Clinician perspectives on having point of care tests made available to them during out of hours home visiting.

BACKGROUND: Little is known about clinicians' perspectives on the use of point of care (POC) tests in assessment of acute illness during primary care out of hours (OOH) care. During a service improvement project, POC tests (including creatinine, electrolytes, haemoglobin and lactate) were made available to clinicians undertaking OOH home visits, with the clinicians allowed absolute discretion about when and whether they used them. METHOD: To explore clinicians' perspectives on having POC tests available during OOH home visits, we undertook a qualitative study with clinicians working in Oxfordshire OOH home visiting teams. We conducted 19 Semi-structured interviews with clinicians working in OOH, including those who had and had not used the POC tests available to them. To explore evolving perspectives over time, including experience and exposure to POC tests, we offered clinicians the opportunity to be interviewed twice throughout the study period. Our sample included 7 GPs (4 interviewed once, 3 interviewed twice - earlier and later during the study), 6 emergency practitioners (EPs) including advanced nurse practitioners and paramedics, 1 Healthcare Assistant, and 2 ambulatory care physicians. Interviews were audio-recorded, transcribed verbatim and analysed thematically. RESULTS: The clinicians reflected on their decision-making to use (or not use) POC tests, including considering which clinical scenarios were "appropriate" and balancing the resources and time taken to do POC tests against what were perceived as likely benefits. The challenges of using the equipment in patients' homes was a potential barrier, though could become easier with familiarity and experience. Clinicians who had used POC tests described benefits, including planning onward care trajectories, and facilitating communication, both between professionals and with patients and their families. CONCLUSION: Clinicians described a discriminatory approach to using POC tests, considering carefully in which situations they were likely to add value to clinical decision-making.

Clinical Reliability of point-of-care tests to support community based acute ambulatory care.

OBJECTIVE: To ensure clinicians can rely on point-of-care testing results, we assessed agreement between point-of-care tests for creatinine, urea, sodium, potassium, calcium, Hb, INR, CRP and subsequent corresponding laboratory tests. PARTICIPANTS: Community-dwelling adults referred to a community-based acute ambulatory care unit. INTERVENTIONS: The Abbott i-STATTM (Hb, clinical chemistry, INR) and the AfinionTM Analyser (CRP) and corresponding laboratory analyses. OUTCOMES: Agreement (Bland-Altman) and bias (Passing-Bablok regression). RESULTS: Among 462 adults we found an absolute mean difference between point-of-care and central laboratory analyses of 6.4g/L (95%LOA -7.9 to +20.6) for haemoglobin, -0.5mmol/L (95%LOA -4.5 to +3.5) for sodium, 0.2mmol/L (95%LOA -0.6 to +0.9) for potassium, 0.0mmol/L (95%LOA -0.3 to +0.3) for calcium, 9.0 µmol/L (95%LOA -18.5 to +36.4) for creatinine, 0.0mmol/L (95%LOA -2.7 to +2.6) for urea, -0.2 (95%LOA -2.4 to +2.0) for INR, -5.0 mg/L (95%LOA -24.4 to +14.4) for CRP. CONCLUSIONS: There was acceptable agreement and bias for these analytes, except for haemoglobin and creatinine.

Antibiotic prescribing for the older adult: beliefs and practices in primary care.

BACKGROUND: Older adults suffer high morbidity and mortality following serious infections, and hospital admissions with these conditions are increasingly common. Antibiotic prescribing in the older adult population, especially in long-term care facilities, has been argued to be inappropriately high. In order to develop the evidence base and provide support to GPs in achieving antimicrobial stewardship in older adults it is important to understand their attitudes and beliefs toward antibiotic prescribing in this population. OBJECTIVES: To understand the attitudes and beliefs held by GPs regarding antibiotic prescribing in older adults. METHODS: Semi-structured qualitative interviews were conducted with 28 GPs working in the UK. Data analysis followed a modified framework approach. RESULTS: GPs described antibiotic prescribing in older adults as differing from prescribing in other age groups in a number of ways, including prescribing broad-spectrum, longer and earlier antibiotics in this population. There were also rationales for situations where antibiotics were prescribed despite there being no clear diagnosis of infection. Trials of antibiotics were used both as diagnostic aids and in an attempt to avoid admission. The risks of antibiotics were understood, but in some cases restrictions on antibiotic use were thought to hamper optimal management of infection in this age group. CONCLUSIONS: Diagnosing serious infections in older adults is challenging and antibiotic prescribing practices reflect this challenge, but also reflect an absence of clear guidance or evidence. Research that can fill the gaps in the evidence base is required in order to support GPs with their critical antimicrobial stewardship role in this population.

Extended genotypic evaluation and comparison of twenty-two cases of lethal EEHV1 hemorrhagic disease in wild and captive Asian elephants in India.

Thirteen new lethal cases of acute hemorrhagic disease (HD) with typical histopathogical features were identified in young Asian elephants (Elephas maximus indicus) in India between 2013 and 2017. Eight occurred amongst free-ranging wild herds, with three more in camp-raised orphans and two in captive-born calves. All were confirmed to have high levels of Elephant Endotheliotropic Herpesvirus type 1A (EEHV1A) DNA detected within gross pathological lesions from necropsy tissue by multi-locus PCR DNA sequencing. The strains involved were all significantly different from one another and from nine previously described cases from Southern India (which included one example of EEHV1B). Overall, eight selected dispersed PCR loci totaling up to 6.1-kb in size were analyzed for most of the 22 cases, with extensive subtype clustering data being obtained at four hypervariable gene loci. In addition to the previously identified U48(gH-TK) and U51(vGPCR1) gene loci, these included two newly identified E5(vGPCR5) and E54(vOX2-1) loci mapping far outside of the classic EEHV1A versus EEHV1B subtype chimeric domains and towards the novel end segments of the genome that had not been evaluated previously. The high levels of genetic divergence and mosaic scrambling observed between adjacent loci match closely to the overall range of divergence found within 45 analyzed North American and European cases, but include some common relatively unique polymorphic features and preferred subtypes that appear to distinguish most but not all Indian strains from both those in Thailand and those outside range countries. Furthermore, more than half of the Indian cases studied here involved calves living within wild herds, whereas nearly all other cases identified in Asia so far represent rescued camp orphans or captive-born calves.

Increase in antibiotic prescriptions in out-of-hours primary care in contrast to in-hours primary care prescriptions: service evaluation in a population of 600 000 patients.

OBJECTIVES: The objective of this study was to describe the frequency and nature of antibiotic prescriptions issued by a primary care out-of-hours (OOH) service and compare time trends in prescriptions between OOH and in-hours primary care. METHODS: We performed a retrospective audit of 496 931 patient contacts with the Oxfordshire OOH primary care service. Comparison of time trends in antibiotic prescriptions from OOH primary care and in-hours primary care for the same population was made using multiple linear regression models fitted to the monthly data for OOH prescriptions, OOH contacts and in-hours prescriptions between September 2010 and August 2014. RESULTS: Compared with the overall population contacting the OOH service, younger age, female sex and patients who were less deprived were independently correlated with an increased chance of a contact resulting in prescription of antibiotics. The majority of antibiotics were prescribed to patients contacting the service at weekends. Despite a reduction in patient contacts with the OOH service [an estimated decrease of 486.5 monthly contacts each year (95% CI -676.3 to -296.8), 5.0% of the average monthly contacts], antibiotic prescriptions from this service rose during the study period [increase of 37.1 monthly prescriptions each year (95% CI 10.6-63.7), 2.5% of the average monthly prescriptions]. A matching increase was not seen for in-hours antibiotic prescriptions; the difference between the year trends was significant (Z test, P = 0.002). CONCLUSIONS: We have demonstrated trends in prescribing that could represent a partial displacement of antibiotic prescribing from in-hours to OOH primary care. The possibility that the trends we describe are evident nationally should be explored.

Genome sequence of vanilla distortion mosaic virus infecting Coriandrum sativum.

The 9573-nucleotide genome of a potyvirus was sequenced from a Coriandrum sativum plant from India with viral symptoms. On analysis, this virus was shown to have greater than 85 % nucleotide sequence identity to vanilla distortion mosaic virus (VDMV). Analysis of the putative coat protein sequence confirmed that this virus was in fact VDMV, with greater than 91 % amino acid sequence identity. The genome appears to encode a 3083-amino-acid polyprotein potentially cleaved into the 10 mature proteins expected in potyviruses. Phylogenetic analysis confirmed that VDMV is a distinct but ungrouped member of the genus Potyvirus.

Evidence for non-communicable diseases: analysis of Cochrane reviews and randomised trials by World Bank classification.

INTRODUCTION: Prevalence of non-communicable diseases (NCDs) is increasing globally, with the greatest projected increases in low-income and middle-income countries. We sought to quantify the proportion of Cochrane evidence relating to NCDs derived from such countries. METHODS: We searched the Cochrane database of systematic reviews for reviews relating to NCDs highlighted in the WHO NCD action plan (cardiovascular, cancers, diabetes and chronic respiratory diseases). We excluded reviews at the protocol stage and those that were repeated or had been withdrawn. For each review, two independent researchers extracted data relating to the country of the corresponding author and the number of trials and participants from countries, using the World Bank classification of gross national income per capita. RESULTS: 797 reviews were analysed, with a reported total number of 12 340 trials and 10 937 306 participants. Of the corresponding authors 90% were from high-income countries (41% from the UK). Of the 746 reviews in which at least one trial had met the inclusion criteria, only 55% provided a summary of the country of included trials. Analysis of the 633 reviews in which country of trials could be established revealed that almost 90% of trials and over 80% of participants were from high-income countries. 438 (5%) trials including 1 145 013 (11.7%) participants were undertaken in low-middle income countries. We found that only 13 (0.15%) trials with 982 (0.01%) participants were undertaken in low-income countries. Other than the five Cochrane NCD corresponding authors from South Africa, only one other corresponding author was from Africa (Gambia). DISCUSSION: The overwhelming body of evidence for NCDs pertains to high-income countries, with only a small number of review authors based in low-income settings. As a consequence, there is an urgent need for research infrastructure and funding for the undertaking of high-quality trials in this area.

Wireless recording of the calls of Rousettus aegyptiacus and their reproduction using electrostatic transducers.

Bats are capable of imaging their surroundings in great detail using echolocation. To apply similar methods to human engineering systems requires the capability to measure and recreate the signals used, and to understand the processing applied to returning echoes. In this work, the emitted and reflected echolocation signals of Rousettus aegyptiacus are recorded while the bat is in flight, using a wireless sensor mounted on the bat. The sensor is designed to replicate the acoustic gain control which bats are known to use, applying a gain to returning echoes that is dependent on the incurred time delay. Employing this technique allows emitted and reflected echolocation calls, which have a wide dynamic range, to be recorded. The recorded echoes demonstrate the complexity of environment reconstruction using echolocation. The sensor is also used to make accurate recordings of the emitted calls, and these calls are recreated in the laboratory using custom-built wideband electrostatic transducers, allied with a spectral equalization technique. This technique is further demonstrated by recreating multi-harmonic bioinspired FM chirps. The ability to record and accurately synthesize echolocation calls enables the exploitation of biological signals in human engineering systems for sonar, materials characterization and imaging.

Six-degree-of-freedom whole-body vibration exposure levels during routine skidder operations.

This research focuses on quantifying six-degree-of-freedom (6-DOF) whole-body vibration (WBV) exposure levels that occur in Northern Ontario skidders during routine field operating tasks. 6-DOF vibration running root-mean-square (RMS) acceleration levels at the operator/seat interface were determined for eight skidders while driving loaded, driving unloaded, picking up a load, dropping off a load and ploughing logs under field operating conditions. The acceleration data were weighted in accordance with ISO 2631-1:1997 and evaluated for both health and comfort outcomes. The mean running RMS weighted translational and rotational accelerations all exceeded 0.36 m/s(2) and 0.14 rad/s(2). The greatest average accelerations occurred while driving unloaded with this condition displaying translational vibration total values (VTV) that exceeded the upper limit of the ISO 2631-1:1997 health caution zone within an average of 2.3 h. Utilizing 6-DOF VTV, virtually all operating conditions would be designated as uncomfortable. STATEMENT OF RELEVANCE: This study provides one of the most comprehensive reports on vibration exposures in seated vehicle operators. The results are geared towards ergonomists with discussions on health effects and measurement concerns, while providing the raw vibration exposure data that will be useful to vehicle, component and vibration sensor designers.

Clinico-pathologic features of fatal disease attributed to new variants of endotheliotropic herpesviruses in two Asian elephants (Elephas maximus).

The first herpesviruses described in association with serious elephant disease were referred to as endotheliotropic herpesviruses (EEHV) because of their ability to infect capillary endothelial cells and cause potentially fatal disease. Two related viruses, EEHV1 and EEHV2, have been described based on genetic composition. This report describes the similarities and differences in clinicopathologic features of 2 cases of fatal endotheliotropic herpesvirus infections in Asian elephants caused by a previously unrecognized virus within the betaherpesvirus subfamily. EEHV3 is markedly divergent from the 2 previously studied fatal probosciviruses, based on polymerase chain reaction sequence analysis of 2 segments of the viral genome. In addition to ascites, widespread visceral edema, petechiae, and capillary damage previously reported, important findings with EEHV3 infection were the presence of grossly visible renal medullary hemorrhage, a tropism for larger veins and arteries in various tissues, relatively high density of renal herpetic inclusions, and involvement of the retinal vessels. These findings indicate a less selective organ tropism, and this may confer a higher degree of virulence for EEHV3.

Modern evolutionary history of the human KSHV genome.

The genomes of several human herpesviruses, including Kaposi sarcoma (KS) herpesvirus (KSHV), display surprisingly high levels of both genetic diversity and clustered subtyping at certain loci. We have been interested in understanding this phenomenon with the hope that it might be a useful diagnostic tool for viral epidemiology, and that it might provide some insights about how these large viral genomes evolve over a relatively short timescale. To do so, we have carried out extensive PCR DNA sequence analysis across the genomes of 200 distinct KSHV samples collected from KS patients around the world. Here we review and summarize current understanding of the origins of KSHV variability, the spread of KSHV and its human hosts out of Africa, the existence of chimeric genomes, and the concept that different segments of the genome have had different evolutionary histories.

Modelling the bioelectric behaviour of halo pin-patient structures during magnetic resonance imaging.

Bioelectric compatibility of electrically conductive halo fixation devices and magnetic resonance (MR) imaging has been largely based on resulting image quality. Previous studies have focused primarily on improving image quality and, although the electrical characteristics of the system during imaging may have been noted, they have not been studied in depth. Utilizing both a theoretical and experimental approximation, this study focuses on the bioelectric characteristics of the pin-patient structures typically enountered in clinical halo fixation systems. Results indicate that the halo pin-patient system can be modelled using a resistor-inductor-capacitor circuit and that simple attempts at improving compatibility through increasing interface resistance by the use of insulated pins may not be an effective approach to improving halo instrumentation compatibility with new, stronger magnetic and higher-frequency resonance imaging systems.

Laterality effects in the recognition of depth-rotated novel objects.

The dissociable neural subsystems theory proposes that left-hemisphere (LH) performance is dominated by a viewpoint-invariant (VI) recognition subsystem, whereas right-hemisphere (RH) performance is dominated by a viewpoint-dependent (VD) subsystem (Marsolek, 1999). Studies supporting this theory have used familiar objects and, therefore, may have been confounded by characteristics beyond perceptual features. Experiment 1, a lateralized sequential-matching task with novel objects, showed VD recognition in both hemispheres. In Experiment 2, some participants learned semantic associations for four novel objects, whereas others were exposed to the novel objects without the semantic associations. Both groups later performed a depth-rotated lateralized sequential-matching task. The participants who had learned semantic associations showed greater VD performance in the RH than in the LH; however, the participants in the control group showed equivalent VD performance in both hemispheres. The results suggest that hemispheric differences in VD performance may be partially attributable to an LH advantage for semantic processing.

Olfactory stimulation of Africanized honey bee (Hymenoptera: Apidae) attacks by insect repellents.

Three common insect repellents (N,N-diethyl-m-toluamide [DEET], Pyranha, and Repel X) were tested to determine whether they affected Africanized honey bee attack behavior. Eight Africanized honey bee (Apis mellifera L.) colonies were exposed in an alternating series to the test repellents or blank controls delivered in a stream of air directed toward the colony entrances. The response generated by the repellents and the controls was measured as the number of attacking honey bees recorded with an electronic temper tester. Neither a citronella-based repellent (Pyranha) nor DEET had any effect on colony behavior; however, Repel X consistently caused a greater attack response after exposure.

The oscillatory activity in the Parkinsonian subthalamic nucleus investigated using the macro-electrodes for deep brain stimulation.

OBJECTIVES: To investigate the oscillatory activity in the Parkinsonian subthalamic nucleus using the macro-electrodes for deep brain stimulation. METHODS: During bilateral deep brain stimulating electrode implantation, spontaneous and evoked field potentials were recorded from the subthalamic nucleus (STN) in two patients with Parkinson's disease (PD) during spontaneous resting tremor, passive manipulation of the wrist, and following electrical stimulation of the contralateral STN. RESULTS: Frequency analysis of the STN field potentials recorded during spontaneous resting tremor showed significant coherence with electromyographic activity in the contralateral arm, suggesting a close involvement of the STN in the generation of resting tremor in PD. The STN responded to passive movement of the contralateral wrist, but not to ipsilateral movement. High frequency (100 Hz) electrical stimulation of the STN induced tremor (4 Hz) in both forearms, and also oscillation of the contralateral STN (4 Hz). In contrast, low frequency (5 Hz) stimulation induced contralateral arrhythmic involuntary movement (3 Hz), but without altering the contralateral STN activity. CONCLUSIONS: We propose that the functional connection between the STN and arm muscles is mainly contralateral, but cross talk may occur between bilateral STN via a frequency-dependent pathway.

Proteasome-independent disruption of PML oncogenic domains (PODs), but not covalent modification by SUMO-1, is required for human cytomegalovirus immediate-early protein IE1 to inhibit PML-mediated transcriptional repression.

Human cytomegalovirus (HCMV) major immediate-early protein IE1 is an abundant 72-kDa nuclear phosphoprotein that is thought to play an important role in efficient triggering of the lytic cycle, especially at low multiplicity of infection. The best-known properties of IE1 at present are its transient targeting to punctate promyelocytic leukemia protein (PML)-associated nuclear bodies (PML oncogenic domains [PODs] or nuclear domain 10 [ND10]), with associated displacement of the cellular PML tumor suppressor protein into a diffuse nucleoplasmic form and its association with metaphase chromosomes. Recent studies have shown that the targeting of PML (and associated proteins such as hDaxx) to PODs is dependent on modification of PML by ubiquitin-like protein SUMO-1. In this study, we provide direct evidence that IE1 is also covalently modified by SUMO-1 in both infected and cotransfected cells, as well as in in vitro assays, with up to 30% of the protein representing the covalently conjugated 90-kDa form in stable U373/IE1 cell lines. Lysine 450 was mapped as the major SUMO-1 conjugation site, but a point mutation of this lysine residue in IE1 did not interfere with its targeting to and disruption of the PODs. Surprisingly, unlike PML or IE2, IE1 did not interact with either Ubc9 or SUMO-1 in yeast two-hybrid assays, suggesting that some additional unknown intranuclear cofactors must play a role in IE1 sumoylation. Interestingly, stable expression of either exogenous PML or exogenous Flag-SUMO-1 in U373 cell lines greatly enhanced both the levels and rate of in vivo IE1 sumoylation during HCMV infection. Unlike the disruption of PODs by the herpes simplex virus type 1 IE110(ICP0) protein, the disruption of PODs by HCMV IE1 proved not to involve proteasome-dependent degradation of PML. We also demonstrate here that the 560-amino-acid PML1 isoform functions as a transcriptional repressor when fused to the GAL4 DNA-binding domain and that wild-type IE1 inhibits the repressor function of PML1 in transient cotransfection assays. Furthermore, both IE1(1-346) and IE1(L174P) mutants, which are defective in displacing PML from PODs, failed to inhibit the repression activity of PML1, whereas the sumoylation-negative IE1(K450R) mutant derepressed as efficiently as wild-type IE1. Taken together, our results suggest that proteasome-independent disruption of PODs, but not IE1 sumoylation, is required for efficient IE1 inhibition of PML-mediated transcriptional repression.

The generation and detection of longitudinal guided waves in thin fibers using a conical transformer.

This paper describes a technique to couple ultrasonic energy from a piezoceramic disc transducer into a fiber waveguide to induce longitudinal propagation. A polymer cone is utilized to bond the fiber waveguide onto the surface of the disc and to behave as a mechanical transformer, converting lateral displacements at its base into longitudinal displacements at its apex. Wideband finite element analysis (FEA) results are provided to show that the bond efficiently couples the radial modes of a disc transducer into fiber waveguides for longitudinal mode excitation. Furthermore, narrowband FEA is utilized to investigate how the geometry and material properties of the bond and waveguide influence the coupling efficiency. The technique is then quantified in terms of signal-to-coherent noise ratio (SCNR), reflecting its ability to generate the desired longitudinal waveguide mode and reject erroneous modes. Finally, design parameters are outlined for the successful implementation of this technique.