Clonal analysis of a human antibody response. Quantitation of precursors of antibody-producing cells and generation and characterization of monoclonal IgM, IgG, and IgA to rabies virus.

We quantitated and characterized the changes in the human B cell repertoire, at the clonal level, before and after immunization with rabies virus. Moreover, we generated 10 monoclonal cell lines producing IgM, IgG, and IgA antibodies to the virus. We found that in healthy subjects, not previously exposed to the virus, nearly 2% of the circulating B lymphocytes were committed to the production of antibodies that bound the virus. These B cells expressed the surface CD5 molecule. The antibodies they produced were polyreactive IgM that displayed a relatively low affinity for the virus components (Kd, 1.0-2.4 x 10(-6) g/microliters). After immunization, different anti-virus (IgG and IgA) antibody-producing cells consistently appeared in the circulation and increased from less than 0.005% to greater than 10% of the total B cells committed to the production of IgG and IgA, respectively. Most of such B cells do not express CD5 and produce monoreactive antibodies of high affinity for rabies virus (Kd, 6.5 x 10(-9) to 1.2 x 10(-10) g/microliters). One of these IgG mAbs efficiently neutralized rabies virus in vitro and in vivo, as detailed elsewhere (Dietzschold, B., P. Casali, Y. Ueki, M. Gore, C. E. Rupprecht, A. L. Notkins, and H. Koprowski, manuscript submitted for publication). Hybridization experiments using probes specific for the different human V gene segment families revealed that cell precursors producing low affinity IgM binding to rabies virus utilized a restricted number of VH gene segments (i.e., only members of the VHIIIb subfamily), whereas cell precursors producing high affinity IgG and IgA to rabies virus utilized an assortment of different VH gene segments (i.e., members of the VHI, VHIII, VHIV, and VHVI families and VHIIIb subfamily). In conclusion, our studies show that EBV transformation in conjunction with limiting dilution technology and somatic cell hybridization techniques are useful methods for quantitating, at the B cell clonal level, the human antibody response to foreign Ags and for generating human mAbs of predetermined specificity and high affinity

A Tomographic Method for the Reconstruction of Local Probability Density Functions

A method of obtaining the probability density function (PDF) of local properties from path integrated measurements is described. The approach uses a discrete probability function (DPF) method to infer the PDF of the local extinction coefficient from measurements of the PDFs of the path integrated transmittance. The local PDFs obtained using the method are compared with those obtained from direct intrusive measurements in propylene/air and ethylene/air diffusion flames. The results of this comparison are good

Hepatitis B testing and treatment in HIV patients in The Gambia - compliance with international guidelines and clinical outcomes

Background Compliance with WHO guidelines on HBV screening and treatment in HIV-coinfected patients is often challenging in resource limited countries and has been poorly assessed in sub-Saharan Africa. Methods Between 2015 and 2016, we assessed physician’s compliance with WHO guidelines on HIV-HBV coinfection in the largest HIV clinic in The Gambia, and the hepatic outcomes in HIV-HBV coinfected patients as compared to randomly selected HIV-monoinfected controls. Results 870 HIV-infected patients regularly seen in this clinic agreed to participate in our study. Only 187 (21.5%, 95% CI 18.8–24.3) had previously been screened for HBsAg, 23 (12.3%, 95% CI 8.0–17.9) were positive of whom none had liver assessment and only 6 (26.1%) had received Tenofovir. Our HBV testing intervention was accepted by all participants and found 94/870 (10.8%, 95% CI 8.8–13.1) positive, 78 of whom underwent full liver assessment along with 40 HBsAg-negative controls. At the time of liver assessment, 61/78 (78.2%) HIV-HBV coinfected patients received ART with 7 (11.5%) on Tenofovir and 54 (88.5%) on Lamivudine alone. HIV-HBV coinfected patients had higher APRI score compared to controls (0.58 vs 0.42, p = 0.002). HBV DNA was detectable in 52/53 (98.1%) coinfected patients with 14/53 (26.4%) having HBV DNA >20,000 IU/L. 10/12 (83.3%) had at least one detectable 3TC-associated HBV resistance, which tended to be associated with increase in liver fibrosis after adjusting for age and sex (p = 0.05). Conclusions Compliance with HBV testing and treatment guidelines is poor in this Gambian HIV programme putting coinfected patients at risk of liver complications. However, the excellent uptake of HBV screening and linkage to care in our study suggests feasible improvements

Continuum modelling of granular particle flow with inelastic inter-particle collisions

The kinetic theory of granular flow is a successful model for gas-solid flows. However, inelastic collisions between particles, among other mechanisms, cause agglomeration of particles, which may be the reason why undue sensitivity of the model to any slight inelasticity in inter-particle collisions has been seen previously. In contrast to a dry (i.e. no interstitial gas) granular system, this tendency to agglomerate in a gas driven two-phase system may be countered by the carrier gas turbulence. In this paper, a heuristic model for particle gas turbulence interaction is introduced within the scope of a generalized kinetic theory model which incorporates the carrier fluid effect on particulate stresses. The numerical results for the flow of granular particles in vertical pipes, which considers slightly inelastic inter-particle collisions, are in reasonably good agreement with published experimental data. Even in this relatively simple model, the results indicate that the interactions between the particle phase and gas turbulence need to be appropriately addressed in any kinetic theory based model for gas solid flows

Cirrus cloud statistics: Temperatures and optical depths

Measurements of the upwelling infrared radiance at 10.5 and 6.5 microns were obtained during the FIRE cirrus Intensive Field Observations using a radiometer with a 15 deg cone nadir field-of-view flown on the NASA Ames ER-2. Data are recorded at a frequency of 1 Hz and the radiometer is continuously calibrated with a liquid nitrogen blackbody source, thereby providing a large number of very accurate radiance values during the course of a several hour flight. For this study, the focus is on the statistical properties of the cirrus deck as deduced from the radiance data. The data acquired on 28 October 1986 is stressed, but some data from the other flights are also shown for comparison purposes

Prescribing patterns of antimicrobial usage in ophthalmology out patients department at tertiary care teaching hospital

Background: Drug utilization provides prescribing behaviors of prescriber. Rational prescribing of antimicrobial drugs plays a crucial role in reducing the antibiotic resistance. The study aim was to analyze the patterns of antimicrobial prescribed ophthalmology outpatient department (OPD) patients.Methods: The study was an observational study completed over a period of 6 months, from July 2014 to December 2014. The study was conducted in Department of Ophthalmology, MGM Medical College, and Hospital Navi Mumbai. A questionnaire was specifically designed factoring patients’ demographical profile, diagnosis of disease, drug regimen.Results: A total 125 prescriptions of patients were analyzed who visited ophthalmology OPD department. Maximum patients belonged to the age group of 41-50 years (27.2%), followed by age group of 31-40 years (25.6%). The proportion of male (59%) patients was more as compared to female patients (41%). Total drug prescribed was 296. Average drug per prescription was 2.36. Among 296 drugs, 144 were antibiotic prescribed. Average antibiotic per prescription was 1.15. Most commonly antibiotic prescribed was moxifloxacin. Most common fixed dose combination (FDC) of antibiotic prescribed was tobramycin plus loteprednol. Among total 125 patients, maximum patients were diagnosed with cataract (25%), followed by meibomitis (12%), conjunctivitis (24%), blephritis (9%), foreign body in eye (12%), psedophakia (10%) and other disease (8%). 96% of antimicrobial were prescribed from essential drug list. The FDC of antimicrobial (40%), fluroquinolone (19%), aminoglycoside (13%), broad spectrum (12%), macrolide (9%), anti-viral (7%) was prescribed. Maximum number of drugs was found in the form eye drops (72%).Conclusion: The present study found that FDC of antibiotic was prescribed maximum. Most common dosage form of prescribed drug was eye drop. Prescription of drugs by brand name was a matter of concern

Temporal and Spatiotemporal Investigation of Tourist Attraction Visit Sentiment on Twitter

In this paper, we propose a sentiment-based approach to investigate the temporal and spatiotemporal effects on tourists\u27 emotions when visiting a city\u27s tourist destinations. Our approach consists of four steps: data collection and preprocessing from social media; visitor origin identification; visit sentiment identification; and temporal and spatiotemporal analysis. The temporal and spatiotemporal dimensions include day of the year, season of the year, day of the week, location sentiment progression, enjoyment measure, and multi-location sentiment progression. We apply this approach to the city of Chicago using over eight million tweets. Results show that seasonal weather, as well as special days and activities like concerts, impact tourists\u27 emotions. In addition, our analysis suggests that tourists experience greater levels of enjoyment in places such as observatories rather than zoos. Finally, we find that local and international visitors tend to convey negative sentiment when visiting more than one attraction in a day whereas the opposite holds for out of state visitors

Simulation for Cybersecurity: State of the Art and Future Directions

In this article, we provide an introduction to simulation for cybersecurity and focus on three themes: (1) an overview of the cybersecurity domain; (2) a summary of notable simulation research efforts for cybersecurity; and (3) a proposed way forward on how simulations could broaden cybersecurity efforts. The overview of cybersecurity provides readers with a foundational perspective of cybersecurity in the light of targets, threats, and preventive measures. The simulation research section details the current role that simulation plays in cybersecurity, which mainly falls on representative environment building; test, evaluate, and explore; training and exercises; risk analysis and assessment; and humans in cybersecurity research. The proposed way forward section posits that the advancement of collecting and accessing sociotechnological data to inform models, the creation of new theoretical constructs, and the integration and improvement of behavioral models are needed to advance cybersecurity efforts

A retrospective study on the impact of comorbid depression or anxiety on healthcare resource use and costs among diabetic neuropathy patients

<p>Abstract</p> <p>Background</p> <p>Diabetic neuropathy (DN) is a common complication of diabetes that has significant economic burden, especially for patients with comorbid depression or anxiety. This study examines and quantifies factors associated with healthcare costs among patients diagnosed with diabetic neuropathy (DN) with or without a comorbid diagnosis of depression or anxiety (DA) using retrospective administrative claims data. No study has examined the differences in economic outcomes depending on the presence of comorbid DA disorders.</p> <p>Methods</p> <p>Over-age-18 individuals with 1+ diagnosis of DN in 2005 were selected. The first observed DN claim was considered the "index date." All individuals had a 12-month pre-index and follow-up period. For both under-age-65 commercially insured and over-age-65 individuals with employer-sponsored Medicare supplemental insurance, we constructed 2 subgroups for individuals with DA (DN-DA) or without (DN-only). Patients' clinical characteristics over pre-index period were compared. Multivariate regressions were performed to assess whether DN-DA patients had higher utilization of healthcare resources and costs than DN-only patients, controlling for demographic and clinical characteristics.</p> <p>Results</p> <p>We identified 16,831 DN-only and 1,699 DN-DA patients in the Medicare supplemental cohort, as well as 17,205 and 3,105 in the commercially insured. DN-DA patients had higher prevalence of diabetes-related comorbidities for cardiovascular disease, cerebrovascular/peripheral vascular disease, nephropathy, obesity, and hypoglycemic events than DN-only patients (all p < 0.05). Controlling for differences in demographic and clinical characteristics, DN-DA patients had $9,235 (p < 0.05) higher total healthcare costs than patients with DN-only among those with Medicare supplemental coverage ($26,718 vs. $17,483), and$10,389 (p < 0.05) more total costs among commercially insured ($29,775 vs.$19,386). Factors associated with increased costs included insurance type, geographical region, diabetes-related comorbidities, and insulin therapy.</p> <p>Conclusion</p> <p>These findings indicate that the healthcare costs were significantly higher for DN patients with depression or anxiety relative to those without such comorbid disorders.</p