Multiparametric analysis of voice following prolonged voice use and voice rest in teachers: evidence from discriminant analysis.

PURPOSE: Even though recent investigations have used multiparametric protocol, the set of robust parameters in determining the effects of vocal fatigue and voice rest in teachers is not clear. The first objective of the study was to document the impact of prolonged voice use and voice rest on the subjective and objective voice parameters among Indian secondary school teachers. The second objective was to determine the set voice parameters sensitive to vocal changes resulting from continuous voice use and voice rest. METHOD: The study included 15 male and 15 female secondary school teachers with a clinically normal voice and no history of voice disorders. Phonation samples were recorded in three different conditions, i.e., condition 1 (before voice use), condition 2 (following voice use), and condition 3 (following voice rest). The vocal Fatigue Index (version 2) was administered before the voice recordings in all three conditions. The objective parameters, namely fundamental frequency, range of fundamental frequency, jitter (%), shimmer (%), harmonic to noise ratio, and smoothened cepstral peak prominence, were extracted. RESULTS: Results revealed that fundamental frequency, jitter, shimmer, Harmonic to noise ratio, and smoothened cepstral peak prominence were significantly different across the three conditions. The discriminant analysis revealed that only three parameters classified 98.3% of samples accurately between the three conditions. CONCLUSION: Further research on the correlation between the other subjective and the objective parameters of voice after vocal fatigue would provide more penetrating and ample in-depth insights into the assessment and quantification of vocal fatigue.

Sense and simplicity in HADDOCK scoring: Lessons from CASP-CAPRI round 1.

Our information-driven docking approach HADDOCK is a consistent top predictor and scorer since the start of its participation in the CAPRI community-wide experiment. This sustained performance is due, in part, to its ability to integrate experimental data and/or bioinformatics information into the modelling process, and also to the overall robustness of the scoring function used to assess and rank the predictions. In the CASP-CAPRI Round 1 scoring experiment we successfully selected acceptable/medium quality models for 18/14 of the 25 targets - a top-ranking performance among all scorers. Considering that for only 20 targets acceptable models were generated by the community, our effective success rate reaches as high as 90% (18/20). This was achieved using the standard HADDOCK scoring function, which, thirteen years after its original publication, still consists of a simple linear combination of intermolecular van der Waals and Coulomb electrostatics energies and an empirically derived desolvation energy term. Despite its simplicity, this scoring function makes sense from a physico-chemical perspective, encoding key aspects of biomolecular recognition. In addition to its success in the scoring experiment, the HADDOCK server takes the first place in the server prediction category, with 16 successful predictions. Much like our scoring protocol, because of the limited time per target, the predictions relied mainly on either an ab initio center-of-mass and symmetry restrained protocol, or on a template-based approach whenever applicable. These results underline the success of our simple but sensible prediction and scoring scheme. Proteins 2017; 85:417-423. © 2016 Wiley Periodicals, Inc.

Predicting Productivity Returns on Investment: Thirty Years of Peer Review, Grant Funding, and Publication of Highly Cited Papers at the National Heart, Lung, and Blood Institute.

There are conflicting data about the ability of peer review percentile rankings to predict grant productivity, as measured through publications and citations. To understand the nature of these apparent conflicting findings, we analyzed bibliometric outcomes of 6873 de novo cardiovascular R01 grants funded by the National Heart, Lung, and Blood Institute (NHLBI) between 1980 and 2011. Our outcomes focus on top-10% articles, meaning articles that were cited more often than 90% of other articles on the same topic, of the same type (eg, article, editorial), and published in the same year. The 6873 grants yielded 62 468 articles, of which 13 507 (or 22%) were top-10% articles. There was a modest association between better grant percentile ranking and number of top-10% articles. However, discrimination was poor (area under receiver operating characteristic curve [ROC], 0.52; 95% confidence interval, 0.51-0.53). Furthermore, better percentile ranking was also associated with higher annual and total inflation-adjusted grant budgets. There was no association between grant percentile ranking and grant outcome as assessed by number of top-10% articles per $million spent. Hence, the seemingly conflicting findings on peer review percentile ranking of grants and subsequent productivity largely reflect differing questions and outcomes. Taken together, these findings raise questions about how best National Institutes of Health (NIH) should use peer review assessments to make complex funding decisions.

Citation impact of NHLBI R01 grants funded through the American Recovery and Reinvestment Act as compared to R01 grants funded through a standard payline.

RATIONALE: The American Recovery and Reinvestment Act (ARRA) allowed National Heart, Lung, and Blood Institute to fund R01 grants that fared less well on peer review than those funded by meeting a payline threshold. It is not clear whether the sudden availability of additional funding enabled research of similar or lesser citation impact than already funded work. OBJECTIVE: To compare the citation impact of ARRA-funded de novo National Heart, Lung, and Blood Institute R01 grants with concurrent de novo National Heart, Lung, and Blood Institute R01 grants funded by standard payline mechanisms. METHODS AND RESULTS: We identified de novo (type 1) R01 grants funded by National Heart, Lung, and Blood Institute in fiscal year 2009: these included 458 funded by meeting Institute's published payline and 165 funded only because of ARRA funding. Compared with payline grants, ARRA grants received fewer total funds (median values, $1.03 versus $1.87 million; P<0.001) for a shorter duration (median values including no-cost extensions, 3.0 versus 4.9 years; P<0.001). Through May 2014, the payline R01 grants generated 3895 publications, whereas the ARRA R01 grants generated 996. Using the InCites database from Thomson-Reuters, we calculated a normalized citation impact for each grant by weighting each article for the number of citations it received normalizing for subject, article type, and year of publication. The ARRA R01 grants had a similar normalized citation impact per $1 million spent as the payline grants (median values [interquartile range], 2.15 [0.73-4.68] versus 2.03 [0.75-4.10]; P=0.61). The similar impact of the ARRA grants persisted even after accounting for potential confounders. CONCLUSIONS: Despite shorter durations and lower budgets, ARRA R01 grants had comparable citation outcomes per $million spent to that of contemporaneously funded payline R01 grants.

Prior publication productivity, grant percentile ranking, and topic-normalized citation impact of NHLBI cardiovascular R01 grants.

RATIONALE: We previously demonstrated absence of association between peer-review-derived percentile ranking and raw citation impact in a large cohort of National Heart, Lung, and Blood Institute cardiovascular R01 grants, but we did not consider pregrant investigator publication productivity. We also did not normalize citation counts for scientific field, type of article, and year of publication. OBJECTIVE: To determine whether measures of investigator prior productivity predict a grant's subsequent scientific impact as measured by normalized citation metrics. METHODS AND RESULTS: We identified 1492 investigator-initiated de novo National Heart, Lung, and Blood Institute R01 grant applications funded between 2001 and 2008 and linked the publications from these grants to their InCites (Thompson Reuters) citation record. InCites provides a normalized citation count for each publication stratifying by year of publication, type of publication, and field of science. The coprimary end points for this analysis were the normalized citation impact per million dollars allocated and the number of publications per grant that has normalized citation rate in the top decile per million dollars allocated (top 10% articles). Prior productivity measures included the number of National Heart, Lung, and Blood Institute-supported publications each principal investigator published in the 5 years before grant review and the corresponding prior normalized citation impact score. After accounting for potential confounders, there was no association between peer-review percentile ranking and bibliometric end points (all adjusted P>0.5). However, prior productivity was predictive (P<0.0001). CONCLUSIONS: Even after normalizing citation counts, we confirmed a lack of association between peer-review grant percentile ranking and grant citation impact. However, prior investigator publication productivity was predictive of grant-specific citation impact.

Adoption of direct oral anticoagulants for stroke prevention in atrial fibrillation.

BACKGROUND: Direct oral anticoagulants (DOAC) are being increasingly utilised for stroke prevention in atrial fibrillation (AF) and atrial flutter. AIMS: To analyse the adoption and application of these drugs in a regional hospital inpatient cohort and compare with national prescribing data. METHODS: Digital medical records identified prescribed anticoagulants for patients admitted with AF and atrial flutter during 2013-2014. Analysis of patient demographics and stroke risk identified trends in prescribing DOAC versus warfarin. For broader comparison, data from the Pharmaceuticals Benefits Scheme were sourced to determine the nation-wide adoption of DOAC. RESULT: Of the 615 patients identified, 505 (255 in 2013, 250 in 2014) had sufficient records to include in the study. From 2013 to 2014, DOAC prescriptions increased from 9 to 28% (P < 0.001), warfarin and aspirin remained comparatively stable (38-34%, 22-20%), and those prescribed no medication declined (17-8%, P < 0.001). DOAC were prescribed to patients with lower CHA2 DS2 VASc scores than warfarin (3.6 vs 4.4; P = 0.005), lower HAS-BLED scores (1.7 vs 2.3; P < 0.01), higher glomerular filtration rates; 70 vs 63 ml/min; P = 0.002) and younger age (74 vs 77 years; P = 0.006). Nationally, warfarin prescriptions are higher in total numbers but increasing at a slower rate than DOAC, which increased 10-fold (101 158 in 2013, 1 095 985 in 2014). CONCLUSION: DOAC prescribing grew rapidly from 2013 to 2014, regionally and nationally. Warfarin prescriptions have remained stable, indicating that more patients are being appropriately anticoagulated for AF who previously were not. DOAC were found to be prescribed to patients with lower CHA2 DS2 VASc and HAS-BLED scores, younger age and higher glomerular filtration rates. Aspirin therapy remains over utilised in AF.

Functional genetic variants in the vesicular monoamine transporter 1 modulate emotion processing.

Emotional behavior is in part heritable and often disrupted in psychopathology. Identification of specific genetic variants that drive this heritability may provide important new insight into molecular and neurobiological mechanisms involved in emotionality. Our results demonstrate that the presynaptic vesicular monoamine transporter 1 (VMAT1) Thr136Ile (rs1390938) polymorphism is functional in vitro, with the Ile allele leading to increased monoamine transport into presynaptic vesicles. Moreover, we show that the Thr136Ile variant predicts differential responses in emotional brain circuits consistent with its effects in vitro. Lastly, deep sequencing of bipolar disorder (BPD) patients and controls identified several rare novel VMAT1 variants. The variant Phe84Ser was only present in individuals with BPD and leads to marked increase monoamine transport in vitro. Taken together, our data show that VMAT1 polymorphisms influence monoamine signaling, the functional response of emotional brain circuits and risk for psychopathology.

Rapid rule out of myocardial infarction with the use of copeptin as a biomarker for cardiac injury.

Copeptin is a non-specific marker of an endogenous stress response. A dual biomarker marker approach involving the simultaneous use of troponin and copeptin assays may assist early exclusion of acute coronary syndrome in Australian emergency departments. The utility and limitations of this approach are discussed.

Crystal structure of 4-acetyl-phenyl 3-methyl-benzoate.

The planes of the aromatic rings of the title compound, C16H14O3, make a dihedral angle of 82.52 (8)°. The acetyl group and the phenyl ring make a dihedral angle of 1.65 (1)°. In the crystal, the molecules are linked by C-H⋯O interactions, generating C(7) chains along the a-axis direction.

Plasma neurological biomarkers as a measure of neurotoxicity in pediatric dental general anesthesia: a prospective observational feasibility study.

PURPOSE: Neurotoxicity concerns have been raised over general anesthesia and sedation medication use in children. Such concerns are largely based on animal studies, historical anesthetic agents, and assessment tools, thus warranting further investigations. Blood biomarkers in detecting neuronal inflammation and apoptosis are novel methods for detecting neuronal damage. Therefore, the aim of this feasibility study was to assess the usefulness of the levels of four plasma biomarkers in dental general anesthesia (DGA) as surrogate markers of neurotoxicity in children. The secondary aim was to compare changes in motor manipulative skills pre- and post-anesthetic exposure. METHODS: This single-center prospective observational study included 22 healthy children aged between 3 and 6 years old who underwent DGA. Subclinical neurotoxicity was measured with a panel of four plasma biomarkers: Caspase-3, neuron-specific enolase (NSE), neurofilament light chain, and S100B at three time points (1; at start, 2; end and 3; on recovery from DGA). The Skillings-Mack test was used to identify the difference in the biomarker levels at three time points. Motor manipulative score assessment, prior and two weeks after DGA was also performed. RESULTS: A total of 22 study participants (mean age = 5 ± 1 years) were included with a median DGA duration of 106 ± 28 min. A reduction in Caspase-3 levels was recorded, with pairwise comparison over three time points, reporting a statistical significance between time point 2 vs. 1 and time point 3 vs. 1. Although fluctuations in NSE levels were recorded, no significant changes were found following pairwise comparison analysis. Among other biomarkers, no significant changes over the three periods were recorded. Furthermore, no significant changes in manipulative motor scores were reported. CONCLUSION: Caspase-3 reduced significantly in the short time frames during day-care DGA; this might be due to the relatively short anesthesia duration associated with dental treatment as compared with more extensive medical-related treatments. Therefore, further studies on Caspase-3 as a potential biomarker in pediatric DGA neurotoxicity are required to further ascertain results of this study.

Interaction between polymorphisms in serotonin transporter (SLC6A4) and serotonin receptor 2A (HTR2A) genes predict treatment response to venlafaxine XR in generalized anxiety disorder.

Variation in genes involved in serotonergic signaling is thought to be associated with antidepressant treatment response in generalized anxiety disorder (GAD). We examined a possible interaction between the serotonin transporter gene (SLC6A4) 5-HTTLPR/rs25531 haplotype and the serotonin 2A receptor gene (HTR2A) single-nucleotide polymorphism (SNP) rs7997012 in antidepressant treatment outcome in GAD. Patients diagnosed with GAD received venlafaxine XR treatment as part of an 18-month relapse prevention study. Genotypes obtained for the 5-HTTLPR/rs25531 (La/La, La/S or S/S) haplotype and rs7997012 SNP (G or A) in the European American population (n=112) were used for pharmacogenetic analysis. Our data show that subjects with genotypes La/La+G/G or La/La+G/A (n=28) had significantly lower Hamilton Anxiety Scale (HAM-A) scores than those with genotypes La/S+A/A or S/S+A/A (n=12) at 6 months (HAM-A difference=10.7; P<0.0001). Single-marker analysis only showed HAM-A differences of 4.3 (5-HTTLPR/rs25531: La/La versus La/S+S/S) and 4.8 (rs7997012: G/G+G/A versus A/A), showing for the first time a significant gene-gene interaction between these markers.

Serotonin receptor 2A (HTR2A) gene polymorphism predicts treatment response to venlafaxine XR in generalized anxiety disorder.

Generalized anxiety disorder (GAD) is a chronic psychiatric disorder with significant morbidity and mortality. Antidepressant drugs are the preferred choice for treatment; however, treatment response is often variable. Several studies in major depression have implicated a role of the serotonin receptor gene (HTR2A) in treatment response to antidepressants. We tested the hypothesis that the genetic polymorphism rs7997012 in the HTR2A gene predicts treatment outcome in GAD patients treated with venlafaxine XR. Treatment response was assessed in 156 patients that participated in a 6-month open-label clinical trial of venlafaxine XR for GAD. Primary analysis included Hamilton Anxiety Scale (HAM-A) reduction at 6 months. Secondary outcome measure was the Clinical Global Impression of Improvement (CGI-I) score at 6 months. Genotype and allele frequencies were compared between groups using χ(2) contingency analysis. The frequency of the G-allele differed significantly between responders (70%) and nonresponders (56%) at 6 months (P=0.05) using the HAM-A scale as outcome measure. Similarly, using the CGI-I as outcome, the G-allele was significantly associated with improvement (P=0.01). Assuming a dominant effect of the G-allele, improvement differed significantly between groups (P=0.001, odds ratio=4.72). Similar trends were observed for remission although not statistically significant. We show for the first time a pharmacogenetic effect of the HTR2A rs7997012 variant in anxiety disorders, suggesting that pharmacogenetic effects cross diagnostic categories. Our data document that individuals with the HTR2A rs7997012 single nucleotide polymorphism G-allele have better treatment outcome over time. Future studies with larger sample sizes are necessary to further characterize this effect in treatment response to antidepressants in GAD.

Diethyl 2,6-dimethyl-4-[4-(3-phenyl-acrylo-yloxy)phen-yl]-1,4-dihydro-pyridine-3,5-dicarboxyl-ate hemihydrate.

In the title ester derivative, C28H29NO6·0.5H2O, the 1,4-dihydro-pyridine ring has a flattened boat conformation. The mean plane is almost perpendicular to the attached benzene ring, making a dihedral angle of 86.87 (9)°. The terminal phenyl ring is inclined to the central benzene ring by 67.56 (12)°. In the crystal, mol-ecules are bridged via O-H⋯O hydrogen bonds involving the partially occupied water mol-ecule, and this arrangement is strengthened by a pair of N-H⋯O hydrogen bonds and C-H⋯O inter-actions. The ethyl atoms of one of the ethyl ester groups are disordered over two sites with an occupancy ratio of 0.716 (5):0.284 (5).

4-Bromo-2-(dieth-oxy-meth-yl)phenyl benzoate.

In the title compound, C18H19BrO4, the aromatic rings enclose a dihedral angle of 81.9 (7)°. There are no short directional contacts in the crystal structure.

Multiparametric Analysis of Dysphonic Voice - An Evidence from the Discriminant Analysis.

Even though earlier studies have investigated the relationship between various subjective and instrumental measures of voice, determining a standardized set of voice parameters in evaluating dysphonic voices can help in better diagnostic distinctions and judgment of the treatment outcomes in voice disorders. Thus, the primary objective was to examine the differences in the objective and subjective measures of voice between the participants with dysphonia and participants with a clinically normal voice. The subsequent objective was to identify the group of parameters sensitive to vocal changes in dysphonia using discriminant analysis. Two groups of participants were included in the study. Group 1 comprised of 15 participants with dysphonia. Group 2 included 15 participants with a clinically normal voice. Sustained phonations of vowels were recorded from the participants of both groups and were analyzed perceptually using the GRBAS rating scale. Acoustic, cepstral, spectral, and electroglottographic measures were analyzed from dysphonic voices and normal controls. There were significant differences in both instrumental and perceptual measures between the participants with and without dysphonia. The set of five parameters that were significant predictors that discriminated the dysphonic voice from the clinically normal voice with 100% accuracy was also determined using discriminant analysis. Future investigations on the relation between the specific instrumental and perceptual measures of voice identified in the present study among individuals with various voice disorders can deliver more promising and comprehendible insights into better diagnostic distinctions of voice disorders.

A Report on Cases with Communication Disorders at a Tertiary care Hospital in Mysore District of Karnataka, India: A Retrospective Study Across Five Years.

Communication disorders affect an individual's social, emotional and behavioural well-being. Estimating the number of clients with various causes of communication disorders can assist in the prevention, early identification, intervention, rehabilitation and counselling process. India is the second-largest populated country with diversity in terms of culture and geography. Therefore, estimating the data on number of clients presenting with communication disorders is warranted across different parts of the country. In a retrospective study, the clinical records of cases reporting to the JSS Institute of Speech and Hearing, Mysore, for the last five years were reviewed. A total of 9511 cases diagnosed with communication disorders were included in the study. The percentage of male cases was higher than the females amongst all the types of communication disorders. The percentage of paediatric cases with speech and language disorders was the highest, followed by adult cases. Across the hearing disorders, the highest number of cases were from the adult age group, and the lowest number of hearing-disordered cases were noted in the paediatric age group throughout all five years. Among all the risk factors, perinatal history was the highest seen risk factor, and consanguinity was the lowest seen risk factor associated with communication disorders. The results of the present study revealed that among cases with communication disorders at the tertiary care hospital in Mysore, hearing impairment was one of the most commonly seen conditions, followed by child language disorders. The history of perinatal factors as a risk for communication disorders was noted in a maximum number of cases.

Prevalence of anxiety, sleep bruxism and temporomandibular disorders during COVID-19 in Qatari children and adolescents: a cross-sectional study.

PURPOSE: Understanding the impact of coronavirus disease-2019 (COVID-19) pandemic social restrictions on the lives of children and adolescents is of utmost importance to enable timely diagnosis and treatment. Therefore, the aim of this study was to explore the prevalence of anxiety, sleep bruxism, temporomandibular disorders (TMD) and change in dietary and brushing habits and their association with COVID-19 social restrictions. METHODS: Parents of fit and healthy Qatari children and adolescents were recruited and interviewed by the research team, whereby validated questioners were used to assess the prevalence of children's/adolescents' anxiety, sleep bruxism and TMD. Furthermore, changes in dietary and brushing habits were also evaluated. RESULTS: A total of 199 parents of children and adolescents (mean age = 9.3 ± 3.2 years old) were included. Overall anxiety symptoms, sleep bruxism and TMD were evident in 29.6%, 5.7% and 23.1%, respectively. An increased consumption of food, sweets and worsening of brushing habits were evident in 51.8%, 62.8% and 31.2%, respectively. CONCLUSION: Within the limitations of this study, pandemic-related social restrictions could result in elevated levels of anxiety, specifically, social phobia, amongst children and adolescents, which could inevitably lead to unwanted dental consequences.

Deep Learning Segmentation of the Nucleus Basalis of Meynert on 3T MRI.

BACKGROUND AND PURPOSE: The nucleus basalis of Meynert is a key subcortical structure that is important in arousal and cognition and has been explored as a deep brain stimulation target but is difficult to study due to its small size, variability among patients, and lack of contrast on 3T MR imaging. Thus, our goal was to establish and evaluate a deep learning network for automatic, accurate, and patient-specific segmentations with 3T MR imaging. MATERIALS AND METHODS: Patient-specific segmentations can be produced manually; however, the nucleus basalis of Meynert is difficult to accurately segment on 3T MR imaging, with 7T being preferred. Thus, paired 3T and 7T MR imaging data sets of 21 healthy subjects were obtained. A test data set of 6 subjects was completely withheld. The nucleus was expertly segmented on 7T, providing accurate labels for the paired 3T MR imaging. An external data set of 14 patients with temporal lobe epilepsy was used to test the model on brains with neurologic disorders. A 3D-Unet convolutional neural network was constructed, and a 5-fold cross-validation was performed. RESULTS: The novel segmentation model demonstrated significantly improved Dice coefficients over the standard probabilistic atlas for both healthy subjects (mean, 0.68 [SD, 0.10] versus 0.45 [SD, 0.11], P = .002, t test) and patients (0.64 [SD, 0.10] versus 0.37 [SD, 0.22], P < .001). Additionally, the model demonstrated significantly decreased centroid distance in patients (1.18 [SD, 0.43] mm, 3.09 [SD, 2.56] mm, P = .007). CONCLUSIONS: We developed the first model, to our knowledge, for automatic and accurate patient-specific segmentation of the nucleus basalis of Meynert. This model may enable further study into the nucleus, impacting new treatments such as deep brain stimulation.