Leveraging Patients' Creative Ideas for Innovation in Health Care.

Policy Points Patients' creative ideas may inform learning and innovation that improve patient-centered care. Routinely collected patient experience surveys provide an opportunity to invite patients to share their creative ideas for improvement. We develop and assess a methodological strategy that validates question wording designed to elicit creative ideas from patients. Health care organizations should consider how to report and use these data in health care delivery and quality improvement, and policymakers should consider promoting the use of narrative feedback to better understand and respond to patients' experiences. CONTEXT: Learning health systems (LHSs) have been promoted for a decade to achieve high-quality, patient-centered health care. Innovation driven by knowledge generated through day-to-day health care delivery, including patient insights, is critical to LHSs. However, the pace of translating patient insights into innovation is slow and effectiveness inadequate. This study aims to evaluate a method for systematically eliciting patients' creative ideas, examine the value of such ideas as a source of insight, and examine patients' creative ideas regarding how their experiences could be improved within the context of their own health systems. METHODS: The first stage of the study developed a survey and tested strategies for elicitation of patients' creative ideas with 600 patients from New York State. The second stage deployed the survey with the most generative open-ended question sequence within a health care system and involved analysis of 1,892 patients' responses, including 2,948 creative ideas. FINDINGS: Actionable, creative feedback was fostered by incorporating a request for transformative feedback into a sequence of narrative elicitation questions. Patients generate more actionable and creative ideas when explicitly invited to share such ideas, especially patients with negative health care experiences, those from minority racial/ethnic backgrounds, and those with chronic illness. The most frequently elicited creative ideas focused on solving challenges, proposing interventions, amplifying exceptional practices, and conveying hopes for the future. CONCLUSIONS: A valid and reliable method for eliciting creative ideas from patients can be deployed as part of routine patient experience surveys that include closed-ended survey items and open-ended narrative items in which patients share their experiences in their own words. The elicited creative ideas are promising for patient engagement and innovation efforts. This study highlights the benefits of engaging patients for quality improvement, offers a rigorously tested method for cultivating innovation using patient-generated knowledge, and outlines how creative ideas can enable organizational learning and innovation.

Clinical evaluation of a machine learning-based early warning system for patient deterioration.

BACKGROUND: The implementation and clinical impact of machine learning-based early warning systems for patient deterioration in hospitals have not been well described. We sought to describe the implementation and evaluation of a multifaceted, real-time, machine learning-based early warning system for patient deterioration used in the general internal medicine (GIM) unit of an academic medical centre. METHODS: In this nonrandomized, controlled study, we evaluated the association between the implementation of a machine learning-based early warning system and clinical outcomes. We used propensity score-based overlap weighting to compare patients in the GIM unit during the intervention period (Nov. 1, 2020, to June 1, 2022) to those admitted during the pre-intervention period (Nov. 1, 2016, to June 1, 2020). In a difference-indifferences analysis, we compared patients in the GIM unit with those in the cardiology, respirology, and nephrology units who did not receive the intervention. We retrospectively calculated system predictions for each patient in the control cohorts, although alerts were sent to clinicians only during the intervention period for patients in GIM. The primary outcome was non-palliative in-hospital death. RESULTS: The study included 13 649 patient admissions in GIM and 8470 patient admissions in subspecialty units. Non-palliative deaths were significantly lower in the intervention period than the pre-intervention period among patients in GIM (1.6% v. 2.1%; adjusted relative risk [RR] 0.74, 95% confidence interval [CI] 0.55-1.00) but not in the subspecialty cohorts (1.9% v. 2.1%; adjusted RR 0.89, 95% CI 0.63-1.28). Among high-risk patients in GIM for whom the system triggered at least 1 alert, the proportion of non-palliative deaths was 7.1% in the intervention period, compared with 10.3% in the pre-intervention period (adjusted RR 0.69, 95% CI 0.46-1.02), with no meaningful difference in subspecialty cohorts (10.4% v. 10.6%; adjusted RR 0.98, 95% CI 0.60-1.59). In the difference-indifferences analysis, the adjusted relative risk reduction for non-palliative death in GIM was 0.79 (95% CI 0.50-1.24). INTERPRETATION: Implementing a machine learning-based early warning system in the GIM unit was associated with lower risk of non-palliative death than in the pre-intervention period. Machine learning-based early warning systems are promising technologies for improving clinical outcomes.

Learning from patients: The impact of using patients' narratives on patient experience scores.

BACKGROUND: Enthusiasm has grown about using patients' narratives-stories about care experiences in patients' own words-to advance organizations' learning about the care that they deliver and how to improve it, but studies confirming association have not been published. PURPOSE: We assessed whether primary care clinics that frequently share patients' narratives with their staff have higher patient experience survey scores. APPROACH: We conducted a 1-year study of 5,545 adult patients and 276 staff affiliated with nine clinics in one health system. We used multilevel models to analyze survey data from patients about their experiences and from staff about exposure to useful narratives. We examined staff confidence in own knowledge as a moderator because confidence can influence use of new information sources. RESULTS: Frequency of sharing useful narratives with staff was associated with patient experience scores for all measures, conditional on staff confidence in own knowledge ( p < .01). For operational measures (e.g., care coordination), increased sharing correlated with subsequently higher performance for more confident staff and lower performance or no difference for less confident staff, depending on measure. For relational measures (e.g., patient-provider communication), increased sharing correlated with higher scores for less confident staff and lower scores for more confident staff. CONCLUSION: Sharing narratives with staff frequently is associated with better patient experience survey scores, conditional on confidence in knowledge. PRACTICE IMPLICATIONS: Frequently sharing useful patient narratives should be encouraged as an organizational improvement strategy. However, organizations need to address how narrative feedback interacts with their staff's confidence to realize higher experience scores across domains.

Reducing Sedative-Hypnotics Among Hospitalized Patients: a Multi-centered Study.

BACKGROUND: Sedative-hypnotics are frequently prescribed for insomnia in hospital but are associated with preventable harms. OBJECTIVE, DESIGN, AND PARTICIPANTS: We aimed to examine whether a sedative-hypnotic reduction quality improvement bundle decreases the rate of sedative-hypnotic use among hospitalized patients, who were previously naïve to sedative-hypnotics. This interrupted time series study occurred between May 2016 and January 2019. Control data for 1 year prior to implementation and intervention data for at least 16 months were collected. The study occurred on 7 inpatient wards (general medicine, cardiology, nephrology, general surgery, and cardiovascular surgery wards) across 5 teaching hospitals in Toronto, Canada. INTERVENTION: Participating wards implemented a sedative-hypnotic reduction bundle (i.e., order set changes, audit-feedback, pharmacist-enabled medication reviews, sleep hygiene, daily sleep huddles, and staff/patient/family education) aimed to reduce in-hospital sedative-hypnotic initiation for insomnia in patients who were previously naïve to sedative-hypnotics. Each inpatient ward adapted the bundle prior to sustaining the intervention for a minimum of 16 months. MAIN MEASURES: The primary outcome measure was the proportion of sedative-hypnotic-naïve inpatients newly prescribed a sedative-hypnotic for sleep in hospital. Secondary measures include prescribing rates of other sedating medications, fall rates, length of stay, and mortality. KEY RESULTS: We included 8,970 patient discharges in the control period and 10,120 in the intervention period. Adjusted sedative-hypnotic prescriptions among naïve patients decreased from 15.48% (95% CI: 6.09-19.42) to 9.08% (p<0.001) (adjusted OR 0.814; 95% CI: 0.667-0.993, p=0.042). Unchanged secondary outcomes included mortality (adjusted OR 1.089; 95% CI: 0.786-1.508, p=0.608), falls (adjusted rate ratio 0.819; 95% CI: 0.625-1.073, p=0.148), or other sedating drug prescriptions (adjusted OR 1.046; 95% CI: 0.873-1.252, p=0.627). CONCLUSIONS: A sedative-hypnotic reduction quality improvement bundle implemented across 5 hospitals was associated with a sustained reduction in sedative-hypnotic prescriptions.

Ribes fasciculatum Ameliorates High-Fat-Diet-Induced Obesity by Elevating Peripheral Thermogenic Signaling.

Ribes fasciculatum has been consumed as a food and as a traditional medicine for treating autoimmune diseases and aging in diverse countries. A previous study showed that a mixture of Ribes fasciculatum and Cornus officinalis prohibited adipocyte differentiation and lipid accumulation in preadipocytes and suppressed diet-induced obesity. Nevertheless, the mechanism of R. fasciculatum to regulate energy homeostasis solely through thermogenic signaling remains unclear. Thus, we investigated its effects on energy homeostasis using R. fasciculatum fed to C57BL/6 mice with a 45% high-fat diet. Chronic consumption of R. fasciculatum decreased the body weight of obese mice with increasing food intakes and improved metabolic-syndrome-related phenotypes. Therefore, we further tested its thermogenic effects. Cold chamber experiments and qPCR studies indicated that R. fasciculatum elevated thermogenic signaling pathways, demonstrated by increased body temperature and uncoupling protein 1 (UCP1) signaling in the white and brown adipose tissues. Afzelin is one major known compound derived from R. fasciculatum. Hence, the isolated compound afzelin was treated with preadipocytes and brown adipocytes for cell viability and luciferase assay, respectively, to further examine its thermogenic effect. The studies showed that the response of afzelin was responsible for cell viability and the increased UCP1. In conclusion, our data indicated that R. fasciculatum elevated peripheral thermogenic signaling through increased UCP1 via afzelin activation and ameliorated diet-induced obesity.

Patient-provider therapeutic connections to improve health care: Conceptual development and systematic review of patient measures.

BACKGROUND: The Triple Aim (improved population health, improved patient experiences, and lower costs) has influenced U.S. health care since it was introduced in 2008. With it, value-based purchasing has brought unprecedented focus on patient experience measurement. Despite having devoted extensive resources toward improving patient experiences, inconsistent improvements suggest there are some dimensions not yet being widely measured or addressed. Furthermore, a renewed focus on health disparities calls for stronger patient-provider connections in order to reduce health care inequities. PURPOSE: The aim of this study was to articulate the concept of therapeutic connections (TCs) in health care and examine existing survey measures, from the patient perspective, to learn whether they capture the TC construct. METHOD: We interviewed subject matter experts ( n = 24) and patients ( n = 22) about measuring TCs and then conducted a systematic review of quantitative measures from three databases using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines and COSMIN (COnsensus-based Standards for the selection of health Measurement INstruments) criteria. RESULTS: Of 31 unique measures, none captured all of the theorized TC dimensions. Most were measures of collaboration and shared decision-making or caring. DISCUSSION: Focusing on the nature of patient-provider connections is vital because they are the backbone of most delivery models seeking to achieve the Triple Aim . Further development of the TC concept and measures is warranted to facilitate organizational and financing policies that meaningfully support widespread improvement. PRACTICE IMPLICATIONS: A focus on barriers and facilitators of TCs is needed. Without advancing our understanding of the role TCs play in care, policymakers and practitioners will be limited in their ability to make impactful changes.

Effects of Leader Tactics on the Creativity, Implementation, and Evolution of Ideas to Improve Healthcare Delivery.

BACKGROUND: Slow progress in quality improvement (QI) has prompted calls to identify new QI ideas. Leaders guiding these efforts are advised to use evidence-based tactics, or specific approaches to address a goal, to promote clinician and staff engagement in the generation and implementation of QI ideas, but little evidence about effective tactics exists. OBJECTIVE: Examine the association between leader tactics and the creativity, implementation outcome, and evolution of QI ideas from clinicians and staff. DESIGN: Prospective panel analysis of 220 ideas generated by 12 leaders and teams (N = 72 members) from federally qualified community health practices in one center over 18 months. Measures were extracted from meeting minutes (note-taking by a member during meetings) and expert panel review. Multi-level models were used. MEASURES: Leader tactics, idea creativity, implementation outcome, evolution pathways, center, and idea-submitter characteristics. RESULTS: Leaders used one of four approaches: no tactic, meeting ground rules, team brainstorming, or reflection on team process. Implemented ideas evolved in three pathways: Plug and Play, Slow Burn, and Iterate and Generate. Compared with no leader tactic, meeting ground rules resulted in ideas not significantly different in creativity, implementation outcome, or evolution pathway. Brainstorming was associated with greater idea creativity, idea implementation, and ideas following a Plug and Play path (low member engagement and implementation over 2 months or less). Reflection on team process was associated with idea implementation (versus not), and ideas following an Iterate and Generate path (high member engagement and implementation over 3 months or more). CONCLUSIONS: Two tactics, brainstorming and reflection, are helpful depending on goals. Brainstorming may aide leaders seeking disruptive change via more creative, rapidly implemented ideas. Reflection on team process may aide leaders seeking high-engagement ideas that may be implemented slowly. Both tactics may help leaders cultivate dynamics that increase implementation of ideas that improve healthcare.

AI-based improvement in lung cancer detection on chest radiographs: results of a multi-reader study in NLST dataset.

OBJECTIVE: Assess if deep learning-based artificial intelligence (AI) algorithm improves reader performance for lung cancer detection on chest X-rays (CXRs). METHODS: This reader study included 173 images from cancer-positive patients (n = 98) and 346 images from cancer-negative patients (n = 196) selected from National Lung Screening Trial (NLST). Eight readers, including three radiology residents, and five board-certified radiologists, participated in the observer performance test. AI algorithm provided image-level probability of pulmonary nodule or mass on CXRs and a heatmap of detected lesions. Reader performance was compared with AUC, sensitivity, specificity, false-positives per image (FPPI), and rates of chest CT recommendations. RESULTS: With AI, the average sensitivity of readers for the detection of visible lung cancer increased for residents, but was similar for radiologists compared to that without AI (0.61 [95% CI, 0.55-0.67] vs. 0.72 [95% CI, 0.66-0.77], p = 0.016 for residents, and 0.76 [95% CI, 0.72-0.81] vs. 0.76 [95% CI, 0.72-0.81, p = 1.00 for radiologists), while false-positive findings per image (FPPI) was similar for residents, but decreased for radiologists (0.15 [95% CI, 0.11-0.18] vs. 0.12 [95% CI, 0.09-0.16], p = 0.13 for residents, and 0.24 [95% CI, 0.20-0.29] vs. 0.17 [95% CI, 0.13-0.20], p < 0.001 for radiologists). With AI, the average rate of chest CT recommendation in patients positive for visible cancer increased for residents, but was similar for radiologists (54.7% [95% CI, 48.2-61.2%] vs. 70.2% [95% CI, 64.2-76.2%], p < 0.001 for residents and 72.5% [95% CI, 68.0-77.1%] vs. 73.9% [95% CI, 69.4-78.3%], p = 0.68 for radiologists), while that in cancer-negative patients was similar for residents, but decreased for radiologists (11.2% [95% CI, 9.6-13.1%] vs. 9.8% [95% CI, 8.0-11.6%], p = 0.32 for residents and 16.4% [95% CI, 14.7-18.2%] vs. 11.7% [95% CI, 10.2-13.3%], p < 0.001 for radiologists). CONCLUSIONS: AI algorithm can enhance the performance of readers for the detection of lung cancers on chest radiographs when used as second reader. KEY POINTS: • Reader study in the NLST dataset shows that AI algorithm had sensitivity benefit for residents and specificity benefit for radiologists for the detection of visible lung cancer. • With AI, radiology residents were able to recommend more chest CT examinations (54.7% vs 70.2%, p < 0.001) for patients with visible lung cancer. • With AI, radiologists recommended significantly less proportion of unnecessary chest CT examinations (16.4% vs. 11.7%, p < 0.001) in cancer-negative patients.

Health Outcomes of Parents of Children with Chronic Illness: A Systematic Review and Meta-Analysis.

OBJECTIVE: To assess health outcomes of parents caring for children with chronic illnesses compared with parents of healthy children. STUDY DESIGN: We searched OvidSP MEDLINE, EBM Reviews-Cochrane Central Register of Controlled Trials, EMBASE, and EBSCOHost CINAHL through September 2019. Included were English-language studies reporting health conditions or mortality of parents of affected children compared with healthy controls. RESULTS: Of 12 181 screened publications, 26 met inclusion criteria. Eight studies reported on anxiety, 23 on depression, 1 on mortality, and 1 on cardiovascular disease. Parents of chronically ill children had greater anxiety (standardized mean difference 0.42; 95% CI 0.24-0.60; P < .001) and depression scores (standardized mean difference 0.35; 95% CI 0.26-0.45; P < .001) than parents of healthy children. Thirty-five percent of parents of affected children met cut-offs for clinical depression, compared with 19% in the control (relative risk 1.75; 95% CI 1.55-1.97). Fifty-seven percent of such parents met cut-offs for anxiety, compared with 38% in the control (relative risk 1.40; 95% CI 1.18-1.67). One study of mothers of children with congenital anomalies reported a greater mortality risk than a comparison (adjusted hazard ratio 1.22; 95% CI 1.15-1.29), and another reported that these mothers experience an increased risk of cardiovascular disease (adjusted hazard ratio 1.15; 95% CI 1.07-1.23). CONCLUSIONS: Parents of chronically ill children experience poorer mental health (more anxiety and depression), and mothers of those with congenital anomalies may have greater risk of cardiovascular disease and mortality than parents of unaffected children. Our findings suggest a need for targeted interventions to attenuate adverse parental caregiver health outcomes. PRIOR REGISTRATION: PROSPERO CRD42018094657 (https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=94657).

UBE3A Suppresses Overnutrition-Induced Expression of the Steatosis Target Genes of MLL4 by Degrading MLL4.

Regulation of the protein stability of epigenetic regulators remains ill-defined despite its potential applicability in epigenetic therapies. The histone H3-lysine 4-methyltransferase MLL4 is an epigenetic transcriptional coactivator that directs overnutrition-induced obesity and fatty liver formation, and Mll4+/- mice are resistant to both. Here we show that the E3 ubiquitin ligase UBE3A targets MLL4 for degradation, thereby suppressing high-fat diet (HFD)-induced expression of the hepatic steatosis target genes of MLL4. In contrast to Mll4+/- mice, Ube3a+/- mice are hypersensitive to HFD-induced obesity and fatty liver development. Ube3a+/-;Mll4+/- mice lose this hypersensitivity, supporting roles of increased MLL4 levels in both phenotypes of Ube3a+/- mice. Correspondingly, our comparative studies with wild-type, Ube3a+/- and Ube3a-/- and UBE3A-overexpressing transgenic mouse livers demonstrate an inverse correlation of UBE3A protein levels with MLL4 protein levels, expression of the steatosis target genes of MLL4, and their decoration by H3-lysine 4-monomethylation, a surrogate marker for the epigenetic action of MLL4. Conclusion: UBE3A indirectly exerts an epigenetic regulation of obesity and steatosis by degrading MLL4. This UBE3A-MLL4 regulatory axis provides a potential therapeutic venue for treating various MLL4-directed pathogeneses, including obesity and hepatic steatosis.

The How Matters: How Primary Care Provider Communication With Team Relates to Patients' Disease Management.

BACKGROUND: Investigating primary care provider (PCP)-team communication can provide insight into how colleagues work together to become high-functioning teams more able to address an increasingly complex set of tasks associated with chronic disease management. OBJECTIVE: To assess how PCP communication with their care team relates to patients' health. RESEARCH DESIGN: Longitudinal study of how 3 aspects of PCP-care team communication-participation, time spent listening, and uninterrupted speaking length-relate to disease management of patients with hypertension or diabetes, and the effect of these team communication behaviors on PCP-patient communication as a pathway by which this relationship might exist. We used multilevel regression models. SUBJECTS: Twenty-seven PCPs and 98 team members, and 18,067 patients with hypertension and 8354 patients with diabetes affiliated with a federally qualified health center with 12 practice sites. MEASURES: Primary data on communication collected using sociometric sensors worn by PCPs and team members, patient-PCP communication data collected with surveys, and patient health, PCP and patient characteristics extracted from electronic records. RESULTS: PCPs participated in 75% of care team conversations, spent 56% of conversation time listening, and had an average uninterrupted speaking length of 2.42 seconds. PCP participation, listening, and length of uninterrupted speaking time were associated with significantly higher odds that their patients had controlled hypertension and diabetes and improvements in disease control over time. PCP-patient communication mediates this relationship. CONCLUSIONS: PCP-team communication is associated with patient health management. How team members speak with one another may be as important as the content of their communication.

Isolation and characterization of low pathogenic H7N7 avian influenza virus from a red-crowned crane in a zoo in South Korea.

BACKGROUND: South Korea conducts annual national surveillance programs to detect avian influenza (AI) in domestic poultry, live bird markets, and wild birds. In March 2017, an AIV was isolated from fecal samples in an outdoor aviary flight cage in a zoo in Korea. RESULTS: Nucleotide sequencing identified the isolate as low pathogenic avian influenza virus (LPAIV) H7N7, and DNA barcoding analysis identified the host species as red-crowned crane. This isolate was designated A/red-crowned crane/Korea/H1026/2017 (H7N7). Genetic analysis and gene constellation analysis revealed that A/red-crowned crane/Korea/H1026/2017 (H7N7) showed high similarity with four H7N7 LPAIVs isolated from wild bird habitats in Seoul and Gyeonggi in early 2017. CONCLUSIONS: Considering the genetic similarity and similar collection dates of the viruses, and the fact that zoo bird cages are vulnerable to AIV, it is likely that fecal contamination from wild birds might have introduced LPAIV H7N7 into the red-crowned crane at the zoo. Therefore, our results emphasize that enhanced biosecurity measures should be employed during the wild bird migration season, and that continued surveillance should be undertaken to prevent potential threats to avian species in zoos and to humans.

A quasi-experiment assessing the six-months effects of a nurse care coordination program on patient care experiences and clinician teamwork in community health centers.

BACKGROUND: Recognition that coordination among healthcare providers is associated with better quality of care and lower costs has increased interest in interventions designed to improve care coordination. One intervention is to add care coordination to nurses' role in a formal way. Little is known about effects of this approach, which tends to be pursued by small organizations and those in lower-resource settings. We assessed effects of this approach on care experiences of high-risk patients (those most in need of care coordination) and clinician teamwork during the first 6 months of use. METHODS: We conducted a quasi-experimental study using a clustered, controlled pre-post design. Changes in staff and patient experiences at six community health center practice locations that introduced the added-role approach for high-risk patients were compared to changes in six locations without the program in the same health system. In the pre-period (6 months before intervention training) and post-period (about 6 months after intervention launch, following 3 months of training), we surveyed clinical staff (N = 171) and program-qualifying patients (3007 pre-period; 2101 post-period, including 113 who were enrolled during the program's first 6 months). Difference-in-differences models examined study outcomes: patient reports about care experiences and clinician-reported teamwork. We assessed frequency of patient office visits to validate access and implementation, and contextual factors (training, resources, and compatibility with other work) that might explain results. RESULTS: Patient care experiences across all high-risk patients did not improve significantly (p > 0.05). They improved somewhat for program enrollees, 5% above baseline reports (p = 0.07). Staff-perceived teamwork did not change significantly (p = 0.12). Office visits increased significantly for enrolled patients (p < 0.001), affirming program implementation (greater accessing of care). Contextual factors were not reported as problematic, except that 41% of nurses reported incompatibility between care coordination and other job demands. Over 75% of nurses reported adequate training and resources. CONCLUSIONS: There were some positive effects of adding care coordination to nurses' role within 6 months of implementation, suggesting value in this improvement strategy. Addressing compatibility between coordination and other job demands is important when implementing this approach to coordination.

Complement C3 Plays a Key Role in Inducing Humoral and Cellular Immune Responses to Influenza Virus Strain-Specific Hemagglutinin-Based or Cross-Protective M2 Extracellular Domain-Based Vaccination.

The complement pathway is involved in eliminating antigen immune complexes. However, the role of the C3 complement system remains largely unknown in influenza virus M2 extracellular (M2e) domain or hemagglutinin (HA) vaccine-mediated protection after vaccination. Using a C3 knockout (C3 KO) mouse model, we found that complement protein C3 was required for effective induction of immune responses to vaccination with M2e-based or HA-based vaccines, which include isotype class-switched antibodies and effector CD4 and CD8 T cell responses. C3 KO mice after active immunization with cross-protective nonneutralizing M2e-based vaccine were not protected against influenza virus, although low levels of M2e-specific antibodies were protective after passive coadministration with virus in wild-type mice. In contrast, C3 KO mice that were immunized with strain-specific neutralizing HA-based vaccine were protected against homologous virus challenge despite lower levels of HA antibody responses. C3 KO mice showed impaired maintenance of innate immune cells and a defect in innate immune responses upon exposure to antigens. The findings in this study suggest that C3 is required for effective induction of humoral and cellular adaptive immune responses as well as protective immunity after nonneutralizing influenza M2e vaccination.IMPORTANCE Complement is the well-known innate immune defense system involved in the opsonization and lysis of pathogens but is less studied in establishing adaptive immunity after vaccination. Influenza virus HA-based vaccination confers protection via strain-specific neutralizing antibodies, whereas M2e-based vaccination induces a broad spectrum of protection by immunity against the conserved M2e epitopes. This study revealed the critical roles of C3 complement in inducing humoral and cellular immune responses after immunization with M2e or HA vaccines. C3 was found to be required for protection by M2e-based but not by HA-based active vaccination as well as for maintaining innate antigen-presenting cells. Findings in this study have insight into better understanding the roles of C3 complement in inducing effective innate and adaptive immunity as well as in conferring protection by cross-protective conserved M2e vaccination.

Overcoming ineffective resistance modulation in p-type NiO gas sensor by nanoscale Schottky contacts.

We present a gas sensor having nanoscale Schottky contacts on an array of helical-shaped p-type NiO to overcome intrinsically ineffective resistance modulation in the bulk of p-type metal oxides upon gas exposure. The Schottky device shows an abnormal n-type sensing behavior despite using the p-type NiO under reducing gas, with the sensitivity of 142.9% at 200 ppm of hydrogen, much higher than the reference Ohmic device with 0.7% sensitivity. Based on our equivalent circuit model with the quantitative estimation of the modulations in both carrier concentration and Schottky barrier height upon gas exposure, such a high sensitivity and the abnormal sensing behavior are attributed to the predominant modulation in the barrier height at the nanoscale Schottky contacts which are uniquely designed to have top-and-bottom electrodes configuration for efficient gas adsorption and sensitive Schottky barrier height modulation.

Roles of Aluminum Hydroxide and Monophosphoryl Lipid A Adjuvants in Overcoming CD4+ T Cell Deficiency To Induce Isotype-Switched IgG Antibody Responses and Protection by T-Dependent Influenza Vaccine.

Vaccine adjuvant effects in the CD4-deficient condition largely remain unknown. We investigated the roles of combined monophosphoryl lipid A (MPL) and aluminum hydroxide (Alum) adjuvant (MPL+Alum) in inducing immunity after immunization of CD4 knockout (CD4KO) and wild-type (WT) mice with T-dependent influenza vaccine. MPL+Alum adjuvant mediated IgG isotype-switched Abs, IgG-secreting cell responses, and protection in CD4KO mice, which were comparable to those in WT mice. In contrast, Alum adjuvant effects were dependent on CD4+ T cells. MPL+Alum adjuvant was effective in recruiting monocytes and neutrophils as well as in protecting macrophages from Alum-mediated cell loss at the injection site in CD4KO mice. MPL+Alum appeared to attenuate MPL-induced inflammatory responses in WT mice, likely improving the safety. Additional studies in CD4-depleted WT mice and MHC class II KO mice suggest that MHC class II+ APCs contribute to providing alternative B cell help in the CD4-deficient condition in the context of MPL+Alum-adjuvanted vaccination.

Study on a Nano-Microstructure and Properties of Geopolymer by Recycling Integrated Gasification Combined Cycle Coal Ash Slag.

In this study, a geopolymer having a nano-scaled structure was fabricated using recycling fly ash slag discharged from IGCC (Integrated Gasification Combined Cycle), to assess the possibility of employing it to replace high strength concrete. Strength, density, crystal phase, and bonding structure, were measured and the nano-size crystal phase of the geopolymers was observed as a function of experimental parameters such as water-to-solid ratio (w/s ratio), flow of paste, and amount of sodium silicate in the alkali activator, NaOH. The geopolymer prepared with NaOH containing 50~70% sodium silicate and a w/s ratio of 0.26~0.28 showed a compressive strength of 75~80 MPa, which satisfied the design standard for high strength concrete in Korea, 40 MPa. The specimen made with NaOH containing 55% sodium silicate had plate-shaped crystals with a nanoscale size, 100 nm or less, and showed compressive strength of 77 MPa, 3.9 times higher than that made with only NaOH. From the viewpoint of microstructure, it was confirmed that nano-sized plate-like crystals and amorphous structure were both effective in improving the strength of the specimen. In conclusion, this study showed that high-strength geopolymer made from IGCC coal ash slag may replace cement used in building materials and concrete secondary products in the near future.

Highly Pathogenic Avian Influenza A(H5N6) in Domestic Cats, South Korea.

In December 2016, highly pathogenic avian influenza (HPAI) infection with systemic pathologic lesions was found in cats in South Korea. Genetic analyses indicated that the feline isolates were similar to HPAI H5N6 viruses isolated in chicken farms nearby. This finding highlights the need for monitoring of domestic mammals during HPAI outbreaks.

A Novel Vaccination Strategy Mediating the Induction of Lung-Resident Memory CD8 T Cells Confers Heterosubtypic Immunity against Future Pandemic Influenza Virus.

The currently used vaccine strategy to combat influenza A virus (IAV) aims to provide highly specific immunity to circulating seasonal IAV strains. However, the outbreak of 2009 influenza pandemic highlights the danger in this strategy. In this study, we tested the hypothesis that universal vaccination that offers broader but weaker protection would result in cross protective T cell responses after primary IAV infection, which would subsequently provide protective immunity against future pandemic strains. Specifically, we used tandem repeat extracellular domain of M2 (M2e) epitopes on virus-like particles (M2e5x VLP) that induced heterosubtypic immunity by eliciting Abs to a conserved M2e epitope. M2e5x VLP was found to be superior to strain-specific current split vaccine in conferring heterosubtypic cross protection and in equipping the host with cross-protective lung-resident nucleoprotein-specific memory CD8(+) T cell responses to a subsequent secondary infection with a new pandemic potential strain. Immune correlates for subsequent heterosubtypic immunity by M2e5x VLP vaccination were found to be virus-specific CD8(+) T cells secreting IFN-γ and expressing lung-resident memory phenotypic markers CD69(+) and CD103(+) as well as M2e Abs. Hence, vaccination with M2e5x VLP may be developable as a new strategy to combat future pandemic outbreaks.

Differences in work environment for staff as an explanation for variation in central line bundle compliance in intensive care units.

BACKGROUND: Central line-associated bloodstream infections (CLABSIs) are a common and costly quality problem, and their prevention is a national priority. A decade ago, researchers identified an evidence-based bundle of practices that reduce CLABSIs. Compliance with this bundle remains low in many hospitals. PURPOSE: The aim of this study was to assess whether differences in core aspects of work environments-workload, quality of relationships, and prioritization of quality-are associated with variation in maximal CLABSI bundle compliance, that is, compliance 95%-100% of the time in intensive care units (ICUs). METHODOLOGY/APPROACH: A cross-sectional study of hospital medical-surgical ICUs in the United States was done. Data on work environment and bundle compliance were obtained from the Prevention of Nosocomial Infections and Cost-Effectiveness Refined Survey completed in 2011 by infection prevention directors, and data on ICU and hospital characteristics were obtained from the National Healthcare Safety Network. Factor and multilevel regression analyses were conducted. FINDINGS: Reasonable workload and prioritization of quality were positively associated with maximal CLABSI bundle compliance. High-quality relationships, although a significant predictor when evaluated apart from workload and prioritization of quality, had no significant effect after accounting for these two factors. PRACTICE IMPLICATIONS: Aspects of the staff work environment are associated with maximal CLABSI bundle compliance in ICUs. Our results suggest that hospitals can foster improvement in ensuring maximal CLABSI bundle compliance-a crucial precursor to reducing CLABSI infection rates-by establishing reasonable workloads and prioritizing quality.