Improving Quality of Care in Rheumatoid Arthritis Through Mobile Patient-Reported Outcome Measurement: Focus Group Study

Background: Patient-reported outcomes (PROs) for chronic disease management can be integrated into the routine workflow by leveraging mobile technology. Objective: The objective of our study was to describe the process of our quality improvement (QI) efforts using tablets for PRO collection in a busy, academic rheumatology practice to support a treat-to-target (TTT) approach for rheumatoid arthritis (RA) management. Methods: Our QI team designed a process for routine collection of PROs for RA patients at the Arthritis Center, employing information technology and an electronic medical record (EMR) system. Patients received a tablet at the clinic check-in desk to complete the Routine Assessment of Patient Index Data 3 (RAPID3) survey, a validated RA PRO. RAPID3 scores were uploaded to the EMR in real time and available for use in shared decision making during routine office visits. Weekly data were collected on RAPID3 completion rates and shared with front desk staff and medical assistants to drive improvement. Patients in our patient family advisory council and focus groups provided informal feedback on the process. Results: From May 1, 2017, to January 31, 2019, a total of 4233 RAPID3 surveys were completed by 1691 patients. The mean age of patients was 63 (SD 14) years; 84.00% (1420/1691) of the patients were female, and 83.00% (1403/1691) of the patients were white. The rates of RAPID3 completion increased from 14.3% (58/405) in May 2017 to 68.00% (254/376) in September 2017 and were sustained over time through January 2019. Informal feedback from patients was positive and negative, relating to the usability of the tablet and the way rheumatologists used and explained the RAPID3 data in shared decision making during the office visit. Conclusions: We designed a sustainable and reliable process for collecting PROs from patients with RA in the waiting room and integrated these data through the EMR during office visits

A multi-exon deletion within WWOX is associated with a 46,XY disorder of sex development

Disorders of sex development (DSD) are congenital conditions where chromosomal, gonad or genital development is atypical. In a significant proportion of 46,XY DSD cases it is not possible to identify a causative mutation, making genetic counseling difficult and potentially hindering optimal treatment. Here, we describe the analysis of a 46,XY DSD patient that presented at birth with ambiguous genitalia. Histological analysis of the surgically removed gonads showed bilateral undifferentiated gonadal tissue and immature testis, both containing malignant germ cells. We screened genomic DNA from this patient for deletions and duplications using an Illumina whole-genome SNP microarray. This analysis revealed a heterozygous deletion within the WWOX gene on chromosome 16, removing exons 6-8. Analysis of parental DNA showed that the deletion was inherited from the mother. cDNA analysis confirmed that the deletion maintained the reading frame, with exon 5 being spliced directly onto exon 9. This deletion is the first description of a germline rearrangement affecting the coding sequence of WWOX in humans. Previously described Wwox knockout mouse models showed gonadal abnormalities, supporting a role for WWOX in human gonad development

HSD3B1 genotype identifies glucocorticoid responsiveness in severe asthma

Asthma resistance to glucocorticoid treatment is a major health problem with unclear etiology. Glucocorticoids inhibit adrenal androgen production. However, androgens have potential benefits in asthma. HSD3B1 encodes for 3β-hydroxysteroid dehydrogenase-1 (3β-HSD1), which catalyzes peripheral conversion from adrenal dehydroepiandrosterone (DHEA) to potent androgens and has a germline missense-encoding polymorphism. The adrenal restrictive HSD3B1(1245A) allele limits conversion, whereas the adrenal permissive HSD3B1(1245C) allele increases DHEA metabolism to potent androgens. In the Severe Asthma Research Program (SARP) III cohort, we determined the association between DHEA-sulfate and percentage predicted forced expiratory volume in 1 s (FEV1PP). HSD3B1(1245) genotypes were assessed, and association between adrenal restrictive and adrenal permissive alleles and FEV1PP in patients with (GC) and without (noGC) daily oral glucocorticoid treatment was determined (n = 318). Validation was performed in a second cohort (SARP I&II; n = 184). DHEA-sulfate is associated with FEV1PP and is suppressed with GC treatment. GC patients homozygous for the adrenal restrictive genotype have lower FEV1PP compared with noGC patients (54.3% vs. 75.1%; P < 0.001). In patients with the homozygous adrenal permissive genotype, there was no FEV1PP difference in GC vs. noGC patients (73.4% vs. 78.9%; P = 0.39). Results were independently confirmed: FEV1PP for homozygous adrenal restrictive genotype in GC vs. noGC is 49.8 vs. 63.4 (P < 0.001), and for homozygous adrenal permissive genotype, it is 66.7 vs. 67.7 (P = 0.92). The adrenal restrictive HSD3B1(1245) genotype is associated with GC resistance. This effect appears to be driven by GC suppression of 3β-HSD1 substrate. Our results suggest opportunities for prediction of GC resistance and pharmacologic intervention

CMB-S4 Science Book, First Edition

This book lays out the scientific goals to be addressed by the next-generation ground-based cosmic microwave background experiment, CMB-S4, envisioned to consist of dedicated telescopes at the South Pole, the high Chilean Atacama plateau and possibly a northern hemisphere site, all equipped with new superconducting cameras. CMB-S4 will dramatically advance cosmological studies by crossing critical thresholds in the search for the B-mode polarization signature of primordial gravitational waves, in the determination of the number and masses of the neutrinos, in the search for evidence of new light relics, in constraining the nature of dark energy, and in testing general relativity on large scales

Vortices enable the complex aerobatics of peregrine falcons

The peregrine falcon (Falco peregrinus) is known for its extremely high speeds during hunting dives or stoop. Here we demonstrate that the superior manoeuvrability of peregrine falcons during stoop is attributed to vortex-dominated flow promoted by their morphology, in the M-shape configuration adopted towards the end of dive. Both experiments and simulations on life-size models, derived from field observations, revealed the presence of vortices emanating from the frontal and dorsal region due to a strong spanwise flow promoted by the forward sweep of the radiale. These vortices enhance mixing for flow reattachment towards the tail. The stronger wing and tail vortices provide extra aerodynamic forces through vortex-induced lift for pitch and roll control. A vortex pair with a sense of rotation opposite to that from conventional planar wings interacts with the main wings vortex to reduce induced drag, which would otherwise decelerate the bird significantly during pull-out. These findings could help in improving aircraft performance and wing suits for human flights

Searching for a Stochastic Background of Gravitational Waves with LIGO

The Laser Interferometer Gravitational-wave Observatory (LIGO) has performed the fourth science run, S4, with significantly improved interferometer sensitivities with respect to previous runs. Using data acquired during this science run, we place a limit on the amplitude of a stochastic background of gravitational waves. For a frequency independent spectrum, the new limit is $\Omega_{\rm GW} < 6.5 \times 10^{-5}$. This is currently the most sensitive result in the frequency range 51-150 Hz, with a factor of 13 improvement over the previous LIGO result. We discuss complementarity of the new result with other constraints on a stochastic background of gravitational waves, and we investigate implications of the new result for different models of this background.Comment: 37 pages, 16 figure

Quantum state preparation and macroscopic entanglement in gravitational-wave detectors

Long-baseline laser-interferometer gravitational-wave detectors are operating at a factor of 10 (in amplitude) above the standard quantum limit (SQL) within a broad frequency band. Such a low classical noise budget has already allowed the creation of a controlled 2.7 kg macroscopic oscillator with an effective eigenfrequency of 150 Hz and an occupation number of 200. This result, along with the prospect for further improvements, heralds the new possibility of experimentally probing macroscopic quantum mechanics (MQM) - quantum mechanical behavior of objects in the realm of everyday experience - using gravitational-wave detectors. In this paper, we provide the mathematical foundation for the first step of a MQM experiment: the preparation of a macroscopic test mass into a nearly minimum-Heisenberg-limited Gaussian quantum state, which is possible if the interferometer's classical noise beats the SQL in a broad frequency band. Our formalism, based on Wiener filtering, allows a straightforward conversion from the classical noise budget of a laser interferometer, in terms of noise spectra, into the strategy for quantum state preparation, and the quality of the prepared state. Using this formalism, we consider how Gaussian entanglement can be built among two macroscopic test masses, and the performance of the planned Advanced LIGO interferometers in quantum-state preparation

Norovirus Recombination in ORF1/ORF2 Overlap

Norovirus (NoV) genogroups I and II (GI and GII) are now recognized as the predominant worldwide cause of outbreaks of acute gastroenteritis in humans. Three recombinant NoV GII isolates were identified and characterized, 2 of which are unrelated to any previously published recombinant NoV. Using data from the current study, published sequences, database searches, and molecular techniques, we identified 23 recombinant NoV GII and 1 recombinant NoV GI isolates. Analysis of the genetic relationships among the recombinant NoV GII isolates identified 9 independent recombinant sequences; the other 14 strains were close relatives. Two of the 9 independent recombinant NoV were closely related to other recombinants only in the polymerase region, and in a similar fashion 1 recombinant NoV was closely related to another only in the capsid region. Breakpoint analysis of recombinant NoV showed that recombination occurred in the open reading frame (ORF)1/ORF2 overlap. We provide evidence to support the theory of the role of subgenomic RNA promoters as recombination hotspots and describe a simple mechanism of how recombination might occur in NoV

FAPRI 1997 U.S. Agricultural Outlook

The Food and Agricultural Policy Research Institute develops a long-term outlook for the world agricultural sector once each year. While the initial steps to develop the new baseline start as soon as the previous year’s baseline is completed, the work begins in earnest in September and October with a discussion of policy and macroeconomic assumptions as well as a review of the models to be used in the upcoming exercise. The preliminary baseline is developed in November and that preliminary baseline is then shared among a number of reviewers. During the first or second week of January, more than 100 respondents are brought together for a two-day review process. Each segment of the baseline is presented and examined in a frank and open exchange of views. Subsequent to that review, the preliminary baseline is finalized