Multi-center evaluation of the hepatitis B surface antigen (HBsAg) assay and HbsAg confirmatory assay for the family of Access immunoassay systems

BACKGROUND: Accurate detection of Hepatitis B Surface Antigen (HBsAg) is an important aid in the diagnosis of patients infected with the hepatitis B virus (HBV). A multi-center study was conducted to characterize the performance of the HBsAg assay on the family of Access immunoassay systems from Beckman Coulter. METHODS: The Access HBsAg assay was characterized in a multi-center study and compared to the Abbott AxSYM* and PRISM* HBsAg assays. The bioMérieux VIDAS* assay was used to resolve discrepant results. Reproducibility studies (intra-assay, inter-assay and inter-lot) were performed with pooled serum samples (negative sample, close to cut off, low, medium and high positive samples). Analytical sensitivity, subtype and genotype detection were studied with various commercial panels (SFTS panel, WHO 80/549, WHO 00/588, Teragenix HBV Genotype panel). A panel of recombinant HBsAg mutant proteins was tested to investigate reactivity towards genetic mutations. Clinical sensitivity was verified with seroconversion panels and samples from subjects with known HBV infection. Analytical specificity was studied with samples from patients with potential cross-reactive infections. Clinical specificity was validated among blood donors and a hospitalized population. RESULTS: The imprecision was < 10%. Analytical sensitivity was < or = 0.1 ng/mL (SFTS panel), 0.020 PEI Units/mL (ad panel), 0.024 PEI Units/mL (ay panel), 0.092 IU/mL with WHO 80/549 and 0.056 IU/mL with WHO 00/588. All genotype samples and HBsAg mutants were reactive with the Access HBsAg assay. Seroconversion panels tested showed no significant difference with the reference method. Sensitivity for subjects with known HBV infection was 100%. No interference with potentially cross-reactive infections was observed after confirmatory testing. Specificity was 99.96% (100% after confirmatory testing) in a blood donor population and 99.5% (100% after confirmatory testing) in a hospitalized population. Excellent separation of positive and negative populations was observed. CONCLUSIONS: The Access HBsAg and HBsAg Confirmatory assays meet all clinical and analytical performance requirements of assays for the detection of HBsAg

Augmented versus Virtual Reality Laparoscopic Simulation: What Is the Difference?: A Comparison of the ProMIS Augmented Reality Laparoscopic Simulator versus LapSim Virtual Reality Laparoscopic Simulator

BACKGROUND: Virtual reality (VR) is an emerging new modality for laparoscopic skills training; however, most simulators lack realistic haptic feedback. Augmented reality (AR) is a new laparoscopic simulation system offering a combination of physical objects and VR simulation. Laparoscopic instruments are used within an hybrid mannequin on tissue or objects while using video tracking. This study was designed to assess the difference in realism, haptic feedback, and didactic value between AR and VR laparoscopic simulation. METHODS: The ProMIS AR and LapSim VR simulators were used in this study. The participants performed a basic skills task and a suturing task on both simulators, after which they filled out a questionnaire about their demographics and their opinion of both simulators scored on a 5-point Likert scale. The participants were allotted to 3 groups depending on their experience: experts, intermediates and novices. Significant differences were calculated with the paired t-test. RESULTS: There was general consensus in all groups that the ProMIS AR laparoscopic simulator is more realistic than the LapSim VR laparoscopic simulator in both the basic skills task (mean 4.22 resp. 2.18, P <0.000) as well as the suturing task (mean 4.15 resp. 1.85, P <0.000). The ProMIS is regarded as having better haptic feedback (mean 3.92 resp. 1.92, P <0.000) and as being more useful for training surgical residents (mean 4.51 resp. 2.94, P <0.000). CONCLUSIONS: In comparison with the VR simulator, the AR laparoscopic simulator was regarded by all participants as a better simulator for laparoscopic skills training on all tested feature

Prostate involvement during sexually transmitted infections as measured by prostate-specific antigen concentration

Background:We investigated prostate involvement during sexually transmitted infections by measuring serum prostate-specific antigen (PSA) as a marker of prostate infection, inflammation, and/or cell damage in young, male US military members.Methods:We measured PSA before and during infection for 299 chlamydia, 112 gonorrhoea, and 59 non-chlamydial, non-gonococcal urethritis (NCNGU) cases, and 256 controls.Results:Chlamydia and gonorrhoea, but not NCNGU, cases were more likely to have a large rise (⩾40%) in PSA than controls (33.6%, 19.1%, and 8.2% vs 8.8%, P<0.0001, 0.021, and 0.92, respectively).Conclusion:Chlamydia and gonorrhoea may infect the prostate of some infected men

JADES: Using NIRCam Photometry to Investigate the Dependence of Stellar Mass Inferences on the IMF in the Early Universe

The detection of numerous and relatively bright galaxies at redshifts z > 9 has prompted new investigations into the star-forming properties of high-redshift galaxies. Using local forms of the initial mass function (IMF) to estimate stellar masses of these galaxies from their light output leads to galaxy masses that are at the limit allowed for the state of the LambdaCDM Universe at their redshift. We explore how varying the IMF assumed in studies of galaxies in the early universe changes the inferred values for the stellar masses of these galaxies. We infer galaxy properties with the SED fitting code Prospector using varying IMF parameterizations for a sample of 102 galaxies from the JWST Advanced Deep Extragalactic Survey (JADES) spectroscopically confirmed to be at z > 6.7, with additional photometry from the JWST Extragalactic Medium Band Survey (JEMS) for twenty-one galaxies. We demonstrate that models with stellar masses reduced by a factor of three or more do not affect the modeled spectral energy distribution (SED).Comment: The Significance statement is required for PNAS submissio

The JWST Advanced Deep Extragalactic Survey: Discovery of an Extreme Galaxy Overdensity at z=5.4z = 5.4 with JWST/NIRCam in GOODS-S

We report the discovery of an extreme galaxy overdensity at $z = 5.4$ in the GOODS-S field using JWST/NIRCam imaging from JADES and JEMS alongside JWST/NIRCam wide field slitless spectroscopy from FRESCO. We identified potential members of the overdensity using HST+JWST photometry spanning $\lambda = 0.4-5.0\ \mu\mathrm{m}$. These data provide accurate and well-constrained photometric redshifts down to $m \approx 29-30\,\mathrm{mag}$. We subsequently confirmed $N = 81$ galaxies at $5.2 < z < 5.5$ using JWST slitless spectroscopy over $\lambda = 3.9-5.0\ \mu\mathrm{m}$ through a targeted line search for $\mathrm{H} \alpha$ around the best-fit photometric redshift. We verified that $N = 42$ of these galaxies reside in the field while $N = 39$ galaxies reside in a density around $\sim 10$ times that of a random volume. Stellar populations for these galaxies were inferred from the photometry and used to construct the star-forming main sequence, where protocluster members appeared more massive and exhibited earlier star formation (and thus older stellar populations) when compared to their field galaxy counterparts. We estimate the total halo mass of this large-scale structure to be $12.6 \lesssim \mathrm{log}_{10} \left( M_{\mathrm{halo}}/M_{\odot} \right) \lesssim 12.8$ using an empirical stellar mass to halo mass relation, which is likely an underestimate as a result of incompleteness. Our discovery demonstrates the power of JWST at constraining dark matter halo assembly and galaxy formation at very early cosmic times.Comment: Resubmitted to ApJ based on reviewer report; main text has 15 pages, 6 figures and 1 table; appendix has 1 page, 2 figure sets, and 2 table

The JWST Advanced Deep Extragalactic Survey: Discovery of an Extreme Galaxy Overdensity at z = 5.4 with JWST/NIRCam in GOODS-S

© 2024 The Author(s). Published by the American Astronomical Society. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY), https://creativecommons.org/licenses/by/4.0/We report the discovery of an extreme galaxy overdensity at $z = 5.4$ in the GOODS-S field using JWST/NIRCam imaging from JADES and JEMS alongside JWST/NIRCam wide field slitless spectroscopy from FRESCO. We identified potential members of the overdensity using HST+JWST photometry spanning $\lambda = 0.4-5.0\ \mu\mathrm{m}$. These data provide accurate and well-constrained photometric redshifts down to $m \approx 29-30\,\mathrm{mag}$. We subsequently confirmed $N = 81$ galaxies at $5.2 < z < 5.5$ using JWST slitless spectroscopy over $\lambda = 3.9-5.0\ \mu\mathrm{m}$ through a targeted line search for $\mathrm{H} \alpha$ around the best-fit photometric redshift. We verified that $N = 42$ of these galaxies reside in the field while $N = 39$ galaxies reside in a density around $\sim 10$ times that of a random volume. Stellar populations for these galaxies were inferred from the photometry and used to construct the star-forming main sequence, where protocluster members appeared more massive and exhibited earlier star formation (and thus older stellar populations) when compared to their field galaxy counterparts. We estimate the total halo mass of this large-scale structure to be $12.6 \lesssim \mathrm{log}_{10} \left( M_{\mathrm{halo}}/M_{\odot} \right) \lesssim 12.8$ using an empirical stellar mass to halo mass relation, which is likely an underestimate as a result of incompleteness. Our discovery demonstrates the power of JWST at constraining dark matter halo assembly and galaxy formation at very early cosmic times.Peer reviewe

Multicenter Phase 2 Trial of Sirolimus for Tuberous Sclerosis: Kidney Angiomyolipomas and Other Tumors Regress and VEGF- D Levels Decrease

Tuberous sclerosis (TSC) related tumors are characterized by constitutively activated mTOR signaling due to mutations in TSC1 or TSC2.We completed a phase 2 multicenter trial to evaluate the efficacy and tolerability of the mTOR inhibitor, sirolimus, for the treatment of kidney angiomyolipomas.36 adults with TSC or TSC/LAM were enrolled and started on daily sirolimus. The overall response rate was 44.4% (95% confidence intervals [CI] 28 to 61); 16/36 had a partial response. The remainder had stable disease (47.2%, 17/36), or were unevaluable (8.3%, 3/36). The mean decrease in kidney tumor size (sum of the longest diameters [sum LD]) was 29.9% (95% CI, 22 to 37; n = 28 at week 52). Drug related grade 1-2 toxicities that occurred with a frequency of >20% included: stomatitis, hypertriglyceridemia, hypercholesterolemia, bone marrow suppression (anemia, mild neutropenia, leucopenia), proteinuria, and joint pain. There were three drug related grade 3 events: lymphopenia, headache, weight gain. Kidney angiomyolipomas regrew when sirolimus was discontinued but responses tended to persist if treatment was continued after week 52. We observed regression of brain tumors (SEGAs) in 7/11 cases (26% mean decrease in diameter), regression of liver angiomyolipomas in 4/5 cases (32.1% mean decrease in longest diameter), subjective improvement in facial angiofibromas in 57%, and stable lung function in women with TSC/LAM (n = 15). A correlative biomarker study showed that serum VEGF-D levels are elevated at baseline, decrease with sirolimus treatment, and correlate with kidney angiomyolipoma size (Spearman correlation coefficient 0.54, p = 0.001, at baseline).Sirolimus treatment for 52 weeks induced regression of kidney angiomyolipomas, SEGAs, and liver angiomyolipomas. Serum VEGF-D may be a useful biomarker for monitoring kidney angiomyolipoma size. Future studies are needed to determine benefits and risks of longer duration treatment in adults and children with TSC.Clinicaltrials.gov NCT00126672

A novel small molecule target in human airway smooth muscle for potential treatment of obstructive lung diseases: a staged high-throughput biophysical screening

<p>Abstract</p> <p>Background</p> <p>A newly identified mechanism of smooth muscle relaxation is the interaction between the small heat shock protein 20 (HSP20) and 14-3-3 proteins. Focusing upon this class of interactions, we describe here a novel drug target screening approach for treating airflow obstruction in asthma.</p> <p>Methods</p> <p>Using a high-throughput fluorescence polarization (FP) assay, we screened a library of compounds that could act as small molecule modulators of HSP20 signals. We then applied two quantitative, cell-based biophysical methods to assess the functional efficacy of these molecules and rank-ordered their abilities to relax isolated human airway smooth muscle (ASM). Scaling up to the level of an intact tissue, we confirmed in a concentration-responsive manner the potency of the cell-based hit compounds.</p> <p>Results</p> <p>Among 58,019 compound tested, 268 compounds caused 20% or more reduction of the polarized emission in the FP assay. A small subset of these primary screen hits, belonging to two scaffolds, caused relaxation of isolated ASM cell <it>in vitro </it>and attenuated active force development of intact tissue <it>ex vivo</it>.</p> <p>Conclusions</p> <p>This staged biophysical screening paradigm provides proof-of-principle for high-throughput and cost-effective discovery of new small molecule therapeutic agents for obstructive lung diseases.</p

Garlic Extract Diallyl Sulfide (DAS) Activates Nuclear Receptor CAR to Induce the Sult1e1 Gene in Mouse Liver

Constituent chemicals in garlic extract are known to induce phase I and phase II enzymes in rodent livers. Here we have utilized Car+/+ and Car−/− mice to demonstrate that the nuclear xenobiotic receptor CAR regulated the induction of the estrogen sulfotransferase Sult1e1 gene by diallyl sulfide (DAS) treatment in mouse liver. DAS treatment caused CAR accumulation in the nucleus, resulting in a remarkable increase of SULT1E1 mRNA (3,200 fold) and protein in the livers of Car+/+ females but not of Car−/− female mice. DAS also induced other CAR-regulated genes such as Cyp2b10, Cyp3a11 and Gadd45β. Compared with the rapid increase of these mRNA levels, which began as early as 6 hourrs after DAS treatment, the levels of SULT1E1 mRNA began increasing after 24 hours. This slow response to DAS suggested that CAR required an additional factor to activate the Sult1e1 gene or that this activation was indirect. Despite the remarkable induction of SULT1E1, there was no decrease in the serum levels of endogenous E2 or increase of estrone sulfate while the clearance of exogenously administrated E2 was accelerated in DAS treated mice

Prostate-specific antigen testing accuracy in community practice

BACKGROUND: Most data on prostate-specific antigen (PSA) testing come from urologic cohorts comprised of volunteers for screening programs. We evaluated the diagnostic accuracy of PSA testing for detecting prostate cancer in community practice. METHODS: PSA testing results were compared with a reference standard of prostate biopsy. Subjects were 2,620 men 40 years and older undergoing (PSA) testing and biopsy from 1/1/95 through 12/31/98 in the Albuquerque, New Mexico metropolitan area. Diagnostic measures included the area under the receiver-operating characteristic curve, sensitivity, specificity, and likelihood ratios. RESULTS: Cancer was detected in 930 subjects (35%). The area under the ROC curve was 0.67 and the PSA cutpoint of 4 ng/ml had a sensitivity of 86% and a specificity of 33%. The likelihood ratio for a positive test (LR+) was 1.28 and 0.42 for a negative test (LR-). PSA testing was most sensitive (90%) but least specific (27%) in older men. Age-specific reference ranges improved specificity in older men (49%) but decreased sensitivity (70%), with an LR+ of 1.38. Lowering the PSA cutpoint to 2 ng/ml resulted in a sensitivity of 95%, a specificity of 20%, and an LR+ of 1.19. CONCLUSIONS: PSA testing had fair discriminating power for detecting prostate cancer in community practice. The PSA cutpoint of 4 ng/ml was sensitive but relatively non-specific and associated likelihood ratios only moderately revised probabilities for cancer. Using age-specific reference ranges and a PSA cutpoint below 4 ng/ml improved test specificity and sensitivity, respectively, but did not improve the overall accuracy of PSA testing