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With known cause of death (CoD), competing risk survival methods are applicable in estimating disease-specific survival. Relative survival analysis may be used to estimate disease-specific survival when cause of death is either unknown or subject to misspecification and not reliable for practical usage. This method is popular for population-based cancer survival studies using registry data and does not require CoD information. The standard estimator is the ratio of all-cause survival in the cancer cohort group to the known expected survival from a general reference population. Disease-specific death competes with other causes of mortality, potentially creating dependence among the CoD. The standard ratio estimate is only valid when death from disease and death from other causes are independent. To relax the independence assumption, we formulate dependence using a copula-based model. Likelihood-based parametric method is used to fit the distribution of disease-specific death without CoD information, where the copula is assumed known and the distribution of other cause of mortality is derived from the reference population. We propose a sensitivity analysis, where the analysis is conducted across a range of assumed dependence structures. We demonstrate the utility of our method through simulation studies and an application to French breast cancer data.

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Individual differences in cortical gray matter (GM) structure are associated with cognitive function and psychiatric disorders with developmental origins. Identifying when individual differences in cortical structure are established in childhood is critical for understanding the timing of abnormal cortical development associated with neuropsychiatric disorders.

The article offers information on Jamaican singer-songwriter Toots Hibbert, one of the pioneers of reggae, music genre that originated in Jamaica in the late 1960s. Topics discussed include his landmark album "Funky Kingston" made him a global superstar opening for the Who and the Eagles bands; his new album, "Got to Be Tough" co-produced by Drummer Zak Starkey for his Trojan Jamaica label; and also mentions that many Toots songs deals with karma and revenge.

ObjectiveAdmission to hospital over a weekend is associated with increased mortality, but the underlying causes of the weekend effect are poorly understood. We explore to what extent differences in emergency department (ED) admission and discharge processes, severity of illness and the seniority of the treating physician explain the weekend effect.MethodsWe analysed linked ED attendances to hospital admissions to Cambridge University Hospital over a 7-year period from 1 January 2007 to 31 December 2013, with 30-day in-hospital death as the primary outcome and discharge as a competing risk. The primary exposure was day of the week of arrival. Subdistribution hazards models controlled for multiple confounders, including physician seniority, calendar year, mode of arrival, triage category, referral from general practice, sex, arrival time, prior attendances and admissions, diagnosis group and age.Results229 401 patients made 424 845 ED attendances, of which 158 396 (37.3%) were admitted to the hospital. The case-mix of admitted patients was more ill at weekends: 2530 (6.4%) admitted at a weekend required immediate resuscitation compared with 6450 (5.4%) admitted on a weekday (p<0.0001). Senior doctors admitted 24.8% of patients on weekdays and 24.0% at weekends, but junior doctors admitted 61.7% of patients on weekdays and 44.2% at weekends. 3947 (3.3%) patients admitted on a weekday and 1454 (3.7%) patients admitted at a weekend died within 30 days. In the adjusted subdistribution hazards model, the HR of in-hospital death was 1.11 (95% CI 1.04 to 1.18) for weekend arrivals. After controlling for confounders, the in-hospital mortality of patients admitted by junior doctors was greater at the weekend (adjusted HR (aHR) 1.15, 95% CI 1.06 to 1.24). In-hospital mortality for patients admitted by senior doctors was not statistically different at the weekend (aHR 1.08, 95% CI 0.98 to 1.19).ConclusionsOur findings suggest that the weekend effect was driven by a higher proportion of admitted patients requiring immediate resuscitation at the weekend. Junior doctors admitted a lower proportion of relatively healthy patients at the weekend compared with the weekday, thus diluting the risk pool of weekday admissions and contributing to the weekend effect. Senior doctors’ admitting behaviour did not change at the weekend, and the corresponding weekend effect was reduced.

Carvedilol and metoprolol are the β-blockers most commonly prescribed to US hemodialysis patients, accounting for ∼80% of β-blocker prescriptions. Despite well-established pharmacologic and pharmacokinetic differences between the 2 medications, little is known about their relative safety and efficacy in the hemodialysis population.

IMPORTANCE: Prior studies demonstrate a high prevalence of burnout and depression among surgeons. Limited data exist regarding how these conditions are perceived by the surgical community. OBJECTIVES: To measure prevalence of burnout and depression among general surgery trainees and to characterize how residents and attendings perceive these conditions. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used unique, anonymous surveys for residents and attendings that were administered via a web-based platform from November 1, 2016, through March 31, 2017. All residents and attendings in the 6 general surgery training programs in North Carolina were invited to participate. MAIN OUTCOMES AND MEASURES: The prevalence of burnout and depression among residents was assessed using validated tools. Burnout was defined by high emotional exhaustion or depersonalization on the Maslach Burnout Inventory. Depression was defined by a score of 10 or greater on the Patient Health Questionnaire–9. Linear and logistic regression models were used to assess predictive factors for burnout and depression. Residents’ and attendings’ perceptions of these conditions were analyzed for significant similarities and differences. RESULTS: In this study, a total of 92 residents and 55 attendings responded. Fifty-eight of 77 residents with complete responses (75%) met criteria for burnout, and 30 of 76 (39%) met criteria for depression. Of those with burnout, 28 of 58 (48%) were at elevated risk of depression (P = .03). Nine of 77 residents (12%) had suicidal ideation in the past 2 weeks. Most residents (40 of 76 [53%]) correctly estimated that more than 50% of residents had burnout, whereas only 13 of 56 attendings (23%) correctly estimated this prevalence (P &lt; .001). Forty-two of 83 residents (51%) and 42 of 56 attendings (75%) underestimated the true prevalence of depression (P = .002). Sixty-six of 73 residents (90%) and 40 of 51 attendings (78%) identified the same top 3 barriers to seeking care for burnout: inability to take time off to seek treatment, avoidance or denial of the problem, and negative stigma toward those seeking care. CONCLUSIONS AND RELEVANCE: The prevalence of burnout and depression was high among general surgery residents in this study. Attendings and residents underestimated the prevalence of these conditions but acknowledged common barriers to seeking care. Discrepancies in actual and perceived levels of burnout and depression may hinder wellness interventions. Increasing understanding of these perceptions offers an opportunity to develop practical solutions.

The concept of competing risks is particularly relevant to survival analyses of diabetic ESRD given the high likelihood of death prior to ESRD. Approaches such as Kaplan-Meier curves and Cox regression models operate on the assumption that there are no competing risks for the event of interest, yielding uninterpretable and generally biased estimates in the presence of competing risks. The cumulative incidence function and Fine-Gray regression are more appropriate methodologies for survival analysis when competing risks are present. We present an example taken from the Action to Control Cardiovascular Risk in Diabetes, a randomized trial of people with type 2 diabetes at high risk for cardiovascular disease. Participants were stratified according to baseline markers of kidney disease: (1) no kidney disease; (2) low estimated glomerular filtration rate; (3) microalbuminuria alone; and (4) macroalbuminuria. The macroalbuminuria group had the highest risk for ESRD and demonstrated the most marked difference between the Kaplan-Meier and cumulative incidence estimator. Cox and Fine-Gray regression models yielded similar risk estimates for baseline characteristics, with the exception of diabetes duration, which was significant in the Cox but not Fine-Gray model. We underscore the importance of competing risk methods, particularly when the competing risk is common, as is the case in diabetic kidney disease.

ABSTRACTInstrumental variable (IV) methods are popular in non-experimental settings to estimate the causal effects of scientific interventions. These approaches allow for the consistent estimation of treatment effects even if major confounders are unavailable. There have been some extensions of IV methods to survival analysis recently. We specifically consider the two-step residual inclusion (2SRI) estimator proposed recently in the literature for the additive hazards regression model in this paper. Assuming linear structural equation models for the hazard function, we may attain a closed-form, two-stage estimator for the causal effect in the additive hazards model. The main contribution of this paper is to provide theoretical works for the 2SRI approach. The asymptotic properties of the estimators are rigorously established and the resulting inferences are shown to perform well in numerical studies.

The article discusses various aspects of the life of 75-year-old American singer and musician Brian Wilson who is known for his role as a member of The Beach Boys musical group, and it mentions concert tours and Wilson's battle with mental depression. The 50th anniversary of the music release "Pet Sounds" is addressed, along with the biographical film "Love & Mercy" and fellow musicians and vocalists such as Al Jardine and Mike Love.

ABSTRACTWe provide a detailed review for the statistical analysis of diagnostic accuracy in a multi-category classification task. For qualitative response variables with more than two categories, many traditional accuracy measures such as sensitivity, specificity and area under the ROC curve are no longer applicable. In recent literature, new diagnostic accuracy measures are introduced in medical research studies. In this paper, important statistical concepts for multi-category classification accuracy are reviewed and their utilities are demonstrated with real medical examples. We offer problem-based R code to illustrate how to perform these statistical computations step by step. We expect such analysis tools will become more familiar to practitioners and receive broader applications in biostatistics. Our program can be adapted to many classifiers among which logistic regression may be the most popular approach. We thus base our discussion and illustration completely on the logistic regression in this paper.

Natural killer (NK) cells are innate lymphocytes that aid in self-nonself discrimination by recognizing cells undergoing pathological alterations. The NKR-P1B inhibitory receptor recognizes Clr-b, a self-encoded marker of cell health downregulated during viral infection. Here, we show that Clr-b loss during mouse cytomegalovirus (MCMV) infection is predicated by a loss of Clr-b (Clec2d) promoter activity and nascent transcripts, driven in part by MCMV ie3(M122) activity. In contrast, uninfected bystander cells near MCMV-infected fibroblasts reciprocally upregulate Clr-b expression due to paracrine type-I interferon (IFN) signaling. Exposure of fibroblasts to type-I IFN augments Clec2dpromoter activity and nascent Clr-b transcripts, dependent upon a cluster of IRF3/7/9 motifs located ∼200 bp upstream of the transcriptional start site. Cells deficient in type-I IFN signaling components revealed IRF9 and STAT1 as key transcription factors involved in Clr-b upregulation. In chromatin immunoprecipitation experiments, the Clec2dIRF cluster recruited STAT2 upon IFN-α exposure, confirming the involvement of ISGF3 (IRF9/STAT1/STAT2) in positively regulating the Clec2dpromoter. These findings demonstrate that Clr-b is an IFN-stimulated gene on healthy bystander cells, in addition to a missing-self marker on MCMV-infected cells, and thereby enhances the dynamic range of innate self-nonself discrimination by NK cells.

Here we conducted a retrospective study to examine the risk of cardiovascular events (CVEs) relative to that of end-stage renal disease (ESRD) in patients with primary membranous nephropathy, in a discovery cohort of 404 patients. The cumulative incidence of CVEs was estimated in the setting of the competing risk of ESRD with risk factors for CVEs assessed by multivariable survival analysis. The observed cumulative incidences of CVEs were 4.4%, 5.4%, 8.2%, and 8.8% at 1, 2, 3, and 5 years respectively in the primary membranous nephropathy cohort. In the first 2 years after diagnosis, the risk for CVEs was similar to that of ESRD in the entire cohort, but exceeded it among patients with preserved renal function. Accounting for traditional risk factors and renal function, the severity of nephrosis at the time of the event (hazard ratio 2.1, 95% confidence interval 1.1 to 4.3) was a significant independent risk factor of CVEs. The incidence and risk factors of CVEs were affirmed in an external validation cohort of 557 patients with primary membranous nephropathy. Thus early in the course of disease, patients with primary membranous nephropathy have an increased risk of CVEs commensurate to, or exceeding that of ESRD. Hence, reduction of CVEs should be considered as a therapeutic outcome measure and focus of intervention in primary membranous nephropathy.

Supplemental Digital Content is available in the text.Competing risks occur frequently in the analysis of survival data. A competing risk is an event whose occurrence precludes the occurrence of the primary event of interest. In a study examining time to death attributable to cardiovascular causes, death attributable to noncardiovascular causes is a competing risk. When estimating the crude incidence of outcomes, analysts should use the cumulative incidence function, rather than the complement of the Kaplan-Meier survival function. The use of the Kaplan-Meier survival function results in estimates of incidence that are biased upward, regardless of whether the competing events are independent of one another. When fitting regression models in the presence of competing risks, researchers can choose from 2 different families of models: modeling the effect of covariates on the cause-specific hazard of the outcome or modeling the effect of covariates on the cumulative incidence function. The former allows one to estimate the effect of the covariates on the rate of occurrence of the outcome in those subjects who are currently event free. The latter allows one to estimate the effect of covariates on the absolute risk of the outcome over time. The former family of models may be better suited for addressing etiologic questions, whereas the latter model may be better suited for estimating a patient’s clinical prognosis. We illustrate the application of these methods by examining cause-specific mortality in patients hospitalized with heart failure. Statistical software code in both R and SAS is provided.

Few trials have examined long-term outcomes of advance care planning (ACP) interventions. We examined the efficacy of an ACP intervention on preparation for end-of-life decision making for dialysis patients and surrogates and for surrogates’ bereavement outcomes.

This study aims to estimate the incidence of first hip or clinical vertebral fracture or major osteoporotic (hip, clinical vertebral, proximal humerus, or wrist) fracture in postmenopausal women undergoing their first bone mineral density (BMD) test before age 65 years.

AbstractThe Net Reclassification Improvement (NRI) and the Integrated Discrimination Improvement (IDI) are used to evaluate the diagnostic accuracy improvement for biomarkers in a wide range of applications. Most applications for these reclassification metrics are confined to nested model comparison. We emphasize the important extensions of these metrics to the non-nested comparison. Non-nested models are important in practice, in particular, in high-dimensional data analysis and in sophisticated semiparametric modeling. We demonstrate that the assessment of accuracy improvement may follow the familiar NRI and IDI evaluation. While the statistical properties of the estimators for NRI and IDI have been well studied in the nested setting, one cannot always rely on these asymptotic results to implement the inference procedure for practical data, especially for testing the null hypothesis of no improvement, and these properties have not been established for the non-nested setting. We propose a generic bootstrap re-sampling procedure for the construction of confidence intervals and hypothesis tests. Extensive simulations and real biomedical data examples illustrate the applicability of the proposed inference methods for both nested and non-nested models.

Abstract: We consider the estimation of three-dimensional ROC surfaces for continuous tests given covariates. Three way ROC analysis is important in our motivating example where patients with Alzheimer’s disease are usually classified into three categories and should receive different category-specific medical treatment. There has been no discussion on how covariates affect the three way ROC analysis. We propose a regression framework induced from the relationship between test results and covariates. We consider several practical cases and the corresponding inference procedures. Simulations are conducted to validate our methodology. The application on the motivating example illustrates clearly the age and sex effects on the accuracy for Mini-Mental State Examination of Alzheimer’s disease.

Background Although acupuncture sensation(also known as de qi) is a cornerstone of traditional acupuncture therapy, most research has accepted the traditional method of defining acupuncture sensationonly through subjective patient reports rather than on any quantifiable physiological basis.Purpose To preliminarily investigate the frequency of key sensations experienced while needling to specific, quantifiable tissue levels (TLs) guided by ultrasound (US) imaging.Methods Five participants received needling at two acupuncture points and two control points at four TLs. US scans were used to determine when each TL was reached. Each volunteer completed 32 sets of modified Southampton Needle Sensation Questionnaires. Part one of the study tested sensations experienced at each TL and part two compared the effect of oscillation alone versus oscillation + rotation.Results In all volunteers, the frequency of pricking, sharp sensations was significantly greater in shallower TLs than deeper (p=0.007); the frequency of sensations described as deep, dull and heavy, as spreading, and as electric shocks was significantly greater in deeper TLs than shallower (p=0.002). Sensations experienced did not significantly differ between real and control points within each of three TLs (p>0.05) except TL 4 (p=0.006). The introduction of needle rotation significantly increased deep, dull, heavy sensations, but not pricking and sharp sensations; within each level, the spectrum of sensation experienced during both oscillation + rotation and oscillation alone did not significantly differ between acupuncture and control points.Conclusion The preliminary study indicates a strong connection between acupuncture sensation and both tissue depth and needle rotation. Furthermore, the new methodology has been proven feasible. A further study with an objective measurement is warranted.

ABSTRACTRapidly growing mycobacteria (RGM) are respiratory pathogens in patients with cystic fibrosis (CF), but detection generally requires specialized cultures for acid-fast bacilli (AFB; AFB cultures). We determined that RGM could be recovered from routine cultures of samples from patients with CF by extending incubation of the Burkholderia cepaciaselective agar (BCSA) from 5 to 14 days. To explore the impact of this modification, we compared results from routine and AFB cultures of samples from CF patients for 2 years before (4,212 samples by routine culture, 1,810 samples by AFB culture, 670 patients) and 2 years after (4,720 samples by routine culture, 2,179 samples by AFB culture, 695 patients) the change. Clinical relevance was assessed with samples from a subgroup of 340 patients followed regularly throughout both periods. Extending incubation of BCSA enhanced RGM recovery from routine cultures (0.7% before, 2.8% after; P< 0.001); recovery from AFB cultures was unchanged (5.5% before, 5.7% after). Estimates of RGM detection sensitivity by culture or patient-based methods ranged from ~65 to 75% for routine cultures (nonsignificantly lower than the ~80 to 85% for AFB cultures) and were adversely affected by coculture with mold or nonpseudomonal, nonfermenting Gram-negative rods. In the after period, 16 CF patients met the criteria for RGM infection by routine culture, including 4 who did not meet the criteria for RGM infection by AFB culture. We conclude that a simple methodological change enhanced recovery of RGM from routine cultures. The modified culture method could be utilized to improve screening for RGM in CF patients or as a simpler method to follow patients with known RGM infection. However, this method should be used cautiously in patients with certain coinfections.

Granulocyte-macrophage colony-stimulating factor (GM-CSF), which stimulates eosinophil recruitment, activation, and survival, is expressed by activated eosinophils. Although eosinophil recruitment and enhanced survival have been associated with nocturnal asthma (NA), the contribution of GM-CSF to NA is unknown.

Abstract: Objectives: To correlate radiographic findings of osteoarthritis on axial knee radiographs with arthroscopic findings of articular cartilage degeneration within the patellofemoral joint in patients with chronic knee pain.Subjects and methods: The study group consisted of 104 patients with osteoarthritis of the patellofemoral joint and 30 patients of similar age with no osteoarthritis of the patellofemoral joint. All patients in the study group had an axial radiograph of the knee performed prior to arthroscopic knee surgery. At the time of arthroscopy, each articular surface of the patellofemoral joint was graded using the Noyes classification system. Two radiologists retrospectively reviewed the knee radiographs to determine the presence of marginal osteophytes, joint-space narrowing, subchondral sclerosis, and subchondral cysts. The sensitivity and specificity of the various radiographic features of osteoarthritis for the detection of articular cartilage degeneration within the patellofemoral joint were determined.Results: The sensitivity of marginal osteophytes, joint-space narrowing, subchondral sclerosis, and subchondral cysts for the detection of articular cartilage degeneration within the patellofemoral joint was 73%, 37%, 4%, and 0% respectively. The specificity of marginal osteophytes, joint-space narrowing, subchondral sclerosis, and subchondral cysts for the detection of articular cartilage degeneration within the patellofemoral joint was 67%, 90%, 100%, and 100% respectively.Conclusion: Marginal osteophytes were the most sensitive radiographic feature for the detection of articular cartilage degeneration within the patellofemoral joint. Joint-space narrowing, subchondral sclerosis, and subchondral cysts were insensitive radiographic features of osteoarthritis, and rarely occurred in the absence of associated osteophyte formation.

Abstract

Interval mapping of quantitative trait loci from breeding experiments plays an important role in understanding the mechanisms of disease, both in humans and other organisms. Standard approaches to estimation involve parametric assumptions for the component distributions and may be sensitive to model misspecification. Some nonparametric tests have been studied. However, nonparametric estimation of the phenotypic distributions has not been considered in the genetics literature, even though such methods might provide essential nonparametric summaries for comparing different loci. We develop a sufficient condition for identifiability of the phenotypic distributions. Simple nonparametric estimators for the distributions are proposed for uncensored and right censored data. They have a closed form and their small and large sample properties are readily established. Their practical utility as numerical summaries which complement nonparametric tests is demonstrated on two recent genetics examples.

Abstract: Introduction: Standard therapy for recurrent or metastatic renal carcinoma includes the biologic response modifiers interferon-alpha (IFN-α) and interleukin-2 (IL-2). The response rate for both agents is modest and toxicity is significant. New agents are needed. Interferon-gamma (IFN-γ) is a type II interferon that demonstrated promising activity in renal carcinoma in early clinical trials. In vitro data suggested synergistic activity when IFN-γ was combined with IFN-α. The Eastern Cooperative Oncology Group conducted a randomized phase II trial to confirm the efficacy of IFN-γ as a single agent and to evaluate the efficacy and toxicity of IFN-γ in combination with IFN-α in the treatment of patients with metastatic or recurrent renal carcinomas. Materials and Methods: Ninety-five patients with recurrent or metastatic renal carcinoma were entered on trial. Patients were stratified based on risk assessment using the Elson method. Patients were randomly assigned to receive either IFN-γ 0.1 mg/m2 weekly (arm A) or IFN-γ 0.3 mg/m2 iv daily × 5 every 3 wk plus IFN-α 10 MU/m2 daily (arm B). Treatment efficacy was evaluated every 6 weeks. Results: Toxicity in the arm A was minimal. Significant toxicity was noted in arm B, with four cases of grade 4 neurotoxicity. No responses were seen with IFN-γ alone. Five responses (two CR and three PR) were noted in the combination arm for an overall response rate of 10%. Four of five responders were classified as “good risk.” Median survival for arm A was 7.0 mo vs 10.4 mo for arm B. Risk stratification was significant in arm B. Conclusion: IFN-γ at this dose and schedule failed to demonstrate activity in metastatic/recurrent renal carcinoma. The combination of IFN-γ and IFN-α demonstrated a response rate similar to IFN-α alone. There was no evidence of synergy between IFN-γ and IFN-α.

In many clinical studies, there are two dependent event times with one of the events being terminal, such as death, and the other being nonfatal, such as myocardial infarction or cancer relapse. Morbidity can be dependently censored by mortality, but not vice versa. Asymptotic theory is developed for simultaneous estimation of the marginal distribution functions in this semi-competing riskssetting. We specify the joint distribution of the event times in the upper wedge, where the nonfatal event happens before the terminal event, with the popular gamma frailty model. The estimators are based on an adaptation of the self-consistency principle. To study their properties, we employ a modification of the functional delta-method applied to Z-estimators. This approach to weak convergence leads naturally to asymptotic validity of both the nonparametric and multiplier bootstraps, facilitating inference in spite of the complexity of the limiting distribution.

ST. PIERRE SCHNEIDER, B., H. SANNES, J. FINE, and T. BEST. Desmin characteristics of CD11b-positive fibers after eccentric contractions. Med. Sci. Sports Exerc., Vol. 34, No. 2, pp. 274–281, 2002.

Summary. In this paper, a semiparametric bivariate linear regression model for survival and quality‐adjusted survival is investigated. Even with a parametric specification for the joint distribution, maximum likelihood is not applicable because of induced informative censoring. We propose inference procedures based on estimating functions. The estimators are consistent and asymptotically normal. Hypothesis tests and confidence intervals may be constructed with easy‐to‐implement resampling techniques. Simultaneous regression modeling of survival and quality‐adjusted survival has not been studied formally. Our methodology gives parameter estimates that are highly interpretable in the context of a cost‐effectiveness analysis. The usefulness of the proposal is illustrated with a breast cancer dataset.

Summary. During the interim stages of most large‐scale clinical trials, knowledge that a patient is alive or dead is usually not up‐to‐date. This is due to the pattern of patient visits to hospitals as well as the administrative set‐up used by the study to obtain information on vital status. On a two‐armed study, if the process of ascertaining vital status is not the same in both treatment groups, then the standard method of testing based on the logrank statistic may not be applicable. Instead, an ad hocmodification to the logrank test, which artificially truncates follow‐up prior to the time of analysis, is often used. These approaches have not been formally addressed in the literature. In the early stages of a clinical trial, severe bias or loss of power may result. For this situation, we propose a class of test statistics that extends the usual class of Ustatistics. Asymptotic normality is derived by reformulating the statistics in terms of counting processes and employing the theory of Ustatistics along with martingale techniques. For early interim analyses, a numerical study indicates that the new tests can be more powerful than the current practice when differential ascertainment is present. To illustrate the potential loss of information when lagging follow‐up to control for ascertainment delays, we reanalyze an AIDS clinical trial with the truncated logrank and the new statistics.

The article discusses the life and career of singer-songwriter Brian Wilson of the 1960's rock group The Beach Boys. Topics include his marriage to his wife Melinda in 1995 who was instrumental in getting Brian proper treatment for his mental illness after being overmedicated by his care taker and unconventional therapist Eugene Landry in the 1980's and early 1990's, the release of his 2015 music album "No Pier Pressure," and actors Paul Dano and John Cusack's portrayal of Wilson at two distinct periods of his life in the motion picture "Love & Mercy."

The article discusses singer-songwriter Brian Wilson of the 1960's music group The Beach Boys. Topics include the release of his 2015 album "No Pier Pressure," Wilson's marriage to wife Melinda in 1995 who was instrumental in removing Wilson's caretaker and unconventional therapist Eugene Landy from his life, getting Wilson proper treatment for his mental illness and orchestrating the comeback of his career, and actors Paul Dano and John Cusack's portrayal of Wilson in the motion picture "Love & Mercy."

An introduction is presented in which the editor discusses various articles published within the issue on topics like the meeting between musicians Taylor Swift and Paul McCartney, music, and a discussion between Mavis Staples and Chris Stapleton.