Fifteen minute consultation: Managing neonatal and childhood herpes encephalitis

Herpes simplex encephalitis (HSE) is the most common single cause of viral encephalitis in infants and children. Treated or untreated, it can be associated with considerable morbidity and mortality, and its presentation is usually insidious and non-specific. Prompt and careful investigation is important in order to establish the diagnosis so that treatment can be optimised. We address some common questions arising when diagnosing and treating presumed HSE throughout childhood

Characterizing Hydrogen Storage Media: Understanding the Interior Pore Structure of a Cu3BTC2 Metal-Organic Framework Infiltrated with NaAlH4

Preliminary results support the nano-confinement of sodium alanate within the pores of a Cu{sub 3}BTC{sub 2} MOF substrate. Increased {sup 1}H and {sup 27}Al NMR T{sub 1} relaxation rates indicate a close proximity of infiltrated sodium alante to the paramagnetic Cu{sup 2+} ions on the BTC paddlewheel units. This is in support of the theory that an interaction due to the electronegative framework with the sodium alanate facilitates thermodynamically-favorable hydrogen adsorption and desorption. Further studies can elucidate the local electronic environment of the sodium ions, further supporting a charge-transfer mechanism as the driving force for thermodynamically-favorable hydrogen adsorption and desorption

Identification and Characterization of Novel Mutations in the Human Gene Encoding the Catalytic Subunit Calpha of Protein Kinase A (PKA)

The genes PRKACA and PRKACB encode the principal catalytic (C) subunits of protein kinase A (PKA) Cα and Cβ, respectively. Cα is expressed in all eukaryotic tissues examined and studies of Cα knockout mice demonstrate a crucial role for Cα in normal physiology. We have sequenced exon 2 through 10 of PRKACA from the genome of 498 Norwegian donors and extracted information about PRKACA mutations from public databases. We identified four interesting nonsynonymous point mutations, Arg45Gln, Ser109Pro, Gly186Val, and Ser263Cys, in the Cα1 splice variant of the kinase. Cα variants harboring the different amino acid mutations were analyzed for kinase activity and regulatory (R) subunit binding. Whereas mutation of residues 45 and 263 did not alter catalytic activity or R subunit binding, mutation of Ser109 significantly reduced kinase activity while R subunit binding was unaltered. Mutation of Cα Gly186 completely abrogated kinase activity and PKA type I but not type II holoenzyme formation. Gly186 is located in the highly conserved DFG motif of Cα and mutation of this residue to Val was predicted to result in loss of binding of ATP and Mg2+, which may explain the kinetic inactivity. We hypothesize that individuals born with mutations of Ser109 or Gly186 may be faced with abnormal development and possibly severe disease

Measurement of the Electric Form Factor of the Neutron at Q^2 = 0.3-0.8 (GeV/c)^2

The electric form factor of the neutron, G_En, has been measured at the Mainz Microtron by recoil polarimetry in the quasielastic D(e_pol,e'n_pol)p reaction. Three data points have been extracted at squared four-momentum transfers Q^2 = 0.3, 0.6 and 0.8 (GeV/c)^2. Corrections for nuclear binding effects have been applied.Comment: 9 pages, 7 figures, 2 tables. Accepted for publication in EPJ

Deletion of the GABAA α2-subunit does not alter self dministration of cocaine or reinstatement of cocaine seeking

Rationale GABAA receptors containing α2-subunits are highly represented in brain areas that are involved in motivation and reward, and have been associated with addiction to several drugs, including cocaine. We have shown previously that a deletion of the α2-subunit results in an absence of sensitisation to cocaine. Objective We investigated the reinforcing properties of cocaine in GABAA α2-subunit knockout (KO) mice using an intravenous self-administration procedure. Methods α2-subunit wildtype (WT), heterozygous (HT) and KO mice were trained to lever press for a 30 % condensed milk solution. After implantation with a jugular catheter, mice were trained to lever press for cocaine (0.5 mg/kg/infusion) during ten daily sessions. Responding was extinguished and the mice tested for cue- and cocaine-primed reinstatement. Separate groups of mice were trained to respond for decreasing doses of cocaine (0.25, 0.125, 0.06 and 0.03 mg/kg). Results No differences were found in acquisition of lever pressing for milk. All genotypes acquired self-administration of cocaine and did not differ in rates of self-administration, dose dependency or reinstatement. However, whilst WT and HT mice showed a dose-dependent increase in lever pressing during the cue presentation, KO mice did not. Conclusions Despite a reported absence of sensitisation, motivation to obtain cocaine remains unchanged in KO and HT mice. Reinstatement of cocaine seeking by cocaine and cocaine-paired cues is also unaffected. We postulate that whilst not directly involved in reward perception, the α2-subunit may be involved in modulating the “energising” aspect of cocaine’s effects on reward-seeking

3D Real-Time Echocardiography Combined with Mini Pressure Wire Generate Reliable Pressure-Volume Loops in Small Hearts

BACKGROUND: Pressure-volume loops (PVL) provide vital information regarding ventricular performance and pathophysiology in cardiac disease. Unfortunately, acquisition of PVL by conductance technology is not feasible in neonates and small children due to the available human catheter size and resulting invasiveness. The aim of the study was to validate the accuracy of PVL in small hearts using volume data obtained by real-time three-dimensional echocardiography (3DE) and simultaneously acquired pressure data. METHODS: In 17 piglets (weight range: 3.6–8.0 kg) left ventricular PVL were generated by 3DE and simultaneous recordings of ventricular pressure using a mini pressure wire (PVL3D). PVL3D were compared to conductance catheter measurements (PVLCond) under various hemodynamic conditions (baseline, alpha-adrenergic stimulation with phenylephrine, beta-adrenoreceptor-blockage using esmolol). In order to validate the accuracy of 3D volumetric data, cardiac magnetic resonance imaging (CMR) was performed in another 8 piglets. RESULTS: Correlation between CMR- and 3DE-derived volumes was good (enddiastolic volume: mean bias -0.03ml ±1.34ml). Computation of PVL3D in small hearts was feasible and comparable to results obtained by conductance technology. Bland-Altman analysis showed a low bias between PVL3D and PVLCond. Systolic and diastolic parameters were closely associated (Intraclass-Correlation Coefficient for: systolic myocardial elastance 0.95, arterial elastance 0.93, diastolic relaxation constant tau 0.90, indexed end-diastolic volume 0.98). Hemodynamic changes under different conditions were well detected by both methods (ICC 0.82 to 0.98). Inter- and intra-observer coefficients of variation were below 5% for all parameters. CONCLUSIONS: PVL3D generated from 3DE combined with mini pressure wire represent a novel, feasible and reliable method to assess different hemodynamic conditions of cardiac function in hearts comparable to neonate and infant size. This methodology may be integrated into clinical practice and cardiac catheterization programs and has the capability to contribute to clinical decision making even in small hearts

2,000 Families: identifying the research potential of an origins-of-migration study

Despite recent advances, critical areas in the analysis of European migration remain underdeveloped. We have only a limited understanding of the consequences of migration for migrants and their descendants, relative to staying behind; and our insights of intergenerational transmission is limited to two generations of those living in the destination countries. These limitations stem from a paucity of studies that incorporate comparison with non-migrants – and return migrants – in countries of origin and which trace processes of intergenerational transmission over multiple generations. This paper outlines the theoretical and methodological discussions in the field, design and data of the 2,000 Families study. The study comprises almost 50,000 members of migrant and non-migrant Turkish families across three family generations, living in Turkey and eight European countries. We provide indicative findings from the study, framed within a theoretical perspective of “dissimilation” from origins, and reflect on its potential for future migration research

Understanding the links between human health, ecosystem health, and food systems in Small Island Developing States using stakeholder-informed causal loop diagrams

This is the final version. Available on open access from Public Library of Science via the DOI in this record. Data Availability: All relevant data are within the paper and its Supporting Information files.Globalized food systems are a major driver of climate change, biodiversity loss, environmental degradation, and the increasing prevalence of overweight and obesity in society. Small Island Developing States (SIDS) are particularly sensitive to the negative effects of rapid environmental change, with many also exhibiting a heavy reliance on food imports and high burdens of nutrition-related disease, resulting in calls to (re)localize their food systems. Such a transition represents a complex challenge, with adaptation interventions in one part of the food system contingent on the success of interventions in other parts. To help address this challenge, we used group model-building techniques from the science of system dynamics to engage food system stakeholders in Caribbean and Pacific SIDS. Our aim was to understand the drivers of unhealthy and unsustainable food systems in SIDS, and the potential role that increased local food production could play in transformative adaptation. We present two causal loop diagrams (CLDs) considered helpful in designing resilience-enhancing interventions in local food systems. These CLDs represent 'dynamic hypotheses' and provide starting points that can be adapted to local contexts for identifying food system factors, understanding the interactions between them, and co-creating and implementing adaptation interventions, particularly in SIDS. The results can help guide understanding of complexity, assist in the co-creation of interventions, and reduce the risk of maladaptive consequences.UK Research and Innovatio

A Measurement of the Electric Form Factor of the Neutron through d⃗(e⃗,e′n)p\vec{d}(\vec{e},e'n)p at Q2=0.5Q^2 = 0.5 (GeV/c)2^2

We report the first measurement of the neutron electric form factor $G_E^n$ via $\vec{d}(\vec{e},e'n)p$ using a solid polarized target. $G_E^n$ was determined from the beam-target asymmetry in the scattering of longitudinally polarized electrons from polarized deuterated ammonia, $^{15}$ND$_3$. The measurement was performed in Hall C at Thomas Jefferson National Accelerator Facility (TJNAF) in quasi free kinematics with the target polarization perpendicular to the momentum transfer. The electrons were detected in a magnetic spectrometer in coincidence with neutrons in a large solid angle segmented detector. We find $G_E^n = 0.04632\pm0.00616 (stat.) \pm0.00341 (syst.)$ at $Q^2 = 0.495$ (GeV/c)$^2$.Comment: Latex2e 5 pages, 3 figure