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ABSTRACTThe high-density microneedle array patch (HD-MAP) is a novel vaccine delivery system with potential for self-administered vaccination. In this study, Vaxxas HD-MAPs were applied by both a trained user and self-administered with application sites compared to determine the response of skin and the level of engagement of the HD-MAP with human skin. Twenty healthy participants were enrolled, and the response of skin including erythema was observed at all application sites and no difference was found between trained user or self-administered applications. The majority of participants (70%) preferred the deltoid upper arm application site for applying HD-MAPs. Fluorescent dermatoscope images confirmed HD-MAPs engaged the skin surface and scanning electron microscopy (SEM) image analysis exhibited similar delivery characteristics for the upper arm and forearm sites when applied by either a trained user or self-administered. This study showed that noninvasive methods including dermatoscopy and SEM image analysis were able to estimate the engagement of HD-MAPs with human skin. HD-MAP self-vaccination technology has a unique proposition in pandemic preparedness by alleviating the need for health-care workers to administer vaccines, however greater awareness and understanding of the potential of this technology is required.

A multicenter study was conducted to test the ability of electrical impedance scanning to differentiate between benign and malignant skin lesions. The performance of a dual electrical impedance scanning/image analysis device was also assessed.

OBJECTIVE: Human fetuin/alpha(2)-HS-glycoprotein (AHSG) is a 49 kDa serum and tissue protein which is a natural inhibitor of insulin receptor signaling. We investigated serum AHSG levels during pregnancy and whether the protein is involved in insulin resistance observed in healthy pregnant women and patients with gestational diabetes. DESIGN: One hundred and four healthy pregnant women and 23 of their neonates, 30 patients with gestational diabetes and their neonates and 30 healthy age-matched non-pregnant females as a control group were investigated in a case-control cross-sectional study. METHODS: Serum AHSG was determined by radial immunodiffusion. RESULTS: We observed an increase of serum AHSG concentration in the second and third trimesters. Gestational diabetes patients had significantly higher AHSG levels than healthy pregnant women and non-pregnant controls. There was a highly significant positive correlation between serum AHSG concentration and indirect parameters of insulin resistance, i.e. tumor necrosis factor-alpha (TNF-alpha), leptin, C-peptide and C-peptide/blood glucose ratio. There was also a negative correlation between maternal AHSG, TNF-alpha, leptin levels and head circumference, body length and body weight of newborns. CONCLUSION: AHSG, TNF-alpha and leptin may contribute to insulin resistance during normal pregnancy and gestational diabetes. AHSG along with these cytokines may also negatively regulate neonatal skeletal development.

When prophylactic antibiotics are used in abdominal surgery it is customary to give the first dose before the operation. Whilst intra-operative antibiotics may be effective in elective surgery, there may be an advantage to starting pre-operatively when there is already an infective focus such as appendicitis. Antibiotics started pre-operatively (group P) have been compared with antibiotics started after initial abdominal exploration (group T). Three intravenous doses of 500 mg metronidazole plus 1 g cephazolin were given in a randomized, double-blind study of 700 emergency and elective high-risk abdominal operations. Antibiotic plasma concentrations at the end of the operation were significantly lower in group P but lay well within the therapeutic range. Wound infection rates, which included minor and delayed infections, were similar in both groups (group P, 57 of 342, 16·7 per cent; group T, 55 of 358, 15·4 per cent; 95 per cent confidence intervals for the difference being −4·1 to +6·7 per cent. In appendicitis, wound infection rates were 12·1 and 13·9 per cent for groups P and T respectively. However, non-fatal deep sepsis was more common in group P(nine cases) than in group T (two cases) (χ2= 4·9, P < 0·05). Postoperative infection was twice as common in obese patients whose body mass index (BMI) was ⩾ 26 (39 of 132, 30 per cent) than in thin patients whose BMI was <24 (41 of 288, 14 per cent; χ2= 13·8, P< 0·001). This study failed to show any advantage to starting antibiotics pre-operatively, even in appendicitis.

The H-mode develops in conditions of low and controlled recycling. The electron and ion collisionality parameters at the plasma periphery are close to, but above, one in the L-phase and drop below one in the H-phase. The realization of the H-phase is easier in the single-null than in the double-null configuration which has higher power and density thresholds. The increased H-mode accessibility of the single-null configuration requires the ion grad B-drift direction to be towards the stagnation point. The experimental observations are in agreement with a recent theory of the H-transition by Hinton.

The highest ?-values derived from diamagnetic flux measurements in H-discharges are found to be close to the ?-limit due to kink and ideal ballooning modes. Both energy and particle confinement are degraded in these discharges and do not recover during the injection period. The energy confinement time decreases by a typical factor of two, the electron thermal diffusivity being correspondingly enhanced. Electron heat conduction is again found to be the dominant energy loss channel. The degradation of confinement close to the ideal-MHD limit suggests that kink and ballooning instabilities occur and are responsible for the enhanced transport. This conclusion is supported by the correlation with the pressure profile and by the result that global and local transport do not change in a reference discharge which is stable against ideal-MHD modes.

The paper summarizes the experiments performed with ion cyclotron resonance heating (ICRH) on ASDEX, from November 1984 until March 1986; the most interesting results are reported and discussed in detail. Heating and confinement studies using the hydrogen second harmonic scheme and the hydrogen minority scheme (PIC< 2.6 MW, tIC< 1.5 s) show a typical L-mode behaviour, i.e. a power dependent confinement degradation, which is rather similar to that found with neutral beam injection (NBI) heating. ICRH is accompanied by a slightly improved particle and energy confinement compared with that of NBI; this is also true for a combined ICRH + NBI scheme, up to Ptot? 4.5 MW, absorbed in the plasma. Particular efforts have been devoted to investigations of the second harmonic regime in H/D plasmas with nH/ne? 0.1 - 1, with a view to heating mixtures in reactor relevant plasmas. The achievement of H-mode transitions with ICRH alone in the hydrogen minority scheme at an absorbed RF power of about 1.1 MW supports the assumption of common confinement properties in auxiliary heated tokamaks, since they appear to be widely independent of the additional heating method. ICRH specific impurity problems, such as the strong release of iron from the vessel walls, have been overcome by applying extensive in situ wall carbonization. The mechanisms responsible for impurity generation have partly been identified and analysed; however, the problem still remains to be solved. Impurities preferentially released from the ICRH antenna do not pose problems.

This letter reports on two experiments undertaken to evaluate the retention of gaseous and target produced impurities in the ASDEX divertor. The retention for gaseous impurities was determined by puffing Ar into the main chamber and simulating the time behaviour of the Ar XVI line intensity with a time dependent impurity transport code including a simple divertor model. During Ohmic heating a factor of 3 and 4.5 enhancement of impurity retention if found relative to the vacuum time constant (90 ms) of the divertor chamber, for ne= 2 × 1013cm?3and ne= 3.5 × 1013cm?3, respectively, while a drastic breakdown of the retention occurs during high power NI heating. - To deduce the retention of impurities generated at the divertor plates, a segment (3.5%) of the plates was covered with copper, a metal previously not used in ASDEX. By measuring the Cu influx at the target plates and the line intensity of the Cu XX line (11.38 Å) in the core plasma and by using the transport code, it is found that during NI heating (ne? 2 × 1013cm?3) Cu atoms originating from the target plates have a ? 3.5 times higher probability to penetrate into the core plasma than if they had when originating from the main chamber walls.

High resolution X-ray spectroscopy was used to evaluate the fractional population of non-thermal electrons generated when electromagnetic waves in the lower hybrid frequency range are launched in the ASDEX tokamak. In complete current drive discharges a typical value of 1% is found for this parameter, in agreement with a theoretical estimate. Furthermore, it is shown that the toroidal electric field is very effective in enhancing tail electron generation, as confimed by ? measurements, and that the wave penetration to the plasma centre is inhibited when interaction of the waves with plasma ions is the dominant damping mechanism.