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This essay explores two interpretative strategies for understanding the point of Yoga. The first understands its point as a negative freedom from object-laden consciousness. The second understands the individual practices that comprise Yoga as the means by which the practitioner takes pure consciousness as her end. The second strategy allows us to see that prāṇāyāma points the way toward epistemic enhancement, much as Descartes' cogito does in his Meditations.

When Freudians use the term repression, they usually mean to suggest that a psychological state in one part of the analysands psychological apparatus is obstructed by some other part. A traumatic memory, for example, might be squirreled away in the unconscious where it can be forgotten, or perhaps a childish desire is held hostage in the id by the superego. There is a more common use of the term that does not require us to posit a complex psychological apparatus, but which nevertheless would have us recognize that a person can have desires that are in some way estranged, alienated, or external. In some cases, the desires might be so repressed that they remain nearly undetected. In other cases, the agent might be very aware of them, but nevertheless wish he was rid of them because he did not see himself as having a reason to satisfy them. When it is the case that the agent has no reason to satisfy the desire, then repression seems perfectly rational as a necessary defense against temptation. There are times, however, when in the grips of repression, an agent is wrong about whether his desire gives him a reason and will admit to the same once he has overcome the repression. It is cases like these that seem ripe with potential insight on the nature of reasons and normativity.

It is often assumed that the extent to which an agent's values contribute to his practical reasoning determines the degree of authenticity and self-control with which he acts. Some philosophers maintain that values track aspects of an agent's psychology like desires, while others maintain that they track principles of rationality. While there is disagreement over what counts as a value, most philosophers agree an agent's actions are authentically his own insofar as they express something about what he values and so long as whatever is being expressed governs or controls his actions. There is much to be said for this work, but suppose that an agent's values are precisely the obstacles that prevent authenticity and self-control. Two of the most widely received views, one broadly neo-Humean, the other broadly neo-Kantian, fail to give us purchase on cases like these. In chapters two and three I examine problems with these camps. In chapter four, I sketch out a positive account of authentic self-governance that considers the lessons learned from what I call \"conversion\" cases in which an agent brings his values in line with newly a recognized antecedent motivation (AM). I take being responsive to AMs to be an integral part of an agent's practical reasoning since action should reflect an agent's own experiences and perceptions of his own well-being. In chapter five, I argue that emotions are paradigmatic, motivational bootstraps. The view of the emotions that I sketch out is cognitivist in that I take emotions to be evaluative beliefs, but I also argue that they have relative strength. A strong emotion can provide reasons for altering one's motivational structure, even when that emotion conflicts with a number of ends that are harmonized and incorporated into an established practical identity. Chapter six responds to objections concerning the justificatory power of motivational bootstrapping and argues that emotions involve evaluative beliefs that require some amount of self-justification. They are beliefs about what we take to be important for our own well-being, and much of what is important to us is important simply because we take it to be.

This essay explores recent trends and major issues related to gay and lesbian philosophy in ethics (including issues concerning the morality of homosexuality, the natural function of sex, and outing and coming out); religion (covering past and present debates about the status of homosexuality and how biblical and qur'anic passages have been interpreted by both sides of the debate); the law (especially a discussion of the debates surroundings sodomy laws, same-sex marriage and its impact on transsexuals, and whether the law should be used to enforce morality); scientific research into the origins of homosexuality (including discussion of arguments against such research); and metaphysics (especially the question of whether homosexuality is socially constructed during particular times and in particular cultures, or whether sexual orientation is an essential trait cutting across times and cultures).

Phase 3 clinical studies showed non-inferiority of long-acting intramuscular cabotegravir and rilpivirine dosed every 4 weeks to oral antiretroviral therapy. Important phase 2 results of every 8 weeks dosing, and supportive modelling, underpin further evaluation of every 8 weeks dosing in this trial, which has the potential to offer greater convenience. Our objective was to compare the week 48 antiviral efficacy of cabotegravir plus rilpivirine long-acting dosed every 8 weeks with that of every 4 weeks dosing. ATLAS-2M is an ongoing, randomised, multicentre (13 countries; Australia, Argentina, Canada, France, Germany, Italy, Mexico, Russia, South Africa, South Korea, Spain, Sweden, and the USA), open-label, phase 3b, non-inferiority study of cabotegravir plus rilpivirine long-acting maintenance therapy administered intramuscularly every 8 weeks (cabotegravir 600 mg plus rilpivirine 900 mg) or every 4 weeks (cabotegravir 400 mg plus rilpivirine 600 mg) to treatment-experienced adults living with HIV-1. Eligible newly recruited individuals must have received an uninterrupted first or second oral standard-of-care regimen for at least 6 months without virological failure and be aged 18 years or older. Eligible participants from the ATLAS trial, from both the oral standard-of-care and long-acting groups, must have completed the 52-week comparative phase with an ATLAS-2M screening plasma HIV-1 RNA less than 50 copies per mL. Participants were randomly assigned 1:1 to receive cabotegravir plus rilpivirine long-acting every 8 weeks or every 4 weeks. The randomisation schedule was generated by means of the GlaxoSmithKline validated randomisation software RANDALL NG. The primary endpoint at week 48 was HIV-1 RNA ≥50 copies per mL (Snapshot, intention-to-treat exposed), with a non-inferiority margin of 4%. The trial is registered at ClinicalTrials.gov, NCT03299049 and is ongoing. Screening occurred between Oct 27, 2017, and May 31, 2018. Of 1149 individuals screened, 1045 participants were randomised to the every 8 weeks (n=522) or every 4 weeks (n=523) groups; 37% (n=391) transitioned from every 4 weeks cabotegravir plus rilpivirine long-acting in ATLAS. Median participant age was 42 years (IQR 34–50); 27% (n=280) female at birth; 73% (n=763) white race. Cabotegravir plus rilpivirine long-acting every 8 weeks was non-inferior to dosing every 4 weeks (HIV-1 RNA ≥50 copies per mL; 2% vs 1%) with an adjusted treatment difference of 0·8 (95% CI −0·6–2·2). There were eight (2%, every 8 weeks group) and two (<1%, every 4 weeks group) confirmed virological failures (two sequential measures ≥200 copies per mL). For the every 8 weeks group, five (63%) of eight had archived non-nucleoside reverse transcriptase inhibitor resistance-associated mutations to rilpivirine at baseline. The safety profile was similar between dosing groups, with 844 (81%) of 1045 participants having adverse events (excluding injection site reactions); no treatment-related deaths occurred. The efficacy and safety profiles of dosing every 8 weeks and dosing every 4 weeks were similar. These results support the use of cabotegravir plus rilpivirine long-acting administered every 2 months as a therapeutic option for people living with HIV-1. ViiV Healthcare and Janssen.

Increasing evidence shows that flaws in machine learning (ML) algorithm validation are an underestimated global problem. In biomedical image analysis, chosen performance metrics often do not reflect the domain interest, and thus fail to adequately measure scientific progress and hinder translation of ML techniques into practice. To overcome this, we created Metrics Reloaded, a comprehensive framework guiding researchers in the problem-aware selection of metrics. Developed by a large international consortium in a multistage Delphi process, it is based on the novel concept of a problem fingerprint—a structured representation of the given problem that captures all aspects that are relevant for metric selection, from the domain interest to the properties of the target structure(s), dataset and algorithm output. On the basis of the problem fingerprint, users are guided through the process of choosing and applying appropriate validation metrics while being made aware of potential pitfalls. Metrics Reloaded targets image analysis problems that can be interpreted as classification tasks at image, object or pixel level, namely image-level classification, object detection, semantic segmentation and instance segmentation tasks. To improve the user experience, we implemented the framework in the Metrics Reloaded online tool. Following the convergence of ML methodology across application domains, Metrics Reloaded fosters the convergence of validation methodology. Its applicability is demonstrated for various biomedical use cases. Metrics Reloaded is a comprehensive framework for guiding researchers in the problem-aware selection of metrics for common tasks in biomedical image analysis.

Every democratic society relies on deliberation and dialogue between social groups with varying perspectives to provide for the representation of the diverse members of the society. Meaningful deliberation is based on open access to information by individuals and free exchange of information between different social groups. Policy developments in the United States since September 2001, however, have altered the roles of information in many social contexts, with impacts on information access and information exchange between social groups. These changes have the potential to be of great consequence to social and political uses of information in society. Libraries, as established guardians of diverse perspectives of information, are in a unique position to protect and preserve information access and exchange in this new policy environment.