What Approach to Watershed Management?

A study of one Iowa watershed by USDA and Iowa State University economists points up the need for examining alternative methods for watershed management in controlling soil erosion and damage-producing runoff

Germline and somatic JAK2 mutations and susceptibility to chronic myeloproliferative neoplasms

Myeloproliferative neoplasms (MPNs) are a group of closely related stem-cell-derived clonal proliferative diseases. Most cases are sporadic but first-degree relatives of MPN patients have a five- to seven-fold increased risk for developing an MPN. The tumors of most patients carry a mutation in the Janus kinase 2 gene (JAK2V617F). Recently, three groups have described a strong association of JAK2 germline polymorphisms with MPN in patients positive for JAK2V617F. The somatic mutation occurs primarily on one particular germline JAK2 haplotype, which may account for as much as 50% of the risk to first-degree relatives. This finding provides new directions for unraveling the pathogenesis of MPN

Demonstration of integrated microscale optics in surface-electrode ion traps

In ion trap quantum information processing, efficient fluorescence collection is critical for fast, high-fidelity qubit detection and ion-photon entanglement. The expected size of future many-ion processors require scalable light collection systems. We report on the development and testing of a microfabricated surface-electrode ion trap with an integrated high numerical aperture (NA) micromirror for fluorescence collection. When coupled to a low NA lens, the optical system is inherently scalable to large arrays of mirrors in a single device. We demonstrate stable trapping and transport of 40Ca+ ions over a 0.63 NA micromirror and observe a factor of 1.9 enhancement in photon collection compared to the planar region of the trap.Comment: 15 pages, 8 figure

Structural variants shape the genomic landscape and clinical outcome of multiple myeloma

Deciphering genomic architecture is key to identifying novel disease drivers and understanding the mechanisms underlying myeloma initiation and progression. In this work, using the CoMMpass dataset, we show that structural variants (SV) occur in a nonrandom fashion throughout the genome with an increased frequency in the t(4;14), RB1, or TP53 mutated cases and reduced frequency in t(11;14) cases. By mapping sites of chromosomal rearrangements to topologically associated domains and identifying significantly upregulated genes by RNAseq we identify both predicted and novel putative driver genes. These data highlight the heterogeneity of transcriptional dysregulation occurring as a consequence of both the canonical and novel structural variants. Further, it shows that the complex rearrangements chromoplexy, chromothripsis and templated insertions are common in MM with each variant having its own distinct frequency and impact on clinical outcome. Chromothripsis is associated with a significant independent negative impact on clinical outcome in newly diagnosed cases consistent with its use alongside other clinical and genetic risk factors to identify prognosis

Timing the initiation of multiple myeloma

The evolution and progression of multiple myeloma and its precursors over time is poorly understood. Here, we investigate the landscape and timing of mutational processes shaping multiple myeloma evolution in a large cohort of 89 whole genomes and 973 exomes. We identify eight processes, including a mutational signature caused by exposure to melphalan. Reconstructing the chronological activity of each mutational signature, we estimate that the initial transformation of a germinal center B-cell usually occurred during the first 2nd-3rd decades of life. We define four main patterns of activation-induced deaminase (AID) and apolipoprotein B mRNA editing catalytic polypeptide-like (APOBEC) mutagenesis over time, including a subset of patients with evidence of prolonged AID activity during the pre-malignant phase, indicating antigen-responsiveness and germinal center reentry. Our findings provide a framework to study the etiology of multiple myeloma and explore strategies for prevention and early detection

Research priorities for liver glycogen storage disease:An international priority setting partnership with the James Lind Alliance

The international liver glycogen storage disease (GSD) priority setting partnership (IGSDPSP) was established to identify the top research priorities in this area. The multiphase methodology followed the principles of the James Lind Alliance (JLA) guidebook. An international scoping survey in seven languages was distributed to patients, carers, and healthcare professionals to gather uncertainties, which were consolidated into summary questions. The existing literature was reviewed to ensure that the summary questions had not yet been answered. A second survey asked responders to prioritize these summary questions. A final shortlist of 22 questions was discussed during an international multi-stakeholder workshop, and a consensus was reached on the top 11 priorities using an adapted nominal group technique.In the first survey, a total of 1388 questions were identified from 763 responders from 58 countries. These original uncertainties were refined into 72 summary questions for a second prioritization survey. In total 562 responders from 58 countries answered the second survey. From the second survey, the top 10 for patients, carers and healthcare professionals was identified and this shortlist of 22 questions was taken to the final workshop. During the final workshop, participants identified the worldwide top 11 research priorities for liver GSD. In addition, a top three research priorities per liver GSD subtype was identified.This unique priority setting partnership is the first international, multilingual priority setting partnership focusing on ultra-rare diseases. This process provides a valuable resource for researchers and funding agencies to foster interdisciplinary and transnational research projects with a clear benefit for patients

A Benchmarking Exercise for Quality Blended Learning. A Challenge for European Universities in the 21st Century

This paper shares the experiences of 5 universities involved in a Benchmarking Exercise oneLearning in 2009 through ESMU. A total of 9 European universities participated in theexercise with the purpose of evaluating their existing eLearning practices and policies andgetting advice on which areas to improve and how.Initially, the paper discusses the benchmarking concept and reasons why institutions shouldengage in benchmarking exercises. Benchmarking is viewed as a method for qualityassurance and enhancement in higher education. Self-assessment is involved at theparticipating institutions, which leads to a high level of awareness and understanding ofexisting practices and policies at different levels of the organisation. Benchmarking is thus anefficient self-improvement tool.In chapter two, the planning of the benchmarking exercise is outlined. A combination of anindividual, collaborative and expert approach to benchmarking was chosen.Chapter three deals with the creation of the benchmarking questionnaire which was acollaborative effort between all nine participating universities, ESMU and EADTU. Takingtheir starting point in the online E-xellence benchmarking tool developed by EADTU,participants reformulated, deleted and added benchmarks within the following six categories:Strategic management, curriculum design, course design, course delivery, staff support andstudent support. An effort was made to translate the E-xellence questions to the blendedlearning context of the participating universities.The internal data collection and formulation of responses are accounted for in chapter 4which also contains reflections on the challenges and benefits of the selected approaches.Chapter five presents the overall conclusions of the benchmarking exercise within each ofthe six benchmark categories.The final chapter discusses and provides examples of how participants can use thebenchmarking results to improve existing practices and policies and outlines potentialexternal collaboration opportunities between participants

Comprehensive detection of recurring genomic abnormalities : a targeted sequencing approach for multiple myeloma

Recent genomic research efforts in multiple myeloma have revealed clinically relevant molecular subgroups beyond conventional cytogenetic classifications. Implementing these advances in clinical trial design and in routine patient care requires a new generation of molecular diagnostic tools. Here, we present a custom capture next-generation sequencing (NGS) panel designed to identify rearrangements involving the IGH locus, arm level, and focal copy number aberrations, as well as frequently mutated genes in multiple myeloma in a single assay. We sequenced 154 patients with plasma cell disorders and performed a head-to-head comparison with the results from conventional clinical assays, i.e., fluorescent in situ hybridization (FISH) and single-nucleotide polymorphism (SNP) microarray. Our custom capture NGS panel had high sensitivity (>99%) and specificity (>99%) for detection of IGH translocations and relevant chromosomal gains and losses in multiple myeloma. In addition, the assay was able to capture novel genomic markers associated with poor outcome such as bi-allelic events involving TP53. In summary, we show that a multiple myeloma designed custom capture NGS panel can detect IGH translocations and CNAs with very high concordance in relation to FISH and SNP microarrays and importantly captures the most relevant and recurrent somatic mutations in multiple myeloma rendering this approach highly suitable for clinical application in the modern era

Guidelines for Acquisition, Interpretation, and Reporting of Whole-Body MRI in Myeloma: Myeloma Response Assessment and Diagnosis System (MY-RADS).

Acknowledging the increasingly important role of whole-body MRI for directing patient care in myeloma, a multidisciplinary, international, and expert panel of radiologists, medical physicists, and hematologists with specific expertise in whole-body MRI in myeloma convened to discuss the technical performance standards, merits, and limitations of currently available imaging methods. Following guidance from the International Myeloma Working Group and the National Institute for Clinical Excellence in the United Kingdom, the Myeloma Response Assessment and Diagnosis System (or MY-RADS) imaging recommendations are designed to promote standardization and diminish variations in the acquisition, interpretation, and reporting of whole-body MRI in myeloma and allow response assessment. This consensus proposes a core clinical protocol for whole-body MRI and an extended protocol for advanced assessments. Published under a CC BY 4.0 license. Online supplemental material is available for this article