Recurrent outbreaks of mumps in Lothian and the impact of waning immunity.

Another large outbreak of mumps occurred in Lothian from October 2017, which coincided with the commencement of the higher education term. During this period 324 cases were notified, most of whom were aged 18-22 years old. Although previous outbreaks had a focus in student populations, 43% of current cases reported that they were not a student. There has been increases in private student housing where students from all universities live, which may have contributed to the wide spread of the outbreak and complicated outbreak control. Information on vaccination status was available for 244 cases (75%), of whom the majority (75.8%) reported having two MMR doses. To investigate potential waning vaccine immunity the mean length of time since last mumps containing vaccine was calculated as 14.3 years. The outbreak was declared over in May 2018 after case numbers returned to background levels. This outbreak highlighted that mumps outbreaks occur cyclically coinciding with new cohorts of susceptible students entering the Lothian population. The lessons from this outbreak are to encourage students to have two MMR doses and also be prepared for mumps outbreaks in the near future. In future outbreaks the utility of a third MMR for outbreak control could be examined.

A method for in situ absolute DD yield calibration of neutron time-of-flight detectors on OMEGA using CR-39-based proton detectors.

Neutron time of flight (nTOF) detectors are used routinely to measure the absolute DD neutron yield at OMEGA. To check the DD yield calibration of these detectors, originally calibrated using indium activation systems, which in turn were cross-calibrated to NOVA nTOF detectors in the early 1990s, a direct in situ calibration method using CR-39 range filter proton detectors has been successfully developed. By measuring DD neutron and proton yields from a series of exploding pusher implosions at OMEGA, a yield calibration coefficient of 1.09 ± 0.02 (relative to the previous coefficient) was determined for the 3m nTOF detector. In addition, comparison of these and other shots indicates that significant reduction in charged particle flux anisotropies is achieved when bang time occurs significantly (on the order of 500 ps) after the trailing edge of the laser pulse. This is an important observation as the main source of the yield calibration error is due to particle anisotropies caused by field effects. The results indicate that the CR-39-nTOF in situ calibration method can serve as a valuable technique for calibrating and reducing the uncertainty in the DD absolute yield calibration of nTOF detector systems on OMEGA, the National Ignition Facility, and laser megajoule.

A compact proton spectrometer for measurement of the absolute DD proton spectrum from which yield and ρR are determined in thin-shell inertial-confinement-fusion implosions.

A compact, step range filter proton spectrometer has been developed for the measurement of the absolute DD proton spectrum, from which yield and areal density (ρR) are inferred for deuterium-filled thin-shell inertial confinement fusion implosions. This spectrometer, which is based on tantalum step-range filters, is sensitive to protons in the energy range 1-9 MeV and can be used to measure proton spectra at mean energies of ∼1-3 MeV. It has been developed and implemented using a linear accelerator and applied to experiments at the OMEGA laser facility and the National Ignition Facility (NIF). Modeling of the proton slowing in the filters is necessary to construct the spectrum, and the yield and energy uncertainties are ±<10% in yield and ±120 keV, respectively. This spectrometer can be used for in situ calibration of DD-neutron yield diagnostics at the NIF.

Empirical assessment of the detection efficiency of CR-39 at high proton fluence and a compact, proton detector for high-fluence applications.

CR-39 solid-state nuclear track detectors are widely used in physics and in many inertial confinement fusion (ICF) experiments, and under ideal conditions these detectors have 100% detection efficiency for ∼0.5-8 MeV protons. When the fluence of incident particles becomes too high, overlap of particle tracks leads to under-counting at typical processing conditions (5 h etch in 6N NaOH at 80 °C). Short etch times required to avoid overlap can cause under-counting as well, as tracks are not fully developed. Experiments have determined the minimum etch times for 100% detection of 1.7-4.3-MeV protons and established that for 2.4-MeV protons, relevant for detection of DD protons, the maximum fluence that can be detected using normal processing techniques is ≲3 × 10(6) cm(-2). A CR-39-based proton detector has been developed to mitigate issues related to high particle fluences on ICF facilities. Using a pinhole and scattering foil several mm in front of the CR-39, proton fluences at the CR-39 are reduced by more than a factor of ∼50, increasing the operating yield upper limit by a comparable amount.

A novel particle time of flight diagnostic for measurements of shock- and compression-bang times in D3He and DT implosions at the NIF.

The particle-time-of-flight (pTOF) diagnostic, fielded alongside a wedge range-filter (WRF) proton spectrometer, will provide an absolute timing for the shock-burn weighted ρR measurements that will validate the modeling of implosion dynamics at the National Ignition Facility (NIF). In the first phase of the project, pTOF has recorded accurate bang times in cryogenic DT, DT exploding pusher, and D(3)He implosions using DD or DT neutrons with an accuracy better than ±70 ps. In the second phase of the project, a deflecting magnet will be incorporated into the pTOF design for simultaneous measurements of shock- and compression-bang times in D(3)He-filled surrogate implosions using D(3)He protons and DD-neutrons, respectively.

Charged-particle spectroscopy for diagnosing shock ρR and strength in NIF implosions.

The compact Wedge Range Filter (WRF) proton spectrometer was developed for OMEGA and transferred to the National Ignition Facility (NIF) as a National Ignition Campaign diagnostic. The WRF measures the spectrum of protons from D-(3)He reactions in tuning-campaign implosions containing D and (3)He gas; in this work we report on the first proton spectroscopy measurement on the NIF using WRFs. The energy downshift of the 14.7-MeV proton is directly related to the total ρR through the plasma stopping power. Additionally, the shock proton yield is measured, which is a metric of the final merged shock strength.

Upgrade of the MIT Linear Electrostatic Ion Accelerator (LEIA) for nuclear diagnostics development for Omega, Z and the NIF.

The MIT Linear Electrostatic Ion Accelerator (LEIA) generates DD and D(3)He fusion products for the development of nuclear diagnostics for Omega, Z, and the National Ignition Facility (NIF). Significant improvements to the system in recent years are presented. Fusion reaction rates, as high as 10(7) s(-1) and 10(6) s(-1) for DD and D(3)He, respectively, are now well regulated with a new ion source and electronic gas control system. Charged fusion products are more accurately characterized, which allows for better calibration of existing nuclear diagnostics. In addition, in situ measurements of the on-target beam profile, made with a CCD camera, are used to determine the metrology of the fusion-product source for particle-counting applications. Finally, neutron diagnostics development has been facilitated by detailed Monte Carlo N-Particle Transport (MCNP) modeling of neutrons in the accelerator target chamber, which is used to correct for scattering within the system. These recent improvements have resulted in a versatile platform, which continues to support the existing nuclear diagnostics while simultaneously facilitating the development of new diagnostics in aid of the National Ignition Campaign at the National Ignition Facility.

Modulators of calcium and potassium channels: their effects on endothelin-1 binding to cardiac membranes.

Endothelin-1 (ET-1) causes long-lasting vasoconstriction associated with a prolonged elevation of intracellular free Ca2+. Because this may be mediated through an effect on membrane ion channels, we investigated the effects of the dihydropyridine calcium channel antagonist nifedipine; two structurally distinct K+ channel openers, pinacidil and levcromakalim; and the inactive stereoisomer of levcromakalim (D-cromakalim), as well as ET-1 and ET-3, on binding of 125I-labeled endothelin-1 to rat cardiac membranes. Specific binding of 125I-ET-1 was inhibited in a concentration-dependent manner by unlabeled ET-1 (IC50 = 1.56 +/- 0.78 nM; slope = -0.49 +/- 0.10) and ET-3 (IC50 = 314 +/- 54 nM; slope = -0.34 +/- 0.11). Nifedipine, in concentrations < or = 10(-5) M, did not affect 125I-ET-1 binding. However, levcromakalim significantly inhibited 125I-ET-1 binding (maximum binding 49 4/- 9%; p = 0.04), whereas the inactive isomer, D-cromakalim, had no effect. Pinacidil also inhibited 125I-ET-1 binding, although to a lesser extent than levcromakalim (maximum binding 63 +/- 7%). These findings provide evidence for a stereospecific interaction between K(+)-channel openers and ET-1 binding in rat cardiac membranes. Because the slope of the logistic fit was substantially less than unity, and the effects of pinacidil and levcromakalim were incomplete, there may be two or more receptors for ET-1 in rat heart, only one of which is sensitive to K(+)-channel openers.

The potassium channel opener BRL 38227 inhibits binding of [125I]-labelled endothelin-1 to rat cardiac membranes.

Binding of [125I]-labelled endothelin-1 (ET-1) to rat cardiac membranes and the effects of endothelin-1 (ET-1), endothelin-3 (ET-3), the calcium channel antagonist nifedipine, and both enantiomers of the potassium channel opener cromakalim (BRL 34915) on binding have been examined. Specific binding of [125I]-ET-1 was inhibited in a concentration dependent manner by both unlabelled ET-1 (10(-12)-10(-7) M) and ET-3 (10(-12)-10(-6) M). Nifedipine (10(-11)-10(-5) M) did not affect [125I]-ET-1 binding. However, BRL 38227 (10(-11)-10(-5) M), the biologically active isomer of cromakalim, significantly inhibited [125I]-ET-1 binding. The inactive isomer, BRL 38226 (10(-11)-10(-5) M) had no effect. These findings provide the first evidence for a stereospecific interaction between BRL 38227 and an ET-1 binding site in rat cardiac membranes.

Lithium pretreatment affects renal and systemic responses to angiotensin II infusion in normal man.

1. Renal and systemic responses to infusion of angiotensin II (1.25 and 2.5 ng min-1 kg-1 body weight) were examined in ten normal males 12 h after single doses of 750 mg of lithium carbonate, 250 mg of lithium carbonate (n = 6) or placebo. 2. Baseline mean arterial pressure [mean (SEM)] was higher after 750 mg of lithium [93.1 (1.7) versus 89.5 (1.9 mmHg, P = 0.014], and the subsequent rise in blood pressure during angiotensin II infusion was lower [8.2 (1.8) versus 12.2 (2.4) mmHg, P less than 0.02]. 3. Lithium at a dose of 750 mg increased overnight urinary sodium excretion before the study. The fall in fractional sodium excretion during angiotensin II infusion was reduced after pretreatment with 750 mg of lithium [750 mg of lithium, 2.73 (0.24) to 1.34 (0.08)%; placebo, 2.69 (0.26) to 1.01 (0.11)%; P = 0.02]. The increases in effective filtration fraction [750 mg of lithium, 5.4 (1.0)%; placebo, 8.6 (0.7)%; P less than 0.05] and total effective renal vascular resistance [750 mg of lithium, 3700 (390) dyn s cm-5; placebo 5100 (460) dyn s cm-5; P = 0.03] during angiotensin II infusion were also attenuated after 750 mg of lithium. Responses after 250 mg of lithium did not differ from those after placebo. 4. The fall in plasma renin activity and the increase in plasma aldosterone concentration during angiotensin II infusion were similar on each study day. 5. Renal responses to exogenous angiotensin II are altered after pretreatment with a 750 mg dose of lithium in normal man. This dose of lithium is not an inert marker of sodium handling.

The sensitivity of human blood platelets to the aggregating agent ADP during different dietary sodium intakes in healthy men.

We have investigated the effect of varying sodium intake on the renin-angiotensin system, ADP-induced platelet aggregation in vitro, and blood 5-HT concentrations in 9 male volunteers. Systolic blood pressure was slightly reduced during a low sodium diet, whereas the diastolic pressure remained unchanged. Plasma renin activity and aldosterone concentration both fell significantly when sodium intake was increased; plasma angiotensin II concentration also fell, but not significantly. There was a significant fall in haematocrit after an increased sodium intake, but there was no change in the whole-blood platelet count after correcting for this. There were no significant changes in either total (i.e. PRP) or platelet 5-HT concentrations. The extent of platelet aggregation induced by 5 and 20 mumol.l-1 of ADP increased significantly when dietary sodium intake was increased. When compared with low or normal sodium intakes, lower concentrations of ADP were required to produce 50% of maximum aggregation after a high sodium intake. The 5-HT2 receptor antagonist ketanserin (1 mumol.l-1 in vitro) reduced the extent of aggregation induced by 5 mumol.l-1 ADP after the volunteers had taken a high sodium diet, whereas the angiotensin II receptor antagonist saralasin (1 nmol.l-1) increased the rate of aggregation after the low sodium diet. Thus, during a high sodium intake, human platelets become more sensitive to the aggregating agent ADP. It is possible that this effect is mediated via platelet 5-HT2 receptors, since ketanserin abolished the increase in salt-induced aggregation seen with 5 mumol.l-1 ADP.

Blood pressure, renin-angiotensin-aldosterone axis and cortisol changes during withdrawal from alcohol.

Nineteen patients who had been drinking on the day of admission had significantly raised levels of renin, aldosterone and cortisol and a non-significant increase in angiotensin II. Five patients were hypertensive (systolic blood pressure greater than 160 mmHg or diastolic blood pressure greater than 95 mmHg) at some point during the study and there was a significant tachycardia. Over the first 4 days of abstinence there were falls in all of the measures reaching significance for renin, cortisol, systolic blood pressure and pulse. There were no correlations between blood pressure and any of the hormones measured although there was a significant association between pulse and both aldosterone and cortisol. It is concluded that the activity in the renin-angiotensin axis and hypothalamic-pituitary-adrenal axis is not responsible for alcohol-related changes in blood pressure.