Search

Abstract Objective Create a timeline of diagnosis and treatment for IPF in the US. Design, setting, and participants A retrospective analysis was performed in collaboration with the OptumLabs Data Warehouse using an administrative claims database of Medicare Fee for Service beneficiaries. Adults 50 and over with IPF were included (2014 to 2019). Exposure To focus on IPF, the following diagnoses were excluded: post-inflammatory fibrosis, hypersensitivity pneumonitis, rheumatoid arthritis, sarcoidosis, scleroderma, and connective tissue disease. Main outcomes and measures Data were collected from periods prior, during, and following initial clinical diagnosis of IPF. This included prior respiratory diagnoses, number of respiratory-related hospitalizations, anti-fibrotic and oxygen use, and survival. Results A total of 44,891 with IPF were identified. The most common diagnoses prior to diagnosis of IPF were upper respiratory infections (47%), acute bronchitis (13%), other respiratory disease (10%), chronic obstructive pulmonary disease and bronchiectasis (7%), and pneumonia (6%). The average time to a diagnosis of IPF was 2.7 years after initial respiratory diagnosis. Half of patients had two or more respiratory-related hospitalizations prior to IPF diagnosis. Also, 37% of patients were prescribed oxygen prior to diagnosis of IPF. These observations suggest delayed diagnosis. We also observed only 10.4% were treated with anti-fibrotics. Overall survival declined each year after diagnosis with median survival of 2.80 years. Conclusions and relevance Our retrospective cohort demonstrates that IPF is often diagnosed late, usually preceded by other respiratory diagnoses and hospitalizations. Use of available therapies is low and outcomes remain poor.

Abstract Background Idiopathic pulmonary fibrosis (IPF) is a chronic progressive lung disease with high morbidity and limited treatment options. Type 2 diabetes mellitus (T2DM) is a common comorbid illness among patients with IPF and is often treated with metformin, the first-line agent in the management of T2DM. There is growing evidence demonstrating metformin’s anti-fibrotic properties; however, there is little real-world clinical data regarding its potential effectiveness in IPF. This study aims to evaluate the clinical benefit of metformin in patients with IPF and T2DM. Methods This nationwide cohort study used de-identified administrative claims data from OptumLabs® Data Warehouse to identify 3599 adults with IPF and concomitant T2DM between January 1, 2014 and June 30, 2019. Two cohorts were created: a cohort treated with metformin (n = 1377) and a cohort not treated with metformin (n = 2222). A final 1:1 propensity score-matched cohort compared 1100 patients with IPF and T2DM receiving metformin to those with both diagnoses but not receiving metformin; matching accounted for age, sex, race/ethnicity, residence region, year, medications, oxygen use, smoking status, healthcare use, and comorbidities. Outcomes were all-cause mortality (primary) and hospitalizations (secondary). Results Among 2200 patients with IPF and T2DM included in this matched analysis, metformin therapy was associated with a reduction in all-cause mortality (hazard ratio [HR], 0.46; 95% confidence interval [CI], 0.36–0.58; p

Abstract Background Idiopathic Pulmonary Fibrosis is a chronic, progressive interstitial lung disease for which there is no cure. However, lung function decline, hospitalizations, and mortality may be reduced with the use of the antifibrotic medications, nintedanib and pirfenidone. Historical outcomes for hospitalized patients with Idiopathic Pulmonary Fibrosis are grim; however there is a paucity of data since the approval of nintedanib and pirfenidone for treatment. In this study, we aimed to determine the effect of nintedanib and pirfenidone on mortality following respiratory-related hospitalizations, intensive care unit (ICU) admission, and mechanical ventilation. Methods Using a large U.S. insurance database, we created a one-to-one propensity score matched cohort of patients with idiopathic pulmonary fibrosis treated and untreated with an antifibrotic who underwent respiratory-related hospitalization between January 1, 2015 and December 31, 2018. Mortality was evaluated at 30 days and end of follow-up (up to 2 years). Subgroup analyses were performed for all patients receiving treatment in an ICU and those receiving invasive and non-invasive mechanical ventilation during the index hospitalization. Results Antifibrotics were not observed to effect utilization of mechanical ventilation or ICU treatment during the index admission or effect mortality at 30-days. If patients survived hospitalization, mortality was reduced in the treated cohort compared to the untreated cohort when followed up to two years (20.1% vs 47.8%). Conclusions Treatment with antifibrotic medications does not appear to directly improve 30-day mortality during or after respiratory-related hospitalizations. Post-hospital discharge, however, ongoing antifibrotic treatment was associated with improved long-term survival.

Background: Student-run health initiatives in the community setting have been utilized to provide practical experience for undergraduate students to develop professional competencies, gain exposure to diverse populations, and to engage in activities of social accountability. There is much literature on student-run health initiatives; however, there is no consensus on a definition of this concept or a comprehensive synthesis of the literature that describes student-run health initiatives offered by students in pre-licensure healthcare education programs. Purpose: To provide a concept analysis of, and propose a definition for, student-run health initiatives that provide community-based services for students during pre-licensure health discipline education. Methods: A systematic literature search and review process was used to identify and synthesize peer-reviewed articles from 7 academic databases covering a range of pre-licensure health disciplines and education. Walker and Avant’s framework for concept analysis was used to guide exploration of attributes, antecedents and consequences of student-run initiatives, and to inform development of a definition for this concept. Results: The review yielded 222 articles for data extraction and represented 17 distinct pre-licensure health disciplines, 18 health-related disciplines, and a range of other baccalaureate and graduate programs. Our analysis revealed 16 definitions, 5 attributes, 6 antecedents, and consequences identified for student-run health initiatives. Attributes were Provision of Service, Service is Free, Target Clientele, Volunteerism, and Student Governance. Antecedents included Purpose/Rationale, Affiliation with Academic Unit, Location and Partnerships, Funding and Resources, Professional Oversight, and Preparation for Student Role. Consequences were improved access to services and outcomes for clients; competency development, personal gains and interprofessional learning for students; and positive outcomes for broader systems, such as decrease of service utilization and cost/benefit. Conclusions: There was no clear conceptual definition for student-run health initiatives, but many defining characteristics and well-described exemplars in the literature. Given the variations in purpose and scope of these initiatives, particularly to distinguish degree of students’ roles in operations and the involvement of academic institutions, we propose 3 distinct conceptual definitions: student-run, student-led, and student-infused health initiatives.

Modern cyber-physical microgrids rely on the information exchanged among power electronics devices (i.e., converters or inverters with local embedded controllers) making them vulnerable to cyber manipulations. The physical devices themselves are susceptible to potential faults and failures. Effects of these cyber and physical anomalies can propagate throughout the entire microgrid due to information exchanged and the inherent low inertia of the distribution network. This work employs the parametric time-frequency logic (PTFL) framework to detect such cyber-physical anomalies. PTFL is a formalism to analyze the time-frequency content of the observable quantities of interest (such as current, voltage, or frequency) of power electronics devices in comparison with the predefined time-frequency properties. PTFL formalism is presented to detect the anomalies such as false data-injection attacks, denial-of-service attacks, and faults on a cluster of four DC microgrids and an inverter-populated IEEE 34-bus feeder system in a controller/hardware-in-the-loop environment.

BackgroundIn 1995, the CDC recommended one-dose routine varicella immunization for children MethodsAn online survey of HCPs was conducted to assess recognition and management of varicella infections. Responses to eight varicella vignettes describing patients with varying varicella symptoms were analyzed and descriptive analyses performed. Stratified analysis comparing responses of those licensed before and in/after 1996 was also performed.Results153 HCPs (50 nurse practitioners, 103 doctors) completed the survey. Mean age of respondents was 44 years. 62% were female, and 82% were licensed before 1996. Varicella infection was correctly diagnosed 79% of the time. HCPs correctly recognized uncomplicated varicella vignettes 85% of the time versus 61% of the time for complicated varicella vignettes. Antibiotics were recommended 17% of the time and antivirals 18% of the time, of which 25% and 69% (respectively) were not appropriate per guidelines. HCPs licensed before 1996 were better able to recognize varicella compared to those licensed later, but prescribed more antimicrobials medications to treat varicella.ConclusionsAlthough most HCPs recognized varicella infection, a sizable proportion could not recognize cases with complications, and some of the varicella cases were inappropriately treated with antibiotics and/or antivirals. Additional HCP training and high vaccination coverage are important strategies to avoid inaccurate diagnoses and minimize unnecessary exposure to antimicrobial/antiviral therapies.

BackgroundTraditionally, promotion of colorectal cancer (CRC) screening among Black men was delivered by community health workers, patient navigators, and decision aids (printed text or video media) at clinics and in the community setting. A novel approach to increase CRC screening of Black men includes developing and utilizing a patient-centered, tailored message delivered via virtual human technology in the privacy of one’s home. ObjectiveThe objective of this study was to incorporate the perceptions of Black men in the development of a virtual clinician (VC) designed to deliver precision messages promoting the fecal immunochemical test (FIT) kit for CRC screening among Black men in a future clinical trial. MethodsFocus groups of Black men were recruited to understand their perceptions of a Black male VC. Specifically, these men identified source characteristics that would enhance the credibility of the VC. The modality, agency, interactivity, and navigability (MAIN) model, which examines how interface features affect the user’s psychology through four affordances (modality, agency, interactivity, and navigability), was used to assess the presumed credibility of the VC and likability of the app from the focus group transcripts. Each affordance triggers heuristic cues that stimulate a positive or a negative perception of trustworthiness, believability, and understandability, thereby increasing source credibility. ResultsIn total, 25 Black men were recruited from the community and contributed to the development of 3 iterations of a Black male VC over an 18-month time span. Feedback from the men enhanced the visual appearance of the VC, including its movement, clothing, facial expressions, and environmental surroundings. Heuristics, including social presence, novelty, and authority, were all recognized by the final version of the VC, and creditably was established. The VC was named Agent Leveraging Empathy for eXams (ALEX) and referred to as “brother-doctor,” and participants stated “wanting to interact with ALEX over their regular doctor.” ConclusionsInvolving Black men in the development of a digital health care intervention is critical. This population is burdened by cancer health disparities, and incorporating their perceptions in telehealth interventions will create awareness of the need to develop targeted messages for Black men.

Clinically significant weight loss is associated with health benefits for overweight and obese adults. Participation in adequate amounts of physical activity is critical for weight maintenance. However, the recommended amount of physical activity needed to promote weight maintenance is based primarily on retrospective studies that quantified physical activity levels through questionnaires which tend to overestimate physical activity levels. In addition, the present literature has provided little data on the impact of these physical activity levels on cardiovascular and diabetes risk factors, which may have equal or more clinical importance than weight changes. The Prescribed Exercise to Reduce Recidivism After Weight Loss-Pilot (PREVAIL-P) study will evaluate the effect of aerobic exercise training amount on weight maintenance following clinically significant weight loss in overweight and obese adults (BMI 25–40 kg/m2) age 30–65 years. Participants (N = 39) will complete a 10-week OPTIFAST® weight loss program with supervised aerobic exercise training. Individuals who achieve ≥7% weight loss from baseline will be subsequently randomized to levels of aerobic training consistent with physical activity recommendations (PA-REC) or weight maintenance recommendations (WM-REC) for 18 additional weeks. The primary outcome of the PREVAIL-P study will be change in weight from the completion of OPTIFAST® program to the end of the study. Notable secondary measures include changes in clinically relevant cardiometabolic risk factors between study groups (e.g. blood lipids concentrations, oral glucose tolerance, arterial stiffness). This pilot study will be used to estimate the effect sizes needed for a randomized controlled trial on this topic.

BackgroundType 1 conventional dendritic cells (cDC1s) possess efficient antigen presentation and cross-presentation activity, as well as potent T cell priming ability. Tissue-resident cDC1s (CD103+ cDC1s in mice, CD141+ cDC1s in humans) are linked with improved tumor control, yet the efficacy of immunotherapy using this population is understudied.MethodsWe generated murine CD103+ cDC1s in vitro and examined their expression of cDC1-related factors, antigen cross-presentation activity, and accumulation in tumor-draining lymph nodes (TdLNs). The antitumor efficacy of the in vitro-generated CD103+ cDC1s was studied in murine melanoma and osteosarcoma models. We evaluated tumor responses on vaccination with CD103+ cDC1s, compared these to vaccination with monocyte-derived DCs (MoDCs), tested CD103+ cDC1 vaccination with checkpoint blockade, and examined the antimetastatic activity of CD103+ cDC1s.ResultsIn vitro-generated CD103+ cDC1s produced cDC1-associated factors such as interleukin-12p70 and CXCL10, and demonstrated antigen cross-presentation activity on stimulation with the toll-like receptor 3 agonist polyinosinic:polycytidylic acid (poly I:C). In vitro-generated CD103+ cDC1s also migrated to TdLNs following poly I:C treatment and intratumoral delivery. Vaccination with poly I:C-activated and tumor antigen-loaded CD103+ cDC1s enhanced tumor infiltration of tumor antigen-specific and interferon-γ+ CD8+ T cells, and suppressed melanoma and osteosarcoma growth. CD103+ cDC1s showed superior antitumor efficacy compared with MoDC vaccination, and led to complete regression of 100% of osteosarcoma tumors in combination with CTLA-4 antibody-mediated checkpoint blockade. In vitro-generated CD103+ cDC1s effectively protected mice from pulmonary melanoma and osteosarcoma metastases.ConclusionsOur data indicate an in vitro-generated CD103+ cDC1 vaccine elicits systemic and long-lasting tumor-specific T cell-mediated cytotoxicity, which restrains primary and metastatic tumor growth. The CD103+ cDC1 vaccine was superior to MoDCs and enhanced response to immune checkpoint blockade. These results indicate the potential for new immunotherapies based on use of cDC1s alone or in combination with checkpoint blockade.

Abstract Intramammary infections (IMI) are prevalent in non-lactating dairy cattle and their occurrence during periods of significant mammary growth and development (i.e. pregnant heifers and dry cows) is believed to interfere with growth, development, and subsequent milk production. However, direct study of IMI impacts on non-lactating but developing mammary glands is lacking. The objectives of this study were to (1) define how IMI affected total and differential mammary secretion somatic cell counts in mammary glands stimulated to rapidly grow using estradiol and progesterone, and (2) characterize changes in mammary morphology in response to IMI. Mammary growth was stimulated in 19 non-pregnant, non-lactating cows and 2 quarters of each cow were subsequently infused with either saline (n = 19) or Staphylococcus aureus (n = 19). Mammary secretions were taken daily until mammary tissues were collected at either 5 or 10 days post-challenge. Staph. aureus quarter secretions yielded greater concentrations of somatic cells than saline quarters and contained a greater proportion of neutrophils. Staph. aureus mammary tissues exhibited higher degrees of immune cell infiltration in luminal and intralobular stroma compartments than saline quarters. Infected tissues also contained reduced areas of epithelium and tended to have greater amounts of intralobular stroma. Results indicate that IMI in non-lactating glands that were stimulated to grow, produced immune cell infiltration into mammary tissues and secretions, which was associated with changes in mammary tissue structure. The observed reduction of mammary epithelium indicates that IMI impair mammary development in rapidly growing mammary glands, which may reduce future reduced milk yields.

Best estimate plus uncertainty is the leading methodology to validate existing safety margins. It remains a challenge to develop and license these approaches, in part due to the high dimensionality of system codes. Uncertainty quantification is an active area of research to develop appropriate methods for propagating uncertainties, offering greater scientific reason, dimensionality reduction and minimising reliance on expert judgement. Inverse uncertainty quantification is required to infer a best estimate back on the input parameters and reduce the uncertainties, but it is challenging to capture the full covariance and sensitivity matrices. Bayesian inverse strategies remain attractive due to their predictive modelling and reduced uncertainty capabilities, leading to dramatic model improvements and validation of experiments. This paper uses state-of-the-art data assimilation techniques to obtain a best estimate of parameters critical to plant safety. Data assimilation can combine computational, benchmark and experimental measurements, propagate sparse covariance and sensitivity matrices, treat non-linear applications and accommodate discrepancies. The methodology is further demonstrated through application to hot zero power tests in a pressurised water reactor (PWR) performed using the BEAVRS benchmark with Latin hypercube sampling of reactor parameters to determine responses. WIMS 11 (dv23) and PANTHER (V.5:6:4) are used as the coupled neutronics and thermal-hydraulics codes; both are used extensively to model PWRs. Results demonstrate updated best estimate parameters and reduced uncertainties, with comparisons between posterior distributions generated using maximum entropy principle and cost functional minimisation techniques illustrated in recent conferences. Future work will improve the Bayesian inverse framework with the introduction of higher-order sensitivities.

The emerging field of socio-hydrology is a special case of social-ecological systems research that focuses on coupled human-water systems, exploring how the hydrologic cycle and human cultural traits coevolve and how such coevolutions lead to phenomena of relevance to water security and sustainability. As such, most problems tackled by socio-hydrology involve some aspects of engineering design, such as large-scale water infrastructure, and self-organization in a broad context, such as cultural change at the population level and the hydrologic shift at the river basin or aquifer level. However, within the field of socio-hydrology, it has been difficult to find general theories that assist our understanding of the dynamics emerging from the interplay between design and self-organization, hindering generalization of phenomena between cases. We address this gap by developing insights on how the theoretical frameworks of robustness-fragility trade-off and cultural multilevel selection can inform our understanding in this regard. We apply the two theories to two cases in the Ganges Brahmaputra Delta in Bangladesh and the Kissimmee River Basin in Florida, illustrating how the two theories may provide general insights into causal mechanisms shaping the socio-hydrological phenomena observed in the two cases. Specifically, we use the two theories to address (1) the transference of system fragility across different domains due to design choices and (2) the multilevel social processes in the nested organizational hierarchy that lead to the formation or collapse of shared cultural traits. We show that these two theories, separately or taken together, can provide richer theoretical grounding for understanding socio-hydrological phenomena.

The Pleckstrin Homology-like Domain (PHLD) class of proteins are multifunctional proteins. The class is comprised of two families of proteins, PHLDA and PHLDB, each with 3 members. All members of the families possess a pleckstrin homology (PH) domain. Though identified nearly 30 years ago, this class of proteins remains understudied with PHLDA family members receiving most of the research attention. Recent studies have also begun to reveal the functions of the PHLDB family proteins in regulation of p53 and AKT signaling pathways important for cancer and metabolism. This review will discuss current research and offer some prospects on the possible roles of both families in cancer and metabolism.

Conventional dendritic cells (cDCs) are a critical immune population, composed of multiple subsets, and responsible for controlling adaptive immunity and tolerance. Although migratory type 1 cDCs (CD103+ cDC1s in mice) are necessary to mount CD8+ T cell-mediated anti-tumor immunity, whether and how tumors modulate CD103+ cDC1 function remain understudied. Signal Transducer and Activator of Transcription 3 (STAT3) mediates the intracellular signaling of tumor-associated immunosuppressive cytokines, such as interleukin (IL)-10; thus, we hypothesized that STAT3 restrained anti-tumor immune responses elicited by CD103+ cDC1s. Herein, we show that in vitro-derived STAT3-deficient (Stat3∆/∆) CD103+ cDC1s are refractory to the inhibitory effects of IL-10 on Toll-like receptor 3 (TLR3) agonist-induced maturation responses. In a tumor vaccination approach, we found Stat3∆/∆ CD103+ cDC1s restrained mammary gland tumor growth and increased mouse survival more effectively than STAT3-sufficient CD103+ cDC1s. In addition, vaccination with Stat3∆/∆ CD103+ cDC1s elicited increased amounts of tumor antigen-specific CD8+ T cells and IFN-γ+ CD4+ T cells in tumors and tumor-draining lymph nodes versus phosphate-buffered saline (PBS)-treated animals. Furthermore, IL-10 receptor-deficient CD103+ cDC1s controlled tumor growth to a similar degree as Stat3∆/∆ CD103+ cDC1s. Taken together, our data reveal an inhibitory role for STAT3 in CD103+ cDC1 maturation and regulation of anti-tumor immunity. Our results also suggest IL-10 is a key factor eliciting immunosuppressive STAT3 signaling in CD103+ cDC1s in breast cancer. Thus, inhibition of STAT3 in cDC1s may provide an important strategy to improve their efficacy in tumor vaccination approaches and cDC1-mediated control of anti-tumor immunity.

Only 45% of people currently living with HIV infection in sub-Saharan Africa are aware of their HIV status. Unmet testing needs may be addressed by utilizing the Emergency Department (ED) as an innovative testing venue in low and middle-income countries (LMICs). The purpose of this review is to examine the burden of HIV infection described in EDs in LMICs, with a focus on summarizing the implementation of various ED-based HIV testing strategies.We performed a systematic review of Pubmed, Embase, Scopus, Web of Science and the Cochrane Library on June 12, 2016. A three-concept search was employed with emergency medicine (e.g., Emergency department, emergency medical services), HIV/AIDS (e.g., human immunodeficiency virus, acquired immunodeficiency syndrome), and LMIC terms (e.g., developing country, under developed countries, specific country names). The search returned 2026 unique articles. Of these, thirteen met inclusion criteria and were included in the final review. There was a large variation in the reported prevalence of HIV infection in the ED population ranging from to 2.14% in India to 43.3% in Uganda. The proportion HIV positive patients with previously undiagnosed infection ranged from 90% to 65.22%.In the United States ED-based HIV testing strategies have been front and center at curbing the HIV epidemic. The limited number of ED-based studies we observed in this study may represent the paucity of HIV testing in this venue in LMICs. All of the studies in this review demonstrated a high prevalence of HIV infection in the ED and an extraordinarily high percentage of previously undiagnosed HIV infection. Although the numbers of published reports are few, these diverse studies imply that in HIV endemic low resource settings EDs carry a large burden of undiagnosed HIV infections and may offer a unique testing venue.

The author argues that ethnography is a kindred of play. Based on her research of play in digital gaming environments, she draws several parallels between the practices of ethnography and the practices of play. She explores the complexities of play in games and expands our understanding of the work of ethnography as play.

The world is moving in the direction of using electricity derived from renewable sources. With the mass production of devices to enable the production of energy from such sources (wind, solar and tides), peak power capacity is competitive with that of deriving the electricity from fossil fuel. The problem is that the profile of power production does not match that of the requirements. This problem is not new, but it has become more acute: due to the extremely peaky nature of the power from the new sources, unless there is efficient energy storage, it is necessary to maintain the capacity to generate power to cover the full load in certain climatic conditions. While nuclear power is clean and would be ideal for satisfying the requirements of base load, the capital cost of nuclear plants (which should include that of decommissioning) makes the real cost of such power more expensive than that which can now obtained from renewables (and from burning gas or coal, of course). Ever since there have been electrical grids, companies have looked for ways to efficiently store energy so that power can be delivered on demand with minimum capital investment. A wide range of technologies is employed, and is being developed, so that everyday needs can be met. Energy storage is resource neutral: it allows us to use electricity from any power source more efficiently. However, it involves considerable capital investment, and can occupy a lot of space. The idea of moving towards reliance on renewable sources of energy has been taken up by a large segment of the population but there is technically still a lot to do, especially with regard to the essential corollary of energy storage. In addition to the challenge of producing the means to store energy, many other issues must be addressed. These include maintainability and longevity of the equipment (both for producing the energy and storing it). In this report we explore and compare the different methods available for storing energy and investigate trends.