In the county of Stockholm, between 1970 and 2002, we have previously reported a 3‐fold parallel increase in the incidence of tonsillar squamous cell carcinoma (SCC) and the proportion of human papillomavirus (HPV) positive tonsillar SCC. Here, we have followed the above parameters in all patients (n = 120) diagnosed with tonsillar SCC during 2003–2007 in the same area, and also in correlation to our previous data. Ninety‐eight pretreatment biopsies were available and presence of HPV DNA and HPV‐16 E6 and E7 RNA were tested by polymerase chain reaction (PCR) and RT‐PCR. Incidence data were obtained from the Swedish Cancer Registry. Data reported from 1970 to 2002 were also obtained for comparison. HPV DNA was present in 83 of 98 (85%) of the tonsillar SCC biopsies from 2003 to 2007 and 77 of these were HPV‐16 positive. HPV‐16 E6 and E7 RNA were found in 98% of 52 analyzed HPV‐16 positive cases. The proportion of HPV‐positive cancers had significantly increased both from 1970 to 2007 (p < 0.0001) as well from 2000 to 2007 (p < 0.01), with 68% (95% confidence interval (CI), 53–81) 2000–2002; 77% (95% CI, 63–87) 2003–2005; and 93% (95% CI, 82–99) 2006–2007. The incidence rate of HPV‐positive tumors almost doubled each decade between 1970 and 2007, in parallel with a decline of HPV‐negative tumors. In conclusion, the incidence of HPV‐positive cancers is still increasing in the County of Stockholm, suggesting an epidemic of a virus‐induced carcinoma, with soon practically all tonsillar SCC being HPV positive, as in cervical cancer. © 2009 UICC

While signatures of attention have been extensively studied in sensory systems, the neural sources and computations responsible for top-down control of attention are largely unknown. Using chronic recordings in mice, we found that fast-spiking parvalbumin (FS-PV) interneurons in medial prefrontal cortex (mPFC) uniformly show increased and sustained firing during goal-driven attentional processing, correlating to the level of attention. Elevated activity of FS-PV neurons on the timescale of seconds predicted successful execution of behavior. Successful allocation of attention was characterized by strong synchronization of FS-PV neurons, increased gamma oscillations, and phase locking of pyramidal firing. Phase-locked pyramidal neurons showed gamma-phase-dependent rate modulation during successful attentional processing. Optogenetic silencing of FS-PV neurons deteriorated attentional processing, while optogenetic synchronization of FS-PV neurons at gamma frequencies had pro-cognitive effects and improved goal-directed behavior. FS-PV neurons thus act as a functional unit coordinating the activity in the local mPFC circuit during goal-driven attentional processing.

Significance: Channelrhodopsins are membrane proteins that enable cellular regulation of transmembrane ion conductance through light-gated pores; these proteins have found application in optogenetics. This paper tests the hypothesis that selectivity of channelrhodopsins is determined by surface potential of the pore region: Cations are conducted by a negatively charged pore, and chloride ions are conducted by a pore that has neutral and positively charged residues. In confirming this hypothesis and applying the resulting principles, we engineer improved chloride-conducting channels with higher chloride selectivity and conductivity. We also provide insights into the distinct mechanisms underlying inhibition mediated by higher-efficiency chloride channels compared with ion pumps. Finally, we demonstrate initial utility of light-gated microbial opsin-based chloride channels in controlling behavior of freely moving animals.

Knowledge of the prevalence of different human papillomavirus (HPV) types in young girls is important for the early detection of changes in HPV prevalence, e.g. due to HPV vaccines. The purpose of this study was to obtain information on the prevalence of 24 different genital HPV types in a group of sexually active young women (aged 15–23 y) attending a major youth healthcare centre in Stockholm, before the introduction of public HPV vaccination of young women in the autumn of 2010. A total of 615 women were analyzed for 24 different, mainly high-risk HPV (HR-HPV) types using multiplex polymerase chain reaction and Luminex technology. A high HPV prevalence in this cohort was demonstrated, particularly with regard to HPV16, but also to all included HR-HPV types. Of the 544 successfully analyzed samples from non-vaccinated individuals, 70% were positive for the HPV types assayed for, and 62% were positive for HR-HPV types. Over a third (34.7%) of the women were infected with HPV16, and a high frequency of infections with HR-HPV types 51 (10.7%), 18 (10.1%), 52 (9.9%) and 73 (9.4%) was also observed. At least 9 different non-vaccine HR-HPV types were present with a prevalence of >6% in this selected group of young women.

The mammalian prefrontal cortex (PFC) is thought to modulate cortical sensory processing during behavior through long-range feedback projections. Subregions of the PFC, such as the anterior cingulate cortex (ACA) and ventrolateral orbitofrontal cortex (ORB), exhibit unique patterns of connectivity that may confer distinct roles in feedback modulation of sensory information. Here, we combined axonal tracing, two-photon calcium imaging, and chemogenetic manipulations in mice to determine how projections from the ACA and ORB influence visual processing in the primary visual cortex (VISp). We found that ACA axons conveyed stronger visual-stimulus information than ORB axons, though both conveyed non-visual, behavior-related information. ACA input enhanced visual encoding in VISp neurons and scaled with behavioral arousal, whereas ORB input shaped behavior-related modulation but reduced high-contrast visual encoding. These results reveal distinct feedback roles of ACA and ORB projections, supporting the modular organization of PFC feedback modulation.