The Timing of Reward-Seeking Action Tracks Visually-Cued Theta Oscillations in Primary Visual Cortex

An emerging body of work challenges the view that primary visual cortex (V1) represents the visual world faithfully. Theta oscillations in the local field potential (LFP) of V1 have been found to convey temporal expectations and, specifically, to express the delay between a visual stimulus and the reward that it portends. We extend this work by showing how these oscillatory states in male, wild-type rats can even relate to the timing of a visually cued reward-seeking behavior. In particular, we show that, with training, high precision and accuracy in behavioral timing tracks the power of these oscillations and the time of action execution covaries with their duration. These LFP oscillations are also intimately related to spiking responses at the single-unit level, which themselves carry predictive timing information. Together, these observations extend our understanding of the role of cortical oscillations in timing generally and the role of V1 in the timing of visually cued behaviors specifically.Fil: Levy, Joshua M.. University Johns Hopkins; Estados UnidosFil: Zold, Camila Lidia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; ArgentinaFil: Namboodiri, Vijay Mohan K.. University of North Carolina; Estados UnidosFil: Hussain Shuler, Marshall G. University Johns Hopkins; Estados Unido

Interfaces among Safety, Security, and Safeguards (3S) -Conflicts and Synergies

ABSTRACT In recent years, the need to achieve a better understanding of the relationships and interfaces among three disciplines related to nuclear power -safety, security, and safeguards (3S) -has become widely recognized. The challenge is to effectively and efficiently integrate the 3S requirements. All stakeholders could benefit from the integration of 3S: designers and operators, shippers and carriers of nuclear material, national and international authorities, and the world population. To address this challenge, the potential for conflicts and opportunities for synergy among the elements of 3S must be identified. This paper identifies the 3S interfaces that have the potential for creating conflicts and synergies. The main step in developing guidance is to examine where and how 3S requirements interface. We start with the International Atomic Energy Agency (IAEA) model Comprehensive Safeguards Agreement (INFCIRC/153) and Additional Protocol (INFCIRC/540). We then identify two types of access that are the basis for conflicts and synergies in 3S. Finally, we provide recommendations for improving overall efficiency and effectiveness to be considered by designers, operators, shippers, and authorities during the integration of the 3S requirements

Clinical and imaging services for TIA and minor stroke: results of two surveys of practice across the UK

Objectives: Transient ischaemic attack (TIA) is a medical emergency requiring rapid access to effective, organised, stroke prevention. There are about 90 000 TIAs per year in the UK. We assessed whether stroke-prevention services in the UK meet Government targets.<p></p> Design: Cross-sectional survey.<p></p> Setting: All UK clinical and imaging stroke-prevention services.<p></p> Intervention: Electronic structured survey delivered over the web with automatic recording of responses into a database; reminders to non-respondents. The survey sought information on clinic frequency, staff, case-mix, details of brain and carotid artery imaging, medical and surgical treatments.<p></p> Results: 114 stroke clinical and 146 imaging surveys were completed (both response rates 45%). Stroke-prevention services were available in most (97%) centres but only 31% operated 7 days/week. Half of the clinic referrals were TIA mimics, most patients (75%) were prescribed secondary prevention prior to clinic referral, and nurses performed the medical assessment in 28% of centres. CT was the most common and fastest first-line investigation; MR, used in 51% of centres, mostly after CT, was delayed up to 2 weeks in 26%; 51% of centres omitted blood-sensitive (GRE/T2*) MR sequences. Carotid imaging was with ultrasound in 95% of centres and 59% performed endarterectomy within 1 week of deciding to operate.<p></p> Conclusions: Stroke-prevention services are widely available in the UK. Delays to MRI, its use in addition to CT while omitting key sequences to diagnose haemorrhage, limit the potential benefit of MRI in stroke prevention, but inflate costs. Assessing TIA mimics requires clinical neurology expertise yet nurses run 28% of clinics. Further improvements are still required for optimal stroke prevention

Integrity of normal-appearing white matter: influence of age, visible lesion burden and hypertension in patients with small vessel disease

White matter hyperintensities accumulate with age and occur in patients with stroke, but their pathogenesis is poorly understood. We measured multiple magnetic resonance imaging biomarkers of tissue integrity in normal-appearing white matter and white matter hyperintensities in patients with mild stroke, to improve understanding of white matter hyperintensities origins. We classified white matter into white matter hyperintensities and normal-appearing white matter and measured fractional anisotropy, mean diffusivity, water content (T1-relaxation time) and blood–brain barrier leakage (signal enhancement slope from dynamic contrast-enhanced magnetic resonance imaging). We studied the effects of age, white matter hyperintensities burden (Fazekas score) and vascular risk factors on each biomarker, in normal-appearing white matter and white matter hyperintensities, and performed receiver-operator characteristic curve analysis. Amongst 204 patients (34.3–90.9 years), all biomarkers differed between normal-appearing white matter and white matter hyperintensities (P < 0.001). In normal-appearing white matter and white matter hyperintensities, mean diffusivity and T1 increased with age (P < 0.001), all biomarkers varied with white matter hyperintensities burden (P < 0.001; P = 0.02 signal enhancement slope), but only signal enhancement slope increased with hypertension (P = 0.028). Fractional anisotropy showed complex age-white matter hyperintensities-tissue interactions; enhancement slope showed white matter hyperintensities-tissue interactions. Mean diffusivity distinguished white matter hyperintensities from normal-appearing white matter best at all ages. Blood–brain barrier leakage increases with hypertension and white matter hyperintensities burden at all ages in normal-appearing white matter and white matter hyperintensities, whereas water mobility and content increase as tissue damage accrues, suggesting that blood–brain barrier leakage mediates small vessel disease-related brain damage

White matter hyperintensity reduction and outcomes after minor stroke

Objective: To assess factors associated with white matter hyperintensity (WMH) change in a large cohort after observing obvious WMH shrinkage 1 year after minor stroke in several participants in a longitudinal study. Methods: We recruited participants with minor ischemic stroke and performed clinical assessments and brain MRI. At 1 year, we assessed recurrent cerebrovascular events and dependency and repeated the MRI. We assessed change in WMH volume from baseline to 1 year (normalized to percent intracranial volume [ICV]) and associations with baseline variables, clinical outcomes, and imaging parameters using multivariable analysis of covariance, model of changes, and multinomial logistic regression. Results: Among 190 participants (mean age 65.3 years, range 34.3–96.9 years, 112 [59%] male), WMH decreased in 71 participants by 1 year. At baseline, participants whose WMH decreased had similar WMH volumes but higher blood pressure (p = 0.0064) compared with participants whose WMH increased. At 1 year, participants with WMH decrease (expressed as percent ICV) had larger reductions in blood pressure (β = 0.0053, 95% confidence interval [CI] 0.00099–0.0097 fewer WMH per 1–mm Hg decrease, p = 0.017) and in mean diffusivity in normal-appearing white matter (β = 0.075, 95% CI 0.0025–0.15 fewer WMH per 1-unit mean diffusivity decrease, p = 0.043) than participants with WMH increase; those with WMH increase experienced more recurrent cerebrovascular events (32%, vs 16% with WMH decrease, β = 0.27, 95% CI 0.047–0.50 more WMH per event, p = 0.018). Conclusions: Some WMH may regress after minor stroke, with potentially better clinical and brain tissue outcomes. The role of risk factor control requires verification. Interstitial fluid alterations may account for some WMH reversibility, offering potential intervention targets

Tocotrienols are good adjuvants for developing cancer vaccines

<p>Abstract</p> <p>Background</p> <p>Dendritic cells (DCs) have the potential for cancer immunotherapy due to their ability to process and present antigens to T-cells and also in stimulating immune responses. However, DC-based vaccines have only exhibited minimal effectiveness against established tumours in mice and humans. The use of appropriate adjuvant enhances the efficacy of DC based cancer vaccines in treating tumours.</p> <p>Methods</p> <p>In this study we have used tocotrienol-rich fraction (TRF), a non-toxic natural compound, as an adjuvant to enhance the effectiveness of DC vaccines in treating mouse mammary cancers. In the mouse model, six-week-old female BALB/c mice were injected subcutaneously with DC and supplemented with oral TRF daily (DC+TRF) and DC pulsed with tumour lysate from 4T1 cells (DC+TL). Experimental mice were also injected with DC pulsed with tumour lysate and supplemented daily with oral TRF (DC+TL+TRF) while two groups of animal which were supplemented daily with carrier oil (control) and with TRF (TRF). After three times vaccination, mice were inoculated with 4T1 cells in the mammary breast pad to induce tumour.</p> <p>Results</p> <p>Our study showed that TRF in combination with DC pulsed with tumour lysate (DC+TL+TRF) injected subcutaneously significantly inhibited the growth of 4T1 mammary tumour cells as compared to control group. Analysis of cytokines production from murine splenocytes showed significant increased productions of IFN-γ and IL-12 in experimental mice (DC+TL+TRF) compared to control, mice injected with DC without TRF, mice injected with DC pulsed with tumour lysate and mice supplemented with TRF alone. Higher numbers of cytotoxic T cells (CD8) and natural killer cells (NK) were observed in the peripheral blood of TRF adjuvanted DC pulsed tumour lysate mice.</p> <p>Conclusion</p> <p>Our study show that TRF has the potential to be an adjuvant to augment DC based immunotherapy.</p

Perceptions of nurse practitioners by emergency department doctors in Australia

BACKGROUND: The Australian Medical Association is strongly opposed to the nurse practitioner (NP) role with concerns that NPs may become doctor substitutes without the requisite training and education that the medical role demands. Despite this, NPs have been heralded by some as a potential solution to the access block, workforce shortage and increased demand affecting emergency departments (EDs). AIMS: The purpose of this study was to determine the perception of NPs by medical staff working in Australian EDs. METHODS: Semi-structured telephone interviews were conducted with closed and open-ended questions. Participants were drawn from a representative stratified sample of two city, two metropolitan and two provincial hospitals of each State/Territory. RESULTS: A total of 95 doctors from 35 EDs participated in this study including 36 Departmental Directors; 36% of participating Directors indicated having an NP on staff. Doctors were strongly opposed to the statement that NPs could replace either nurses or other prevocational doctors; 71 interviewees commented on the role of NPs in the ED. Thematic analyses revealed polarised views held by doctors. Eight major themes were identified, the most common being that there is a lack of clarity of the NP role definition, their scope of practice and differentiation from the medical role. CONCLUSION: Although ED NPs represent a highly skilled professional group their role is poorly understood by ED doctors. Opposition to the NP role is a significant barrier to the introduction of great numbers of ED NPs as a strategy to overcome the medical workforce shortage. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s12245-010-0214-8) contains supplementary material, which is available to authorized users

Influence of Dopaminergically Mediated Reward on Somatosensory Decision-Making

This pharmacological fMRI study shows that during reward-based sensory decision-making, dopamine is crucially involved in reward-related modulation of human primary sensory cortex

Oral Antimicrobial Peptides and Biological Control of Caries

The presence of antimicrobial peptides (AMPs) in saliva may be a biological factor that contributes to susceptibility or resistance to caries. This manuscript will review AMPs in saliva, consider their antimicrobial and immunomodulatory functions, and evaluate their potential role in the oral cavity for protection of the tooth surface as well as the oral mucosa. These AMPs are made in salivary gland and duct cells and have broad antimicrobial activity. Alpha-defensins and LL37 are also released by neutrophils into the gingival crevicular fluid. Both sources may account for their presence in saliva. A recent study in middle school children aimed to determine a possible correlation between caries prevalence in children and salivary concentrations of the antimicrobial peptides human beta-defensin-3 (hBD-3), the cathelicidin, LL37, and the alpha-defensins. The levels of these AMPs were highly variable in the population. While levels of LL37 and hBD-3 did not correlate with caries experience, the mean alpha-defensin level was significantly higher in children with no caries than in children with caries (p < 0.005). We conclude that several types of AMPs that may have a role in oral health are present in unstimulated saliva. Low salivary levels of alpha-defensin may represent a biological factor that contributes to caries susceptibility. Our observation could lead to new ways to prevent caries and to a new tool for caries risk assessment

Immunogenicity and Cross-Reactivity of 2009–2010 Inactivated Seasonal Influenza Vaccine in US Adults and Elderly

The campaign of 2009–2010 Northern Hemisphere seasonal vaccination was concurrent with the 2009 H1N1 pandemic. Using a hemagglutination inhibition (HAI) assay, we evaluated the immunogenicity and cross-reactivity of 2009–2010 inactivated trivalent influenza vaccine (TIV) in US adult and elderly populations. Vaccination of TIV resulted in a robust boost on the antibody response of all subjects to seasonal A/Brisbane/59/2007 (H1N1) and A/Uruguay/716/2007 (H3N2) with over 70% of recipients reaching a seroprotective titer of 40. B/Brisbane/60/2008 was the least immunogenic among the three seasonal vaccine strains with <30% of TIV recipients reaching a seroprotective titer of 40. TIV vaccination also induced a moderate boost on the pandemic specific antibody responses. Twenty-four percent of adults and 36% of elderly reached a seroprotective HAI titer of 40 or more against pandemic A/South Carolina/18/2009 (H1N1) after receiving TIV compared to 4% and 7% at the beginning of vaccination, respectively. In addition, 22% of adults and 34% of elderly showed an increase of 4-fold or more in A/South Carolina/18/2009 specific HAI titers after TIV vaccination. The pandemic specific cross-reactive antibodies strongly correlated with the post-vaccination HAI titers against the seasonal H3N2 vaccine strain in all subjects