Search

Introduction and Problem StatementNeurology residency training is inpatient focused, underemphasizing outpatient disorders. We implemented a novel didactic series of facilitated discussions between a patient and their outpatient neurologist to expose residents to outpatient topics and management skills.Objectives(1) Improve residents' understanding of the roles and responsibilities of the neurologist in the outpatient setting; (2) share with residents the patient's perspective of living with chronic neurologic disease; and (3) improve residents' understanding of what effective shared decision making entails.Methods and Curriculum DescriptionResidents in an academic neurology program participated. Six bimonthly, 1-hour sessions were piloted in person in 2016; participants were surveyed after each session to refine the format. The formal program (6 sessions) was held virtually in 2020–2021. Each session focused on 1 disorder. The format was conversational and moderated by a course director. Discussion points were preplanned and focused on patients' experiences living with chronic neurologic disease and shared decision making. Residents, participating faculty, and patients were surveyed at the conclusion of the 2020–2021 series to evaluate its effectiveness.Results and Assessment DataFifty-five survey responses were completed by residents during the pilot. Only 12 residents (22%) indicated that they longitudinally followed more than 1 patient with the condition represented in the session. Qualitative comments from residents and faculty (n = 5) identified that hearing the patient perspective was the most valuable component of the series. Twenty-one of 54 residents evaluated the final program. A majority of residents, 100% of faculty (n = 6), and 100% of patients (n = 6) felt that the program's 3 learning objectives were met. Forty-eight percent of residents reported increased interest in outpatient careers. Faculty agreed that the session format was as effective as traditional lecture, without added preparation burden. Patients felt that sharing their experiences would help physicians better understand their illness and improve care for future patients; all would participate again.Discussion and Lessons LearnedOur series effectively educated residents about underrepresented outpatient topics. Hearing patients' perspectives was instrumental in achieving our learning objectives. Key factors for successful implementation included a faculty moderator, preplanned questions, and teaching slides to emphasize key learning points. Future work should evaluate whether residents' increased knowledge and interest translates into sustained behavior change and more residents selecting outpatient careers.

Myasthenia gravis is an antibody-mediated autoimmune disorder of the post-synaptic neuromuscular junction resulting in fluctuating, fatigable weakness. Most patients first present with extraocular symptoms (diplopia and/or ptosis), and in 15% of cases symptoms will remain restricted to only the extraocular muscles (ocular myasthenia gravis [OMG]). The history and clinical examination are of the utmost importance in correctly identifying OMG patients, as supportive serologic or electrodiagnostic studies are frequently nondiagnostic. In this review, we outline a diagnostic approach to OMG (focusing on key clinical features), discuss therapeutic options, and highlight recent developments in the understanding of OMG.

This article reviews the pathogenesis, clinical features, and management of toxic myopathy related to common medications, critical illness, and illicit substances.Muscle symptoms are common among statin users and are usually reversible after discontinuation of the statin; rarely, however, statins trigger an immune-mediated necrotizing myopathy that persists and requires immunomodulatory therapy. Autoantibodies targeting 3-hydroxy-3-methylglutaryl coenzyme A reductase can distinguish the toxic and immune-mediated forms. Immune checkpoint inhibitors, increasingly used in the treatment of advanced cancer, have recently been associated with the development of inflammatory myositis. A reversible mitochondrial myopathy has long been associated with zidovudine, but recent reports elucidate the risk of myopathy with newer antivirals, such as telbivudine and raltegravir.The medications most commonly associated with myopathy include statins, amiodarone, chloroquine, hydroxychloroquine, colchicine, certain antivirals, and corticosteroids, and myopathy can occur with chronic alcoholism. Certain clinical, electrodiagnostic, and histologic features can aid in early recognition. Stopping the use of the offending agent reverses symptoms in most cases, but specific and timely treatment may be required in cases related to agents that trigger immune-mediated muscle injury.

INTRODUCTION/AIMS Optimal management of myasthenia gravis (MG) in individuals ≥65 y old is unknown and patient factors may limit therapeutic choices. Safety and efficacy of rituximab in older patients with MG has not been well-studied. METHODS This retrospective study examined 40 patients (14 patients ≥65 y old) treated with rituximab for MG. The primary efficacy outcome was the proportion of patients reaching "Improved" or better on Myasthenia Gravis Foundation of America (MGFA) Post-Intervention Status (PIS) at 12 mo, compared between younger and older patients. RESULTS Ninety-two percent of patients ≥65 y old achieved MGFA PIS Improved or better at 12 mo compared to 69% of those

Expanding the US Food and Drug Administration–approved indications for immune checkpoint inhibitors in patients with cancer has resulted in therapeutic success and immune-related adverse events (irAEs). Neurologic irAEs (irAE-Ns) have an incidence of 1%–12% and a high fatality rate relative to other irAEs. Lack of standardized disease definitions and accurate phenotyping leads to syndrome misclassification and impedes development of evidence-based treatments and translational research. The objective of this study was to develop consensus guidance for an approach to irAE-Ns including disease definitions and severity grading. A working group of four neurologists drafted irAE-N consensus guidance and definitions, which were reviewed by the multidisciplinary Neuro irAE Disease Definition Panel including oncologists and irAE experts. A modified Delphi consensus process was used, with two rounds of anonymous ratings by panelists and two meetings to discuss areas of controversy. Panelists rated content for usability, appropriateness and accuracy on 9-point scales in electronic surveys and provided free text comments. Aggregated survey responses were incorporated into revised definitions. Consensus was based on numeric ratings using the RAND/University of California Los Angeles (UCLA) Appropriateness Method with prespecified definitions. 27 panelists from 15 academic medical centers voted on a total of 53 rating scales (6 general guidance, 24 central and 18 peripheral nervous system disease definition components, 3 severity criteria and 2 clinical trial adjudication statements); of these, 77% (41/53) received first round consensus. After revisions, all items received second round consensus. Consensus definitions were achieved for seven core disorders: irMeningitis, irEncephalitis, irDemyelinating disease, irVasculitis, irNeuropathy, irNeuromuscular junction disorders and irMyopathy. For each disorder, six descriptors of diagnostic components are used: disease subtype, diagnostic certainty, severity, autoantibody association, exacerbation of pre-existing disease or de novo presentation, and presence or absence of concurrent irAE(s). These disease definitions standardize irAE-N classification. Diagnostic certainty is not always directly linked to certainty to treat as an irAE-N (ie, one might treat events in the probable or possible category). Given consensus on accuracy and usability from a representative panel group, we anticipate that the definitions will be used broadly across clinical and research settings.

A Man with Weakness and Difficulty Chewing A 60-year-old man was evaluated in the neurology clinic of this hospital because of difficulty chewing and progressive, generalized weakness. Physical exa...

Upper extremity entrapment neuropathies are common and can cause pain, sensory loss, and muscle weakness that lead to functional disability. In this article, the authors review common entrapment neuropathies of the upper extremities, including median neuropathy at the wrist (carpal tunnel syndrome), ulnar neuropathy at the elbow, and radial neuropathy. The authors discuss the pathophysiology of nerve compression and typical etiologies, as well as strategies for differentiating between common mimics such as cervical radiculopathy and for selecting between various treatment modalities.

Background: Peripheral neuropathy occurs in 20-25% of patients with an IgM paraprotein and 40-50% of patients with an IgM monoclonal gammopathy have a detectable anti-myelin associated glycoprotein (MAG) antibody. The presence of an anti-MAG antibody is often associated with a chronic, progressive symmetric demyelinating polyneuropathy that can lead to sensory deficits and gait dysfunction, significantly altering a patient’s quality of life. Prior clinical trials have failed to demonstrate an effective long-term therapy for anti-MAG neuropathy. Additionally, the best manner to assess the evolution of this type of neuropathy has not been elucidated. We designed this clinical trial to evaluate a potential therapy for anti-MAG related neuropathy based on previous reports of subjective improvement in patients with anti-MAG neuropathy treated with rituximab or Bruton’s tyrosine kinase inhibitors. We included multiple neurologic outcome measures so their responsiveness and performance could be assessed in a clinical trial setting. Methods: This is a single-arm open-label phase II trial investigating the use of acalabrutinib and an anti-CD20 monoclonal antibody for the treatment of an IgM-associated anti-MAG mediated neuropathy. Eligible patients must have positive anti-MAG antibody titers with an IgM monoclonal gammopathy of undetermined significance (MGUS) or Waldenström macroglobulinemia (WM). Patients must have a predominantly sensory neuropathy characterized by demyelinating features in nerve conduction studies with a modified Rankin score of ≥1 with progressive symptoms or a modified Rankin score of ≥2. The ECOG performance status must be ≤2. Acceptable organ and marrow function are required. Prior exposure to chemotherapy, Bruton Tyrosine Kinase inhibitors, or other therapies for WM are not permitted except for steroids, IVIg, or an anti-CD20 monoclonal antibody given at least 90 days before study drug initiation. Approximately 33 patients will be enrolled in this study. Patients will be treated with acalabrutinib 100 mg orally twice daily on days 1-28 of each cycle and treatment will be administered until disease progression or unacceptable toxicity. Rituximab (or a biosimilar) will be administered on days 1, 8, 15, and 22 of cycles 1 and 4. The primary endpoint of this trial is to evaluate the overall hematologic response rate (defined as ≥25% reduction in serum IgM) associated with the treatment. The key secondary endpoint is to evaluate the proportion of patients that achieve improvement or stability in neuropathic symptoms based on the Inflammatory Rasch-built Overall Disability Scale (I-RODS) patient-reported disability scale. Additional secondary neurologic endpoints include the INCAT disability score, exam-based outcomes (the MRC distal sum score and INCAT-ISS), measures of function (10-meter walk test, 9-hole peg test), a pain scale, a fatigue scale (FSS), and a neuropathy-specific quality of life scale (IN-QOL). Additional secondary endpoints include time to next treatment, overall survival, hematologic response based on MYD88 and CXCR4 mutational status, change in bone marrow disease burden, and proportion of adverse events associated with treatment. This study is currently open and accruing patients. Clinical trial information: NCT05065554 Sponsor: AstraZeneca Citation Format: Shayna Sarosiek, Christopher T. Doughty, Andrew Branagan, Catherine A. Flynn, Kirsten Meid, Timothy P. White, Megan Little, Carly Leventoff, Steven P. Treon, Jorge J. Castillo. Phase II study of acalabrutinib and an anti-CD20 monoclonal antibody in patients with anti-MAG mediated neuropathy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr CT550.

BackgroundIntegrating advanced practice providers (APPs) into neurological practice can improve access, promote patient education, and reduce healthcare costs. APPs receive limited formal education in neurology, so on-the-job training is essential. We set out to identify common challenges and best practices for onboarding, training, and integrating APPs into neurological practice.MethodsWe conducted a survey and focus group with eight APPs currently practicing within an academic neurology department as part of a clinical quality improvement initiative. We explored their roles in multidisciplinary teams, challenges faced during onboarding and training, and strategies for success. Qualitative thematic analysis was performed.ResultsNeurology APPs serve diverse roles including caring for hospitalized and ambulatory patients, performing procedures, assisting trainees, and performing research. Participants reported limited formal neurological education prior to their job and a need for educational sessions and resources tailored to APPs. Neuroanatomy, neuroimaging, and generating a neurologic differential diagnosis were key knowledge gaps identified. We identified seven informal strategies for on-the-job training, seven challenges to on-the-job training, and factors promoting or threatening job satisfaction. Graded responsibility and clinical mentorship were essential for successful onboarding. APPs desired peer-to-peer mentorship and structured educational opportunities.ConclusionsCommon challenges and success strategies identified can inform the design of a formal curriculum for onboarding neurology APPs. Our findings suggest an optimal APP training process involves graded responsibility and support for self-directed learning, employs peer mentors, and targets education of the multidisciplinary team including physicians and patients. Our results may inform other institutions recruiting, hiring, and training APPs.

A 63-year-old Hispanic woman presented with 5 days of abrupt onset bilateral leg pain. The pain was maximal at onset and worst in her hamstrings and calves. She described it as “soreness, like lactic acid buildup after a workout.” Touch or muscle use exacerbated the pain. It was not accompanied by muscle spasm, numbness, or tingling. She reported mild weakness and difficulty walking due to pain. She reported no symptoms above the waist. There were no constitutional symptoms, swollen joints, or bowel or bladder incontinence. She had no known infections in the weeks before symptom onset. There was no recent strenuous exercise or physical activity. She had 2+ pitting edema of both legs at baseline.

Single-fiber EMG (SFEMG) is a highly sensitive test for ocular myasthenia gravis (OMG) that provides quantitative measurement of neuromuscular transmission.1,2 It plays a pivotal role in diagnosing patients with OMG because serologic testing is positive in 90% of patients.4 SFEMG, however, is not a perfect test. Whereas serologic testing is highly specific, abnormal jitter on SFEMG is nonspecific and can be seen in other neurogenic and myopathic disorders. SFEMG can be lengthy, may not be tolerated by all patients, and is available only at specialized centers.

The major forms of autoimmune myopathies include dermatomyositis (DM), polymyositis (PM), myositis associated with antisynthetase syndrome (ASS), immune-mediated necrotizing myopathy (IMNM), and inclusion body myositis (IBM). While each of these conditions has unique clinical and histopathological features, they all share an immune-mediated component. These conditions can occur in isolation or can be associated with systemic malignancies or connective tissue disorders (overlap syndromes). As more has been learned about these conditions, it has become clear that traditional classification schemes do not adequately group patients according to shared clinical features and prognosis. Newer classifications are now utilizing myositis-specific autoantibodies which correlate with clinical and histopathological phenotypes and risk of malignancy, and help in offering prognostic information with regard to treatment response. Based on observational data and expert opinion, corticosteroids are considered first-line therapy for DM, PM, ASS, and IMNM, although intravenous immunoglobulin (IVIG) is increasingly being used as initial therapy in IMNM related to statin use. Second-line agents are often required, but further prospective investigation is required regarding the optimal choice and timing of these agents.

A 53-year-old woman presented with headache and confusion. Three weeks prior, she experienced bifrontal thunderclap headache after lifting a laundry basket. There was photophobia but no nausea, emesis, sensorimotor complaints, autonomic features, or positional component. She was evaluated in the emergency department (ED). CT scan of the head was unremarkable, her headache improved spontaneously, and she was discharged. Within 2 weeks, thunderclap headache recurred and was accompanied by confusion. Her husband noted she forgot how to wash her hands and poured water into the toaster instead of the sink. At one point, she fell out of bed, was incontinent of urine, was unable to stand independently, and dropped things with her right hand. MRI of the brain was performed, which was reported as unremarkable but limited due to patient motion. The patient was prescribed topiramate, but headache and confusion persisted, so 4 days later her husband brought her to our ED for evaluation.

This corrects the article DOI: 10.1103/PhysRevLett.121.051301.

Upper extremity entrapment neuropathies are common and can cause pain, sensory loss, and muscle weakness that lead to functional disability. In this article, the authors review common entrapment neuropathies of the upper extremities, including median neuropathy at the wrist (carpal tunnel syndrome), ulnar neuropathy at the elbow, and radial neuropathy. The authors discuss the pathophysiology of nerve compression and typical etiologies, as well as strategies for differentiating between common mimics such as cervical radiculopathy and for selecting between various treatment modalities.

Background and Purpose— A decrease in fractional anisotropy (FA) of the ipsilesional corticospinal tract (CST) distal to stroke lesions in the subacute (eg, 30 days) and chronic phase has been correlated with poor motor outcomes, but it is unclear whether FA values obtained within the acute stroke phase (here defined as 80 hours after onset) can predict later outcome. Methods— Fifty-eight patients underwent an assessment of motor impairment in the acute phase and at 3 months using the upper extremity Fugl-Meyer assessment. FA values, obtained within 80 hours after stroke onset, were determined in 2 regions of interest: cerebral peduncle and a stretch of the CST caudal to each stroke lesion (nearest-5-slices). Results— The FA laterality index for the cerebral peduncle-regions of interest was a poor predictor of 3-month outcome ( R 2 =0.044; P =0.137), whereas the slope over the FA laterality index of the nearest-5-slices showed a relatively weak but significant prediction ( R 2 =0.11; P =0.022) with the affected side having lower FA values. Initial upper extremity Fugl-Meyer ( R 2 =0.69; P R 2 =0.71; P Conclusions— FA reductions of the CST can be detected near the ischemic lesion in the acute stroke phase, but offer minimal predictive value to motor outcomes at 3 months.

Entrapment neuropathies are frequently encountered by rheumatologists, not only because they are common but also because of their association with certain rheumatological and systemic disorders. Recognizing entrapment neuropathy early can help avoid progressive neurological deficits, as well as facilitate appropriate treatment measures, which can effectively minimize a patient's symptoms. Entrapment neuropathies may be distinguished from other musculoskeletal causes of lower extremity pain by identifying characteristic patterns of weakness and/or sensory loss, so a focused bedside neurological examination is key for diagnosis. In this chapter, we review the most common entrapment neuropathies that occur in the lower extremities, review the relevant neuroanatomy, outline a diagnostic approach to distinguish them from other mimics, and highlight appropriate management options.

The Cryogenic Dark Matter Search (CDMS II) experiment aims to detect dark matter particles that elastically scatter from nuclei in semiconductor detectors. The resulting nuclear-recoil energy depositions are detected by ionization and phonon sensors. Neutrons produce a similar spectrum of low-energy nuclear recoils in such detectors, while most other backgrounds produce electron recoils. The absolute energy scale for nuclear recoils is necessary to interpret results correctly. The energy scale can be determined in CDMS II silicon detectors using neutrons incident from a broad-spectrum $^{252}$Cf source, taking advantage of a prominent resonance in the neutron elastic scattering cross section of silicon at a recoil (neutron) energy near 20 (182) keV. Results indicate that the phonon collection efficiency for nuclear recoils is $4.8^{+0.7}_{-0.9}$% lower than for electron recoils of the same energy. Comparisons of the ionization signals for nuclear recoils to those measured previously by other groups at higher electric fields indicate that the ionization collection efficiency for CDMS II silicon detectors operated at $\sim$4 V/cm is consistent with 100% for nuclear recoils below 20 keV and gradually decreases for larger energies to $\sim$75% at 100 keV. The impact of these measurements on previously published CDMS II silicon results is small., Comment: 22 pages, 17 figures, 1 table, 1 appendix

Future direct searches for low-mass dark matter particles with germanium detectors, such as SuperCDMS SNOLAB, are expected to be limited by backgrounds from radioactive isotopes activated by cosmogenic radiation inside the germanium. There are limited experimental data available to constrain production rates and a large spread of theoretical predictions. We examine the calculation of expected production rates, and analyze data from the second run of the CDMS low ionization threshold experiment (CDMSlite) to estimate the rates for several isotopes. We model the measured CDMSlite spectrum and fit for contributions from tritium and other isotopes. Using the knowledge of the detector history, these results are converted to cosmogenic production rates at sea level. The production rates in atoms/(kg$\cdot$day) are 74$\pm$9 for $^3$H, 1.5$\pm$0.7 for $^{55}$Fe, 17$\pm$5 for $^{65}$Zn, and 30$\pm$18 for $^{68}$Ge., 14 pages, 10 figures, 5 tables. v5 contains the extended data release (and documentation) of the CDMSlite Run 2 data as ancillary files

We present the first limits on inelastic electron-scattering dark matter and dark photon absorption using a prototype SuperCDMS detector having a charge resolution of 0.1 electron-hole pairs (CDMS HVeV, a 0.93 gram CDMS HV device). These electron-recoil limits significantly improve experimental constraints on dark matter particles with masses as low as 1 MeV/$\mathrm{c^2}$. We demonstrate a sensitivity to dark photons competitive with other leading approaches but using substantially less exposure (0.49 gram days). These results demonstrate the scientific potential of phonon-mediated semiconductor detectors that are sensitive to single electronic excitations., 6 pages + title and references, 6 figures, includes erratum submitted to PRL and data release

We report the result of a blinded search for weakly interacting massive particles (WIMPs) using the majority of the SuperCDMS Soudan data set. With an exposure of 1690 kg d, a single candidate event is observed, consistent with expected backgrounds. This analysis (combined with previous Ge results) sets an upper limit on the spin-independent WIMP–nucleon cross section of 1.4×10−44 (1.0×10−44) cm2 at 46 GeV/c2. These results set the strongest limits for WIMP–germanium-nucleus interactions for masses >12 GeV/c2.

Objective The aim of this work was to investigate whether an imaging measure of corticospinal tract (CST) injury in the acute phase can predict motor outcome at 3 months in comparison to clinical assessment of initial motor impairment. Methods A two-site prospective cohort study followed up a group of first-ever ischemic stroke patients using the Upper-Extremity Fugl-Meyer (UE-FM) Scale to measure motor impairment in the acute phase and at 3 months. A weighted CST lesion load (wCST-LL) was calculated by overlaying the patient's lesion map on magnetic resonance imaging with a probabilistic CST constructed from healthy control subjects. Regression models were fit to assess the predictive value of wCST-LL and compared with initial motor impairment. Results Seventy-six patients (37 from cohort 1 and 39 from cohort 2) completed the study. wCST-LL as well as assessment of motor impairment (UE-FM) in the acute phase correlated with motor impairment (UE-FM) at 3 months in both cohort 1 (R2 = 0.69 vs. R2 = 0.67; p = 0.43) and cohort 2 (R2 = 0.69 vs. R2 = 0.62; p = 0.25). In the severely impaired subgroup (defined as UE-FM ≤ 10 at baseline), wCST-LL correlated with outcomes significantly better than clinical assessment (R2 = 0.47 vs. R2 = 0.11; p = 0.03). In the nonseverely impaired subgroup, stroke patients recovered approximately 70% of their maximal recovery potential. All stroke patients in both cohorts had poor motor outcomes at 3 months (defined as UE-FM ≤ 25) when wCST-LL was ≥ 7.0 cc (positive predictive value was 100%). Interpretation wCST-LL, an imaging biomarker determined in the acute phase, can predict poststroke motor outcomes at 3 months, especially in patients with severe impairment at baseline. Ann Neurol 2015

SuperCDMS SNOLAB will be a next-generation experiment aimed at directly detecting low-mass (< 10 GeV/c$^2$) particles that may constitute dark matter by using cryogenic detectors of two types (HV and iZIP) and two target materials (germanium and silicon). The experiment is being designed with an initial sensitivity to nuclear recoil cross sections ~ 1 x 10$^{-43}$ cm$^2$ for a dark matter particle mass of 1 GeV/c$^2$, and with capacity to continue exploration to both smaller masses and better sensitivities. The phonon sensitivity of the HV detectors will be sufficient to detect nuclear recoils from sub-GeV dark matter. A detailed calibration of the detector response to low energy recoils will be needed to optimize running conditions of the HV detectors and to interpret their data for dark matter searches. Low-activity shielding, and the depth of SNOLAB, will reduce most backgrounds, but cosmogenically produced $^{3}$H and naturally occurring $^{32}$Si will be present in the detectors at some level. Even if these backgrounds are x10 higher than expected, the science reach of the HV detectors would be over three orders of magnitude beyond current results for a dark matter mass of 1 GeV/c$^2$. The iZIP detectors are relatively insensitive to variations in detector response and backgrounds, and will provide better sensitivity for dark matter particle masses (> 5 GeV/c$^2$). The mix of detector types (HV and iZIP), and targets (germanium and silicon), planned for the experiment, as well as flexibility in how the detectors are operated, will allow us to maximize the low-mass reach, and understand the backgrounds that the experiment will encounter. Upgrades to the experiment, perhaps with a variety of ultra-low-background cryogenic detectors, will extend dark matter sensitivity down to the "neutrino floor", where coherent scatters of solar neutrinos become a limiting background., SuperCDMS SNOLAB Projected sensitivity reach

Arboviruses are arthropod-borne viruses transmitted by the bite of mosquitoes, ticks, or other arthropods. Arboviruses are a common and an increasing cause of human illness in North America. Powassan virus, Chikungunya virus, and Zika virus are arboviruses that have all recently emerged as increasing causes of neurologic illness. Powassan virus almost exclusively causes encephalitis, but cases are rare, sporadic, and restricted to portions of North America and Russia. Chikungunya virus has spread widely across the world, causing millions of infections. Encephalitis is a rare manifestation of illness but is more common and severe in neonates and older adults. Zika virus has recently spread through much of the Americas and has been associated mostly with microcephaly and other congenital neurologic complications. Encephalitis occurring in infected adults has also been recently reported. This review will discuss the neuropathogenesis of these viruses, their transmission and geographic distribution, the spectrum of their neurologic manifestations, and the appropriate method of diagnosis.

OBJECTIVE Pneumonia is a morbid complication of stroke, but evidence-based strategies for its prevention are lacking. Acid-suppressive medications have been associated with increased risk for nosocomial pneumonia in hospitalized patients. It is unclear whether these results can be extrapolated to stroke patients, where other factors strongly modulate pneumonia risk. We investigated the association between acid-suppressive medication and hospital-acquired pneumonia in patients with acute stroke. METHODS All patients hospitalized with acute ischemic stroke or intracerebral hemorrhage in a large, urban academic medical center in Boston, Massachusetts from June 2000 to June 2010 who were ≥18 years of age and hospitalized for ≥2 days were eligible for inclusion. Acid-suppressive medication use was defined as any pharmacy charge for a proton-pump inhibitor or histamine-2 receptor antagonist. Multivariate logistic regression was used to control for confounders. The main outcome measure was hospital-acquired pneumonia, defined via International Classification of Diseases, Ninth Revision, Clinical Modification codes. RESULTS The cohort comprised 1,676 admissions. Acid-suppressive medication was ordered in 1,340 (80%) and hospital-acquired pneumonia occurred in 289 (17.2%). The unadjusted incidence of hospital-acquired pneumonia was higher in the group exposed to acid-suppressive medication compared to those unexposed (20.7% vs 3.6%, odds ratio [OR] = 7.0, 95% confidence interval [CI] = 3.9-12.7). After adjustment, the OR of hospital-acquired pneumonia in the exposed group was 2.3 (95% CI = 1.2-4.6). The association was significant for proton-pump inhibitors (OR = 2.7, 95% CI = 1.4-5.4), but not for histamine-2 receptor antagonists (OR = 1.6, 95% CI = 0.8-3.4). INTERPRETATION In this large hospital-based cohort of patients presenting with acute stroke, acid-suppressive medication use was associated with increased odds of hospital-acquired pneumonia.

© 2016 American Physical Society. The CDMS low ionization threshold experiment (CDMSlite) uses cryogenic germanium detectors operated at a relatively high bias voltage to amplify the phonon signal in the search for weakly interacting massive particles (WIMPs). Results are presented from the second CDMSlite run with an exposure of 70 kg day, which reached an energy threshold for electron recoils as low as 56 eV. A fiducialization cut reduces backgrounds below those previously reported by CDMSlite. New parameter space for the WIMP-nucleon spin-independent cross section is excluded for WIMP masses between 1.6 and 5.5 GeV/c2.

Interleaved ionization electrode geometries offer the possibility of efficient rejection of near-surface events. The CDMS collaboration has implemented this interleaved approach for the charge and phonon readout for our germanium detectors. During a recent engineering run with negligible ambient radiation, the detectors were found to lose ionization stability more quickly than expected. This paper summarizes studies done in order to determine the underlying cause of the instability, as well as possible running modes that maintain stability without unacceptable loss of livetime. Additionally, first results are shown for the new version IZIP mask which attempts to improve the overall stability of the detectors.

The SuperCDMS collaboration is a dark matter search effort aimed at detecting the scattering of WIMP dark matter from nuclei in cryogenic germanium targets. The CDMS Detector Monte Carlo (CDMS-DMC) is a simulation tool aimed at achieving a deeper understanding of the performance of the SuperCDMS detectors and aiding the dark matter search analysis. We present results from validation of the phonon physics described in the CDMS-DMC and outline work towards utilizing it in future WIMP search analyses., National Science Foundation (U.S.) (Grant No. PHY-0847342)

We report a first search for weakly interacting massive particles (WIMPs) using the background rejection capabilities of SuperCDMS. An exposure of 577 kg days was analyzed for WIMPs with mass

The SuperCDMS collaboration is presently operating a 9 kg Ge payload at the Soudan Underground Laboratory in their direct search for dark matter. The Ge detectors utilize double-sided athermal phonon sensors with an interdigitated electrode structure (iZIPs) to reject near-surface electron-recoil events. These detectors each have a mass of 0.6 kg and were fabricated with photolithographic techniques. The detector fabrication advances required and the production yield encountered are described.

We report results of a search for Weakly Interacting Massive Particles (WIMPS) with the silicon detectors of the CDMS II experiment. This blind analysis of 140.2 kg-days of data taken between July 2007 and September 2008 revealed three WIMP-candidate events with a surface-event background estimate of 0.41^{+0.20}_{-0.08}(stat.)^{+0.28}_{-0.24}(syst.). Other known backgrounds from neutrons and 206Pb are limited to < 0.13 and, 5 pages, 4 figures, as accepted by PRL

Precambrian basement rocks exposed within tectonic windows in the North American Cordillera help to define the Precambrian crustal structure of western North America and possible reconstructions of the Late Proterozoic supercontinent Rodinia. New geologic mapping and U-Pb dating in the infrastructure of the Priest River metamorphic complex, northern Idaho, documents the first Archean basement (2651 ± 20 Ma) north of the Snake River Plain in the North American Cordillera. The Archean rocks are exposed in the core of an antiform and mantled by a metaquartzite that may represent the nonconformity between basement and the overlying Hauser Lake gneiss, which is correlated with the Prichard Formation of the Belt Supergroup. A structurally higher sheet of augen gneiss interleaved with the Hauser Lake gneiss yields a U-Pb zircon crystallization age somewhat greater than 1577 Ma. The slivers of augen gneiss were tectonically interleaved with the surrounding Hauser Lake gneiss near the base of the Spokane dome mylonite zone, which arches across this part of the Priest River complex. We conclude that the Spokane dome mylonite zone lies above the Archean basement-cover contact and that it was, in part, equivalent to the basal décollement of the Rocky Mountain fold and thrust belt. New U-Pb dates on metamorphic monazite and xenotime reveal peak metamorphism at ca. 72 Ma, compatible with movement along the Spokane dome mylonite zone at that time. The Archean basement could be interpreted as the western extension of the Hearne province, or a new Archean basement terrane separated from the Hearne province by an Early Proterozoic suture. The unique assemblage of 2.65 Ga basement, ~1.58 Ga felsic intrusive rocks, and the Middle Proterozoic Belt Supergroup can be used as a piercing point for the identification of the conjugate margin to Laurentia. Our new dating supports previous correlations of Australia's Gawler craton (2.55-2.65 Ga) and its 1590 Ma plutons with the Priest River complex basement gneisses. The Priest River complex basement may be a piece of eastern Australia stranded during rifting of the supercontinent Rodina in the Late Proterozoic.

The SuperCDMS experiment in the Soudan Underground Laboratory searches for dark matter with a 9-kg array of cryogenic germanium detectors. Symmetric sensors on opposite sides measure both charge and phonons from each particle interaction, providing excellent discrimination between electron and nuclear recoils, and between surface and interior events. Surface event rejection capabilities were tested with two [superscript 210] Pb sources producing ∼130 beta decays/hr. In ∼800 live hours, no events leaked into the 8–115 keV signal region, giving upper limit leakage fraction 1.7 × 10[superscript −5] at 90% C.L., corresponding to, United States. Dept. of Energy (Contract No. DE-AC03-76SF00098), United States. Dept. of Energy (Contract No. DE-FG02-92ER40701), United States. Dept. of Energy (Contract No. DE-FG02-94ER40823), United States. Dept. of Energy (Contract No. DE-FG03-90ER40569), United States. Dept. of Energy (Contract No. DE-FG03-91ER40618), United States. Dept. of Energy (Contract No. DE-SC0004022), National Science Foundation (U.S.) (Grant No. AST-9978911), National Science Foundation (U.S.) (Grant No. NSF-0847342), National Science Foundation (U.S.) (Grant No. PHY-1102795), National Science Foundation (U.S.) (Grant No. NSF-1151869), National Science Foundation (U.S.) (Grant No. PHY-0542066), National Science Foundation (U.S.) (Grant No. PHY-0503729), National Science Foundation (U.S.) (Grant No. PHY-0503629), National Science Foundation (U.S.) (Grant No. PHY-0503641), National Science Foundation (U.S.) (Grant No. PHY-0504224), National Science Foundation (U.S.) (Grant No. PHY-0705052), National Science Foundation (U.S.) (Grant No. PHY-0801708), National Science Foundation (U.S.) (Grant No. PHY-0801712), National Science Foundation (U.S.) (Grant No. PHY-0802575), National Science Foundation (U.S.) (Grant No. PHY-0847342), National Science Foundation (U.S.) (Grant No. PHY-0855299), National Science Foundation (U.S.) (Grant No. PHY-0855525), National Science Foundation (U.S.) (Grant No. PHY-1205898)

SuperCDMS is an experiment designed to directly detect weakly interacting massive particles (WIMPs), a favored candidate for dark matter ubiquitous in the Universe. In this Letter, we present WIMP-search results using a calorimetric technique we call CDMSlite, which relies on voltage-assisted Luke-Neganov amplification of the ionization energy deposited by particle interactions. The data were collected with a single 0.6 kg germanium detector running for ten live days at the Soudan Underground Laboratory. A low energy threshold of 170 eVee (electron equivalent) was obtained, which allows us to constrain new WIMP-nucleon spin-independent parameter space for WIMP masses below 6 GeV/c2, Funding and support were received from the National Science Foundation, the Department of Energy, a Fermilab URA Visiting Scholar Award, NSERC Canada, and MULTIDARK. Fermilab is operated by the Fermi Research Alliance, LLC under Contract No. De-AC02- 07CH11359. SLAC is operated under Contract No. DEAC02- 76SF00515 with the United States Department of Energy

Matter, as we know it, makes up less than 5% of the Universe. Various astrophysical observations have confirmed that one quarter of the Universe and most of the matter content in the Universe is made up of Dark Matter. The nature of Dark Matter is yet to be discovered and is one of the biggest questions in Physics. Particle Physics combined with astrophysical measurements of the abundance gives rise to a Dark Matter candidate called Weakly Interacting Massive Particle (WIMP). The low density of WIMPs in the galaxies and the extremely weak nature of the interaction with ordinary matter make detection of the WIMP an extraordinarily challenging task, with abundant fakes from various radioactive and cosmogenic backgrounds with much stronger electromagnetic interaction. The extremely weak nature of the WIMP interaction dictates detectors that have extremely low naturally occurring radioactive background, a large active volume (mass) of sensitive detector material to maximize statistics, a highly efficient detector based rejection mechanism for the dominant electromagnetic background and sophisticated analysis techniques to reject any residual background. This paper describes the status of the SuperCDMS experiment.

Artículo escrito por un elevado número de autores, solo se referencian el que aparece en primer lugar, el nombre del grupo de colaboración, si le hubiere, y los autores pertenecientes a la UAM, We report results of a search for weakly interacting massive particles (WIMPs) with the Si detectors of the CDMS II experiment. This report describes a blind analysis of the first data taken with CDMS II’s full complement of detectors in 2006–2007; results from this exposure using the Ge detectors have already been presented. We observed no candidate WIMP-scattering events in an exposure of 55.9 kg-days before analysis cuts, with an expected background of ˞1.1 events. The exposure of this analysis is equivalent to 10.3 kg-days over a recoil energy range of 7–100 keV for an ideal Si detector and a WIMP mass of 10 GeV/c2. These data set an upper limit of 1.7 x 10-41 cm2 on the WIMP-nucleon spin-independent cross section of a 10 GeV/c2 WIMP. These data exclude parameter space for spin-independent WIMP-nucleon elastic scattering that is relevant to recent searches for low-mass WIMPs, This work is supported in part by the National Science Foundation (Grants No. AST-9978911, No. NSF-1102795, No. PHY- 0847342, No. PHY-0542066, No. PHY-0503729, No. PHY- 0503629, No. PHY-0503641, No. PHY-0504224, No. PHY-0705052, No. PHY-0801708, No. PHY-0801712, No. PHY-0802575, No. PHY-0847342, No. PHY-0855299, No. PHY-0855525, No. PHY-1151869, and No. PHY- 1205898), by the Department of Energy (Contracts No. DE-AC03-76SF00098, No. DE-FG02-92ER40701, No. DE-FG03-90ER40569, No. DE-FG03-91ER40618, and No. DE-SC0004022), by the Swiss National Foundation (SNF Grant No. 20-118119), by NSERC Canada (Grants No. SAPIN 341314 and No. SAPPJ 386399), and by MULTIDARK CSD2009-00064 and FPA2012-34694. Fermilab is operated by Fermi Research Alliance, LLC under Contract No. De-AC02-07CH11359, while SLAC is operated under Contract No. DE-AC02- 76SF00515 with the U.S. Department of Energy

Dysphagia is a major complication of stroke, but factors influencing its recovery are incompletely understood. The goal of this study was to identify important prognostic variables affecting swallowing recovery after acute ischemic stroke.We retrospectively reviewed our patient database to identify acute ischemic stroke patients who developed dysphagia after stroke but were free of other confounding conditions affecting swallowing. Of the 1774 patients screened, 323 met the study criteria. We assessed the effect of age, sex, baseline National Institutes of Health Stroke Scale (NIHSS) score, level of consciousness (LOC), facial weakness, dysarthria, neglect, bihemispheric infarcts, right hemispheric infarcts, brainstem infarcts, intubation, aspiration, acute stroke therapies, occurrence of symptomatic hemorrhagic transformation, seizures, pneumonia, and length of hospitalization (LOH) on persistence of dysphagia at hospital discharge in a logistic regression analysis.The mean age and NIHSS scores (mean ± standard deviation) were 75.9 ± 13.6 years and 13.5 ± 6.9, respectively; 58.5% were women. In a multivariate analysis, aspiration detected on a clinical swallowing evaluation (odds ratio [OR] 21.83; 95% confidence interval [CI] 8.16-58.42; P .0001), aspiration on videofluoroscopic swallowing study (OR 10.50; 95% CI 3.35-32.96; P .0001), bihemispheric infarcts (OR 3.72; 95% CI 1.33-10.43; P = .0123), dysarthria (OR 3.4; 95% CI 1.57-7.35; P = .0019), intubation (OR 2.86; 95% CI 1.10-7.39; P = .0301), NIHSS score ≥12 (OR 2.51; 95% CI 1.19-5.23; P = .0157) were significant predictors of persistent dysphagia. The area under the curve and Somer's Dxy statistics of the model were 0.8918 and 0.78, respectively, indicating good calibration and discriminative power.Prognostic factors affecting swallowing recovery identified in this study can help advance dysphagia research methodologies and the clinical care of stroke patients.

The properties of films produced by the cast or blown film processes can be altered by varying the fabrication parameters. An experimental design is used to determine the effect of cast film fabrication variables on the performance of LLDPE stretch films. A three-variable Box–Behnken designed experiment was conducted to study the effects of air gap, melt temperature, and line speed on the key cast stretch film properties. In addition, the differences in molecular orientation in the films were studied using optical birefringence and shrinkage methods. The key film properties are correlated with the fabrication conditions using a statistical analysis program. The results of this study are explained in terms of web tensile stresses before solidification and the degree of molecular orientation developed in the film due to the stresses. © 1994 John Wiley & Sons, Inc.

The Cryogenic Dark Matter Search (CDMS) utilizes large mass, 3" diameter x 1" thick target masses as particle detectors. The target is instrumented with both phonon and ionization sensors, the later providing a $\sim$1 V cm$^{-1}$ electric field in the detector bulk. Cumulative radiation exposure which creates $\sim 200\times 10^6$ electron-hole pairs is sufficient to produce a comparable reverse field in the detector thereby degrading the ionization channel performance. To study this, the existing CDMS detector Monte Carlo has been modified to allow for an event by event evolution of the bulk electric field, in three spatial dimensions. Our most resent results and interpretation are discussed., Low Temperature Detectors 14 conference proceeding to be published in the Journal of Low Temperature Physics

We briefly review a simple model of superconducting-normal phase-separation in transition-edge sensors (TESs) in the SuperCDMS experiment. After discussing some design considerations relevant to the TESs in the experiment, we study noise sources in both the phase-separated and phase-uniform cases. Such simulations will be valuable for optimizing the critical temperature and TES length of future SuperCDMS detectors., National Science Foundation (U.S.) (Grant No. PHY-0847342)

Objective: To assess the operating characteristics of the Beck-Depression Inventory-II (BDI-II) and the BDI-II cognitive subscale (BDI-II-cog) in screening for major depression (MDD) in post-myocardial infarction (MI) patients. Methods: Between October 2003 and July 2005, 131 post-MI patients admitted to an urban academic medical center completed the BDI-II and a semi-structured interview for depression within 72 hours of symptom onset. Sensitivity, specificity, positive and negative predictive values, overall correct classification, and likelihood ratios for various cutoff values on both scales were evaluated by comparing scores to interview diagnosis of MDD. Receiver-operator curves (ROC) were also calculated and area under the curve (AUC) measured. Results: The optimal cutoff value for the BDI-II was > 16, with a sensitivity of 88.2% and a specificity of 92.1%. Cutoff values of > 3 or > 4 were both acceptable for the BDI-II-cog (sensitivity = 88.2% and 82.4%, respectively; specificity = 81.6% and 88.6%, respectively). AUC was 0.96 for the BDI-II and 0.89 for the cognitive subscale. Conclusions: Effective depression screening is important in post-MI patients because of depression's independent association with morbidity and mortality following MI. Our results suggest that the BDI-II and its cognitive subscale are effective tools for screening for MDD in post-MI patients.

A restoration that the patient reports as "high" is a common problem for the restorative dentist. Check bite, dual bite, or closed mouth impressions address this problem effectively by eliminating the opposing arch impression and articulating the opposing cast accurately. In this article a procedure that combines irreversible hydrocolloid and reversible hydrocolloid results in a rapid, clean, and effective solution.

This paper describes the contract management and administration of a US $441m United States Navy contract to expand facilities on Diego Garcia in the Indian Ocean. Following a brief history of the island, details are provided on the fragile ecology of this coral atoll and the steps taken during construction to protect the environment. The cost plus award fee type of contract is discussed together with reasons for its selection, how it was administered and the benefits and shortcomings of this type of contract. More than one hundred separate facilities were constructed, all buildings being of simple and utilitarian design with either a concrete block infill walls or pre-engineered steel frame with metal roof and cladding. A section on special construction requirements details only those portions of the work that were unusual or of particular interest. A description is also provided on logistics, contractors' temporary facilities and project control systems employed. Work was completed in January 1987 after five and a half years of construction, ahead of schedule and within budget.