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Background: Vaccination prevents severe morbidity and mortality from COVID-19 in the general population. The immunogenicity and efficacy of SARS-CoV-2 vaccines in patients with antibody deficiency is poorly understood. Objectives: COVID-19 in patients with antibody deficiency (COV-AD) is a multi-site UK study that aims to determine the immune response to SARS-CoV-2 infection and vaccination in patients with primary or secondary antibody deficiency, a population that suffers from severe and recurrent infection and does not respond well to vaccination. Methods: Individuals on immunoglobulin replacement therapy or with an IgG less than 4 g/L receiving antibiotic prophylaxis were recruited from April 2021. Serological and cellular responses were determined using ELISA, live-virus neutralisation and interferon gamma release assays. SARS-CoV-2 infection and clearance were determined by PCR from serial nasopharyngeal swabs. Results: A total of 5.6% (n = 320) of the cohort reported prior SARS-CoV-2 infection, but only 0.3% remained PCR positive on study entry. Seropositivity, following two doses of SARS-CoV-2 vaccination, was 54.8% (n = 168) compared with 100% of healthy controls (n = 205). The magnitude of the antibody response and its neutralising capacity were both significantly reduced compared to controls. Participants vaccinated with the Pfizer/BioNTech vaccine were more likely to be seropositive (65.7% vs. 48.0%, p = 0.03) and have higher antibody levels compared with the AstraZeneca vaccine (IgGAM ratio 3.73 vs. 2.39, p = 0.0003). T cell responses post vaccination was demonstrable in 46.2% of participants and were associated with better antibody responses but there was no difference between the two vaccines. Eleven vaccine-breakthrough infections have occurred to date, 10 of them in recipients of the AstraZeneca vaccine. Conclusion: SARS-CoV-2 vaccines demonstrate reduced immunogenicity in patients with antibody deficiency with evidence of vaccine breakthrough infection. [ABSTRACT FROM AUTHOR]

Microfluidics typically uses either a syringe pump that regulates the flow rate in microchannels or a pressure pump that controls the inlet pressures to drive the flow. In the context of pressure-driven flow, a reservoir holder containing liquid samples is normally used to interface the pressure pump with the microfluidic chip via soft tubing. The tubing connecting the pump and holder transports the pressurized air while the tubing connecting the holder and chip transports the liquid samples. The pressure output from the pump is usually assumed to be stable and the same as that applied to the liquid in the chip; however, in practice this assumption is often incorrect and may negatively impact chip performance. This assumption is critically challenged when applied to microfluidic chips involving dynamic control of fluids since the pressures are constantly varied (at > 10 Hz). This study presents a method for investigating, quantifying and modelling the pump stability and the dynamics of the air tubing using two pressure sensors. The relationship between the pressure output from the pump and the reservoir holder pressure is generalized as a first-order linear system. This relationship allows the software that controls the pressure pump to output the required pressure to the reservoir holder and thus to the microfluidic chip. These results should significantly improve the performance of microfluidic chips using active fluid control, and may also benefit passive fluid control applications. [ABSTRACT FROM AUTHOR]

Gas extraction in the Groningen Province in the Netherlands has caused seismicity. A method was needed for probabilistic assessments of the seismic performance of the levees that protect low-lying polders against flooding. By combining the First Order Reliability Method with response surfaces it proved possible to strongly reduce the required number of simulations with advanced numerical models to obtain reliable failure probability estimates. To illustrate the workings of the method, an application to a levee cross-section along the Eemscanal with a sheet pile wall is presented. The probabilistic method can be used for probabilistic assessments and the probability-based calibration of partial factors, and it could serve as a starting point for quantitative risk analyses for levee systems in earthquake prone regions. [ABSTRACT FROM AUTHOR]

Background: Immunologists are increasingly being asked to assess patients with non-classical and secondary antibody deficiency to determine their potential need for immunoglobulin replacement therapy (IGRT). Immunoglobulin is a limited, expensive resource and no clear guidance exists for this broad patient group. The purpose of this survey is to establish what factors influence the decision to commence IGRT in adult patients, when diagnostic criteria for primary antibody deficiency are not fulfilled.Methods: Under the auspices of the United Kingdom Primary Immunodeficiency Network (UKPIN), a study group was established which circulated an online questionnaire to the consultant body across the UK and Ireland. Results provided a snapshot of the current clinical practice of 71% of consultant immunologists, from 30 centers.Results: In order of importance, factors which influence the decision to commence IGRT include number of hospital admissions with infection, serum IgG level, bronchiectasis, radiologically proven pneumonia, number of positive sputum cultures, number of antibiotic courses, and results of immunization studies. The commonest test vaccine used was Pneumovax 23 with measurement of serotype-specific responses at 4 weeks, with a threshold of 0.35 μg/ml in 2/3 of serotypes measured. Eighty-six percent of patients are treated with a trial of prophylactic antibiotics prior to consideration of IGRT. Efficacy of IGRT trial is assessed at between 6 and 12 months.Conclusions: There was consistency in clinical practice using a combination of clinical history, evidence of infections, and vaccination testing for diagnosis. However, there was some variation in the implementation of this practice, particularly in vaccine choice and assessment of response to vaccination. [ABSTRACT FROM AUTHOR]

This paper considers the fast and accurate estimation of motion variables of a rigid body object whose movement occurs from intermittent contacts with coordinating manipulators in nonprehensile manipulation tasks. The estimator operates under multiple sensory data including visual, joint torque, joint position and/or tactile measurements which are combined at the lower level to compensate for the latency and the slow sampling of the visual data. The estimator is real-time in the sense that it provides the motion data of the target object at the same fast sample rate of the servo controller without delay. The basic formulation is the multi-rate Kalman filter with the contact force vector as its process input, and the visual observation as its measurement output signal which is the down-sampled and delayed version of the configuration of the target object. Experimental tests are conducted for the case of planar object manipulation as well as the non-centroidal rotation under gravity using a robotic hand, and their results are presented to demonstrate the validity of the proposed estimation scheme. [ABSTRACT FROM AUTHOR]

Introduction: Complement immunodeficiencies (excluding hereditary angioedema and mannose binding lectin deficiency) are rare. Published literature consists largely of case reports and small series. We collated data from 18 cities across Europe to provide an overview of primarily homozygous, rather than partial genotypes and their impact and management. Methods: Patients were recruited through the ESID registry. Clinical and laboratory information was collected onto standardized forms and analyzed using SPSS software. Results: Seventy-seven patients aged 1 to 68 years were identified. 44 % presented in their first decade of life. 29 % had C2 deficiency, defects in 11 other complement factors were found. 50 (65 %) had serious invasive infections. 61 % of Neisseria meningitidis infections occurred in patients with terminal pathway defects, while 74 % of Streptococcus pneumoniae infections occurred in patients with classical pathway defects ( p < 0.001). Physicians in the UK were more likely to prescribe antibiotic prophylaxis than colleagues on the Continent for patients with classical pathway defects. After diagnosis, 16 % of patients suffered serious bacterial infections. Age of the patient and use of prophylactic antibiotics were not associated with subsequent infection risk. Inflammatory/autoimmune diseases were not seen in patients with terminal pathway, but in one third of patients classical and alternative pathway defects. Conclusion: The clinical phenotypes of specific complement immunodeficiencies vary considerably both in terms of the predominant bacterial pathogen, and the risk and type of auto-inflammatory disease. Appreciation of these phenotypic differences should help both immunologists and other specialists in their diagnosis and management of these rare and complex patients. [ABSTRACT FROM AUTHOR]

The thermal control of a die is crucial for the development of high efficiency injection moulds. For an effective thermal management, this research provides a strategy to identify a thermal dynamic model and to design a controller. The neural network techniques and finite element analysis enable modeling to deal with various cycle-times for moulding process and uncertain dynamics of a die. Based on the system identification which is experimentally validated using a real system, controllers are designed using fuzzy-logic and self-tuning PID methods with backpropagation and radial basis function neural networks to tune control parameters. Through a comparative study, each controller's performance is verified in terms of response time and tracking accuracy under different moulding processes with multiple cycle-times. [ABSTRACT FROM AUTHOR]

phase change (PC) microvalve with an integrated two-level cooling/heating system is developed for microfluidic applications in this article. This PC microvalve utilizes the liquid-solid PC of a small portion of the working medium in a microchannel to switch on/off the flow in the microchannel. The size of the working medium for the PC microvalve is 5-mm long, 50-μm high, and 80-μm wide (50 μm × 80 μm is the cross-sectional area of the channel) in this study. The switch is actuated by using a two-level cooling/heating system integrated on the chip. The first-level cooling/heating unit keeps the working medium in the valve area in the temperature range of supercooling state. Based on the supercooling state, the second-level cooling/heating unit either heats up or cools down the medium in the valve area to trigger its PC between liquid and solid for valving purposes. The proposed microfluidic PC microvalve is characterized experimentally in microfluidic chips. The thermal impact of one PC microvalve in one particular microchannel on its adjacent channels is discussed by establishing a preliminary analytical model and a numerical model. In addition to no leakage and no moving element, this PC microvalve with a two-level cooling/heating system can achieve a very short cooling time (i.e., 2.72 s). [ABSTRACT FROM AUTHOR]

Abstract  In this paper, a four hot-arm U-shape electro-thermal actuator that can achieve bidirectional motion in two axes is introduced. By selectively applying voltage to different pairs of its four arms, the device can provide actuation in four directions starting from its rest position. It is shown that independent in-plane and out-of-plane motions can be obtained by tailoring the geometrical parameters of the system. The lumped model of the microactuator was developed using electro-thermal and thermo-mechanical analyses and validated using finite element simulations. The device has been fabricated using PolyMUMPs and experimental results are in good agreement with the theoretical predictions. Total in-plane deflections of 4.8 μm (2.4 μm in either direction) and upward out-of-plane deflections of 8.2 μm were achieved at 8 V of input voltage. The large achievable deflections and the higher degree-of-freedom of the proposed device compared to its counterparts, foresee its use in diverse MEMS applications. [ABSTRACT FROM AUTHOR]

Dimensional error appears nonlinearly in the computer numerical control (CNC) grinding process. The analysis of dimensional error variation for CNC grinding of cutter inserts is presented in this paper. A new intelligent error pre-compensation technique, the intelligent CNC system structure with which this is implemented, and the algorithm are introduced. The input-output response and the simulation of the intelligent error compensation system are also presented, and show the superiority of the technique. [ABSTRACT FROM AUTHOR]

We describe two adolescents who presented with end-stage renal failure and clinical features suggestive of Sjögren’s syndrome (SS). They both demonstrated severe, chronic, tubulointerstitial inflammation on renal biopsy, high-titre antinuclear antibodies, high immunoglobulin A and G concentrations, positive anti-SSA and anti-SSB antibodies, and negative anti-double-stranded DNA antibodies. One had subjective and objective evidence of the sicca complex (dry eyes and/or dry mouth) and fulfilled the commonly accepted SS consensus criteria. The other showed no evidence of the sicca complex but fulfilled modified criteria for juvenile SS. SS may be underrecognised as a cause of end-stage renal failure in childhood. [ABSTRACT FROM AUTHOR]

Abstract  Various applications of micro-robotic technology suggest the use of new actuator systems which allow motions to be realized with micrometer accuracy. Conventional actuation techniques such as hydraulic or pneumatic systems are no longer capable of fulfilling the demands of hi-tech micro-scale areas such as miniaturized biomedical devices and MEMS production equipment. These applications pose significantly different problems from actuation on a large scale. In particular, large scale manipulation systems typically deal with sizable friction, whereas micro manipulation systems must minimize friction to achieve submicron precision and avoid generation of static electric fields. Recently, the magnetic levitation technique has been shown to be a feasible actuation method for micro-scale applications. In this paper, a magnetic levitation device is recalled from the authors’ previous work and a control approach is presented to achieve precise motion control of a magnetically levitated object with sub-micron positioning accuracy. The stability of the controller is discussed through the Lyapunov method. Experiments are conducted and showed that the proposed control technique is capable of performing a positioning operation with rms accuracy of 16 μm over a travel range of 30 mm. The nonlinear control strategy proposed in this paper showed a significant improvement in comparison with the conventional control strategies for large gap magnetic levitation systems. [ABSTRACT FROM AUTHOR]

: The aim of the study was to examine the clinical outcome of patients presenting to an early arthritis clinic with synovitis of the knee. The patients were assessed at presentation for evidence and pattern of joint inflammation. These patients were then reassessed at 3, 6 and 12 months and thereafter annually to determine clinical outcome. One thousand six hundred and thirty-three consecutive referrals were examined, 903 of whom had early synovitis. One hundred and thirty had knee synovitis at presentation, of whom 73 fulfilled ACR criteria for rheumatoid arthritis (RA) during the study. All 73 presented with a symmetrical polyarthritis that included the small joints and had persistent disease at 1 year. Of the remaining 57 patients, 61% of those presenting with an oligoarthritis and 33% with a polyarthritis (including knee synovitis) were in remission at 1 year. None of those presenting as a monoarthritis of the knee had inflammation at 1 year or fulfilled ACR criteria for RA at any time. It was concluded that patients presenting with knee synovitis in the absence of a small joint polyarthritis usually have a benign course following standard therapy. No patient who presented with monoarthritis developed RA. Knee synovitis as part of a polyarthritis (even when not fulfilling ACR criteria) probably justifies disease-modifying antirheumatic drug at presentation. [ABSTRACT FROM AUTHOR]

Angiotensin-1 converting enzyme inhibitors (ACEI) have been shown to reduce proteinuria in azotaemic diabetics and in other glomerulopathies, and such treatment has also slowed the development of experimentally-induced glomerulosclerosis in animals. We have treated 13 patients with focal segmental glomerulosclerosis (FSGS) and IgA nephropathy (IgAN) with Captopril 12.5 mg twice daily for six months and assessed their response in terms of 24 hour urinary protein excretion, blood pressure, glomerular filtration rate, effective renal plasma flow and derived values for filtration fraction and renal vascular resistance. A mean fall of 29 per cent in urinary protein excretion was observed over the six months treatment schedule. No significant changes were observed in other parameters of renal haemodynamics measured. We conclude that Captopril therapy in patients with FSGS and IgAN reduces urinary protein excretion consistently over a six month period, and that this may in the longer term retard the progression of their renal failure. [ABSTRACT FROM AUTHOR]

Background: Allergies cause a considerable burden to both its sufferers and the National Health Service. There is growing interest in acupuncture as a treatment for a range of conditions. Since acupuncture may modulate the immune system it could be a useful treatment for allergic rhinitis (AR) sufferers. We therefore assessed the evidence for the clinical effectiveness of acupuncture in patients with AR by performing a systematic review of the literature. Methods: Searches (up to 2007) were conducted in all major databases for randomised controlled trials (RCTs) evaluating the clinical effectiveness of acupuncture in the treatment of AR. No limits were placed on language. Studies were included if they compared acupuncture to a sham or inactive acupuncture treatment (placebo) with or without standard care. Meta-analysis was performed where feasible. Results: Seven relevant RCTs were included after screening and application of inclusion and exclusion criteria. The trials were generally of poor quality as assessed by a modified Jadad scale, with the exception of two studies which scored highly. A wide variety of outcomes was measured but most assessed symptom severity on a visual analogue scale. A meta-analysis failed to show any summary benefits of acupuncture treatment for symptom severity scores or serum IgE measures which could not have been accounted for by chance alone. Acupuncture was not associated with any additional adverse events in the trials. Conclusion: There is currently insufficient evidence to support or refute the use of acupuncture in patients with AR. A large well conducted RCT, which overcomes identified methodological problems in the existing RCTs, would be required to resolve this question. [Copyright &y& Elsevier]