Broadband Squeezed Microwaves and Amplification with a Josephson Traveling-Wave Parametric Amplifier

Squeezing of the electromagnetic vacuum is an essential metrological technique used to reduce quantum noise in applications spanning gravitational wave detection, biological microscopy, and quantum information science. In superconducting circuits, the resonator-based Josephson-junction parametric amplifiers conventionally used to generate squeezed microwaves are constrained by a narrow bandwidth and low dynamic range. In this work, we develop a dual-pump, broadband Josephson traveling-wave parametric amplifier that combines a phase-sensitive extinction ratio of 56 dB with single-mode squeezing on par with the best resonator-based squeezers. We also demonstrate two-mode squeezing at microwave frequencies with bandwidth in the gigahertz range that is almost two orders of magnitude wider than that of contemporary resonator-based squeezers. Our amplifier is capable of simultaneously creating entangled microwave photon pairs with large frequency separation, with potential applications including high-fidelity qubit readout, quantum illumination and teleportation

Post-intervention Status in Patients With Refractory Myasthenia Gravis Treated With Eculizumab During REGAIN and Its Open-Label Extension

OBJECTIVE: To evaluate whether eculizumab helps patients with anti-acetylcholine receptor-positive (AChR+) refractory generalized myasthenia gravis (gMG) achieve the Myasthenia Gravis Foundation of America (MGFA) post-intervention status of minimal manifestations (MM), we assessed patients' status throughout REGAIN (Safety and Efficacy of Eculizumab in AChR+ Refractory Generalized Myasthenia Gravis) and its open-label extension. METHODS: Patients who completed the REGAIN randomized controlled trial and continued into the open-label extension were included in this tertiary endpoint analysis. Patients were assessed for the MGFA post-intervention status of improved, unchanged, worse, MM, and pharmacologic remission at defined time points during REGAIN and through week 130 of the open-label study. RESULTS: A total of 117 patients completed REGAIN and continued into the open-label study (eculizumab/eculizumab: 56; placebo/eculizumab: 61). At week 26 of REGAIN, more eculizumab-treated patients than placebo-treated patients achieved a status of improved (60.7% vs 41.7%) or MM (25.0% vs 13.3%; common OR: 2.3; 95% CI: 1.1-4.5). After 130 weeks of eculizumab treatment, 88.0% of patients achieved improved status and 57.3% of patients achieved MM status. The safety profile of eculizumab was consistent with its known profile and no new safety signals were detected. CONCLUSION: Eculizumab led to rapid and sustained achievement of MM in patients with AChR+ refractory gMG. These findings support the use of eculizumab in this previously difficult-to-treat patient population. CLINICALTRIALSGOV IDENTIFIER: REGAIN, NCT01997229; REGAIN open-label extension, NCT02301624. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that, after 26 weeks of eculizumab treatment, 25.0% of adults with AChR+ refractory gMG achieved MM, compared with 13.3% who received placebo

The Power of Community Voices for Enhancing Community Health Needs Assessments.

As required by the Affordable Care Act, Community Health Needs Assessments (CHNAs) are formalized processes nonprofit hospitals must perform at least every 3 years. CHNAs are designed to help hospitals better tailor health services to the needs of local residents. However, CHNAs most often use quantitative, population-level data, and rarely incorporate the actual voices of local community members. This is particularly a problem for meeting the needs of residents who are also racial or ethnic minorities. This article discusses one model for integrating residents' voices into the CHNA process. In this model, we videotaped interviews with community members and then coded and analyzed interview data to identify underlying themes. We created a short video aimed at starting conversations about community members' concerns. In addition to demonstrating how other nonprofit hospitals may use qualitative data in the CHNA process, this article illustrates how adding qualitative data may change how we think about health promotion. We find that community members requested that health care providers view culture as a health resource, foster community connections, and be present in the community

Hyperendemic Chlamydia trachomatis sexually transmitted infections among females represent a high burden of asymptomatic disease and health disparity among Pacific Islanders in Fiji.

BackgroundChlamydia trachomatis is the most common bacterial sexually transmitted infection worldwide with some of the highest prevalence rates among Pacific Island Countries where syndromic management is practiced. However, little is known about the true prevalence and risk indicators for infection among neglected populations in these countries that suffer from health disparities.Methodology/principal findingsConsecutive sampling was used to enroll sexually active females, aged 18-40 years, attending 12 Fijian Ministry of Health and Medical Services Health Centers and outreach locations from February to December, 2018. A Behavioral Surveillance Survey was administered to assess risk indicators for infection. Signs and symptoms were recorded, and vaginal swabs were tested for C. trachomatis, Neisseria gonorrhoeae, Trichomonas vaginalis, Candida and bacterial vaginosis. Bivariate and multivariate logistic regression analyses were performed using R-Studio. Of 577 participants, 103 (17.85%) were infected with C. trachomatis of whom 80% were asymptomatic and only 11 met criteria for syndromic management; 38.8% of infected women were 18-24 years old with a prevalence of 30.5%. 91.7% of participants intermittently or did not use condoms. C. trachomatis infection was associated with iTaukei ethnicity (OR 21.41 [95% CI: 6.38-133.53]); two lifetime partners (OR 2.12 [95% CI: 1.08-4.18]); and N. gonorrhoeae co-infection (OR 9.56 [95% CI: 3.67-28.15]) in multivariate analyses.ConclusionsA disproportionately high burden of C. trachomatis is present among young asymptomatic women in Fiji of iTaukei ethnicity despite the low number of lifetime partners. Syndromic management and lack of barrier contraceptives contribute to hyperendemic levels. Strategic STI education and screening of at-risk adolescents, young women, and their partner(s) with appropriate treatment are urgently needed to control the epidemic

Hyperendemic Chlamydia trachomatis sexually transmitted infections among females represent a high burden of asymptomatic disease and health disparity among Pacific Islanders in Fiji.

BackgroundChlamydia trachomatis is the most common bacterial sexually transmitted infection worldwide with some of the highest prevalence rates among Pacific Island Countries where syndromic management is practiced. However, little is known about the true prevalence and risk indicators for infection among neglected populations in these countries that suffer from health disparities.Methodology/principal findingsConsecutive sampling was used to enroll sexually active females, aged 18-40 years, attending 12 Fijian Ministry of Health and Medical Services Health Centers and outreach locations from February to December, 2018. A Behavioral Surveillance Survey was administered to assess risk indicators for infection. Signs and symptoms were recorded, and vaginal swabs were tested for C. trachomatis, Neisseria gonorrhoeae, Trichomonas vaginalis, Candida and bacterial vaginosis. Bivariate and multivariate logistic regression analyses were performed using R-Studio. Of 577 participants, 103 (17.85%) were infected with C. trachomatis of whom 80% were asymptomatic and only 11 met criteria for syndromic management; 38.8% of infected women were 18-24 years old with a prevalence of 30.5%. 91.7% of participants intermittently or did not use condoms. C. trachomatis infection was associated with iTaukei ethnicity (OR 21.41 [95% CI: 6.38-133.53]); two lifetime partners (OR 2.12 [95% CI: 1.08-4.18]); and N. gonorrhoeae co-infection (OR 9.56 [95% CI: 3.67-28.15]) in multivariate analyses.ConclusionsA disproportionately high burden of C. trachomatis is present among young asymptomatic women in Fiji of iTaukei ethnicity despite the low number of lifetime partners. Syndromic management and lack of barrier contraceptives contribute to hyperendemic levels. Strategic STI education and screening of at-risk adolescents, young women, and their partner(s) with appropriate treatment are urgently needed to control the epidemic

MPI of SuperSPIO20-labeled ALS patient-derived, genome-edited iPSCs and iPSC-derived motor neurons

Genome-edited induced pluripotent stem cells (iPSCs), iPSC-derived neural precursor cells (NPCs) and iPSC-derived motorneurons (MNs) have shown considerable potential for neurorepair in transgenic amyotrophic lateral sclerosis (ALS) rodent models.When pursuing mutant gene-edited iPSC cell therapy in patients, it is highly desirable to have non-invasive imaging techniquesavailable that can report longitudinally on the fate of transplanted cells. With magnetic particle imaging (MPI), one can visualize andquantify the distribution of superparamagnetic iron oxide (SPIO)-labeled stem cells in the body. Here, we report an optimized magneticlabeling protocol for MPI tracking of gene-edited iPSCs and iPSC-derived MNs. We used SuperSPIO20® and Resovist® for celllabeling and found that the MPI performance of SuperSPIO20® is about 20% higher than that for Resovist® when it comes to imagingof labeled cells. Furthermore, we compared the detection sensitivity of MPI with T2-W MRI and concluded that MPI has at least10-fold higher sensitivity in cell detection

Limited disease progression in endocrine surgery patients with treatment delays due to COVID-19.

BackgroundThe COVID-19 pandemic profoundly impacted the delivery of care and timing of elective surgical procedures. Most endocrine-related operations were considered elective and safe to postpone, providing a unique opportunity to assess clinical outcomes under protracted treatment plans.MethodsAmerican Association of Endocrine Surgeon members were surveyed for participation. A Research Electronic Data Capture survey was developed and distributed to 27 institutions to assess the impact of COVID-19-related delays. The information collected included patient demographics, primary diagnosis, resumption of care, and assessment of disease progression by the surgeon.ResultsTwelve out of 27 institutions completed the survey (44.4%). Of 850 patients, 74.8% (636) were female; median age was 56 (interquartile range, 44-66) years. Forty percent (34) of patients had not been seen since their original surgical appointment was delayed; 86.2% (733) of patients had a delay in care with women more likely to have a delay (87.6% vs 82.2% of men, χ2 = 3.84, P = .05). Median duration of delay was 70 (interquartile range, 42-118) days. Among patients with a delay in care, primary disease site included thyroid (54.2%), parathyroid (37.2%), adrenal (6.5%), and pancreatic/gastrointestinal neuroendocrine tumors (1.3%). In addition, 4.0% (26) of patients experienced disease progression and 4.1% (24) had a change from the initial operative plan. The duration of delay was not associated with disease progression (P = .96) or a change in operative plan (P = .66).ConclusionAlthough some patients experienced disease progression during COVID-19 delays to endocrine disease-related care, most patients with follow-up did not. Our analysis indicated that temporary delay may be an acceptable course of action in extreme circumstances for most endocrine-related surgical disease

Using genome and transcriptome data from African-ancestry female participants to identify putative breast cancer susceptibility genes

African-ancestry (AA) participants are underrepresented in genetics research. Here, we conducted a transcriptome-wide association study (TWAS) in AA female participants to identify putative breast cancer susceptibility genes. We built genetic models to predict levels of gene expression, exon junction, and 3' UTR alternative polyadenylation using genomic and transcriptomic data generated in normal breast tissues from 150 AA participants and then used these models to perform association analyses using genomic data from 18,034 cases and 22,104 controls. At Bonferroni-corrected P < 0.05, we identified six genes associated with breast cancer risk, including four genes not previously reported (CTD-3080P12.3, EN1, LINC01956 and NUP210L). Most of these genes showed a stronger association with risk of estrogen-receptor (ER) negative or triple-negative than ER-positive breast cancer. We also replicated the associations with 29 genes reported in previous TWAS at P < 0.05 (one-sided), providing further support for an association of these genes with breast cancer risk. Our study sheds new light on the genetic basis of breast cancer and highlights the value of conducting research in AA populations