BCG Vaccination in HIV-Infected Children

Despite the use of Bacillus Calmette-Guérin (BCG) vaccination for many years, infants and young children exposed to adults with infectious forms of tuberculosis (TB) are at high risk of developing complicated TB disease. This risk is much higher among HIV-infected children, and data on BCG protective efficacy in HIV-infected children is lacking. Recent research on BCG safety in HIV-infected infants has resulted in policy shifts, but implementation is challenging. New approaches to preventing TB among infants and children, particularly HIV-infected infants, are needed. This paper briefly reviews BCG safety and efficacy considerations in HIV-infected infants and discusses other approaches to preventing TB, including new TB vaccines and vaccination strategies

Weight-band dosing tables: Simplifying paediatric ART

One of the obstacles to scaling up paediatric antiretroviral therapy (ART) coverage in resource-limited settings (RLS) is the relative complexity of paediatric dosing. There is a need to simplify ART in order to facilitate treatment initiation and ongoing management of infants and children by healthcare providers, as well as to support adherence within the home. This article reviews the development of weight band dosing tables as a simplification strategy for the delivery of paediatric ART

The c-terminal extension of a hybrid immunoglobulin A/G heavy chain is responsible for its Golgi-mediated sorting to the vacuole

We have assessed the ability of the plant secretory pathway to handle the expression of complex heterologous proteins by investigating the fate of a hybrid immunoglobulin A/G in tobacco cells. Although plant cells can express large amounts of the antibody, a relevant proportion is normally lost to vacuolar sorting and degradation. Here we show that the synthesis of high amounts of IgA/G does not impose stress on the plant secretory pathway. Plant cells can assemble antibody chains with high efficiency and vacuolar transport occurs only after the assembled immunoglobulins have traveled through the Golgi complex. We prove that vacuolar delivery of IgA/G depends on the presence of a cryptic sorting signal in the tailpiece of the IgA/G heavy chain. We also show that unassembled light chains are efficiently secreted as monomers by the plant secretory pathway

High-Volume Oil Discovery in Clinton County, Kentucky

The Syndicated Options Limited of Austria No. 9372 Ferguson Brothers well, located in southern Clinton County, Kentucky, has recently produced oil at reported initial rates of 400 to 130 barrels per hour. Cumulative production for the first 8 weeks of flow following discovery on September 25, 1990, is reported to be nearly 150,000 barrels. The well is the result of deepening a previously abandoned well. Production is from the Middle Ordovician High Bridge Group (equivalent to the Stones River Group of Tennessee) at a depth of 1,008 feet. The reservoir is apparently a fractured carbonate rock, and the fracturing is probably associated with reactivation of a basement fault during the Acadian orogeny of Early to Late Devonian age

Tight multi-messenger constraints on the neutron star equation of state from GW170817 and a forward model for kilonova light curve synthesis

We present a rapid analytic framework for predicting kilonova light curves following neutron star (NS) mergers, where the main input parameters are binary-based properties measurable by gravitational wave detectors (chirp mass and mass ratio, orbital inclination) and properties dependent on the nuclear equation of state (tidal deformability, maximum NS mass). This enables synthesis of a kilonova sample for any NS source population, or determination of the observing depth needed to detect a live kilonova given gravitational wave source parameters in low latency. We validate this code, implemented in the public MOSFiT package, by fitting it to GW170817. A Bayes factor analysis overwhelmingly ($B>10^{10}$) favours the inclusion of an additional luminosity source in addition to lanthanide-poor dynamical ejecta during the first day. This is well fit by a shock-heated cocoon model, though differences in the ejecta structure, opacity or nuclear heating rate cannot be ruled out as alternatives. The emission thereafter is dominated by a lanthanide-rich viscous wind. We find the mass ratio of the binary is $q=0.92\pm0.07$ (90% credible interval). We place tight constraints on the maximum stable NS mass, $M_{\rm TOV}=2.17^{+0.08}_{-0.11}$ M$_\odot$. For a uniform prior in tidal deformability, the radius of a 1.4 M$_\odot$ NS is $R_{1.4}\sim 10.7$ km. Re-weighting with a prior based on equations of state that support our credible range in $M_{\rm TOV}$, we derive a final measurement $R_{1.4}=11.06^{+1.01}_{-0.98}$ km. Applying our code to the second gravitationally-detected neutron star merger, GW190425, we estimate that an associated kilonova would have been fainter (by $\sim0.7$ mag at one day post-merger) and declined faster than GW170817, underlining the importance of tuning follow-up strategies individually for each GW-detected NS merger.Comment: Updated to match accepted version in MNRA

Evoked responses to rhythmic visual stimulation vary across sources of intrinsic alpha activity in humans

Rhythmic flickering visual stimulation produces steady-state visually evoked potentials (SSVEPs) in electroencephalogram (EEG) recordings. Based on electrode-level analyses, two dichotomous models of the underpinning mechanisms leading to SSVEP generation have been proposed: entrainment or superposition, i.e., phase-alignment or independence of endogenous brain oscillations from flicker-induced oscillations, respectively. Electrode-level analyses, however, represent an averaged view of underlying ‘source-level’ activity, at which variability in SSVEPs may lie, possibly suggesting the co-existence of multiple mechanisms. To probe this idea, we investigated the variability of SSVEPs derived from the sources underpinning scalp EEG responses during presentation of a flickering radial checkerboard. Flicker was presented between 6 and 12 Hz in 1 Hz steps, and at individual alpha frequency (IAF i.e., the dominant frequency of endogenous alpha oscillatory activity). We tested whether sources of endogenous alpha activity could be dissociated according to evoked responses to different flicker frequencies relative to IAF. Occipitoparietal sources were identified by temporal independent component analysis, maximal resting-state alpha power at IAF and source localisation. The pattern of SSVEPs to rhythmic flicker relative to IAF was estimated by correlation coefficients, describing the correlation between the peak-to-peak amplitude of the SSVEP and the absolute distance of the flicker frequency from IAF across flicker conditions. We observed extreme variability in correlation coefficients across sources, ranging from −0.84 to 0.93, with sources showing largely different coefficients co-existing within subjects. This result demonstrates variation in evoked responses to flicker across sources of endogenous alpha oscillatory activity. Data support the idea of multiple SSVEP mechanisms

Versatile Diphosphine Chelators for Radiolabeling Peptides with ^99mTc and ⁶⁴Cu

We have developed a diphosphine (DP) platform for radiolabeling peptides with 99mTc and 64Cu for molecular SPECT and PET imaging, respectively. Two diphosphines, 2,3-bis(diphenylphosphino)maleic anhydride (DP Ph) and 2,3-bis(di- p-tolylphosphino)maleic anhydride (DP Tol), were each reacted with a Prostate Specific Membrane Antigen-targeted dipeptide (PSMAt) to yield the bioconjugates DP Ph-PSMAt and DP Tol-PSMAt, as well as an integrin-targeted cyclic peptide, RGD, to yield the bioconjugates DP Ph-RGD and DP Tol-RGD. Each of these DP-PSMAt conjugates formed geometric cis/ trans-[MO 2(DP X-PSMAt) 2] + (M = 99mTc, 99gTc, natRe; X = Ph, Tol) complexes when reacted with [MO 2] + motifs. Furthermore, both DP Ph-PSMAt and DP Tol-PSMAt could be formulated into kits containing reducing agent and buffer components, enabling preparation of the new radiotracers cis/ trans-[ 99mTcO 2(DP Ph-PSMAt) 2] + and cis/ trans-[ 99mTcO 2(DP Tol-PSMAt) 2] + from aqueous 99mTcO 4 - in 81% and 88% radiochemical yield (RCY), respectively, in 5 min at 100 °C. The consistently higher RCYs observed for cis/ trans-[ 99mTcO 2(DP Tol-PSMAt) 2] + are attributed to the increased reactivity of DP Tol-PSMAt over DP Ph-PSMAt. Both cis/ trans-[ 99mTcO 2(DP Ph-PSMAt) 2] + and cis/ trans-[ 99mTcO 2(DP Tol-PSMAt) 2] + exhibited high metabolic stability, and in vivo SPECT imaging in healthy mice revealed that both new radiotracers cleared rapidly from circulation, via a renal pathway. These new diphosphine bioconjugates also furnished [ 64Cu(DP X-PSMAt) 2] + (X = Ph, Tol) complexes rapidly, in a high RCY (&gt;95%), under mild conditions. In summary, the new DP platform is versatile: it enables straightforward functionalization of targeting peptides with a diphosphine chelator, and the resulting bioconjugates can be simply radiolabeled with both the SPECT and PET radionuclides, 99mTc and 64Cu, in high RCYs. Furthermore, the DP platform is amenable to derivatization to either increase the chelator reactivity with metallic radioisotopes or, alternatively, modify the radiotracer hydrophilicity. Functionalized diphosphine chelators thus have the potential to provide access to new molecular radiotracers for receptor-targeted imaging. </p

Prevalence and Determinants of Vitamin D Deficiency in 1825 Cape Town Primary Schoolchildren: A Cross-Sectional Study

Vitamin D deficiency (25-hydroxyvitamin D[25(OH)D] &lt;50 nmol/L) is common among adults in Cape Town, South Africa, but studies investigating vitamin D status of children in this setting are lacking. We conducted a cross-sectional study to determine the prevalence and determinants of vitamin D deficiency in 1825 Cape Town schoolchildren aged 6&ndash;11 years. Prevalence of vitamin D deficiency was 7.6% (95% Confidence Interval [CI] 6.5% to 8.9%). Determinants of vitamin D deficiency included month of sampling (adjusted odds ratio [aOR] for July&ndash;September vs. January&ndash;March 10.69, 95% CI 5.02 to 22.77; aOR for October&ndash;December vs. January&ndash;March 6.73, 95% CI 2.82 to 16.08), older age (aOR 1.25 per increasing year, 95% CI: 1.01&ndash;1.53) and higher body mass index (BMI; aOR 1.24 per unit increase in BMI-for-age Z-score, 95% CI: 1.03&ndash;1.49). In a subset of 370 participants in whom parathyroid hormone (PTH) concentrations were measured; these were inversely related to serum 25(OH)D concentrations (p &lt; 0.001). However, no association between participants with hyperparathyroidism (PTH &gt;6.9 pmol/L) and vitamin D deficiency was seen (p = 0.42). In conclusion, we report that season is the major determinant of vitamin D status among Cape Town primary schoolchildren, with prevalence of vitamin D deficiency ranging from 1.4% in January&ndash;March to 22.8% in July&ndash;September