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This paper presents a design optimization of valveless micropump using Genetic Algorithms (GA). The micropump is designed with a diaphragm, pumping chamber and diffuser/nozzle element functions as inlet and outlet of micropump with outer dimension of (5×1.75×5) mm3. The main objectives of this research are to determine the optimum pressure to be applied at micropump’s diaphragm and to find the optimum coupling parameters of the micropump to achieve high flow rate with low power consumption. In order to determine the micropump design performance, the total deformation, strain energy density, equivalent stress for diaphragm, velocity and net flow rate of micropump are investigated. An optimal resonant frequency range for the diaphragm of valveless micropump is obtained through the result assessment. With the development of GA-ANSYS model, a maximum total displacement of diaphragm, 5.3635 µm, with 12 kPa actuation pressure and optimum net flowrate of 7.467 mL/min are achieved.

The C1q binding assay and the nephelometric monoclonal rheumatoid factor assay were able to discriminate 79% and 57% respectively of rheumatoid arthritis (RA) patients from healthy blood donors. In addition these assays could distinguish those patients with active arthritis from those with inactive disease, and the C1q binding assay correlated significantly with other laboratory indices of the rheumatoid process, including the erythrocyte sedimentation rate, low molecular weight or 7S IgM, and the rheumatoid factor titre. High levels of C1q binding were also seen in rheumatoid vasculitis. Both assays gave higher mean values in synovial fluid compared with the corresponding serum, but it appeared from ultracentrifugal analysis and from a lack of a consistent correlation between these assays that each assay was measuring different forms of immunecomplex-like material which may be involved in the immunopathogenesis of this disease. The C1q binding assay is of some value in the laboratory assessment of rheumatoid arthritis and appears to offer greater advantages than the monoclonal rheumatoid factor assay, although the usefulness of this latter assay may be very dependent on the monoclonal rheumatoid factor used. [ABSTRACT FROM PUBLISHER]

Laser nephelometric estimation of IgM in the eluate fractions following Sepharose 6B chromatography has enabled the calculation of the proportion of low molecular weight IgM (7S IgM) in normal and pathological sera. This figure has then been used to determine the absolute amount of 7S IgM. Twenty-seven of 36 (75%) patients with rheumatoid arthritis had 7S IgM with a mean value of 17 mg/100 ml (170 mg/l) (range 2.5-59 mg/100 ml). No sera from 10 healthy controls were found to contain 7S IgM. Patients with active rheumatoid arthritis had significantly more 7S IgM than those with inactive disease, but there was no significant difference between those patients with and without rheumatoid vasculitis. Significant correlations occurred between 7S IgM and the absolute IgM level (P < 0.01), the Rose-Waaler titre (P < 0.01), and the erythrocyte sedimentation rate (P = 0.01). However, there was no significant correlation with the age of the patient, the duration of the disease, or the level of circulating immune complexes as measured by the Clq binding assay. It is concluded that 7S IgM commonly occurs in rheumatoid arthritis, and it is postulated that a common immunological stimulus is responsible for the production of 7S IgM and rheumatoid factors, serological abnormalities that characterise this disease. [ABSTRACT FROM PUBLISHER]

The unstimulated random migration and the serum-induced chemokinesis of neutrophils obtained from the peripheral blood of patients with rheumatoid arthritis (n = 19) was not different from those of controls (ii = 20). However, neutrophils obtained from the joint fluid of rheumatoid patients (n = 10) demonstrated a reduced serum-induced chemokinesis which was correlated with the amount of immune complexes present in the synovial fluid. The chemotactic response of peripheral blood neutrophils from subjects with rheumatoid arthritis taking aspirin (n = 11) was increased while that of those rheumatoid subjects not taking aspirin (n = 8) was the same as controls. It is concluded that although there is no impairment of the in vitro migratory capacities of peripheral blood neutrophils obtained from patients with rheumatoid arthritis, neutrophils obtained from synovial fluids exhibit a marked defect in chemokinesis which may be related to the ingestion of immune complexes within the joint space. [ABSTRACT FROM AUTHOR]

Sera from patients with rheumatoid arthritis inhibited the migration of human neutrophils in 63% (twenty-two out of thirty-five) of the cases tested. The inhibition was not due to a toxic effect of the serum as it was reversed by a chemotactic stimulus. There was a strong correlation between the degree of inhibition of neutrophil migration and the amount of immune complexes present in the sera its determined by the Clq binding activity. It is suggested that the inhibition of neutrophil migration is due to the presence of circulating immune complexes, and that the capacity of immune complexes to inhibit neutrophil migration in vitro may also contribute to the accumulation of neutrophils at sites of immune complex formation in vivo. [ABSTRACT FROM AUTHOR]

Background: The prevalence of diabetes is rising in older people. In 2018, over 574,000 Australians reported having diabetes. The highest prevalence (19.4%) of diabetes has been observed in people aged 85 years and older. Clinical guidelines recommend that diabetes management should be individualized; however, there is limited information regarding the current management patterns of diabetes in older people, given most clinical trials exclude participants from this age group. Available data identify that few individuals achieve optimal glycemic levels in the general population, potentially leading to adverse health outcomes and impact on quality of life. The data on glycemic profiles of older population are limited., Objective: The aim of this study is to examine individualized diabetes management intervention for older people through home visits with a credentialed diabetes educator (CDE) and telehealth consultations with an endocrinologist located at a tertiary hospital., Methods: This paper describes the design and methodology of a mixed methods feasibility and safety study to identify the current management of type 2 diabetes in people aged 65 years or older. We will implement and evaluate a personalized approach to management in the community of an Australian metropolitan city. This management approach will utilize flash glucose monitoring and home visits with the support of a community home nursing service CDE and telehealth consultation with an endocrinologist located at a local tertiary hospital., Results: The study commenced in February 2017 and has recruited 43 participants, with final data collection to be completed by July 2019. Data analysis will commence after final data collection, with results expected to be published by the end of 2019., Conclusions: This study is the first of its kind to explore individualized diabetes management for community-dwelling older people, with an aim to achieve optimal glycemic levels (glycated hemoglobin between 53 and 69 mmol/mol [7%-8.5%] depending on the fitness and frailness of the older individual). The data drawn from this study may be used to inform policy makers, service providers, clinicians, and older adults living with diabetes., International Registered Report Identifier (irrid): DERR1-10.2196/13986., (©Rajna Ogrin, Sandra Neoh, Tracy Aylen, Ralph Audehm, Leonid Churilov, Lorenna Thurgood, Georgia Major, Jeffrey Zajac, Elif I Ekinci. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 07.06.2019.)

This research proposes an intelligent decision support system for acute lymphoblastic leukaemia diagnosis from microscopic blood images. A novel clustering algorithm with stimulating discriminant measures (SDM) of both within- and between-cluster scatter variances is proposed to produce robust segmentation of nucleus and cytoplasm of lymphocytes/lymphoblasts. Specifically, the proposed between-cluster evaluation is formulated based on the trade-off of several between-cluster measures of well-known feature extraction methods. The SDM measures are used in conjuction with Genetic Algorithm for clustering nucleus, cytoplasm, and background regions. Subsequently, a total of eighty features consisting of shape, texture, and colour information of the nucleus and cytoplasm sub-images are extracted. A number of classifiers (multi-layer perceptron, Support Vector Machine (SVM) and Dempster-Shafer ensemble) are employed for lymphocyte/lymphoblast classification. Evaluated with the ALL-IDB2 database, the proposed SDM-based clustering overcomes the shortcomings of Fuzzy C-means which focuses purely on within-cluster scatter variance. It also outperforms Linear Discriminant Analysis and Fuzzy Compactness and Separation for nucleus-cytoplasm separation. The overall system achieves superior recognition rates of 96.72% and 96.67% accuracies using bootstrapping and 10-fold cross validation with Dempster-Shafer and SVM, respectively. The results also compare favourably with those reported in the literature, indicating the usefulness of the proposed SDM-based clustering method.

Many patients with acute lymphoblastic leukemia (ALL) are not cured by current therapy because of the development of drug resistance. It is not clear when resistance develops during the growth of the leukemic clone and whether resistant cells are already present at diagnosis or develop later during treatment. Twenty-two uniformly treated children with ALL were studied throughout induction treatment. The size of the leukemic clone in blood and marrow was estimated by limiting dilution PCR analysis, using the rearranged immunoglobulin heavy chain gene as a molecular marker. The decline in the number of leukemic cells was biphasic in virtually all patients. For both marrow and blood, the logarithmic mean of the number of leukemic cells fell by approximately four orders of magnitude during the first 2 weeks, one order of magnitude during the third week, and not at all during the last two weeks of induction treatment. For marrow, the median of the fraction of leukemic cells in each patient that survived per week of treatment was 0.008 for the first 2 weeks, 0.12 for the third week, and 1.4 for the last 2 weeks; for blood, the corresponding figures were 0.003, 0.14, and 0.69, respectively. In individual patients, the results for marrow and blood showed good correlation. The biphasic decline of leukemic cell number suggests that most leukemic cells were sensitive to treatment and were rapidly killed, leaving behind a minor but substantial population of drug-resistant cells. The most likely explanation for this phenomenon is that these resistant cells were already present at diagnosis, their resistance having originated from genetic or epigenetic mutations during prior growth of the leukemic clone.

In children with acute lymphoblastic leukemia (ALL), the level of minimal residual disease (MRD) at the end of induction strongly predicts outcome, presumably because it measures both drug sensitivity and the number of leukemic cells requiring elimination. Children with high levels (> 10(-3) leukemic cells per marrow cell) nearly always relapse, whereas those with low levels (<2 x 10(-5)) seldom do. However, the importance of MRD in adult ALL is unclear. We studied 27 patients aged 14 to 74 who were treated with a standard protocol and who attained morphological remission. MRD in the marrow at first remission was quantified by using the polymerase chain reaction (PCR), with the rearranged immunoglobulin heavy chain gene as a molecular marker. Levels of MRD varied from 3 x 10(-1) to <7 x 10(-7). The probability of long-term relapse-free survival was significantly related to the level of MRD and only one of nine patients with MRD >10(-3) did not relapse. For patients who did relapse, there was an inverse relationship between MRD level and the length of remission. Overall, MRD in adults in whom a translocation had not been identified was significantly higher than in comparably-treated children, suggesting that ALL in adults is more drug-resistant than in children.

We describe our 10 years experience in assaying over 15,000 clinical specimens for immune complexes (IC) using the C1q binding assay. Normal ranges were initially established using a large panel of blood donor sera and precision of the assay was optimized by inclusion of heat aggregated IgG (HAGG) as standards. Nevertheless some variability was observed due to variation in C1q binding from batch to batch and with aging of this reagent. In an empirically selected 2 year period involving over 3,000 clinical specimens, 25% had elevated concentrations of IC. Of these the majority were from patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), other connective tissue disorders, infective endocarditis (IE), diffuse interstitial lung disease (DILD) and vasculitis (VASC). In RA, IE and VASC, significant correlations were observed between concentrations of IC and rheumatoid factor (RF) and the addition of a purified monoclonal RF to normal serum caused increased C1q binding. Longitudinal studies in RA and IE demonstrated a striking decline in IC in response to effective treatment. We conclude that the measurement of IC provides little additional useful diagnostic information in those diseases associated with high levels of RF but appears more useful in disorders such as SLE, IE and DILD in which RF is absent or present in low concentration. Sequential monitoring of IC in RA and IE reflects response to treatment.