The impact of COVID-19 on major trauma (ISS>15) in London, across its four Level 1 centres.

INTRODUCTION: The COVID-19 pandemic has led to reconfiguration of healthcare resources to manage increased demand for acute hospital beds and intensive care places. Concerns were raised regarding continuing provision of critical care for non-COVID patients during the pandemic. The aim of this study was to assess the impact of the COVID-19 pandemic on patients admitted with major trauma (Injury Severity Score >15) across the four Level 1 trauma centres in London. METHODS: Data were collected from all four major trauma centres (MTCs) in London using the Trauma Audit and Research Network database and from local databases at each centre. A 2-month period from 5 March to 5 May 2020 was selected and the same period during 2019 was used to compare changes due to the pandemic. RESULTS: There was a 31% decrease in overall number of patients presenting to the four MTCs during the COVID-19 period compared with 2019. There was no difference in patient demographics or mechanism of injury between the two periods. Sports-related injuries and proportion of self-presentation to hospital were reduced slightly during the pandemic, although the differences were not statistically significant. The mortality rate and association between mortality and injury severity were similar. Proportion of patients requiring intensive care unit facilities also did not change. CONCLUSION: Despite diversion of critical care resources to deal with COVID-related admissions, we did not observe a change in mortality rate or proportion of severely injured patients requiring critical care. Our results suggest London MTCs were able to provide their usual standard of care for critically injured major trauma (Injury Severity Score >15) patients during the pandemic.

Noise creates polarization artefacts.

The accuracy of calculations of both the degree and angle of polarization depend strongly on the noise in the measurements used. The noise in the measurements recorded by both camera based systems and spectrometers can lead to significant artefacts and incorrect conclusions about high degrees of polarization when in fact none exist. Three approaches are taken in this work: firstly, the absolute error introduced as a function of the signal to noise ratio for polarization measurements is quantified in detail. An important finding here is the reason for why several studies incorrectly suggest that black (low reflectivity) objects are highly polarized. The high degree of polarization is only an artefact of the noise in the calculation. Secondly, several simple steps to avoid such errors are suggested. Thirdly, if these points can not be followed, two methods are presented for mitigating the effects of noise: a maximum likelihood estimation method and a new denoising algorithm to best calculate the degree of polarization of natural polarization information.

Informed consent and the readability of the written consent form.

Introduction The aim of this study was to objectively ascertain the level of readability of standardised consent forms for orthopaedic procedures. Methods Standardised consent forms (both in summary and detailed formats) endorsed by the British Orthopaedic Association (BOA) were retrieved from orthoconsent.com and assessed for readability. This involved using an online tool to calculate the validated Flesch reading ease score (FRES). This was compared with the FRES for the National Health Service (NHS) Consent Form 1. Data were analysed and interpreted according to the FRES grading table. Results The FRES for Consent Form 1 was 55.6, relating to the literacy expected of an A level student. The mean FRES for the BOA summary consent forms (n=27) was 63.6 (95% confidence interval [CI]: 61.2-66.0) while for the detailed consent forms (n=32), it was 68.9 (95% CI: 67.7-70.0). All BOA detailed forms scored >60, correlating to the literacy expected of a 13-15-year-old. The detailed forms had a higher FRES than the summary forms (p<0.001). Conclusions This study demonstrates that the BOA endorsed standardised consent forms are much easier to read and understand than the NHS Consent Form 1, with the detailed BOA forms being the easiest to read. Despite this, owing to varying literacy levels, a significant proportion of patients may struggle to give informed consent based on the written information provided to them.

Separating heart and brain: on the reduction of physiological noise from multichannel functional near-infrared spectroscopy (fNIRS) signals.

OBJECTIVE: Functional near-infrared spectroscopy (fNIRS) is an emerging technique for the in vivo assessment of functional activity of the cerebral cortex as well as in the field of brain-computer interface (BCI) research. A common challenge for the utilization of fNIRS in these areas is a stable and reliable investigation of the spatio-temporal hemodynamic patterns. However, the recorded patterns may be influenced and superimposed by signals generated from physiological processes, resulting in an inaccurate estimation of the cortical activity. Up to now only a few studies have investigated these influences, and still less has been attempted to remove/reduce these influences. The present study aims to gain insights into the reduction of physiological rhythms in hemodynamic signals (oxygenated hemoglobin (oxy-Hb), deoxygenated hemoglobin (deoxy-Hb)). APPROACH: We introduce the use of three different signal processing approaches (spatial filtering, a common average reference (CAR) method; independent component analysis (ICA); and transfer function (TF) models) to reduce the influence of respiratory and blood pressure (BP) rhythms on the hemodynamic responses. MAIN RESULTS: All approaches produce large reductions in BP and respiration influences on the oxy-Hb signals and, therefore, improve the contrast-to-noise ratio (CNR). In contrast, for deoxy-Hb signals CAR and ICA did not improve the CNR. However, for the TF approach, a CNR-improvement in deoxy-Hb can also be found. SIGNIFICANCE: The present study investigates the application of different signal processing approaches to reduce the influences of physiological rhythms on the hemodynamic responses. In addition to the identification of the best signal processing method, we also show the importance of noise reduction in fNIRS data.

Motor imagery-induced EEG patterns in individuals with spinal cord injury and their impact on brain-computer interface accuracy.

OBJECTIVE: Assimilating the diagnosis complete spinal cord injury (SCI) takes time and is not easy, as patients know that there is no 'cure' at the present time. Brain-computer interfaces (BCIs) can facilitate daily living. However, inter-subject variability demands measurements with potential user groups and an understanding of how they differ to healthy users BCIs are more commonly tested with. Thus, a three-class motor imagery (MI) screening (left hand, right hand, feet) was performed with a group of 10 able-bodied and 16 complete spinal-cord-injured people (paraplegics, tetraplegics) with the objective of determining what differences were present between the user groups and how they would impact upon the ability of these user groups to interact with a BCI. APPROACH: Electrophysiological differences between patient groups and healthy users are measured in terms of sensorimotor rhythm deflections from baseline during MI, electroencephalogram microstate scalp maps and strengths of inter-channel phase synchronization. Additionally, using a common spatial pattern algorithm and a linear discriminant analysis classifier, the classification accuracy was calculated and compared between groups. MAIN RESULTS: It is seen that both patient groups (tetraplegic and paraplegic) have some significant differences in event-related desynchronization strengths, exhibit significant increases in synchronization and reach significantly lower accuracies (mean (M) = 66.1%) than the group of healthy subjects (M = 85.1%). SIGNIFICANCE: The results demonstrate significant differences in electrophysiological correlates of motor control between healthy individuals and those individuals who stand to benefit most from BCI technology (individuals with SCI). They highlight the difficulty in directly translating results from healthy subjects to participants with SCI and the challenges that, therefore, arise in providing BCIs to such individuals.

Health effects of subchronic exposure to diesel-water-methanol emulsion emission.

The U.S. Environmental Protection Agency's National Ambient Air Quality Standards for ozone and particulate matter (PM) require urban non-attainment areas to implement pollution-reduction strategies for anthropogenic source emissions. The type of fuel shown to decrease combustion emissions components versus traditional diesel fuel, is the diesel emulsion. The Lubrizol Corporation, in conjunction with Lovelace Respiratory Research Institute and several subcontracting laboratories, recently conducted a health assessment of the combustion emissions of PuriNOx diesel fuel emulsion (diesel-water-methanol) in rodents. Combustion emissions from either of two, 2002 model Cummins 5.9L ISB engines, were diluted with charcoal-filtered air to exposure concentrations of 125, 250 and 500 microg total PM/m3. The engines were operated on a continuous, repeating, heavy-duty certification cycle (U.S. Code of Federal Regulations, Title 40, Chapter I) using Rotella-T 15W-40 engine oil. Nitrogen oxide (NO) and PM were reduced when engines were operated on PuriNOx versus California Air Resources Board diesel fuel under these conditions. Male and female F344 rats were housed in Hazleton H2000 exposure chambers and exposed to exhaust atmospheres 6 h/day, five days/week for the first 11 weeks and seven days/week thereafter. Exposures ranged from 61 to 73 days depending on the treatment group. Indicators of general toxicity (body weight, organ weight, clinical pathology and histopathology), neurotoxicity (glial fibrillary acidic protein assay), genotoxicity (Ames assay, micronucleus, sister chromatid exchange), and reproduction and development were measured. Overall, effects observed were mild. Emulsion combustion emissions were not associated with neurotoxicity, reproductive/developmental toxicity, or in vivo genotoxicity. Small decreases in serum cholesterol in the 500-microg/m3 exposure group were observed. PM accumulation within alveolar macrophages was evident in all exposure groups. The latter findings are consistent with normal physiological responses to particle inhalation. Other statistically significant effects were present in some measured parameters of other exposed groups, but were not clearly attributed to emissions exposure. Positive mutagenic responses in several strains of Salmonella typhimurium were observed subsequent to treatment with emulsion emissions subfractions. Based on the cholesterol results, it can be concluded that the 250-microg/m3 exposure level was the no observed effect level. In general, biological findings in exposed rats and bacteria were consistent with exposure to petroleum diesel exhaust in the F344 rat and Ames assays.

Health effects of subchronic exposure to diesel-water emulsion emission.

The U.S. Environmental Protection Agency (EPA) National Ambient Air Quality Standards for ozone and particulate matter are requiring urban nonattainment areas to implement pollution-reduction strategies for anthropogenic source emissions. A type of fuel shown to decrease combustion emissions components versus traditional diesel fuels is the diesel-water emulsion. The Lubrizol Corporation in conjunction with Lovelace Respiratory Research Institute and several subcontracting laboratories recently conducted a rodent health assessment of inhaled combustion emissions of PuriNO(x) diesel fuel emulsion. Combustion emissions from either of two 2001 model Cummins 5.9-L ISB engines were diluted with charcoal-filtered air to exposure concentrations of 100, 200, and 400 microg total particulate matter/m(3). The engines were operated on a continuously repeating, heavy-duty certification cycle (U.S. Code of Federal Regulations, Title 40, Chapter I) using Rotella-T 15W-40 engine oil. Nitrogen oxide and particulate matter were reduced when engines were operated on PuriNO(x) versus California Air Resources Board diesel fuel under these conditions. Male and female F344 rats were housed in Hazleton H2000 exposure chambers and exposed to exhaust atmospheres 6 h/day, 5 days/wk for the first 11 wk and 7 days/wk threafter. Exposures ranged from 58 to 70 days, depending on the treatment group. Indicators of general toxicity (body weight, organ weight, clinical pathology, and histopathology), neurotoxicity (glial fibrillary acidic protein assay), genotoxicity (Ames assay, micronucleus, sister chromatid exchange), and reproduction and development were measured. Overall, effects observed were mild. Emulsion combustion emissions were not associated with neurotoxicity, reproductive/developmental toxicity, or in vivo genotoxicity. Small decreases in serum cholesterol and small increases in platelet values in some groups of exposed animals were observed. Particulate matter accumulation within alveolar macrophages was evident in all exposure groups. These findings are consistent with normal physiological responses to particle inhalation. Other statistically significant effects were present in some measured parameters of other exposed groups but were not clearly attributed to emissions exposure. Positive mutagenic responses in several strains of Salmonella typhimurium were observed subsequent to treatment with emulsion emissions subfractions. Based on the cholesterol and platelet results, it can be concluded that the 100 microg/m(3) exposure level was the no-observed-effect level. In general, biological findings in diesel emulsion emission-exposed animals and bacteria were consistent with exposure to petroleum diesel exhaust in the F344 rat and Ames assays.

Familial dysautonomia is caused by mutations of the IKAP gene.

The defective gene DYS, which is responsible for familial dysautonomia (FD) and has been mapped to a 0.5-cM region on chromosome 9q31, has eluded identification. We identified and characterized the RNAs encoded by this region of chromosome 9 in cell lines derived from individuals homozygous for the major FD haplotype, and we observed that the RNA encoding the IkappaB kinase complex-associated protein (IKAP) lacks exon 20 and, as a result of a frameshift, encodes a truncated protein. Sequence analysis reveals a T-->C transition in the donor splice site of intron 20. In individuals bearing a minor FD haplotype, a missense mutation in exon 19 disrupts a consensus serine/threonine kinase phosphorylation site. This mutation results in defective phosphorylation of IKAP. These mutations were observed to be present in a random sample of Ashkenazi Jewish individuals, at approximately the predicted carrier frequency of FD. These findings demonstrate that mutations in the gene encoding IKAP are responsible for FD.

First admission incidence study of mania, 1975-1981.

BACKGROUND: A previous cross-national epidemiological study of first admission rates in London and in Aarhus, Denmark, found that the incidence of mania was virtually identical for both centres. This study sought to examine the corresponding rate for a defined catchment area in Dublin, Ireland, and to establish whether the impression of a higher rate could be validated. METHOD: The study combined a six-year retrospective review and one-year prospective collection of first-admission cases of mania from a defined catchment area. Diagnosis was according to ICD criteria and the Syndrome Check List of the Present State Examination (PSE). Cross-national comparisons were made using standardised incidence rate ratios (SIRs). RESULTS: The crude incidence rate for Dublin in the age range 18-60 years was established at 4.5 per 100,000 per year. A comparison of SIRs for the three centres showed the Dublin rate to be higher than expected (P < 0.02). Age-specific analysis indicated that this increase came mainly from the age range 18-29 (chi 2 = 9.08, P = 0.01). CONCLUSIONS: The study confirmed the impression that the local incidence of mania in Dublin is higher than that reported from two other North European centres. A variation in rates from contrasting socioeconomic districts within the catchment area points to some caution in the interpretation of the results and suggests further study from wider catchment areas.

[A six-month intraperitoneal repeated dose toxicity study of tazobactam/piperacillin and tazobactam in rats].

Tazobactam (TAZ) is a newly developed beta-lactamase inhibitor. Tazobactam/Piperacillin (TAZ/PIPC) is a formulation consisting of TAZ and PIPC in a ratio of 1:4. A six-month intraperitoneal repeated dose toxicity study of TAZ/PIPC and TAZ including a one-month recovery period were carried out using male and female rats. The doses were 200, 400 and 800 mg/kg/day for TAZ/PIPC, and 40, 80 and 160 mg/kg/day for TAZ. The results were as follows. 1. No test article-related deaths occurred during the study period. No effect on clinical finding of survival rats was evident. 2. There was no dose-related increases of food consumption in both the males and females given TAZ/PIPC and PIPC. Slight reductions in body weight gain occurred in males given 800 mg/kg/day of TAZ/PIPC. 3. Decreases in erythrocyte, hemoglobin and hematocrit, and increases in reticulocytes were seen only at study termination in the group given 800 mg/kg/day of TAZ/PIPC. Increases in reticulocytes were seen only at study termination in the females given 80 or 160 mg/kg/day of TAZ. 4. A decrease in triglyceride levels was observed in the males given 800 mg/kg/day of TAZ/PIPC or 160 mg/kg/day of TAZ. 5. The ophthalmoscopic examination or urinalysis show no test article-related changes. 6. Enlarged ceca in all groups of animals given TAZ/PIPC and in the females given 160 mg/kg/day of TAZ were observed. 7. An increase of relative organ weight in liver was noted in the males and females given 800 mg/kg/day of TAZ/PIPC, in the males given 80 or 160 mg/kg/day of TAZ and in the females given 160 mg/kg/day of TAZ. 8. In the hepatocytes, accumulation of PAS-positive materials which was identified histochemically and ultrastructurally as glycogen, was present in the males given 800 mg/kg/day of TAZ/PIPC and in the males given 80 or 160 mg/kg/day of TAZ. 9. After a one-month recovery period, the changes of liver had generally disappeared, suggesting that they were reversible. 10. From the histopathological changes of liver, the no-toxic dose level in both the males and females was 400 mg/kg/day and 40 mg/kg/day for TAZ/PIPC and TAZ, respectively.

Subchronic and chronic inhalation toxicity of antimony trioxide in the rat.

Fischer 344 rats were exposed by inhalation to Sb2O3 (antimony trioxide) dust at exposure levels of 0, 0.25, 1.08, 4.92, and 23.46 mg/m3 for 6 hr/day, 5 days/week for 13 weeks followed by a 27-week observation period. Subsequently, an inhalation oncogenicity study was conducted at exposure levels of 0, 0.06, 0.51, and 4.50 mg/m3 for 12 months followed by a 12-month observation period. The Sb2O3 in the subchronic study had a mass median aerodynamic diameter (MMAD) of 3.05 +/- 0.21 microns (mean +/- SD) with a geometric standard deviation (GSD) of 1.57 +/- 0.06. In the chronic study, the MMAD was 3.76 +/- 0.84 and the GSD was 1.79 +/- 0.32. Except for the eyes, no adverse clinical observations were attributed to Sb2O3 in either study. In the subchronic study, corneal irregularities were seen after about 2 weeks of exposure and did not abate during the observation period. In the chronic study, ophthalmoscopic evaluation at 24 months revealed a dose-related increase in cataracts of 11, 24, 28, and 32% (both sexes combined) for each group, respectively. Body weights were significantly lower (6%) than the control group's weights in the 23.46 mg/m3 males in the subchronic study. These rats did not recover this weight during the 27-week observation period. Body weights of the females in both studies and males in the chronic study were unaffected. There were no Sb2O3 effects on clinical chemistry or hematology in either study. Mean absolute and relative lung weights were significantly increased in the 4.92 and 23.46 mg/m3 groups in the subchronic study. The 23.46 mg/m3 group's lung weights did not recover to control levels during the 27-week observation period. Lung weights for rats in the chronic study were unaffected. Microscopic changes in the lungs in the subchronic and chronic study were limited to subacute-chronic interstitial inflammation, increased numbers of alveolar-intraalveolar macrophages, foreign material in the alveolar-intraalveolar macrophages in the peribronchial and perivascular (chronic study only) lymphoid aggregates and in the peribronchial lymph nodes, granulomatous inflammation/granulomas, and fibrosis. In the chronic study, any observed neoplasms occurred with comparable incidence among all groups and were within the historical range for controls. Clearance of Sb2O3 from the lung was burden dependent and was reduced by 80% in the 4.50 mg/m3 group in the chronic study. The previously reported studies, which found Sb2O3 to be a carcinogen, were run at higher lung burdens. Under the exposure conditions of the current study, Sb2O3 was not a carcinogen.

Subchronic oral toxicity of cellulose acetate in rats.

Cellulose acetate was administered by way of a dietary admixture to Sprague-Dawley rats (20/sex/group) at dose levels of 0, 500, 2500 and 5000 mg/kg body weight/day for 94-96 days. Physical observations, body weight and food consumption measurements were made before testing and throughout the study. Ophthalmoscopic examinations were conducted on all animals before testing and just prior to study termination. Haematology, clinical chemistry and urinalysis were performed at 1.5 and 3 months on 10 animals/sex/group. After 3 months of treatment the animals were killed, terminal body weights and organ weights were measured and ratios calculated. Histopathological examination of tissues from the control and high-dose groups was conducted. The evaluation of physical observations, ophthalmology, body weight, food consumption, haematology, clinical chemistry, organ-to-body-weight ratios, gross pathology and histopathology revealed no evidence of an adverse effect related to treatment with cellulose acetate.

Subchronic inhalation toxicity of ethylbenzene in mice, rats, and rabbits.

Mice, rats, and rabbits (five/sex/group) were exposed by inhalation to ethylbenzene (EB) vapors for 6 hr/day, 5 days/week for 4 weeks (20 exposures). Rats and mice received 0, 99, 382, or 782 ppm EB while rabbits received 0, 382, 782, or 1610 ppm. No changes were evident in mortality patterns, clinical chemistries, urinalyses, or treatment-related gross/microscopic (including ophthalmologic) lesions. Rats exhibited sporadic lacrimation and salivation, as well as significantly increased liver weights at 382 and 782 ppm, and small increases in leukocyte counts at 782 ppm. Males at this exposure level also showed marginal elevations in platelet counts. In mice, females showed statistically increased absolute and relative liver weights at 382 and 782 ppm, while males had statistically increased relative liver-to-brain weight ratios only at 782 ppm. Female rabbits at the high exposure level of 1610 ppm gained weight more slowly than controls (not statistically significant); males showed a similar transient downward trend after 1 week, but showed no differences from controls at study's end. A no observed adverse effect level (NOAEL) of 382 ppm appears appropriate for rats and mice with a lowest observed adverse effect level (LOAEL) of 782 ppm. A NOAEL of 782 ppm and LOAEL of 1610 ppm are appropriate for rabbits.

Subchronic inhalation and oral toxicity of hydrogenated terphenyls in rats.

The subchronic toxicity of a commercial blend of partially hydrogenated terphenyl was evaluated in rats by inhalation and oral routes of exposure. Animals were exposed to target concentrations of 0, 10, 100, or 500 mg/m3 for 6 hr/day, 5 days/week or were offered diets daily with concentrations of 0, 50, 200, or 2000 ppm. Each study lasted approximately 14 weeks. The study designs included observations for clinical signs, body weights, ophthalmic exams, hematology and clinical chemistry, major organ weights, and gross and histopathology. No treatment-related effects were noted in the ophthalmic exams. Body weights were slightly depressed in high-dose males from the inhalation study and high-dose females in the dietary study. Liver and liver/body weights were increased in high-dose animals of both sexes and high- and mid-dose males in the dietary and inhalation studies, respectively. In the high-dose females of the dietary study, kidney and kidney/body weights were increased with increased adrenal and adrenal/body weights were also observed. No compound-related gross lesions nor pathological correlates to the organ weight changes were observed in either study. The no-adverse effect levels were considered to be 100 mg/m3 and 200 ppm (15.9 mg/kg) for the inhalation and dietary studies, respectively. These data indicate that a wide margin of safety exists for hydrogenated terphenyl workplace exposure.