Background. Rotavirus vaccine is recommended for routine use in all countries globally. To facilitate decision making on rotavirus vaccine adoption by countries, help donors prioritize investments in health interventions, and monitor vaccine impact, we estimated rotavirus mortality for children 60 countries worldwide by the end of 2013, the majority of countries using rotavirus vaccine during the review period were low-mortality countries and the impact of rotavirus vaccine on global estimates of rotavirus mortality has been limited. Continued monitoring of rotavirus mortality rates and deaths through rotavirus surveillance will aid in monitoring the impact of vaccination.
Infections caused by antibiotic-resistant bacteria, especially the "ESKAPE" pathogens, continue to increase in frequency and cause significant morbidity and mortality. New antimicrobial agents are greatly needed to treat infections caused by gram-negative bacilli (GNB) resistant to currently available agents. The Infectious Diseases Society of America (IDSA) continues to propose legislative, regulatory, and funding solutions to this continuing crisis. The current report updates the status of development and approval of systemic antibiotics in the United States as of early 2013. Only 2 new antibiotics have been approved since IDSA's 2009 pipeline status report, and the number of new antibiotics annually approved for marketing in the United States continues to decline. We identified 7 drugs in clinical development for treatment of infections caused by resistant GNB. None of these agents was included in our 2009 list of antibacterial compounds in phase 2 or later development, but unfortunately none addresses the entire spectrum of clinically relevant GNB resistance. Our survey demonstrates some progress in development of new antibacterial drugs that target infections caused by resistant GNB, but progress remains alarmingly elusive. IDSA stresses our conviction that the antibiotic pipeline problem can be solved by the collaboration of global leaders to develop creative incentives that will stimulate new antibacterial research and development. Our aim is the creation of a sustainable global antibacterial drug research and development enterprise with the power in the short term to develop 10 new, safe, and efficacious systemically administered antibiotics by 2020 as called for in IDSA's "10 x '20 Initiative."
Gliomas are the most common primary intracranial tumor, representing 81% of malignant brain tumors. Although relatively rare, they cause significant mortality and morbidity. Glioblastoma, the most common glioma histology (similar to 45% of all gliomas), has a 5-year relative survival of similar to 5%. A small portion of these tumors are caused by Mendelian disorders, including neurofibromatosis, tuberous sclerosis, and Li-Fraumeni syndrome. Genomic analyses of glioma have also produced new evidence about risk and prognosis. Recently discovered biomarkers that indicate improved survival include O-6-methylguanine-DNA methyltransferase methylation, isocitrate dehydrogenase mutation, and a glioma cytosine-phosphate-guanine island methylator phenotype. Genome-wide association studies have identified heritable risk alleles within 7 genes that are associated with increased risk of glioma. Many risk factors have been examined as potential contributors to glioma risk. Most significantly, these include an increase in risk by exposure to ionizing radiation and a decrease in risk by history of allergies or atopic disease(s). The potential influence of occupational exposures and cellular phones has also been examined, with inconclusive results. We provide a "state of the science" review of current research into causes and risk factors for gliomas in adults.
The network architecture of functional connectivity within the human brain connectome is poorly understood at the voxel level. Here, using resting state functional magnetic resonance imaging data from 1003 healthy adults, we investigate a broad array of network centrality measures to provide novel insights into connectivity within the whole-brain functional network (i.e., the functional connectome). We first assemble and visualize the voxel-wise (4 mm) functional connectome as a functional network. We then demonstrate that each centrality measure captures different aspects of connectivity, highlighting the importance of considering both global and local connectivity properties of the functional connectome. Beyond "detecting functional hubs," we treat centrality as measures of functional connectivity within the brain connectome and demonstrate their reliability and phenotypic correlates (i.e., age and sex). Specifically, our analyses reveal age-related decreases in degree centrality, but not eigenvector centrality, within precuneus and posterior cingulate regions. This implies that while local or (direct) connectivity decreases with age, connections with hub-like regions within the brain remain stable with age at a global level. In sum, these findings demonstrate the nonredundancy of various centrality measures and raise questions regarding their underlying physiological mechanisms that may be relevant to the study of neurodegenerative and psychiatric disorders.
Cytomegalovirus (CMV) infection and disease are important causes of morbidity and mortality in transplant recipients. For the purpose of developing consistent reporting of CMV outcomes in clinical trials, definitions of CMV infection and disease were developed and most recently published in 2002. Since then, there have been major developments in its diagnosis and management. Therefore, the CMV Drug Development Forum consisting of scientists, clinicians, regulators, and industry representatives has produced an updated version incorporating recent knowledge with the aimto support clinical research and drug development. The main changes compared to previous definitions are the introduction of a "probable disease" category and to incorporate quantitative nucleic acid testing in some end-organ disease categories. As the field evolves, the need for updates of these definitions is clear, and collaborative efforts between scientists, regulators, and industry can provide a platform for this work.
Face recognition is of major social importance and involves highly selective brain regions thought to be organized in a distributed functional network. However, the exact architecture of interconnections between these regions remains unknown. We used functional magnetic resonance imaging to identify face-responsive regions in 22 participants and then employed diffusion tensor imaging with probabilistic tractography to establish the white-matter pathways between these functionally defined regions. We identified strong white-matter connections between the occipital face area (OFA) and fusiform face area (FFA), with a significant right-hemisphere predominance. We found no evidence for direct anatomical connections between FFA and superior temporal sulcus (STS) or between OFA and STS, contrary to predictions based on current cognitive models. Instead, our findings point to segregated processing along a ventral extrastriate visual pathway to OFA-FFA and another more dorsal system connected to STS and frontoparietal areas. In addition, early occipital areas were found to have direct connections to the amygdala, which might underlie a rapid recruitment of limbic brain areas by visual inputs bypassing more elaborate extrastriate cortical processing. These results unveil the structural neural architecture of the human face recognition system and provide new insights on how distributed face-responsive areas may work together.
The after-effects of repetitive transcranial magnetic stimulation (rTMS) are highly variable between individuals. Because different populations of cortical neurons are stimulated more easily or are more excitable in different people at different times, the variability may not be due to differences between individuals in the plasticity of cortical synapses, but may instead be due to individual differences in the recruitment of cortical neurons. In this study, we examined the effects of rTMS in 56 healthy volunteers. The responses to excitatory and inhibitory theta burst stimulation (TBS) protocols were highly variable between individuals. Surprisingly, the TBS effect was highly correlated with the latency of motor-evoked potentials (MEPs) evoked by TMS pulses that induced an anterior-posterior (AP) directed current across the central sulcus. Finally, we devised a new plasticity protocol using closely timed pairs of oppositely directed TMS current pulses across the central sulcus. Again, the after-effects were related to the latency of MEPs evoked by AP current. Our results are consistent with the idea that variation in response to rTMS plasticity probing protocols is strongly influenced by which interneuron networks are recruited by the TMS pulse.
Background. Reports of acute hepatitis C in young persons in the United States have increased. We examined data from national surveillance and supplemental case follow-up at selected jurisdictions to describe the US epidemiology of hepatitis C virus (HCV) infection among young persons (aged <= 30 years). Methods. We examined trends in incidence of acute hepatitis C among young persons reported to the Centers for Disease Control and Prevention (CDC) during 2006-2012 by state, county, and urbanicity. Sociodemographic and behavioral characteristics of HCV-infected young persons newly reported from 2011 to 2012 were analyzed from case interviews and provider follow-up at 6 jurisdictions. Results. From 2006 to 2012, reported incidence of acute hepatitis C increased significantly in young persons-13% annually in nonurban counties (P = .003) vs 5% annually in urban counties (P = .028). Thirty (88%) of 34 reporting states observed higher incidence in 2012 than 2006, most noticeably in nonurban counties east of the Mississippi River. Of 1202 newly reported HCV-infected young persons, 52% were female and 85% were white. In 635 interviews, 75% of respondents reported injection drug use. Of respondents reporting drug use, 75% had abused prescription opioids, with first use on average 2.0 years before heroin. Conclusions. These data indicate an emerging US epidemic of HCV infection among young nonurban persons of predominantly white race. Reported incidence was higher in 2012 than 2006 in at least 30 states, with largest increases in nonurban counties east of the Mississippi River. Prescription opioid abuse at an early age was commonly reported and should be a focus for medical and public health intervention.