A study to examine the operation and function of a virtual UK environmental specimen bank (UK-ESB). Final report

Executive Summary: 1. Environmental specimen banking is recognised internationally as an integral part of long-term environmental research and monitoring. Analysis of preserved environmental samples is often needed to detect and quantify patterns and rate of environmental change, and the emergence and progression of environmental hazards and risks. 2. National Environmental Specimen Banks have been established in several countries; they vary in scope and breadth. There are a few specialised environmental specimen holdings in the UK but no national-scale catalogue of holdings, despite an estimated annual spend of £16 million to store specimens. This lack of information results in under-exploitation of archived specimens and is a lost opportunity to facilitate world-class science and identify emerging pressures and threats on the environment. 3. An earlier project had identified key stakeholder organisations either engaged in archiving nationally important environmental specimens or who wished to utilise such specimens. These stakeholders had agreed there was a need for a national metadata catalogue of environmental specimens (subsequently termed a virtual UK-ESB). The objective of the current project was to further develop a virtual UK-ESB. Specifically, the aim was to work with stakeholders to establish the correct metadata entry fields, the search capabilities, the functionality and the nature of the hosting website of a virtual UK-ESB. 4. More than 80 stakeholder organisations that had previously expressed an interest in a UK-ESB were approached to provide feedback either electronically or by attending a stakeholder workshop. Thirty eight organisations responded. All remained interested in the UK-ESB concept and seventeen answered the survey questions. 5. Mock-ups of data entry screens, search screens and ideas around the functionality of a UK-ESB were developed by the CEH project team. These were mailed to stakeholders for feedback. Initial feedback was incorporated into the mock-ups which were then presented for discussion at a workshop comprising 15 attendees from across the specimen archiving community, CEH and the UK-EOF. 6. Workshop participants reviewed and agreed the format of 23 mandatory or optional data-entry fields for a virtual UK-ESB that, in the absence of standard for material samples and archives, were aligned with ISO19115 (geospatial metadata standard) and DublinCore (metadata standard). These fields were sub-divided into the following headings: Sample description, Categorisation, keywords and links, Storage Information and Contact information. Workshop participants also made a number of recommendations as to the format of the data entry screens and inclusion of extra fields. 7. Workshop participants reviewed options for search capabilities and made recommendations as to simple and advanced searching methods and their formats. It was also recommended that search facilities of the ESBs of other countries be examined to determine what is used, ease of use, and how they match the recommendations from the workshop. 8. Workshop participants reviewed options for functionality and agreed a detailed list of prioritised requirements. 9. Workshop participants agreed that a virtual UK-ESB should be hosted through a dedicated website that would also provide wider information, such as recently updated or added specimen holdings, most downloaded information, links to other groups, standard operating procedures, etc. 10. The next step for the development of a virtual UK-ESB is to implement the design and development ideas captured in the current report and build a test version of a virtual UK-ESB. This would be tested and refined, and could then be launched on a specifically designed website. This would need to be accompanied by a communication strategy. There is potential to link and co-brand a virtual UK-ESB with the UK-Environmental Observation Framework (UK-EOF)

A Survey Paper on Sequence Pattern Mining with Incremental Approach

Sequential pattern mining finds frequently occurring patterns ordered by time. The problem was first introduced by Agrawal and Srikant [1]. An example of a sequential pattern is “A customer who purchased a new Ford Explorer two years ago, is likely to respond favourably to a trade-in option now”. Let X be the clause “purchased a new Ford Explorer” and Y be the clause “responds favourably to a trade-in”. Then notice that the pattern XY above, is different from pattern YX which states that “A customer who responded favourably to a trade-in two years ago, will purchase a Ford Explorer now”. The order in which X and Y appear is important, and hence XY and YX are mined as two separate patterns.Sequential pattern mining is widely applicable since many types of data have a time component to them. For example, it can be used in the medical domain to help determine a correct diagnosis from the sequence of symptoms experienced; over customer data to help target repeat customers; and with web-log data to better structure a company’s website for easier access to the most popular links[2]

Identification of Germline Variants in Tumor Genomic Sequencing Analysis

This Correspondence relates to the article by Li et al (Standards and Guidelines for the Interpretation and Reporting of Sequence Variants in Cancer: A Joint Consensus Recommendation of the Association for Molecular Pathology, American Society of Clinical Oncology, and the College of American Pathologists. J Mol Diagn 2017, 19:4–23)

Nd3+ and Yb3+ doped phosphate glass waveguides fabricated using electric field assisted Ag+ diffusion

Solid-state waveguide lasers offer several attractive features that may make high efficiency and effective thermal management possible. Due to the ability to confine pump light to high intensity over distances much longer than the Rayleigh range, as well as maintaining good overlap between the pump and Iasing modes over the entire guiding region, effcient operation with high slope efficiency should be possible, even for quasi-three level laser systems. Since the waveguide region is typically only a few microns of thickness, heat can be extracted efficiently from the structure. The effects of heating are of less significance than in bulk solid-state lasers because mode confinement is maintained by an index of refraction difference, usually much larger than tnat induced by dn/dT or stress-optic effects. Rare earth doped waveguide laser action has been reported in numerous papers [14]. The processes for fabricating waveguides include film deposition methods such as epitaxial growth, RF sputtering, and most recently, thermal bonding of precision finished crystals [5]. In addition, ion implantation, ion exchange in a molten salt and electric field assisted solid film diffusion [6] have been utilized. The ion exchange method remains the simplest, particularly for many common laser glasses that already have mobile ions, and has received considerable attention in recent years. An excellent review is found in reference [7]. Our work has focused on developing process conditions for the fabrication of waveguides in phosphate laser glasses using solid silver film diffusion. These processes are important in determining the overall structure and properties of the guiding region, such as propagation loss, modal profile, and modal overlap between the pump and laser wavelengths. Phosphate laser glass was chosen as the solid state laser medium due to the useful spectroscopic properties of rare earth ions in these materials, as well as the range of material properties and compositions possible

Aortic Arch Morphology and Aortic Length in Patients with Dissection, Traumatic, and Aneurysmal Disease

ObjectivesTo assess aortic arch morphology and aortic length in patients with dissection, traumatic injury, and aneurysm undergoing TEVAR, and to identify characteristics specific to different pathologies.MethodThis was a retrospective analysis of the aortic arch morphology and aortic length of dissection, traumatic injury, and aneurysmal patients. Computed tomography imaging was evaluated of 210 patients (49 dissection, 99 traumatic injury, 62 aneurysm) enrolled in three trials that received the conformable GORE TAG thoracic endoprosthesis. The mean age of trauma patients was 43 ± 19.6 years, 57 ± 11.7 years for dissection and 72 ± 9.6 years for aneurysm patients. A standardized protocol was used to measure aortic arch diameter, length, and take-off angle and clockface orientation of branch vessels. Differences in arch anatomy and length were assessed using ANOVA and independent t tests.ResultsOf the 210 arches evaluated, 22% had arch vessel common trunk configurations. The aortic diameter and the distance from the left main coronary (LMC) to the left common carotid (LCC) were greater in dissection patients than in trauma or aneurysm patients (p < .001). Aortic diameter in aneurysm patients was greater compared with trauma patients (p < .05). The distances from the branch vessels to the celiac artery (CA) were greater in dissection and aneurysm patients than in trauma patients (p < .001). The take-off angle of the innominate (I), LCCA, and left subclavian (LS) were greater, between 19% and 36%, in trauma patients than in dissection and aneurysm patients (p < .001). Clockface orientation of the arch vessels varies between pathologies.ConclusionsArch anatomy has significant morphologic differences when comparing aortic pathologies. Describing these differences in a large sample of patients is beneficial for device designs and patient selection

Hybrid-Aligned Nematic Liquid-Crystal Modulators Fabricated On Vlsi Circuits

A new method for fabricating analog Light modulators on VLSI devices is described. The process is fully compatible with devices fabricated by commercial VLSI foundries, and the assembly of the modulator structures requires a small number of simple processing steps. The modulators are capable of analog amplitude or phase modulation and can operate at video rates and at low voltages (2.2 V). The modulation mechanism and the process yielding the modulator structures are described. Experimental data are presented. (C) 1995 Optical Society of Americ

Dynamical test of phase transition order

FWN – Publicaties zonder aanstelling Universiteit Leide

Subtyping sub-Saharan esophageal squamous cell carcinoma by comprehensive molecular analysis

Esophageal squamous cell carcinoma (ESCC) is endemic in regions of sub-Saharan Africa (SSA), where it is the third most common cancer. Here, we describe whole-exome tumor/normal sequencing and RNA transcriptomic analysis of 59 patients with ESCC in Malawi. We observed similar genetic aberrations as reported in Asian and North American cohorts, including mutations of TP53, CDKN2A, NFE2L2, CHEK2, NOTCH1, FAT1, and FBXW7. Analyses for nonhuman sequences did not reveal evidence for infection with HPV or other occult pathogens. Mutational signature analysis revealed common signatures associated with aging, cytidine deaminase activity (APOBEC), and a third signature of unknown origin, but signatures of inhaled tobacco use, aflatoxin and mismatch repair were notably absent. Based on RNA expression analysis, ESCC could be divided into 3 distinct subtypes, which were distinguished by their expression of cell cycle and neural transcripts. This study demonstrates discrete subtypes of ESCC in SSA, and suggests that the endemic nature of this disease reflects exposure to a carcinogen other than tobacco and oncogenic viruses

Association between Reimbursement Incentives and Physician Practice in Oncology: A Systematic Review

Importance: Significant controversy exists regarding whether physicians factor personal financial considerations into their clinical decision making. Within oncology, several reimbursement policies may incentivize physicians to increase health care use. Objective: To evaluate whether the financial incentives presented by oncology reimbursement policies affect physician practice patterns. Evidence Review: Studies evaluating an association between reimbursement incentives and changes in reimbursement policy on oncology care delivery were reviewed. Articles were identified systematically by searching PubMed/MEDLINE, Web of Science, Proquest Health Management, Econlit, and Business Source Premier. English-language articles focused on the US health care system that made empirical estimates of the association between a measurement of physician reimbursement/compensation and a measurement of delivery of cancer treatment services were included. The Risk of Bias in Non-Randomized Studies of Interventions tool was used to assess risk of bias. There were no date restrictions on the publications, and literature searches were finalized on February 14, 2018. Findings: Eighteen studies were included. All were observational cohort studies, and most had a moderate risk of bias. Heterogeneity of reimbursement policies and outcomes precluded meta-analysis; therefore, a qualitative synthesis was performed. Most studies (15 of 18 [83%]) reported an association between reimbursement and care delivery consistent with physician responsiveness to financial incentives, although such an association was not identified in all studies. Findings consistently suggested that self-referral arrangements may increase use of radiotherapy and that profitability of systemic anticancer agents may affect physicians' choice of drug. Findings were less conclusive as to whether profitability of systemic anticancer therapy affects the decision of whether to use any systemic therapy. Conclusions and Relevance: To date, this study is the first systematic review of reimbursement policy and clinical care delivery in oncology. The findings suggest that some oncologists may, in certain circumstances, alter treatment recommendations based on personal revenue considerations. An implication of this finding is that value-based reimbursement policies may be a useful tool to better align physician incentives with patient need and increase the value of oncology care

Mucosa-associated invariant T cells link intestinal immunity with antibacterial immune defects in alcoholic liver disease

Background/aims: Intestinal permeability with systemic distribution of bacterial products are central in the immunopathogenesis of alcoholic liver disease (ALD), yet links with intestinal immunity remain elusive. Mucosa-associated invariant T cells (MAIT) are found in liver, blood and intestinal mucosa and are a key component of antibacterial host defences. Their role in ALD is unknown. Methods/design: We analysed frequency, phenotype, transcriptional regulation and function of blood MAIT cells in severe alcoholic hepatitis (SAH), alcohol-related cirrhosis (ARC) and healthy controls (HC). We also examined direct impact of ethanol, bacterial products from faecal extracts and antigenic hyperstimulation on MAIT cell functionality. Presence of MAIT cells in colon and liver was assessed by quantitative PCR and immunohistochemistry/gene expression respectively. Results: In ARC and SAH, blood MAIT cells were dramatically depleted, hyperactivated and displayed defective antibacterial cytokine/cytotoxic responses. These correlated with suppression of lineage-specific transcription factors and hyperexpression of homing receptors in the liver with intrahepatic preservation of MAIT cells in ALD. These alterations were stronger in SAH, where surrogate markers of bacterial infection and microbial translocation were higher than ARC. Ethanol exposure in vitro, in vivo alcohol withdrawal and treatment with Escherichia coli had no effect on MAIT cell frequencies, whereas exposure to faecal bacteria/antigens induced functional impairments comparable with blood MAIT cells from ALD and significant MAIT cell depletion, which was not observed in other T cell compartments. Conclusions: In ALD, the antibacterial potency of MAIT cells is compromised as a consequence of contact with microbial products and microbiota, suggesting that the ‘leaky’ gut observed in ALD drives MAIT cell dysfunction and susceptibility to infection in these patients