The Psycho-Affective Echoes of Colonialism in Fieldwork Relations

This article describes the varieties of relations with African immigrant interviewees in Tuscany as experienced by a white male interviewer from the United States. Franz FANON\u27s discussion of the psycho-affective consequences of colonialism is vital for understanding how naïve and romantic notions of fieldwork relations are disingenuous, counter-productive and perhaps destructive in a neo-colonial landscape

Circulating adrenomedullin estimates survival and reversibility of organ failure in sepsis: the prospective observational multinational Adrenomedullin and Outcome in Sepsis and Septic Shock-1 (AdrenOSS-1) study

Background: Adrenomedullin (ADM) regulates vascular tone and endothelial permeability during sepsis. Levels of circulating biologically active ADM (bio-ADM) show an inverse relationship with blood pressure and a direct relationship with vasopressor requirement. In the present prospective observational multinational Adrenomedullin and Outcome in Sepsis and Septic Shock 1 (, AdrenOSS-1) study, we assessed relationships between circulating bio-ADM during the initial intensive care unit (ICU) stay and short-term outcome in order to eventually design a biomarker-guided randomized controlled trial. Methods: AdrenOSS-1 was a prospective observational multinational study. The primary outcome was 28-day mortality. Secondary outcomes included organ failure as defined by Sequential Organ Failure Assessment (SOFA) score, organ support with focus on vasopressor/inotropic use, and need for renal replacement therapy. AdrenOSS-1 included 583 patients admitted to the ICU with sepsis or septic shock. Results: Circulating bio-ADM levels were measured upon admission and at day 2. Median bio-ADM concentration upon admission was 80.5 pg/ml [IQR 41.5-148.1 pg/ml]. Initial SOFA score was 7 [IQR 5-10], and 28-day mortality was 22%. We found marked associations between bio-ADM upon admission and 28-day mortality (unadjusted standardized HR 2.3 [CI 1.9-2.9]; adjusted HR 1.6 [CI 1.1-2.5]) and between bio-ADM levels and SOFA score (p < 0.0001). Need of vasopressor/inotrope, renal replacement therapy, and positive fluid balance were more prevalent in patients with a bio-ADM > 70 pg/ml upon admission than in those with bio-ADM ≤ 70 pg/ml. In patients with bio-ADM > 70 pg/ml upon admission, decrease in bio-ADM below 70 pg/ml at day 2 was associated with recovery of organ function at day 7 and better 28-day outcome (9.5% mortality). By contrast, persistently elevated bio-ADM at day 2 was associated with prolonged organ dysfunction and high 28-day mortality (38.1% mortality, HR 4.9, 95% CI 2.5-9.8). Conclusions: AdrenOSS-1 shows that early levels and rapid changes in bio-ADM estimate short-term outcome in sepsis and septic shock. These data are the backbone of the design of the biomarker-guided AdrenOSS-2 trial. Trial registration: ClinicalTrials.gov, NCT02393781. Registered on March 19, 2015

Myocardial tagging by Cardiovascular Magnetic Resonance: evolution of techniques--pulse sequences, analysis algorithms, and applications

Cardiovascular magnetic resonance (CMR) tagging has been established as an essential technique for measuring regional myocardial function. It allows quantification of local intramyocardial motion measures, e.g. strain and strain rate. The invention of CMR tagging came in the late eighties, where the technique allowed for the first time for visualizing transmural myocardial movement without having to implant physical markers. This new idea opened the door for a series of developments and improvements that continue up to the present time. Different tagging techniques are currently available that are more extensive, improved, and sophisticated than they were twenty years ago. Each of these techniques has different versions for improved resolution, signal-to-noise ratio (SNR), scan time, anatomical coverage, three-dimensional capability, and image quality. The tagging techniques covered in this article can be broadly divided into two main categories: 1) Basic techniques, which include magnetization saturation, spatial modulation of magnetization (SPAMM), delay alternating with nutations for tailored excitation (DANTE), and complementary SPAMM (CSPAMM); and 2) Advanced techniques, which include harmonic phase (HARP), displacement encoding with stimulated echoes (DENSE), and strain encoding (SENC). Although most of these techniques were developed by separate groups and evolved from different backgrounds, they are in fact closely related to each other, and they can be interpreted from more than one perspective. Some of these techniques even followed parallel paths of developments, as illustrated in the article. As each technique has its own advantages, some efforts have been made to combine different techniques together for improved image quality or composite information acquisition. In this review, different developments in pulse sequences and related image processing techniques are described along with the necessities that led to their invention, which makes this article easy to read and the covered techniques easy to follow. Major studies that applied CMR tagging for studying myocardial mechanics are also summarized. Finally, the current article includes a plethora of ideas and techniques with over 300 references that motivate the reader to think about the future of CMR tagging

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Der psychoaffektive Widerhall des Kolonialismus in der Feldforschung

Este artículo describe las variedades de relaciones con africanos inmigrantes entrevistados en Toscana tales como fueron experimentadas, por un entrevistador blanco, varón de los Estados Unidos. La discusión de Franz FANON de las consecuencias psico-afectivas del colonialismo es vital para la comprensión acerca de cómo las nociones ingenuas y románticas de relaciones de trabajo en el campo no son ingenuas, contraproductivas y quizás destructivas en un horizonte neo-colonial.URN: http://nbn-resolving.de/urn:nbn:de:0114-fqs1401125This article describes the varieties of relations with African immigrant interviewees in Tuscany as experienced by a white male interviewer from the United States. Franz FANON's discussion of the psycho-affective consequences of colonialism is vital for understanding how naïve and romantic notions of fieldwork relations are disingenuous, counter-productive and perhaps destructive in a neo-colonial landscape.URN: http://nbn-resolving.de/urn:nbn:de:0114-fqs1401125In diesem Beitrag reflektiere ich Forschungserfahrungen im Rahmen von Interviews, die ich als weißer, nordamerikanischer Forscher mit afrikanischen Immigrant/innen in der Toskana geführt habe. Dabei war für mich das Konzept der psychoaffektiven Konsequenzen des Kolonialismus, wie von Franz FANON thematisiert, von herausragender Bedeutung, um zu verstehen, in welcher Weise naive und romantisierende Vorstellungen von Feldforschung in einem neokolonialen Kontext unaufrichtig bzw. deplatziert sein und im schlimmsten Falls auch destruktiv wirken können.URN: http://nbn-resolving.de/urn:nbn:de:0114-fqs140112

Curtis Jackson-Jacobs Fifty Years after "Becoming a Marihuana User"

1 Thanks to the following for comments on versions of this article and/or the interview: Jack Katz, Robert Emerson, Melvin Pollner, Jonathan Turner, Scott Jacobs, Sally Jackson, Robert Garot, and Simon Gottschalk; and, of course, to Diane Hagaman and to Howie for graciously opening their home and sharing the story

The IgH Eμ -MAR regions promote UNG-dependent error-prone repair to optimize somatic hypermutation

Abstract Two scaffold/matrix attachment regions (5’- and 3’- MARs Eμ ) flank the intronic core enhancer (c Eμ ) within the immunoglobulin heavy chain locus ( IgH ). Besides their conservation in mice and humans, the physiological role of MARs Eμ is still unclear and their involvement in somatic hypermutation (SHM) has never been deeply evaluated. By analysing a mouse model devoid of MARs Eμ , we observed an inverted substitution pattern: SHM being decreased upstream from cEμ and increased downstream of it. Strikingly, the SHM defect induced by MARs Eμ -deletion was accompanied by an increase of sense transcription of the IgH V region, excluding a direct transcription-coupled effect. Interestingly, by breeding to DNA repair-deficient backgrounds, we showed that the SHM defect, observed upstream from cEμ in this model, was not due to a decrease in AID deamination but rather the consequence of a defect in base excision repair-associated unfaithful repair process. Our study pointed out an unexpected “fence” function of MARs Eμ regions in limiting the error-prone repair machinery to the variable region of Ig gene loci

The IgH Eµ-MAR regions promote UNG-dependent error-prone repair to optimize somatic hypermutation

International audienceIntroduction: Two scaffold/matrix attachment regions (5'-and 3'-MARs Eμ) flank the intronic core enhancer (cEμ) within the immunoglobulin heavy chain locus (IgH). Besides their conservation in mice and humans, the physiological role of MARs Eμ is still unclear and their involvement in somatic hypermutation (SHM) has never been deeply evaluated.Methods: Our study analyzed SHM and its transcriptional control in a mouse model devoid of MARs Eμ , further combined to relevant models deficient for base excision repair and mismatch repair. Results: We observed an inverted substitution pattern in of MARs Eμ-deficient animals: SHM being decreased upstream from cEμ and increased downstream of it. Strikingly, the SHM defect induced by MARs Eμ-deletion was accompanied by an increase of sense transcription of the IgH V region, excluding a direct transcription-coupled effect. Interestingly, by breeding to DNA repair-deficient backgrounds, we showed that the SHM defect, observed upstream from cEμ in this model, was not due to a decrease in AID deamination but rather the consequence of a defect in base excision repair-associated unfaithful repair process.Discussion: Our study pointed out an unexpected "fence" function of MARs Eμ regions in limiting the error-prone repair machinery to the variable region of Ig gene loci