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David Temperley's book, "The Musical Language of Rock," explores the conventions and language of rock music. Temperley argues that experienced rock listeners unconsciously understand these conventions and can detect deviations from them. The book combines theory and analysis, using musical examples to develop theoretical models. Temperley examines various aspects of rock music, including harmony, emotion, complexity, melody, rhythm, and form. He also considers the historical development of rock and its formal functions. The book offers new insights and perspectives on the musical language of rock. [Extracted from the article]

Business students have long been noted for their differential proclivity to engage in academic misconduct. Unfortunately, the potential for misconduct has been exacerbated in recent years by rapid advances in technology, easy access to information, competitive pressures, and the proliferation of websites that provide students access to information that allows them to directly circumvent the learning process. Using a convenience sample of 631 students matriculating in various business majors at four U.S. universities and structural equations modeling procedures, this study assesses the effects of psychological factors on business students' propensities to utilize the services of homework assistance websites. Specifically, we examine how "Dark Triad" personality traits (i.e., narcissism, Machiavellianism, and psychopathy) interact with Fraud Diamond elements to influence student decisions to engage the services of these websites. We find that each Dark Triad trait exerts a significant influence on at least one of the Fraud Diamond elements, which in turn have a significant direct or indirect positive association with students' reported intentions to utilize, and reported utilization of, these websites. [ABSTRACT FROM AUTHOR]

Trees continuously regulate leaf physiology to acquire CO2 while simultaneously avoiding excessive water loss. The balance between these two processes, or water use efficiency (WUE), is fundamentally important to understanding changes in carbon uptake and transpiration from the leaf to the globe under environmental change. While increasing atmospheric CO2 (iCO2) is known to increase tree intrinsic water use efficiency (iWUE), less clear are the additional impacts of climate and acidic air pollution and how they vary by tree species. Here, we couple annually resolved long‐term records of tree‐ring carbon isotope signatures with leaf physiological measurements of Quercus rubra (Quru) and Liriodendron tulipifera (Litu) at four study locations spanning nearly 100 km in the eastern United States to reconstruct historical iWUE, net photosynthesis (Anet), and stomatal conductance to water (gs) since 1940. We first show 16%–25% increases in tree iWUE since the mid‐20th century, primarily driven by iCO2, but also document the individual and interactive effects of nitrogen (NOx) and sulfur (SO2) air pollution overwhelming climate. We find evidence for Quru leaf gas exchange being less tightly regulated than Litu through an analysis of isotope‐derived leaf internal CO2 (Ci), particularly in wetter, recent years. Modeled estimates of seasonally integrated Anet and gs revealed a 43%–50% stimulation of Anet was responsible for increasing iWUE in both tree species throughout 79%–86% of the chronologies with reductions in gs attributable to the remaining 14%–21%, building upon a growing body of literature documenting stimulated Anet overwhelming reductions in gs as a primary mechanism of increasing iWUE of trees. Finally, our results underscore the importance of considering air pollution, which remains a major environmental issue in many areas of the world, alongside climate in the interpretation of leaf physiology derived from tree rings. [ABSTRACT FROM AUTHOR]

Introduction: US pneumococcal vaccination recommendations for adults aged 65 years or older recently changed, with options for either 20-valent pneumococcal conjugate vaccine (PCV20) or the combination of 15-valent conjugate vaccine (PCV15) followed by 23-valent polysaccharide vaccine (PPSV23) 1 year later. Underserved minority adults are at higher risk for pneumococcal disease. Methods: A Markov decision analysis model estimated the incremental cost-effectiveness of the newly adopted general population pneumococcal vaccination strategies in older underserved minority adults. The model examined hypothetical 65-year-old US Black cohorts (serving as a proxy for underserved minorities) and non-Black cohorts receiving PCV20 or PCV15/PPSV23, or no vaccination. Main outcome measures included incremental cost-effectiveness per quality-adjusted life year (QALY) gained and pneumococcal disease public health outcomes. Results: Black cohorts had a greater risk of pneumococcal disease hospitalization compared to non-Black cohorts. In Black cohorts, total per person PCV20 strategy costs, compared to no vaccination, were $124 higher while gaining 0.00073 QALY, or $169,540/QALY gained. PCV15/PPSV23 cost $535,797/QALY compared to PCV20. In the non-Black cohort, PCV20 cost $210,529/QALY gained compared to no vaccination and PCV15/PPSV23 cost $728,423/QALY. Plausible variation of vaccine effectiveness minimally affected PCV20 strategy results and made PCV15/PPSV23 more unfavorable. In scenarios where the simpler one-vaccine PCV20 strategy increased absolute vaccine uptake by 10%, PCV20 cost-effectiveness changed minimally while PCV15/PPSV23 cost in excess of $6 million/QALY in the Black cohort. In probabilistic sensitivity analyses that varied all parameters simultaneously, PCV15/PPSV23 was unlikely to be favored at thresholds less than $500,000/QALY gained. Conclusion: General population recommendations for PCV20 use are substantially more economically reasonable in Black and non-Black older adult populations than PCV15/PPSV23. If using a single vaccine increases uptake, which is potentially more likely in the underserved, then PCV20 use becomes even more favorable. [ABSTRACT FROM AUTHOR]

This article explores music's role in radio drama. While musical aspects of early experimental radio dramas have often been explored, the music that figures in the Anglo-American radio play tradition has remained under-theorized. Borrowing interpretative tools from audiovisual discourses can help to elucidate some of the subtleties of the medium, but methodological inadequacies soon become apparent. As exemplars of modern radio dramatic technique, the BBC's complete adaptations of Sherlock Holmes stories (1989–98) are explored, their music interwoven into the drama with consistent levels of subtlety. I draw primarily from Michel Chion's application of the 'acousmatic', showing how the ambiguity concerning the location of the enveloping solo violin music – Holmes's instrument – offers twists and turns to the agency of the unfolding narrative. I examine further how a sustained technique of intertextual allusion creates what I call a paradiegetic space, in which pre-existing music, heard within the dramas, provides a parenthetical narrative that unravels in parallel with the primary narrative, reflecting back on its themes, changing its meanings and moreover challenging our preconceptions about radio's particular acousmatic zone. [ABSTRACT FROM AUTHOR]

Background and Objective: Methicillin-resistant Staphylococcus aureus bloodstream infections (MRSAB) cause significant mortality, and often require extended antibiotic therapy. Vancomycin, the most common initial MRSAB treatment, carries significant monitoring burden and nephrotoxicity risks. Our objective was to compare the cost-effectiveness of vancomycin and other antibiotic regimens against MRSAB. Methods: We estimated the cost-effectiveness of intravenous antibiotics (vancomycin, daptomycin, linezolid, ceftaroline/daptomycin) for Veterans Health Administration patients with MRSAB using an exploratory decision-tree model. Primary effectiveness outcome was composite of microbiological failure at 7 days and adverse drug event (ADE)-related discontinuation after at least 7 days. Results: In base-case analyses, intravenous linezolid was the least expensive regimen at 4 and 6 weeks. Daptomycin was more expensive and more effective than linezolid, with an incremental cost-effectiveness ratio (ICER) of ~$13,000 (4 weeks) per composite failure avoided. With 6 weeks of treatment, daptomycin was more expensive and more effective than vancomycin (ICER ~$21,000 per composite failure avoided). Vancomycin and ceftaroline/daptomycin were dominated strategies at both 4 and 6 weeks. In one-way sensitivity analyses, vancomycin was favored when its microbiological failure risk was less than 20.1% (base-case: 27.2%), assuming a willingness to pay (WTP) threshold of $40,000/composite treatment failure avoided. In two-way sensitivity analyses, intravenous linezolid was favored if linezolid microbiological failure and ADE-related discontinuation rates were < 22.5% and < 17.3%, respectively. Daptomycin, vancomycin, and linezolid were favored in 50%, 31%, and 17% of 4-week probabilistic iterations, respectively, at $40,000 WTP. Conclusion: Daptomycin is likely less expensive and more effective than vancomycin or other initial regimens for MRSAB. More data are needed on the safety of linezolid against MRSAB. [ABSTRACT FROM AUTHOR]

Objectives Methods Results Interpretation Hypoperfusion and tissue hypoxia have been implicated as contributory mechanisms in the neuropathology of multiple sclerosis (MS). Our objective has been to study cortical oxygenation in vivo in patients with MS and age‐matched controls.A custom, multiwavelength time‐domain near‐infrared spectroscopy system was developed for assessing tissue hypoxia from the prefrontal cortex. A cross‐sectional case–control study was undertaken assessing patients with secondary progressive MS (SPMS) and age‐matched controls. Co‐registered magnetic resonance imaging was used to verify the location from which near‐infrared spectroscopy data were obtained through Monte Carlo simulations of photon propagation. Additional clinical assessments of MS disease severity were carried out by trained neurologists. Linear mixed effect models were used to compare cortical oxygenation between cases and controls, and against measures of MS severity.Thirty‐three patients with secondary progressive MS (median expanded disability status scale 6 [IQR: 5–6.5]; median age 53.0 [IQR: 49–58]) and 20 age‐matched controls were recruited. Modeling of photon propagation confirmed spectroscopy data were obtained from the prefrontal cortex. Patients with SPMS had significantly lower cortical hemoglobin oxygenation compared with controls (−6.0% [95% CI: −10.0 to −1.9], P = 0.004). There were no significant associations between cortical oxygenation and MS severity.Using an advanced, multiwavelength time‐domain near‐infrared spectroscopy system, we demonstrate that patients with SPMS have lower cortical oxygenation compared with controls. [ABSTRACT FROM AUTHOR]

• Childhood vaccination has decreased during the pandemic, potentially leading to increased pneumococcal disease. • As a result, changes to older adult pneumococcal vaccination recommendations could be considered. • Plausible pneumococcal illness increases do not favor heightened PCV13 use in older adults. • Current vaccination recommendations for older adults should not change based on pediatric vaccination rates. The COVID-19 pandemic is causing declines in childhood immunization rates. We examined potential COVID-19-related changes in pediatric 13-valent pneumococcal conjugate vaccine (PCV13) use, subsequent impact on childhood and adult pneumococcal disease rates, and how those changes might affect the favorability of PCV13 use in non-immunocompromised adults aged ≥65 years. A Markov model estimated pediatric disease resulting from decreased PCV13 use in children aged <5 years; absolute decreases from 10 to 50% for 1–2 years duration were examined, assuming no catch-up vaccination and that decreased vaccination led to proportionate increases in PCV13 serotype pneumococcal disease in children and seniors. Integrating pediatric model output into a second Markov model examining 65-year-olds, we estimated the cost effectiveness of older adult pneumococcal vaccination strategies while accounting for potential epidemiologic changes from decreased pediatric vaccination. One year of 10–50% absolute decreases in PCV13 use in <5-year-olds increased pneumococcal disease by an estimated 4–19% in seniors; 2 years of decreased use increased senior rates by 8–38%. In seniors, a >53% increase in pneumococcal disease was required to favor PCV13 use in non-immunocompromised seniors at a $200,000 per quality-adjusted life-year gained threshold, which corresponded to absolute decreases in pediatric PCV13 vaccination of >50% over a 2-year period. In sensitivity analyses, senior PCV13 vaccination was unfavorable if absolute decreases in pediatric PCV13 receipt were within plausible ranges, despite model assumptions favoring PCV13 use in seniors. COVID-19-related decreases in pediatric PCV13 use would need to be both substantial and prolonged to make heightened PCV13 use in non-immunocompromised seniors economically favorable. [ABSTRACT FROM AUTHOR]

Introduction: Use of the 13-valent pneumococcal conjugate vaccine in nonimmunocompromised adults aged ≥65 years is controversial. Higher-valency conjugate vaccines (15-valent and 20-valent ) are under development; their potential cost effectiveness in older adults is unknown, particularly when potential indirect (herd immunity) effects from childhood vaccination are considered.Methods: A Markov model estimated the cost effectiveness of current U.S. recommendations and alternative strategies using currently available and in-development pneumococcal conjugate vaccines in seniors. Separately, strategies using a hypothetical 20-valent vaccine adding the 7 most common disease-causing non-13-valent vaccine serotypes were considered. Sensitivity analyses were performed and alternative scenarios were examined. Data were gathered and the analyses were performed in 2020.Results: In analyses considering only existing and in-development vaccines, sole 20-valent vaccine use cost $172,491/quality-adjusted life year gained compared with current U.S. recommendations under baseline assumptions (equal serotype effectiveness and no childhood vaccination indirect effects). Strategies using 15-valent vaccine were more costly and less effective. When 13-valent/20-valent vaccines were assumed ineffective against pneumococcal serotype 3 and 15-valent vaccine was fully effective, 15-valent vaccine cost $237,431/quality-adjusted life year gained. With indirect effects considered, 15-valent or 20-valent vaccine cost >$449,000/quality-adjusted life year gained. When adding hypothetical 20-valent vaccine under baseline assumptions, hypothetical 20-valent vaccine cost $139,348/quality-adjusted life year gained.Conclusions: In-development pneumococcal conjugate vaccines may be economically unreasonable in older adults, regardless of serotype effectiveness assumptions, particularly when considering potential indirect effects from use of those vaccines in children. Adult vaccines containing high-risk serotypes not contained in childhood vaccines may be more promising. [ABSTRACT FROM AUTHOR]

This article considers music that stages the decline of the tonal system through "entropy"—the process conceived in the domain of thermodynamics by which energy is wasted through randomized dispersal or decrease in organization. Tonal organization faced challenges at the turn of the twentieth century, much of the music possessing a sense of tonal drive but with an increased array of outlets for this drive's tension to be released. This article regards the dominant-seventh complex and its variant configurations as paradigms of this tonal drive and attempts to understand their new ambiguities and the increased richness of possibility they enjoy. In order to achieve this, the study engages in probability theory to create a unique profile for each tonal drive in a given piece, effectively measuring its strength. The fluctuating strengths can be mapped and the process of entropy tracked through a single piece, potentially even across repertoires. Using a new method of visually laying out the patterns of these dominant drives, combined with concepts from information theory that allow us to measure and compare levels of entropy mathematically, I attempt to combine qualitative and quantitative data to model the entropic processes that inhere in early twentieth-century music. [ABSTRACT FROM AUTHOR]

New Findings: What is the central question of this study?The compound sodium phenylbutyrate (PB) has been shown to promote branched‐chain amino acid (BCAA) catabolism, and as such has been proposed as a treatment for disorders with enhanced BCAA levels: does PB induce muscle protein catabolism by forcing BCAA degradation away from muscle protein synthesis and mechanistic target of rapamycin (mTOR) inhibition?What is the main finding and its importance?Accelerated BCAA catabolism using PB resulted in adverse effects related to mTOR signalling and muscle protein metabolism in skeletal muscle cells, which may limit its application in conditions where muscle wasting is a risk. The compound sodium phenylbutyrate (PB) has been used for reducing ammonia in patients with urea cycle disorders and proposed as a treatment for disorders with enhanced branched‐chain amino acid (BCAA) levels, due to its effects on promoting BCAA catabolism. In skeletal muscle cells, we hypothesised that PB would induce muscle protein catabolism due to forcing BCAA degradation away from muscle protein synthesis and downregulating mechanistic target of rapamycin (mTOR). PB reduced medium BCAA and branched‐chain keto acid (BCKA) concentrations, while total cell protein (−21%; P < 0.001 vs. control) and muscle protein synthesis (−25%; P < 0.001 vs. control; assessed by measurement of puromycin incorporation into polypeptides) were decreased with PB. The regulator of anabolic pathways mTOR and its downstream components were impaired with PB treatment. The present results indicate that accelerated BCAA catabolism using PB resulted in adverse effects related to mTOR signalling and muscle protein metabolism, which may limit its application in settings where muscle wasting is a risk. [ABSTRACT FROM AUTHOR]

This paper discusses the first French edition of Capital volume 1, revised by Marx, analyzed by Kevin Anderson (1983) in this journal and subsequent work, and partially incorporated into the new German edition by Thomas Kuczynski (2017), based largely on the second German edition. We argue that both Marx and Anderson are too generous (and Engels too negative) in their respective assessments of the translation and that it has found its appropriate place in the now definitive German version which will, we hope, be translated into other languages. [ABSTRACT FROM AUTHOR]

The use of artificial intelligence (AI) computer software to interpret data has become part of our everyday lives, and these AI algorithms are becoming part of our everyday laboratory practices. Many AI tools are beginning to demonstrate their real or potential utility in clinical microbiology laboratory practice. In this introduction to applications of AI in clinical microbiology diagnostic testing, the authors introduce AI and machine learning to those familiar with routine clinical microbiology practice. The discussion explores the role of AI for image analysis including Gram stains, ova and parasite exam, and digital plate reading of bacterial cultures. AI's role in advanced analysis of matrix-assisted laser desorption-ionization/time of flight mass spectrometry (MALDI-TOF) mass spectral data and whole genome sequence data of microbes is also discussed. In the future, computers and clinical laboratory scientists will work more closely together to provide optimal efficiency and quality in clinical microbiology laboratory practice, and this close collaboration between humans and machines is expected to improve patient care. [ABSTRACT FROM AUTHOR]

It has been widely documented that positive school climate significantly contributes to academic success and student well-being. This study explored teachers, students, and parents' perceptions of school climate as measured by the Inviting School Survey- R (ISS-R). The ISS-R was administered to over 10,000 school community members from over 60 schools across the United States. The ISS-R was used to identify perceptions of school climate between factors such as participants, gender, type of school, size of school, and student age. Results showed there were statistically significant association with self-reported perceptions of school climate and these five factors on the six ISS-R scales. The implications of the results are discussed, and it is concluded that the study's findings will facilitate the development of more inviting schools. [ABSTRACT FROM AUTHOR]

Discusses the role that academic and research libraries play in advancing student learning through outcomes assessment in the United States. Development of learning outcomes from the library's perspective; Development of curriculum segments through which the library would achieve the outcomes; Measurement of how well outcomes are being achieved.

Research on the self-concept and postulated causal links among a number of correlates has been particularly prolific. Yet at the present time there still persists disagreement on a number of pertinent issues. One major issue that has been shown in the review of correlates of self-concept is the need to specifically identify what is being studied -- global self-concept or specific areas (domains) of self-concept. The lack of a clear definition of what is being measured has been a significant reason for the lack of consistency in previous research results. Theories of causation must be formulated in a thorough, logical manner. The complexity of the many combinations of the self-concept and its correlates demands a clear statement of research goals and hypotheses. [ABSTRACT FROM AUTHOR]

Dryland (semiarid and arid) ecosystems are responsible for most of the interannual variation in atmospheric CO2 concentrations and contain a considerable fraction of the globe's soil carbon (C) stock. Despite their important contribution to the global land C sink, we have a poor mechanistic understanding of the processes that drive C cycling patterns in drylands. In this study in eastern Utah, we examined the natural variation of soil C pools and fluxes along semiorthogonal gradients of climate and soil texture in order to determine the pertinent environmental controls on soil C cycling dynamics. Our study revealed a high degree of collinearity among C stocks and fluxes, which were related to climate, vegetation, and soil clay content. Soil C pools were positively correlated with both soil clay content and precipitation, which in turn was linked to aboveground plant biomass. By contrast, enzyme activities were negatively associated with temperature. We observed a strong decoupling of C pools and fluxes (for example, total C, DOC, microbial biomass C, and respiration) from the enzyme activities involved in organic matter decomposition. Overall, our findings indicate that the within- and between-site variation of soil C pools across diverse dryland ecosystems was strongly linked to both climate and edaphic characteristics, but the high degree of local variability within sites could challenge interpretations of environmental controls at broader scales. [ABSTRACT FROM AUTHOR]

Both microvascular decompression (MVD) and Gamma Knife radiosurgery (GKRS) are time-tested treatment modalities for trigeminal neuralgia (TN). There is little evidence in the literature studying these modalities head to head in a cost-effectiveness comparison. To evaluate the cost-effectiveness of MVD compared with GKRS for treating patients with TN. We developed a Markov cost-effectiveness model for the U.S. health care system to account for all costs related to MVD and GKRS as treatment modalities for TN, from the health care system perspective, over a patient lifetime horizon. A base case was estimated using data from previous studies, from our own GKRS experience, and from a current data analysis of patients undergoing MVD. We derived model inputs, including health care costs, survival, and utility estimates, from the literature. We used age-specific, sex-specific, and race-specific mortality from national registries. Costs studied included those for MVD, for GKRS, for treating complications from either procedure, and for medications throughout patient lifetimes. We performed multiple 1-way, 2-way, and probabilistic sensitivity analyses to confirm the robustness of model assumptions and results. The incremental cost-effectiveness ratio (ICER), with a threshold of $50,000 per quality-adjusted life-year (QALY) gained, defined cost-effectiveness. The base case had an ICER of $12,154 per QALY for MVD compared with GKRS. Probabilistic sensitivity (Monte Carlo) analysis showed that MVD was cost-effective in 70% of model iterations. GKRS was favored when the willingness to pay threshold was <$12,000 per QALY gained. In patients medically eligible for either procedure, we found MVD to be the most cost-effective modality to treat TN, primarily because of its reported greater durability. MVD remained the most cost-effective strategy across a broad range of model input values in sensitivity analyses. [ABSTRACT FROM AUTHOR]

Introduction: Tradeoffs exist between efforts to increase influenza vaccine uptake, including early season vaccination, and potential decreased vaccine effectiveness if protection wanes during influenza season. U.S. older adults increasingly receive vaccination before October. Influenza illness peaks vary from December to April.Methods: A Markov model compared influenza likelihood in older adults with (1) status quo vaccination (August-May) to maximize vaccine uptake or (2) vaccination compressed to October-May (to decrease waning vaccine effectiveness impact). The Centers for Disease Control and Prevention data were used for influenza incidence and vaccination parameters. Prior analyses showed that absolute vaccine effectiveness decreased by 6%-11% per month, favoring later season vaccination. However, compressed vaccination could decrease overall vaccine uptake. Influenza incidence was based on average monthly incidence with earlier and later peaks also examined. Influenza strain distributions from two seasons were modeled in separate scenarios. Sensitivity analyses were performed to test result robustness. Data were collected and analyzed in 2018.Results: Compressed vaccination would avert ≥11,400 influenza cases in older adults during a typical season if it does not decrease vaccine uptake. However, if compressed vaccination decreases vaccine uptake or there is an early season influenza peak, more influenza can result. In probabilistic sensitivity analyses, compressed vaccination was never favored if it decreased absolute vaccine uptake by >5.5% in any scenario; when influenza peaked early, status quo vaccination was favored.Conclusions: Compressed vaccination could decrease waning vaccine effectiveness and decrease influenza cases in older adults. However, this positive effect is negated when early season influenza peaks occur and diminished by decreased vaccine uptake that could occur with shortening the vaccination season. [ABSTRACT FROM AUTHOR]

Background Patients undergoing posterior spinal fusion surgery can lose a substantial amount of blood. This can prolong operative time and require transfusion of allogeneic blood components, which increases the risk of infection and can be the harbinger of serious complications. Does a saline-irrigated bipolar radiofrequency hemostatic sealer (RFHS) help reduce transfusion requirements? Methods In an observational cohort study, we compared transfusion requirements in 30 patients undergoing surgery for adult spinal deformity using the RFHS with that of a historical control group of 30 patients in which traditional hemostasis was obtained with bipolar electrocautery and matched them for blood loss–related variables. Total expense to the hospital for the RFHS, laboratory expenses, and blood transfusions was used for cost calculations. The incremental cost-effectiveness ratio was calculated using the number of blood transfusions avoided as the effectiveness payoff. Results Using a multivariable linear regression model, we found that only estimated blood loss (EBL) was an independent significant predictor of transfusion requirement in both groups. We evaluated the variables of age, EBL, time duration of surgery, preoperative hemoglobin, hemoglobin nadir during surgery, body mass index, length of stay, and number of levels operated on. Mean EBL was greater in the control group (2201 vs. 1416 mL, P = 0.0099). The number of transfusions also was greater in the control group (14.5 vs. 6.5, P = 0.0008). In the cost-effectiveness analysis, we found that the RFHS cost $108 more (compared with not using the RFHS) to avoid 1 unit of blood transfusion. Conclusions The cost-effectiveness analysis revealed that if we are willing to pay $108 to avoid 1 unit of blood transfusion, the use of the RFHS is a reasonable choice to use in open surgery for adult spinal deformity. [ABSTRACT FROM AUTHOR]

The American Academy of Social Work and Social Welfare (AASWSW) identified 12 Grand Challenges of Social Work to unify the profession with focused research, practice and policy applications for the most pressing social issues. Virtual Reality (VR), specifically three-dimensional immersive computer-generated environments, has a history of research and applications to address social and behavioral problems. VR is becoming more readily available, as the technology is becoming more common in mainstream platforms such as mobile technology. While social work interventions are often tailored for vulnerable populations that may not have access to VR computing, it appears that virtual reality is gaining accessibility with these advances. Within the framework of the 12 Grand Challenges of Social Work, researchers from three social work virtual reality laboratories in the United States, Texas State University, the University of Houston, and the University of Alabama, review applications previously tested and currently in development to focus future research and intervention in social work practice. [ABSTRACT FROM AUTHOR]

"Virtual Reality" interventions in human services may include 360° video, augmented reality, mixed reality, and fully immersive 3-dimensional virtual reality simulations. A variety of applications have been evaluated in various fields of study, including medicine, social work, psychology, and human performance training. Currently, the state of research of VR interventions in human services has primarily focused on efficacy and effectiveness research, with few studies evaluating "scaling up" or implementation of VR interventions in larger populations. Unfortunately, the state of efficacy and effectiveness studies of VR interventions still remains weak with some applications due to smaller sample sizes, lack of randomized control trials, and a gap in reporting key intervention qualities, dosage, and outcomes. With new developments in combining artificial intelligence with VR, realism and the potential for human interaction with computer generated simulations may boost presence and immersion within these applications. This editorial provides an overview of the state of virtual reality applications in human service provision, potential gaps to be addressed by research in the future, and the development of AI based interactive sequences that may boost use presence. [ABSTRACT FROM AUTHOR]

Hyperammonaemia and hyperethanolaemia are thought to be driving factors behind skeletal muscle myopathy in liver disease, that is, cirrhosis. Despite this, the singular and combined impacts of ethanol‐ and ammonia‐induced protein catabolism are poorly defined. As such, we aimed to dissect out the effects of ammonia and ethanol on muscle catabolism. Murine C2C12 myotubes were treated with ammonium acetate (10 mM) and ethanol (100 mM) either alone or in combination for 4 hr and/or 24 hr. Myotube diameter, muscle protein synthesis and anabolic and catabolic signalling pathways were assessed. In separate experiments, cells were cotreated with selected inhibitors of protein breakdown to assess the importance of proteolytic pathways in protein loss with ammonia and ethanol. Ammonia and ethanol in combination resulted in a reduction in myotube width and total protein content, which was greater than the reduction observed with ammonia alone. Both ammonia and ethanol caused reductions in protein synthesis, as assessed by puromycin incorporation. There was also evidence of impairments in regulation of protein translation, and increased protein expression of markers of muscle protein breakdown. Myotube protein loss with ammonia plus ethanol was not affected by autophagy inhibition, but was completely prevented by proteasome inhibition. Thus, combined ammonia and ethanol incubation of C2C12 myotubes exacerbated myotube atrophy and dysregulation of anabolic and catabolic signalling pathways associated with either component individually. Ubiquitin proteasome‐mediated protein breakdown appears to play an important role in myotube protein loss with ethanol and ammonia. The findings from this study indicate that a combination of ammonia and ethanol incubation of C2C12 myotubes exacerbated muscle atrophy and dysregulation of anabolic and catabolic signalling pathways associated with either component individually. Our findings provide novel insight into the interactions between hyperammonaemia and hyperethanolaemia in relation to their regulation of muscle catabolism in vitro. [ABSTRACT FROM AUTHOR]

The distribution of fixed steel offshore platforms around the world reveals a global fleet that has exceeded or is approaching the end of the design life of the facility. In many operating areas, there is an attraction to continue using these ageing facilities due to continued production or as an adjoining structure to facilitate a new field development or expansion. To justify continued life extension of the fixed platform, various integrity assessment techniques are often used. One of the major techniques used is based on the phenomenon of local joint flexibility (LJF). While the phenomenon of LJF has been well known in the offshore industry since the early 1980s, there has been little experimental data available. In 1983, Amoco conducted an experimental study primarily to determine stress concentration factors associated with gapped K-type steel tubular joints. The LJFs calculated were based on the effects of in-plane bending, out-of-plane bending and axial compression and tension. The derivations of the existing LJF equations have evolved in many ways including use of finite element (FE) methods to predict the joint behavior. There has been no benchmarking exercise to large-scale experimental data. This paper provides an improvement on existing LJF equations by benchmarking the Amoco K-joints test results to a FE model and through a detailed parametric study. Improved formulations are provided for local joint flexibilities for gapped uni-planar K-type tubular steel joints. [ABSTRACT FROM AUTHOR]

Investigates the dynamics of self-assembling surfactant systems for amphiphile A2B2. Use of stochastic dynamic simulations in the study; Employment of temperature jump computer experiments; Interpretation of results based on the Aniansson-Wall theory of micellar kinetics.

Investigates the self-assembly of short amphiphilic molecules in surfactants using stochastic dynamics simulations with a scalar frictional coefficient. Calculation of equilibrium properties; Explanation of calculated results in the context of existing thermodynamic theories.

Introduction: Occupational noise threatens U.S. worker health and safety and commands a significant financial burden on state and federal government worker compensation programs. Previous studies suggest that hearing conservation programs have contributed to reduced occupational hearing loss for noise-exposed workers. Many military personnel are overexposed to noise and are provided hearing conservation services. Select military branches require all active duty personnel to follow hearing conservation program guidelines, regardless of individual noise exposure. We evaluated the cost-effectiveness of a military hearing conservation program, relative to no intervention, in relation to cases of hearing loss prevented.Methods: We employed cost-effectiveness analytic methods to compare the costs and effectiveness, in terms of hearing loss cases prevented, of a military hearing conservation program relative to no program. We used costs and probability estimates available in the literature and publicly available sources. The effectiveness of the interventions was analyzed based on whether hearing loss occurred over a 20-yr time frame.Results: The incremental cost-effectiveness ratio of the hearing conservation program compared with no intervention was $10,657 per case of hearing loss prevented. Workers were 28% less likely to sustain hearing loss in our model when they received the hearing conservation program compared with no intervention, which reflected the greater effectiveness of the hearing conservation program. Cost-effectiveness results were sensitive to estimated values for the probability of acquiring hearing loss from both interventions and the cost of hearing protection. We performed a Monte Carlo probabilistic sensitivity analysis where we simultaneously varied all the model parameters to their extreme plausible bounds. When we ran 10,000 Monte Carlo iterations, we observed that the hearing conservation program was more cost-effective in 99% of cases when decision makers were willing to pay $64,172 per case of hearing loss prevented.Conclusions: Conceding a lifetime cost for service-related compensation for hearing loss per individual of $64,172, the Department of Defense Hearing Conservation Program is an economically reasonable program relative to no intervention, if a case of hearing loss avoided costs $10,657. Considering the net difference of the costs and comparative benefits of both treatment strategies, providing a hearing conservation program for all active duty military workers may be a cost-effective intervention for the Department of Defense. [ABSTRACT FROM AUTHOR]

Summary: High‐throughput sequencing of the DNA/RNA encoding antibody heavy‐ and light‐chains is rapidly transforming the field of adaptive immunity. It can address key questions, including: (i) how the B‐cell repertoire differs in health and disease; and (ii) if it does differ, the point(s) in B‐cell development at which this occurs. The advent of technologies, such as whole‐genome sequencing, offers the chance to link abnormalities in the B‐cell antibody repertoire to specific genomic variants and polymorphisms. Here, we discuss the current research using B‐cell antibody repertoire sequencing in three polygenic autoimmune diseases where there is good evidence for a pathological role for B‐cells, namely systemic lupus erythematosus, multiple sclerosis and rheumatoid arthritis. These autoimmune diseases exhibit significantly skewed B‐cell receptor repertoires compared with healthy controls. Interestingly, some common repertoire defects are shared between diseases, such as elevated IGHV4‐34 gene usage. B‐cell clones have effectively been characterized and tracked between different tissues and blood in autoimmune disease. It has been hypothesized that these differences may signify differences in B‐cell tolerance; however, the mechanisms and implications of these defects are not clear. [ABSTRACT FROM AUTHOR]

Background: Several studies have compared the cost effectiveness of non-vitamin K antagonist oral anticoagulants (NOACs) and warfarin using results from clinical trials evaluating NOACs. However, the time in therapeutic range (TTR) of warfarin groups ranged across clinical trials, and all were below the therapeutic goal of 70%. We compared the cost effectiveness of edoxaban 60 mg, apixaban 5 mg, dabigatran 150 mg, dabigatran 110 mg, rivaroxaban 20 mg, and well-managed warfarin with a TTR of 70% in preventing stroke among patients with atrial fibrillation at high risk of bleeding.Methods: For the six treatments, we used a Markov state-transition model to quantify lifetime costs in $US and effectiveness in quality-adjusted life-years (QALYs). We simulated relative risk ratios of clinical events with each NOAC versus warfarin with a TTR of 70% using published regression models that predict how the incidence of thrombotic or hemorrhagic events changes for each unit change in TTR. We re-ran our analysis for two other estimates of TTR: 65 and 75%.Results: Treatment with edoxaban 60 mg cost $US127,520/QALY gained compared with warfarin with a TTR of 70% and cost $US41,860/QALY gained compared with warfarin with a TTR of 65%. However, warfarin with a TTR of 75% was more effective and less expensive than all NOACs. For three levels of TTR, apixaban 5 mg, dabigatran 150 mg, dabigatran 110 mg, and rivaroxaban 20 mg were dominated strategies.Conclusions: The comparative cost effectiveness of edoxaban and warfarin is highly sensitive to TTR. At the $US100,000/QALY willingness-to-pay threshold, our results suggest that warfarin is the most cost-effective treatment for patients who can achieve a TTR of 70%. [ABSTRACT FROM AUTHOR]

Background: Several operative techniques exist for Achilles tendinopathy. The purpose of our study was to compare the clinical and functional outcomes of flexor hallucis longus (FHL) transfer and V-Y advancement for the treatment of chronic insertional Achilles tendinopathy.Methods: Retrospective chart review from 2010 to 2016 of patients that underwent FHL transfer or V-Y advancement for chronic insertional Achilles tendinopathy. Outcome measures were compared for these two procedures.Results: In total, 46 patients (49 ankles) with a mean age of 55.0 (range 33-73) years. Mean follow-up time 44.7 +/- 25.5 months. FHL group had 21 patients (21 ankles) with 89% satisfaction, 14% complication rate, final VAS of 0.4, final VISA-A of 89.1, subjective strength improvement following surgery of 78%, and 94% would recommend the procedure. V-Y group had 25 patients (28 ankles) with 74% subjective satisfaction, 21% complication rate, final VAS of 1.4, final VISA-A of 78.4, subjective strength improvement following surgery of 67%, and 84% would recommend the procedure. There was no significant difference in any of the results rates between the two groups (p > .05).Conclusion: V-Y advancement is comparable to FHL transfer for the operative management of insertional Achilles tendinopathy. Though our results trend towards less satisfactory results following V-Y advancement, we found high satisfaction rates with similar functional outcomes and complication rates in both operative groups. We suggest considering V-Y advancement as a viable option for the primary treatment of chronic insertional Achilles tendinopathy in patients who may not be an ideal candidate for FHL transfer. [ABSTRACT FROM AUTHOR]

Background Annual influenza vaccination is a key to preventing widespread influenza infections. Recent reports of influenza vaccine effectiveness (VE) indicate that vaccination in prior years may reduce VE in the current season, suggesting vaccine interference. The purpose of this study is to evaluate the potential effect of repeat influenza vaccinations in the presence of vaccine interference. Methods Using literature-based parameters, an age-structured influenza equation-based transmission model was used to determine the optimal vaccination strategy, while considering the effect of varying levels of interference. Results The model shows that, even in the presence of vaccine interference, revaccination reduces the influenza attack rate and provides individual benefits. Specifically, annual vaccination is a favored strategy over vaccination in alternate years, as long as the level of residual protection is less than 58% or vaccine interference effect is minimal. Furthermore, the negative impact of vaccine interference may be offset by increased vaccine coverage levels. Conclusions Even in the presence of potential vaccine interference, our work provides a population-level perspective on the potential merits of repeated influenza vaccination. This is because repeat vaccination groups had lower attack rates than groups that omitted the second vaccination unless vaccine interference was at very high, perhaps implausible, levels. [ABSTRACT FROM AUTHOR]

The reactions of furan and 2-methylfuran with methylidyne CH (X²Π) radical were investigated at 298 K using synchrotron radiation produced at the Advanced Light Source of the Lawrence Berkeley National Laboratory. Reaction products were observed by multiplexed photoionization mass spectrometry and characterized based on their photoionization spectra and kinetic time traces. Primary products observed in furan + CH are 2,4-cyclopentadien-1-one (m/z = 80), 2-penten-4-ynal (m/z = 80), and vinylacetylene (m/z = 52). From 2-methylfuran + CH, 2-4-cyclopentadien-1-carbaldehyde (m/z = 94), 2,3,4-hexatrienal (m/z = 94), 1,3 cyclopentadiene (m/z = 66), 3-penten-1-yne (Z) (m/z = 66), and vinylacetylene (m/z = 52) are the primary products observed. Using potential energy surface scans, thermodynamically favorable reaction pathways are proposed. CH addition to the π-bonds in furan and 2-methylfuran rings was found to be the entrance channel that led to formation of all identified primary products. Both reactions follow patterns of H loss and CHO loss, as well as formation of cyclic and acyclic isomers. [ABSTRACT FROM AUTHOR]

Background. Limited information exists regarding the cost-effectiveness of rehabilitation strategies for individuals with knee osteoarthritis (OA). Objective. The study objective was to compare the cost-effectiveness of 4 different combinations of exercise, manual therapy, and booster sessions for individuals with knee OA. Design. This economic evaluation involved a cost-effectiveness analysis performed alongside a multicenter randomized controlled trial. Setting. The study took place in Pittsburgh, Pennsylvania; Salt Lake City, Utah; and San Antonio, Texas. Participants. The study participants were 300 individuals taking part in a randomized controlled trial investigating various physical therapy strategies for knee OA. Intervention. Participants were randomized into 4 treatment groups: exercise only (EX), exercise plus booster sessions (EX+B), exercise plus manual therapy (EX+MT), and exercise plus manual therapy and booster sessions (EX+MT+B). Measurements. For the 2-year base case scenario, a Markov model was constructed using the United States societal perspective and a 3% discount rate for costs and quality- adjusted life years (QALYs). Incremental cost-effectiveness ratios were calculated to compare differences in cost per QALY gained among the 4 treatment strategies. Results. In the 2-year analysis, booster strategies (EX+MT+B and EX+B) dominated no-booster strategies, with both lower health care costs and greater effectiveness. EX+ MT+B had the lowest total health care costs. EX+B cost $1061 more and gained 0.082 more QALYs than EX+MT+B, for an incremental cost-effectiveness ratio of $12,900/QALY gained. Limitations. The small number of total knee arthroplasty surgeries received by individuals in this study made the assessment of whether any particular strategy was more successful at delaying or preventing surgery in individuals with knee OA difficult. Conclusions. Spacing exercise-based physical therapy sessions over 12 months using periodic booster sessions was less costly and more effective over 2 years than strategies not containing booster sessions for individuals with knee OA. [ABSTRACT FROM AUTHOR]

The precise roles that the major proteolytic pathways play in the regulation of skeletal muscle mass remain incompletely understood, in part due to technical limitations associated with current techniques used to quantify muscle protein breakdown (MPB). We aimed to develop a method to assess MPB in cells, based on loss of puromycin labelling of translated polypeptide chains. Following an initial 24 h incubation period with puromycin (1 μM), loss of puromycin labelling from murine C2C12 myotubes was assessed over 48 h, both in the presence or absence of protein synthesis inhibitor cycloheximide (CHX). To validate the method, loss of puromycin labelling was determined from cells treated with selected compounds known to influence MPB (e.g. serum starvation, Dexamethasone (Dex), tumour necrosis factor alpha (TNF-α) and MG-132)). Reported established (static) markers of MPB were measured following each treatment. Loss of puromycin labelling from cells pre-incubated with puromycin was evident over a 48 h period, both with and without CHX. Treatment with Dex (−14 ± 2% vs. Ctl; P < 0.01), TNF-α (−20 ± 4% vs. Ctl; P < 0.001) and serum starvation (−14 ± 4% vs. Ctl; P < 0.01) caused a greater loss of puromycin labelling than untreated controls, while the proteasome inhibitor MG-132 caused a relatively lower loss of puromycin labelling (+15 ± 8% vs. Ctl; P < 0.05). Thus, we have developed a novel decorporation method for measuring global changes in MPB, validated in vitro using an established muscle cell line. It is anticipated this non isotopic-tracer alternative to measuring MPB will facilitate insight into the mechanisms that regulate muscle mass/MPB both in vitro , and perhaps, in vivo . [ABSTRACT FROM AUTHOR]

The deep and periventricular white matter is preferentially affected in several neurological disorders, including cerebral small vessel disease (SVD) and multiple sclerosis (MS), suggesting that common pathogenic mechanisms may be involved in this injury. Here we consider the potential pathogenic role of tissue hypoxia in lesion development, arising partly from the vascular anatomy of the affected white matter. Specifically, these regions are supplied by a sparse vasculature fed by long, narrow end arteries/arterioles that are vulnerable to oxygen desaturation if perfusion is reduced (as in SVD, MS and diabetes) or if the surrounding tissue is hypoxic (as in MS, at least). The oxygen crisis is exacerbated by a local preponderance of veins, as these can become highly desaturated 'sinks' for oxygen that deplete it from surrounding tissues. Additional haemodynamic deficiencies, including sluggish flow and impaired vasomotor reactivity and vessel compliance, further exacerbate oxygen insufficiency. The cells most vulnerable to hypoxic damage, including oligodendrocytes, die first, resulting in demyelination. Indeed, in preclinical models, demyelination is prevented if adequate oxygenation is maintained by raising inspired oxygen concentrations. In agreement with this interpretation, there is a predilection of lesions for the anterior and occipital horns of the lateral ventricles, namely regions located at arterial watersheds, or border zones, known to be especially susceptible to hypoperfusion and hypoxia. Finally, mitochondrial dysfunction due to genetic causes, as occurs in leucodystrophies or due to free radical damage, as occurs in MS, will compound any energy insufficiency resulting from hypoxia. Viewing lesion formation from the standpoint of tissue oxygenation not only reveals that lesion distribution is partly predictable, but may also inform new therapeutic strategies. [ABSTRACT FROM AUTHOR]

Purpose High-dose trivalent inactivated influenza vaccine (HD-IIV3) or recombinant trivalent influenza vaccine (RIV) may increase influenza vaccine effectiveness (VE) in adults with conditions that place them at high risk for influenza complications. This analysis models the public health impact and cost-effectiveness (CE) of these vaccines for 50–64 year-olds. Methods Markov model CE analysis compared 5 strategies in 50–64 year-olds: no vaccination; only standard-dose IIV3 offered (SD-IIV3 only), only quadrivalent influenza vaccine offered (SD-IIV4 only); high-risk patients receiving HD-IIV3, others receiving SD-IIV3 (HD-IIV3 & SD-IIV3); and high-risk patients receiving HD-IIV3, others receiving SD-IIV4 (HD-IIV3 & SD-IIV4). In a secondary analysis, RIV replaced HD-IIV3. Parameters were obtained from U.S. databases, the medical literature and extrapolations from VE estimates. Effectiveness was measured as 3%/year discounted quality adjusted life year (QALY) losses avoided. Results The least expensive strategy was SD-IIV3 only, with total costs of $99.84/person. The SD-IIV4 only strategy cost an additional $0.91/person, or $37,700/QALY gained. The HD-IIV3 & SD-IIV4 strategy cost $1.06 more than SD-IIV4 only, or $71,500/QALY gained. No vaccination and HD-IIV3 & SD-IIV3 strategies were dominated. Results were sensitive to influenza incidence, vaccine cost, standard-dose VE in the entire population and high-dose VE in high-risk patients. The CE of RIV for high-risk patients was dependent on as yet unknown parameter values. Conclusions Based on available data, using high-dose influenza vaccine or RIV in middle-aged, high-risk patients may be an economically favorable vaccination strategy with public health benefits. Clinical trials of these vaccines in this population may be warranted. [ABSTRACT FROM AUTHOR]

Introduction: Decreased live attenuated influenza vaccine (LAIV) effectiveness in the U.S. prompted the Advisory Committee on Immunization Practices in August 2016 to recommend against this vaccine's use. However, overall influenza uptake increases when LAIV is available and, unlike the U.S., LAIV has retained its effectiveness in other countries. These opposing countercurrents create a dilemma.Methods: To examine the potential consequences of the decision to not recommend LAIV, which may result in decreased influenza vaccination coverage in the U.S. population, a Markov decision analysis model was used to examine influenza vaccination options in U.S. children aged 2-8 years. Data were compiled and analyzed in 2016.Results: Using recently observed low LAIV effectiveness values, fewer influenza cases will occur if LAIV is not used compared with having LAIV as a vaccine option. However, having the option to use LAIV may be favored if LAIV effectiveness returns to prior levels or if the absence of vaccine choice substantially decreases overall vaccine uptake.Conclusions: Continued surveillance of LAIV effectiveness and influenza vaccine uptake is warranted, given their importance in influenza vaccination policy decisions. [ABSTRACT FROM AUTHOR]

The in vitro activity of apramycin was compared to that of amikacin, gentamicin, and tobramycin against multidrug-resistant, extensively drug-resistant, and pandrug-resistant Acinetobacter baumannii and Pseudomonas aeruginosa . Apramycin demonstrated an MIC 50 /MIC 90 of 8/32 μg/ml for A. baumannii and 16/32 μg/ml for P. aeruginosa . Only 2% of A. baumannii and P. aeruginosa had an MIC greater than an epidemiological cutoff value of 64 μg/ml. In contrast, the MIC 50 /MIC 90 for amikacin, gentamicin, and tobramycin were ≥64/>256 μg/ml for A. baumannii with 57%, 95%, and 74% of isolates demonstrating resistance, respectively, and the MIC 50 /MIC 90 were ≥8/256 μg/ml for P. aeruginosa with 27%, 50%, and 57% of strains demonstrating resistance, respectively. Apramycin appears to offer promising in vitro activity against highly resistant pathogens. It therefore may warrant further pre-clinical study to assess potential for repurposing as a human therapeutic and relevance as a scaffold for further medicinal chemistry exploration. [ABSTRACT FROM AUTHOR]

Offering a choice of influenza vaccine type may increase vaccine coverage and reduce disease burden, but it is more costly. This study calculated the public health impact and cost-effectiveness of 4 strategies: no choice, pediatric choice, adult choice, or choice for both age groups. Using agent-based modeling, individuals were simulated as they interacted with others, and influenza was tracked as it spread through a population in Washington, DC. Influenza vaccination coverage derived from data from the Centers for Disease Control and Prevention was increased by 6.5% (range, 3.25%-11.25%), reflecting changes due to vaccine choice. With moderate influenza infectivity, the number of cases averaged 1,117,285 for no choice, 1,083,126 for pediatric choice, 1,009,026 for adult choice, and 975,818 for choice for both age groups. Averted cases increased with increased coverage and were highest for the choice-for-both-age-groups strategy; adult choice also reduced cases in children. In cost-effectiveness analysis, choice for both age groups was dominant when choice increased vaccine coverage by ≥3.25%. Offering a choice of influenza vaccines, with reasonable resultant increases in coverage, decreased influenza cases by >100,000 with a favorable cost-effectiveness profile. Clinical trials testing the predictions made based on these simulation results and deliberation of policies and procedures to facilitate choice should be considered. [ABSTRACT FROM AUTHOR]

Objectives To estimate the cost-effectiveness of an intervention to increase pneumococcal, influenza, and pertussis-containing vaccine uptake in adults aged 65 and older in primary care practices. Design Markov decision analysis model, comparing the cost-effectiveness of the 4 Pillars Practice Transformation Program with no intervention. Setting Diverse primary care practices in two U.S. cities. Participants Clinical trial participants aged 65 and older. Measurements Quality-adjusted life years ( QALYs), public health outcomes, and costs. Vaccination rates and intervention costs were derived from a randomized controlled cluster trial. Other parameters were derived from the medical literature and Centers for Disease Control and Prevention data. All parameters were individually and simultaneously varied over their distributions. Results With the intervention program and extrapolating over 10 years, there would be approximately 60,920 fewer influenza cases, 2,031 fewer pertussis cases, and 13,842 fewer pneumococcal illnesses in adults aged 65 and older. Total per-person vaccination and illness costs with the intervention were $23.93 higher than without the intervention, with a concurrent increase in effectiveness of 0.0031 QALYs, or $7,635 per QALY gained. In sensitivity analyses, no individual parameter variation caused the intervention to cost more than $50,000 per QALY gained. Conclusions Implementing an intervention based on the 4 Pillars Practice Transformation Program is a cost-effective undertaking in primary care practices for individuals aged 65 and older, with predicted public health benefits. [ABSTRACT FROM AUTHOR]

ABSTRACT The first two studio albums from Suede (in America, 'The London Suede'), fruits of a collaboration between Bernard Butler and Brett Anderson, served as the erotically twisted underbelly of early 1990s Britpop, adding bizarre, seductive alternatives to the relatively normalised sexual experiences described in the songs of Pulp or Blur. A vital part of the band's aesthetics, Suede's harmonic progressions prove to be extremely dexterous, with sinuous voice leading and meandering key changes, often based on common-tone modulations and parsimony rather than any sense of dominant-to-tonic resolution. Using a range of songs from an extensive corpus study, I theorise the chord patterns that were to become recognisable Suede clichés (the ♭VI-V progressions and the III/♭VII/♭II dominant substitutes). In doing so I posit a sense of substituted functionality ( T, S or D) and a sense of flow in a D-wards or S-wards direction. Uncovering a strong predilection for the latter, I return to examine their earlier work in a new light with readings of 'Sleeping Pills' and 'Pantomime Horse' from their debut album, Suede. [ABSTRACT FROM AUTHOR]

This essay claims to discover the point at which Marx worked out his theory of surplus value sometime during the 10-year period between 1857 and the publication of Capital Vol. I in 1867. This, it is claimed, was due to his reading of a well-known pamphlet by an English Oxford University professor of political economy, Nassau W. Senior. Senior had claimed that capitalist manufacturers made all of their profit during the last hour of the then normal 12-hour working day. Marx knew that this was incorrect since, if Senior was right, the capitalists might just as well employ their workers for this 1 hour alone and not bother with the other 11 hours of the working day. The workers must then have been doing something else which was of value to the capitalists over and above merely producing their profit. This something else Marx realised was nothing less than the renewal of the worn out fabric of the capitalist enterprise and hence, along with this, the recreation year after year of the capitalists claims to be the legitimate owners of the enterprise. This essay then also claims to have identified two letters by Marx written just 11 months apart which might help to further date the discovery of surplus value, in the first of which, written in 1862, Marx gives Senior’s incorrect view of surplus value as profit and in the second of which, written in 1863, he gives his mature view of surplus value as profit plus the recreation of the capitalist mode of production itself. Having made this theoretical breakthrough by 1863, Marx finally stopped making notebooks and threw himself into the writing of Capital Vol. I in 1864, the year in which by chance Nassau Senior died. [ABSTRACT FROM AUTHOR]

Introduction The comparative cost-effectiveness of all oral anticoagulants approved up to date has not been evaluated from the US perspective. The objective of this study was to compare the cost-effectiveness of edoxaban 60 mg, apixaban 5 mg, dabigatran 150 mg, dabigatran 110 mg, rivaroxaban 20 mg and warfarin in stroke prevention in atrial fibrillation patients at high-risk of bleeding (defined as HAS-BLED score ≥ 3). Materials and methods We constructed a Markov state-transition model to evaluate lifetime costs and quality-adjusted life years (QALYs) with each of the six treatments from the perspective of US third-party payers. Probabilities of clinical events were obtained from the RE-LY, ROCKET-AF, ARISTOTLE and ENGAGE AF-TIMI trials; costs were derived from the Healthcare Cost and Utilization Project, and other studies. Because edoxaban is only indicated in patients with creatinine clearance ≤ 95 ml/min, we re-ran our analyses after excluding edoxaban from the analysis. Results Treatment with edoxaban 60 mg cost $77,565/QALY gained compared to warfarin, and apixaban 5 mg cost $108,631/QALY gained compared to edoxaban 60 mg. When edoxaban was not included in the analysis, treatment with apixaban 5 mg cost $84,128/QALY gained, compared to warfarin. Dabigatran 150 mg, dabigatran 110 mg and rivaroxaban 20 mg were dominated strategies. Conclusions For patients with creatinine clearance between 50 and 95 ml/min, apixaban 5 mg was the most cost-effective treatment for willingness-to-pay thresholds (WTP) above $115,000/QALY gained, and edoxaban 60 mg was cost-effective when the WTP was between $75,000 and $115,000/QALY gained. For patients with creatinine clearance > 95 ml/min, apixaban 5 mg was the most cost-effective treatment for WTP thresholds above $80,000/QALY gained. [ABSTRACT FROM AUTHOR]

T cell exhaustion represents a continuous spectrum of cellular dysfunction induced during chronic viral infection, facilitating viral persistence and associating with poor clinical outcome. Modulation of T cell exhaustion can restore function in exhausted CD8 T cells, promoting viral clearance. Exhaustion has also been implicated as playing an important role in anti-tumour responses, whereby exhausted tumour-infiltrating lymphocytes fail to control tumour progression. More recently exhaustion has been linked to long-term clinical outcome in multiple autoimmune diseases but, in contrast to cancer or infection, it is associated with a favourable clinical outcome characterised by fewer relapses. An increasing understanding of key inhibitory signals promoting exhaustion has led to advances in therapy for chronic infection and cancer. An increasing understanding of this biology may facilitate novel treatment approaches for autoimmunity through the therapeutic induction of exhaustion. [ABSTRACT FROM AUTHOR]

Background and aims: Atmospheric nitrogen (N) deposition can influence forest ecosystem N status, and the resilience of forests to the effects of N deposition depends on a number of co-occurring environmental factors that regulate N retention or loss. In this study, we test the idea that N deposition may have important and long-lasting impacts on patterns of N cycling by using field and laboratory techniques to assess N status in seven high-elevation Central Appalachian red spruce ( Picea rubens Sarg.) forests located at sites that historically received moderate to high inputs of N atmospheric deposition. Methods: During 2011 and 2012, we measured multiple indices of N availability (e.g. foliar/soil C:N and δN, resin ion-exchange, and N transformation rates) that integrate N cycling over seasonal to decadal time scales. Using a model selection approach, we compared the strength of the association between various environmental factors and temporally-integrated indices of N status in a series of regression models. Results: Site-level differences in the relative importance value of broadleaf deciduous (BD) trees consistently explained most of the observed variation in N status. Soil C:N was significantly lower for sites with greater BD importance ( R = 0.67-0.77), and there was a strong positive relationship between BD importance and soil δN content ( R = 0.64-0.85). Despite a four-fold difference in historic deposition across the seven forest sites, we did not observe any significant relationships between site N status and N deposition. Conclusions: These findings suggest that potential legacy effects of N deposition were obscured by the influence of BD importance on N status at these sites. Our results add strong support to the idea that predicting the resilience of forests to the effects of N deposition requires detailed knowledge on the contribution of tree species composition to soil N cycling and retention. [ABSTRACT FROM AUTHOR]

During acute viral infection CD8 T cells rapidly expand before contracting down to a persistent memory population that confers long‐lasting immunity. However when the antigen persists, such as during chronic viral infection, a dysfunctional process termed ‘exhaustion’ limits the antiviral response, facilitating ongoing viraemia and poor clinical outcome. CD8 T‐cell exhaustion was originally identified in lymphocytic choriomeningitis virus infection of mice; however, new evidence has shown that exhaustion is associated with the control of a wide range of human chronic inflammatory states, including chronic viral infection, autoimmunity and cancer. Consequently, an understanding of the mechanisms controlling exhaustion during chronic infection may also indicate new strategies for controlling other chronic inflammatory diseases. In particular, the success of immune checkpoint blockade as a form of cancer immunotherapy has prompted renewed efforts to understand how T‐cell immunity to chronic antigenic stimulation might similarly be measured or modulated in autoimmune diseases. Here we summarise the mechanisms controlling T‐cell exhaustion and how they relate to the control of autoimmune responses, providing a future perspective on measuring or manipulating exhaustion to personalise therapy. The November/December 2016 issue contains a Special Feature on Novel aspects of autoimmunity. Major scientific advances often arise at the interface of disciplines, or are made possible by transformative technological advances. Progress in our understanding of the basis of autoimmunity over recent years provides great examples of this, and we have selected four of these to highlight in this ICB Special Feature. Together these articles reveal how recent technological advances have revealed important mechanisms underlying autoimmune disease, mechanisms that can now be examined in humans as well as mouse models. Our increasing ability to conduct in‐depth studies in humans promises to continue to unlock the mysteries underlying autoimmunity, with inevitable benefits to patients with these diseases. Immunology & Cell Biology thanks the coordinators of this Special Feature ‐ Ken Smith and Arthur Kaser ‐ for their planning and input. [ABSTRACT FROM AUTHOR]

Objectives To compare the cost-effectiveness of four influenza vaccines available in the United States for persons aged 65 and older: trivalent inactivated influenza vaccine ( IIV3), quadrivalent inactivated influenza vaccine ( IIV4), a more-expensive high-dose IIV3, and a newly approved adjuvanted IIV3. Design Cost-effectiveness analysis using a Markov model and sensitivity analyses. Setting A hypothetical influenza vaccination season modeled according to possible U.S. influenza vaccination policies. Participants Hypothetical cohort of individuals aged 65 and older in the United States. Measurements Cost-effectiveness and public health benefits of available influenza vaccination strategies in U.S. elderly adults. Results IIV3 cost $3,690 per quality-adjusted life year ( QALY) gained, IIV4 cost $20,939 more than IIV3 per QALY gained, and high-dose IIV3 cost $31,214 more per QALY than IIV4. The model projected 83,775 fewer influenza cases and 980 fewer deaths with high-dose IIV3 than with the next most-effective vaccine: IIV4. In a probabilistic sensitivity analysis, high-dose IIV3 was the favored strategy if willingness to pay is $25,000 or more per QALY gained. Adjuvanted IIV3 cost-effectiveness depends on its price and effectiveness (neither yet determined in the United States) but could be favored if its relative effectiveness is 15% greater than that of IIV3. Conclusion From economic and public health standpoints, high-dose IIV3 for adults aged 65 years and older is likely to be favored over the other vaccines, based on currently available data. The cost-effectiveness of adjuvanted IIV3 should be reviewed after its effectiveness has been compared with that of other vaccines and its U.S. price is established. [ABSTRACT FROM AUTHOR]