1,052 research outputs found
Ready ... Go: Amplitude of the fMRI Signal Encodes Expectation of Cue Arrival Time
What happens when the brain awaits a signal of uncertain arrival time, as when a sprinter waits for the starting pistol? And what happens just after the starting pistol fires? Using functional magnetic resonance imaging (fMRI), we have discovered a novel correlate of temporal expectations in several brain regions, most prominently in the supplementary motor area (SMA). Contrary to expectations, we found little fMRI activity during the waiting period; however, a large signal appears after the “go” signal, the amplitude of which reflects learned expectations about the distribution of possible waiting times. Specifically, the amplitude of the fMRI signal appears to encode a cumulative conditional probability, also known as the cumulative hazard function. The fMRI signal loses its dependence on waiting time in a “countdown” condition in which the arrival time of the go cue is known in advance, suggesting that the signal encodes temporal probabilities rather than simply elapsed time. The dependence of the signal on temporal expectation is present in “no-go” conditions, demonstrating that the effect is not a consequence of motor output. Finally, the encoding is not dependent on modality, operating in the same manner with auditory or visual signals. This finding extends our understanding of the relationship between temporal expectancy and measurable neural signals
Using NMF for analyzing war logs
We investigate a semi-automated identification of technical problems occurred by armed forces weapon systems during mission of war. The proposed methodology is based on a semantic analysis of textual information in reports from soldiers (war logs). Latent semantic indexing (LSI) with non-negative matrix factorization (NMF) as technique from multivariate analysis and linear algebra is used to extract hidden semantic textual patterns from the reports. NMF factorizes the term-by-war log matrix - that consists of weighted term frequencies into two non-negative matrices. This enables natural parts-based representation of the report information and it leads to an easy evaluation by human experts because human brain also uses parts-based representation. For an improved research and technology planning, the identified technical problems are a valuable source of information. A case study extracts technical problems from military logs of the Afghanistan war. Results are compared to a manual analysis written by journalists of 'Der Spiegel'
Pain outcomes in patients with bone metastases from advanced cancer: assessment and management with bone-targeting agents
Bone metastases in advanced cancer frequently cause painful complications that impair patient physical activity and negatively affect quality of life. Pain is often underreported and poorly managed in these patients. The most commonly used pain assessment instruments are visual analogue scales, a single-item measure, and the Brief Pain Inventory Questionnaire-Short Form. The World Health Organization analgesic ladder and the Analgesic Quantification Algorithm are used to evaluate analgesic use. Bone-targeting agents, such as denosumab or bisphosphonates, prevent skeletal complications (i.e., radiation to bone, pathologic fractures, surgery to bone, and spinal cord compression) and can also improve pain outcomes in patients with metastatic bone disease. We have reviewed pain outcomes and analgesic use and reported pain data from an integrated analysis of randomized controlled studies of denosumab versus the bisphosphonate zoledronic acid (ZA) in patients with bone metastases from advanced solid tumors. Intravenous bisphosphonates improved pain outcomes in patients with bone metastases from solid tumors. Compared with ZA, denosumab further prevented pain worsening and delayed the need for treatment with strong opioids. In patients with no or mild pain at baseline, denosumab reduced the risk of increasing pain severity and delayed pain worsening along with the time to increased pain interference compared with ZA, suggesting that use of denosumab (with appropriate calcium and vitamin D supplementation) before patients develop bone pain may improve outcomes. These data also support the use of validated pain assessments to optimize treatment and reduce the burden of pain associated with metastatic bone disease
Functional Brain Imaging in the Clinical Assessment of Consciousness
Recent findings suggest that functional brain imaging might be used to identify consciousness in patients diagnosed with persistent vegetative state and minimally conscious state. Michael Rafii and James Brewer discuss the potential for fMRI's wider implementation in clinical practice, and associated caveats
Emergent complex neural dynamics
A large repertoire of spatiotemporal activity patterns in the brain is the
basis for adaptive behaviour. Understanding the mechanism by which the brain's
hundred billion neurons and hundred trillion synapses manage to produce such a
range of cortical configurations in a flexible manner remains a fundamental
problem in neuroscience. One plausible solution is the involvement of universal
mechanisms of emergent complex phenomena evident in dynamical systems poised
near a critical point of a second-order phase transition. We review recent
theoretical and empirical results supporting the notion that the brain is
naturally poised near criticality, as well as its implications for better
understanding of the brain
Preferential Gs protein coupling of the galanin Gal1 receptor in the μ-opioid-Gal1 receptor heterotetramer
Recent studies have proposed that heteromers of μ-opioid receptors (MORs) and galanin Gal1 receptors (Gal1Rs) localized in the mesencephalon mediate the dopaminergic effects of opioids. The present study reports converging evidence, using a peptide-interfering approach combined with biophysical and biochemical techniques, including total internal reflection fluorescence microscopy, for a predominant homodimeric structure of MOR and Gal1R when expressed individually, and for their preference to form functional heterotetramers when co-expressed. Results show that a heteromerization-dependent change in the Gal1R homodimeric interface leads to a switch in G-protein coupling from inhibitory Gi to stimulatory Gs proteins. The MOR-Gal1R heterotetramer, which is thus bound to Gs via the Gal1R homodimer and Gi via the MOR homodimer, provides the framework for a canonical Gs-Gi antagonist interaction at the adenylyl cyclase level. These novel results shed light on the intense debate about the oligomeric quaternary structure of G protein-coupled receptors, their predilection for heteromer formation, and the resulting functional significance
Performance-optimized hierarchical models predict neural responses in higher visual cortex
Current perspectives on bone metastases in castrate-resistant prostate cancer
Prostate cancer is the most frequent noncutaneous cancer occurring in men. On average, men with localized prostate cancer have
a high 10-year survival rate, and many can be cured. However, men with metastatic castrate-resistant prostate cancer have
incurable disease with poor survival despite intensive therapy. This unmet need has led to recent advances in therapy aimed at
treating bone metastases resulting from prostate cancer. The bone microenvironment lends itself to metastases in castrate-resistant
prostate cancer, as a result of complex interactions between the microenvironment and tumor cells. The development of 223radium
dichloride (Ra-223) to treat symptomatic bone metastases has improved survival in men with metastatic castrate-resistant
prostate cancer. Moreover, Ra-223 may have effects on the tumor microenvironment that enhance its activity. Ra-223 treatment
has been shown to prolong survival, and its effects on the immune system are under investigation. Because prostate cancer affects
a sizable portion of the adult male population, understanding how it metastasizes to bone is an important step in advancing
therapy. Clinical trials that are underway should yield new information on whether Ra-223 synergizes effectively with immunotherapy
agents and whether Ra-223 has enhancing effects on the immune system in patients with prostate cancer
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