Monoclonal Gammopathy of Undetermined Significance and Multiple Myeloma in Older Adults

Multiple myeloma (MM) and monoclonal gammopathy of undetermined significance (MGUS) are plasma cell disorders of aging. The landscape of the diagnosis and management of MM and MGUS are rapidly changing. This article provides an updated understanding of the clinical presentation, evaluation, diagnosis, and management of older adults with MM and MGUS. Because most oncology providers are not formally trained in geriatric medicine, geriatricians play a key role in providing oncologists with a broader understanding of patient health status in the hope of improving outcomes for older adults with MM

Study of a high spatial resolution 10B-based thermal neutron detector for application in neutron reflectometry: the Multi-Blade prototype

Although for large area detectors it is crucial to find an alternative to detect thermal neutrons because of the 3He shortage, this is not the case for small area detectors. Neutron scattering science is still growing its instruments' power and the neutron flux a detector must tolerate is increasing. For small area detectors the main effort is to expand the detectors' performances. At Institut Laue-Langevin (ILL) we developed the Multi-Blade detector which wants to increase the spatial resolution of 3He-based detectors for high flux applications. We developed a high spatial resolution prototype suitable for neutron reflectometry instruments. It exploits solid 10B-films employed in a proportional gas chamber. Two prototypes have been constructed at ILL and the results obtained on our monochromatic test beam line are presented here

Assessing the Influence of Letter Position in Reading Normal and Transposed Texts Using a Letter Detection Task

During word recognition, some letters appear to play a more important role than others. Although some studies have suggested that the first and last letters of a word have a privileged status, there is no consensus with regards to the importance of the different letter positions when reading connected text. In the current experiments, we used a simple letter search task to examine the impact of letter position on word identification in connected text using a classic paper and pencil procedure (Experiment 1) and an eye movement monitoring procedure (Experiment 2). In Experiments 3 and 4, a condition with transposed letters was included. Our results show that the first letter of a word is detected more easily than the other letters, and transposing letters in a word revealed the importance of the final letter. It is concluded that both the initial and final letters play a special role in word identification during reading but that the underlying processes might differ

Some Restrictions Abroad Affecting Corporations

A neutron detector concept based on solid layers of boron carbide enriched in 1 B has been in development for the last few years as an alternative for He-3 by collaboration between the ILL, ESS and Linkoping University. This Multi-Grid detector uses layers of aluminum substrates coated with (B4C)-B-10 on both sides that are traversed by the incoming neutrons. Detection is achieved using a gas counter readout principle. By segmenting the substrate and using multiple anode wires, the detector is made inherently position sensitive. This development is aimed primarily at neutron scattering instruments with large detector areas, such as time-of-flight chopper spectrometers. The most recent prototype has been built to be interchangeable with the He-3 detectors of IN6 at ILL. The 1 B detector has an active area of 32 x 48 cm(2). It was installed at the IN6 instrument and operated for several weeks, collecting data in parallel with the regularly scheduled experiments, thus providing the first side-by-side comparison with the conventional He-3 detectors. Results include an efficiency comparison, assessment of the in-detector scattering contribution, sensitivity to gamma-rays and the signal-to-noise ratio in time-of-flight spectra. The good expected performance has been confirmed with the exception of an unexpected background count rate. This has been identified as natural alpha activity in aluminum. New convertor substrates are under study to eliminate this source of background

Multimodal Chemical Imaging of Amyloid Plaque Polymorphism Reveals A beta Aggregation Dependent Anionic Lipid Accumulations and Metabolism

Amyloid plaque formation constitutes one of the main pathological hallmarks of Alzheimer’s disease (AD) and is suggested to be a critical factor driving disease pathogenesis. Interestingly, in patients that display amyloid pathology but remain cognitively normal, Aβ deposits are predominantly of diffuse morphology suggesting that cored plaque formation is primarily associated with cognitive deterioration and AD pathogenesis. Little is known about the molecular mechanism responsible for conversion of monomeric Aβ into neurotoxic aggregates and the predominantly cored deposits observed in AD. The structural diversity among Aβ plaques, including cored/compact- and diffuse, may be linked to their distinct Aβ profile and other chemical species including neuronal lipids. We developed a novel, chemical imaging paradigm combining matrix assisted laser desorption/ionization imaging mass spectrometry (MALDI IMS) and fluorescent amyloid staining. This multimodal imaging approach was used to probe the lipid chemistry associated with structural plaque heterogeneity in transgenic AD mice (tgAPPSwe) and was correlated to Aβ profiles determined by subsequent laser microdissection and immunoprecipitation-mass spectrometry. Multivariate image analysis revealed an inverse localization of ceramides and their matching metabolites to diffuse and cored structures within single plaques, respectively. Moreover, phosphatidylinositols implicated in AD pathogenesis, were found to localize to the diffuse Aβ structures and correlate with Aβ1–42. Further, lysophospholipids implicated in neuroinflammation were increased in all Aβ deposits. The results support previous clinical findings on the importance of lipid disturbances in AD pathophysiology and associated sphingolipid processing. These data highlight the potential of multimodal imaging as a powerful technology to probe neuropathological mechanisms

A comparison of transgenic rodent mutation and in vivo comet assay responses for 91 chemicals.

A database of 91 chemicals with published data from both transgenic rodent mutation (TGR) and rodent comet assays has been compiled. The objective was to compare the sensitivity of the two assays for detecting genotoxicity. Critical aspects of study design and results were tabulated for each dataset. There were fewer datasets from rats than mice, particularly for the TGR assay, and therefore, results from both species were combined for further analysis. TGR and comet responses were compared in liver and bone marrow (the most commonly studied tissues), and in stomach and colon evaluated either separately or in combination with other GI tract segments. Overall positive, negative, or equivocal test results were assessed for each chemical across the tissues examined in the TGR and comet assays using two approaches: 1) overall calls based on weight of evidence (WoE) and expert judgement, and 2) curation of the data based on a priori acceptability criteria prior to deriving final tissue specific calls. Since the database contains a high prevalence of positive results, overall agreement between the assays was determined using statistics adjusted for prevalence (using AC1 and PABAK). These coefficients showed fair or moderate to good agreement for liver and the GI tract (predominantly stomach and colon data) using WoE, reduced agreement for stomach and colon evaluated separately using data curation, and poor or no agreement for bone marrow using both the WoE and data curation approaches. Confidence in these results is higher for liver than for the other tissues, for which there were less data. Our analysis finds that comet and TGR generally identify the same compounds (mainly potent mutagens) as genotoxic in liver, stomach and colon, but not in bone marrow. However, the current database content precluded drawing assay concordance conclusions for weak mutagens and non-DNA reactive chemicals

Survivorship care for older adults with cancer: U13 conference report

Older adult cancer survivors currently account for almost 60% of all cancer survivors. The number of older cancer survivors will continue to increase as the population ages and as patients’ live longer after a cancer diagnosis. As part of cancer center accreditation, the American College of Surgeons Commission on Cancer® (CoC) has placed great importance on survivorship care planning. While the CoC has set standards for general survivorship care, there is sparse evidence on how to best care for older adult cancer survivors. Concern exists among the medical community that survivorship care plans could increase paperwork without improving outcomes. Given the diverse and unique needs of older adult cancer survivors, the inter-professional team provides a structure and process for survivorship care built around the particular needs of older adults. The Cancer and Aging Research Group (CARG), in partnership with the NIA/NCI, held a U13 conference in May 2015 in part to discuss survivorship care for older adults with cancer. This report discusses four themes that emerged from one section of the conference: (1) survivorship care is a process that continually evolves to meet the needs of older adults; (2) older adult cancer survivors have unique needs and care plans should be tailored to meet these needs; (3) the inter-professional team is ideally suited to structure survivorship care of older adults; (4) patient advocacy must be encouraged throughout the cancer care continuum. As evidence based survivorship practices develop, the unique needs of older adults need to be given substantial attention

Determination of absolute neutrino masses from Z-bursts

Ultrahigh energy neutrinos (UHE\nu) scatter on relic neutrinos (R\nu) producing Z bosons, which can decay hadronically producing protons (Z-burst). We compare the predicted proton spectrum with the observed ultrahigh energy cosmic ray (UHECR) spectrum and determine the mass of the heaviest R\nu via a maximum likelihood analysis. Our prediction depends on the origin of the power-like part of the UHECR spectrum: m_\nu=2.75^{+1.28}_{-0.97} eV for Galactic halo and 0.26^{+0.20}_{-0.14} eV for extragalactic (EG) origin. The necessary UHE\nu flux should be detected in the near future.Comment: slight rewording, revised neutrino fluxes, conclusions unchanged, version to appear in Phys. Rev. Let

Assessing medical student knowledge and attitudes about shared decision making across the curriculum: protocol for an international online survey and stakeholder analysis

Introduction: Shared decision making (SDM) is a goal of modern medicine; however, it is not currently embedded in routine care. Barriers include clinicians’ attitudes, lack of knowledge and training and time constraints. Our goal is to support the development and delivery of a robust SDM curriculum in medical education. Our objective is to assess undergraduate medical students’ knowledge of and attitudes towards SDM in four countries. Methods and analysis: The first phase of the study involves a web-based cross-sectional survey of undergraduate medical students from all years in selected schools across the United States (US), Canada and undergraduate and graduate students in the Netherlands. In the United Kingdom (UK), the survey will be circulated to all medical schools through the UK Medical School Council. We will sample students equally in all years of training and assess attitudes towards SDM, knowledge of SDM and participation in related training. Medical students of ages 18 years and older in the four countries will be eligible. The second phase of the study will involve semistructured interviews with a subset of students from phase 1 and a convenience sample of medical school curriculum experts or stakeholders. Data will be analysed using multivariable analysis in phase 1 and thematic content analysis in phase 2. Method, data source and investigator triangulation will be performed. Online survey data will be reported according to the Checklist for Reporting the Results of Internet E-Surveys. We will use the COnsolidated criteria for REporting Qualitative research for all qualitative data. Ethics and dissemination: The study has been approved for dissemination in the US, the Netherlands, Canada and the UK. The study is voluntary with an informed consent process. The results will be published in a peer-reviewed journal and will help inform the inclusion of SDM-specific curriculum in medical education worldwide

Recent advances in non-surgical management of cancer in the elderly [version 1; referees: 2 approved]

This article summarizes the seminal publications from mid-2016 through 2017 in the area of medical care for older adults with cancer. Areas addressed include chemotherapy tolerance and efficacy in the aged, geriatric fitness assessments, and advancements in palliative and supportive care. The practice-changing finding from this past year’s publications is that antipsychotics should not be used in the management of terminal delirium in older adults receiving palliative care. The other trials demonstrated an improved understanding of the utility of geriatric assessments in patients with cancer, developed the body of information about which chemotherapy agents are safe and effective in older adults (and which are not), and expanded our understanding of good palliative and supportive care