Studies on Complex Formation by Di(2-pyridyl)amine & 2-Aminopyridine with Metal Ions in Aqueous Solution: Evaluation of Enthalpies & Entropies of Complex Formation with Mn(II), Co(II), Ni(II), Cu(II), Zn(II) & Cd(II) & Ligand Field Stabilization Energies of the Metal Complexes

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The immunogenicity of colorectal cancers with high-degree microsatellite instability

BACKGROUND: High-degree microsatellite instability (MSI-H) is a feature of approximately 15% of sporadic colorectal cancers. Patients with MSI-H cancers have been reported to have a better prognosis than those with non-MSI-H cancers. The MSI-H subset is also characterised by a dense infiltrate of intra-epithelial lymphocytes and the hypothesis that the latter represents an efficacious immune response contributing to improved outcome is very attractive. METHODS: Data for this review were identified by searches of MEDLINE, PubMed, and cross references from relevant articles using the search terms 'microsatellite instability', 'colorectal cancer' and 'immunology', 'immune response' or 'immunogenicity'. RESULTS: A total of 38 articles were identified by the search criteria and a further 95 articles by cross-referencing. The relevance of the articles to be interviewed was established by hand searching. Out of a total of 133 articles identified, 47 articles were rejected due to lack of relevance. A total of 86 articles were included in the review, pertaining to microsatellite instability in colorectal cancer, and immune mechanisms in colorectal cancer. CONCLUSION: It is suggested that this distinct group of colorectal cancers may have inherent immunogenic properties and that further elucidation of these may be invaluable to the development of successful immunotherapy

Studies in the Brahmanas.

The study is concerned in the first place with an investigation of evidence for clan exogamy during the period of the Brahmanas, an the allied question of relationship-terminology. In the second place it deals with an elucidation of the complex problem of the Vratyas. An intermediary chapter is devoted to a description of the social and functional groups. Finally, a discussion of the available evidence for 'sapinda' restrictions is added. With regard to clan exogamy the word 'Aril in the Rgveda is of particular significance. 'Jana' and 'jami in the Brahmanas have also been found to be of similar importance in as such as the former signifies the marriage- able exogamous group and the latter the non-marriageable group. In the context of relationship-terminology the words 'agredidhisu' (the woman wooed before) 'didhistrpatil (the husband of 'agredidhisu') 'parivitta' (the unmarried elder brother) 'parivividana' (the younger brother married while the elder brother remains a bachelor) 'anujavara' (the posthumous son, or the younger brother of inferior status) 'bhrarvya' (the brother-in-law) and 'sajata' (fellow-clansman), are analysed. Amon the social and functional groups the distinction between those of the 'Taksan' and the 'Rathakgra' has be-n noticed. In dealing with the problem of the 'Vratyast', firstly former contributions in this field have be n reviewed in detail. Secondly, previous suggestions in connection with the etymologioal explanation of the word Vratyal have been considered. Thirdly, it has been pointed out that the 'Viatya' book of the Atharvaveda is, in all probability, compiled from fragments of a lost Brahmana text. Fourthly, the references to the 'Vratyas' in the Tandya and Jaiminiya have been duly noted and inter-pretations hitherto proposed, scrutinised. Lastly, the conolusion is arrived at, that the 'Vratyas were non-Brahmanical Aryans, possibly similar to the Ksatriyas, and having alien ritual practices. In conclusion it has been conjectured that the passage in the Satapatha bearing on 'Sapiada' restrictions ex-presses diapproval of the marriage-practice to which it refers

P20-05. Emergence of HIV-1 circulatory recombinant forms (CRFs) and unique recombinant forms (URFs) in North India: functional and pathogenic implications

No description supplie

A service evaluation of FIT and anaemia for risk stratification in the two week wait pathway for colorectal cancer

Introduction: New national guidance on urgent referral for investigation for Colorectal Cancer (CRC) included faecal occult blood testing in 2015. We evaluated faecal immunochemical testing (FIT) and anaemia as risk stratification tools in symptomatic patients suspected of having CRC.Methods: Postal FIT was incorporated into the CRC two week wait (2WW) pathway for all patients without rectal bleeding in 2016. Patients were investigated in the 2WW pathway as normal and outcomes of investigations were prospectively recorded. Anaemia was defined as haemoglobin less than 120g/L in women and less than 130g/L in men.Results: FIT kits were sent to 1106 patients with an 80.9% return rate; 810 patients completed investigation with 40 CRCs diagnosed (4.9%). Median FIT results were significantly higher in patients who were anaemic (median 4.8 iqr 0.8-34.1 versus 1.2 iqr 0-6.4, Mann-Whitney p less than 0.001).Some 538 (60.4%) had a result of less than 4 µgHb/gFaeces (limit of detectability) and 621 (69.7%) a result less than 10 µgHb/gFaeces. Sixty per cent of CRCs had a FIT reading of >150 µgHb/gFaeces. Five CRCs diagnosed in patients with a FIT4 µgHb/gFaeces had 97.5% sensitivity and 64.5% specificity for CRC diagnosis. A FIT result of >4 µgHb/gFaeces and/or anaemia had a 100% sensitivity and 45.3% specificity for CRC diagnosis.Conclusion: FIT is most useful at the extremes of detectability; strongly positive readings predict high rates of CRC and other significant pathology, whilst very low readings in the absence of anaemia or palpable rectal mass identify a group with very low risk. High return rates for FIT within this 2WW pathway indicate its acceptability

Dynamics of Transformation from Segregation to Mixed Wealth Cities

We model the dynamics of the Schelling model for agents described simply by a continuously distributed variable - wealth. Agents move to neighborhoods where their wealth is not lesser than that of some proportion of their neighbors, the threshold level. As in the case of the classic Schelling model where segregation obtains between two races, we find here that wealth-based segregation occurs and persists. However, introducing uncertainty into the decision to move - that is, with some probability, if agents are allowed to move even though the threshold level condition is contravened - we find that even for small proportions of such disallowed moves, the dynamics no longer yield segregation but instead sharply transition into a persistent mixed wealth distribution. We investigate the nature of this sharp transformation between segregated and mixed states, and find that it is because of a non-linear relationship between allowed moves and disallowed moves. For small increases in disallowed moves, there is a rapid corresponding increase in allowed moves, but this tapers off as the fraction of disallowed moves increase further and finally settles at a stable value, remaining invariant to any further increase in disallowed moves. It is the overall effect of the dynamics in the initial region (with small numbers of disallowed moves) that shifts the system away from a state of segregation rapidly to a mixed wealth state. The contravention of the tolerance condition could be interpreted as public policy interventions like minimal levels of social housing or housing benefit transfers to poorer households. Our finding therefore suggests that it might require only very limited levels of such public intervention - just sufficient to enable a small fraction of disallowed moves, because the dynamics generated by such moves could spur the transformation from a segregated to mixed equilibrium.Comment: 12 pages, 7 figure

Colorectal cancers with microsatellite instability display mRNA expression signatures characteristic of increased immunogenicity

BACKGROUND: Colorectal cancers displaying high-degree microsatellite instability (MSI-H) have an improved prognosis compared to microsatellite stable (MSS) cancers. The observation of pronounced lymphocytic infiltrates suggests that MSI-H cancers are inherently more immunogenic. We aimed to compare the gene expression profiles of MSI-H and MSS cancers to provide evidence for an activated immune response in the former. RESULTS: We analysed tissue from 133 colorectal cancer patients with full consent and Local Ethics Committee approval. Genomic DNA was analysed for microsatellite instability in BAT-26. High-quality RNA was used for microarray analysis on the Affymetrix(® )HG-U133A chip. Data was analysed on GeneSpring software version 6.0. Confirmatory real-time RT-PCR was performed on 28 MSI-H and 26 MSS cancers. A comparison of 29 MSI-H and 104 MSS cancers identified 2070 genes that were differentially expressed between the two groups [P < 0.005]. Significantly, many key immunomodulatory genes were up-regulated in MSI-H cancers. These included antigen chaperone molecules (HSP-70, HSP-110, Calreticulin, gp96), pro-inflammatory cytokines (Interleukin (IL)-18, IL-15, IL-8, IL-24, IL-7) and cytotoxic mediators (Granulysin, Granzyme A). Quantitative RT-PCR confirmed up-regulation of HSP-70 [P = 0.016], HSP-110 [P = 0.002], IL-18 [P = 0.004], IL-8 [0.002] and Granulysin [P < 0.0001]. CONCLUSIONS: The upregulation of a large number of genes implicated in immune response supports the theory that MSI-H cancers are immunogenic. The novel observation of Heat Shock Protein up-regulation in MSI-H cancer is highly significant in light of the recognised roles of these proteins in innate and antigen-specific immunogenicity. Increased mRNA levels of pro-inflammatory cytokines and cytotoxic mediators also indicate an activated anti-tumour immune response