Archon Genomics X PRIZE Validation Protocol

This document is a collective assembly of techniques designed to test the quality and accuracy of 100 whole human genome sequences resulting from the $10 Million Archon Genomics X PRIZE (AGXP) competition. The purpose of this article is to enlist constructive criticism from the genomic and genetic community on the outlined approaches. The intent for the final version of this Validation Protocol is to become a useful standard by which to gauge the capabilities of whole genome sequencing technologies that emerge even after 2012

Faculty Mentoring: Shaping A Program

A well developed mentoring program should not be just considered another faculty activity but rather a significant program that can define a preeminent academic institution. A Faculty Learning Community (FLC) at Metropolitan State University of Denver (MSU Denver) was charged with determining whether the needs of new faculty members and the institution were being addressed in a manner that would optimize the productivity, acclimation, and professional enhancement of those new faculty members who would eventually be the foundation of the institution’s future. The FLC conducted a year-long study and an extensive survey in order to provide the administration with findings, suggestions, and recommendations for shaping a faculty mentoring program for the future

What do part-time geographically dispersed faculty members need for their professional development?

As the landscape of higher education has changed over the past decade, many institutions of higher education find that they are employing an ever increasing number of part-time, temporary faculty members. While many of the part-time temporary faculty members come to the institution with high levels of experience and skills in their disciplinary area, they are often not well grounded in the workings of institutions of higher education or in providing high-quality instruction to the young adult and adult learners who populate the classrooms in higher education. One way institutions of higher education can promote high levels of student success and student achievement is through providing high-quality professional development that equips the faculty member with the tools needed to provide effective instruction and a strong focus on student learning. Yet a review of literature in this area yields few examples of institutions that have analyzed the professional development needs of their part-time temporary faculty and addressed these needs in any depth. As a result, the professional development activities offered by the current faculty professional development programs may not meet their unique needs. This project, a collaborative venture between the Faculty Professional Development program and Extended Campuses undertook a purposive sampling of part-time faculty members in geographically distributed locations in an attempt to identify themes and issues related to providing effective professional development activities. This poster session will provide a summary of the findings of this sampling and plans for subsequent follow up surveys to more accurately understand the range of potential needs of faculty members distributed across and outside the state

Different prognostic impact of recurrent gene mutations in chronic lymphocytic leukemia depending on IGHV gene somatic hypermutation status: a study by ERIC in HARMONY

Cancer genetics; Genetics researchGenètica del càncer; Recerca genèticaGenética del cáncer; Investigación genéticaRecent evidence suggests that the prognostic impact of gene mutations in patients with chronic lymphocytic leukemia (CLL) may differ depending on the immunoglobulin heavy variable (IGHV) gene somatic hypermutation (SHM) status. In this study, we assessed the impact of nine recurrently mutated genes (BIRC3, EGR2, MYD88, NFKBIE, NOTCH1, POT1, SF3B1, TP53, and XPO1) in pre-treatment samples from 4580 patients with CLL, using time-to-first-treatment (TTFT) as the primary end-point in relation to IGHV gene SHM status. Mutations were detected in 1588 (34.7%) patients at frequencies ranging from 2.3–9.8% with mutations in NOTCH1 being the most frequent. In both univariate and multivariate analyses, mutations in all genes except MYD88 were associated with a significantly shorter TTFT. In multivariate analysis of Binet stage A patients, performed separately for IGHV-mutated (M-CLL) and unmutated CLL (U-CLL), a different spectrum of gene alterations independently predicted short TTFT within the two subgroups. While SF3B1 and XPO1 mutations were independent prognostic variables in both U-CLL and M-CLL, TP53, BIRC3 and EGR2 aberrations were significant predictors only in U-CLL, and NOTCH1 and NFKBIE only in M-CLL. Our findings underscore the need for a compartmentalized approach to identify high-risk patients, particularly among M-CLL patients, with potential implications for stratified management.The European Research Initiative on CLL (ERIC) is a partner in the HARMONY Alliance, the EHA Scientific Working group on CLL and the ELN Workpackage 7 on CLL. This work was in part supported by; Associazione Italiana per la Ricerca sul Cancro—AIRC, Milano, Italy (Investigator Grant #20246 and Special Program on Metastatic Disease—5 per mille #21198); ERA NET TRANSCAN-2 Joint Transnational Call for Proposals: JTC 2014 (project #143 GCH-CLL) and JTC 2016 (project #179 NOVEL), project code (MIS) 5041673; Bando della Ricerca Finalizzata 2018, Ministero della Salute, Roma, Italy (progetto RF-2018–12368231); “la Caixa” Foundation (Health Research 2017 Program HR17-00221); the American Association for Cancer Research (2021 AACR-Amgen Fellowship in Clinical/Translational Cancer Research, 21-40-11-NADE), the European Hematology Association (EHA Junior Research Grant 2021, RG-202012-00245), and the Lady Tata Memorial Trust (International Award for Research in Leukaemia 2021-2022, LADY_TATA_21_3223); the Hellenic Precision Medicine Network in Oncology; project ODYSSEAS (Intelligent and Automated Systems for enabling the Design, Simulation and Development of Integrated Processes and Products) implemented under the “Action for the Strategic Development on the Research and Technological Sector”, funded by the Operational Programme “Competitiveness, Entrepreneurship and Innovation” (NSRF 2014-2020) and co-financed by Greece and the European Union, with grant agreement no: MIS 5002462”; MH CZ—DRO (FNBr, 65269705), NV19-03-00091 and the project National Institute for Cancer Research (Programme EXCELES, ID Project No. LX22NPO5102)—Funded by the European Union—Next-Generation EU; Instituto de Salud Carlos III (ISCIII), “PI21/00983”, co-funded by the European Union; the EU’s Horizon 2020 research and innovation program under grant agreement No. 739593, by the Ministry of Innovation and Technology of Hungary from the National Research, Development and Innovation Fund, financed under the K21_137948, FK20_134253, TKP2021-EGA-24 and TKP2021-NVA-15 funding schemes, and Elixir Hungary; Instituto de Salud Carlos III (ISCIII), “PI21/00983”, co-funded by the European Union; Fondo di Ateneo per la Ricerca (FAR) 2019, 2020 and 2021 of the University of Ferrara (GMR; AC), Associazione Italiana contro le Leucemie-Linfomi e Mieloma ONLUS Ferrara (AC; GMR), BEAT Leukemia Foundation Milan Italy (AC); the Danish Cancer Society and the CLL-CLUE project under the frame of ERA PerMed; Cancer Research UK (ECRIN-M3 accelerator award C42023/A29370, Southampton Experimental Cancer Medicine Centre grant C24563/A15581, Cancer Research UK Southampton Centre grant C34999/A18087, and programme C2750/A23669); the Swedish Cancer Society (19 0425 Pj 01 H), the Swedish Research Council (2020-01750), the Knut and Alice Wallenberg Foundation (2016.0373), Region Stockholm (ALF/FoUI-962423), and Radiumhemmets Forskningsfonder (194133), Stockholm; and Lion’s Cancer Research Foundation, Uppsala

IgG-Switched CLL Has a Distinct Immunogenetic Signature from the Common MD Variant: Ontogenetic Implications

Abstract Purpose: Immunoglobulin G–switched chronic lymphocytic leukemia (G-CLL) is a rare variant of CLL, whose origin and ontogenetic relationship to the common IgM/IgD (MD-CLL) variant remains undefined. Here, we sought for clues about the ontogeny of G-CLL versus MD-CLL by profiling the relevant IG gene repertoires. Experimental Design: Using purpose-built bioinformatics methods, we performed detailed immunogenetic profiling of a multinational CLL cohort comprising 1,256 cases, of which 1,087 and 169 expressed IG mu/delta and gamma heavy chains, respectively. Results: G-CLL has a highly skewed IG gene repertoire that is distinct from MD-CLL, especially in terms of (i) overuse of the IGHV4-34 and IGHV4-39 genes and (ii) differential somatic hypermutation (SHM) load. Repertoire differences were also found when comparing subgroups with similar SHM status and were mainly attributed to the exclusive representation in G-CLL of two major subsets with quasi-identical (stereotyped) B-cell receptors. These subsets, namely #4 (IGHV4-34/IGKV2-30) and #8 (IGHV4-39/IGKV1(D)-39), were found to display sharply contrasting SHM and clinical behavior. Conclusions: G-CLL exhibits an overall distinct immunogenetic signature from MD-CLL, prompting speculations about distinct ontogenetic derivation and/or immune triggering. The reasons underlying the differential regulation of SHM among G-CLL cases remain to be elucidated. Clin Cancer Res; 20(2); 323–30. ©2013 AACR

Temporary Bridging Agents for use in Drilling and Completion of Enhanced Geothermal Systems

CSI Technologies, in conjunction with Alta Rock Energy and the University of Utah have undergone a study investigating materials and mechanisms with potential for use in Enhanced Geothermal Systems wells as temporary diverters or lost circulation materials. Studies were also conducted with regards to particle size distribution and sealing effectiveness using a lab-scale slot testing apparatus to simulate fractures. From the slot testing a numerical correlation was developed to determine the optimal PSD for a given fracture size. Field trials conducted using materials from this study were also successful

Breakthrough Energy Savings with Waterjet Technology

Experiments performed at the University of Missouri-Rolla's Waterjet Laboratory have demonstrated clearly the ability of waterjets to disaggregate, in a single step, four different mineral ores, including ores containing iron, lead and copper products. The study focused mainly on galena-bearing dolomite, a lead ore, and compared the new technology with that of traditional mining and milling to liberate the valuable constituent for the more voluminous host rock. The technical term for the disintegration of the ore to achieve this liberation is comminution. The potential for energy savings if this process can be improved, is immense. Further, if this separation can be made at the mining face, then the potential energy savings include avoidance of transportation (haulage and hoisting) costs to move, process and store this waste at the surface. The waste can, instead, be disposed into the available cavities within the mine. The savings also include the elimination of the comminution, crushing and grinding, stages in the processing plant. Future prototype developments are intended to determine if high-pressure waterjet mining and processing can be optimized to become cheaper than traditional fragmentation by drilling and blasting and to optimize the separation process. The basic new mining process was illustrated in tests on two local rock types, a low-strength sandstone with hematite inclusions, and a medium to high-strength dolomite commonly used for construction materials. Illustrative testing of liberation of minerals, utilized a lead-bearing dolomite, and included a parametric study of the optimal conditions needed to create a size distribution considered best for separation. The target goal was to have 50 percent of the mined material finer than 100 mesh (149 microns). Of the 21 tests that were run, five clearly achieved the target. The samples were obtained as run-of-mine lumps of ore, which exhibited a great deal of heterogeneity within the samples. This, in turn, reduced the ability to apply detailed statistical tests to the product outcomes. Nonetheless, a regression analysis showed that operating pressures between 105 (10,000psi) and 140 (15,000psi) MegaPascals (MPa) at traverse speeds no greater than 10 cm/min (4 in/min), best generated the target result. Variation in other parameters, rotation speed, nozzle diameter, and nozzle separation angle, during the preliminary tests did not substantially change the product, and so were kept fixed during the ore mining tests. The experimental protocols were developed to include proper treatment of the lead-bearing materials, which may be considered hazardous. In anticipation of the creation of a mineral processing design for separation of the concentrates from the tailings (waste), assays were made of the metal content of each screen size for each of the 21 runs; with three screens and a pan for undersize, to give a total of 84 assays. This information will enable Dr. McNulty, project consultant, to create a flow sheet for the prototype mining machine. As a preliminary component to such a system, the experimental layout included a product-recovery system that delivered all of the fragmented product to the nest of screens which allowed study of the liberation at the different size levels. Where incomplete liberation is found, a secondary process was demonstrated for using pressurized cavitation to further comminute the material. This concept was successfully demonstrated, with a small cavitation chamber illustrating the much smaller space that such a tool requires, relative to conventional ball and rod mills. Additional testing is ongoing, external to this program, to find whether an one-step process using higher jet pressures and longer dwell times to achieve all the required comminution in mining, is more efficient than a two-step process in which normal jet pressures and feed rates do the initial mining, but full particle liberation is achieved only through secondary processing of the product in a cavitation chamber. Subsequent testing is also planned, to determine preferred methods for separating ore minerals from the waste. Tests with this system have included both the galena samples, and copper ores from Poland. The development of this tool lies within an expanding market for the use of high-pressure waterjet equipment across a broad spectrum of applications. As the industry develops new tools, it is anticipated that the research team will investigate the development of a prototype machine based on these tools, since this will simplify and speed up equipment development. It is hoped that once this is developed that can be taken into an active mine. Such a machine should be able to produce large enough samples to allow assessment of optimal operating conditions

Association between proton pump inhibitor therapy and clostridium difficile infection: a contemporary systematic review and meta-analysis.

Abstract Introduction Emerging epidemiological evidence suggests that proton pump inhibitor (PPI) acid-suppression therapy is associated with an increased risk of Clostridium difficile infection (CDI). Methods Ovid MEDLINE, EMBASE, ISI Web of Science, and Scopus were searched from 1990 to January 2012 for analytical studies that reported an adjusted effect estimate of the association between PPI use and CDI. We performed random-effect meta-analyses. We used the GRADE framework to interpret the findings. Results We identified 47 eligible citations (37 case-control and 14 cohort studies) with corresponding 51 effect estimates. The pooled OR was 1.65, 95% CI (1.47, 1.85), I2 = 89.9%, with evidence of publication bias suggested by a contour funnel plot. A novel regression based method was used to adjust for publication bias and resulted in an adjusted pooled OR of 1.51 (95% CI, 1.26–1.83). In a speculative analysis that assumes that this association is based on causality, and based on published baseline CDI incidence, the risk of CDI would be very low in the general population taking PPIs with an estimated NNH of 3925 at 1 year. Conclusions In this rigorously conducted systemic review and meta-analysis, we found very low quality evidence (GRADE class) for an association between PPI use and CDI that does not support a cause-effect relationship