Here, we review genomic target site selection during retroviral integration as a multistep process in which specific biases are introduced at each level. The first asymmetries are introduced when the virus takes a specific route into the nucleus. Next, by co‐opting distinct host cofactors, the integration machinery is guided to particular chromatin contexts. As the viral integrase captures a local target nucleosome, specific contacts introduce fine‐grained biases in the integration site distribution. In vivo, the established population of proviruses is subject (...) to both positive and negative selection, thereby continuously reshaping the integration site distribution. By affecting stochastic proviral expression as well as the mutagenic potential of the virus, integration site choice may be an inherent part of the evolutionary strategies used by different retroviruses to maximise reproductive success. (shrink)

Although the capacity to infect non-dividing cells is a hallmark of lentiviruses, nuclear import is still barely understood. More than 100 research papers have been dedicated to this topic during the last 15 years, yet, more questions have been raised than answers. The signal-facilitating translocation of the viral preintegration complex (PIC) through the nuclear pore complex (NPC) remains unknown. It is clear, however, that nuclear import is the result of a complex interplay between viral and cellular components. In this review, (...) we discuss the current knowledge on nuclear import. We focus on the controversies and pitfalls and discuss the interplay between virus and host. (shrink)

How do work motivations and sector perceptions differ between graduate students at prestigious Business Schools and Public Policy in Asia? Where do Asia’s future business and government leaders want to work, and why? To answer these questions, we compare Asian Master of Business Administration students with Master of Public Policy and Master of Public Administration students from three leading Schools based in Singapore through a survey study and a series of seven focus groups. Our findings indicate that work motivations, sector (...) perceptions, and career preferences differ between both groups but slightly less so than between their Western counterparts. Moreover, future Asian leaders equally value being successful while many view government as bureaucratic and prone to cronyism regardless of degree program and employment preference. We discuss how our findings may advance a more robust management and leadership research agenda for Asia. (shrink)

Throughout the career of the renowned sociologist Zygmunt Bauman, who passed away on January 9, 2017, a strand of the utopian impulse continued to manifest itself in his work. From his early socialist orientation to his later, more humanistic expressions and his analysis and critique of the liquid modern society, a development poignantly described by Michael Jacobsen in an article in this journal in 2004,1 Bauman's sociology was driven by seeking possibilities and alternatives to the society that he described and (...) explained, a quest for hope in the long term in a situation that justified pessimism in the short and middle term. His utopianism was not an attempt to sketch a blueprint of another society but an impulse... (shrink)

Abstract:Since Homeric times, psychotherapy has been an essential part of the medical act. Initially, the word of physicians had a magical character. Plato rationalizes this in many of his dialogues. In "Charmides," he dives deeper into this matter and proposes to apply it to every disease. Analysing this dialogue has fundamental consequences for psychotherapy: 1) Remedy and epodé (charm) must be applied in every doctor–patient relationship. 2) The body can only be healed if the soul is cured first by a (...) charm. Patients must "offer" their souls to the physician, which implies the need for confidence and the unavoidable asymmetry which characterize doctor–patient relationships. 3) The openness of the patient's soul to the physician and the physician's "beautiful speech" to the patient will enable the latter to reach the state of sophrosyne (temperance), the condition of the possibility of true health. In the discussion of the meaning of sophrosyne, Socrates questions every one of the disciples' propositions and concludes that the only thing one can be sure of is that sophrosyne is a way of searching for virtue (areté). Later, in Theaetetus, Plato adds another element: temperance is a homoiosis theó, that is, the assimilation of patient with God. With this, Plato seals the ethical character of psychotherapy forever. (shrink)

First, I would like to thank Dr. Phillips for his generous words about the potential interest of my work. He speaks about the fact that it is "insightful" and thought-provoking ("it offers us much to think about"). In his comment Dr. Phillips reviews the main moments of the evolution of treatment by words in the Greek world and he focuses on Plato's Dialogue Charmides, whose analysis is the center of my article. He even quotes some parts of the dialogue, which (...) I mention too, although in a different translation. He rightfully underlines the moment in which Socrates tells Charmides: "And the soul... my dear friend, is cured by means of certain charms, and these charms consist of beautiful words. It is a result of... Read More. (shrink)

There is a claim that clinical ethics support services (CESS) improve healthcare quality within healthcare organisations. However, there is lack of strong evidence supporting this claim. Rather, the current focus is on the quality of CESS themselves or on individual learning outcomes. In response, this article proposes a theoretical framework leading to empirical hypotheses that describe the relationship between a specific type of CESS, moral case deliberation and the quality of care at the organisational level. We combine insights from the (...) literature on CESS, organisational learning and quality improvement and argue that moral case deliberation causes healthcare professionals to acquire practical wisdom. At the organisational level, where improving quality is a continuous and collective endeavour, this practical wisdom can be aggregated into morisprudence, which is an ongoing formulation of moral judgements across cases encountered within the organisation. Focusing on the development of morisprudence enables refined scrutinisation of CESS-related quality claims. (shrink)

Se plantea la pregunta de si efectivamente el delirio es idéntico a la irracionalidad,como se ha postulado desde la Ilustración. Se hace una breve síntesis de la forma como ha sido concebida la locura desde la Antigüedad Clásica hasta nuestros días. De esta revisión es importante destacar cómo el carácter absoluto del "ego cogito" de Descartes hace impensable la locura como posibilidad humana y abre el camino a su conceptualización como enemiga de la razón, vale decir, como irracionalidad. Como argumento (...) en favor a la tesis contraria al racionalismo, se menciona el sentido biográfico de la locura, ejemplificado en figuras literarias, como Edipo, Ofelia y Don Quijote. Lo común a todas estas vidas que terminan en la locura es un afán desmedido por permanecer en lo ilusorio, en el autoocultamiento, de tal modo que cuando una circunstancia los obliga a ver su propia verdad transforman "una realidad imposible en una posible irrealidad", vale decir, enloquecen. Ahora bien, tanto en las figuras literarias como en los esquizofrénicos de la práctica diaria, encontramos que el desborde se produce no hacia lo irracional y dionisíaco, sino exactamente en la dirección opuesta: hacia lo apolíneo y racional. La tesis de que en la base de la locura habría un exceso y no una falta de racionalidad, tratamos de demostrarla a través del análisis de dos casos paradigmáticos, en los que aparece tematizada la entrega al dominio absoluto de la razón como capacidad analítica y sintética y a la razón como luz que saca a los objetos cognoscibles desde las sombras. El delirio sería, entonces, el producto de un imperio sin contrapeso de la razón,entendida ésta ya sea como "ratio" o como "logos". (shrink)

How do work motivations and sector perceptions differ between graduate students at prestigious Business Schools and Public Policy in Asia? Where do Asia’s future business and government leaders want to work, and why? To answer these questions, we compare Asian Master of Business Administration students with Master of Public Policy and Master of Public Administration students from three leading Schools based in Singapore through a survey study and a series of seven focus groups. Our findings indicate that work motivations, sector (...) perceptions, and career preferences differ between both groups but slightly less so than between their Western counterparts. Moreover, future Asian leaders equally value being successful while many view government as bureaucratic and prone to cronyism regardless of degree program and employment preference. We discuss how our findings may advance a more robust management and leadership research agenda for Asia. (shrink)

This review discusses Zygmunt Bauman’s Retrotopia, published shortly after the renowned sociologist’s death, in the light of his engagement with the thought of Pope Francis during the last years of his life. It traces some of the main themes of this engagement, and addresses its role and importance in the context of the book as well as in the aims of Bauman’s sociology as a whole. As the insecurities and anxieties of liquid modernity in our increasingly violent world lead many (...) to give up on the effort of building a better future and turn towards the ‘retrotopia’ of an ideal past, a crucial sign of hope is found in the words of Pope Francis. In his efforts as a sociologist, Zygmunt Bauman seeks to redirect our gaze to the future and to engage in dialogue, understood as the art of living together. (shrink)

Kolbe and de Melo-Martin (2023) provide a much needed reflection on the methods by which we measure moral distress. Their analysis, however, gives off the impression that the measures of moral dist...

We are grateful for the thoughtful replies to our article. 1 We are especially encouraged that all respondents agree that it is of value to develop a theoretical framework which helps to study how clinical ethics support services (CESS) induce individual and organisational learning. We have focused on the relations between moral case deliberation (MCD), organisational learning and quality improvement from a predominantly sociological perspective. The goal of our theoretical framework was to establish hypotheses which allow for empirical evaluation of (...) the relation between CESS and quality of care. Two major concerns seem to underly the commentaries: the framework (1) lacks a normative standard which allows for ethical justification of the outcome of repeated MCD, 2 and (2) the focus on morisprudence does not sufficiently emphasise the need for ‘structured, consistent, and facilitated processes for fair and robust moral case deliberation’. 3 In other words, it... (shrink)

There have been few empirical studies into what non-medical factors influence physicians and nurses when deciding about admission and discharge of ICU patients. Information about the attitudes of healthcare professionals about this process can be used to improve decision-making about resource allocation in intensive care. To provide insight into ethical problems that influence the ICU admission and discharge process, we aimed to identify and explore ethical dilemmas healthcare professionals are faced with.

This study reports on the hierarchy of organizational values in public and private sector organizations in Slovenia and the Netherlands. We surveyed 400 managers in Slovenia and 382 in the Netherlands using an identical questionnaire on the importance of a selection of values in everyday decision making. In Slovenia, impartiality, incorruptibility, and transparency were rated significantly higher in the public sector, while profitability, obedience, and reliability were rated more important in business organizations. In contrast, in the Netherlands, 11 values differed (...) significantly between the sectors. Thus, a greater value congruence exists between the sectors in Slovenia than in the Netherlands, with a larger “common core” of values in Slovenia (14) compared with the Netherlands (9), just as we hypothesized. Historical and cultural developments, such as the communist rule in Slovenia and the different influences of the Protestant work ethic in both countries, led to more similarities between business and government organizations in the “new” EU member state, Slovenia. (shrink)

This study reports on the hierarchy of organizational values in public and private sector organizations in Slovenia and the Netherlands. We surveyed 400 managers in Slovenia and 382 in the Netherlands using an identical questionnaire on the importance of a selection of values in everyday decision making. In Slovenia, impartiality, incorruptibility, and transparency were rated significantly higher in the public sector, while profitability, obedience, and reliability were rated more important in business organizations. In contrast, in the Netherlands, 11 values differed (...) significantly between the sectors. Thus, a greater value congruence exists between the sectors in Slovenia than in the Netherlands, with a larger “common core” of values in Slovenia (14) compared with the Netherlands (9), just as we hypothesized. Historical and cultural developments, such as the communist rule in Slovenia and the different influences of the Protestant work ethic in both countries, led to more similarities between business and government organizations in the “new” EU member state, Slovenia. (shrink)

PurposeAlthough an increasing body of literature suggests a relationship between brain irradiation and deterioration of neurocognitive function, it remains as the standard therapeutic and prophylactic modality in patients with brain tumors. This review was aimed to abstract and evaluate the prediction models for radiation-induced neurocognitive decline in patients with primary or secondary brain tumors.MethodsMEDLINE was searched on October 31, 2021 for publications containing relevant truncation and MeSH terms related to “radiotherapy,” “brain,” “prediction model,” and “neurocognitive impairments.” Risk of bias was (...) assessed using the Prediction model Risk Of Bias ASsessment Tool.ResultsOf 3,580 studies reviewed, 23 prediction models were identified. Age, tumor location, education level, baseline neurocognitive score, and radiation dose to the hippocampus were the most common predictors in the models. The Hopkins verbal learning and the trail making tests were the most frequent outcome assessment tools. All studies used regression as machine learning method. All models were judged to have a high risk of bias mainly due to issues in the analysis.ConclusionExisting models have limited quality and are at high risk of bias. Following recommendations are outlined in this review to improve future models: developing cognitive assessment instruments taking into account the peculiar traits of the different brain tumors and radiation modalities; adherence to model development and validation guidelines; careful choice of candidate predictors according to the literature and domain expert consensus; and considering radiation dose to brain substructures as they can provide important information on specific neurocognitive impairments. (shrink)

Dr. Otto Doerr-Zegers's article is so interesting and insightful that I have nothing critical to say about it. On the other hand, in finding Greek, mainly Platonic, origins for psychotherapy, he offers us much to think about. In this brief commentary I will attempt to draw out some of the implications of his analysis for contemporary psychotherapy.Doerr-Zegers's analysis begins with a reflection on Socrates' Maieutics, Socrates' invoking the midwife metaphor to convey his use of dialectics to bring forth the ignorance (...) of his interlocutor. Dörr recognizes that Maieutics is a kind of psychotherapy in that, like psychotherapy, it involves a "treatment by the word." He takes this verbal dimension of the treatment back... Read More. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:From the Patient's Perspective:Engaging With the OtherGiovanni Stanghellini*, MD, DPhil Honoris Causa (bio)Homo homini salusOne century after the first conference gathering first-generation clinical phenomenologists in Zurich in 1922, today's psychiatry is far from exploring phenomena from the patient's perspective—that is, "letting-be" the Other, and "giving or compromising"—that is, engaging with the Other (Doerr-Zegers, 2022).The motto of phenomenology has been since its beginning "To things themselves!". Edmund Husserl—the founder of (...) phenomenology in the field of philosophy—exhorted to go back to the things themselves, that is, to render self-evident in fully fledged intuitions that what is usually given in preformed abstractions like "concepts," "judgments," "truths," and so on (Husserl, 1970).Clinical phenomenology has taken up Husserl's motto and added another: "To understand is to cure." Put together, the result is: "To cure is to understand the things themselves." But what does exactly mean "To the things themselves"? And what does it mean "to understand"? What is the use of understanding in the clinical setting? And, ultimately, what does the "cure" consist of?What Are the "Things Themselves" in PsychiatryIn the clinical setting, the "things themselves" (Stanghellini & Ikkos, in press) are the patients' own experiences, that is the patient's psychopathological world as experienced in the first person's perspective—what clinical phenomenology calls the "phenomena." Clinical phenomenology's very conception of the object of psychiatry, that is the patient's abnormal experiences lived in the first-person perspective and embedded in anomalous forms of consciousness and existential patterns, has been vastly oversimplified by current assessment procedures (Stanghellini, 2013). Today, there is a risk that clinical blinkering results in clinicians being only able to view the symptoms relevant to diagnosis and classification and excludes the scrutiny of the diverse and varied nature of what is really there in the patient's experience—the essential prerequisite to understanding his/her condition (Stanghellini & Broome, 2014). This oversimplification has been reinforced by reliance on techniques (e.g., an emphasis on behavioral symptoms and on reliability rather than validity) that are unable to capture the subtle distinctions [End Page 287] in experience that constitute the essentials of the "things themselves" in psychopathology, and to acknowledge that what the patient manifests is not a series of mutually independent, isolated symptoms, but rather certain meaning-structures of interwoven experiences, beliefs, and actions, all permeated by biographical details (Nordengaard & Parnas, 2013).The Problem of the Causes and Meanings of PhenomenaTo go to the "things themselves"—to "let them be"—we should acknowledge that to understand is neither to interpret nor to explain. It is not to interpret, i.e. to attribute a meaning, that is, to replace a manifest content, considered superficial and misleading, with a latent content, considered profound and authentic. Psychiatry as a branch of bio-medicine (as it is known) does not principally deal with meanings, but certainly not because it aims to the "things themselves." Psychiatry first and foremost deals with the causes of phenomena, that is, it tries to explain (scire per causas)—not to understand. The dream of psychiatry is to trace the causes of the symptoms to neutralize the symptoms in statu nascendi. Psychiatry is (would like to be) a science of the mechanisms leading to the formation of mental symptoms.Compared with the intentions of psychiatry, the intentions of psychological hermeneutics, which deals with revealing the meanings of phenomena, may seem a relief and progress, at least if seen from a "humanitarian" angle. The dream of psychology—or at least of certain psychology (such as that of psychoanalytic inspiration)—is to bring to light the authentic meaning of a symptom. Hermeneutic psychology, for example, a psychoanalytic one, is (would like to be) an archaeology of the symptom, unearthing its profound significance.I am not arguing against explanations and interpretations per se, rather underscoring the way these may stand in the way of engaging with the patient in a third mode of approaching clinical phenomena, that is understanding. Both psychiatry's attempts at explanation and hermeneutic psychology's attempts at interpretation may suffocate... (shrink)