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Background: The NHLBI has not developed clinical practice guidelines since 2007. As a result, multiple organizations have released competing guidelines. This has created confusion and debate among clinicians as to which recommendations are most applicable for practice. Objectives: To explore preliminary attitudes, awareness, and usage of clinical practice guidelines in practice and teaching for hypertension, dyslipidemia and asthma among clinical pharmacists. Methods: Clinical pharmacists across the US were surveyed electronically over a two week period in Spring 2019 regarding utilization and knowledge of practice guidelines for hypertension, dyslipidemia, and asthma. Clinical cases were included to evaluate application of guidelines. Descriptive statistics, Chi-square analysis, and Wilcoxon signed-rank test were conducted. Statistical significance level was set to 0.01 to account for multiple tests conducted on the same survey participants. Results: Forty-eight, 34, and 28 pharmacists voluntarily completed hypertension, dyslipidemia, and asthma survey questions, respectively. Interactions by disease state (p < 0.001) revealed more pharmacists (93%) reporting to have ≤50% patient load in managing asthma and more pharmacists (95%) had read the full summary/report of the most recent hypertension guideline. Primary reasons why the most recent guideline was not selected were also significantly different by disease state (interaction; p < 0.001). For dyslipidemia and asthma, pharmacists had a higher mean rating of agreement (p < 0.007) in having the most confidence in the most recent as compared to older guidelines. Proportionally more clinical cases were answered correctly (interaction; p < 0.001) when pharmacists applied the most recent guideline for hypertension (84%), while the opposite outcome was found for asthma (27%). Conclusion: While more pharmacists selected the most recent guideline for practice and teaching, there was inconsistent application of guidelines to clinical cases. Further studies with a larger representation of pharmacists are warranted to more definitively determine factors influencing guideline preference and usage.

The cyclotron resonance of monolayer graphene, encapsulated in hexagonal boron nitride and with a graphite backgate, is explored via infrared transmission magnetospectroscopy as a function of the filling factor at fixed magnetic fields. The impact of many-particle interactions in the regime of broken spin and valley symmetries is observed spectroscopically. As the occupancy of the zeroth Landau level is increased from half-filling, a nonmonotonic progression of multiple cyclotron resonance peaks is seen for several interband transitions, revealing the evolution of underlying many-particle-enhanced gaps. Analysis of the peak energies shows significant exchange enhancements of spin gaps both at and below the Fermi energy, a strong filling-factor dependence of the substrate-induced Dirac mass, and also the smallest particle-hole asymmetry reported to date in graphene cyclotron resonance.

IntroductionMany decarbonization technologies have the added co-benefit of reducing short-lived climate pollutants, such as particulate matter (PM), nitrogen oxides (NOx), and sulfur dioxide (SO2), creating a unique opportunity for identifying strategies that promote both climate change solutions and opportunities for air quality improvement. However, stakeholders and decision-makers may struggle to quantify how these co-benefits will impact public health for the communities most affected by industrial air pollution.MethodsTo address this problem, the LOCal Air Emissions Tracking Atlas (LOCAETA) fills a data availability and analysis gap by providing estimated air quality benefits from industrial decarbonization options, such as carbon capture and storage (CCS). These co-benefits are calculated using an algorithm that connects disparate datasets that separately report greenhouse gas emissions and other pollutants at U.S. industrial facilities.ResultsVersion 1.0 of LOCAETA displays the estimated primary PM2.5 emission reduction co-benefits from additional pretreatment equipment for CCS on industrial and power facilities across the state of Louisiana, as well as the potential for VOC and NH3 generation. The emission reductions are presented in the tool alongside facility pollutant emissions information and relevant air quality, environmental, demographic, and public health datasets, such as air toxics cancer risk, satellite and in situ pollutant measurements, and population vulnerability metrics.DiscussionLOCAETA enables regulators, policymakers, environmental justice communities, and industrial and commercial users to compare and contrast quantifiable public health benefits due to air quality impacts from various climate change mitigation strategies using a free and publicly-available tool. Additional pollutant reductions can be calculated using the same methodology and will be available in future versions of the tool.

Type I IFNs, a family of cytokines that signal through a single receptor and signaling mechanism, were originally named for their ability to interfere with viral replication. While type II IFN (IFN-γ) largely protects against intracellular bacteria and protozoa, type I IFNs largely protect from viral infections. Inborn errors of immunity in humans have demonstrated this point and its clinical relevance with increasing clarity. In this issue of the JCI, Bucciol, Moens, et al. report the largest series of patients to date with deficiency of STAT2, an important protein for type I IFN signaling. Individuals with STAT2 loss demonstrated a clinical phenotype of viral susceptibility and inflammatory complications, many of which remain poorly understood. These findings further illustrate the very specific and critical role that type I IFNs play in host defense against viruses.

The addition of hydrogen peroxide (H2O2) to cultured cells is widely used as a method to modulate redox-regulated cellular pathways, including the induction of programmed cell death in cell culture experiments and the testing of pro- and antioxidant compounds. Here, we assessed the effect on the cellular response to H2O2 of pre-adapting squamous cell carcinoma cells (A431) to the standard cell culture oxygenation of 18.6% O2, compared to cells pre-adapted to a physiological skin O2 concentration (3.0% O2). We showed that cells pre-adapted to 18.6% O2 resisted H2O2-induced cell death compared to cells pre-adapted to 3.0% O2 for 96 h prior to treatment with H2O2. Moreover, the enzymatic activities of catalase and glutathione reductase, as well as the protein expression levels of catalase, were higher in cells pre-adapted to 18.6% O2 compared to cells pre-adapted to 3.0% O2. H2O2-resistant cells, pre-adapted to 18.6% O2, exhibited increased nuclear Nrf-2 levels. It is concluded that A431 cells pre-adapted to standard cell culture oxygenation conditions resist H2O2-induced cell death. This effect may be related to their heightened activation of Nrf-2.

Objective To evaluate the reporting of results from the projects and programmes funded by the Health Research Council (HRC) New Zealand.Design A cross-sectional analysis.Setting Research projects and programmes funded by the HRC New Zealand from 2006 to 2014.Participants Publicly available data provided by the HRC.Main outcome measures The number and proportion with evidence of publication and dissemination of a research output from HRC grants and the time taken to disseminate the results.Results Of the 374 HRC grants from 2006 to 2014, there was no evidence of publication or reporting of any research output for 48 studies (13%). Of the 326 (87%) grants with research outputs, there was a mean dissemination time of 4.73 years (SD 2.37). The total funding provided by the HRC was NZ$471 663 336, while the 48 grants with no evidence of dissemination represented NZ$47 095 727 (10%).Conclusions Thirteen per cent of the HRC projects and programmes from 2006 to 2014 have not contributed to the healthcare evidence as their results remain unknown.

Introduction: We conducted a prospective validation study at Cincinnati Children's Hospital Medical Center and Ohio State University Medical Center to test if absolute CD38 bright CD8+TEM cells > 30/µL would predict acute GVHD, similar to our pilot data. Methods: Blood was collected twice weekly following HSCT. If CD38 bright CD8+ TEM ≥ 30 cells/µL, Epstein-Barr virus and cytomegalovirus specificity was determined by tetramer staining, granzyme B content was assessed, Ki-67 staining performed to assess T-cell proliferation. Cells were incubated with alemtuzumab, daratumumab and cyclophosphamide in vitro to determine susceptibility to depletion. Results: Of the 182 enrolled patients, 83 (45.6%) developed acute GVHD by day+100 but 171 patients were evaluable (acute GVHD n = 77 and no GVHD n = 94). There was no difference in the maximum absolute CD38 bright CD8+TEM cells prior to clinical symptoms and also after CMV and EBV tetramer positive patients were excluded from both cohorts. Ki-67 or Granzyme B expression in patients were comparable between patients with and without acute GVHD. Lastly CD38 bright CD8+ T-cells were effectively depleted with alemtuzumab and cyclophosphamide in vitro. Conclusion: Absolute peripheral blood CD38 bright CD8+TEM cells ≥30 do not predict acute GVHD in a large validation cohort of adult and pediatric HSCT recipients.

Macrophage activation syndrome (MAS) is a life-threatening cytokine storm complicating systemic juvenile idiopathic arthritis (SJIA) driven by IFN-γ. SJIA and MAS are also associated with an unexplained emerging inflammatory lung disease (SJIA-LD), with our recent work supporting pulmonary activation of IFN-γ pathways pathologically linking SJIA-LD and MAS. Our objective was to mechanistically define the potentially novel observation of pulmonary inflammation in the TLR9 mouse model of MAS. In acute MAS, lungs exhibit mild but diffuse CD4-predominant, perivascular interstitial inflammation with elevated IFN-γ, IFN-induced chemokines, and alveolar macrophage (AMϕ) expression of IFN-γ–induced genes. Single-cell RNA sequencing confirmed IFN-driven transcriptional changes across lung cell types with myeloid expansion and detection of MAS-specific macrophage populations. Systemic MAS resolution was associated with increased AMϕ and interstitial lymphocytic infiltration. AMϕ transcriptomic analysis confirmed IFN-γ–induced proinflammatory polarization during acute MAS, which switches toward an antiinflammatory phenotype after systemic MAS resolution. Interestingly, recurrent MAS led to increased alveolar inflammation and lung injury, and it reset AMϕ polarization toward a proinflammatory state. Furthermore, in mice bearing macrophages insensitive to IFN-γ, both systemic features of MAS and pulmonary inflammation were attenuated. These findings demonstrate that experimental MAS induces IFN-γ–driven pulmonary inflammation replicating key features of SJIA-LD and provides a model system for testing potentially novel treatments directed toward SJIA-LD.

Although skin cancer incidence is highest among non-Hispanic Whites, minority populations are often diagnosed with more advanced stage disease and are more likely to experience poor outcomes. Fewer people of color do not practice primary prevention of skin cancer according to recommendations, but public health education and interventions to promote sun protection behaviors have consistently targeted non-Hispanic Whites. This study examines performance of sun protection behaviors in a multiethnic sample and whether demographic, lifestyle and psychosocial predictors of these behaviors differ by race and ethnicity. In this study, a probability-based sample of 1742 adults completed an online survey in 2015. Main outcomes of interest included sunscreen use, wearing a sleeved shirt, and seeking shade. We stratified the sample into racial/ethnic groups (White, Black, Hispanic, Asian) and investigated demographic, lifestyle and psychosocial correlates of these behaviors in each group. Differences in adjusted estimates from each behavior-specific model were tested across strata. Racial/ethnic groups were significantly different in regards to sunscreen use and wearing a sleeved shirt, but similarly engaged in seeking shade. Results from multivariate ordered logistic regression models for each behavior revealed important demographic, lifestyle and psychosocial predictors and the importance of some demographic correlates varied between racial/ethnic groups. This study provides insight into the practice and correlates of skin cancer prevention among a multiethnic sample. Our findings suggest that targeting public health education efforts and interventions to promote sun protection in minority populations may be a beneficial approach to addressing heightened skin cancer morbidity and mortality in these groups. Keywords: Skin cancer, Primary prevention, Public health

Deep-learning (DL)-based object detection algorithms can greatly benefit the community at large in fighting fires, advancing climate intelligence, and reducing health complications caused by hazardous smoke particles. Existing DL-based techniques, which are mostly based on convolutional networks, have proven to be effective in wildfire detection. However, there is still room for improvement. First, existing methods tend to have some commercial aspects, with limited publicly available data and models. In addition, studies aiming at the detection of wildfires at the incipient stage are rare. Smoke columns at this stage tend to be small, shallow, and often far from view, with low visibility. This makes finding and labeling enough data to train an efficient deep learning model very challenging. Finally, the inherent locality of convolution operators limits their ability to model long-range correlations between objects in an image. Recently, encoder–decoder transformers have emerged as interesting solutions beyond natural language processing to help capture global dependencies via self- and inter-attention mechanisms. We propose Nemo: a set of evolving, free, and open-source datasets, processed in standard COCO format, and wildfire smoke and fine-grained smoke density detectors, for use by the research community. We adapt Facebook’s DEtection TRansformer (DETR) to wildfire detection, which results in a much simpler technique, where the detection does not rely on convolution filters and anchors. Nemo is the first open-source benchmark for wildfire smoke density detection and Transformer-based wildfire smoke detection tailored to the early incipient stage. Two popular object detection algorithms (Faster R-CNN and RetinaNet) are used as alternatives and baselines for extensive evaluation. Our results confirm the superior performance of the transformer-based method in wildfire smoke detection across different object sizes. Moreover, we tested our model with 95 video sequences of wildfire starts from the public HPWREN database. Our model detected 97.9% of the fires in the incipient stage and 80% within 5 min from the start. On average, our model detected wildfire smoke within 3.6 min from the start, outperforming the baselines.

AimsThe COVID-19 pandemic forced closure of most U.S. university campuses in March 2020, obliging millions of students to finish their semesters via remote learning. This study examines whether and how students' prior and current experiences of digital inequality-defined as constrained access to the internet and internet-connecting devices-were associated with their remote learning experiences.MethodAn anonymous, online survey of 2,913 undergraduate college students from 30 U.S. universities completing their spring term remotely was conducted between April and May 2020. Hypothesis testing utilized a structural equation model with cluster-bootstrapped standard errors and p-values, to account for students being clustered by university.ResultsFindings revealed that students' challenges with internet connectivity and digital devices during remote learning were associated with lower remote learning proficiency (RLP). Difficulty communicating with professors and teaching assistants was also associated with lower RLP. Prior experience with online coursework was associated with higher RLP, and digital inequality challenges during the year prior to the pandemic with lower RLP. Moreover, students who reported greater financial hardship since the start of the pandemic experienced significantly more connectivity, device, and faculty communication challenges during remote learning, and had significantly lower RLP.ConclusionsMany students will continue to learn remotely in some form until the pandemic recedes. We identify key factors associated with students' remote learning proficiency: (1) consistent, high-speed internet connectivity and functioning devices to connect to it, and (2) the ability to relate to and communicate easily with professors and teaching assistants. This study identifies potential barriers to effective remote learning, as well as possible opportunities to improve students' experiences.

The world is currently in a pandemic of COVID-19 (Coronavirus disease-2019) caused by a novel positive-sense, single-stranded RNA β-coronavirus referred to as SARS-CoV-2. Here we investigated rates of SARS-CoV-2 infection in the greater Cincinnati, Ohio, USA metropolitan area from August 13 to December 8, 2020, just prior to initiation of the national vaccination program. Examination of 9,550 adult blood donor volunteers for serum IgG antibody positivity against the SARS-CoV-2 Spike protein showed an overall prevalence of 8.40%, measured as 7.56% in the first 58 days and 9.24% in the last 58 days, and 12.86% in December 2020, which we extrapolated to ~20% as of March, 2021. Males and females showed similar rates of past infection, and rates among Hispanic or Latinos, African Americans and Whites were also investigated. Donors under 30 years of age had the highest rates of past infection, while those over 60 had the lowest. Geographic analysis showed higher rates of infectivity on the West side of Cincinnati compared with the East side (split by I-75) and the lowest rates in the adjoining region of Kentucky (across the Ohio river). These results in regional seroprevalence will help inform efforts to best achieve herd immunity in conjunction with the national vaccination campaign.

Abstract Background In Traditional Chinese Medicine (TCM) theories, the typical clinical manifestations of gout are attributed to the “dampness-heat pouring downward.” Therefore, TCM practitioners always consider prescribing the formulae which are believed to clear heat and drain dampness for the management of gout. This clinical trial aims: (1) to determine the hypouricemic effect of “Yellow-dragon Wonderful-seed Formula” (YWF) decoction in gout patients with dampness-heat pouring downward pattern and (2) to determine if gypsum could provide additional significant benefits to YWF. Methods A total of 72 hyperuricemic individuals with gout and dampness-heat pouring downward pattern were included with 62 of them completing the trial. Participants were randomly assigned to the YWF group, the YWF + gypsum group, or the allopurinol group. YWF and YWF + gypsum decoctions were orally administered for four weeks. Allopurinol was also orally administered for four weeks as the active control. Serum uric acid (sUA) level was the primary outcome measure. Urine urate level, scores on the SF-36 scale, erythrocyte sedimentation rate (ESR), X ray film, and C reactive protein (CRP) level were the secondary outcome measures. Results Compared with the values at week 0, YWF and YWF + gypsum did not significantly decrease the sUA level at each weekend reading. YWF, YWF + gypsum, and allopurinol decreased the urine urate levels and there were significant differences between the YWF group and the YWF + gypsum group. All the changes in the eight structures of SF-36 during the intervention period were not significantly different among the three groups and there was no significant difference in the CRP level among the three groups at each weekend reading. Conclusions YWM, which modified on the basis of Two Wonderful Herbs Powder (2WHP), does not show significant hypouricemic effect. There is a possibility that Gypsum Fibrosum may provide additional effects to YWF in decreasing the urine urate levels but cannot add benefits to YWF in other outcome measures. Trial registration Chinese Clinical Trial Registry, ChiCTR-TRC-12001933. Registered on 10 February 2012.

Abstract: Serum soluble interleukin-2 receptor (sIL-2r) is an important disease marker in hemophagocytic lymphohistiocytosis (HLH), but there are no published data on its diagnostic value in adults. We conducted a single-center retrospective study of 78 consecutive adults who had sIL-2r measured for suspected HLH. Serum sIL-2r levels were measured by enzyme-linked immunosorbent assay (adult reference range, 241-846 U/mL). There were 38 patients with HLH and 40 with a non-HLH diagnosis (such as sepsis, liver disease, histiocyte disorders, autoimmune disease, leukemia, or lymphoma). The receiver operating characteristic curve demonstrated that sIL-2r is a good to excellent diagnostic test for adult HLH, with an area under the curve (AUC) of 0.90 (95% confidence interval, 0.83-0.97) compared with AUC 0.78 (95% confidence interval, 0.67-0.88) for ferritin. The optimal threshold for sIL-2r was 2515 U/mL (sensitivity, 100%; specificity, 72.5%). Although there was a large indeterminate range for sIL-2r, a level of 2400 U/mL or less was helpful for ruling out HLH (sensitivity, 100%), and more than 10 000 U/mL was helpful for ruling in HLH (specificity, 93%). Higher mean sIL-2r levels were seen in malignancy-associated HLH (20 241 U/mL) compared with infection-associated HLH and macrophage activation syndrome (9720 and 5008 U/mL, respectively; P < .05). Levels above 10 000 U/mL were not associated with worse prognosis in patients with HLH. Serum sIL-2r is a sensitive test for diagnosis of adult HLH, but is not as specific as previously reported in children. Additional studies enriched with patients without HLH who have conditions associated with T-cell activation, such as lymphoma and autoimmune lymphoproliferative syndrome, are needed.