Importance of right heart catheterization in advanced heart failure management.

Patients with chronic congestive heart failure belong to a population with reduced quality of life, poor functional class, and increased risk of mortality and morbidity. In these patients, assessment of invasive hemodynamics both serves therapeutic purposes and is useful for stratification roles. The right heart catheterization has become a cornerstone diagnostic tool for patients in refractory heart failure or cardiogenic shock, as well as for the assessment of candidacy for heart replacement therapies, and the management of patients following mechanical circulatory assist device implantation and heart transplantation.

The Role of Perpetrator Tactics on Physical and Mental Health Outcomes Associated With Intimate Partner Sexual Violence: A Sex-Specific Analysis.

Intimate partner sexual violence (IPSV) is a concerning, yet understudied form of intimate partner violence. Using data from the National Intimate Partner and Sexual Violence Survey (NISVS), the current study builds on prior research to explore variation in tactics used to facilitate IPSV and their relationship with physical and mental health outcomes. Further, this study examines sex differences in both tactics and their associated health outcomes. Results show that all forms of IPSV are related to adverse health outcomes, with physical force being associated with the greatest number physical and mental health consequences. Women are more likely to report a greater number of negative physical health outcomes and posttraumatic stress disorder symptoms, while male IPSV victims are more likely to report overall worse mental health.

The Relationship between Adult Height and Blood Pressure.

BACKGROUND: Identification and modification of cardiovascular risk factors is paramount to reducing cardiovascular disease morbidity and mortality. Hypertension is a major risk factor for cardiovascular disease, but its association with height remains largely underrecognized. OBJECTIVES: The objective of this manuscript is to review the evidence examining the association between blood pressure and human stature and to summarize the plausible pathophysiological mechanisms behind such an association. METHODS: A systematic review of adult human height and its association with hypertension and coronary artery disease was undertaken. The literature evidence is summarized and tabulated, and an overview of the pathophysiological basis for this association is presented. RESULTS: Shorter arterial lengths found in shorter individuals may predispose to hypertension in a complex hemodynamic interplay, which is explained predominantly by summated arterial wave reflections and an elevated augmentation index. Our systemic review suggests that an inverse relationship between adult height and blood pressure exists. However, differences in the studied populations and heterogeneity in the methods applied across the various studies limit the generalizability of these findings and their clinical application. CONCLUSION: Physiological studies and epidemiological data suggest a potential inverse association between adult height and blood pressure. Further research is required to define the relationship more clearly between adult height and blood pressure and to assess whether antihypertensive therapeutic approaches and goals should be modified according to patients' heights.

Juveniles arrested for murder: A latent class analysis of male offenders.

Researchers and practitioners have a need for valid and generalizable typologies of juvenile homicide offenders (JHOs) to better understand the heterogeneous nature of JHOs, and use this knowledge to inform prevention efforts. Prior studies of JHOs have typically utilized a clinical approach, which is rich in data but based on small nonrepresentative samples, or relied on larger aggregate datasets which are more reliable but have few measures available. This study aimed to address these limitations by examining the latent heterogeneity (i.e. unapparent differences) in JHOs, their victims, and incident characteristics among more than 40,000 male JHOs arrested in the United States between 1976 and 2016 using latent class analysis, to allow for the objective identification of latent taxonomies. Six distinct subtypes of male JHOs are found in the analysis, which contributes to the theoretical and substantive knowledge base regarding JHOs, and may be used to develop and implement more effective interventions and violence prevention programs for these young offenders.

A theory of the piezoelectric slotted cylinder projector.

The energy method is used on the radial and circumferential displacement mode shapes of tapered piezoelectric slotted cylinder projectors to determine the electro-mechanical equivalent circuit parameters for the transducer. Results are determined for acoustically unloaded conditions for any degree of shell tapering. The resonance frequency (fr), mechanical quality factor (Qm), and electro-mechanical coupling factor (keff) are calculated and compared to measured data.

An examination of the effects of mental disorders as mitigating factors on capital sentencing outcomes.

Mentally ill and emotionally disturbed offenders comprise a significant component of those whose criminal conduct has swept them into the criminal justice system, including a subset who are tried and convicted of capital murder. The present study employs the population of capital cases advanced to penalty phase in the state of North Carolina (1990-2009) to examine whether presentation to the jury of the statutory mitigators of extreme mental and emotional disturbance and capacity impaired, and specific mental illness diagnoses, often referred to as mental disorders, at the sentencing phase mitigate against a sentence of death. Mental disorders included mood disorders, psychotic disorders, anxiety disorders, brain disorders, multiple mental illness diagnoses, learning disabilities, and personality disorders. Results from these 835 cases indicate that with the exception of one, the diagnosis of a learning disability, the capital jury's acceptance of various mental health conditions does not effectively mitigate against a capital sentence. In addition, jury rejection of a diagnosis of mental illness or the two mental health statutory mitigators, capacity impaired and extreme emotional disturbance, as a mitigating factor has a counter-mitigating effect in that it significantly increases the odds of a death penalty recommendation by about 85-200%.

CsF-Mediated in Situ Desilylation of TMS-Alkynes for Sonogashira Reaction.

A practical and mild set of conditions for the Sonogashira reaction utilizing CsF-mediated in situ TMS-alkyne desilylation followed by Sonogashira coupling has been developed for the synthesis of a variety of alkynyl benzenes and heteroarenes in good to excellent yields. This methodology demonstrates excellent functional group tolerance and simple purification, which allows large-scale industrial applications. This one-pot protocol enables a high-yielding Sonogashira coupling with volatile alkynes by avoiding challenging isolation of free alkynes.

"Blueprinting" thrombogenicity and antithrombotic drug response at the bedside in patients presenting emergently with symptoms of acute stroke.

Early assessment of thrombogenicity and antithrombotic drug effects may be important for therapeutic decision making in patients presenting with acute stroke. In this prospective, single center, pilot study, a bedside thrombelastography assay (TEG6s) was used to measure thrombogenicity and antithrombotic drug response in serial patients presenting emergently with symptoms of acute stroke (n = 90). TEG6s measures were compared against diagnosis obtained by NIH Stroke Scale/Score and imaging. Acute ischemic stroke (AIS) was diagnosed in 30 patients, intracerebral hemorrhage (ICH) in 19, transient ischemic attack (TIA) in 10 and stroke mimic (SM) in 31. Patients with AIS had a higher prevalence of A-Fib (33.3% vs. 11.6%, p = 0.01), and ACE inhibitor use (56.3% vs. 21.6%, p < 0.001) compared to combined non-AIS group. Time to initial clot formation (R) was shorter in AIS vs. TIA, ICH, and SM (p < 0.05). Comparing patients with AIS and combined non-AIS group the AUC for R was 0.83 (cut point of ≤ 4.8, sensitivity = 67%; specificity = 84%, p < 0.001). In AIS patients, 46% had suboptimal response (< 30% MAAA inhibition) to aspirin and 80% of patients on P2Y12 therapy had high platelet reactivity (> 50% ADP-induced platelet aggregation). Patients receiving tissue plasminogen activator had significant reduction in clot strength and near complete lysis at 30 min which normalized within 2 h after treatment (p < 0.001 for both). The rapid bedside measurement of thrombogenicity and antithrombotic drug effects is feasible in patients presenting with symptoms of acute stroke. Our preliminary data suggest that AIS is associated with faster ex-vivo clot formation, and poor antiplatelet response. Future study of the TEG6s to "blueprint" hemostasis is warranted in the stroke population.

Can empathy close the racial divide and gender gap in death penalty support?

Public opinion data indicate that the majority of US respondents support the death penalty. Research has consistently indicated, however, that Blacks and females are significantly less likely to support capital punishment than their White and male counterparts. Past research efforts attempting to account for these differences have, at best, only partially accounted for them: the racial divide and gender gap in death penalty support, while narrowed, remained evident. This study proposes that empathy, particularly ethnocultural empathy, may be a key explanatory correlate of death penalty support and that racial and gender differences in empathy may fully explain the observed racial and gender differences in death penalty support. This study uses three forms of empathy measures (cognitive, affective, and ethnocultural) to test this hypothesis using survey data from a sample of undergraduate students. Our results show that neither a variety of other "known correlates" of death penalty support nor cognitive or affective empathy scales were able to fully account for the observed racial difference in death penalty support. Ethnocultural empathy, however, was successful in reducing the effect of race on death penalty support to nonsignificance. To the best of our knowledge, this is the first study to have done so.

Application of design of experiments (DoE) optimization to the one-pot synthesis of 4,6-dihydropteridinones.

A design of experiments (DoE) analysis of a tandem SnAr-amidation cyclization reaction between 4-chloropyrimidin-5-amine and (S)-N-methylalanine to form (S)-7,8-dimethyl-7,8-dihydropteridin-6(5H)-one is reported. Five reaction variables were optimized using DoE and conversion was improved from 26% to 74%, with a significant reduction in reaction time while retaining high optical purity. The optimized conditions were applied to the synthesis of a wide variety of analogs and the expanded reaction substrate scope included a variety of amino acids and pyrimidines. Products were obtained in isolated yields up to 95% and enantiomeric excess as high as 98%.

The World Trade Center Health Program: Cancer screening and cancer care best practices.

The events of September 11, 2001 (9/11) exposed nearly a half million persons to many carcinogenic chemicals and dusts, as well as psychological and physical stressors. Subsequent epidemiologic studies of 9/11-exposed persons have suggested elevated risks for some cancers, e.g., prostate cancer, thyroid cancer, and melanoma. To detect cancer at an early stage, the US Preventive Services Task Force recommends screening certain asymptomatic persons for lung, colorectal, cervical and breast cancer, but not for other cancers. High quality cancer diagnosis and treatment guidelines are available from the National Comprehensive Cancer Network and the National Cancer Institute. For enrolled members, the WTC Health Program provides coverage for cancer screening and diagnosis, and covers medically necessary treatment costs for all types of cancer, assuming 9/11-exposure and minimum latency requirements are met, and a Program-affiliated physician attests that 9/11 exposures were substantially likely to have been a significant factor in aggravating, contributing to, or causing the enrolled WTC member's cancer.

The World Trade Center Health Program: an introduction to best practices.

More than 20 years have elapsed since the September 11, 2001 (9/11) terrorist attacks on the World Trade Center (WTC), Pentagon and at Shanksville, PA. Many persons continue to suffer a variety of physical and mental health conditions following their exposures to a mixture of incompletely characterized toxicants and psychological stressors at the terrorist attack sites. Primary care and specialized clinicians should ask patients who may have been present at any of the 9/11 sites about their 9/11 exposures, especially patients with cancer, respiratory symptoms, chronic rhinosinusitis, gastroesophageal reflux disease, psychiatric symptoms, and substance use disorders. Clinicians, especially those in the NY metropolitan area, should know how to evaluate, diagnose, and treat patients with conditions that could be associated with exposure to the 9/11 attacks and its aftermath. As such, this issue of Archives contains a series of updates to clinical best practices relevant to medical conditions whose treatment is covered by the WTC Health Program. This first paper in the 14-part series describes the purpose of this series, defines the WTC Health Program and its beneficiaries, and explains how relevant Clinical Practice Guidelines were identified. This paper also reminds readers that because physical and mental health conditions are often intertwined, a coordinated approach to care usually works best and referral to health centers affiliated with the WTC Health Program may be necessary, since all such Centers offer multidisciplinary care.

Ketoreductase-Catalyzed Access to Axially Chiral 2,6-Disubstituted Spiro[3.3]heptane Derivatives.

The desymmetrization of a prochiral 6-oxaspiro[3.3]heptane-2-carboxylic acid derivative via biocatalytic ketoreductase-mediated reduction has provided access to both enantiomers in high ee. The axially chiral alcohol was converted to the corresponding ester alcohol, amino acid, and amino alcohol building blocks while high enantiopurity was maintained.

Direct Oral Anticoagulants in the Treatment of Left Ventricular Thrombus: A Retrospective, Multicenter Study and Meta-Analysis of Existing Data.

AIM: To compare the safety and efficacy of direct oral anticoagulants (DOAC) relative to vitamin K antagonists (VKA) for the treatment of left ventricular thrombus (LVT). METHODS: This retrospective study enrolled patients diagnosed with LVT from 2014-2017. Patient characteristics and outcomes within 12 months of LVT diagnosis were recorded and analyzed. A meta-analysis was also performed by pooling our results with existing data in literature. RESULTS: 14 DOAC and 59 VKA patients were included. Baseline demographic and clinical characteristics were similar except for age. Although more strokes within 12 months occurred in VKA (15%) than in DOAC (0%) patients, this was not statistically significant (P = 0.189). There were no significant differences in outcomes between patients on DOAC and VKA for acute coronary syndrome (ACS) (7%, vs 3.4%, P = .477), LVT resolution (86% vs 76%, P = .499) or bleeding (14% vs 14%, P = 1) within 12 months. The meta-analysis included 6 studies (n = 408 for DOACs; n = 1207 for VKA). There were no significant differences between DOACs versus VKAs with respect to odds for unresolved thrombus (OR 0.61, 95% CI 0.26,1.41), embolic events (OR 1.24, 95% CI 0.90,1.69), embolic events and death (OR 1.10, 95% CI 0.84,1.45) or bleeding events (OR 1.13, 95% CI 0.74,1.72). CONCLUSIONS: Our study and meta-analysis suggest similar efficacy and safety of DOACs in the treatment of LVT compared to VKA. These findings underscore the need for a randomized controlled trial.

Discovery of Novel, Orally Bioavailable Pyrimidine Ether-Based Inhibitors of ELOVL1.

In our efforts to identify novel small molecule inhibitors for the treatment of adrenoleukodystrophy (ALD), we conducted a high-throughput radiometric screen for inhibitors of elongation of very long chain fatty acid 1 (ELOVL1) enzyme. We developed a series of highly potent, central nervous system (CNS)-penetrant pyrimidine ether-based compounds with favorable pharmacokinetics culminating in compound 22. Compound 22 is a selective inhibitor of ELOVL1, reducing C26:0 VLCFA synthesis in ALD patient fibroblasts and lymphocytes in vitro. Compound 22 reduced C26:0 lysophosphatidyl choline (LPC), a subtype of VLCFA, in the blood of ATP binding cassette transporter D1 (ABCD1) KO mice, a murine model of ALD to near wild-type levels. Compound 22 is a low-molecular-weight, potent ELOVL1 inhibitor that may serve as a useful tool for exploring therapeutic approaches to the treatment of ALD.

Racial Differences Among Juvenile Homicide Offenders: An Empirical Analysis of 37 Years of U.S. Arrest Data.

Homicides by juvenile offenders have been of great interest to the public and policymakers in the United States for four decades. Despite the concern over young murderers, many analyses have been limited to small clinical samples. Empirical studies using Supplementary Homicide Report (SHR) data, a national database maintained by the Federal Bureau of Investigation, have largely concentrated on analyzing basic victim, offender, and offense data or exploring gender differences. Racial differences, when explored with respect to juvenile homicide offenders (JHOs), largely have concentrated on White and Black offenders, given the low percentage involvement of American Indians and Alaskan Natives, and Asian and Pacific Islanders. This article used 37 years of SHR data (1976-2012; n = 52,916) to investigate differences between the four racial groups (White, Black, American Indian/Alaskan Native, and Asian American/Pacific Islander). This article focused on three questions: First, did the offender and offense characteristics of all JHOs arrested during the study period vary by race? Second, did the characteristics of victims, weapons used, crime circumstances, and offender count in incidents in which JHOs killed single victims differ across racial groups? Third, are offender, victim, and offense characteristics predictive of racial classification? Bivariate and multivariate analyses were conducted. The findings revealed more similarities than differences across the racial groups. Multinomial regression analyses revealed, however, that several variables were found to distinguish racial groups of JHOs in a predictive way: region, location, White victim, family victim, gun use, and homicide circumstance. Importantly, American Indian/Alaskan Native and Asian/Pacific Islander JHOs significantly differed from White and Black JHOs. In contrast to media depiction, gang-related homicides were significantly more likely to involve Asian/Pacific Islander juveniles than juveniles from the other racial groups. Implications of the findings and directions for future research are discussed.

A Social Learning Model of Antisocial Coaching Behavior.

Studies of antisocial behavior in sports are important, although most lack a theoretical framework. The current study examines the endorsement of antisocial behavior in a sample of coaches using social learning theory. This features a survey of 268 Head Coaches and Assistant Coaches in the Tehran Provincial League, Iran. Results indicate that differential association, differential reinforcement, definitions, and imitation have a significant impact on antisocial behavior, with differential association being the most influential construct. Higher education in coaches was associated with lower levels of antisocial behavior. This suggests that antisocial coaching behavior is learned in a similar manner to prosocial behaviors, and that desistance requires assessment of the learning process.

Social Learning Theory, Gender, and Intimate Partner Violent Victimization: A Structural Equations Approach.

The purpose of this study is to examine the applicability of Akers's Social Learning Theory (SLT) to explain intimate partner violence (IPV) victimization. In doing so, we draw on the Intergenerational Transmission of Violence Theory (IGT) to extend the scope of SLT to the explanation of victimization and for a consideration of uniquely gendered pathways in its causal structure. Using a structural equation modeling approach with self-report data from a sample of college students, the present study tests the extent to which SLT can effectively explain and predict IPV victimization and the degree, if any, to which the social learning model is gender invariant. Although our findings are largely supportive of SLT and, thus, affirm its extension to victimization as well as perpetration, the findings are also somewhat mixed. More significantly, in line with IGT literature, we find that the social learning process is not gender invariant. The implications of the latter are discussed.

Discovery and SAR of novel 4-thiazolyl-2-phenylaminopyrimidines as potent inhibitors of spleen tyrosine kinase (SYK).

A series of SYK inhibitors based on the phenylamino pyrimidine thiazole lead 4 were prepared and evaluated for biological activity. Lead optimization provided compounds with nanomolar K(i)'s against SYK and potent inhibition in mast cell degranulation assays.

Cardiac Sarcoidosis as an Uncommon Etiology for Posterior Circulation Stroke Presenting with Alexia without Agraphia.

Sarcoidosis is a systemic disease with cardiac involvement occurring in 20-50% of cases. Cardiogenic stroke caused by cardiac sarcoidosis, especially PCA infarction, is a rare clinical presentation that necessitates timely diagnosis and may warrant treatment prophylaxis against CVA. In this case report, we describe a 54-year-old Caucasian male presenting with left PCA stroke in the setting of cardiac and pulmonary sarcoidosis, and hypertension. His presenting symptoms included right partial hemianopia, difficulty with naming, memory, and recall, and alexia without agraphia. Cardiogenic stroke is an uncommon manifestation of cardiac sarcoidosis, and given the disabling nature of these sequelae, the importance of early diagnosis and prevention with anticoagulation is crucial to prevent morbidity and mortality.