An epidemiological investigation of COVID-19 outbreaks in a group of care homes in Wales, UK: a retrospective cohort study.

BACKGROUND: This study describes the epidemiology of COVID-19 outbreaks in four care homes in terms of spread, severity, presentation and interventions. METHODS: Participants were 100 residents and 102 staff from four co-located care homes in Wales. Data were collected from the homes and Public Health Wales, including demographics, presentations, test status and results, hospital admissions and deaths. Genomic sequencing of confirmed case samples was completed, where possible. Epi-curves, crude attack rates, a Kaplan-Meier survival curve and adjusted hazard ratios were calculated using R. RESULTS: About 14 confirmed and 43 possible resident cases, 23 confirmed and 47 possible staff cases occurred. Crude attack rates of possible and confirmed cases were 57% (residents) and 69% (staff). Genomic sequencing for 10 confirmed case PCR samples identified at least 5 different UK lineages of COVID-19.42 (42%) residents died, 23 (55%) with COVID-19 or suspected COVID-19 recorded on the death certificate. The hazard ratio for death amongst resident possible and confirmed cases compared to null cases, adjusting for age and sex, was 13.26 (95% CI 5.61-31.34). CONCLUSIONS: There were extensive outbreaks of COVID-19 in these homes with high crude attack rates and deaths. Universal testing and early isolation of residents are recommended.

Mycosands: Fungal diversity and abundance in beach sand and recreational waters - Relevance to human health.

The goal of most studies published on sand contaminants is to gather and discuss knowledge to avoid faecal contamination of water by run-offs and tide-retractions. Other life forms in the sand, however, are seldom studied but always pointed out as relevant. The Mycosands initiative was created to generate data on fungi in beach sands and waters, of both coastal and freshwater inland bathing sites. A team of medical mycologists and water quality specialists explored the sand culturable mycobiota of 91 bathing sites, and water of 67 of these, spanning from the Atlantic to the Eastern Mediterranean coasts, including the Italian lakes and the Adriatic, Baltic, and Black Seas. Sydney (Australia) was also included in the study. Thirteen countries took part in the initiative. The present study considered several fungal parameters (all fungi, several species of the genus Aspergillus and Candida and the genera themselves, plus other yeasts, allergenic fungi, dematiaceous fungi and dermatophytes). The study considered four variables that the team expected would influence the results of the analytical parameters, such as coast or inland location, urban and non-urban sites, period of the year, geographical proximity and type of sediment. The genera most frequently found were Aspergillus spp., Candida spp., Fusarium spp. and Cryptococcus spp. both in sand and in water. A site-blind median was found to be 89 Colony-Forming Units (CFU) of fungi per gram of sand in coastal and inland freshwaters, with variability between 0 and 6400 CFU/g. For freshwater sites, that number was 201.7 CFU/g (0, 6400 CFU/g (p = 0.01)) and for coastal sites was 76.7 CFU/g (0, 3497.5 CFU/g). For coastal waters and all waters, the median was 0 CFU/ml (0, 1592 CFU/ml) and for freshwaters 6.7 (0, 310.0) CFU/ml (p < 0.001). The results advocate that beaches should be monitored for fungi for safer use and better management.

A pragmatic assessment of the British Thyroid Association "U classification" of thyroid nodules with a focus on their follow-up.

AIM: To assess the predictive value of the U classification and the significance of follow-up ultrasound in those managed conservatively. MATERIALS AND METHODS: A retrospective observational study was carried out among 1,465 patients who underwent thyroid ultrasound in 2016 at a teaching hospital in UK. Details regarding U classification of nodules, cytology, histology in patients who underwent surgery, and follow-up ultrasound in those managed conservatively were obtained. RESULTS: Thyroid surgery was performed in 129 patients of which malignancy was seen in 35 (27.1%). The proportion of patients with cancer in U1-U5 categories were 0%, 13.6%, 30.4%, 40%, and 100%, respectively (Fisher's exact test p=0.001). There was no significant difference in U stage, cytology, or histology between incidental and symptomatic nodules. Among patients who did not undergo surgery 5% of U1, 14.6% of U2, 75% of U3, and 71.4% of U4 underwent repeat ultrasound. Radiological progression in nodule size was seen in 4.2% of U1, 1.9% of U2, 0% of U3, and 40% of U4 nodules at median duration of 306, 439, 274, and 748 days, respectively. CONCLUSIONS: U classification is reliable in risk-stratifying thyroid nodules. Patients with benign nodules without high-risk features do not require follow-up. The interval between scans in patients with indeterminate nodules can be extended to a period of 6-12 months.

The role of imaging in malignant pleural mesothelioma: an update after the 2018 BTS guidelines.

Malignant pleural mesothelioma (MPM) is a primary malignancy of the pleura and is associated with a poor outcome. The symptoms and signs of malignant mesothelioma present late in the natural history of the disease and are non-specific, making the diagnosis challenging and imaging key. In 2018, the British Thoracic Society (BTS) updated the guideline on diagnosis, staging, and follow-up of patients with MPM. These recommendations are discussed in this review of the current literature on imaging of MPM. It is estimated MPM will continue to cause serious morbidity and mortality in the UK late into the 21st century, and internationally, people continue to be exposed to asbestos. We aim to update the reader on current and future imaging strategies, which could aid early diagnosis of pleural malignancy and provide an update on staging and assessment of tumour response.

A systematic review and computational modelling analysis of unilateral montages in electroconvulsive therapy.

OBJECTIVE: To examine the clinical outcomes of ECT unilateral placements compared in prior studies and apply insights from computational modelling to understand differences between placements. METHODS: PubMed, Embase, Scopus and PsycINFO and reference lists were systematically searched for studies of depressed patients where two unilateral placements were compared and clinical outcomes were reported. Computational modelling was done to generate electric field maps for each unilateral placement identified in the systematic review. RESULTS: A total of 29 studies met criteria for inclusion. Eight studies reported efficacy outcomes and 23 studies reported cognitive outcomes. Most studies found no significant difference in efficacy between right unilateral (RUL) and left unilateral (LUL) ECT, and no difference was found between temporo-parietal and fronto-temporal ECT. For the majority of studies, RUL placements had better verbal anterograde memory outcomes compared with the LUL placements. There was some evidence suggestive of cognitive advantages for fronto-frontal and fronto-parietal placements relative to temporo-parietal ECT. CONCLUSIONS: For efficacy, studies mainly focused on the comparison of right vs. left hemispheric stimulation, with the available evidence suggesting no substantive difference. RUL placements tended to have better verbal anterograde memory outcomes relative to LUL placements, though limited differences were found between the RUL placements.

Evidence of persistence of Prevotella spp. in the cystic fibrosis lung.

Purpose. Prevotella spp. represent a diverse genus of bacteria, frequently identified by both culture and molecular methods in the lungs of patients with chronic respiratory infection. However, their role in the pathogenesis of chronic lung infection is unclear; therefore, a more complete understanding of their molecular epidemiology is required.Methodology. Pulsed Field Gel Electrophoresis (PFGE) and Random Amplified Polymorphic DNA (RAPD) assays were developed and used to determine the degree of similarity between sequential isolates (n=42) from cystic fibrosis (CF) patients during periods of clinical stability and exacerbation.Results. A wide diversity of PFGE and RAPD banding patterns were observed, demonstrating considerable within-genus heterogeneity. In 8/12 (66.7 %) cases, where the same species was identified at sequential time points, pre- and post-antibiotic treatment of an exacerbation, PFGE/RAPD profiles were highly similar or identical. Congruence was observed between PFGE and RAPD (adjusted Rand coefficient, 0.200; adjusted Wallace RAPD->PFGE 0.459, PFGE->RAPD 0.128). Furthermore, some isolates could not be adequately assigned a species name on the basis of 16S rRNA analysis: these isolates had identical PFGE/RAPD profiles to Prevotella histicola.Conclusion. The similarity in PFGE and RAPD banding patterns observed in sequential CF Prevotella isolates may be indicative of the persistence of this genus in the CF lung. Further work is required to determine the clinical significance of this finding, and to more accurately distinguish differences in pathogenicity between species.

Improved Force Spectroscopy Using Focused-Ion-Beam-Modified Cantilevers.

Atomic force microscopy (AFM) is widely used in biophysics, including force-spectroscopy studies of protein folding and protein-ligand interactions. The precision of such studies increases with improvements in the underlying quality of the data. Currently, data quality is limited by the mechanical properties of the cantilever when using a modern commercial AFM. The key tradeoff is force stability vs short-term force precision and temporal resolution. Here, we present a method that avoids this compromise: efficient focused-ion-beam (FIB) modification of commercially available cantilevers. Force precision is improved by reducing the cantilever's hydrodynamic drag, and force stability is improved by reducing the cantilever stiffness and by retaining a cantilever's gold coating only at its free end. When applied to a commonly used short cantilever (L=40µm), we achieved sub-pN force precision over 5 decades of bandwidth (0.01-1000Hz) without significantly sacrificing temporal resolution (~75µs). Extending FIB modification to an ultrashort cantilever (L=9µm) also improved force precision and stability, while maintaining 1-µs-scale temporal resolution. Moreover, modifying ultrashort cantilevers also eliminated their inherent underdamped high-frequency motion and thereby avoided applying a rapidly oscillating force across the stretched molecule. Importantly, fabrication of FIB-modified cantilevers is accessible after an initial investment in training. Indeed, undergraduate researchers routinely modify 2-4 cantilevers per hour with the protocol detailed here. Furthermore, this protocol offers the individual user the ability to optimize a cantilever for a particular application. Hence, we expect FIB-modified cantilevers to improve AFM-based studies over broad areas of biophysical research.

The preclinical pharmacokinetic disposition of a series of perforin-inhibitors as potential immunosuppressive agents.

The cytolytic protein perforin is a key component of the immune response and is implicated in a number of human pathologies and therapy-induced conditions. A novel series of small molecule inhibitors of perforin function have been developed as potential immunosuppressive agents. The pharmacokinetics and metabolic stability of a series of 16 inhibitors of perforin was evaluated in male CD1 mice following intravenous administration. The compounds were well tolerated 6 h after dosing. After intravenous administration at 5 mg/kg, maximum plasma concentrations ranged from 532 ± 200 to 10,061 ± 12 ng/mL across the series. Plasma concentrations were greater than the concentrations required for in vitro inhibitory activity for 11 of the compounds. Following an initial rapid distribution phase, the elimination half-life values for the series ranged from 0.82 ± 0.25 to 4.38 ± 4.48 h. All compounds in the series were susceptible to oxidative biotransformation. Following incubations with microsomal preparations, a tenfold range in in vitro half-life was observed across the series. The data suggests that oxidative biotransformation was not singularly responsible for clearance of the compounds and no direct relationship between microsomal clearance and plasma clearance was observed. Structural modifications however, do provide some information as to the relative microsomal stability of the compounds, which may be useful for further drug development.

The application of geographic information systems and spatial data during Legionnaires disease outbreak responses.

A literature review was conducted to highlight the application and potential benefit of using geographic information systems (GIS) during Legionnaires' disease outbreak investigations. Relatively few published sources were identified, however, certain types of data were found to be important in facilitating the use of GIS, namely: patient data, locations of potential sources (e.g. cooling towers), demographic data relating to the local population and meteorological data. These data were then analysed to gain a better understanding of the spatial relationships between cases and their environment, the cases' proximity to potential outbreak sources, and the modelled dispersion of contaminated aerosols. The use of GIS in an outbreak is not a replacement for traditional outbreak investigation techniques, but it can be a valuable supplement to a response.

Pre-existing oral contrast from lanthanum carbonate: a confounding factor in CT mesenteric angiography.

A 69-year-old male was referred from the renal unit to radiology for investigation of bleeding per rectum. A CT mesenteric angiogram was performed. However, it was noted on the pre-contrast images that the large bowel contained positive oral contrast media. The procedure was abandoned as it would have been difficult to see extravasation of intravenous contrast from a bleeding point in the large bowel. The initial belief was that either the patient had been given oral contrast by ward staff on the assumption that it would be needed, or had had a recent radiological study requiring contrast, which was still present. Neither was the case; it emerged that the patient was taking Fosrenol (Shire Pharmaceuticals, Wayne, PA), a lanthanum carbonate medication used in the treatment of hyperphosphataemia. Lanthanum is densely radio-opaque and appears as positive bowel contrast on CT and plain radiography studies. When considering radiological studies specifically requiring the absence of oral contrast, it is important to be aware of the patient's drug history to avoid non-diagnostic scans with the associated radiation exposure.

Strong and consistently synergistic inactivation of spores of spoilage-associated Bacillus and Geobacillus spp. by high pressure and heat compared with inactivation by heat alone.

The inactivation of spores of four low-acid food spoilage organisms by high pressure thermal (HPT) and thermal-only processing was compared on the basis of equivalent thermal lethality calculated at a reference temperature of 121.1°C (F(z)(121.1)(°)(C, 0.1 MPa or 600 MPa)) and characterized as synergistic, not different or protective. In addition, the relative resistances of spores of the different spoilage microorganisms to HPT processing were compared. Processing was performed and inactivation was compared in both laboratory and pilot scale systems and in model (diluted) and actual food products. Where statistical comparisons could be made, at least 4 times and up to around 190 times more inactivation (log(10) reduction/minute at F(T)(z)(121.1)(°)(C)) of spores of Bacillus amyloliquefaciens, Bacillus sporothermodurans, and Geobacillus stearothermophilus was achieved using HPT, indicating a strong synergistic effect of high pressure and heat. Bacillus coagulans spores were also synergistically inactivated in diluted and undiluted Bolognese sauce but were protected by pressure against thermal inactivation in undiluted cream sauce. Irrespective of the response characterization, B. coagulans and B. sporothermodurans were identified as the most HPT-resistant isolates in the pilot scale and laboratory scale studies, respectively, and G. stearothermophilus as the least in both studies and all products. This is the first study to comprehensively quantitatively characterize the responses of a range of spores of spoilage microorganisms as synergistic (or otherwise) using an integrated thermal-lethality approach (F(T)(z)). The use of the F(T)(z) approach is ultimately important for the translation of commercial minimum microbiologically safe and stable thermal processes to HPT processes.

Potentials and limitations of low-concentration contrast medium (150 mg iodine/ml) in CT pulmonary angiography.

AIM: To assess the feasibility of producing diagnostic multidetector computed tomography (MDCT) pulmonary angiography with low iodine concentration contrast media (150 mg iodine/ml) in patients with suspected acute pulmonary embolism. MATERIALS AND METHODS: Ninety-five randomized patients underwent MDCT (64 row) pulmonary angiography with 100ml iopromide either at low concentration (LC) of 150 mg iodine/ml (n=45) or high concentration (HC) of 300 mg iodine/ml (n=50), delivered at the rate of 5 ml/s via a power injector. Two experienced radiologists, blinded to the concentration used, subjectively assessed the diagnostic quality and confidence using a four-point scale [1=poor (not diagnostic), 2=satisfactory, 3=good, 4=excellent]. Attenuation values (in HU) were measured in the main proximal branches of the pulmonary arteries. RESULTS: The median diagnostic quality score for both observers was 3.5 (interquartile range 3-4) in the HC group and 2.5 (interquartile range 1.5-3) in the LC group (p<0.01). The median diagnostic confidence score for both observers was 4 (interquartile range 3-4) in the HC group and 3 (interquartile range 1.5-4) in the LC group (p<0.01). Both observers rated examinations as diagnostic in 69% of cases in the LC group, compared with 96% of cases in the HC group. Good interobserver agreement was found in both groups (K value 0.72 in the LC group and 0.73 in the HC). Obesity, poor scan timing, and dilution by venous return of non-opacified blood were the main reasons for a reduction in diagnostic quality of examinations in the LC group. CONCLUSION: Despite a 50% reduction of contrast medium dose in comparison to the standard technique, 150 mg iodine/ml can produce diagnostic MDCT pulmonary angiogram studies in the absence of obesity or high cardiac output and hyper-dynamic pulmonary circulation. Reducing the dose of contrast media would minimize the risk of contrast nephropathy in patients at risk of this complication, particularly those suffering from congestive heart failure in whom intravenous hydration is contraindicated.

Electromyographic validation of the muscles deltoid (anterior portion) and pectoralis major (clavicular portion) in military press exercises with open grip.

It was analized the deltoid muscle anterior portion and the pectoralis major clavicular portion in 24 male volunteers using a two-channel electromyograph TECA TE 4, and Hewllet Packard surface electrodes, in 4 modalities of military press exercises with open grip. The results showed high inactivity for PMC in almost all the modalities while DA developed very high levels of action potentials in all the modalities assessed.

Synergistic inactivation of spores of proteolytic Clostridium botulinum strains by high pressure and heat is strain and product dependent.

The combined high pressure and heat resistances of spores of five proteolytic Clostridium botulinum strains and of the nonpathogenic surrogate strain Clostridium sporogenes PA3679 were compared with their heat-only resistances on the basis of equivalent accumulated thermal lethality, expressed as equivalent minutes at a reference temperature of 105 degrees C (F(105 degrees C). Comparisons were made with three model (i.e., diluted) products, namely, 30% (wt/wt) Bolognese sauce, 50% (wt/wt) cream sauce, and rice water agar. Pressure was determined to act synergistically with heat during high-pressure thermal (HPT) processing for C. botulinum FRRB 2802 (NCTC 7273) and C. botulinum FRRB 2804 (NCTC 3805 and 62A) in the Bolognese and cream sauces and for C. botulinum FRRB 2807 (213B) in the Bolognese sauce only. No synergy was observed for C. botulinum FRRB 2803 (NCTC 2916) or FRRB 2806 (62A) or C. sporogenes FRRB 2790 (NCTC 8594 and PA3679) in any of the model products. No significant protective effect of pressure against spore inactivation was determined for any Clostridium strain in any product. Because synergy was not consistently observed among strains of C. botulinum or among products, the prediction of inactivation of C. botulinum spores by HPT sterilization (HPTS) for the present must assume a complete lack of synergy. Therefore, any HPTS process for low-acid shelf-stable foods must be at least thermally equivalent to an F(0) process of 2.8 min, in line with current good manufacturing practices. The results of this study suggest that the use of C. sporogenes PA3679 as a surrogate organism may risk overestimating inactivation of C. botulinum by HPT processing.

Car safety seats for children: rear facing for best protection.

OBJECTIVE: To compare the injury risk between rear-facing (RFCS) and forward-facing (FFCS) car seats for children less than 2 years of age in the USA. METHODS: Data were extracted from a US National Highway Traffic Safety Administration vehicle crash database for the years 1988-2003. Children 0-23 months of age restrained in an RFCS or FFCS when riding in passenger cars, sport utility vehicles, or light trucks were included in the study. Logistic regression models and restraint effectiveness calculations were used to compare the risk of injury between children restrained in RFCSs and FFCSs. RESULTS: Children in FFCSs were significantly more likely to be seriously injured than children restrained in RFCSs in all crash types (OR=1.76, 95% CI 1.40 to 2.20). When considering frontal crashes alone, children in FFCSs were more likely to be seriously injured (OR=1.23), although this finding was not statistically significant (95% CI 0.95 to 1.59). In side crashes, however, children in FFCSs were much more likely to be injured (OR=5.53, 95% CI 3.74 to 8.18). When 1 year olds were analyzed separately, these children were also more likely to be seriously injured when restrained in FFCSs (OR=5.32, 95% CI 3.43 to 8.24). Effectiveness estimates for RFCSs (93%) were found to be 15% higher than those for FFCSs (78%). CONCLUSIONS: RFCSs are more effective than FFCSs in protecting restrained children aged 0-23 months. The same findings apply when 1 year olds are analyzed separately. Use of an RFCS, in accordance with restraint recommendations for child size and weight, is an excellent choice for optimum protection up to a child's second birthday.

Electromyographic analysis of the arm muscles in "back support" exercises.

This study aims at quantifying through electromyography the actions of the biceps brachii-BB (long head), triceps brachii-TB (long head) and deltoideus-DA (clavicular portion) muscles, during the going (G) and return (R) phases in "back support" exercises. Surface electrodes were placed at the muscles, according to DELAGI (1981). It was used a specific software and a A/D plate to take the signals. After being collected, the records were processed resulting in efficient values (RMS), were normalized by maximum isometric contraction (MVIC = 100%) and statistically analysed using the Friedman, DSM and Wilcox non-parametric tests. All the muscles presented electromyographic activity of the movements. The triceps brachii was the muscle with higher activity in both phases of the movement. It was concluded that the exercise is indicated for the arm muscle strength development.

Electromyographic validation of the deltoideus (anterior portion) and pectoralis major (clavicular portion) muscles in pull-over exercises.

The electromyographic activity of the deltoideus (anterior portion) and pectoralis major (clavicular portion) muscles was analyzed in 24 male volunteers in two different modalities of pull-over exercises. The PMC activity varied from weak to moderate in both modalities, while the DA activity was moderate in the pull-over and strong in the pull-over with bent arms exercises.