). Body weight change varied between the two groups, with untagged beavers on average gaining daily weight whilst tagged beavers on average lost weight daily, indicating a negative effect of tagging. The average reduction in percentage body weight change per day for tagged beavers was small (0.1 ± 0.3%), and with large individual variation. Neither tag weight, number of tagging days, nor season were important in explaining body weight change of tagged animals. In other words, we found that tagging reduced daily body weight during the tagging period but were unable to determine the mechanism(s) responsible for this decline. Detrimental effects of tagging have important implications for animal welfare and can introduce bias in data that are collected. This calls for careful consideration in the use of tags. We conclude that studies investigating the effects of tagging should consider individual variation in the effects of tagging and, where possible, compare tagged animals with a control group.

Comparative longitudinal variation of total IgG and IgA anti-SARS-CoV-2 antibodies in recipients of BNT162b2 vaccination

Objectives This article aims to summarize the 6-month variation of a vast array of anti-SARS-CoV-2 antibodies in recipients of BNT162b2 mRNA-based vaccination. Methods The study population consisted of 84 baseline SARS-CoV-2 seronegative healthcare employees (median age 45 years, 53.6% females), receiving mRNA-based BNT162b2 primary vaccination cycle. Blood was collected before the first and second BNT162b2 vaccine doses, as well as 1, 3 and 6 months afterwards. The serum titers of the following anti-SARS-CoV-2 antibodies were assayed: total anti-RBD (receptor binding domain), anti-spike trimeric IgG, anti-RBD IgG and anti-spike S1 IgA. Results All antibodies’ levels peaked 1 month after vaccination, but then displayed a considerable decrease. The median rates of 6-month decline were −95% for IgG anti-SARS-CoV-2 RBD, −85% for IgG anti-SARS-CoV-2 trimeric spike, −73% for IgA anti-SARS-CoV-2 S1 and −56% for total anti-SARS-CoV-2 RBD antibodies, respectively. The median time of seronegativization was estimated at 579 days for total anti-SARS-CoV-2 RBD antibodies, 271 days for IgG anti-SARS-CoV-2 trimeric spike, 264 days for IgG anti-SARS-CoV-2 RBD and 208 days for IgA anti-SARS-CoV-2 S1, respectively. The rate of seropositive subjects declined from 98–100% at the peak to 50–100% after 6 months. The inter-individual variation of anti-SARS-CoV-2 antibodies reduction at 6 months was 3–44% from the peak. Conclusions The results of this longitudinal serosurvey demonstrate that the titer of anti-SARS-CoV-2 antibodies declined 6 months after BNT162b2 vaccination, with median time of IgG/IgA seronegativization estimated between 7 and 9 months, thus supporting the opportunity of administering vaccine boosters approximately 5 to 6 months after the last dose of the primary vaccination cycle.

Generalization Across Acetone Peroxide Homemade Explosives by Detection Dogs

Effective explosives detection requires dogs to generalize their response to untrained variations of targets that are related to those with which they were trained. Previous research suggests that dogs tend to be highly specific to their trained odors, and are sensitive to alterations in odor profiles. Triacetone triperoxide (TATP) is an increasingly popular homemade explosive due to the widespread accessibility of starting materials. The large variety of reagent sources and production approaches yields high variability in deployed formulations. Whether dogs trained with pure forms of TATP generalize to other variations is unknown, representing a potentially significant security gap. In the current study, we tested dogs (n = 11) previously trained to detect pure TATP with four variants: diacetone diperoxide (DADP), a homologue often created as a TATP byproduct, and three different clandestine TATP formulations designed to emulate those used by terrorists or insurgents. On average, dogs detected each untrained variant at rates equivalent to the trained TATP (ps &gt; 0.07), with individual variability in first-trial alerts for some of the variants. Chemical analyses paralleled the canine results, showing distinct similarities and differences. For the TATP samples, the laboratory-grade was the purest sample tested and did not contain DADP or the TATP homologue that the three clandestine versions showed in their respective headspace profiles. The headspace results showed that each sample could be clearly identified as TATP, yet they showed recognizable differences due to their individual syntheses. These findings suggest that training on pure TATP may be effective for generalization to untrained variants. Further research is necessary to identify factors that influence individual variation in generalization between dogs, as well as other explosives.

Heterogeneity of Hematological Response to Hypoxia and Short-Term or Medium-Term Bed Rest

Hematological changes are commonly observed following prolonged exposure to hypoxia and bed rest. Typically, such responses have been reported as means and standard deviations, however, investigation into the responses of individuals is insufficient. Therefore, the present study retrospectively assessed individual variation in the hematological responses to severe inactivity (bed rest) and hypoxia. The data were derived from three-bed rest projects: two 10-d (LunHab project: 8 males; FemHab project: 12 females), and one 21-d (PlanHab project: 11 males). Each project comprised a normoxic bed rest (NBR; PIO2=133mmHg) and hypoxic bed rest (HBR; PIO2=91mmHg) intervention, where the subjects were confined in the Planica facility (Rateče, Slovenia). During the HBR intervention, subjects were exposed to normobaric hypoxia equivalent to an altitude of 4,000m. NBR and HBR interventions were conducted in a random order and separated by a washout period. Blood was drawn prior to (Pre), during, and post bed rest (R1, R2, R4) to analyze the individual variation in the responses of red blood cells (RBC), erythropoietin (EPO), and reticulocytes (Rct) to bed rest and hypoxia. No significant differences were found in the mean ∆(Pre-Post) values of EPO across projects (LunHab, FemHab, and PlanHab; p&gt;0.05), however, female EPO responses to NBR (Range - 17.39, IQR – 12.97 mIU.ml−1) and HBR (Range – 49.00, IQR – 10.91 mIU.ml−1) were larger than males (LunHab NBR Range – 4.60, IQR – 2.03; HBR Range – 7.10, IQR – 2.78; PlanHab NBR Range – 7.23, IQR – 1.37; HBR Range – 9.72, IQR – 4.91 mIU.ml−1). Bed rest duration had no impact on the heterogeneity of EPO, Rct, and RBC responses (10-d v 21-d). The resultant hematological changes that occur during NBR and HBR are not proportional to the acute EPO response. The following cascade of hematological responses to NBR and HBR suggests that the source of variability in the present data is due to mechanisms related to hypoxia as opposed to inactivity alone. Studies investigating hematological changes should structure their study design to explore these mechanistic responses and elucidate the discord between the EPO response and hematological cascade to fully assess heterogeneity.

Dairy Cattle Response to a Virtual Fence When Pasture on Offer Is Restricted to the Post-grazing Residual

Pasture-based dairy systems rely on the accurate allocation of pasture to both meet livestock requirements and maintain the growth of herbage. Currently, physical fences are used to contain livestock however they can be labor-intensive to shift and maintain. Alternatively, virtual fence (VF) systems offer flexibility and real-time control of livestock location. Pre-commercial neckbands (eShepherd®, Agersens, Melbourne, VIC) emit a warning audio tone (AT) when a cow approaches a VF boundary, paired with an electrical pulse (EP) if the cow continues forward into the exclusion zone (EZ). However, the ability of VF technology to control animal location when pasture is restricted to the previous day's residual, remains unknown. Ten non-lactating Holstein-Friesian dairy cows were trained to use a VF system for 6 days before strip grazing a 1.2 ha paddock of annual ryegrass. Over 10 days the cows grazed eight pasture allocations at a pre-grazing pasture mass of 2,324 ± 81 kg DM/ha (mean ± SE) and post-grazing pasture-mass (post-grazing residual) of 1,649 ± 48 kg/DM/ha with a front VF. The allocations had a physical backing fence that included the fresh allocation and a small area of residual to cater for any GPS drift of the front VF. On each day, with the exception of days 5 and 10, the VF was moved forward, and the cows were provided a new pasture allocation. On days 5 and 10, the VF was not shifted, and cows were only offered the previous allocation's residual pasture. The location of each animal (inclusion, buffer, and exclusion zones) and number of stimuli (AT and EP) delivered were recorded. The number of stimuli delivered between the grazing and hold-off days was similar. Cows spent 89% of time within the inclusion zone (IZ), with significant peaks observed on day 5 and 10. Distance that cows traveled into the EZ reduced across time. There was also evidence of individual variation in the number of stimuli and thus time spent in each zone. Overall, the VF system was successful in containing the dairy cows during strip grazing even when only offered the previous days post-grazing residual.