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We compared the mortality risk in Alaska among persons with symptomatic coronavirus disease 2019 (COVID-19) during the period the Delta variant was predominant to the risk among those with symptomatic COVID-19 before Delta predominance. The Delta period was associated with 2.43-fold higher odds of death. Unvaccinated persons were 4.49 times more likely to die than fully vaccinated persons.

Although subsidized summer jobs programs have been shown to improve youth outcomes, little is known about the effects of private sector employment experiences. We study a unique program that brokers employer-paid summer internships for youth across a variety of industries and occupations. Using administrative data, we employ fixed effects and matching models to estimate the impact of these internships on academic outcomes. We find that private sector job experience significantly increases attendance, reduces course failures, and raises proficiency on statewide exams. Participants are more likely to take the SAT and enroll in college with a shift from two-year to four-year institutions.

Modulation of PD-L1, IDO-1 and B7-H4 levels by cytokines in lung adenocarcinoma cells.

Lung cancer cohorts description.

The seductive allure of neuroscience explanations (SANE) is controversial. Irrelevant neuroscience information in the form of text or imagery has been found to improve ratings of quality of, and agreement with, scientific explanations, and to possibly affect jury decisions in court. On the other hand, several studies have yielded little to no effect. To establish the magnitude of this effect, we conducted a random-effects meta-analysis on all studies that compared neuroscience to non-neuroscience information for impact on ratings or judgment, including mock juror decisions. This analysis used 60 experiments from 28 publications comprising 13,088 participants, and yielded a mild but highly significant effect of neuroscience information (Hedges’ g = .25, CI = [0.18, 0.31]). There was evidence of publication bias and heterogeneity (PI = [-0.22, 0.72], I2 = 87.2%). After removing outliers, we conducted planned subgroup analyses, which revealed that within-subjects studies, in which participants compare neuroscience to non-neuroscience, have significantly stronger effects than between-subjects designs, and studies using text yield a stronger average effect than those using brain images. We also serendipitously found that effect sizes were stronger in studies where participants evaluate satisfaction or metacomprehension, compared with jury verdicts or assessments of convincingness. Overall, the heterogeneity indicates there is more than one type of SANE effect, having more to do with stimuli used and outcomes assessed, than with participant characteristics, such as dualistic beliefs. Irrelevant neuroscience does appear to have a seductive allure, especially on self-appraised satisfaction and understanding, and when presented as text.

A 'high resolution' Single Locus Sequence Typing (SLST) scheme has been described for the anaerobic skin bacterium Cutibacterium acnes that seemingly discriminates sequence types (STs) to a level commensurate with previously described Multilocus Sequence Typing (MLST) methods (MLSTSimpson's index of diversity (D) was used for quantitative comparison of the resolving power of the SLST and MLST schemes for 186 isolates of C. acnes covering all three subspecies.When strains were considered collectively, SLST and all three MLST approaches had similar D values 90%. However, at the subspecies level there were significant differences between the methods, most strikingly a reduced discrimination of type II and type III strains (D80%) by SLST versus MLSTCUTIS-SEQ provides an opportunity to improve differentiation of C. acnes isolates by SLST without significantly impacting laboratory workload, or compromising application to complex biological communities. A CUTIS-SEQ isolate database is now available as part of the C. acnes PubMLST database at https://pubmlst.org.

Objective: Clostridium perfringens and Bacillus cereus are common causes of reported foodborne illness. On August 6, 2021, the Alaska Division of Public Health identified a multipathogen gastrointestinal outbreak among hospital staff in Homer, Alaska. The objectives of this study were to identify the outbreak source and prevent future illness. Methods: We conducted a retrospective cohort study of hospital staff who participated in luncheon events during August 5-7, 2021, and used an online survey to identify hospital staff with gastrointestinal illness. We defined case patients as people who reported new-onset gastrointestinal illness (diarrhea or abdominal cramping) after food consumption during the luncheon events. We calculated adjusted odds ratios of gastrointestinal illness associated with reported food exposures. We tested available food samples for C perfringens and B cereus and tested case patient stool specimens for C perfringens. We conducted an environmental investigation at the implicated vendor site. Results: Of 202 survey responses, 66 (32.7%) people reported acute gastrointestinal illness: 64 (97.0%) reported diarrhea, 62 (94.9%) reported abdominal cramps, and none were hospitalized. Of 79 people who consumed ham and pulled pork sandwiches, 64 (81.0%) met the case definition; this food item was significantly associated with increased odds of gastrointestinal illness (adjusted odds ratio = 296.4; 95% CI, 76.7-2019.1). C perfringens and B cereus were isolated at confirmatory levels from sandwich samples. C perfringens enterotoxin was detected in all 5 stool specimens tested. Environmental investigators observed other food items at the sandwich vendor that were refrigerated outside the required temperature range (>41 °F); no clear handling deficiencies for the implicated food were identified. Conclusion: Quick notification and effective collaboration can help detect an outbreak, identify the responsible food vehicle, and mitigate further risk.

With Hotel London, Barbara Black completes her insightful trilogy on three significant Victorian social institutions. In earlier work on museum culture in On Exhibit: Victorians and their Museums (...

Progressive macular hypomelanosis (PMH) is a skin condition that normally causes symmetrically distributed hypopigmented macules on the front and back of the trunk, but rarely the face. To date, the pathophysiology of the condition is not well understood, but a role for the anaerobic skin bacterium Cutibacterium (previously Propionibacterium) acnes in the development of the disease has been proposed due to its sole presence within lesional, but not normal peri-lesional, skin. The success of antimicrobials in the treatment of PMH also provides circumstantial evidence that this association may be causal, although this is still to be proven. More recent culture and metagenomic typing studies indicate that strains of C. acnes subsp. elongatum (type III) may be important in the aetiology of the condition, which would help to explain why PMH does not normally affect the face since such strains are rarely present there, and why no association between this condition and acne vulgaris is found; acne appears to primarily involve type IA1 strains from C. acnes subsp. acnes (type I). In this review, we summarize current knowledge on the relationship between C. acnes and PMH, and re-examine previous challenges to the view that the bacterium plays a role in the condition against the backdrop of newly emerged data.

Purpose: To determine the expression level, associations, and biological role of PD-L1, IDO-1, and B7-H4 in non–small cell lung cancer (NSCLC). Experimental Design: Using multiplexed quantitative immunofluorescence (QIF), we measured the levels of PD-L1, IDO-1, B7-H4, and different tumor-infiltrating lymphoycte (TIL) subsets in 552 stages I–IV lung carcinomas from two independent populations. Associations between the marker levels, TILs, and major clinicopathologic variables were determined. Validation of findings was performed using mRNA expression data from The Cancer Genome Atlas (TCGA) and in vitro stimulation of lung adenocarcinoma A549 cells with IFNγ and IL10. Results: PD-L1 was detected in 16.9% and 21.8% of cases in each population. IDO-1 was expressed in 42.6% and 49.8%; and B7-H4 in 12.8% and 22.6% of cases, respectively. Elevated PD-L1 and IDO-1 were consistently associated with prominent B- and T-cell infiltrates, but B7-H4 was not. Coexpression of the three protein markers was infrequent, and comparable results were seen in the lung cancer TCGA dataset. Levels of PD-L1 and IDO-1 (but not B7-H4) were increased by IFNγ stimulation in A549 cells. Treatment with IL10 upregulated B7-H4 but did not affect PD-L1 and IDO-1 levels. Conclusions: PD-L1, IDO-1, and B7-H4 are differentially expressed in human lung carcinomas and show limited co-expression. While PD-L1 and IDO-1 are associated with increased TILs and IFNγ stimulation, B7-H4 is not. The preferential expression of discrete immune evasion pathways in lung cancer could participate in therapeutic resistance and support design of optimal clinical trials. Clin Cancer Res; 23(2); 370–8. ©2016 AACR.

Introduction EGFR is a therapeutic target in NSCLC for EGFR-mutant patients. Proximity ligation assay (PLA) is a method to detect functional signaling associated protein complexes. Growth factor receptor bound protein 2 (GRB2) is an adaptor protein that binds to the phosphorylated residues of active EGFR. Interaction of EGFR and GRB2 correlates with active EGFR signaling and leads to activation of the MAPK/ERK pathway. Methods A PLA developed to detect EGFR-GRB2 interaction was measured by quantitative immunofluorescence using Automated Quantitative Analysis technology. EGFR pathway activation was assessed in patients with NSCLC with different mutation status along with overall EGFR expression. Additionally, the PLA to detect EGFR-GRB2 interaction was evaluated as a prognostic marker in two cohorts of patients with lung adenocarcinoma. Results The PLA to detect EGFR-GRB2 interaction was unrelated to overall EGFR expression or mutation in a series of patients with NSCLC with known mutation status. EGFR-mutant ( p = 0.04) and EGFR/KRAS wild-type tumors ( p = 0.0049) had significantly higher EGFR pathway activation compared with KRAS-mutant cases, with no significant difference shown between mutation sites. In two series of patients with lung adenocarcinoma, the PLA to detect EGFR-GRB2 interaction was independently associated with longer survival (hazard ratio = 0.46, 95% confidence interval: 0.2–0.78, p = 0.0085 and hazard ratio = 0.48, 95% confidence interval: 0.2–0.85, p = 0.017). Total EGFR protein expression alone was not correlated with outcome. Conclusions EGFR colocalization with GRB2 as assessed by PLA is not correlated with EGFR expression levels or mutation status, defining a patient group that may show EGFR pathway activation, as illustrated by its prognostic value. Future studies may determine whether this group is more likely to respond to EGFR-targeted therapies.

Hand osteoarthritis (HOA) includes different subsets; a particular and uncommon form is erosive HOA (EHOA). Interleukin- (IL-) 1βplays a crucial role in the pathogenesis of osteoarthritis (OA); it is synthesized as an inactive precursor which requires the intervention of a cytosolic multiprotein complex, named inflammasome, for its activation. The aim of this study was to investigate the involvement of IL-1βand the NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasome in patients with EHOA and nonerosive HOA (NEHOA) compared to healthy controls. In particular, we evaluated the gene expression of IL-1βand NLRP3, the serum levels of IL-1β, IL-6, IL-17, and tumor necrosis factor- (TNF-)α, and the protein levels of IL-1βand NLRP3. We also assessed the relationships between IL-1βand NLRP3 and clinical, laboratory, and radiological findings. Fifty-four patients with HOA (25 EHOA and 29 NEHOA) and 20 healthy subjects were included in the study. Peripheral blood mononuclear cell (PBMC) gene and protein expressions of IL-1βand NLRP3 were quantified by quantitative real-time PCR and western blot. IL-1β, IL-6, IL-17, and TNF-αserum levels were determined by ELISA. IL-1βgene expression was significantly reduced (p=0.0208) in EHOA compared to healthy controls. NLRP3 protein levels were significantly increased in the NEHOA group versus the control (p=0.0063) and EHOA groups (p=0.0038). IL-1βserum levels were not significantly different across the groups; IL-6, IL-17, and TNF-αwere not detectable in any sample. IL-1βconcentrations were negatively correlated with the Kellgren-Lawrence score in the whole population (r=−0.446;p=0.0008) and in NEHOA (r=−0.608;p=0.004), while IL-1βgene expression was positively correlated with the number of joint swellings in the EHOA group (r=0.512;p=0.011). Taken together, our results, showing poorly detectable IL-1βconcentrations and minimal inflammasome activity in the PBMCs of HOA patients, suggest a low grade of systemic inflammation in HOA. This evidence does not preclude a possible involvement of these factors at the local level.

BACKGROUND Chronic blood transfusion is the standard of care in the management of overt stroke due to sickle cell anemia (SS) to prevent recurrence of stroke. The problem arises when children are transitioned to adult care where blood transfusion may be discontinued. The purpose of this study was to report the outcome of 22 patients with SS and overt stroke who were transitioned to our adult program between 1993 and 2009. STUDY DESIGN AND METHODS Transitioned patients were kept on chronic blood transfusion they had as children. Blood bank data were performed and computerized according to FDA and AABB regulations. Records were kept prospectively. Blood counts and percent hemoglobin (Hb)S were obtained before and after transfusion. HbS was kept below 30% after transfusion. Metabolic profiles were obtained every 6 months or more often if needed. Statistical analysis was by the two-tailed t-test. RESULTS Patients who were compliant with blood transfusion were rarely hospitalized for painful crises. Alloimmunization and iron overload were the major complications of blood transfusion. Eight patients who refused to be maintained on chronic blood transfusion or who were noncompliant died within 1 to 5 years after transition. Causes of death included stroke in two, sudden in three, and multiorgan failure in three. The overall rate of death after transition was 36% and the major cause was discontinuation of blood transfusion. CONCLUSION Efforts must be made to maintain adequate chronic simple or exchange blood transfusion for children with SS and stroke after transition to adult care.

With the proliferation of neuroscience-related messages in popular media, it is more important than ever to understand their impact on the lay public. Previous research has found that people believed news stories more when irrelevant neuroscientific explanations were added. We sought to reveal whether such information could cause a change in social behavior. Specifically, based on publicized findings of the relationship between social behavior and the neurotransmitter oxytocin, we proposed that participants would accept more strangers into their in-group, or alternatively decrease in-group size, if told that there were oxytocin-based (relative to psychological construct-based) health benefits for doing so. In two tasks, participants were shown faces and written information about stimuli that could match their race, politics, and religion to varying degrees. In spite of evidence that participants processed the primes, and were sensitive to their level of similarity with stimuli, oxytocin-based priming did not alter categorization, or pupil dilation. It did not alter cross-race viewing behavior, as measured by an eye tracker, in consistent ways. Unexpectedly, pupil dilation increased when viewing stimuli of the same religion, an effect entirely related to White liberal Christians viewing other Christians. Overall, these results suggest that neuroscience information may impact some judgments, but lay people will not alter their likelihood of acceptance of strangers simply because they were primed with a neuroscience- (or more specifically, neurotransmitter-) based reason for doing so.

The anaerobic bacterium Propionibacterium acnes is believed to play an important role in the pathophysiology of the common skin disease acne vulgaris. Over the last 10 years our understanding of the taxonomic and intraspecies diversity of this bacterium has increased tremendously, and with it the realisation that particular strains are associated with skin health while others appear related to disease. This extensive review will cover our current knowledge regarding the association of P. acnes phylogroups, clonal complexes and sequence types with acne vulgaris based on multilocus sequence typing of isolates, and direct ribotyping of the P. acnes strain population in skin microbiome samples based on 16S rDNA metagenomic data. We will also consider how multi-omic and biochemical studies have facilitated our understanding of P. acnes pathogenicity and interactions with the host, thus providing insights into why certain lineages appear to have a heightened capacity to contribute to acne vulgaris development, while others are positively associated with skin health. We conclude with a discussion of new therapeutic strategies that are currently under investigation for acne vulgaris, including vaccination, and consider the potential of these treatments to also perturb beneficial lineages of P. acnes on the skin.

PD-L1 is expressed in a percentage of lung cancer patients and those patients show increased likelihood of response to PD-1 axis therapies. However, the methods and assays for the assessment of PD-L1 using immunohistochemistry are variable and PD-L1 expression appears to be highly heterogeneous. Here, we examine assay heterogeneity parameters toward the goal of determining variability of sampling and the variability due to pathologist-based reading of the immunohistochemistry slide. SP142, a rabbit monoclonal antibody, was used to detect PD-L1 by both chromogenic immunohistochemistry and quantitative immunofluorescence using a laboratory-derived test. Five pathologists scored the percentage of PD-L1 positivity in tumor- and stromal-immune cells of 35 resected non-small cell lung cancer cases, each represented on three separate blocks. An intraclass correlation coefficient of 94% agreement was seen among the pathologists for the assessment of PD-L1 in tumor cells, but only 27% agreement was seen in stromal/immune cell PD-L1 expression. The block-to-block reproducibility of each pathologist's score was 94% for tumor cells and 75% among stromal/immune cells. Lin's concordance correlation coefficient between pathologists' readings and the mean immunofluorescence score among blocks was 94% in tumor and 68% in stroma. Pathologists were highly concordant for PD-L1 tumor scoring, but not for stromal/immune cell scoring. Pathologist scores and immunofluorescence scores were concordant for tumor tissue, but not for stromal/immune cells. PD-L1 expression was similar among all the three blocks from each tumor, indicating that staining of one block is enough to represent the entire tumor and that the spatial distribution of heterogeneity of expression of PD-L1 is within the area represented in a single block. Future studies are needed to determine the minimum representative tumor area for PD-L1 assessment for response to therapy.

The objective of this capstone project was to build a simulated system using the Joint Capabilities Integration and Development System/Defense Acquisition System (JCIDS/DAS) process to gain insight into JCIDS/DAS as it relates to unmanned robotics systems. JCIDS and DAS are the Department of Defenses procedures and guidelines for acquiring military programs. Using JCIDS/DAS and system engineering (SE) methodology, the team developed a radiological clearance system (RCS) and an unmanned ground vehicle (UGV) using LEGO MINSTORMS. The UGV was named the Threat Exposure and Clearing Hardware Manipulated Autonomously or Networked (TECHMAN). The team researched UGVs, software platforms and the JCIDS /DAS regulations to tailor an SE approach in designing and building the TECHMAN robot, starting with the mission needs and requirements followed by system architecture development. The team tested and evaluated two TECHMAN systems. One system was teleoperated and the other was autonomous. The team compared the test results and other system attributes of the two platforms. The knowledge gained from the project results was used to provide insight into the JCIDS/DAS process with regard to procurement of robotics systems.

Tumor PD-L1 expression is associated with increased tumor-infiltrating lymphocytes (TILs) in diverse solid tumors, including lung cancer. In addition, PD-L1 upregulation in tumor and/or stromal immune cells has been associated with increased clinical benefit to PD-1/PD-L1 axis blockers. The significance of PD-L1 expression in different immune cell subpopulations at the tumor microenvironment remains poorly understood. Here, we measured PD-L1 protein specifically in tumor-associated macrophages using objective methods and analyzed its clinical significance in human lung cancer.

Amid the concerns about high unemployment rates for all age groups, there is always an assumption that workers will ultimately get jobs back when the economy recovers. But the number of workers who have permanently lost their jobs is high. The authors add up the enormous losses to the workers and the economy.

The labor market fate of the nation’s male teens and young adults (ages 20—29) has deteriorated along most employment, weekly wages, and annual earnings dimensions in recent decades. The employment rates reached new post—World War II lows in 2009, with the less well educated faring the worst. The deterioration in the labor market well-being of these young men has had a number of adverse consequences on their social behavior. Less-educated young men, especially high school dropouts, are far more likely to be incarcerated than their peers in earlier decades. They are considerably less likely to be married and more likely to be absent fathers, with gaps in marriage rates across educational groups widening substantially since the 1970s. The decline in marriage among less-educated young adults, high assortative mating among younger married couples, and growing gaps in earnings across educational groups have contributed to a substantial widening in income and wealth disparities among the nation’s young families.

Profits are rising sharply in the United States, but wages are not. The unemployment rate remains high, and a rapid increase in jobs is not forecast. Clearly, American business has shed jobs in short order. The resulting rise in productivity is not being shared by workers. How much longer can this go on? The authors analyze the disturbing numbers.

Blue-collar workers have been devastated in the current recession. And their jobs are not likely to come back. Andrew Sum and his economics team dissect the disturbing facts. There is a crying need, they argue, for new jobs programs.

One of the important building blocks of a workforce development system has long been the ability of teenagers to get jobs while on summer vacation. But the employment rate of teens in the summer has fallen dramatically in recent years. In fact, the decline is unprecedented, the authors find, and represents a "massive" underutilization of the country's capacities.

In case you wondered whether workers in securities firms and investment bankers have fared better than the rest of American workers, the answer is, resoundingly, "Yes." Andrew Sum and his colleagues here present the most comprehensive evidence so far. It is eye-opening.

Tumor-infiltrating lymphocytes (TILs) are usually measured using subjective methods. Studies suggest that TIL subtypes have independent roles in cancer and that they could support the use of novel immunostimulatory therapies. We simultaneously measured TIL subtypes in non-small cell lung cancer (NSCLC) samples using objective methods and determined their relationship with clinico-pathologic characteristics and survival.Using multiplexed quantitative fluorescence (QIF), we measured the levels of CD3, CD8, and CD20 in 552 NSCLC from two independent collections represented in tissue microarrays (YTMA79, n = 202 and YTMA140, n = 350). The level of TILs was obtained in different tumor compartments using cytokeratin stain to define tumor cells and 4',6-Diamidino-2-Phenylindole. Association of TILs with clinical parameters was determined using univariate and multivariable analyses. All statistical tests were two-sided.In both NSCLC collections there was a low correlation between the three TIL markers (linear regression coefficients (R(2)) = 0.19-0.22, P.001 for YTMA79 and R(2) = 0.23-0.32, P.001 for YTMA140). No consistent association between the level of TIL subtypes and age, sex, smoking history, tumor size, stage, and histology type was found. In univariate analysis, an elevated CD3 or CD8 signal was statistically significantly associated with longer survival in both collections. However, only CD8 was independent from age, tumor size, histology, and stage in multivariable analysis. High CD20 was associated with longer survival in the YTMA79 cohort.Increased levels of CD3 and CD8 + TILs are associated with better outcome in NSCLC, but only CD8 is independent from other prognostic variables. Objective measurement of TIL subpopulations could be useful to predict response or evaluate the local immune effect of anticancer immune checkpoint inhibitors.

The Making of the West End Stage: Marriage, Management and the Mapping of Gender in London, 1830-1870 Jacky Bratton Cambridge: Cambridge UP, 2011 Vii + 222, 1 map and 11 illustrations. ISBN 978-0-5...

Early in the development of the ultra long duration balloon (ULDB), Zylon was selected as the tendon material due to its favorable stress–strain properties. It is a next generation fiber whose strength and modulus are almost double those of the Kevlar fibers. In addition there are two versions of the Zylon, as spun (AS) and high modulus (HM). Data will be presented on why HM was chosen. Early in the development process, it was learned that this material exhibited an unusual sensitivity to degradation by ambient light. This is in addition to the expected sensitivity to UV (Ultraviolet) radiation. The fiber manufacturer reported all of these properties in their literature. Due to the operating environment of the ULDB it is necessary to protect the tendons from both visible and UV radiation. Methods to protect the tendons will be discussed. In addition, information on the long term exposure of the braided tendon over a thirty-two month period in a controlled manufacturing plant will be provided. Special testing methods will be noted.

We evaluated the direct and the residual efficacy of selected traditional, safer, and biological insecticides that are either registered or are candidates for registration for use by arborists and nurserymen in Integrated Pest Management (IPM) programs for gypsy moth (Lymantria dispar} management in urban settings. The study compared 5 biological insecticide treatments (1 Bacillus thuringiensis[Bf] and 4 gypsy moth nuclear polyhedrosis virus [NPV] treatments) and 2 reduced-risk insecticides (neem and tebufenozide) against 2 commonly used standard insecticides (diflubenzuron and cyfluthrin). Significant details pertaining to the use of the specific control materials were clarified in support of a decision matrix around which an IPM system can be formulated for use by arborists and nurserymen. The standard insecticides, cyfluthrin and diflubenzuron, and the ecdysone agonist tebufenozide, demonstrated excellent activity against all instars in both a 1 - hour residue study and a 35-day residue study, Bt was clearly more effective against second instar larvae than against fourth instar larvae and lost significant activity against the gypsy moth after 7 days. The efficacy of the neem product was similar to that of Bt in that it controlled younger instars better than it did older instars. Although its speed of action was slower than that of Bt, it remained highly active against gypsy moth 21 days after treatment. NPV without the activity enhancer Blankophor BBH gave significant levels of control for all 4 larval instars fed on 1 -hour residues, although mortality was higher for younger instars than for older instars. Residual effectiveness was significantly reduced after 1 day. The addition of Blankophor BBH to the NPV tank mix led to improved kill in the 1-hour study and to vastly improved residual activity (up to 35 days).