Neurocysticercosis in Radiographically Imaged Seizure Patients in U.S. Emergency Departments1

Neurocysticercosis appears to be on the rise in the United States, based on immigration patterns and published cases series, including reports of domestic acquisition. We used a collaborative network of U.S. emergency departments to characterize the epidemiology of neurocysticercosis in seizure patients. Data were collected prospectively at 11 university-affiliated, geographically diverse, urban U.S. emergency departments from July 1996 to September 1998. Patients with a seizure who underwent neuroimaging were included. Of the 1,801 patients enrolled in the study, 38 (2.1%) had seizures attributable to neurocysticercosis. The disease was detected in 9 of the 11 sites and was associated with Hispanic ethnicity, immigrant status, and exposure to areas where neurocysticercosis is endemic. This disease appears to be widely distributed and highly prevalent in certain populations (e.g., Hispanic patients) and areas (e.g., Southwest)

Yukawa Unification and the Superpartner Mass Scale

Naturalness in supersymmetry (SUSY) is under siege by increasingly stringent LHC constraints, but natural electroweak symmetry breaking still remains the most powerful motivation for superpartner masses within experimental reach. If naturalness is the wrong criterion then what determines the mass scale of the superpartners? We motivate supersymmetry by (1) gauge coupling unification, (2) dark matter, and (3) precision b-tau Yukawa unification. We show that for an LSP that is a bino-Higgsino admixture, these three requirements lead to an upper-bound on the stop and sbottom masses in the several TeV regime because the threshold correction to the bottom mass at the superpartner scale is required to have a particular size. For tan beta about 50, which is needed for t-b-tau unification, the stops must be lighter than 2.8 TeV when A_t has the opposite sign of the gluino mass, as is favored by renormalization group scaling. For lower values of tan beta, the top and bottom squarks must be even lighter. Yukawa unification plus dark matter implies that superpartners are likely in reach of the LHC, after the upgrade to 14 (or 13) TeV, independent of any considerations of naturalness. We present a model-independent, bottom-up analysis of the SUSY parameter space that is simultaneously consistent with Yukawa unification and the hint for m_h = 125 GeV. We study the flavor and dark matter phenomenology that accompanies this Yukawa unification. A large portion of the parameter space predicts that the branching fraction for B_s to mu^+ mu^- will be observed to be significantly lower than the SM value.Comment: 34 pages plus appendices, 20 figure

Molecular remission of infant B-ALL after infusion of universal TALEN gene-edited CAR T cells

Autologous T cells engineered to express chimeric antigen receptor against the B cell antigen CD19 (CAR19) are achieving marked leukemic remissions in early-phase trials but can be difficult to manufacture, especially in infants or heavily treated patients. We generated universal CAR19 (UCART19) T cells by lentiviral transduction of non-human leukocyte antigen-matched donor cells and simultaneous transcription activator-like effector nuclease (TALEN)-mediated gene editing of T cell receptor α chain and CD52 gene loci. Two infants with relapsed refractory CD19(+) B cell acute lymphoblastic leukemia received lymphodepleting chemotherapy and anti-CD52 serotherapy, followed by a single-dose infusion of UCART19 cells. Molecular remissions were achieved within 28 days in both infants, and UCART19 cells persisted until conditioning ahead of successful allogeneic stem cell transplantation. This bridge-to-transplantation strategy demonstrates the therapeutic potential of gene-editing technology

A two-domain elevator mechanism for sodium/proton antiport

Sodium/proton (Na+/H+) antiporters, located at the plasma membrane in every cell, are vital for cell homeostasis1. In humans, their dysfunction has been linked to diseases, such as hypertension, heart failure and epilepsy, and they are well-established drug targets2. The best understood model system for Na+/H+ antiport is NhaA from Escherichia coli1, 3, for which both electron microscopy and crystal structures are available4, 5, 6. NhaA is made up of two distinct domains: a core domain and a dimerization domain. In the NhaA crystal structure a cavity is located between the two domains, providing access to the ion-binding site from the inward-facing surface of the protein1, 4. Like many Na+/H+ antiporters, the activity of NhaA is regulated by pH, only becoming active above pH 6.5, at which point a conformational change is thought to occur7. The only reported NhaA crystal structure so far is of the low pH inactivated form4. Here we describe the active-state structure of a Na+/H+ antiporter, NapA from Thermus thermophilus, at 3 Å resolution, solved from crystals grown at pH 7.8. In the NapA structure, the core and dimerization domains are in different positions to those seen in NhaA, and a negatively charged cavity has now opened to the outside. The extracellular cavity allows access to a strictly conserved aspartate residue thought to coordinate ion binding1, 8, 9 directly, a role supported here by molecular dynamics simulations. To alternate access to this ion-binding site, however, requires a surprisingly large rotation of the core domain, some 20° against the dimerization interface. We conclude that despite their fast transport rates of up to 1,500 ions per second3, Na+/H+ antiporters operate by a two-domain rocking bundle model, revealing themes relevant to secondary-active transporters in general

Driven diffusion in a periodically compartmentalized tube: homogeneity versus intermittency of particle motion

We study the effect of a driving force F on drift and diffusion of a point Brownian particle in a tube formed by identical ylindrical compartments, which create periodic entropy barriers for the particle motion along the tube axis. The particle transport exhibits striking features: the effective mobility monotonically decreases with increasing F, and the effective diffusivity diverges as F → ∞, which indicates that the entropic effects in diffusive transport are enhanced by the driving force. Our consideration is based on two different scenarios of the particle motion at small and large F, homogeneous and intermittent, respectively. The scenarios are deduced from the careful analysis of statistics of the particle transition times between neighboring openings. From this qualitative picture, the limiting small-F and large-F behaviors of the effective mobility and diffusivity are derived analytically. Brownian dynamics simulations are used to find these quantities at intermediate values of the driving force for various compartment lengths and opening radii. This work shows that the driving force may lead to qualitatively different anomalous transport features, depending on the geometry design

Telephone Triage Service Data for Detection of Influenza-Like Illness

Background: Surveillance for influenza and influenza-like illness (ILI) is important for guiding public health prevention programs to mitigate the morbidity and mortality caused by influenza, including pandemic influenza. Nontraditional sources of data for influenza and ILI surveillance are of interest to public health authorities if their validity can be established. Methods/Principal Findings: National telephone triage call data were collected through automated means for purposes of syndromic surveillance. For the 17 states with at least 500,000 inhabitants eligible to use the telephone triage services, call volume for respiratory syndrome was compared to CDC weekly number of influenza isolates and percentage of visits to sentinel providers for ILI. The degree to which the call data were correlated with either CDC viral isolates or sentinel provider percentage ILI data was highly variable among states. Conclusions: Telephone triage data in the U.S. are patchy in coverage and therefore not a reliable source of ILI surveillance data on a national scale. However, in states displaying a higher correlation between the call data and the CDC data, call data may be useful as an adjunct to state-level surveillance data, for example at times when sentinel surveillance is not in operation or in areas where sentinel provider coverage is considered insufficient. Sufficient population coverage, a specific ILI syndrome definition, and the use of a threshold of percentage of calls that are for ILI would likely improve the utility of such data for ILI surveillance purposes

Surveillance for Anthrax Cases Associated with Contaminated Letters, New Jersey, Delaware, and Pennsylvania, 2001

In October 2001, two inhalational anthrax and four cutaneous anthrax cases, resulting from the processing of Bacillus anthracis–containing envelopes at a New Jersey mail facility, were identified. Subsequently, we initiated stimulated passive hospital-based and enhanced passive surveillance for anthrax-compatible syndromes. From October 24 to December 17, 2001, hospitals reported 240,160 visits and 7,109 intensive-care unit admissions in the surveillance area (population 6.7 million persons). Following a change to reporting criteria on November 8, the average of possible inhalational anthrax reports decreased 83% from 18 to 3 per day; the proportion of reports requiring follow-up increased from 37% (105/286) to 41% (47/116). Clinical follow-up was conducted on 214 of 464 possible inhalational anthrax patients and 98 possible cutaneous anthrax patients; 49 had additional laboratory testing. No additional cases were identified. To verify the limited scope of the outbreak, surveillance was essential, though labor-intensive. The flexibility of the system allowed interim evaluation, thus improving surveillance efficiency

Disease Surveillance and the Academic, Clinical, and Public Health Communities

The Emerging Infections Programs (EIPs), a population-based network involving 10 state health departments and the Centers for Disease Control and Prevention, complement and support local, regional, and national surveillance and research efforts. EIPs depend on collaboration between public health agencies and clinical and academic institutions to perform active, population-based surveillance for infectious diseases; conduct applied epidemiologic and laboratory research; implement and evaluate pilot prevention and intervention projects; and provide capacity for flexible public health response. Recent EIP work has included monitoring the impact of a new conjugate vaccine on the epidemiology of invasive pneumococcal disease, providing the evidence base used to derive new recommendations to prevent neonatal group B streptococcal disease, measuring the impact of foodborne diseases in the United States, and developing a systematic, integrated laboratory and epidemiologic method for syndrome-based surveillance