Rapid development of a ventilator for use during the COVID-19 pandemic: Clinical, human factor & engineering considerations.

The arrival of the COVID-19 pandemic in early 2020 threatened to overwhelm the NH ability to provide sufficient critical care support to patients in the UK. In response to a rapid rise in cases in March 2020, the UK Government issued a call to industry to rapidly design and develop additional ventilators to expand the UK's capacity for mechanical ventilation. Three NHS consultants working in conjunction with TTP Plc (The Technology Partnership), were at the forefront, evolving the Government brief and developing a safe and effective ventilator, the CoVent™, in less than 5 weeks. The project demonstrates the ability of physicians to guide industry and pool knowledge and resources to rapidly develop and evolve technology in the face of a national emergency. This article discusses key aspects of the design process, highlights the unique human factors and engineering aspects of undertaking this amidst the coronavirus pandemic. Overall we demonstrated that when industry, healthcare and regulatory bodies collaborate and communicate efficiently, huge progress can be made in a fraction of the usual timescales.

Initiating and imaging the coherent surface dynamics of charge carriers in real space.

The tip of a scanning tunnelling microscope is an atomic-scale source of electrons and holes. As the injected charge spreads out, it can induce adsorbed molecules to react. By comparing large-scale 'before' and 'after' images of an adsorbate covered surface, the spatial extent of the nonlocal manipulation is revealed. Here, we measure the nonlocal manipulation of toluene molecules on the Si(111)-7 × 7 surface at room temperature. Both the range and probability of nonlocal manipulation have a voltage dependence. A region within 5-15 nm of the injection site shows a marked reduction in manipulation. We propose that this region marks the extent of the initial coherent (that is, ballistic) time-dependent evolution of the injected charge carrier. Using scanning tunnelling spectroscopy, we develop a model of this time-dependent expansion of the initially localized hole wavepacket within a particular surface state and deduce a quantum coherence (ballistic) lifetime of ∼10 fs.

Atomically resolved real-space imaging of hot electron dynamics.

The dynamics of hot electrons are central to understanding the properties of many electronic devices. But their ultra-short lifetime, typically 100 fs or less, and correspondingly short transport length-scale in the nanometre range constrain real-space investigations. Here we report variable temperature and voltage measurements of the nonlocal manipulation of adsorbed molecules on the Si(111)-7 × 7 surface in the scanning tunnelling microscope. The range of the nonlocal effect increases with temperature and, at constant temperature, is invariant over a wide range of electron energies. The measurements probe, in real space, the underlying hot electron dynamics on the 10 nm scale and are well described by a two-dimensional diffusive model with a single decay channel, consistent with 2-photon photo-emission (2PPE) measurements of the real time dynamics.

Mapping the site-specific potential energy landscape for chemisorbed and physisorbed aromatic molecules on the Si(1 1 1)-7 × 7 surface by time-lapse STM.

We present a scanning tunnelling microscope study of site-specific thermal displacement (desorption or diffusion) of benzene, toluene, and chlorobenzene molecules on the Si(1 1 1)-7 × 7 surface. Through time-lapse STM imaging and automated image analysis we probe both the chemisorbed and the physisorbed states of these molecules. For the chemisorption to physisorption transition there are distinct site-specific variations in the measured rates, however their kinetic origin is ambiguous. There is also significant variation in the competing rates out of the physisorbed state into chemisorption at the various surface sites, which we attribute to differences in site-specific Arrhenius pre-factors. A prediction of the outcome of the competing rates and pre-factors for benzene over three hours matches experiment.

Pancreatic abscess involving the aortic graft following repair of a ruptured aortic aneurysm: successful replacement with femoro-popliteal vein.

Acute pancreatitis is a rare complication after aortic surgery and carries a high mortality. We report the successful management of an infected aortic graft secondary to complicated severe pancreatitis in a 77-year-old man by open drainage of the abscess and replacement of the prosthetic graft with superficial femoro-popliteal vein (SFPV). The patient remains free from infection with a patent graft 8 months later.

Microbiological quality of food in relation to hazard analysis systems and food hygiene training in UK catering and retail premises.

A meta-analysis of eight UK food studies was carried out to determine the microbiological quality of food and its relationship with the presence in food businesses of hazard analysis systems and food hygiene training. Of the 19,022 premises visited to collect food samples in these studies between 1997 and 2002, two thirds (66%) were catering premises and one third (34%) were retail premises. Comparison with PHLS Microbiological Guidelines revealed that significantly more ready-to-eat food samples from catering premises (20%; 2,511/12,703) were of unsatisfactory or unacceptable microbiological quality compared to samples from retail premises (12%; 1,039/8,462) (p < 0.00001). Three quarters (76%) of retail premises had hazard analysis systems in place compared with 59% of catering premises (p < 0.00001). In 87% of retail premises the manager had received some form of food hygiene training compared with 80% of catering premises (p < 0.00001). From premises where the manager had received no food hygiene training a greater proportion of samples were of unsatisfactory and unacceptable microbiological quality (20% retail, 27% catering) compared with premises where the manager had received food hygiene training (11% retail, 19% catering) (p < 0.00001). Where the manager of the premises had received food hygiene training, documented hazard analysis systems were more likely to be in place (p < 0.00001). Higher proportions of samples of unsatisfactory and unacceptable microbiological quality (17% retail, 22% catering) were from premises where there was no hazard analysis system in place compared to premises that had a documented hazard analysis system in place (10% retail, 18% catering) (p < 0.00001). Our meta-analysis suggests that the lower microbiological quality of ready-to-eat foods from catering premises compared with those collected from retail premises may reflect differences in management food hygiene training and the presence of a hazard analysis system. The importance of adequate training for food handlers and their managers as a pre-requisite for effective hazard analysis and critical control point (HACCP) based controls is therefore emphasised.

[Dental complaints are found always between the ears. Somatization in the dental practice]. / Een tandheelkundige klacht zit altijd tussen de oren. Somatisatie in de tandartspraktijk.

The aim of the present study was to investigate the occurrence of somatization-specific behaviour in the dental setting and its relationship with patients' report of both dental and psychological complaints. Somatization-specific behaviour was operationalized as an unexplained dental complaint, high dental attendance, a high treatment consumption or an unreasonable demand with regard to treatment. Of the 309 patients 8.7% fulfilled the criteria for somatization-specific behaviour, which was mainly expressed as a high frequency of attendance (6.8%). Women showed significantly more often (73%) somatization-specific behaviour than men (27%). Further, a relation between depression and somatization-specific behaviour was found. Particularly patients with a relatively high level of long-lasting dental complaints demonstrated somatization-specific behaviour.

Pulmonary sequelae of treatment for breast cancer: a prospective study.

PURPOSE: To prospectively study the effects of loco-regional radiotherapy in women with breast cancer. METHODS AND MATERIALS: Thirty consecutive patients with breast resection underwent clinical, lung function, radiographic, and thoracic high-resolution computed tomography evaluation before and at 1, 3, 6, and 12 months after adjuvant radiotherapy. Chemotherapy was also administered to 15 patients. RESULTS: Nineteen patients reported mild respiratory symptoms at 1 month, which resolved completely at 6 months after radiotherapy. Opacities were present on 80% of chest radiographs and in all patients on high-resolution computed tomography by 3 months. These opacities became compact and persisted on high-resolution computed tomography at 12 months. Lung function indices, including FEV1, FVC, TLC, and DLCO, progressively declined after radiotherapy, and was irreversible at 12 months (p < 0.05). Patients who received chemotherapy did not have significantly different lung function indices compared with their counterparts at all time points (p > 0.05). CONCLUSIONS: Our results have shown that adjuvant loco-regional radiotherapy, a common practice in breast cancer treatment, is associated with irreversible reduction in lung function parameters. These changes are accompanied by radiological evidence of persistent lung injury. Further studies should be performed to evaluate the incidence and long-term pulmonary sequelae of current treatment for breast cancer.

Serial HRCT lung changes after 3-field radiation treatment of breast cancer.

AIMS: To document serial high resolution computed tomography (HRCT) features of lung injury after 3-field radiotherapy for breast cancer. MATERIALS AND METHODS: Thirty women who received opposing tangential chest wall and supraclavicular field (SCF) irradiation after breast surgery were recruited. Thoracic HRCT was performed before and at 1, 3, 6 and 12 months after radiotherapy (RT). Lung injury at 3 months was quantified by applying a scoring system to each HRCT section. Findings were correlated with spirometric lung function tests. RESULTS: There was HRCT evidence of lung injury in 27 (90%) women at 1 month and in all 30 patients at 3 months. Spirometric lung function declined post-RT (P < 0.05), correlating with an increased SCF acute lung injury score at 3 months [r = -0.54 and -0.46, P = 0.01 and 0.03 for forced expiratory volume in 1st (FEV(1)) and forced vital capacity (FVC), respectively]. Lung injury on HRCT progressed from ground glass opacification at 1 month to nodular consolidation (3 months), increasing linear densities (6 months), and finally to residual subpleural linear and dense opacities (12 months). CONCLUSION: There is a high incidence of lung injury associated with 3-field radiotherapy for breast cancer, with concurrent SCF irradiation increasing the risk of lung damage and functional impairment. A characteristic sequence of HRCT changes is seen in most patients receiving this type of radiotherapy.Ooi, G. C. (2000). Clinical Radiology55, 817-824.

Severe hepatotoxicity on beginning propylthiouracil therapy.

We report a case of propylthiouracil (PTU)-induced cholestatic hepatotoxicity in Graves' disease that developed 1 day after beginning PTU. After clinical recover, liver abnormalities persisted for 5 years. Percutaneous liver biopsy and the eventual normalization of enzyme levels excluded permanent liver damage as a result of PTU therapy. Thus prolonged elevation of serum enzymes is consistent with the diagnosis of PTU-induced hepatotoxicity, which may recover completely.

Glycemic indices of various foods given to pregnant diabetic subjects.

The applicability of the glycemic index concept in pregnancy has not been established. The postprandial glucose curves were measured for nine foods (glucose, bread, raisins, dates, sweet corn, bananas, oranges, spaghetti, and green peas) in 28 gestational diabetic subjects. Uniform glycemic indices were observed for each food, similar to those reported by others in nonpregnant subjects. Postprandial glucose levels reached their peak later after glucose and bread ingestion than after the remaining seven foods. These results demonstrate that despite known changes in gastrointestinal function in pregnancy, glycemic indices are uniform after the ingestion of foods. Pregnancy does not appear to alter the glycemic indices of the foods tested.

Treatment with oral piperazine oestrone sulphate for genuine stress incontinence in postmenopausal women.

The use of oestrogens in the treatment of genuine stress incontinence was assessed by a double-blind prospective trial in 36 postmenopausal women with genuine stress incontinence who received 3 months of cyclical treatment with either piperazine oestrone sulphate or a matching placebo. Patients were assessed subjectively and objectively before and after treatment by 7-day bladder charts, urethral pressure profiles (UPP), the Urilos nappy test, vaginal cytology and hormone assays (plasma oestrogens and gonadotrophins). There was no statistical difference in the subjective response to treatment between the two groups. After 6 weeks of treatment there was a greater reduction in the number of pad changes/24 h in the oestrogen-treated patients that approached statistical significance but, because of a marked response in the placebo group, this difference was not significant after 3 months of treatment. There were also no significant differences between the two groups with respect to the UPP or Urilos measurements but the vaginal cytology and hormone profiles were significantly affected by oestrogens. In view of the possible risks of oestrogen therapy its use in genuine stress incontinence is limited.

Hormonal changes in postmenopausal women with breast cancer treated with trilostane and dexamethasone.

Postmenopausal women with metastatic breast cancer were treated with trilostane, initially 240 mg daily increasing after 3 days to 480 mg daily and after a further three days to 960 mg daily. After 3 days at this dose dexamethasone 1 mg daily was added and this combination was continued until disease progression occurred. Partial remission was seen in 26% and stabilization of previously progressive disease in a further 13% of the first twenty-three patients studied. During therapy with trilostane alone significant increases in DHEAS, androstenedione, 17-hydroxypregnenolone, progesterone, testosterone and oestradiol were seen. A significant fall in oestrone concentration occurred at the same time. After dexamethasone was added the elevated steroid concentrations fell back to the baseline while oestrone remained depressed below this and testosterone was also significantly lowered. No change was seen in cortisol or ACTH concentration while patients were on trilostane alone but cortisol levels were undetectable after dexamethasone was added though, in most patients, ACTH remained detectable. There was no change in the ratio of delta 5:delta 4 steroids at any stage of therapy but a highly significant increase in the androstenedione: oestrone ratio was seen. We conclude that in long-term use in vivo it is difficult to demonstrate that trilostane inhibits 3 beta-hydroxysteroid dehydrogenase but it may produce inhibition of aromatase.

Study of the effect of estradiol on gonadotrophin levels in untreated male-to-female transsexuals.

This project was an attempt to test Dörner's theory that aspects of gender identity and sexual behavior depend on a defect in a normal imprinting mechanism of testicular testosterone (T) on the male hypothalamus. It has been suggested that such an action by T is incomplete in male-to-female transsexuals and that in this disorder the hypothalamus retains a cyclic pattern of gonadotrophin secretion and a positive feedback response to estrogens, such as is seen in the normal female. Five untreated male-to-female transsexuals and five normal male controls were each given 2 mg IM of estradiol, and T, estradiol, LH, and FSH globulin was measured serially over the following five days. No significant differences were found in the gonadotrophin or any of the other hormone responses in the transsexuals compared to normal controls. If there is a defect in imprinting of the hypothalamus in transsexual men, it does not seem to affect the basal levels of gonadotrophins or the pattern of their response to estrogen, at least in the intact male.

Distribution of apolipoproteins A-I and B among intestinal lipoproteins.

Chylomicrons and very low density lipoproteins (VLDL) are produced by the intestine and these nascent particles are thought to be similar to their counterparts in intestinal lymph. To study the relationship between these lipoproteins within the cell and those secreted into the lamina propria and lymph, we have isolated enterocytes, lamina propria, and mesenteric lymph from rats while fasted and after corn oil feeding. Apolipoprotein A-I and B content were measured by radioimmunoassay in cell, lamina propria, and lymph fractions separated by Sepharose 6B and 10% agarose chromatography, and by KBr isopycnic density centrifugation. ApoA-I in the cell and the underlying lamina propria was found partly in those fractions in which chylomicron and very low density lipoproteins (chylo-VLDL) and high density lipoproteins (HDL) elute, but more abundantly where unassociated 125I-labeled apoA-I was eluted. In the lymph, however, 74% of apoA-I eluted in the HDL region and no peak of free apoA-I was found. ApoB and apoC-III within the enterocyte were found distributed in the position of particles eluting not only with chylomicrons and VLDL, but also in the regions corresponding to LDL and HDL. In the lamina propria and lymph, on the other hand, most of the apoB was found in the region of VLDL and chylomicrons. These results indicate that the patterns in lymph lipoproteins and the lamina propria do not exactly mirror the distribution of apoA-I and B among lipoproteins inside the cell. This may be because intracellular apoproteins may be unassociated with lipoproteins, or they could be associated with lipoproteins in various stages of assembly of protein with lipids. Furthermore, the apoprotein composition of intestinal lipoproteins is altered after secretion from the enterocyte. Finally, not all apoproteins seem to be secreted in association with identifiable lipoprotein particles from the enterocyte.