Digital Frequency Domain Multiplexer for mm-Wavelength Telescopes

An FPGA based digital signal processing (DSP) system for biasing and reading out multiplexed bolometric detectors for mm-wavelength telescopes is presented. This readout system is being deployed for balloon-borne and ground based cosmology experiments with the primary goal of measuring the signature of inflation with the Cosmic Microwave Background Radiation. The system consists of analog superconducting electronics running at 250mK and 4K, coupled to digital room temperature backend electronics described here. The digital electronics perform the real time functionality with DSP algorithms implemented in firmware. A soft embedded processor provides all of the slow housekeeping control and communications. Each board in the system synthesizes multi-frequency combs of 8 to 32 carriers in the MHz band to bias the detectors. After the carriers have been modulated with the sky-signal by the detectors, the same boards digitize the comb directly. The carriers are mixed down to base-band and low pass filtered. The signal bandwidth of 0.050 Hz - 100 Hz places extreme requirements on stability and requires powerful filtering techniques to recover the sky-signal from the MHz carriers.Comment: 6 pages, 6 figures, Submitted May 2007 to IEEE Transactions on Nuclear Science (TNS

34587 Efficacy of ruxolitinib cream for the treatment of atopic dermatitis by anatomic region: Pooled analysis from two randomized phase 3 studies

Atopic dermatitis (AD) is a highly pruritic inflammatory skin disease. Two phase 3 studies (TRuE-AD1/TRuE-AD2) enrolled patients aged ≥12 years with AD for ≥2 years, an Investigator’s Global Assessment (IGA) score of 2/3, and 3%–20% affected body surface area. Patients (total N = 1249; median age, 32 years) were randomized (2:2:1) to twice-daily 0.75% ruxolitinib (Janus kinase [JAK] 1/JAK2 inhibitor) cream, 1.5% ruxolitinib cream, or vehicle cream for 8 weeks of double-blind treatment, and thereafter continued in a long-term, 44-week period of the studies. In this pooled analysis, mean percentage change from baseline in Eczema Area and Severity Index (EASI) anatomic region subscores is reported up to Week 8 (n = 1208). For the head and neck region, patients applying 0.75%/1.5% ruxolitinib cream (vs vehicle) achieved mean improvements of 59.3%/55.8% (vs 13.4%), 70.4%/71.3% (vs 22.4%), and 70.0%/78.7% (vs 45.0%) at Weeks 2, 4, and 8, respectively (all P \u3c.0001). Results were similar for the upper limbs region (48.5%/54.7% [vs 13.3%], 66.6%/70.3% [vs 25.0%], and 73.5%/74.9% [vs 35.1%] all P \u3c.0001). For the trunk region, patients achieved mean improvements of 49.8%/60.0% (vs 12.1%), 67.3%/73.8% (vs 15.0%), and 72.7%/81.0% (vs 15.6%) at Weeks 2, 4, and 8, respectively (all P \u3c.0001). Similar results were observed for the lower limbs region (46.0%/48.2% [vs 16.3%], 65.9%/66.2% [vs 13.9%], and 76.3%/74.9% [vs 39.8%]; all P \u3c.0001). Ruxolitinib cream was well tolerated, with an adverse event profile similar to vehicle. In summary, ruxolitinib cream demonstrated significant improvements vs vehicle in patients with AD across anatomic regions as early as Week 2

Tuning of Kilopixel Transition Edge Sensor Bolometer Arrays with a Digital Frequency Multiplexed Readout System

A digital frequency multiplexing (DfMUX) system has been developed and used to tune large arrays of transition edge sensor (TES) bolometers read out with SQUID arrays for mm-wavelength cosmology telescopes. The DfMUX system multiplexes the input bias voltages and output currents for several bolometers on a single set of cryogenic wires. Multiplexing reduces the heat load on the camera's sub-Kelvin cryogenic detector stage. In this paper we describe the algorithms and software used to set up and optimize the operation of the bolometric camera. The algorithms are implemented on soft processors embedded within FPGA devices operating on each backend readout board. The result is a fully parallelized implementation for which the setup time is independent of the array size.Comment: 5 pages, 4 figure

International observational atopic dermatitis cohort to follow natural history and treatment course: TARGET-DERM AD study design and rationale

INTRODUCTION: As new topical and systemic treatments become available for atopic dermatitis (AD), there is a need to understand how treatments are being used in routine clinical practice, their comparative effectiveness and their long-term safety in diverse clinical settings. METHODS AND ANALYSIS: The TARGET-DERM AD cohort is a longitudinal, observational study of patients with AD of all ages, designed to provide practical information on long-term effectiveness and safety unobtainable in traditional registration trials. Patients with physician-diagnosed AD receiving prescription treatment (topical or systemic) will be enrolled at academic and community clinical centres. Up to 3 years of retrospective medical records, 5 years of prospective medical records, and optional biological samples and patient-reported outcomes will be collected. The primary aims include characterisation of AD treatment regimens, evaluation of response to therapy, and description of adverse events. ETHICS AND DISSEMINATION: TARGET-DERM has been approved by a central IRB (Copernicus Group IRB, 5000 Centregreen Way Suite 200, Cary, North Carolina 27513) as well as local and institutional IRBs. No additional Ethics Committee reviews. Results will be reviewed by a publications committee and submitted to peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT03661866, pre-results

Treat-to-target in dermatology:A scoping review and International Eczema Council survey on the approach in atopic dermatitis

Treat-to-target (T2T) is a pragmatic therapeutic strategy being gradually introduced into dermatology after adoption in several other clinical areas. Atopic dermatitis (AD), one of the most common inflammatory skin diseases, may also benefit from this structured and practical therapeutic approach. We aimed to evaluate existing data regarding the T2T approach in dermatology, with a specific focus on AD, as well as the views of International Eczema Council (IEC) members on the potential application of a T2T approach to AD management. To do so, we systematically searched for peer-reviewed publications on the T2T approach for any skin disease in the PubMed and Scopus databases up to February 2022 and conducted a survey among IEC members regarding various components to potentially include in a T2T approach in AD. We identified 21 relevant T2T-related reports in dermatology, of which 14 were related to psoriasis, five to AD, one for juvenile dermatomyositis and one for urticaria. In the IEC member survey, respondents proposed treatable traits (with itch, disease severity and sleep problems getting the highest scores), relevant comorbidities (with asthma being selected most commonly, followed by anxiety and depression in adults), recommended specialists that should define the approach in AD (dermatologists, allergists and primary care physicians were most commonly selected in adults), and applicable assessment tools (both physician- and patient-reported), in both adult and paediatric patients, for potential future utilization of the T2T approach in AD. In conclusion, while the T2T approach may become a useful tool to simplify therapeutic goals and AD management, its foundation in AD is only starting to build. A multidisciplinary approach, including a wide range of stakeholders, including patients, is needed to further define the essential components needed to utilize T2T in AD.</p

Characterization of the Two-Component Abortive Phage Infection Mechanism AbiT from Lactococcus lactis

During the production of fermented dairy products, virulent bacteriophages infecting Lactococcus lactis can delay or stop the milk acidification process. A solution to this biological problem consists of introducing natural phage barriers into the strains used by the dairy industry. One such hurdle is called abortive infection (Abi) and causes premature cell death with no or little phage progeny. Here, we describe the isolation and characterization of a novel Abi mechanism encoded by plasmid pED1 from L. lactis. The system is composed of two constitutively cotranscribed genes encoding putative proteins of 127 and 213 amino acids, named AbiTi and AbiTii, respectively. Site-directed mutagenesis indicated that a hydrophobic region at the C-terminal extremity of AbiTi is essential to the antiphage phenotype. The AbiT system is effective against phages of the 936 and P335 species (efficiency of plaquing between 10(−5) and 10(−7)) and causes a 20-fold reduction in the efficiency to form centers of infection as well as a 10- to 12-fold reduction in the burst size. Its efficacy could be improved by raising the plasmid copy number, but changing the intrinsic ratio of AbiTi and AbiTii did not greatly affect the antiphage activity. The monitoring of the intracellular phage infection process by DNA replication, gene expression, and electron microscopy as well as the study of phage mutants by genome mapping indicated that AbiT is likely to act at a later stage of the phage lytic cycle

Chronic Hand Eczema Guidelines From an Expert Panel of the International Eczema Council

BACKGROUND: Assessment of chronic hand eczema (CHE) is complex and warrants standardization. OBJECTIVE: We sought to guide clinicians on the assessment of CHE. METHODS: An electronic questionnaire regarding the diagnosis and assessment of CHE was completed by councilors (n=45) of the International Eczema Council, an international group of clinicians and researchers with expertise in CHE. The survey consisted of 52 statements for consensus. RESULTS: Overall, nine statements (17.3%) had strong, twenty-three (44.2%) moderate, 12 (23.1%) low, and 8 (15.4%) very low levels of agreement. Five statements had considerable disagreement, including the value of conducting a skin biopsy (62.2% disagreement), investigating for possible type 1 reactions (60.0%), conducting a fungal culture (44.4%), finding no history of relevant allergens and/or irritants (31.1%) in most or all cases, and performing patch testing irrespective of lesion location and morphology (28.9%). Agreement was generally highest among respondents from Europe (28.6–77.8% agreement), followed by Asia (7.1%–35.7% agreement), North America (0%–35.5% agreement), and other (0%–13.3% agreement). CONCLUSIONS: There were substantial differences of agreement, suggesting there are many knowledge and/or practice gaps with respect to CHE. Future research is needed to inform evidence-based and/or consensus guidelines for CHE