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Neural mass models are ubiquitous in large-scale brain modelling. At the node level, they are written in terms of a set of ordinary differential equations with a non-linearity that is typically a sigmoidal shape. Using structural data from brain atlases, they may be connected into a network to investigate the emergence of functional dynamic states, such as synchrony. With the simple restriction of the classic sigmoidal non-linearity to a piecewise linear caricature, we show that the famous Wilson–Cowan neural mass model can be explicitly analysed at both the node and network level. The construction of periodic orbits at the node level is achieved by patching together matrix exponential solutions, and stability is determined using Floquet theory. For networks with interactions described by circulant matrices, we show that the stability of the synchronous state can be determined in terms of a low-dimensional Floquet problem parameterised by the eigenvalues of the interaction matrix. Moreover, this network Floquet problem is readily solved using linear algebra to predict the onset of spatio-temporal network patterns arising from a synchronous instability. We further consider the case of a discontinuous choice for the node non-linearity, namely the replacement of the sigmoid by a Heaviside non-linearity. This gives rise to a continuous-time switching network. At the node level, this allows for the existence of unstable sliding periodic orbits, which we explicitly construct. The stability of a periodic orbit is now treated with a modification of Floquet theory to treat the evolution of small perturbations through switching manifolds via the use of saltation matrices. At the network level, the stability analysis of the synchronous state is considerably more challenging. Here, we report on the use of ideas originally developed for the study of Glass networks to treat the stability of periodic network states in neural mass models with discontinuous interactions.
Metastatic cutaneous squamous cell carcinoma is the most common parotid malignancy in Australasia. Prognostic indicators are not clearly defined and the extent of surgical resection required is controversial.
A retrospective analysis was conducted of 63 patients who underwent surgery for metastatic cutaneous squamous cell carcinoma of the parotid gland at a tertiary hospital over a 10-year period.
The five-year overall survival rate was 53 per cent, the disease-specific survival rate was 78 per cent and the locoregional control rate was 72 per cent. Immunosuppression and no adjuvant radiotherapy were associated with a significant reduction in disease-specific survival. None of the factors analysed had a significant effect on locoregional control rates.
More extensive surgery, including lateral temporal bone resection, may improve local control rates in cases of more advanced disease. The reduced survival of immunocompromised patients must be considered when planning their management.
Arboviruses are pathogens that widely affect the health of people in different communities around the world. Recently, a few successful approaches toward production of effective vaccines against some of these pathogens have been developed, but treatment and prevention of the resulting diseases remain a major health and research concern. The arbovirus infection and replication processes are complex, and many factors are involved in their regulation. Apoptosis, autophagy and the unfolded protein response (UPR) are three mechanisms that are involved in pathogenesis of many viruses. In this review, we focus on the importance of these pathways in the arbovirus replication and infection processes. We provide a brief introduction on how apoptosis, autophagy and the UPR are initiated and regulated, and then discuss the involvement of these pathways in regulation of arbovirus pathogenesis.
Parotid gland tumours are complex neoplasms with a broad histological range. The parotid gland is also a common site of face and scalp skin cancer metastases.
Parotidectomies performed by ENT department in the Gold Coast health district from 2006 to 2013.
A total of 158 specimens were examined. Of these, 53.80 per cent were benign and 46.20 per cent were malignant. Pleomorphic adenoma was the most common tumour (29.11 per cent), followed by cutaneous squamous cell carcinoma (23.42 per cent) and Warthin's tumour (12.03 per cent).
Metastatic squamous cell carcinoma accounted for a large proportion of parotid masses in our case series, reflecting the high prevalence of non-melanoma skin cancer in Australia. Primary parotid neoplasms had similar incidence rates to other studies.
Diverse strain types of methicillin-resistant Staphylococcus aureus (MRSA) cause infections in community settings worldwide. To examine heterogeneity of spread within households and to identify common risk factors for household transmission across settings, primary data from studies conducted in New York (USA), Breda (The Netherlands), and Melbourne (Australia) were pooled. Following MRSA infection of the index patient, household members completed questionnaires and provided nasal swabs. Swabs positive for S. aureus were genotyped by spa sequencing. Poisson regression with robust error variance was used to estimate prevalence odds ratios for transmission of the clinical isolate to non-index household members. Great diversity of strain types existed across studies. Despite differences between studies, the index patient being colonized with the clinical isolate at the home visit (P < 0·01) and the percent of household members aged <18 years (P < 0·01) were independently associated with transmission. Targeted decolonization strategies could be used across geographical settings to limit household MRSA transmission.
Our aim was to describe the epidemiology and incidence of community-onset invasive S. aureus disease in children presenting to our hospital, and to compare the clonal complexes and virulence genes of S. aureus strains causing invasive and non-invasive disease. The virulence gene repertoire of invasive disease isolates was characterized using DNA microarray and compared with the virulence gene repertoire of non-invasive S. aureus isolates. Over the study period, 163 children had an invasive S. aureus infection. There was no difference in the distribution of clonal complexes or in the prevalence of genes encoding virulence factors between invasive and non-invasive isolates. Future research should include a strong focus on identifying the host and environmental factors that, along with organism virulence factors, are contributing to the patterns of invasive S. aureus disease observed in New Zealand.
Community-acquired Staphylococcus aureus infections are a public health concern, yet little is known about infections that do not present to hospital. We identified community-onset S. aureus infections via specimens submitted to a community-based pathology service. Referring doctors confirmed eligibility and described infection site, severity and treatment. Isolates were characterized on antibiotic resistance, PFGE, MLST/SCCmec, and Panton–Valentine leukocidin (PVL), representing 106 community-onset infections; 34 non-multiresistant methicillin-resistant S. aureus (nmMRSA) (resistant to <3 non-β-lactam antibiotics), 15 multiply antibiotic-resistant MRSA (mMRSA) and 57 methicillin-sensitive S. aureus (MSSA). Most (93%) were skin and soft tissue infections. PVL genes were carried by 42% of nmMRSA isolates [95% confidence interval (CI) 26–61] and 15% of MSSA (95% CI 8–28). PVL was associated with infections of the trunk, head or neck (56·4% vs. 24·3%, P = 0·005) in younger patients (23 vs. 52 years, P < 0·001), and with boils or abscesses (OR 8·67, 95% CI 2·9–26·2), suggesting underlying differences in exposure and/or pathogenesis.
The results of a phase I/II study in advanced breast cancer in postmenopausal women of the aromatase inhibitors 4-hydroxyandrostenedione (40HA), miconazole and CGS16949A are described. 40HA, a steroidal compound which is an irreversible inhibitor of aromatase, has been administered to 131 patients by weekly (500 mg) or fortnightly (250 mg) i.m. injections, and daily (500 mg) by mouth. The overall response rate (complete regression (CR) and partial regression (PR)) was 33%; all three dose schedules had similar clinical efficacy. Oestradiol levels were suppressed to a mean of 37–45% of pretreatment values with oral and with weekly i.m. 40HA; suppression was marginally suboptimal with 250 mg i.m. fortnightly. 40HA was well tolerated, especially when administered by fortnightly injections; this dose schedule is to be preferred to weekly injections.
Significant oestradiol suppression and clinical responses did not occur with the imidazole antifungal, miconazole, which was administered to twenty-two patients at doses of 500–1000 mg daily. The non-steroidal aromatase inhibitor, CGS16949A, induced comparable oestradiol suppression to 40HA at doses of 0.6–4 mg daily; 0.6 mg daily appears to be suboptimal. Five of thirty-one patients treated had objective responses, and disease stabilised for at least six months in nine patients. Some suppression of aldosterone occurred with doses of 2 and 4 mg daily, but clinical toxicity of the compound was minor.
No consensus exists on optimal treatment for Graves’ disease once anti-thyroid medication fails to induce remission. Total thyroidectomy is a more cost-effective treatment than radioactive iodine or life-long anti-thyroid medication, but hypocalcaemia is an important complication, leading to longer hospital admissions and increased prescription costs. This study aimed to compare the relative risk of hypocalcaemia requiring medical treatment for patients with Graves’ disease.
Prospective cohort study of patients undergoing total thyroidectomy for Graves’ disease and for multinodular goitre, calculating serum calcium levels 24-hours post-operatively and prescription rates.
Mean corrected calcium concentrations 24 hours post-operatively were 2.05 mmol/l for Graves’ disease patients and 2.14 mmol/l for multinodular goitre patients (p = 0.003). Biochemical hypocalcaemia developed in 92 per cent (n = 34) of Graves’ disease patients and 71 per cent (n = 43) of multinodular goitre patients (p = 0.012). Graves’ disease patients were more likely to be prescribed calcium supplementation pre-discharge (p = 0.037).
Total thyroidectomy for Graves’ disease carries an increased risk of hypocalcaemia at 24 hours, and of calcium supplementation pre-discharge. Graves’ disease patients should be informed of the increased risk of hypocalcaemia associated with total thyroidectomy, and this risk must be factored into future cost-effectiveness analysis.
Plasma sprayed Hydroxyapatite (HA) coatings are applied to metal prostheses to allow for implant fixation through chemical bonding of the coating with surrounding bone tissue. Without a well-adhering coating, this fixation is threatened. Thus, a thorough characterization of the metal / ceramic interface is necessary. This study used a novel composite short bar interfacial fracture toughness technique with high resolution electron spectroscopic imaging to examine Ti-6AI-4V plasma spray coated with 100μm of HA. For this system, an interfacial fracture toughness value of 1.31 +/− 0.08 MPa·m1/2 was obtained, with a corresponding tensile adhesive bond strength of 6.7 +/− 1.5 MPa. High resolution ESI revealed distinct phosphorous segregation to the interface and diffusion into the underlying titanium. A 24-hour post-heat treatment at 960°C greatly increased the bond strength at this interface. Observations from ESI suggested that this effect may be due to enhanced diffusion of both phosphorous and calcium into the metal substrate.
The laboratory experiments described here, were aimed at examining the interaction of microbes with mineralogical surfaces involved with groundwater flow. These experiments were designed to study simple systems and were aimed at identifying relevant reactions both chemical and biological. They contained groundwater with either sulphate reducing bacteria (SRB), iron reducing bacteria (IRB) or a mixture of both, together with control experiments without bacteria. The results of the chemical analyses of fluid phases showed evidence for dissolution of primary minerals. Microbial analysis showed both SRB and IRB appeared to be active albeit for a limited period due to exhaustion of nutrient and energy supplies. SRB seem to have a greater effect on groundwater chemistry than IRB with sulphide being produced. However, when the two types of bacteria are mixed together, the IRB appear to dominate the system. Further work is underway to give detailed mineralogical analysis of the solids in order to better understand the influence of microbial interaction on the redox reactions.
Experiments were conducted to identify the rock-water and microbial interactions influencing accelerated smectite-clay formation. Packed columns and stirred batch reactors contained Äspö granodiorite, artificial groundwater mimicking that from Äspö and combinations of three types of subsurface chemolithotrophic bacteria, two of which were indigenous to the Äspö rocks. Results showed evidence that, within 5 days under anaerobic reducing conditions, all three of the bacterial types produced copious biofilamentous ‘meshes’ across porespaces, apparently using the larger grains as anchor points. The biofilaments quickly became encrusted with fine grained material and surrounded with neoformed clay-like deposits. In contrast, the abiotic controls showed little or no evidence of clay formation suggesting that this process is biologically induced or controlled. A second series of abiotic experiments to determine the effects of increased acidity showed evidence of mineral pitting and dissolution along with an increase in concentration of soluble species thought to be important in smectite formation (i.e. Si, Al, Mg, Fe, Ca, Na). However, there was no evidence of clay formation, and the biotic experiments showed no signs of bulk scale pH change, suggesting that either the bacteria are actively concentrating relevant chemical species at a local level or they are acting as templates or nucleation points for clay formation.
A red-cell IgM-antibody capture assay has been developed for detecting Mycoplasma pneumoniae-specific IgM, which is based on the adsorption or ‘capture’ of IgM from patients' sera onto so-called ‘inagglutinable’ bovine red cells, chemically linked with anti-human μ When M. pneumoniae antigen is added to the system, the red cells agglutinate in the presence of M. pneumoniae-specific IgM.
The test was compared with the μ-capture ELISA described by Wreghitt & Sillis (1985), and was found to give comparable results. The two tests had similar sensitivity and specificity and could detect M. pneumoniae-spcific IgM for a similar time (up to 6 months) after proven M. pneumoniae infection.
However, the red-cell antibody capture assay is a much more simple and rapid test, taking only 1 h to perform (compared to 24 h for μ-capture ELISA). The redcell IgM-antibody capture assay is therefore amenable to rapid diagnosis of M. pneumoniae infection and the institution of early appropriate antibiotic therapy.
1. An investigation has been carried out into the conditions necessary for the production of immuno-conglutinin in rabbits.
2. The inoculation of complement adsorbed on sensitized cells stimulates the production of immuno-conglutinin. We have called this procedure hetero-stimulation.
3. Immuno-conglutinin also results from the inoculation of untreated but killed bacteria. This procedure for its production we call auto-stimulation. Gram-negative bacteria appear to be more effective stimulants than Gram-positive bacteria. Soluble antigens did not appear to be as effective as bacterial suspensions.
4. The necessity for clarifying the part played by immuno-conglutinin in in vivo immune processes has been stressed.
The authors would like to thank the following for gifts of experimental materials: Mr H. I. Field, strains of S. pullorum; Dr J. Boissard, strain of C. hofmanni; Dr C. H. Lea and Dr R. S. Hannan, purified casein; Miss Dunkerley, Bence Jones protein. Cx polysaccharide for testing acute phase protein in rabbit serum was made available by the kindness of Dr McCarty of the Hospital of the Rockefeller Institute for Medical Research, New York; and much of the work on this aspect was done in consultation with Dr H. C. Anderson, to whom we are most grateful.
1. Anti-mallein and anti-typhoid sera produced in various animal species, including man, have been examined for complement-absorbing antibodies using the complements of the pig, horse, cat, man, dog, and guinea-pig, which is possible if use is made of the conglutinating complement-absorption test as well as the haemolytic complement-fixation test.
2. Complement-fixing antibodies which are not demonstrable when some complements are used may be detected when other complements are used; for example, antibodies to mallein in human antisera were only detected when the sera were tested with horse and cat complements.
3. These early results are published at this stage because of the obvious possible application of these methods in laboratory serological diagnosis. Further work is in progress to elucidate the underlying reasons for these observations.
4. The implications of the results are discussed from the practical and theoretical aspects.
1. Salmonella antisera from a number of animals, including man, have been examined by conglutinating complement-absorption and haemolytic complement-fixation tests for the presence of anitbodies. Both a soluble antigen and a particulate antigen of washed suspended orgainsms have been used. The behavior of the antisera was comparable with that previously recorded with the mallein antimallein system, in so far as the reactions obtained with the different complements followed the same general pattern.
2. Two factors were found to explain the failure of certain antisera, in conjunction with the antigen, to adsorb certain complements. On the one hand, a few antibodies themselves appeared incapable of fixing a particular complement. On the other hand, although some antisera failed to fix specific complements, their antibodies, isolated from the serum, were able to fix the complements concerned. In these cases it appeared that the heated serum contained a non-specific factor that prevented the adsorption of the complements.
3. The existence of such non-specific factors in certain heat-inactivated sera is illustrated in Figs. 11–14. An examination of the mechanism involved does not appear to implicate the procomplementary effect of sera, although this effect in itself is a complex problem requiring further elucidation. The few experiments carried out indicate that the factor in the inactivated serum does not come into play and inhibit the adsorption of complement by an antigen-antibody complex without the initial intervention of some component of complement. Only after this has occurred is the inhibitory factor able to block any further complement adsorption.
4. We have discussed the implications of these experiments and their possible relationships to the complementoid phenomena described by previous workers.
Techniques for the fractionation of C′ 1 and C′ 2, and for the specific inactivation of C′ 4 of horse complement are described, and shown to be satisfactory. These three components of complement and also conglutinin are found to be essential to the process of conglutination.
The experiments reported do not exclude the possibility of additional or unidentified fractions of horse serum playing a part in the reaction. Whether or not C′ 3 is essential to the process of conglutination could not be determined from the evidence available.
It was found that by the procedures employed the C′ 4 fraction may be supplied either from the horse complement or from the heated bovine serum added as a source of conglutinin or from both.
When horse complement and bovine antibody against sheep cells are used it is found that conglutination will only result when the complement components are absorbed on to the immune complex in a particular sequence. The sequence is that C′ 1 is absorbed first on to the sensitized cells, and then C′ 2 and C′ 4 are absorbed together. Both these components must be presented together to the sensitized cells carrying C′ 1 if conglutination is to result. Finally, conglutinin acts on the sensitized cells which have absorbed the three complement components, and conglutination results.
The significance of these findings, together with matters of a more general nature, is discussed.
1. Observations on the sera of ponies, taken at frequent intervals for 321 days after oral administration of P. mallei, are described.
2. It was found that the conglutinating complement absorption test was more sensitive than the haemolytic complement fixation test as a means of diagnosis. It detected the antibodies earlier in the course of the disease and demonstrated their presence over a longer period of time.
3. The possibility of another practical use of this reaction as an adjunct to the allergic test is considered. Ten days after an intradermo-palpebral test a pony, which had been previously sensitized and whose serum antibody titre at that time was below 10, developed a serum titre of over 160 as demonstrated by the conglutinating complement absorption test. Under similar circumstances 11 unsensitized ponies developed no detectable serum antibodies.
1. Anti-mallein sera produced in thirteen species of mammals (including man) and one species of bird have been examined by the haemolytic complement fixation test using guinea-pig complement, and by the conglutinating complement absorption test using pig, horse and cat complements. Two methods of fixation have been used and compared, namely, fixation for half an hour at room temperature and fixation overnight at 4° C.
2. The complement of the horse proved to be the most sensitive in nearly every case in demonstrating the specific antibodies in the different sera; in the few instances where it was not markedly the most sensitive it was for practical purposes the equal of any other complement used, independent of the method of fixation. This is clearly indicated in the text figures.
3. The effects of overnight fixation on the titres obtained with the different complements are discussed.
4. The sera of six fowls inoculated with mallein failed to show fixation of any of the four complements in the presence of the homologous antigen. The presence of immune bodies was demonstrated however by the Indirect Complement Fixation technique of Rice (1948b).