Non-Linear Magnetic Ringing of Spin-Ordered Solid He-3

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Default mode network connectivity predicts sustained attention deficits following traumatic brain injury

Traumatic brain injury (TBI) frequently produces impairments of attention in humans. These can result in a failure to maintain consistent goal-directed behavior. A predominantly right-lateralized frontoparietal network is often engaged during attentionally demanding tasks. However, lapses of attention have also been associated with increases in activation within the default mode network (DMN). Here, we study TBI patients with sustained attention impairment, defined on the basis of the consistency of their behavioral performance over time. We show that sustained attention impairments in patients are associated with an increase in DMN activation, particularly within the precuneus and posterior cingulate cortex. Furthermore, the interaction of the precuneus with the rest of the DMN at the start of the task, i.e., its functional connectivity, predicts which patients go on to show impairments of attention. Importantly, this predictive information is present before any behavioral evidence of sustained attention impairment, and the relationship is also found in a subgroup of patients without focal brain damage. TBI often results in diffuse axonal injury, which produces cognitive impairment by disconnecting nodes in distributed brain networks. Using diffusion tensor imaging, we demonstrate that structural disconnection within the DMN also correlates with the level of sustained attention. These results show that abnormalities in DMN function are a sensitive marker of impairments of attention and suggest that changes in connectivity within the DMN are central to the development of attentional impairment after TBI

Evapotranspiration and crop coefficients of rice (Oryza sativa L.) under sprinkler irrigation in a semiarid climate determined by the surface renewal method

The evapotranspiration (ETc) of sprinkler-irrigated rice was determined for the semiarid conditions of NE Spain during 2001, 2002 and 2003. The surface renewal method, after calibration against the eddy covariance method, was used to obtain values of sensible heat flux (H) from high-frequency temperature readings. Latent heat flux values were obtained by solving the energy balance equation. Finally, lysimeter measurements were used to validate the evapotranspiration values obtained with the surface renewal method. Seasonal rice evapotranspiration was about 750–800 mm. Average daily ETc for mid-season (from 90 to 130 days after sowing) was 5.1, 4.5 and 6.1 mm day−1 for 2001, 2002 and 2003, respectively. The experimental weekly crop coefficients fluctuated in the range of 0.83–1.20 for 2001, 0.81–1.03 for 2002 and 0.84–1.15 for 2003. The total growing season was about 150–160 days. In average, the crop coefficients for the initial (Kcini), mid-season (Kcmid) and late-season stages (Kcend) were 0.92, 1.06 and 1.03, respectively, the length of these stages being about 55, 45 and 25 days, respectively

Topical microbicides to prevent the transmission of HIV: formulation gaps and challenges

The efforts of the topical microbicide field to identify a safe and effective topical microbicide were realized in July of 2010 with the reporting of the results of the Centre for the AIDS Programme of Research in South Africa 004 trial. In this trial, a 1% tenofovir gel was found to reduce women’s risk for HIV acquisition by 39% compared to placebo. To understand the impact of this trial on future microbicide development, we must view it from the historical perspective of previous phases 2 and 3 clinical trials with detergents and sulfated polyanions. This knowledge and emerging information must then be parlayed into the next steps needed to create a safe, effective, and acceptable topical microbicide. This review will look at the lessons learned from preclinical and clinical development of topical microbicides, focusing on two significant future challenges: (1) topical microbicide formulation safety and (2) the critical role that adherence to product use has in determining safety and efficacy in clinical trials and ultimately commercial viability of the licensed product. In addition to framing these issues within our current understanding of formulation and prevention of HIV acquisition, recent advances in our understanding of the mechanism of HIV transmission and how it informs on future formulation strategies will be briefly discussed

Context specificity of post-error and post-conflict cognitive control adjustments

There has been accumulating evidence that cognitive control can be adaptively regulated by monitoring for processing conflict as an index of online control demands. However, it is not yet known whether top-down control mechanisms respond to processing conflict in a manner specific to the operative task context or confer a more generalized benefit. While previous studies have examined the taskset-specificity of conflict adaptation effects, yielding inconsistent results, controlrelated performance adjustments following errors have been largely overlooked. This gap in the literature underscores recent debate as to whether post-error performance represents a strategic, control-mediated mechanism or a nonstrategic consequence of attentional orienting. In the present study, evidence of generalized control following both high conflict correct trials and errors was explored in a task-switching paradigm. Conflict adaptation effects were not found to generalize across tasksets, despite a shared response set. In contrast, post-error slowing effects were found to extend to the inactive taskset and were predictive of enhanced post-error accuracy. In addition, post-error performance adjustments were found to persist for several trials and across multiple task switches, a finding inconsistent with attentional orienting accounts of post-error slowing. These findings indicate that error-related control adjustments confer a generalized performance benefit and suggest dissociable mechanisms of post-conflict and post-error control. © 2014 Forster, Cho

Evaluation of the Oscillatory Interference Model of Grid Cell Firing through Analysis and Measured Period Variance of Some Biological Oscillators

Models of the hexagonally arrayed spatial activity pattern of grid cell firing in the literature generally fall into two main categories: continuous attractor models or oscillatory interference models. Burak and Fiete (2009, PLoS Comput Biol) recently examined noise in two continuous attractor models, but did not consider oscillatory interference models in detail. Here we analyze an oscillatory interference model to examine the effects of noise on its stability and spatial firing properties. We show analytically that the square of the drift in encoded position due to noise is proportional to time and inversely proportional to the number of oscillators. We also show there is a relatively fixed breakdown point, independent of many parameters of the model, past which noise overwhelms the spatial signal. Based on this result, we show that a pair of oscillators are expected to maintain a stable grid for approximately t = 5µ3/(4πσ)2 seconds where µ is the mean period of an oscillator in seconds and σ2 its variance in seconds2. We apply this criterion to recordings of individual persistent spiking neurons in postsubiculum (dorsal presubiculum) and layers III and V of entorhinal cortex, to subthreshold membrane potential oscillation recordings in layer II stellate cells of medial entorhinal cortex and to values from the literature regarding medial septum theta bursting cells. All oscillators examined have expected stability times far below those seen in experimental recordings of grid cells, suggesting the examined biological oscillators are unfit as a substrate for current implementations of oscillatory interference models. However, oscillatory interference models can tolerate small amounts of noise, suggesting the utility of circuit level effects which might reduce oscillator variability. Further implications for grid cell models are discussed

Alternative Ii-independent antigen-processing pathway in leukemic blasts involves TAP-dependent peptide loading of HLA class II complexes

During HLA class II synthesis in antigen-presenting cells, the invariant chain (Ii) not only stabilizes HLA class II complexes in the endoplasmic reticulum, but also mediates their transport to specialized lysosomal antigen-loading compartments termed MIICs. This study explores an alternative HLA class II presentation pathway in leukemic blasts that involves proteasome and transporter associated with antigen processing (TAP)-dependent peptide loading. Although HLA-DR did associate with Ii, Ii silencing in the human class II-associated invariant chain peptide (CLIP)-negative KG-1 myeloid leukemic cell line did not affect total and plasma membrane expression levels of HLA-DR, as determined by western blotting and flow cytometry. Since HLA-DR expression does require peptide binding, we examined the role of endogenous antigen-processing machinery in HLA-DR presentation by CLIP− leukemic blasts. The suppression of proteasome and TAP function using various inhibitors resulted in decreased HLA-DR levels in both CLIP− KG-1 and ME-1 blasts. Simultaneous inhibition of TAP and Ii completely down-modulated the expression of HLA-DR, demonstrating that together these molecules form the key mediators of HLA class II antigen presentation in leukemic blasts. By the use of a proteasome- and TAP-dependent pathway for HLA class II antigen presentation, CLIP− leukemic blasts might be able to present a broad range of endogenous leukemia-associated peptides via HLA class II to activate leukemia-specific CD4+ T cells

Physician-assisted suicide: a review of the literature concerning practical and clinical implications for UK doctors

BACKGROUND: A bill to legalize physician-assisted suicide in the UK recently made significant progress in the British House of Lords and will be reintroduced in the future. Until now there has been little discussion of the clinical implications of physician-assisted suicide for the UK. This paper describes problematical issues that became apparent from a review of the medical and psychiatric literature as to the potential effects of legalized physician-assisted suicide. DISCUSSION: Most deaths by physician-assisted suicide are likely to occur for the illness of cancer and in the elderly. GPs will deal with most requests for assisted suicide. The UK is likely to have proportionately more PAS deaths than Oregon due to the bill's wider application to individuals with more severe physical disabilities. Evidence from other countries has shown that coercion and unconscious motivations on the part of patients and doctors in the form of transference and countertransference contribute to the misapplication of physician-assisted suicide. Depression influences requests for hastened death in terminally ill patients, but is often under-recognized or dismissed by doctors, some of whom proceed with assisted death anyway. Psychiatric evaluations, though helpful, do not solve these problems. Safeguards that are incorporated into physician-assisted suicide criteria probably decrease but do not prevent its misapplication. SUMMARY: The UK is likely to face significant clinical problems arising from physician-assisted suicide if it is legalized. Terminally ill patients with mental illness, especially depression, are particularly vulnerable to the misapplication of physician-assisted suicide despite guidelines and safeguards

Oestrogen is important for maintenance of cartilage and subchondral bone in a murine model of knee osteoarthritis

Introduction: Oestrogen depletion may influence onset and/or progression of osteoarthritis. We investigated in an ovariectomized mouse model the impact of oestrogen loss and oestrogen supplementation on articular cartilage and subchondral bone in tibia and patella, and assessed bone changes in osteoarthritis development.Methods: C3H/HeJ mice were divided into four groups: sham-operated, oestrogen depletion by ovariectomy (OVX), OVX with estradiol supplementation (OVX+E) and OVX with bisphosphonate (OVX+BP). Each mouse had one knee injected with low-dose iodoacetate (IA), and the contralateral knee was injected with saline. Cartilage was analysed histologically 12 weeks postsurgery; bone changes were monitored over time using in vivo micro-computed tomography.Results: In tibiae, OVX alone failed to induce cartilage damage, but OVX and IA combination significantly induced cartilage damage. In patellae, OVX alone induced significant cartilage damage, whic