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In view of the increasing complexity of both cardiovascular implantable electronic devices (CIEDs) and patients in the current era, practice guidelines, by necessity, have become increasingly specific. This document is an expert consensus statement that has been developed to update and further delineate indications and management of CIEDs in pediatric patients, defined as ≤21 years of age, and is intended to focus primarily on the indications for CIEDs in the setting of specific disease categories. The document also highlights variations between previously published adult and pediatric CIED recommendations and provides rationale for underlying important differences. The document addresses some of the deterrents to CIED access in low- and middle-income countries and strategies to circumvent them. The document sections were divided up and drafted by the writing committee members according to their expertise. The recommendations represent the consensus opinion of the entire writing committee, graded by class of recommendation and level of evidence. Several questions addressed in this document either do not lend themselves to clinical trials or are rare disease entities, and in these instances recommendations are based on consensus expert opinion. Furthermore, specific recommendations, even when supported by substantial data, do not replace the need for clinical judgment and patient-specific decision-making. The recommendations were opened for public comment to Pediatric and Congenital Electrophysiology Society (PACES) members and underwent external review by the scientific and clinical document committee of the Heart Rhythm Society (HRS), the science advisory and coordinating committee of the American Heart Association (AHA), the American College of Cardiology (ACC), and the Association for European Paediatric and Congenital Cardiology (AEPC). The document received endorsement by all the collaborators and the Asia Pacific Heart Rhythm Society (APHRS), the Indian Heart Rhythm Society (IHRS), and the Latin American Heart Rhythm Society (LAHRS). This document is expected to provide support for clinicians and patients to allow for appropriate CIED use, appropriate CIED management, and appropriate CIED follow-up in pediatric patients.

Introduction/Background Functional electrical stimulation (FES) can be used on individuals with upper motoneuron dysfunctions to restore grasping functions. To be functional and useful in daily tasks, the patient must be able to pilot the device by means of an interface. We have investigated two techniques that could address the situation of persons with tetraplegia: electromyography (EMG) and inertial measurement units (IMU), respectively measuring muscle activity and limb movements. Material and method One group of 8 tetraplegic patients (EMG group) was equipped with two pairs of EMG electrodes located on muscles of the upper arm. Selected muscles could be voluntary activated in a comfortable way. Another group of 9 tetraplegic patients (IMU group) was equipped with one IMU (3-axis accelerometer and 3-axis gyroscope) located on the arm. In the EMG group a threshold detection algorithm was used to detect muscle contractions while in IMU group a classification algorithm was used to detect two distinct movements of the limb where the IMU was located. The detection algorithms outputs were used to trigger two postures of a robot hand. The same outputs were also used, for patients where FES of arm muscles lead to visible hand movements, to trigger the contractions of two muscles on their contralateral lower arm. Results All the patients were able to control muscle contraction or limb movements to trigger different actions. Patients were asked to control the robotic hand, following a randomized sequence of two pre-defined postures. In EMG group the success score was of 95 and 92% in IMU group. Whenever FES was used, patients could activate grasping movements and wrist extension. Three patients were able to perform functional tasks such as grasping and relocating objects. Conclusion Despite little training, all the patients were able to voluntarily control a robotic hand and, when it was possible to test, their own hand with FES.

Cancellous bone is a porous composite of calcified tissue interspersed with soft marrow. Sea ice is also a porous composite, consisting of pure ice with brine, air, and salt inclusions. Interestingly, the microstructures of bone and sea ice exhibit notable similarities. In recent years, we have developed mathematical and experimental techniques for imaging and characterizing the brine microstructure of sea ice, such as its volume fraction and connectivity, as well as a range of theoretical approaches for studying fluid, thermal, and electromagnetic transport in sea ice. Here we explore the application of our sea ice techniques to investigate trabecular bone. For example, percolation theory that quantifies brine connectivity and its thermal evolution can also help assess the impact of osteoporosis on trabecular structure. Central to our approach is the spectral measure of a composite material, which contains detailed information about the mixture geometry, and can be used in powerful integral representations to compute the effective properties. The spectral measure is obtained from the eigenvalues and eigenvectors of a self-adjoint operator determined exclusively by the composite microgeometry. Here we compute the spectral measures for discretizations of images of healthy and osteoporotic bone. The measures are used to compute the effective electromagnetic properties of the bone specimens. These data are then inverted to reconstruct the porosity of the original specimens, with excellent agreement.

Proton pump inhibitor (PPI) use increases the risk of Clostridium difficile infection (CDI) despite C. difficile spores being acid resistant. Swallowed saliva contains nitrite which reacts with gastric acid, producing bactericidal nitrogen oxides. With 5mM nitrite at pH 2 (reflecting normal gastric conditions) all C. difficile spores were killed within 15 min. No reduction in count was seen with the same nitrite concentration at pH 5, representing gastric conditions in patients taking PPIs, even after 60 min. Reduced gastric acidification of salivary nitrite may explain the increased risk of CDI in patients taking PPIs.

Summary Background Blood pressure may contribute to 50% of the global cardiovascular disease epidemic. By understanding the genes predisposing to common disorders such as human essential hypertension we may gain insights into novel pathophysiological mechanisms and potential therapeutic targets. In the Medical Research Council BRItish Genetics of HyperTension (BRIGHT) study, we aim to identify these genetic factors by scanning the human genome for susceptibility genes for essential hypertension. We describe the results of a genome scan for hypertension in a large white European population. Methods We phenotyped 2010 affected sibling pairs drawn from 1599 severely hypertensive families, and completed a 10 centimorgan genome-wide scan. After rigorous quality control, we analysed the genotypic data by non-parametric linkage, which tests whether genes are shared in excess among the affected sibling pairs. Lod scores, calculated at regular points along each chromosome, were used to assess the support for linkage. Findings Linkage analysis identified a principle locus on chromosome 6q, with a lod score of 3·21 that attained genome-wide significance (p=0·042). The inclusion of three further loci with lod scores higher than 1·57 (2q, 5q, and 9q) also show genome-wide significance (p=0·017) when assessed under a locus-counting analysis. Interpretation These findings imply that human essential hypertension has an oligogenic element (a few genes may be involved in determination of the trait) possibly superimposed on more minor genetic effects, and that several genes may be tractable to a positional cloning strategy.

SummaryCryptosporidium parvum is an important human pathogen and potential bioterrorism agent. No vaccines exist against C. parvum, the drugs currently approved to treat cryptosporidiosis are ineffective, and drug discovery is challenging because the parasite cannot be maintained continuously in cell culture. Mining the sequence of the C. parvum genome has revealed that the only route to guanine nucleotides is via inosine-5′-monophosphate dehydrogenase (IMPDH). Moreover, phylogenetic analysis suggests that the IMPDH gene was obtained from bacteria by lateral gene transfer. Here we exploit the unexpected evolutionary divergence of parasite and host enzymes by designing a high-throughput screen to target the most diverged portion of the IMPDH active site. We have identified four parasite-selective IMPDH inhibitors that display antiparasitic activity with greater potency than paromomycin, the current gold standard for anticryptosporidial activity.

The psychological reactions of 259 female and 130 male medical and surgical patients were examined. Both when they were discharged and when they were followed up 12 months later, women who received crisis intervention counseling during their hospitalisation showed the predicted psychological gains when compared with non-counseled women. They expressed fewer feelings of helplessness and more of competence in the short term and fewer feelings of anxiety and helplessness in the long term. Men showed some improvements in the short term but fewer in the long term when, although they later expressed more feelings of competence, there were also more of helplessness. Women and men also showed the predicted benefits of counseling similarly in fewer indirect expressions of anger on both occasions. They also showed less anxiety on discharge and fewer depressive feelings on follow-up. Explanations of the sex differences in terms of sex role stereotypes, the extent of each patient's crisis and possible methodological artefacts were considered.

Summary The results of our study indicate a caution in the use of the Copeland intraocular lens because of the comparatively high complication rate associated with irritation causing uveitis, resulting in irreversible cystoid macular edema, irreversible corneal edema, .rid retinal detachment. Our results indicate that the use of any other type of cataract extraction with the other types of intraocular lenses used in this review show no higher incidence of complications than a routine intracapsular cataract extraction.