Exogenous dopamine reduces GABA receptor availability in the human brain

Background: While it has recently been shown that dopamine release stimulates conscious self‐monitoring through the generation of gamma oscillations in medial prefrontal/anterior cingulate cortex, and that the GABAergic system is effective in producing such oscillations, interaction of the two transmitter systems has not been demonstrated in humans. We here hypothesize that dopamine challenge stimulates the GABA system directly in the medial prefrontal/anterior cingulate region in the human brain. // Methods: Positron emission tomography (PET) with the GABA receptor α1/α5 subtype ligand [11C] Ro15‐4513 was used to detect changes in GABA receptor availability after clinical oral doses of levodopa in a double blind controlled study. // Results: We here provide the first direct evidence for such coupling in the cerebral cortex, in particular in the medial prefrontal anterior cingulate region, by showing that exogenous dopamine decreases [11C] Ro15‐4513 binding widely in the human brain compatible with a fall in α1 subtype availability in GABA complexes due to increased GABA activity

The relationship between the systemic inflammatory response, tumour proliferative activity, T-lymphocytic and macrophage infiltration, microvessel density and survival in patients with primary operable breast cancer

The significance of the inter-relationship between tumour and host local/systemic inflammatory responses in primary operable invasive breast cancer is limited. The inter-relationship between the systemic inflammatory response (pre-operative white cell count, C-reactive protein and albumin concentrations), standard clinicopathological factors, tumour T-lymphocytic (CD4+ and CD8+) and macrophage (CD68+) infiltration, proliferative (Ki-67) index and microvessel density (CD34+) was examined using immunohistochemistry and slide-counting techniques, and their prognostic values were examined in 168 patients with potentially curative resection of early-stage invasive breast cancer. Increased tumour grade and proliferative activity were associated with greater tumour T-lymphocyte (P<0.05) and macrophage (P<0.05) infiltration and microvessel density (P<0.01). The median follow-up of survivors was 72 months. During this period, 31 patients died; 18 died of their cancer. On univariate analysis, increased lymph-node involvement (P<0.01), negative hormonal receptor (P<0.10), lower albumin concentrations (P<0.01), increased tumour proliferation (P<0.05), increased tumour microvessel density (P<0.05), the extent of locoregional control (P<0.0001) and limited systemic treatment (Pless than or equal to0.01) were associated with cancer-specific survival. On multivariate analysis of these significant covariates, albumin (HR 4.77, 95% CI 1.35–16.85, P=0.015), locoregional treatment (HR 3.64, 95% CI 1.04–12.72, P=0.043) and systemic treatment (HR 2.29, 95% CI 1.23–4.27, P=0.009) were significant independent predictors of cancer-specific survival. Among tumour-based inflammatory factors, only tumour microvessel density (P<0.05) was independently associated with poorer cancer-specific survival. The host inflammatory responses are closely associated with poor tumour differentiation, proliferation and malignant disease progression in breast cancer

Scientific Case for Avoiding Dangerous Climate Change to Protect Young People and Nature

28 pages, 6 figures; version submitted to Proceedings of the National Academy of SciencesGlobal warming due to human-made gases, mainly CO2, is already 0.8{\deg}C and deleterious climate impacts are growing worldwide. More warming is 'in the pipeline' because Earth is out of energy balance, with absorbed solar energy exceeding planetary heat radiation. Maintaining a climate that resembles the Holocene, the world of stable shorelines in which civilization developed, requires rapidly reducing fossil fuel CO2 emissions. Such a scenario is economically sensible and has multiple benefits for humanity and other species. Yet fossil fuel extraction is expanding, including highly carbon-intensive sources that can push the climate system beyond tipping points such that amplifying feedbacks drive further climate change that is practically out of humanity's control. This situation raises profound moral issues as young people, future generations, and nature, with no possibility of protecting their future well-being, will bear the principal consequences of actions and inactions of today's adults

Comparative efficacy of topical tetraVisc versus lidocaine gel in cataract surgery

<p>Abstract</p> <p>Background</p> <p>To compare the clinical efficacy of lidocaine 2% with tetracaine 0.5% for cataract surgery.</p> <p>Methods</p> <p>In a randomized, multi-surgeon, controlled clinical trial,122 consecutive cataract cases eligible for topical anesthesia, were randomly assigned to receive lidocaine 2% gel (1 ml) or tetracaine solution 0.5% (TetraVisc, 0.5 ml) before clear corneal phacoemulsification. Main outcome measure was visual analog scale (0 to 10), which was used to measure intra-operative pain. Secondary outcome measures included patients' discomfort due to tissue manipulation and surgeon graded patients' cooperation. Duration of surgery and intra-operative complications were also recorded.</p> <p>Results</p> <p>The mean age in TetraVisc (TV) group was 70.4 years and in the lidocaine gel group (LG) it was 70.6 years (p = 0.89). Patient reported mean intra-operative pain scores by visual analog scale were 0.70 ± 0.31 in TV group and 1.8 ± 0.4 in LG group (<it>P </it>< 0.001). Mean patient cooperation was also marginally better in the TV group (8.3 ± 0.3) compared to LG group (8.4 ± 0.6) (P = 0.25). 96% of patients in TV group showed intra-operative corneal clarity compared to 91% in LG group. TV group had less (1 out of 61 patients, 1.6%) intra-operative complications than LG group (3 out of 61 patients, 4.8%). No anesthesia related complications were noted in either group</p> <p>Conclusion</p> <p>Topical TetraVisc solution was superior to lidocaine 2% gel for pain control in patients undergoing clear corneal phacoemulsification. Lidocaine 2% gel is similar to TetraVisc in patient comfort and surgeon satisfaction.</p> <p>Trial Registration</p> <p><b>Clinical trials number</b>: ISRCTN78374774</p

Common carotid intima media thickness and ankle-brachial pressure index correlate with local but not global atheroma burden:a cross sectional study using whole body magnetic resonance angiography

Common carotid intima media thickness (CIMT) and ankle brachial pressure index (ABPI) are used as surrogate marker of atherosclerosis, and have been shown to correlate with arterial stiffness, however their correlation with global atherosclerotic burden has not been previously assessed. We compare CIMT and ABPI with atheroma burden as measured by whole body magnetic resonance angiography (WB-MRA).50 patients with symptomatic peripheral arterial disease were recruited. CIMT was measured using ultrasound while rest and exercise ABPI were performed. WB-MRA was performed in a 1.5T MRI scanner using 4 volume acquisitions with a divided dose of intravenous gadolinium gadoterate meglumine (Dotarem, Guerbet, FR). The WB-MRA data was divided into 31 anatomical arterial segments with each scored according to degree of luminal narrowing: 0 = normal, 1 = <50%, 2 = 50-70%, 3 = 70-99%, 4 = vessel occlusion. The segment scores were summed and from this a standardized atheroma score was calculated.The atherosclerotic burden was high with a standardised atheroma score of 39.5±11. Common CIMT showed a positive correlation with the whole body atheroma score (β 0.32, p = 0.045), however this was due to its strong correlation with the neck and thoracic segments (β 0.42 p = 0.01) with no correlation with the rest of the body. ABPI correlated with the whole body atheroma score (β -0.39, p = 0.012), which was due to a strong correlation with the ilio-femoral vessels with no correlation with the thoracic or neck vessels. On multiple linear regression, no correlation between CIMT and global atheroma burden was present (β 0.13 p = 0.45), while the correlation between ABPI and atheroma burden persisted (β -0.45 p = 0.005).ABPI but not CIMT correlates with global atheroma burden as measured by whole body contrast enhanced magnetic resonance angiography in a population with symptomatic peripheral arterial disease. However this is primarily due to a strong correlation with ilio-femoral atheroma burden

The stellar halo of the Galaxy

Stellar halos may hold some of the best preserved fossils of the formation history of galaxies. They are a natural product of the merging processes that probably take place during the assembly of a galaxy, and hence may well be the most ubiquitous component of galaxies, independently of their Hubble type. This review focuses on our current understanding of the spatial structure, the kinematics and chemistry of halo stars in the Milky Way. In recent years, we have experienced a change in paradigm thanks to the discovery of large amounts of substructure, especially in the outer halo. I discuss the implications of the currently available observational constraints and fold them into several possible formation scenarios. Unraveling the formation of the Galactic halo will be possible in the near future through a combination of large wide field photometric and spectroscopic surveys, and especially in the era of Gaia.Comment: 46 pages, 16 figures. References updated and some minor changes. Full-resolution version available at http://www.astro.rug.nl/~ahelmi/stellar-halo-review.pd

Finding needles in haystacks: linking scientific names, reference specimens and molecular data for Fungi

DNA phylogenetic comparisons have shown that morphology-based species recognition often underestimates fungal diversity. Therefore, the need for accurate DNA sequence data, tied to both correct taxonomic names and clearly annotated specimen data, has never been greater. Furthermore, the growing number of molecular ecology and microbiome projects using high-throughput sequencing require fast and effective methods for en masse species assignments. In this article, we focus on selecting and re-annotating a set of marker reference sequences that represent each currently accepted order of Fungi. The particular focus is on sequences from the internal transcribed spacer region in the nuclear ribosomal cistron, derived from type specimens and/or ex-type cultures. Re-annotated and verified sequences were deposited in a curated public database at the National Center for Biotechnology Information (NCBI), namely the RefSeq Targeted Loci (RTL) database, and will be visible during routine sequence similarity searches with NR_prefixed accession numbers. A set of standards and protocols is proposed to improve the data quality of new sequences, and we suggest how type and other reference sequences can be used to improve identification of Fungi

Characterization of digital medical images utilizing support vector machines

BACKGROUND: In this paper we discuss an efficient methodology for the image analysis and characterization of digital images containing skin lesions using Support Vector Machines and present the results of a preliminary study. METHODS: The methodology is based on the support vector machines algorithm for data classification and it has been applied to the problem of the recognition of malignant melanoma versus dysplastic naevus. Border and colour based features were extracted from digital images of skin lesions acquired under reproducible conditions, using basic image processing techniques. Two alternative classification methods, the statistical discriminant analysis and the application of neural networks were also applied to the same problem and the results are compared. RESULTS: The SVM (Support Vector Machines) algorithm performed quite well achieving 94.1% correct classification, which is better than the performance of the other two classification methodologies. The method of discriminant analysis classified correctly 88% of cases (71% of Malignant Melanoma and 100% of Dysplastic Naevi), while the neural networks performed approximately the same. CONCLUSION: The use of a computer-based system, like the one described in this paper, is intended to avoid human subjectivity and to perform specific tasks according to a number of criteria. However the presence of an expert dermatologist is considered necessary for the overall visual assessment of the skin lesion and the final diagnosis

No association of breast cancer risk with integrin beta3 (ITGB3) Leu33Pro genotype

To pursue a borderline increased risk of breast cancer for carriers of two integrin beta3 (ITGB3) 33Pro alleles found in a recent prospective study, we conducted a case–control study of 1088 women with breast cancer and 4815 female controls. Leu33Pro heterozygotes, homozygotes and heterozygotes+homozygotes vs noncarriers had odds ratios for breast cancer of 1.0 (95% confidence interval: 0.8–1.1), 0.8 (0.5–1.2) and 1.0 (0.8–1.1), respectively. After stratification for conventional risk factors, odds ratio for breast cancer in heterozygotes, homozygotes and heterozygotes+homozygotes vs noncarriers were not increased above 1.0 in any of the 14 strata examined. This was also true after stratification for tumour histological subtype and cancer stage at the time of diagnosis