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The past several years have seen the emergence of a standard cosmological model, in which small temperature differences in the cosmic microwave background (CMB) radiation on angular scales of the order of a degree are understood to arise from acoustic oscillations in the hot plasma of the early Universe, arising from primordial density fluctuations. Within the context of this model, recent measurements of the temperature fluctuations have led to profound conclusions about the origin, evolution and composition of the Universe. Using the measured temperature fluctuations, the theoretical framework predicts the level of polarization of the CMB with essentially no free parameters. Therefore, a measurement of the polarization is a critical test of the theory and thus of the validity of the cosmological parameters derived from the CMB measurements. Here we report the detection of polarization of the CMB with the Degree Angular Scale Interferometer (DASI). The polarization is deteced with high confidence, and its level and spatial distribution are in excellent agreement with the predictions of the standard theory.

Summary Cigarette smoking is a leading cause of preventable morbidity and mortality in the United States. Although public policies have resulted in a decreased number of new smokers, smoking rates remain stubbornly high in certain demographics with 20% of all American middle‐aged men smoking. In addition to the well‐established harmful effects of smoking (i.e. coronary artery disease and lung cancer), the past three decades have led to a compendium of evidence being compiled into the development of a relationship between cigarette smoking and erectile dysfunction. The main physiologic mechanism that appears to be affected includes the nitric oxide signal transduction pathway. This review details the recent literature linking cigarette smoking to erectile dysfunction, epidemiological associations, dose dependency and the effects of smoking cessation on improving erectile quality.

As millimeter instrumentalists push the precision and mapping speed of their instruments ever-higher to make ever-deeper measurements, the need for a precise understanding of the complex permittivity of the dielectrics used in these instruments at their operating temperature heightens. To address this need, we have developed high quality factor quasioptical Fabry-Pérot open resonators spanning 75 GHz-330 GHz, optimized for rapid use in a quick-turnaround 4K cryostat. These hemispherical resonators enable precise metrology of low-loss bulk and thin dielectrics. We present the design and characterization of, and some complex permittivity measurements from, a W-band open resonator.

BackgroundChildren infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) usually present minimal symptoms or are asymptomatic. Nevertheless, a subset of children 2-6 weeks after the initial SARS-CoV-2 infection develops a postinfectious SARS-CoV-2-related multisystem inflammatory syndrome in (MIS-C). Recently, transient expansion of TRBV11-2 T cell clonotypes in MIS-C was associated with signatures of inflammation and T cell activation, however, the underlying pathophysiology of MIS-C is not fully understood [1].ObjectivesThe purpose of our project is to characterize the complexity of cell populations and capture cellular heterogeneity to uncover the regulatory networks and interactions that are disrupted during MIS-C flare with simultaneous profiling of gene expression and open chromatin regions from the same nuclei.MethodsSamples of peripheral blood mononuclear cells from patients with MIS-C diagnosed at the University Children’s Hospital, University Medical Center Ljubljana, were collected during the initial presentation before any treatment and at 6-12 months in remission. The primary aim is to identify which regulatory networks are driving inflammation in MIS-C flare, for which we are performing single cell Multiome ATAC + Gene Expression Sequencing. To enable simultaneous profiling of epigenomic landscape and gene expression from the same nuclei, we are using Chromium Next GEM Single Cell Multiome ATAC + Gene Expression kit from 10X Genomics.ResultsWe included 32 patients with MIS-C from whom we collected paired blood samples during the initial presentation before treatment and at 6-12 months in remission. In single cell multiomic experiment we included 10 patients with paired samples, with the most viable cell count prior cryopreservation. All samples that are included into multiomic single cell analysis have 75% - 99% viability prior cryopreservation. In the protocol the key is to remove remaining granulocytes causing high mitochondrial RNA burden and extensively optimize the dilution factor of lysis buffer and the length of cell lysis step in order to get intact nuclei with no significant blebbing. Afterward, the single cell ATAC libraries as well as single-cell gene expression libraries are constructed and sequenced. Data are undergoing pairwise analysis to compare the cell population heterogeneity, expression profile and open chromatin landscape in the time of the initial presentation of MIS-C and in the remission, with Cell ranger software as well as with R package scREG [2], and custom scripting. In the second step we will inspect if the resulting altered transcriptomic signature from single-cell experiment is present on larger cohort. In that regard, we will perform bulk transcriptomic profiling on all paired collected samples during the initial presentation of MIS-C before treatment and at 6-12 months in remission.ConclusionThe results of this project are expected to enlighten the underlying pathophysiology of MIS-C flare and thus support clinical decision on more targeted treatment. The identified disrupted networks during MIS-C flare could lead the way to establish an early diagnosis and improve long-term outcome, including prevention of myocardial and neuropsychological impairment. Moreover, a better understanding of the disrupted regulatory networks that are driving inflammation in MIS-C, could lead to new insights into diseases with similar clinical presentations as is Kawasaki Disease.References[1]Sacco, K., Castagnoli, R., Vakkilainen, S. et al. Immunopathological signatures in multisystem inflammatory syndrome in children and pediatric COVID-19. Nat Med 28, 1050–1062 (2022).[2]Duren, Z., Chang, F., Naqing, F. et al. Regulatory analysis of single cell multiome gene expression and chromatin accessibility data with scREG. Genome Biol 23, 114 (2022).AcknowledgementsThis research was supported by Slovenian research agency grant J3-3061 and Interreg ITA-SLO project Cattedra.Disclosure of InterestsNone Declared.

The aim of this prospective study was to investigate the accuracy and inter-observer reliability of MRI in detection of local recurrence (LR) of pancreatic adenocarcinoma (PAC) after surgery, which was proved by PET-CT and access correlation between functional MRI and PET parameters. Forty-five patients who underwent PET-CT and MRI for follow-up purposes after radical operation of PAC were included. Twenty-three were PET positive (study group) and 22 negative for LR (control group). MR examination was performed within one month after PET-CT and three readers who were blind for PET-CT findings searched LR in T2W, 3D-dynamic post-contrast T1W-FS and DWI sequences, respectively. Sensitivity and specificity were calculated while inter-reader agreement was estimated by Cronbach’s Alpha reliability coefficient (CARC). Apparent diffusion coefficient (ADC) of LR was correlated with the size (maximal diameter) and functional PET-CT parameters: mean and maximum standardized uptake values (SUVmean, SUVmax), metabolic tumor volume (MTV) and total lesion glycolysis (TLG), using Spearman’s correlation coefficient (r S ). Sensitivity and specificity among three readers in detecting the LR were 70% and 77–84% in T2W (CARC 0.806), 91–100% and 100% in 3D post-contrast T1W-FS (CARC 0.980), and both 100% in DWI sequences (CARC 1.000). Moderate inverse correlation was found between the ADC and SUVmean ( r S  = − 0.484), MTV ( r S  = − 0.494), TLG ( r S  = − 0.519) and lesion size ( r S  = − 0.567). MRI with DWI shows high diagnostic accuracy in detecting the LR of PAC in comparison to PET-CT as reference standard. ADC significantly inversely correlates with standard and advanced PET parameters and size of LR.

Polarization observations of the cosmic microwave background with the Cosmic Background Imager from September 2002 to May 2004 provide a significant detection of the f-mode polarization and reveal an angular power spectrum of polarized emission showing peaks and valleys that are shifted in phase by half a cycle relative to those of the total intensity spectrum. This key agreement between the phase of the observed polarization spectrum and that predicted on the basis of the total intensity spectrum provides support for the standard model of cosmology, in which dark matter and dark energy are the dominant constituents, the geometry is close to flat, and primordial density fluctuations are predominantly adiabatic with a matter power spectrum commensurate with inflationary cosmological models.

Background:Periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA) syndrome is the most common autoinflammatory disease in children, often grouped together with hereditary periodic fever syndromes, although its cause and hereditary nature remain unexplained.Objectives:We investigated whether a differential DNA methylation was present in DNA from peripheral blood mononuclear cells (PBMC) in patients with PFAPA versus a group of healthy young individuals.Methods:A whole epigenome analysis (MeDIP and MBD) was performed using pooled DNA libraries enriched for methylated genomic regions. Of identified candidate genes, two with most significantly different methylation leves were further evaluated with methylation specific restriction enzymes coupled with qPCR (MSRE-qPCR).Results:The analysis showed that PIK3AP1 and SPON2 intronic gene regions are differentially methylated in patients with PFAPA. MSRE-qPCR proved as a quick, reliable and cost-effective method to confirm results from MeDIP and MBD.Conclusion:Our findings indicate that B cell adapter protein (BCAP) as PI3K binding inhibitor of inflammation and spondin-2 (SPON2) as a pattern recognition molecule and integrin ligand could play a role in etiology of PFAPA. Their role and impact of changed DNA methylation in PFAPA etiology and autoinflammation need further investigation.References:[1]Wekell P. Periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis syndrome – PFAPA syndrome. Press Medicale [Internet]. 2019;48(1):e77–87. Available from: https://doi.org/10.1016/j.lpm.2018.08.016[2]K. Theodoropoulou, F. Vanoni, and M. Hofer, “Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Cervical Adenitis (PFAPA) Syndrome: a Review of the Pathogenesis,” Curr. Rheumatol. Rep., vol. 18:18, 2016.[3]Carpentier SJ, Ni M, Duggan JM, James RG, Cookson BT, Hamerman JA. The signaling adaptor BCAP inhibits NLRP3 and NLRC4 inflammasome activation in macrophages through interactions with Flightless-1. Sci Signal. 2019;12(581).[4]He YW, Li H, Zhang J, Hsu CL, Lin E, Zhang N, et al. The extracellular matrix protein mindin is a pattern-recognition molecule for microbial pathogens. Nat Immunol. 2004;5(1):88–97.Disclosure of Interests:None declared

Branches of cosmic inflationary models, such as slow-roll inflation, predict a background of primordial gravitational waves that imprints a unique odd-parity “B-mode” pattern in the Cosmic Microwave Background (CMB) at amplitudes that are within experimental reach. The BICEP/Keck (BK) experiment targets this primordial signature, the amplitude of which is parameterized by the tensor-to-scalar ratio r , by observing the polarized microwave sky through the exceptionally clean and stable atmosphere at the South Pole. B-mode measurements require an instrument with exquisite sensitivity, tight control of systematics, and wide frequency coverage to disentangle the primordial signal from the Galactic foregrounds. BICEP Array represents the most recent stage of the BK program and comprises four BICEP3-class receivers observing at 30/40, 95, 150 and 220/270 GHz. The 30/40 GHz receiver will be deployed at the South Pole during the 2019/2020 austral summer. After 3 full years of observations with 30,000+ detectors, BICEP Array will measure primordial gravitational waves to a precision σ ( r ) between 0.002 and 0.004, depending on foreground complexity and the degree of lensing removal. In this paper, we give an overview of the instrument, highlighting the design features in terms of cryogenics, magnetic shielding, detectors and readout architecture as well as reporting on the integration and tests that are ongoing with the first receiver at 30/40 GHz.

The BICEP/ Keck series of experiments target the cosmic microwave background at degree-scale resolution from the South Pole. Over the next few years, the “Stage-3” BICEP Array (BA) telescope will improve the program’s frequency coverage and sensitivity to primordial B-mode polarization by an order of magnitude. The first receiver in the array, BA1, began observing at 30/40 GHz in early 2020. The next two receivers, BA2 and BA3, are currently being assembled and will map the southern sky at frequencies ranging from 95 to 150 GHz. Common to all BA receivers is a refractive, on-axis, cryogenic optical design that focuses microwave radiation onto a focal plane populated with antenna-coupled bolometers. High-performance antireflective coatings up to 760 mm in aperture are needed for each element in the optical chain, and must withstand repeated thermal cycles down to 4 K. Here, we present the design and fabrication of the 30/40 GHz anti-reflection coatings for the recently deployed BA1 receiver, with indices matched to its various polyethylene, nylon and alumina optical components. We describe an epoxy coating technique designed for alumina optics, which achieves better than 80% transmission at room temperature. For polyethylene optical elements, we present a new heat-compression approach that allows low-density polytetrafluoroethylene AR layers to reach sub-percent reflected power. We describe the planned use of these methods for the next BA cryostats, which may inform technological choices for future small-aperture telescopes of the CMB-S4 experiment.

Summary We examined whether men with anabolic‐steroid‐induced hypogonadism (ASIH) seeking testosterone supplementation therapy (TST) regretted their decision to use anabolic‐androgenic steroids (AAS) and what their reasons were for this regret. An anonymous, prospective survey was distributed to 382 men seeking follow‐up treatment for hypogonadism. Prior AAS use was confirmed by self‐report, and men were categorised based upon whether they regretted (R) or did not regret (NR) their use of AAS. The average patient age was 40 ± 0.9 years (n = 79) and 15.2% expressed regret over AAS use. No demographic differences were identified between those who regretted AAS use (n = 12) and those who did not (n = 67). Regret was not related to ASIH diagnosis or to AAS‐related side effects like increased aggression, mood disorders, erectile dysfunction, acne, fluid retention or dyslipidemia. Those who regretted AAS use were significantly more likely to have not comprehended the negative impact on future fertility (P < 0.030). Actual fertility issues were comparable in men who regretted AAS use (16.7%) and those who did not (13%). A total of 15.2% of men regretted using AAS. A lack of awareness regarding the negative long‐term effects on fertility was the primary factor related to regret of AAS use in men with ASIH.