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Optogenetic techniques provide genetically targeted, spatially and temporally precise approaches to correlate cellular activities and physiological outcomes. In the nervous system, G protein-coupled receptors (GPCRs) have essential neuromodulatory functions through binding extracellular ligands to induce intracellular signaling cascades. In this work, we develop and validate an optogenetic tool that disrupts Gαq signaling through membrane recruitment of a minimal regulator of G protein signaling (RGS) domain. This approach, Photo-induced Gα Modulator--Inhibition of Gαq (PiGM-Iq), exhibited potent and selective inhibition of Gαq signaling. Using PiGM-Iq we alter the behavior of Caenorhabditis elegans and Drosophila with outcomes consistent with GPCR-Gαq disruption. PiGM-Iq changes axon guidance in cultured dorsal root ganglia neurons in response to serotonin. PiGM-Iq activation leads to developmental deficits in zebrafish embryos and larvae resulting in altered neuronal wiring and behavior. Furthermore, by altering the minimal RGS domain, we show that this approach is amenable to Gαi signaling. Our unique and robust optogenetic Gα inhibiting approaches complement existing neurobiological tools and can be used to investigate the functional effects neuromodulators that signal through GPCR and trimeric G proteins. [ABSTRACT FROM AUTHOR]

Prolonged exposure therapy (PE) is a well‐established first‐line treatment for posttraumatic stress disorder (PTSD) that is based on emotional processing theory. PE has been rigorously evaluated and tested in a large number of clinical trials in many countries covering a wide range of trauma populations. In this review, we summarize the evidence base supporting the efficacy of PE across populations, including adults with sexual assault–related PTSD and mixed trauma–related PTSD, military populations, and adolescents. We highlight important strengths and gaps in the research on PE with individuals from marginalized communities. We discuss the efficacy of PE on associated psychopathology and in the presence of the most commonly comorbid conditions, either alone or integrated with other treatments. In addition, we provide an overview of research examining strategies to augment PE. Much of this work remains preliminary, but numerous trials have tested PE in combination with other psychological or pharmacological approaches, interventions to facilitate extinction learning, and behavioral approaches, in the hopes of further increasing the efficiency and efficacy of PE. There are now several trials testing PE in novel formats that may have advantages over standard in‐person PE, such as lower dropout and increased scalability. We examine this recent work on new models of delivering PE, including massed treatment, telehealth, and brief adaptations for primary care, all of which have the potential to increase access to PE. Finally, we highlight several promising areas for future research. [ABSTRACT FROM AUTHOR]

Advancements in photonics technologies have significantly enhanced their capability to facilitate experiments involving quantum light, even at room temperature. Nevertheless, fully integrating photonic chips that include quantum light sources, effective manipulation and transport of light minimizing losses, and appropriate detection systems remains an ongoing challenge. Topological photonic systems have emerged as promising platforms to protect quantum light properties during propagation, beyond merely preserving light intensity. In this work, we delve into the dynamics of non-classical light traversing a Su-Schrieffer-Heeger photonic lattice with topological domain walls. Our focus centers on how topology influences the quantum properties of light as it moves across the array. By precisely adjusting the spacing between waveguides, we achieve dynamic repositioning and interaction of domain walls, facilitating effective beam-splitting operations. Our findings demonstrate high-fidelity transport of non-classical light across the lattice, replicating known results that are now safeguarded by the topology of the system. This protection is especially beneficial for quantum communication protocols with continuous variable states. Our study enhances the understanding of light dynamics in topological photonic systems and paves the way for high-fidelity, topology-protected quantum communication. [ABSTRACT FROM AUTHOR]

Background: Early access program (formerly cohort Temporary Authorization for Use) was granted for trastuzumab deruxtecan (T‐DXd) in France based on DESTINY‐Breast01 trial which demonstrated its efficacy and safety in HER2‐positive metastatic/unresectable breast cancer after ≥2 anti‐HER2‐based regimens received at metastatic stage. Method s : This multicenter real‐world early access program included HER2‐positive metastatic/unresectable breast patients pretreated with at least two lines of anti‐HER2 regimens who received T‐DXd 5.4 mg/kg intravenously in monotherapy every 3 weeks. Results: Four hundred and fifty‐nine patients (median age, 58 years; hormone receptor‐positive, 67%; brain metastases, 28.1%) received T‐DXd. Before inclusion, 81.7% of patients had radiation therapy and 76.5% had undergone surgery. Median number of prior metastatic treatment lines was four (range, 2–22); 99.8% patients had received trastuzumab, 94.8% trastuzumab emtansine and 79.3% pertuzumab. Follow‐up was performed from September 30, 2020 to March 30, 2021; when the early access program stopped, the median duration of T‐DXd treatment was 3.4 (range, 0–7.8) months. In 160 patients with available tumor assessment, objective response rate was 56.7% and 12.1% had progression. In 57 patients with available brain tumor assessment, complete or partial intracranial response was reported for 35.7% patients and 5.4% had progression. A total of 17 (3.7%) patients with interstitial lung disease (ILD) was reported with no cases of ILD‐related death. Conclusions: In this early access program in patients with heavily pretreated HER2‐positive metastatic/unresectable breast cancer, T‐DXd had antitumor activity with a similar response to that reported in previous clinical studies. T‐DXd was well tolerated and no new safety signals were observed. [ABSTRACT FROM AUTHOR]

Pericytes play several important functions in the neurovascular unit including contractile control of capillaries, maintenance of the BBB, regulation of angiogenesis, and neuroinflammation. There exists a continuum of pericyte subtypes along the vascular tree which exhibit both morphological and transcriptomic differences. While different functions have been associated with the pericyte subtypes in vivo, numerous recent publications have used a primary human brain vascular pericytes (HBVP) cell line where this pericyte heterogeneity has not been considered. Here, we used primary HBVP cultures, high-definition imaging, cell motility tracking, and immunocytochemistry to characterise morphology, protein expression, and contractile behaviour to determine whether heterogeneity of pericytes also exists in cultures. We identified five distinct morphological subtypes that were defined using both qualitative criteria and quantitative shape analysis. The proportion of each subtype present within the culture changed as passage number increased, but pericytes did not change morphological subtype over short time periods. The rate and extent of cellular and membrane motility differed across the subtypes. Immunocytochemistry revealed differential expression of alpha-smooth muscle actin (αSMA) across subtypes. αSMA is essential for cell contractility, and consequently, only subtypes with high αSMA expression contracted in response to physiological vasoconstrictors endothelin-1 (ET1) and noradrenaline (NA). We conclude that there are distinct morphological subtypes in HBVP culture, which display different behaviours. This has significance for the use of HBVP when modelling pericyte physiology in vitro where relevance to in vivo pericyte subtypes along the vascular tree must be considered. [ABSTRACT FROM AUTHOR]

Copyright of Studia Politicae is the property of Studia Politicae and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

We assessed the interrater reliability, convergent validity, and discriminant validity of the Self-Injurious Thoughts and Behaviors Interview-Short Form (SITBI-SF) in a sample of 1,944 active duty service members and veterans seeking services for posttraumatic stress disorder (PTSD) and related conditions. The SITBI-SF demonstrated high interrater reliability and good convergent and discriminant validity. The measurement properties of the SITBI-SF were comparable across service members and veterans. Approximately 8% of participants who denied a history of suicidal ideation on the SITBI-SF reported suicidal ideation on a separate self-report questionnaire (i.e., discordant responders). Discordant responders reported significantly higher levels of PTSD symptoms than those who denied suicidal ideation on both response formats. Findings suggest that the SITBI-SF is a reliable and valid interview-based measure of suicide-related thoughts and behaviors for use with military service members and veterans. Suicide risk assessment might be optimized if the SITBI-SF interview is combined with a self-report measure of related constructs. [ABSTRACT FROM AUTHOR]

Purpose: To compare retinal changes in young adults with previous SARS-CoV-2 infection with healthy young controls using optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA). Methods: This prospective single-center study was conducted at the University Hospital of Zurich, Zurich, Switzerland. Participants were imaged from May to November 2021 using the SOLIX device (Visionix International SAS, Pont-de-l'Arche, France). We performed 12 mm × 12 mm, 6.4 mm × 6.4 mm, 6 mm × 6 mm and 3 mm × 3 mm OCT and OCTA scans, as well as fundus photography of each participant's eyes. Results: In total, 466 participants were imaged. Of these, 233 were healthy controls with negative RT-PCR tests for SARS-CoV-2, 168 were young adults who had a SARS-CoV-2 infection at least 180 days previously, 19 were participants who had a SARS-CoV-2 infection < 180 days previously, and 46 were participants with asymptomatic SARS-CoV-2 infection (i.e., serologically positive but with no symptoms). Compared with healthy controls, statistically significant differences were found for OCTA recordings of the optic disc for the whole image (WI) and WI capillary vessel density, with both being higher in the SARS-CoV-2 group. Conclusion: Statistically significant results were only observed for selected variables, and in parts, only unilaterally, with relatively large p values (p = 0.02–0.03). Thus, we did not interpret these as clinically significant, leading to the conclusion that young and otherwise healthy individuals (mainly men) seem to recover from mild COVID-19 infections with no ophthalmological residues. [ABSTRACT FROM AUTHOR]

Objective: Previous research with civilian populations has found strong associations between fibromyalgia (FM) and posttraumatic stress disorder (PTSD). We undertook this study to investigate the prevalence of FM in military service members with and without PTSD. Methods: Participants were active duty military personnel recruited into either an epidemiologic cohort study of service members before a military deployment or 1 of 3 PTSD treatment trials. Instruments used to document FM and PTSD included the PTSD Checklist–Stressor‐Specific Version, the PTSD Symptom Scale‐Interview, and the 2012 American College of Rheumatology FM questionnaire. Results: Across the 4 studies, 4,376 subjects completed surveys. The prevalence of FM was 2.9% in the predeployment cohort, and the prevalence was significantly higher in individuals with PTSD (10.8%) compared with those without PTSD (0.8%). In the treatment trials, all of the participants met criteria for PTSD before starting treatment, and the prevalence of FM was 39.7%. Conclusion: The prevalence of FM in active duty service members preparing to deploy is similar to that reported for the general population of the US but is higher than expected for a predominantly male cohort. Furthermore, the prevalence of FM was significantly higher in service members with comorbid PTSD and was highest among those seeking treatment for PTSD. Further investigation is needed to determine the factors linking PTSD and FM. [ABSTRACT FROM AUTHOR]

Purpose: To assess the usability and image quality of a smartphone adapter for direct slit lamp imaging. Methods: A single-center, prospective, clinical study conducted in the Department of Ophthalmology at the University Hospital Zurich, Switzerland. The smartphone group consisted of 26 medical staff (consultants, residents, and students). The control group consisted of one ophthalmic photographer. Both groups took images of the anterior and the posterior eye segment of the same proband. The control group used professional photography equipment. The participant group used an Apple iPhone 11 mounted on a slit lamp via a removable SlitREC smartphone adapter (Custom Surgical GmbH, Munich, Germany). The image quality was graded independently by two blinded ophthalmologists on a scale from 0 (low) to 10 (high quality). Images with a score ≥ 7.0/10 were considered as good as the reference images. The acquisition time was measured. A questionnaire on usability and experience in smartphone and slit lamp use was taken by all of the participants. Results: Each participant had three attempts at the same task. The overall smartphone quality was 7.2/10 for the anterior and 6.4/10 for the posterior segment. The subjectively perceived difficulty decreased significantly over the course of three attempts (Kendall's W). Image quality increased as well but did not improve significantly from take 1 to take 3. However, the image quality of the posterior segment was significantly, positively correlated (Spearman's Rho) with work experience. The mean acquisition time for anterior segment imaging was faster in the smartphone group compared to the control group (156 vs. 206 s). It was vice versa for the posterior segment (180 vs. 151 s). Conclusion: Slit lamp imaging with the presented smartphone adapter provides high-quality imaging of the anterior segment. Posterior segment imaging remains challenging in terms of image quality. The adapter constitutes a cost-effective, portable, easy-to-use solution for recording ophthalmic photos and videos. It can facilitate clinical documentation and communication among colleagues and with the patient especially outside normal consultation hours. Direct slit lamp imaging allows for time to be saved and increases the independence of ophthalmologists in terms of patient mobility and the availability of photographic staff. [ABSTRACT FROM AUTHOR]

What do we know, after so many pages devoted to the lieu de mémoire 'Saint-Barthélemy', of the thousands of Protestants thrown into the Seine or flung into the Saône, of those anonymous men, women and children exterminated in the summer and autumn of 1572? What do we know about the executioners during those nights, about those rare people who put their heart and soul into massacring their Huguenot neighbours? The responsibility of Catherine de Médicis or the Guise has been the subject of much interest; the torments of Charles IX and Spanish manipulation have long been scrutinized. This article will eschew these legitimate investigations in order to focus on the humble lives behind that night, the faces of the victims and the names of the killers, to discover who the ordinary actors were in this extraordinary event. [ABSTRACT FROM AUTHOR]

Objective: Based on feedback received during post-training consultation within a Prolonged Exposure (PE) implementation initiative, additional assessment training was added to help community providers identify patients who met criteria for posttraumatic stress disorder (PTSD) symptom severity and were considered appropriate for PTSD treatment. The current study investigated the rates of trauma exposure and PTSD in the community sample, as well as the percentage of individuals deemed "appropriate" for PE by community therapists. Method: Clinicians involved in the PE Initiative administered the Post-traumatic Diagnostic Scale for DSM-5 (PDS-5) to 10,260 individuals across 13 community agencies. Clinicians were also asked to report whether patients were perceived as appropriate for PE. Results: Consistent with our hypothesis, the rates of potential PTSD in Philadelphia community mental health (58.2% of our total sample) far exceeded national averages (8.3%). Contrary to our hypothesis, 100% of patients who scored above the clinical cutoff for PTSD were considered appropriate for PE by their community clinician. Conclusions: The results of this study emphasize the high prevalence of PTSD among individuals presenting for treatment to community mental health centers. Despite common misconceptions that patients are often perceived as ineligible or not appropriate for PE, 100% of patients in the PE Initiative who scored above the clinical cutoff for PTSD were considered good candidates for treatment according to their clinicians. This suggests that with sufficient training and post-training consultation, as provided in this community initiative, community clinicians may be more likely to perceive PE as an appropriate treatment option. [ABSTRACT FROM AUTHOR]

Accurate modelling type 2 diabetes and diabetic complications in rodents has proven a challenge, largely as a result of the long‐time course of disease development in humans. In the present study, we aimed to develop and comprehensively characterise a new rodent model of type 2 diabetes. To do this, we fed Sprague–Dawley rats a high fat/high sugar diet (HFD) to induce obesity and dyslipidaemia. After 3 weeks, we s.c. implanted osmotic mini pumps to enable a 14 day, slow infusion of streptozotocin (STZ; lower dose = 100 mg kg−1; higher dose = 120 mg kg−1) to dose‐dependently reduce pancreatic beta cell mass. After removing the mini pumps, we monitored animals for 4 months using a battery of tests to assess both metabolic and neurodegenerative changes across time. Our data demonstrate the combination of the HFD and lower dose STZ leads to induction of early‐stage type 2 diabetes defined by moderate hyperglycaemia, hyperinsulinaemia and impaired glucose tolerance, at the same time as the retention of an obese phenotype. By contrast, combining the HFD and higher dose STZ leads to induction of later‐stage type 2 diabetes defined by frank hyperglycaemia, hypoinsulinaemia (but not insulin depletion) and severely impaired glucose tolerance, at the same time as retaining an obese phenotype. Regardless of dose of STZ (and level of hyperglycaemia), all diabetic rats exhibited signs of peripheral neurodegeneration in the skin and muscle. Thus, this model recapitulates many of the complex metabolic disturbances seen in type 2 diabetes and provides an excellent platform for investigating the pathophysiological mechanisms that lead to diabetic complications such as peripheral neuropathy. Key points: Type 2 diabetes is a major health concern and markedly increases risk cardiovascular and neurodegenerative diseases.Accurate modelling of type 2 diabetes is a major challenge and has impeded our ability to understand the mechanisms that contribute to complications of type 2 diabetes.We have developed a method of inducing different stages of type 2 diabetes using a high fat/high sugar diet and 14 day infusion of streptozotocin to dose‐dependently destroy pancreatic beta cell mass.Over 4 months, we comprehensively characterised these animals and confirmed that they develop sustained metabolic dysfunction and progressive peripheral neurodegeneration as seen in type 2 diabetes.This new model will improve our ability to investigate the pathophysiological mechanisms that link type 2 diabetes with complications such as neurodegeneration. [ABSTRACT FROM AUTHOR]

Importance: Serotonin reuptake inhibitors (SRIs) are the only medications approved for obsessive-compulsive disorder (OCD), yet most patients taking SRIs exhibit significant symptoms. Adding exposure/response prevention (EX/RP) therapy improves symptoms, but it is unknown whether patients maintain wellness after discontinuing SRIs.Objective: To assess whether patients with OCD who are taking SRIs and have attained wellness after EX/RP augmentation can discontinue their SRI with noninferior outcomes compared with those who continue their SRI therapy.Design, Setting, and Participants: A 24-week, double-blind, randomized clinical trial was performed from May 3, 2013, to June 25, 2018. The trial took place at US academic medical centers. Participants included 137 adults with a principal diagnosis of OCD (≥1 year) who were taking an SRI (≥12 weeks), had at least moderate symptoms (defined as Yale-Brown Obsessive-Compulsive Scale [Y-BOCS] score ≥18 points), and received as many as 25 sessions of EX/RP therapy. Those who attained wellness (Y-BOCS score ≤14 points; 103 patients [75.2%]) were study eligible. Data were analyzed from June 29, 2019, to October 2, 2021.Intervention: Participants were randomly assigned either to receive taper to placebo (taper group) or to continue their SRI (continuation group) and monitored for 24 weeks.Main Outcome and Measures: The Y-BOCS score (range, 0-40 points) was the primary outcome; the Hamilton Depression Rating Scale (HDRS; range, 0-52 points) and the Quality-of-Life Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q-SF; range, 0%-100%) scores were secondary outcomes. Outcomes were assessed at 8 time points by independent evaluators who were blinded to randomization. The taper regimen was hypothesized to be noninferior to continuation at 24 weeks using a 1-sided α value of .05.Results: A total of 101 patients (mean [SD] age, 31.0 [11.2] years; 55 women [54.5%]) participated in the trial: 51 patients (50.5%) in the taper group and 50 patients (49.5%) in the continuation group. At 24 weeks, patients in the taper group had noninferior results compared with patients in the continuation group (mean [SD] Y-BOCS score: taper group, 11.47 [6.56] points; continuation group: 11.51 [5.97] points; difference, -0.04 points; 1-sided 95% CI, -∞ to 2.09 points [below the noninferiority margin of 3.0 points]; mean [SD] HDRS score: taper group, 5.69 [3.84] points; continuation group, 4.61 [3.46] points; difference, 1.08 points; 1-sided 95% CI, -∞ to 2.28 points [below the noninferiority margin of 2.5 points]; mean [SD] Q-LES-Q-SF score: taper group, 68.01% [15.28%]; continuation group, 70.01% [15.59%]; difference, 2.00%; 1-sided 95% CI, -∞ to 6.83 [below the noninferiority margin of 7.75]). However, the taper group had higher rates of clinical worsening (23 of 51 [45%] vs 12 of 50 [24%]; P = .04).Conclusions and Relevance: Results of this randomized clinical trial show that patients with OCD who achieve wellness after EX/RP therapy could, on average, discontinue their SRI with noninferior outcomes compared with those who continued their SRI. Those who tapered the SRI had higher clinical worsening rates. Future research should evaluate if SRI half-life alters these rates.Trial Registration: ClinicalTrials.gov Identifier: NCT01686087. [ABSTRACT FROM AUTHOR]

We investigate how subjective well-being varied over the course of the global COVID-19 pandemic, with a special attention to periods of lockdown. We use weekly data from YouGov's Great Britain Mood Tracker Poll, and daily reports from Google Trends, that cover the entire period from six months before until eighteen months after the global spread of COVID-19. Descriptive trends and time-series models suggest that negative mood associated with the imposition of lockdowns returned to baseline within 1–3 weeks of lockdown implementation, whereas pandemic intensity, measured by the rate of fatalities from COVID-19 infection, was persistently associated with depressed affect. The results support the hypothesis that country-specific pandemic severity was the major contributor to increases in negative affect observed during the COVID-19 pandemic, and that lockdowns likely ameliorated rather than exacerbated this effect. [ABSTRACT FROM AUTHOR]

In recent years, public-opinion scholars have raised concerns about declining satisfaction with democracy's performance and, in some countries, eroding democratic support. While these trends raise questions regarding democratic stability, other scholars have suggested that measures of social liberalism offer a more optimistic picture. Social-liberal values are rising globally, they assert, and since the presence of such values have correlated with past democratic transitions, a bright future for democracy awaits. However, in this article we find little evidence to link social liberalism to democratization—or even that social-liberal values are rising outside of existing democracies. While there are good reasons to envisage a future wave of democratic transitions, such global-values measures cannot inform their timing, location, or rationale. [ABSTRACT FROM AUTHOR]

Childhood is a developmental period associated with high risk of posttraumatic stress disorder (PTSD). Available validated pencil-and-paper diagnostic tools can be difficult for younger children to engage with given format and length. This study investigated psychometric properties of a briefer, more interactive game version of the Child PTSD Symptom Scale for DSM-5 (CPSS-5). Participants (n = 49) were children attending primary care appointments between 8 to 12 years of age who were exposed to a DSM-5 Criterion A trauma. Participants completed the 6-item screening version of the CPSS-5 delivered in mobile tablet game format (the CPSS-5 Screen Team Game) and a self-report version of the full CPSS-5 (CPSS-5-SR) before their medical appointments. The mobile game showed adequate internal consistency (α = 0.79), was significantly positively correlated to the total CPSS-5-SR (r =.74, p <.001, n = 49), and with the total of the six identical items of the CPSS-5-SR (r =.79, p <.001, n = 49), demonstrating good convergent validity. Receiver operating characteristic (ROC) analyses revealed a cut-off score of 9 on the screening game as indicative of probable PTSD. Implementation of this screening game into primary care settings could be a low-burden method to greatly increase the detection of pediatric PTSD for referral to appropriate integrated care interventions. [ABSTRACT FROM AUTHOR]

In recent years, the debate about the state of democracy in the United States has split political scientists into two camps: those who believed that American democracy was stable, and those who feared that former President Donald J. Trump might engage in significant violations of executive authority, such as using a declaration of national emergency to postpone elections. In this article, we argue that this debate rests on an overly simple juxtaposition between democracy and authoritarianism, and has misidentified the true danger faced by American institutions. The United States is in the process of becoming a less functional democracy in which both major parties retain a feasible prospect of winning elections but the nature of their competition is transformed in a manner that undermines the informal norms of healthy democratic life. This entails a shift from "clean" forms of competition which largely take the rules of the democratic game for granted towards what we term "dirty" democracy, in which competition consists, to a significant extent, of attempts to change the rules of the democratic game. [ABSTRACT FROM AUTHOR]

The prognostic role of lymphocyte doubling time (LDT) in chronic lymphocytic leukemia (CLL) was recognized more than three decades ago when the neoplastic clone's biology was almost unknown. LDT was defined as the time needed for the peripheral blood lymphocyte count to double the of the initial observed value. Herein, the LDT prognostic value for time to first treatment (TTFT) was explored in our prospective O-CLL cohort and validated in in two additional CLL cohorts. Specifically, newly diagnosed Binet stage A CLL patients from 40 Italian Institutions, representative of the whole country, were prospectively enrolled into the O-CLL1-GISL protocol (clinicaltrial.gov identifier: NCT00917540). Two independent cohorts of newly diagnosed CLL patients recruited respectively at the Division of Hematology in Novara, Italy, and at the Hospital Clinic in Barcelona, Spain, were utilized as validation cohorts. In the training cohort, TTFT of patients with LDT >12 months was significantly longer related to those with a shorter LDT. At Cox multivariate regression model, LDT ≤ 12 months maintained a significant independent relationship with shorter TTFT along with IGHV unmutated (IGHV unmut) status, 11q and 17p deletions, elevated β2M, Rai stage I-II, and NOTCH1 mutations. Based on these statistics, two regression models were constructed including the same prognostic factors with or without the LDT. The model with the LTD provided a significantly better data fitting (χ2 = 8.25, P=0.0041). The risk prediction developed including LDT had better prognostic accuracy than those without LDT. Moreover, the Harrell'C index for the scores including LDT were higher than those without LDT, although the accepted 0.70 threshold exceeded in both cases. These findings were also confirmed when the same analysis was carried out according to TTFT's explained variation. When data were further analyzed based on the combination between LDT and IGHV mutational status in the training and validation cohorts, IGHV unmut and LDT>12months group showed a predominant prognostic role over IGHV mut LTD ≤ 12 months (P=0.006) in the O-CLL validation cohort. However, this predominance was of borden-line significance (P=0.06) in the Barcelona group, while the significant prognostic impact was definitely lost in the Novara group. Overall, in this study, we demonstrated that LDT could be re-utilized together with the more sophisticated prognostic factors to manage the follow-up plans for Binet stage A CLL patients. [ABSTRACT FROM AUTHOR]

In the past few decades, political theorists have attempted to articulate a nontheological basis for a special human place in the moral universe. These attempts, I argue, generally fall into two groups, one centered around the concept of "dignity" and the other around ideas of "difference." Both of these attempts ultimately fail, I maintain, but their failures are instructive and help us along a path toward a better kind of relationship with nature and the earth as well as one another. In the face of increased scientific knowledge about the environment, animals, and our own species, we have every reason to recalibrate our stance toward nature as a whole. But in doing so we must acknowledge that the human relationship with nature is ultimately a representative one that can therefore never achieve the kind of reciprocity available in human society. Whatever form our respect for nature takes, it will always be distinct from the relationships we have with those we consider co-citizens. [ABSTRACT FROM AUTHOR]

Copyright of Direito e Práxis is the property of Editora da Universidade do Estado do Rio de Janeiro (EdUERJ) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The neurotransmitter serotonin has been implicated in a range of complex neurological disorders linked to alterations of neuronal circuitry. Serotonin is synthesized in the developing brain before most neuronal circuits become fully functional, suggesting that serotonin might play a distinct regulatory role in shaping circuits prior to its function as a classical neurotransmitter. In this study, we asked if serotonin acts as a guidance cue by examining how serotonin alters growth cone motility of rodent sensory neurons in vitro. Using a growth cone motility assay, we found that serotonin acted as both an attractive and repulsive guidance cue through a narrow concentration range. Extracellular gradients of 50 µM serotonin elicited attraction, mediated by the serotonin 5-HT2a receptor while 100 µM serotonin elicited repulsion mediated by the 5-HT1b receptor. Importantly, high resolution imaging of growth cones indicated that these receptors signalled through their canonical pathways of endoplasmic reticulum-mediated calcium release and cAMP depletion, respectively. This novel characterisation of growth cone motility in response to serotonin gradients provides compelling evidence that secreted serotonin acts at the molecular level as an axon guidance cue to shape neuronal circuit formation during development. [ABSTRACT FROM AUTHOR]

We consider the generation of a pure spin-current at zero bias voltage with a single time-dependent potential. To such end we study a device made of a mesoscopic ring connected to electrodes and clarify the interplay between a magnetic flux, spin-orbit coupling, and non-adiabatic driving in the production of a spin and electrical current. By using Floquet theory, we show that the generated spin to charge current ratio can be controlled by tuning the spin-orbit coupling. [ABSTRACT FROM AUTHOR]

Copyright of Desde el Jardín de Freud is the property of Universidad Nacional de Colombia, Escuela de Estudios en Psicoanalisis y Cultura and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Endovascular treatment of intracranial aneurysms (IAs) has evolved considerably over the past decades. The technological advances have been driven by the experience that coils fail to completely exclude all IAs from the blood circulation, the need to treat the diseased parent vessel segment leading to the aneurysm formation, and expansion of endovascular therapy to treat more complex IAs. Stents were initially developed to support the placement of coils inside wide neck aneurysms. However, early work on stent-like tubular braided structure led to a more sophisticated construct that then later was coined as a flow diverter (FD) and found its way into clinical application. Although FDs were initially used to treat wide-neck large and giant internal carotid artery aneurysms only amenable to surgical trap with or without a bypass or endovascular vessel sacrifice, its use in other types of IAs and cerebrovascular pathology promptly followed. Lately, we have witnessed an explosion in the application of FDs and subsequently their modifications leading to their ubiquitous use in endovascular therapy. In this review we aim to compile the available FD technology, evaluate the devices' peculiarities from the authors' perspective, and analyze the current literature to support initial and expanded indications, recognizing that this may be outdated soon. [ABSTRACT FROM AUTHOR]

Copyright of European Journal of Psychotraumatology is the property of Taylor & Francis Ltd and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objective: Adolescents with posttraumatic stress disorder (PTSD) are at higher risk for suicide compared to adolescents without PTSD. This study aimed to explore whether PTSD treatment reduces suicidal ideation in adolescents and whether the degree of reduction in PTSD was associated with reduction in suicidal ideation. Methods: Adolescent females with PTSD from a sexual assault (55% Black, 15.3 years, SD = 1.5) were randomized to either prolonged exposure therapy for adolescents (PE-A, n= 31) or client-centered therapy (CCT, n = 30). They reported on suicidal ideation, depression and PTSD at pre- and post-treatment, every therapy session, and follow-up, and about 40% endorsed suicidal ideation at baseline. Results: There was a significant reduction in a single-item measure of suicidal ideation during treatment across all participants. The Time in Treatment × Condition interaction was significant (p <.05, d = 0.52), indicating a significantly steeper reduction in suicidal ideation in PE-A compared to in CCT. The degree of reduction in PTSD (ps <.05, d = 0.26–0.54) and depression symptoms (ps <.05, d= 0.54–0.81) in treatment and follow-up was associated with the speed of suicidal ideation reduction in treatment and follow-up. Conclusions: Adolescents randomized to PE-A had significantly faster reductions in suicidal ideation compared to those randomized to CCT. Greater reduction in PTSD and depression symptoms were associated with faster reduction in suicidal ideation. Clinically, this study demonstrates that adolescents who have suicidal ideation without current intent may benefit from PE-A. [ABSTRACT FROM AUTHOR]

Edgar Degas's stay in New Orleans in 1872–73, which marked his only visit to the New World, resulted in two remarkable paintings of a cotton office. Linking Southern cotton to the French textiles he frequently depicted and to his works' paper supports demonstrates the centrality of the material to the artist's corpus. More broadly, Degas's cotton office paintings, as well as drawings and letters produced during his time abroad, reflect his meditation on the connections that bound the Old and New Worlds together and the transportation technology that facilitated the global circulation of people, goods, and communications. [ABSTRACT FROM AUTHOR]

Background: Prolonged exposure therapy (PE) is an evidence-based treatment for posttraumatic stress disorder (PTSD) that is underutilized in the military health system. Standard workshop training in PE may not be sufficient to alter provider behavior, but post-workshop consultation requires significant resources. Therefore, it is important to determine the incremental utility of post-workshop consultation.Methods: This study used a hybrid type III randomized implementation trial at 3 US Army installations. Providers were randomized to receive a 4-day prolonged exposure workshop (Standard training condition, n = 60), or the prolonged exposure workshop followed by 6-8 months of post-workshop expert case consultation (Extended training condition, n = 43). The effects training condition were examined on provider attitudes (self-efficacy in delivering PE, expectations for patient improvement, and beliefs about PE), use of PE and PE components, and clinical outcomes of patients with PTSD (using the Clinician-Administered PTSD Scale (CAPS-5)).Results: Extended condition providers reported greater improvements in self-efficacy, b = .83, 95% CI [.38, 1.27], t(79) = 3.71, p = .001, and d = .63. A greater proportion of patients in the Extended condition (44%) than in the Standard condition (27%) received at least 1 PE session, b = .76, t(233) = 2.53, p = .012, and OR = 2.13. Extended condition providers used more PE components (M = .9/session) than did Standard condition providers (M = .5/session), b = .54, 95% CI [.15, .93], t(68) = 2.70, p = .007, and d = .68. Finally, decrease in patients' PTSD symptoms was faster for patients of Extended condition providers than for patients of Standard condition providers, b = - 1.81, 95% CI [- 3.57, - .04], t(263) = - 2.02, p = .045, and d = .66, and their symptoms were lower at the second assessment, b = - 5.47, 95% CI [- 9.30, - 1.63], t(210) = - 2.81, p = .005, and d = .66.Conclusions: Post-workshop consultation improved self-efficacy for delivering PE, greater use of PE, faster PTSD reduction, and lower PTSD severity at the second assessment. To our knowledge, this is the first demonstration that post-workshop case consultation for PE improves patient outcomes.Trial Registration: Clinicaltrials.gov , NCT02982538 . Registered December 5, 2016; retrospectively registered. [ABSTRACT FROM AUTHOR]

Background: Effective treatments for posttraumatic stress disorder (PTSD) (e.g., prolonged exposure (PE); cognitive processing therapy (CPT)) exist and are widely adopted by the Departments of Veterans Affairs (VA) and Defense (DoD). Unfortunately, dropout from these treatments regularly exceeds 30%. However, in a recent survey of patients who dropped out of PE, approximately half indicated a greater likelihood of completion if a peer who had completed treatment were available to help with the in vivo exposure homework.Methods: We will use a between-groups randomized controlled design with repeated assessment at baseline, post treatment, and 3- and 6-month follow-up across measures of PTSD, depression, and functioning with 150 veterans who have indicated that they intend to drop out of treatment. Participants will be randomly assigned to one of two PE + Peer Support conditions: (1) a peer will offer support directly during in vivo exposure homework for 3-4 weeks; vs (2) a peer will call weekly for 3-4 weeks to offer general support and to check in on treatment progress.Discussion: The present study was designed to test the hypothesis that dropout from exposure-based PTSD treatment may be mitigated by using peers as support agents directly during PE in vivo homework experiences. Specifically, we intend to determine: whether patients who have dropped out of PE and are offered the "in vivo peer" adjunctive component to PE therapy will (1) return and complete treatment and (2) evince reduced PTSD symptomatology, compared to the same PE treatment, but with general peer support more reflective of current VA practices.Trial Registration: This study protocol is approved and information is available at ClinicalTrials.gov, ID: NCT03485391. Registered on 2 April 2018. [ABSTRACT FROM AUTHOR]

Objectives: Survival outcomes from a single‐arm phase 2 blinatumomab study in patients with minimal residual disease (MRD)‐positive B‐cell precursor (BCP)‐acute lymphoblastic leukaemia (ALL) were compared with those receiving standard of care (SOC) in a historic data set. Methods: The primary analysis comprised adult Philadelphia chromosome (Ph)‐negative patients in first complete haematologic remission (MRD ≥ 10−3). Relapse‐free survival (RFS) and overall survival (OS) were compared between blinatumomab‐ and SOC‐treatment groups. Baseline differences between groups were adjusted by propensity scores. Results: The primary analysis included 73 and 182 patients from the blinatumomab and historic data sets, respectively. When weighted by age to the blinatumomab‐treatment group, median RFS was 7.8 months and median OS was 25.9 months in the SOC‐treated group. In the blinatumomab study, median RFS was 35.2 months; median OS was not evaluable. Propensity score weighting achieved balance with seven baseline prognostic factors. With adjustment for haematopoietic stem cell transplantation (HSCT) status, a 50% reduction in risk of relapse or death was observed with blinatumomab vs SOC. Median RFS, unadjusted for HSCT status, was 35.2 months with blinatumomab and 8.3 months with SOC. Conclusions: These analyses suggest that blinatumomab improves RFS, and possibly OS, in adults with MRD‐positive Ph‐negative BCP‐ALL vs SOC. [ABSTRACT FROM AUTHOR]

Copyright of Quaestio Iuris (QI) is the property of Editora da Universidade do Estado do Rio de Janeiro (EdUERJ) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Despite advances in understanding the pathogenesis of acute myeloid leukemia (AML), the standard therapy remained nearly unchanged for several decades. There have been many efforts to improve the response and survival by either increasing the cytarabine (ARA-C) dose or adding a third agent to the standard chemotherapy regimen. Several studies have evaluated the addition of cladribine (CdA) to standard induction, exploiting its property to potentiate ARA-C uptake. Response rates for combination regimens including CdA in relapsed/refractory (R/R) adults are approximately 50% and approximately 70% in de novo AML. Recently, a low intensity combination of CdA and ARA‐C alternating with decitabine has shown promising results in older patients with AML. In this review, we will discuss the role of CdA in the treatment of AML, summarizing the recent clinical data regarding its incorporation into the induction therapy for adult AML. [ABSTRACT FROM AUTHOR]

Copyright of Desde el Jardín de Freud is the property of Universidad Nacional de Colombia, Escuela de Estudios en Psicoanalisis y Cultura and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

This paper describes a statistical methodology that can be deployed in order to conduct evidence-based scenario planning. Scenario-planning techniques have recently become widespread in strategic consultancy, market research and government planning, but methodological vagueness often results in scenarios that are excessively arbitrary, implausible or non-specific in their outputs. By detailing the Monte Carlo process, via which a set of scenarios were constructed for the Department for Environment, Food and Rural Affairs (Defra), the authors argue that it is possible to take a non-linear, non-deterministic but empirically grounded approach to the formulation of strategic and contingency plans for the future. The process is explained in such a way that it can be adopted by industry practitioners, with key lessons detailed for future scenario-planning exercises. [ABSTRACT FROM AUTHOR]

An introduction is presented in which the author discusses about the articles in the issue including racism and totalitarianism, Anthropocene and feminist, racialized, and colonial politics.

Copyright of Canadian Journal of Psychiatry is the property of Sage Publications Inc. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Revista Neuropsicologia Latinoamericana is the property of Yves Joannette and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Few studies have investigated the patterns of posttraumatic stress disorder (PTSD) symptom change in prolonged exposure (PE) therapy. In this study, we aimed to understand the patterns of PTSD symptom change in both PE and present-centered therapy (PCT). Methods: Participants were active duty military personnel (N = 326, 89.3% male, 61.2% white, 32.5 years old) randomized to spaced-PE (S-PE; 10 sessions over 8 weeks), PCT (10 sessions over 8 weeks), or massed-PE (M-PE; 10 sessions over 2 weeks). Using latent profile analysis, we determined the optimal number of PTSD symptom change classes over time and analyzed whether baseline and follow-up variables were associated with class membership. Results: Five classes, namely rapid responder (7–17%), steep linear responder (14–22%), gradual responder (30–34%), non-responder (27–33%), and symptom exacerbation (7–13%) classes, characterized each treatment. No baseline clinical characteristics predicted class membership for S-PE and M-PE; in PCT, more negative baseline trauma cognitions predicted membership in the non-responder v. gradual responder class. Class membership was robustly associated with PTSD, trauma cognitions, and depression up to 6 months after treatment for both S-PE and M-PE but not for PCT. Conclusions: Distinct profiles of treatment response emerged that were similar across interventions. By and large, no baseline variables predicted responder class. Responder status was a strong predictor of future symptom severity for PE, whereas response to PCT was not as strongly associated with future symptoms. [ABSTRACT FROM AUTHOR]

The current study examined the role of trauma-related guilt on posttraumatic stress disorder (PTSD) symptom change during prolonged exposure therapy (PE) as well as the efficacy of PE in reducing three dimensions of guilt (responsibility, wrongdoing, and lack of justification) during treatment. Participants were 331 active duty U.S. military personnel seeking treatment for PTSD who were randomized to one of four groups: massed PE (10 sessions delivered over 2 weeks), spaced PE (10 sessions delivered over 8 weeks), present-centered therapy (PCT; 10 sessions delivered over 8 weeks), or minimal contact control (MCC; weekly therapist phone check-in for 4 weeks). The results showed that baseline guilt did not predict reductions in PTSD symptoms for spaced PE or for PCT, ps = .178-.387, ds = -0.02-0.07. Treatment condition (massed PE vs. MCC; spaced PE vs. PCT) did not moderate reductions in guilt for spaced PE versus PCT. Guilt decreased significantly over treatment in all groups, p < .001 to p = .038, ds = -0.19 to -0.42, except concerning justification in the spaced PE and PCT groups, p = .140, d = -0.10. The findings suggest that guilt may be reduced significantly following active PTSD treatment and attention control and that PTSD recovery is not impacted by baseline levels of trauma-related guilt in military personnel with PTSD, although reported levels of guilt were low to moderate in this sample. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Traumatic Stress is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The spatial and temporal regulation of calcium signaling in neuronal growth cones is essential for axon guidance. In growth cones, the endoplasmic reticulum (ER) is a significant source of calcium signals. However, it is not clear whether the ER is remodeled during motile events to localize calcium signals in steering growth cones. The expression of the ER-calcium sensor, stromal interacting molecule 1 (STIM1) is necessary for growth cone steering toward the calcium-dependent guidance cue BDNF, with STIM1 functioning to sustain calcium signals through store-operated calcium entry. However, STIM1 is also required for growth cone steering away from semaphorin-3a, a guidance cue that does not activate ER-calcium release, suggesting multiple functions of STIM1 within growth cones (Mitchell et al., 2012). STIM1 also interacts with microtubule plus-end binding proteins EB1/EB3 (Grigoriev et al., 2008). Here, we show that STIM1 associates with EB1/EB3 in growth cones and that STIM1 expression is critical for microtubule recruitment and subsequent ER remodeling to the motile side of steering growth cones. Furthermore, we extend our data in vivo, demonstrating that zSTIM1 is required for axon guidance in actively navigating zebrafish motor neurons, regulating calcium signaling and filopodial formation. These data demonstrate that, in response to multiple guidance cues, STIM1 couples microtubule organization and ER-derived calcium signals, thereby providing a mechanism where STIM1-mediated ER remodeling, particularly in filopodia, regulates spatiotemporal calcium signals during axon guidance. [ABSTRACT FROM AUTHOR]