To characterize the change in frequency of infectious disease outbreaks over time worldwide, we encoded and analysed a novel 33-year dataset of 12 102 outbreaks of 215 human infectious diseases, comprising more than 44 million cases occuring in 219 nations. We merged these records with ecological characteristics of the causal pathogens to examine global temporal trends in the total number of outbreaks, disease richness (number of unique diseases), disease diversity (richness and outbreak evenness) and per capita cases. Bacteria, viruses, zoonotic diseases (originating in animals) and those caused by pathogens transmitted by vector hosts were responsible for the majority of outbreaks in our dataset. After controlling for disease surveillance, communications, geography and host availability, we find the total number and diversity of outbreaks, and richness of causal diseases increased significantly since 1980 ( p , 0.0001). When we incorporate Internet usage into the model to control for biased reporting of outbreaks (starting 1990), the overall number of outbreaks and disease richness still increase significantly with time ( p , 0.0001), but per capita cases decrease significantly ( p ¼ 0.005). Temporal trends in outbreaks differ based on the causal pathogen's taxonomy, host requirements and transmission mode. We discuss our preliminary findings in the context of global disease emergence and surveillance.

In Huntington’s disease (HD) mouse models, spontaneous inhibitory synaptic activity is enhanced in a subpopulation of medium-sized spiny neurons (MSNs), which could dampen striatal output. We examined the potential source(s) of increased inhibition using electrophysiological and optogenetic methods to assess feedback and feedforward inhibition in two transgenic mouse models of HD. Single whole-cell patch-clamp recordings demonstrated that increased GABA synaptic activity impinges principally on indirect pathway MSNs. Dual patch recordings between MSNs demonstrated reduced connectivity between MSNs in HD mice. However, while connectivity was strictly unidirectional in controls, in HD mice bidirectional connectivity occurred. Other sources of increased GABA activity in MSNs also were identified. Dual patch recordings from fast spiking (FS) interneuron–MSN pairs demonstrated greater but variable amplitude responses in MSNs. In agreement, selective optogenetic stimulation of parvalbumin-expressing, FS interneurons induced significantly larger amplitude MSN responses in HD compared with control mice. While there were no differences in responses of MSNs evoked by activating single persistent low-threshold spiking (PLTS) interneurons in recorded pairs, these interneurons fired more action potentials in both HD models, providing another source for increased frequency of spontaneous GABA synaptic activity in MSNs. Selective optogenetic stimulation of somatostatin-expressing, PLTS interneurons did not reveal any significant differences in responses of MSNs in HD mice. These findings provide strong evidence that both feedforward and to a lesser extent feedback inhibition to MSNs in HD can potentially be sources for the increased GABA synaptic activity of indirect pathway MSNs.

Sudden cardiac death due to ventricular tachycardia (VT) is a major health issue worldwide. Efforts to identify patients at risk, determine VT mechanisms, and effectively prevent and treat VT with a mechanism-based approach would benefit from continuous noninvasive imaging of the arrhythmia over the entire heart. This paper presents the first noninvasive images of human ventricular arrhythmias using electrocardiographic imaging (ECGI), highlighting the large diversity of human VT in terms of activation patterns, mechanisms, and sites of initiation. Based on comparison with catheter mapping, ECGI provided high spatial resolution; a property that overcomes a limitation of the body surface electrocardiogram, which provides only global information. The spatial resolution and ability to image the activation sequences over the entire ventricular surfaces in a single beat allowed us to make observations regarding VT initiation and continuation, and regarding relationships to ventricular substrates, including anatomical scars and abnormal electrophysiological substrate. The ability of ECGI to provide patient-specific physiologic insights, to map the VT activation sequence and to identify the location and depth of VT origin from a single beat has important clinical implications in treating patients with ventricular arrhythmias.

The strategic use of remote pacemaker interrogation follow-up detects actionable events that are potentially important more quickly and more frequently than transtelephonic rhythm strip recordings. The use of transtelephonic rhythm strips for pacemaker follow-up is of little value except for battery status determinations. (PREFER [Pacemaker Remote Follow-up Evaluation and Review]; NCT00294645).