The CATH Domain Structure Database and related resources Gene3D and DHS provide comprehensive domain family information for genome analysis

The CATH database of protein domain structures (http://www.biochem.ucl.ac.uk/bsm/cath/) currently contains 43 229 domains classified into 1467 superfamilies and 5107 sequence families. Each structural family is expanded with sequence relatives from GenBank and completed genomes, using a variety of efficient sequence search protocols and reliable thresholds. This extended CATH protein family database contains 616 470 domain sequences classified into 23 876 sequence families. This results in the significant expansion of the CATHHMMmodel library to include models built from the CATH sequence relatives, giving a10%increase in coveragefor detecting remote homologues. An improved Dictionary of Homologous superfamilies (DHS) (http://www.biochem.ucl.ac.uk/bsm/dhs/) containing specific sequence, structural and functional information for each superfamily in CATH considerably assists manual validation of homologues. Information on sequence relatives in CATH superfamilies, GenBank and completed genomes is presented in the CATH associated DHS and Gene3D resources. Domain partnership information can be obtained from Gene3D (http://www.biochem.ucl.ac.uk/bsm/cath/Gene3D/). A new CATH server has been implemented (http://www.biochem.ucl.ac.uk/cgi-bin/cath/CathServer.pl) providing automatic classification of newly determined sequences and structures using a suite of rapid sequence and structure comparison methods. The statistical significance of matches is assessed and links are provided to the putative superfamily or fold group to which the query sequence or structure is assigned

Structure-guided selection of specificity determining positions in the human kinome

Background: The human kinome contains many important drug targets. It is well-known that inhibitors of protein kinases bind with very different selectivity profiles. This is also the case for inhibitors of many other protein families. The increased availability of protein 3D structures has provided much information on the structural variation within a given protein family. However, the relationship between structural variations and binding specificity is complex and incompletely understood. We have developed a structural bioinformatics approach which provides an analysis of key determinants of binding selectivity as a tool to enhance the rational design of drugs with a specific selectivity profile. Results: We propose a greedy algorithm that computes a subset of residue positions in a multiple sequence alignment such that structural and chemical variation in those positions helps explain known binding affinities. By providing this information, the main purpose of the algorithm is to provide experimentalists with possible insights into how the selectivity profile of certain inhibitors is achieved, which is useful for lead optimization. In addition, the algorithm can also be used to predict binding affinities for structures whose affinity for a given inhibitor is unknown. The algorithm’s performance is demonstrated using an extensive dataset for the human kinome. Conclusion: We show that the binding affinity of 38 different kinase inhibitors can be explained with consistently high precision and accuracy using the variation of at most six residue positions in the kinome binding site. We show for several inhibitors that we are able to identify residues that are known to be functionally important

Extraction of Stride Events From Gait Accelerometry During Treadmill Walking

Objective: evaluating stride events can be valuable for understanding the changes in walking due to aging and neurological diseases. However, creating the time series necessary for this analysis can be cumbersome. In particular, finding heel contact and toe-off events which define the gait cycles accurately are difficult. Method: we proposed a method to extract stride cycle events from tri-axial accelerometry signals. We validated our method via data collected from 14 healthy controls, 10 participants with Parkinson's disease, and 11 participants with peripheral neuropathy. All participants walked at self-selected comfortable and reduced speeds on a computer-controlled treadmill. Gait accelerometry signals were captured via a tri-axial accelerometer positioned over the L3 segment of the lumbar spine. Motion capture data were also collected and served as the comparison method. Results: our analysis of the accelerometry data showed that the proposed methodology was able to accurately extract heel and toe-contact events from both feet. We used t-tests, analysis of variance (ANOVA) and mixed models to summarize results and make comparisons. Mean gait cycle intervals were the same as those derived from motion capture, and cycle-to-cycle variability measures were within 1.5%. Subject group differences could be similarly identified using measures with the two methods. Conclusions: a simple tri-axial accelerometer accompanied by a signal processing algorithm can be used to capture stride events. Clinical impact: the proposed algorithm enables the assessment of stride events during treadmill walking, and is the first step toward the assessment of stride events using tri-axial accelerometers in real-life settings

Simulator sickness when performing gaze shifts within a wide field of view optic flow environment: preliminary evidence for using virtual reality in vestibular rehabilitation

BACKGROUND: Wide field of view virtual environments offer some unique features that may be beneficial for use in vestibular rehabilitation. For one, optic flow information extracted from the periphery may be critical for recalibrating the sensory processes used by people with vestibular disorders. However, wide FOV devices also have been found to result in greater simulator sickness. Before a wide FOV device can be used in a clinical setting, its safety must be demonstrated. METHODS: Symptoms of simulator sickness were recorded by 9 healthy adult subjects after they performed gaze shifting tasks to locate targets superimposed on an optic flow background. Subjects performed 8 trials of gaze shifting on each of the six separate visits. RESULTS: The incidence of symptoms of simulator sickness while subjects performed gaze shifts in an optic flow environment was lower than the average reported incidence for flight simulators. The incidence was greater during the first visit compared with subsequent visits. Furthermore, the incidence showed an increasing trend over the 8 trials. CONCLUSION: The performance of head unrestrained gaze shifts in a wide FOV optic flow environment is tolerated well by healthy subjects. This finding provides rationale for testing these environments in people with vestibular disorders, and supports the concept of using wide FOV virtual reality for vestibular rehabilitation

Isometric and isokinetic back and arm lifting strengths: Device and measurement

This study was conducted to measure isometric (static) and isokinetic (dynamic) back and arm lifting strengths at 20, 60 and 100 cm s-1 of young adults. Ten male and ten female volunteers without a history of back pain participated. The isokinetic lifting task was achieved by designing and fabricating a servo controlled motorized dynamic strength tester (DST). A regression analysis and analysis of variance was carried out on the strength data. The peak static strength values were significantly greater from the peak dynamic strength values. The peak dynamic strength was inversely related to the speed of motion. There were significant differences between the dynamic strengths at different stages of lift.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/27450/1/0000490.pd

Projections of Agricultural and Fish and Wildlife Water Demand in the Ouachita River Basin: A Linear Programming Approach

The availability of an abundant water supply has been a major resource of the Ouachita River Basin. In recent years, water requirements for a number of uses have increased, raising the concern that future water shortages could occur in the basin. The purpose of the study reported here was to estimate future water demand for irrigation, commercial fisheries, and fish and wildlife uses

High-pass filtering to remove electrocardiographic interference from torso EMG recordings

SummaryRemoval of electrocardiographic (ECG) contamination of electromyographic (EMG) signals from torso muscles is often attempted by high-pass filtering. This study investigated the effects of the cut-off frequency used in this high-pass filtering technique on the resulting EMG signal. Surface EMGs were recorded on five subjects from the rectus abdominis, external oblique, and erector spinae muscles. These signals were then digitally high-pass filtered at cut-off frequencies of 10, 30, and 60 Hz. Integration and power analyses of the filtered EMGs were subsequently performed. It was found that an increase in the cut-off frequency affects the integrated EMG signal by (1) reducing the ECG contamination, (2) decreasing the amplitude, and (3) smoothing the signal. It was concluded that the use of a high-pass filter is effective in reducing ECG interference in integrated EMG recordings, and a cut-off frequency of approximately 30 Hz was optimal.RelevanceElectromyographic recordings of torso muscles are often used in the development of low-back biomechanical models. Unfortunately, these recordings are usually contaminated by electrocardiographic interference. High-pass filtering methods are sometimes used to diminish the influence of ECG from surface EMGs; however, the effects of these filters on the recorded and processed EMG have not been reported. The findings show that high-pass filtering is effective in reducing ECG contamination and motion artefact from integrated EMGs when the appropriate cut-off frequency is used. Inappropriate cut-off frequencies lead to either incomplete ECG removal or excess filtering of the EMG signal.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/31029/1/0000706.pd

Utilisation of government-subsidised chronic disease management plans and cardiovascular care in Australian general practices

BACKGROUND: Government-subsidised general practice management plans (GPMPs) facilitate chronic disease management; however, impact on cardiovascular disease (CVD) is unknown. We aimed to determine utilisation and impact of GPMPs for people with or at elevated risk of CVD. METHODS: Secondary analysis of baseline data from the CONNECT randomised controlled trial linked to Medicare Benefits Schedule (MBS) and Pharmaceutical Benefits Scheme (PBS) claims. Multivariate regression examining the association of GPMP receipt and review with: (1) ≥ 1 MBS-subsidised allied health visit in the previous 24 months; (2) adherence to dual cardioprotective medication (≥ 80% of days covered with a dispensed PBS prescription); and (3) meeting recommended LDL-cholesterol and blood pressure (BP) targets concurrently. RESULTS: Overall, 905 trial participants from 24 primary health care services consented to data linkage. Participants with a GPMP (46.6%, 422/905) were older (69.4 vs 66.0 years), had lower education (32.3% vs 24.7% high school or lower), lower household income (27.5% vs 17.0% in lowest bracket), and more comorbidities, particularly diabetes (42.2% vs 17.6%) compared to those without a GPMP. After adjustment, a GPMP was strongly associated with allied health visits (odds ratio (OR) 14.80, 95% CI: 9.08–24.11) but not higher medication adherence rates (OR 0.82, 95% CI: 0.52–1.29) nor meeting combined LDL and BP targets (OR 1.31, 95% CI: 0.72–2.38). Minor differences in significant covariates were noted in models using GPMP review versus GPMP initiation. CONCLUSIONS: In people with or at elevated risk of CVD, GPMPs are under-utilised overall. They are targeting high-needs populations and facilitate allied health access, but are not associated with improved CVD risk management, which represents an opportunity for enhancing their value in supporting guideline-recommended care. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12875-022-01763-2

Prognostic value of National Early Warning Scores (NEWS2) and component physiology in hospitalised patients with COVID-19:a multicentre study

BACKGROUND: National Early Warning Scores (NEWS2) are used to detect all-cause deterioration. While studies have looked at NEWS2, the use of virtual consultation and remote monitoring of patients with COVID-19 mean there is a need to know which physiological observations are important. AIM: To investigate the relationship between outcome and NEWS2, change in NEWS2 and component physiology in COVID-19 inpatients. METHODS: A multi-centre retrospective study of electronically recorded, routinely collected physiological measurements between March and June 2020. First and maximum NEWS2, component scores and outcomes were recorded. Areas under the curve (AUCs) for 2-day, 7-day and 30-day mortality were calculated. RESULTS: Of 1263 patients, 26% died, 7% were admitted to intensive care units (ICUs) before discharge and 67% were discharged without ICU. Of 1071 patients with initial NEWS2, most values were low: 50% NEWS2=0–2, 27% NEWS2=3–4, 14% NEWS2=5–6 and 9% NEWS2=7+. Maximum scores were: 14% NEWS2=0–2, 22% NEWS2=3–4, 17% NEWS2=5–6 and 47% NEWS2=7+. Higher first and maximum scores were predictive of mortality, ICU admission and longer length of stay. AUCs based on 2-day, 7-day, 30-day and any hospital mortality were 0.77 (95% CI 0.70 to 0.84), 0.70 (0.65 to 0.74), 0.65 (0.61 to 0.68) and 0.65 (0.61 to 0.68), respectively. The AUCs for 2-day mortality were 0.71 (0.65 to 0.77) for supplemental oxygen, 0.65 (0.56 to 0.73) oxygen saturation and 0.64 (0.56 to 0.73) respiratory rate. CONCLUSION: While respiratory parameters were most predictive, no individual parameter was as good as a full NEWS2, which is an acceptable predictor of short-term mortality in patients with COVID-19. This supports recommendation to use NEWS2 alongside clinical judgement to assess patients with COVID-19