Lipophilicity of fentalogs: Comparison of experimental and computationally derived data

Although fentanyl and a small number of derivatives used for medical or veterinary procedures are well characterized, physiochemical properties have not been determined for many of the newer fentanyl analogs. Partition coefficients (Log P) were determined for 19 fentalogs using the shake-flask method and liquid chromatography–tandem mass spectrometry (LC–MS/MS). Experimentally determined partition coefficients were compared with computationally derived data using six independent software sources (ACD/LogP, LogKOWWIN v 1.69, miLogP 2.2, OsirisP, XLOGP 3.0, ALogPS 2.1). Fentalogs with a wide variety of structural modifications were intentionally selected, yielding Log P values ranging from 1.21 to 4.90. Comparison of experimental and computationally derived Log P values were highly correlated (R² 0.854–0.967). Overall, substructure-based modeling using fragmental methods or property-based topological approaches aligned more closely with experimentally determined Log P values. LC–MS/MS was also used to estimate pK_a values for fentalogs with no previously reported data. Lipophilicity and pK_a are important considerations for analytical detection and toxicological interpretation. In silico methods allow the determination of physicochemical information prior to certified reference materials being readily available for in vitro or in vivo studies. Computationally derived data can provide insight regarding physiochemical characteristics of future fentalogs and other classes of synthetic analogs that have yet to emerge.     

Longitudinal Intra-Individual and Inter-Individual Relations Between Cognitive and Emotional Self-Regulation Across Adolescence

Journal of Youth and Adolescence - Development in multidimensional self-regulation is important because it can be leveraged to enable healthy long-term adjustment. This four-wave study investigated...     

Effects of storage time on DNA profiling success from archived latent fingerprint samples using an optimised workflow

Due to recent improvements in forensic DNA testing kit sensitivity,there has been an increased demand in the criminal justice community to revisit past convictions or cold cases.Some of these cases have little biological evidence other than touch DNA in the form of archived latent fingerprint lift cards.In this study,a previously developed optimised workflow for this sample type was tested on aged fingerprints to determine if improved short tandem repeat(STR)profiles could be obtained.Two-year-old samples processed with the optimised workflow produced an average of approximately five more STR alleles per profile over the traditional method.The optimised workflow also produced detectable alleles in samples aged out to 28 years.Of the methods tested,the optimised workflow resulted in the most informative profiles from evidence samples more representative of the forensic need.This workflow is recommended for use with archived latent fingerprint samples,regardless of the archival time.     

Business conflict and international law: The political economy of copyright in the United States

The internet industry has emerged as an important economic and political actor, both within the United States and internationally. Internet companies depend on exceptions from copyright law in order to operate. As a result, internet companies have considerable incentive to try and influence international copyright law. However, the current literature has neglected the role of the internet industry, instead focusing on the influence of copyright owning media companies. This has largely homogenized the concerns of business interests, neglecting the interests of business actors which do not favor stricter copyright protection. By examining business conflict over recent copyright initiatives by the United States, this article criticizes the literature. It illustrates that the internet industry has been able to alter the negotiating preferences of the United States against the wishes of copyright owners. This argues against the homogenization of business interests regarding copyright while illustrating the importance of material over discursive factors in determining political outcomes.     

DNA Purification Cell Lysis and Wash Step Modifications for Low-Template DNA Sample Processing,

As DNA technology becomes increasingly sensitive, forensic laboratories are receiving more low-template DNA samples. These samples, already low in DNA content, become even more challenging to process as the available DNA becomes further reduced during the extraction step. In this study, two extraction modifications were tested to determine if the cause of DNA loss could be identified and mitigated. A double lysis technique was used to test for DNA loss in the sample collection substrate, and lysate eluates were re-extracted to determine DNA loss from inefficient binding to the silica column. Both modifications showed DNA was lost at these steps. However, resulting STR profiles from these samples had fewer peaks and lower peak heights when compared to samples processed with no extraction modifications. Overall, the potential benefits of adding these extraction modifications for low-template DNA sample processing are not enough to justify the risk associated with additional manipulation.     

Longitudinal Change in High-Cost Prosocial Behaviors of Defending and Including during the Transition to Adulthood

Despite high profile examples that are highlighted in the popular media, we know little about high-cost prosocial behaviors such as defending and including, and how these behaviors might change over time and vary by individual. Thus, this study explored defending and including behaviors across the transition to adulthood by assessing growth and profiles of these high-cost prosocial behaviors over a four-year time span. In addition the study explored gender, emotional (sympathy), cognitive (personal values), individual (self-esteem), and relational (maternal warmth) factors during adolescence that predicted profiles of defending and including during the transition to adulthood. Participants were 469 individuals (52% female, 70% European American) who participated at four time points (ages 18–21). Growth curve analyses showed that defending and including behaviors decreased slightly across the transition to adulthood and these behaviors tended to vary as a function of the target of the behavior. Latent profile analyses revealed three groups at each age, one with low, one with medium, and one with high levels of defending and including. The discussion focused on the prevalence and change in defending and including behaviors during the transition to adulthood, as well as the variability that exists in high-cost behavioral profiles.     

Decisional Capacity and Personality Disorders: Substantially Unable or Substantially Unwilling?

Capacity assessments are performed when there is suspicion that a person is unable to adequately care for their physical, medical, or financial well-being. The purpose of these assessments is to inform the legal system as to whether or not guardianship may be necessary. It is well established that certain mental illnesses, such as neurocognitive disorders (dementia) or psychotic disorders (like schizophrenia), may diminish capacity and, in some cases, lead to the need for establishment of a legal guardian. However, personality disorders are another common category of mental illness which may impair decision-making. There is very little information in the literature about how or why these disorders could impair capacity, and thus, it can often be difficult to discern whether clients with personality disorders are substantially unable to care for themselves—versus unwilling to act in a way contrary to their ingrained habits. We present a series of three cases in which clients are determined to lack capacity primarily mediated by a personality disorder diagnosis. They are demonstrated to have mild deficits in cognitive functioning, but they show impaired decision-making out of proportion to these deficits. In all three cases, it is apparent that the personality disorder is substantially impairing their ability to care for themselves. Discussion includes consideration for ways to incorporate evaluations of cognitive function, activities of daily living, and personality considerations into capacity assessments, and how to approach recommendations (such as guardianship vs. less restrictive option) based on both level and scope of impairment.     

Competitive intelligence and national intelligence estimates

National Intelligence Estimates are consensus-driven intelligence products. Yet there is considerable evidence supporting the use of competitive intelligence at every level of activity, including the presentation of finished products to consumers. We examine NIEs from two important periods in US foreign policy: the buildup in Vietnam and Gorbachev's reforms. We find in both cases alternate viewpoints were not presented in the US IC's premier intelligence product when such views could have made a difference. Consistent with contemporary findings in cognitive psychology, we argue the manner in which NIEs are structured and presented should be reformed to offer better decision support.     

Preferential trade agreements and power asymmetries: the case of technological protection measures in Australia

Since the 1980s states have sought to harmonise economic standards to aid the flow of goods, services and finance across borders. The founding agreements of the World Trade Organisation (WTO), for example, harmonised standards on services, intellectual property and investment. However, mutlilateral trade negotiations in the WTO have since stalled. In response, the United States (US) has engaged in forum shopping, using preferential trade agreements at the bilateral, regional and multinational level to harmonise international standards. This article argues that through forum shopping the US has been able to export standards that support the commercial interests of US-based industries more than they encourage economic exchange across borders. Furthermore, because power asymmetries are starker in preferential trade negotiations smaller and middle power states should not enter trade agreements, which include regulatory harmonisation. This is illustrated with the case of the US-Australia free trade agreement, looking specifically at a copyright standard known as technological protection measures (TPMs). It was clear before, during and after the agreement was signed that Australia’s existing standard on TPMs was more popular than the US-style standard. Nevertheless, a US-style standard is in effect domestically because of the trade agreement.     

Understanding Leadership in Public Administration: The Biographical Approach

This essay reviews the range of literature that uses a biographical approach to probe leadership in public administration. What are the variations in this approach? What have we learned? What should be done in the future? The genre is examined through several books and articles that have studied agency leaders and government departments.