Retinoid orphan receptor gamma t (rorγt) promotes inflammatory eosinophilia but is dispensable for innate immune-mediated colitis.

Inflammatory bowel diseases (IBD) result from uncontrolled inflammation in the intestinal mucosa leading to damage and loss of function. Both innate and adaptive immunity contribute to the inflammation of IBD and innate and adaptive immune cells reciprocally activate each other in a forward feedback loop. In order to better understand innate immune contributions to IBD, we developed a model of spontaneous 100% penetrant, early onset colitis that occurs in the absence of adaptive immunity by crossing villin-TNFAIP3 mice to RAG1-/- mice (TRAG mice). This model is driven by microbes and features increased levels of innate lymphoid cells in the intestinal mucosa. To investigate the role of type 3 innate lymphoid cells (ILC3) in the innate colitis of TRAG mice, we crossed them to retinoid orphan receptor gamma t deficient (Rorγt-/-) mice. Rorγt-/- x TRAG mice exhibited markedly reduced eosinophilia in the colonic mucosa, but colitis persisted in these mice. Colitis in Rorγt-/- x TRAG mice was characterized by increased infiltration of the intestinal mucosa by neutrophils, inflammatory monocytes, macrophages and other innate cells. RNA and cellular profiles of Rorγt-/- x TRAG mice were consistent with a lack of ILC3 and ILC3 derived cytokines, reduced antimicrobial factors, increased activation oof epithelial repair processes and reduced activation of epithelial cell STAT3. The colitis in Rorγt-/- x TRAG mice was ameliorated by antibiotic treatment indicating that microbes contribute to the ILC3-independent colitis of these mice. Together, these gene expression and cell signaling signatures reflect the double-edged sword of ILC3 in the intestine, inducing both proinflammatory and antimicrobial protective responses. Thus, Rorγt promotes eosinophilia but Rorγt and Rorγt-dependent ILC3 are dispensable for the innate colitis in TRAG mice.

Effect of a direct-fed microbial (10-G Armor) on feedlot performance, carcass characteristics, and prevalence of Salmonella in fed-beef heifers.

Crossbred beef heifers (N = 1,394; initial shrunk body weight [BW] 291 ±â€…9.9 kg) were used to investigate the efficacy of 10-G Armor (Life Products, Inc., Norfolk, NE; 10-G) upon feedlot performance, carcass characteristics, and fecal and subiliac lymph nodes Salmonella prevalence. Heifers were blocked by day of arrival and allocated to 1 of 20 pens (N = 70 heifers/pen) and assigned one of two treatments (10 pens/treatment): no direct-fed microbial (CON) or 2 g/heifer/d of Lactobacillus acidophilus, Enterococcus faecium, Pediococcus pentosaceus, Lactobacillus brevis and Lactobacillus plantarum, respectively (Life Products, Inc., Norfolk, NE; 10-G). Twenty-four animals were randomly selected from each pen for Salmonella sampling. Recto-anal mucosal swab samples (RAMS) were obtained at initial processing and harvest; subiliac lymph nodes were collected at harvest. In addition, pen surface fecal pats were collected and composited by pen (10 pats per composite, 5 composites per pen) on days 0, 52, 120, and 192. Data were analyzed as a generalized complete block design, and pen served as the experimental unit. No differences were observed in live growth performance metrics (P ≥ 0.55). Yield grade distributions did not differ between treatments (P ≥ 0.62); however, cattle fed 10-G tended (P = 0.06; 14.6% vs. 18.9%) to have fewer USDA Select carcasses and more (P = 0.09; 73.6% vs. 78.0%) USDA Choice carcasses. Cattle fed 10-G tended (P = 0.10; 9.2% vs. 12.3%) to have fewer liver abscesses and had fewer (P = 0.04; 5.3% vs. 8.5%) severe liver abscesses. Salmonella prevalence of RAMS did not differ between treatments at initial processing (P = 0.97; CON = 11.6%, 10-G = 11.5%) or at harvest (P = 0.91; CON = 99.0%, 10-G = 98.6%); however, RAMS differed (P < 0.01) in Salmonella prevalence between the two collection times. Cattle fed 10-G had a lower frequency of Salmonella positive lymph nodes (P = 0.01; CON = 15.8%, 10-G = 7.4%) than CON. However, Salmonella log (mpn/g) of lymph nodes did not differ between treatments at harvest (P = 0.34; CON = 0.73, 10-G = 0.34). These data indicate that cattle fed 10-G have decreased rates of severe liver abscesses without altering live animal performance or carcass characteristics. Supplementation of 10-G significantly reduced the prevalence rate of Salmonella recovered from the subiliac lymph nodes. The factors responsible for the observed difference in the effects of 10-G on Salmonella warrant further investigation.

Impact of a Best Practice Prevention Bundle on Central Line-associated Bloodstream Infection (CLABSI) Rates and Outcomes in Pediatric Hematology, Oncology, and Hematopoietic Cell Transplantation Patients in Inpatient and Ambulatory Settings.

BACKGROUND: Pediatric hematology, oncology, and hematopoietic cell transplantation (HCT) patients are at increased risk for bloodstream infections. The authors sought to evaluate the influence of a standardized best practice central venous catheter (CVC) maintenance bundle on the burden of and risk factors for mucosal barrier injury (MBI) and non-MBI central line-associated bloodstream infections (CLABSIs) across a common inpatient and ambulatory continuum in this high-risk population. METHODS: A retrospective cohort study of patients with underlying malignancy, hematologic disorders, and HCT recipients with a CVC in place at the time of CLABSI diagnosis in both inpatient and ambulatory settings from January 1, 2012 to December 31, 2016. Descriptive, nonparametric statistics were used to describe patient characteristics and outcomes. Logistic regression analyses were applied to identify potential risk factors for inpatient versus ambulatory and MBI versus non-MBI CLABSI. RESULTS: During the 5-year period, 118 of 808 (14.6%) patients had 159 laboratory-confirmed CLABSIs for ambulatory and inpatient CLABSI rates of 0.27 CLABSI/1000 and 2.2 CLABSI/1000 CVC days, respectively. CLABSI occurred more frequently in hospitalized patients after HCT and with underlying leukemia, most frequently caused by Gram-negative bacteria. MBI CLABSI accounted for 42% of all CLABSI with a 3-fold higher risk in hospitalized patients. Having multiple CVC or a CVC that was not a port independently associated with higher CLABSI risk. CONCLUSIONS: In our cohort, non-MBI CLABSI continued to account for the majority of CLABSI. CVC type is independently associated with higher overall CLABSI risk. Further studies are needed to reliably define additional prevention strategies when CLABSI maintenance bundles elements are optimized in this high-risk population.

Developing citizen report cards for primary health care in low and middle-income countries: Results from cognitive interviews in rural Tajikistan.

Citizen report cards on health care providers have been identified as a potential means to increase citizen engagement, provider accountability and health systems performance. Research in high-income settings indicates that the wording, presentation and display of performance information are critical to achieve these goals. However, there are limited insights on developing effective report card designs for middle- and low-income settings. We conducted cognitive interviews to assess consumers' understanding, interpretation of and preferences for displaying information for a health care report card in rural Tajikistan. We recruited a convenience sample of 40 citizens (20 women and 20 men aged 18-45) from rural areas of two provinces of Tajikistan (Soghd and Khatlon oblasts). The interview protocol was adapted from the model of cognitive interviews used in social science research to improve survey questionnaires. We used multivariate regression to assess understanding and interpretation of the report card; chi2 tests to assess differences in preferences for displaying information; and tests of proportions to assess the preferred comparison group. Respondents understood the main idea of the report card and are not confused by the indicators or display. However, many respondents had difficulties making comparisons, and when asked to identify worst-performing services. Respondents preferred detailed rankings using school grades, comparisons of their local clinic with the regional or national average performance, and the use of color in the report card. We found some heterogeneity across the two provinces. Overall, our findings are promising regarding the citizens' comprehension of health care report cards in rural Tajikistan, while underscoring the challenges of effectively providing health care performance information to communities. Cognitive interviews and iterative testing can support an effective implementation of reporting initiatives.

Outcome of Expedited Rotator Cuff Surgery in Injured Workers: Determinants of Successful Recovery.

BACKGROUND: Work-related rotator cuff injuries are a common cause of disability and employee time loss. PURPOSE: To examine the effectiveness of expedited rotator cuff surgery in injured workers who underwent rotator cuff decompression or repair and to explore the impact of demographic, clinical, and psychosocial factors in predicting the outcome of surgery. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Injured workers who were seen at a shoulder specialty program and who underwent expedited arthroscopic rotator cuff decompression or repair were observed for a period of 6 to 12 months based on their type of surgery and recovery trajectory. The primary outcome measure was the American Shoulder and Elbow Surgeons (ASES) Standardized Shoulder Assessment Form. The impact of surgery was assessed by whether the change in the ASES score exceeded the minimal clinically important difference (MCID) of 17 points. Secondary outcomes were range of motion (ROM), medication consumption, and work status. RESULTS: One hundred forty-six patients (43 women [29%], 103 men [71%]; mean age, 52 years; SD, 8 years) completed the study. Sixty-seven (46%) patients underwent rotator cuff repair. The mean time between the date the patient consented to have surgery and the date of surgery was 82 (SD, 44) days. There was a statistically significant improvement in ASES score and ROM and work status (52 returned to regular duties and 59 to modified duties) (P < .0001). Eighty-four percent (n = 122) of patients exceeded the MCID of 17 points. Individual factors that affected patient overall disability were preoperative ASES, work status prior to surgery, access to care, and autonomy at work. Achieving a minimal clinically meaningful change was influenced by perceived access to care, autonomy and stress at work, and overall satisfaction with the job. CONCLUSION: Expedited rotator cuff surgery improved disability, ROM, and work status in injured workers. Successful recovery after work-related shoulder injuries may further be facilitated by improving the psychosocial work environment and increasing access to care.

Building a Values-Informed Mental Model for New Orleans Climate Risk Management.

Individuals use values to frame their beliefs and simplify their understanding when confronted with complex and uncertain situations. The high complexity and deep uncertainty involved in climate risk management (CRM) lead to individuals' values likely being coupled to and contributing to their understanding of specific climate risk factors and management strategies. Most mental model approaches, however, which are commonly used to inform our understanding of people's beliefs, ignore values. In response, we developed a "Values-informed Mental Model" research approach, or ViMM, to elicit individuals' values alongside their beliefs and determine which values people use to understand and assess specific climate risk factors and CRM strategies. Our results show that participants consistently used one of three values to frame their understanding of risk factors and CRM strategies in New Orleans: (1) fostering a healthy economy, wealth, and job creation, (2) protecting and promoting healthy ecosystems and biodiversity, and (3) preserving New Orleans' unique culture, traditions, and historically significant neighborhoods. While the first value frame is common in analyses of CRM strategies, the latter two are often ignored, despite their mirroring commonly accepted pillars of sustainability. Other values like distributive justice and fairness were prioritized differently depending on the risk factor or strategy being discussed. These results suggest that the ViMM method could be a critical first step in CRM decision-support processes and may encourage adoption of CRM strategies more in line with stakeholders' values.

Less Use of Extreme Response Options by Asians to Standardized Care Scenarios May Explain Some Racial/Ethnic Differences in CAHPS Scores.

BACKGROUND: Asian Americans (hereafter "Asians") generally report worse experiences with care than non-Latino whites (hereafter "whites"), which may reflect differential use of response scales. Past studies indicate that Asians exhibit lower Extreme Response Tendency (ERT)-they less frequently use responses at extreme ends of the scale than whites. OBJECTIVE: To explore whether lower ERT is observed for Asians than whites in response to standardized vignettes depicting patient experiences of care and whether ERT might in part explain Asians reporting worse care than whites. PROCEDURE: A representative US sample (n=575 Asian; n=505 white) was presented with 5 written vignettes describing doctor-patient encounters with differing levels of physician responsiveness. Respondents evaluated the encounters using modified CAHPS communication questions. RESULTS: Case-mix-adjusted repeated-measures multivariate models show that Asians provided more positive responses than whites to several vignettes with less-responsive physicians but less positive responses than whites for the vignette with the most physician responsiveness (P<0.01 for each). While all respondents provided more positive ratings for vignettes with greater physician responsiveness, the increase was 15% less for Asian than white respondents. CONCLUSIONS: Asians exhibit lower ERT than whites in response to standardized scenarios. Because CAHPS reponses are predominantly near the positive end of the scale and the most responsive scenario is most typical of the score observed in real-world settings, lower ERT in Asians may partially explain observations of lower observed mean CAHPS scores for Asians in real-world settings. Case-mix adjustment for Asian race/ethnicity or its correlates may improve quality of care measurement.

Use of CAHPS patient experience surveys to assess the impact of health care innovations.

BACKGROUND: The Consumer Assessment of Healthcare Providers and Systems (CAHPS) surveys are the standard for collecting information about patient experience of care in the United States. However, despite their widespread use, including in pay-for-performance and public reporting efforts and various provisions of the Affordable Care Act, knowledge about the use of CAHPS in assessing the impact of quality improvement efforts is limited. A study was conducted to examine the use of patient experience surveys in assessing the impact of innovations implemented in health care settings. METHODS: Innovation profiles identified on the Agency for Healthcare Research and Quality (AHRQ) Health Care Innovations Exchange website that included patient experience (including patient satisfaction) as an outcome (N = 201), were analyzed with a variety of qualitative analysis methods. RESULTS: Fewer than half of the innovations used a patient experience measure, most commonly employing global measures such as an overall rating. Most innovations assessed patient experience at a single time point, with only one third using techniques such as pre-post comparisons, time trends, or comparisons to control groups. Ten domains of measures addressed reports of patient experience, all of which could be assessed by existing CAHPS instruments. Similarly, CAHPS measures are available to assess all of the organizational processes that are addressed by innovations in the profiles and for which patients are the best source of information. While 120 of the innovations that use patient experience measures report using surveys to collect these data, only 6 reported using a CAHPS measure. CONCLUSIONS: Although innovations targeting quality improvement are often evaluated using surveys, there is considerable untapped potential for using CAHPS measures or surveys to assess their effectiveness.

Informed public choices for low-carbon electricity portfolios using a computer decision tool.

Reducing CO2 emissions from the electricity sector will likely require policies that encourage the widespread deployment of a diverse mix of low-carbon electricity generation technologies. Public discourse informs such policies. To make informed decisions and to productively engage in public discourse, citizens need to understand the trade-offs between electricity technologies proposed for widespread deployment. Building on previous paper-and-pencil studies, we developed a computer tool that aimed to help nonexperts make informed decisions about the challenges faced in achieving a low-carbon energy future. We report on an initial usability study of this interactive computer tool. After providing participants with comparative and balanced information about 10 electricity technologies, we asked them to design a low-carbon electricity portfolio. Participants used the interactive computer tool, which constrained portfolio designs to be realistic and yield low CO2 emissions. As they changed their portfolios, the tool updated information about projected CO2 emissions, electricity costs, and specific environmental impacts. As in the previous paper-and-pencil studies, most participants designed diverse portfolios that included energy efficiency, nuclear, coal with carbon capture and sequestration, natural gas, and wind. Our results suggest that participants understood the tool and used it consistently. The tool may be downloaded from http://cedmcenter.org/tools-for-cedm/informing-the-public-about-low-carbon-technologies/ .

A comprehensive analysis of translational missense errors in the yeast Saccharomyces cerevisiae.

The process of protein synthesis must be sufficiently rapid and sufficiently accurate to support continued cellular growth. Failure in speed or accuracy can have dire consequences, including disease in humans. Most estimates of the accuracy come from studies of bacterial systems, principally Escherichia coli, and have involved incomplete analysis of possible errors. We recently used a highly quantitative system to measure the frequency of all types of misreading errors by a single tRNA in E. coli. That study found a wide variation in error frequencies among codons; a major factor causing that variation is competition between the correct (cognate) and incorrect (near-cognate) aminoacyl-tRNAs for the mutant codon. Here we extend that analysis to measure the frequency of missense errors by two tRNAs in a eukaryote, the yeast Saccharomyces cerevisiae. The data show that in yeast errors vary by codon from a low of 4 x 10(-5) to a high of 6.9 x 10(-4) per codon and that error frequency is in general about threefold lower than in E. coli, which may suggest that yeast has additional mechanisms that reduce missense errors. Error rate again is strongly influenced by tRNA competition. Surprisingly, missense errors involving wobble position mispairing were much less frequent in S. cerevisiae than in E. coli. Furthermore, the error-inducing aminoglycoside antibiotic, paromomycin, which stimulates errors on all error-prone codons in E. coli, has a more codon-specific effect in yeast.