Invasive Pneumococcal Disease in UK Children <1 Year of Age in the Post–13-Valent Pneumococcal Conjugate Vaccine Era: What Are the Risks Now?

Background Invasive pneumococcal disease (IPD) has declined significantly since the introduction of pneumococcal conjugate vaccines (PCVs). It is not known whether certain infant populations remain at higher risk of IPD in countries with established 13-valent PCV (PCV13) programs. We aimed to describe the epidemiology, clinical characteristics, serotype distribution, and outcomes of IPD in infants, and to estimate the relative risk of PCV13-type, non-PCV13-type, and overall IPD in premature infants compared to term infants during a 4-year period after the PCV13 program was established. Methods This was a prospective, enhanced national surveillance of laboratory-confirmed IPD in England in infants aged <1 year diagnosed during 2013–2016. Results There were 517 cases of IPD (incidence: 19/100000 infants). Incidence was significantly higher in premature infants compared with those born at term (49/100000 vs 17/100000; incidence rate ratio [IRR], 2.87; P < .001), with infants born before 28 weeks’ gestation having the highest incidence (150/100000; IRR, 8.8; P < .001). Of the 454 IPD cases with serotyped isolates, most were caused by non-PCV13 serotypes (369 cases, 71.4%), with 85 cases (16.4%) due to PCV13 serotypes. There were 31 deaths (case fatality rate [CFR], 6.2% [95% confidence interval, 4.3%–8.6%]). Premature infants did not have a higher CFR than term infants (P = .62). Conclusions IPD incidence in infants remains lower than rates reported prior to PCV7 introduction in England. The risk of IPD remains significantly higher in premature infants compared to infants born at term, for both PCV13 and non-PCV13 serotypes. Any changes to the infant PCV13 immunization schedule may disproportionally affect premature infants

Signal Propagation in Feedforward Neuronal Networks with Unreliable Synapses

In this paper, we systematically investigate both the synfire propagation and firing rate propagation in feedforward neuronal network coupled in an all-to-all fashion. In contrast to most earlier work, where only reliable synaptic connections are considered, we mainly examine the effects of unreliable synapses on both types of neural activity propagation in this work. We first study networks composed of purely excitatory neurons. Our results show that both the successful transmission probability and excitatory synaptic strength largely influence the propagation of these two types of neural activities, and better tuning of these synaptic parameters makes the considered network support stable signal propagation. It is also found that noise has significant but different impacts on these two types of propagation. The additive Gaussian white noise has the tendency to reduce the precision of the synfire activity, whereas noise with appropriate intensity can enhance the performance of firing rate propagation. Further simulations indicate that the propagation dynamics of the considered neuronal network is not simply determined by the average amount of received neurotransmitter for each neuron in a time instant, but also largely influenced by the stochastic effect of neurotransmitter release. Second, we compare our results with those obtained in corresponding feedforward neuronal networks connected with reliable synapses but in a random coupling fashion. We confirm that some differences can be observed in these two different feedforward neuronal network models. Finally, we study the signal propagation in feedforward neuronal networks consisting of both excitatory and inhibitory neurons, and demonstrate that inhibition also plays an important role in signal propagation in the considered networks.Comment: 33pages, 16 figures; Journal of Computational Neuroscience (published

DNA Electrophoretic Migration Patterns Change after Exposure of Jurkat Cells to a Single Intense Nanosecond Electric Pulse

Intense nanosecond pulsed electric fields (nsPEFs) interact with cellular membranes and intracellular structures. Investigating how cells respond to nanosecond pulses is essential for a) development of biomedical applications of nsPEFs, including cancer therapy, and b) better understanding of the mechanisms underlying such bioelectrical effects. In this work, we explored relatively mild exposure conditions to provide insight into weak, reversible effects, laying a foundation for a better understanding of the interaction mechanisms and kinetics underlying nsPEF bio-effects. In particular, we report changes in the nucleus of Jurkat cells (human lymphoblastoid T cells) exposed to single pulses of 60 ns duration and 1.0, 1.5 and 2.5 MV/m amplitudes, which do not affect cell growth and viability. A dose-dependent reduction in alkaline comet-assayed DNA migration is observed immediately after nsPEF exposure, accompanied by permeabilization of the plasma membrane (YO-PRO-1 uptake). Comet assay profiles return to normal within 60 minutes after pulse delivery at the highest pulse amplitude tested, indicating that our exposure protocol affects the nucleus, modifying DNA electrophoretic migration patterns

Leading an Interprofessional Geriatric Clinical Skills Fair: A Train the Trainer Seminar

Objectives • Practice teaching skills related to interprofessional education (IPE) and geriatric competencies • Formulate an Action Plan and prepare to introduce an Interprofessional Geriatric Clinical Skills Fair at their own institutions • Recognize essential elements of a measurement tool that evaluates the effectiveness of an Interprofessional Geriatric Clinical Skills Fai

Tuberculosis in cattle: the results of the four-area project

<p/> <p>The four-area project was undertaken to further assess the impact of badger removal on the control of tuberculosis in cattle herds in Ireland. It was conducted between 1997 and 2002 in matched removal and reference areas in four counties, namely Cork, Donegal, Kilkenny and Monaghan, representing a wide range of Irish farming environments. In the removal areas, a proactive programme of badger removal was conducted, on two or three occasions each year, whereas in the reference areas, badger removal was entirely reactive following severe outbreaks of tuberculosis amongst cattle. A detailed statistical analysis of this study has already been presented by Griffin <it>et al. </it><abbrgrp><abbr bid="B13">13</abbr></abbrgrp>; this paper presents further, mainly descriptive, findings from the study. In total, 2,360 badgers were captured in the removal areas of which 450 (19.5%) were considered positive for tuberculosis and 258 badgers were captured in the reference areas, with 57 (26.1%) positive for tuberculosis. The annual incidence of confirmed herd restrictions was lower in the removal area compared to the reference area in every year of the study period in each of the four counties. These empirical findings were consistent with the hazard ratios found by Griffin <it>et al. </it><abbrgrp><abbr bid="B13">13</abbr></abbrgrp>. Further, the effect of proactive badger removal on cattle tuberculosis in the four-area project and in the earlier east-Offaly project, as measured using the number of reactors per 1,000 cattle tested, were very similar, providing compelling evidence of the role of badgers in the epidemiology of tuberculosis in Irish cattle herds. The validity of the four-area project was discussed in detail. Efforts to minimise badger-to-cattle transmission in Ireland must be undertaken in association with the current comprehensive control programme, which has effectively minimised opportunities for cattle-to-cattle transmission.</p

The Developmental Significance of Adolescent Romantic Relationships: Parent and Peer Predictors of Engagement and Quality at Age 15

From a longitudinal sample (n = 957; 49.9% male; 77.3% White/non-Hispanic) of participants studied from infancy through age 15, adolescents’ depth of engagement in, and quality of romantic relationships were predicted from early and contemporaneous parent–child interactive quality and peer social competence. High quality maternal parenting and peer experiences prior to and during adolescence tended to be negatively associated with the depth of engagement in this domain for the full sample, yet positively associated with the quality of adolescents’ romantic relationships for the sub-set of individuals currently dating at age 15. Results reconcile contrasting views of the origins of romantic relationship engagement and quality and the positive versus negative developmental salience of romantic relationships in adolescence

Design principles for riboswitch function

Scientific and technological advances that enable the tuning of integrated regulatory components to match network and system requirements are critical to reliably control the function of biological systems. RNA provides a promising building block for the construction of tunable regulatory components based on its rich regulatory capacity and our current understanding of the sequence–function relationship. One prominent example of RNA-based regulatory components is riboswitches, genetic elements that mediate ligand control of gene expression through diverse regulatory mechanisms. While characterization of natural and synthetic riboswitches has revealed that riboswitch function can be modulated through sequence alteration, no quantitative frameworks exist to investigate or guide riboswitch tuning. Here, we combined mathematical modeling and experimental approaches to investigate the relationship between riboswitch function and performance. Model results demonstrated that the competition between reversible and irreversible rate constants dictates performance for different regulatory mechanisms. We also found that practical system restrictions, such as an upper limit on ligand concentration, can significantly alter the requirements for riboswitch performance, necessitating alternative tuning strategies. Previous experimental data for natural and synthetic riboswitches as well as experiments conducted in this work support model predictions. From our results, we developed a set of general design principles for synthetic riboswitches. Our results also provide a foundation from which to investigate how natural riboswitches are tuned to meet systems-level regulatory demands

Primary cardiac sarcoma presenting as acute left-sided heart failure

Primary cardiac sarcomas are rare malignant tumors of the heart. Clinical features depend on the site of tumor and vary from symptoms of congestive heart failure to thromboembolism and arrhythmias. Echocardiography is helpful but definitive diagnosis is established by histopathology. Surgical resection is the mainstay of treatment, and the role of chemotherapy and radiotherapy is unclear. We report a case of primary cardiac sarcoma which presented with signs and symptoms of acute left-sided heart failure

The BrainMap strategy for standardization, sharing, and meta-analysis of neuroimaging data

<p>Abstract</p> <p>Background</p> <p>Neuroimaging researchers have developed rigorous community data and metadata standards that encourage meta-analysis as a method for establishing robust and meaningful convergence of knowledge of human brain structure and function. Capitalizing on these standards, the BrainMap project offers databases, software applications, and other associated tools for supporting and promoting quantitative coordinate-based meta-analysis of the structural and functional neuroimaging literature.</p> <p>Findings</p> <p>In this report, we describe recent technical updates to the project and provide an educational description for performing meta-analyses in the BrainMap environment.</p> <p>Conclusions</p> <p>The BrainMap project will continue to evolve in response to the meta-analytic needs of biomedical researchers in the structural and functional neuroimaging communities. Future work on the BrainMap project regarding software and hardware advances are also discussed.</p