Temporal trends in mode, site and stage of presentation with the introduction of colorectal cancer screening: a decade of experience from the West of Scotland

background:  Population colorectal cancer screening programmes have been introduced to reduce cancer-specific mortality through the detection of early-stage disease. The present study aimed to examine the impact of screening introduction in the West of Scotland. methods:  Data on all patients with a diagnosis of colorectal cancer between January 2003 and December 2012 were extracted from a prospectively maintained regional audit database. Changes in mode, site and stage of presentation before, during and after screening introduction were examined. results:  In a population of 2.4 million, over a 10-year period, 14 487 incident cases of colorectal cancer were noted. Of these, 7827 (54%) were males and 7727 (53%) were socioeconomically deprived. In the postscreening era, 18% were diagnosed via the screening programme. There was a reduction in both emergency presentation (20% prescreening vs 13% postscreening, P0.001) and the proportion of rectal cancers (34% prescreening vs 31% pos-screening, P0.001) over the timeframe. Within non-metastatic disease, an increase in the proportion of stage I tumours at diagnosis was noted (17% prescreening vs 28% postscreening, P0.001). conclusions:  Within non-metastatic disease, a shift towards earlier stage at diagnosis has accompanied the introduction of a national screening programme. Such a change should lead to improved outcomes in patients with colorectal cancer

Functional significance may underlie the taxonomic utility of single amino acid substitutions in conserved proteins

We hypothesized that some amino acid substitutions in conserved proteins that are strongly fixed by critical functional roles would show lineage-specific distributions. As an example of an archetypal conserved eukaryotic protein we considered the active site of ß-tubulin. Our analysis identified one amino acid substitution—ß-tubulin F224—which was highly lineage specific. Investigation of ß-tubulin for other phylogenetically restricted amino acids identified several with apparent specificity for well-defined phylogenetic groups. Intriguingly, none showed specificity for “supergroups” other than the unikonts. To understand why, we analysed the ß-tubulin Neighbor-Net and demonstrated a fundamental division between core ß-tubulins (plant-like) and divergent ß-tubulins (animal and fungal). F224 was almost completely restricted to the core ß-tubulins, while divergent ß-tubulins possessed Y224. Thus, our specific example offers insight into the restrictions associated with the co-evolution of ß-tubulin during the radiation of eukaryotes, underlining a fundamental dichotomy between F-type, core ß-tubulins and Y-type, divergent ß-tubulins. More broadly our study provides proof of principle for the taxonomic utility of critical amino acids in the active sites of conserved proteins

Application of Graphene within Optoelectronic Devices and Transistors

Scientists are always yearning for new and exciting ways to unlock graphene's true potential. However, recent reports suggest this two-dimensional material may harbor some unique properties, making it a viable candidate for use in optoelectronic and semiconducting devices. Whereas on one hand, graphene is highly transparent due to its atomic thickness, the material does exhibit a strong interaction with photons. This has clear advantages over existing materials used in photonic devices such as Indium-based compounds. Moreover, the material can be used to 'trap' light and alter the incident wavelength, forming the basis of the plasmonic devices. We also highlight upon graphene's nonlinear optical response to an applied electric field, and the phenomenon of saturable absorption. Within the context of logical devices, graphene has no discernible band-gap. Therefore, generating one will be of utmost importance. Amongst many others, some existing methods to open this band-gap include chemical doping, deformation of the honeycomb structure, or the use of carbon nanotubes (CNTs). We shall also discuss various designs of transistors, including those which incorporate CNTs, and others which exploit the idea of quantum tunneling. A key advantage of the CNT transistor is that ballistic transport occurs throughout the CNT channel, with short channel effects being minimized. We shall also discuss recent developments of the graphene tunneling transistor, with emphasis being placed upon its operational mechanism. Finally, we provide perspective for incorporating graphene within high frequency devices, which do not require a pre-defined band-gap.Comment: Due to be published in "Current Topics in Applied Spectroscopy and the Science of Nanomaterials" - Springer (Fall 2014). (17 pages, 19 figures

Preliminary study on the utilization of Ca2+ and HCO3 − in karst water by different sources of Chlorella vulgaris

This article aims to present a picture of how a university discipline has been created in Lithuania, given the background of changes caused by the Lithuania’s emancipation from the Soviet Union. The theoretical frame of reference is provided by a modified model of Bronfenbrenners developmental ecology. Data collection has primarily been in the form of interviews with university staff from Lithuanian institutions for higher education. In addition to the interviews, literature lists, course schedules and other key documents have been collected and analysed. The analysis focuses on individual’s conceptualisation of three main areas. The study demonstrates how the creation of management and economics as a university discipline in Lithuania has been formed by a combination of political/ideological, economic, institutional and individual factors. One of the study’s main contributions is to highlight the significance of the concept of academic freedom and to focus on the paradox, where constraint under the old system is replaced by another form of constraint. In this case, where the rigidity of the old Soviet doctrine is replaced by a new freedom; but instead of being given greater opportunities to influence and change the subject, the academic staff are forced into a position where, once again they are subjugated to the influences of international sources

Spatial constancy of attention across eye movements is mediated by the presence of visual objects

Recent studies have shown that attentional facilitation lingers at the retinotopic coordinates of a previously attended position after an eye movement. These results are intriguing, because the retinotopic location becomes behaviorally irrelevant once the eyes have moved. Critically, in these studies participants were asked to maintain attention on a blank location of the screen. In the present study, we examined whether the continuing presence of a visual object at the cued location could affect the allocation of attention across eye movements. We used a trans-saccadic cueing paradigm in which the relevant positions could be defined or not by visual objects (simple square outlines). We find an attentional benefit at the spatiotopic location of the cue only when the object (the placeholder) has been continuously present at that location. We conclude that the presence of an object at the attended location is a critical factor for the maintenance of spatial constancy of attention across eye movements, a finding that helps to reconcile previous conflicting results

The incidence of unpleasant dreams after sub-anaesthetic ketamine

Ketamine is an N-methyl-D-aspartate (NMDA)receptor antagonist with psychotogenic effects and for whichthere are diverse reports of whether pleasant or unpleasantdreams result during anaesthesia, post-operatively or aftersub-anaesthetic use. The aim was to assess in healthy volunteers the incidence ofunpleasant dreams over the three nights after receiving asub-anaesthetic dose of ketamine, in comparison to placebo,and with retrospective home nightmare frequency as acovariate.Thirty healthy volunteers completed questionnairesabout retrospective home dream recall and were then giveneither ketamine or placebo. Ketamine resulted in significantly more meandream unpleasantness relative to placebo and caused athreefold increase in the odds ratio for the incidence of anunpleasant dream. The number of dreams reported over thethree nights did not differ between the groups. Theincidence of unpleasant dreams after ketamine use waspredicted by retrospectively assessed nightmare frequencyat home.Ketamine causes unpleasant dreams over thethree post-administration nights. This may be evidence of aresidual psychotogenic effect that is not found on standardself-report symptomatology measures or a result of disturbedsleep electrophysiology. The results have theoretical implications for the relationship between nightmares and schizotypy

Whole-genome sequencing identifies genetic alterations in pediatric low-grade gliomas

The most common pediatric brain tumors are low-grade gliomas (LGGs). We used whole-genome sequencing to identify multiple new genetic alterations involving BRAF, RAF1, FGFR1, MYB, MYBL1 and genes with histone-related functions, including H3F3A and ATRX, in 39 LGGs and low-grade glioneuronal tumors (LGGNTs). Only a single non-silent somatic alteration was detected in 24 of 39 (62%) tumors. Intragenic duplications of the portion of FGFR1 encoding the tyrosine kinase domain (TKD) and rearrangements of MYB were recurrent and mutually exclusive in 53% of grade II diffuse LGGs. Transplantation of Trp53-null neonatal astrocytes expressing FGFR1 with the duplication involving the TKD into the brains of nude mice generated high-grade astrocytomas with short latency and 100% penetrance. FGFR1 with the duplication induced FGFR1 autophosphorylation and upregulation of the MAPK/ERK and PI3K pathways, which could be blocked by specific inhibitors. Focusing on the therapeutically challenging diffuse LGGs, our study of 151 tumors has discovered genetic alterations and potential therapeutic targets across the entire range of pediatric LGGs and LGGNTs.Jinghui Zhang, Gang Wu, Claudia P Miller, Ruth G Tatevossian, James D Dalton, Bo Tang, Wilda Orisme, Chandanamali Punchihewa, Matthew Parker, Ibrahim Qaddoumi, Fredrick A Boop, Charles Lu, Cyriac Kandoth, Li Ding, Ryan Lee, Robert Huether, Xiang Chen, Erin Hedlund, Panduka Nagahawatte, Michael Rusch, Kristy Boggs, Jinjun Cheng, Jared Becksfort, Jing Ma, Guangchun Song, Yongjin Li, Lei Wei, Jianmin Wang, Sheila Shurtleff, John Easton, David Zhao, Robert S Fulton, Lucinda L Fulton, David J Dooling, Bhavin Vadodaria, Heather L Mulder, Chunlao Tang, Kerri Ochoa, Charles G Mullighan, Amar Gajjar, Richard Kriwacki, Denise Sheer, Richard J Gilbertson, Elaine R Mardis, Richard K Wilson, James R Downing, Suzanne J Baker and David W Elliso

Genome of the Avirulent Human-Infective Trypanosome—Trypanosoma rangeli

Background: Trypanosoma rangeli is a hemoflagellate protozoan parasite infecting humans and other wild and domestic mammals across Central and South America. It does not cause human disease, but it can be mistaken for the etiologic agent of Chagas disease, Trypanosoma cruzi. We have sequenced the T. rangeli genome to provide new tools for elucidating the distinct and intriguing biology of this species and the key pathways related to interaction with its arthropod and mammalian hosts.  Methodology/Principal Findings: The T. rangeli haploid genome is ,24 Mb in length, and is the smallest and least repetitive trypanosomatid genome sequenced thus far. This parasite genome has shorter subtelomeric sequences compared to those of T. cruzi and T. brucei; displays intraspecific karyotype variability and lacks minichromosomes. Of the predicted 7,613 protein coding sequences, functional annotations could be determined for 2,415, while 5,043 are hypothetical proteins, some with evidence of protein expression. 7,101 genes (93%) are shared with other trypanosomatids that infect humans. An ortholog of the dcl2 gene involved in the T. brucei RNAi pathway was found in T. rangeli, but the RNAi machinery is non-functional since the other genes in this pathway are pseudogenized. T. rangeli is highly susceptible to oxidative stress, a phenotype that may be explained by a smaller number of anti-oxidant defense enzymes and heatshock proteins.  Conclusions/Significance: Phylogenetic comparison of nuclear and mitochondrial genes indicates that T. rangeli and T. cruzi are equidistant from T. brucei. In addition to revealing new aspects of trypanosome co-evolution within the vertebrate and invertebrate hosts, comparative genomic analysis with pathogenic trypanosomatids provides valuable new information that can be further explored with the aim of developing better diagnostic tools and/or therapeutic targets

Temporal Dynamics of Visual Attention Allocation

We often temporally prepare our attention for an upcoming event such as a starter pistol. In such cases, our attention should be properly allocated around the expected moment of the event to process relevant sensory input efficiently. In this study, we examined the dynamic changes of attention levels near the expected moment by measuring contrast sensitivity to a target that was temporally cued by a five-second countdown. We found that the overall attention level decreased rapidly after the expected moment, while it stayed relatively constant before it. Results were not consistent with the predictions of existing explanations of temporal attention such as the hazard rate or the stimulus-driven oscillations. A control experiment ruled out the possibility that the observed pattern was due to biased time perception. In a further experiment with a wider range of cue-stimulus-intervals, we observed that attention level increased until the last 500 ms of the interval range, and thereafter, started to decrease. Based on the performances of a generative computational model, we suggest that our results reflect the nature of temporal attention that takes into account the subjectively estimated hazard rate and the probability of relevant events occurring in the near future

The experience of linking Victorian emergency medical service trauma data

<p>Abstract</p> <p>Background</p> <p>The linking of a large Emergency Medical Service (EMS) dataset with the Victorian Department of Human Services (DHS) hospital datasets and Victorian State Trauma Outcome Registry and Monitoring (VSTORM) dataset to determine patient outcomes has not previously been undertaken in Victoria. The objective of this study was to identify the linkage rate of a large EMS trauma dataset with the Department of Human Services hospital datasets and VSTORM dataset.</p> <p>Methods</p> <p>The linking of an EMS trauma dataset to the hospital datasets utilised deterministic and probabilistic matching. The linking of three EMS trauma datasets to the VSTORM dataset utilised deterministic, probabilistic and manual matching.</p> <p>Results</p> <p>There were 66.7% of patients from the EMS dataset located in the VEMD. There were 96% of patients located in the VAED who were defined in the VEMD as being admitted to hospital. 3.7% of patients located in the VAED could not be found in the VEMD due to hospitals not reporting to the VEMD. For the EMS datasets, there was a 146% increase in successful links with the trauma profile dataset, a 221% increase in successful links with the mechanism of injury only dataset, and a 46% increase with sudden deterioration dataset, to VSTORM when using manual compared to deterministic matching.</p> <p>Conclusion</p> <p>This study has demonstrated that EMS data can be successfully linked to other health related datasets using deterministic and probabilistic matching with varying levels of success. The quality of EMS data needs to be improved to ensure better linkage success rates with other health related datasets.</p