The Cosmological Switchback Effect

The volume behind the black hole horizon was suggested as a holographic dual for the quantum computational complexity of the boundary state in AdS/CFT. This identification is strongly motivated by the switchback effect: a characteristic delay of complexity growth in reaction to an inserted perturbation, modelled as a shockwave in the bulk. Recent proposals of de Sitter (dS) holography suggest that a dual theory could be living on a stretched horizon near the cosmological horizon. We study how the spacetime volume behind the cosmological horizon in Schwarzschild-dS space reacts to the insertion of shockwaves in an attempt to characterize the properties of this dual theory. We demonstrate that a switchback effect can be observed in dS space. That is, the growth of complexity is delayed in reaction to a perturbation. This delay is longer for earlier shocks and depends on a scrambling time which is logarithmic in the strength of the shockwave and proportional to the inverse temperature of the cosmological dS horizon. This behavior is very similar to what happens for AdS black holes, albeit the geometric origin of the effect is different.Comment: 78 pages, 30 figure

Functional Classification of Immune Regulatory Proteins

SummaryThe members of the immunoglobulin superfamily (IgSF) control innate and adaptive immunity and are prime targets for the treatment of autoimmune diseases, infectious diseases, and malignancies. We describe a computational method, termed the Brotherhood algorithm, which utilizes intermediate sequence information to classify proteins into functionally related families. This approach identifies functional relationships within the IgSF and predicts additional receptor-ligand interactions. As a specific example, we examine the nectin/nectin-like family of cell adhesion and signaling proteins and propose receptor-ligand interactions within this family. Guided by the Brotherhood approach, we present the high-resolution structural characterization of a homophilic interaction involving the class-I MHC-restricted T-cell-associated molecule, which we now classify as a nectin-like family member. The Brotherhood algorithm is likely to have a significant impact on structural immunology by identifying those proteins and complexes for which structural characterization will be particularly informative

Experimental Studies on State Self-Objectification: A Review and an Integrative Process Model

This paper provides an organizing framework for the experimental research on the effects of state self-objectification on women. We explain why this body of work, which had grown rapidly in the last 20 years, departs from the original formulation of objectification theory (Fredrickson and Roberts, 1997). We compare the different operationalizations of state self-objectification and examine how they map onto its theoretical definition, concluding that the operationalizations have focused mostly on one component of this construct (concerns about one's physical appearance) while neglecting others (adopting a third-person perspective and treating oneself as a dehumanized object). We review the main findings of studies that experimentally induced state self-objectification and examined its affective, motivational, behavioral, cognitive, and physiological outcomes. We note that three core outcomes of this state as specified by objectification theory (safety anxiety, reduced flow experiences, and awareness of internal body states) have hardly been examined so far. Most importantly, we introduce an integrative process model, suggesting that the reported effects are triggered by four different mechanisms: appearance monitoring, experience of discrepancy from appearance standards, stereotype threat, and activation of the “sex object” schema. We propose strategies for distinguishing between these mechanisms and explain the theoretical and practical importance of doing so

Exploding Head Syndrome: Clinical Features, Theories about Etiology, and Prevention Strategies in a Large International Sample

OBJECTIVE: Exploding head syndrome (EHS) is a benign sensory parasomnia characterized by the perception of loud noises or a sense of explosion in the head. Few studies have assessed clinical features and little is known about demographic differences or prevention strategies. PATIENTS/METHODS: A cross-sectional study of 3286 individuals with and 2954 without lifetime EHS episodes was conducted via online questionnaires. RESULTS: Those with EHS had shorter sleep durations, longer sleep onset latencies, poorer sleep quality, and less sleep efficiency, but effect sizes for these differences were small. Females were slightly more likely than males to endorse EHS. 44.4% of individuals with EHS experienced significant fear during episodes, but fewer reported clinically significant distress (25.0%) or interference (10.1%) as a result of EHS. Most sufferers believed it to be a brain-based phenomenon, but a small minority endorsed anomalous causes. Five prevention strategies with >50% reported effectiveness were identified. CONCLUSIONS: EHS was assessed in the largest sample to date. Though associated with clinical impacts, no empirically supported interventions yet exist. The five prevention strategies may prove useful for treatment development

Not Just Efficiency: Insolvency Law in the EU and Its Political Dimension

Certain insolvency law rules, like creditors’ priorities and set-off rights, have a distributive impact on creditors. Distributional rules reflect the hierarchies of values and interests in each jurisdiction and, as a result, have high political relevance and pose an obstacle to reforming the EU Insolvency Regulation. This paper will show the difficulty of reform by addressing two alternative options to regulate cross-border insolvencies in the European Union. The first one is the ‘choice model’, under which companies can select the insolvency law they prefer. Although such a model would allow distressed firms to select the most efficient insolvency law, it would also displace Member States’ power to protect local constituencies. The choice model therefore produces negative externalities and raises legitimacy concerns. The opposite solution is full harmonisation of insolvency law at EU level, including distributional rules. Full harmonisation would have the advantage of internalising all externalities produced by cross-border insolvencies. However, the EU legislative process, which is still based on negotiations between states, is not apt to decide on distributive insolvency rules; additionally, if harmonisation includes such rules, it will indirectly modify national social security strategies and equilibria. This debate shows that the choice regarding power allocation over bankruptcies in the EU depends on the progress of European integration and is mainly a matter of political legitimacy, not only of efficiency

S-Nitrosylation of α1-Antitrypsin Triggers Macrophages Toward Inflammatory Phenotype and Enhances Intra-Cellular Bacteria Elimination

Background: Human α1-antitrypsin (hAAT) is a circulating anti-inflammatory serine-protease inhibitor that rises during acute phase responses. in vivo, hAAT reduces bacterial load, without directly inhibiting bacterial growth. In conditions of excess nitric-oxide (NO), hAAT undergoes S-nitrosylation (S-NO-hAAT) and gains antibacterial capacity. The impact of S-NO-hAAT on immune cells has yet to be explored.Aim: Study the effects of S-NO-hAAT on immune cells during bacterial infection.Methods: Clinical-grade hAAT was S-nitrosylated and then compared to unmodified hAAT, functionally, and structurally. Intracellular bacterial clearance by THP-1 macrophages was assessed using live Salmonella typhi. Murine peritoneal macrophages were examined, and signaling pathways were evaluated. S-NO-hAAT was also investigated after blocking free mambranal cysteine residues on cells.Results: S-NO-hAAT (27.5 uM) enhances intracellular bacteria elimination by immunocytes (up to 1-log reduction). S-NO-hAAT causes resting macrophages to exhibit a pro-inflammatory and antibacterial phenotype, including release of inflammatory cytokines and induction of inducible nitric oxide synthase (iNOS) and TLR2. These pro-inflammatory effects are dependent upon cell surface thiols and activation of MAPK pathways.Conclusions: hAAT duality appears to be context-specific, involving S-nitrosylation in a nitric oxide rich environment. Our results suggest that S-nitrosylation facilitates the antibacterial activity of hAAT by promoting its ability to activate innate immune cells. This pro-inflammatory effect may involve transferring of nitric oxide from S-NO-hAAT to a free cysteine residue on cellular targets

Nutrition in Pediatric Inflammatory Bowel Disease: A Position Paper on Behalf of the Porto Inflammatory Bowel Disease Group of the European Society of Pediatric Gastroenterology, Hepatology and Nutrition

Background and Aims:A growing body of evidence supports the need for detailed attention to nutrition and diet in children with inflammatory bowel disease (IBD). We aimed to define the steps in instituting dietary or nutritional management in light of the current evidence and to offer a useful and practical guide to physicians and dieticians involved in the care of pediatric IBD patients.Methods:A group of 20 experts in pediatric IBD participated in an iterative consensus process including 2 face-to-face meetings, following an open call to Nutrition Committee of the European Society of Pediatric Gastroenterology, Hepatology and Nutrition Porto, IBD Interest, and Nutrition Committee. A list of 41 predefined questions was addressed by working subgroups based on a systematic review of the literature.Results:A total of 53 formal recommendations and 47 practice points were endorsed with a consensus rate of at least 80% on the following topics: nutritional assessment;macronutrients needs;trace elements, minerals, and vitamins;nutrition as a primary therapy of pediatric IBD;probiotics and prebiotics;specific dietary restrictions;and dietary compounds and the risk of IBD.Conclusions:This position paper represents a useful guide to help the clinicians in the management of nutrition issues in children with IBD

Mapping the availability of translated versions of posttraumatic stress disorder screening questionnaires for adults: A scoping review

Background: The most used questionnaires for PTSD screening in adults were developed in English. Although many of these questionnaires were translated into other languages, the procedures used to translate them and to evaluate their reliability and validity have not been consistently documented. This comprehensive scoping review aimed to compile the currently available translated and evaluated questionnaires used for PTSD screening, and highlight important gaps in the literature. Objective: This review aimed to map the availability of translated and evaluated screening questionnaires for posttraumatic stress disorder (PTSD) for adults. Methods: All peer-reviewed studies in which a PTSD screening questionnaire for adults was translated, and which reported at least one result of a qualitative and /or quantitative evaluation procedure were included. The literature was searched using Embase, MEDLINE, and APA PsycInfo, citation searches and contributions from study team members. There were no restrictions regarding the target languages of the translations. Data on the translation procedure, the qualitative evaluation, the quantitative evaluation (dimensionality of the questionnaire, reliability, and performance), and open access were extracted. Results: A total of 866 studies were screened, of which 126 were included. Collectively, 128 translations of 12 different questionnaires were found. Out of these, 105 (83.3%) studies used a forward and backward translation procedure, 120 (95.2%) assessed the reliability of the translated questionnaire, 60 (47.6%) the dimensionality, 49 (38.9%) the performance, and 42 (33.3%) used qualitative evaluation procedures. Thirty-four questionnaires (27.0%) were either freely available or accessible on request. Conclusions: The analyses conducted and the description of the methods and results varied substantially, making a quality assessment impractical. Translations into languages spoken in middle- or low-income countries were underrepresented. In addition, only a small proportion of all translated questionnaires were available. Given the need for freely accessible translations, an online repository was developed

Long-term viability and function of transplanted islets macroencapsulated at high density are achieved by enhanced oxygen supply

Transplantation of encapsulated islets can cure diabetes without immunosuppression, but oxygen supply limitations can cause failure. We investigated a retrievable macroencapsulation device wherein islets are encapsulated in a planar alginate slab and supplied with exogenous oxygen from a replenishable gas chamber. Translation to clinically-useful devices entails reduction of device size by increasing islet surface density, which requires increased gas chamber pO Here we show that islet surface density can be substantially increased safely by increasing gas chamber pO to a supraphysiological level that maintains all islets viable and functional. These levels were determined from measurements of pO profiles in islet-alginate slabs. Encapsulated islets implanted with surface density as high as 4,800 islet equivalents/cm in diabetic rats maintained normoglycemia for more than 7 months and provided near-normal intravenous glucose tolerance tests. Nearly 90% of the original viable tissue was recovered after device explantation. Damaged islets failed after progressively shorter times. The required values of gas chamber pO were predictable from a mathematical model of oxygen consumption and diffusion in the device. These results demonstrate feasibility of developing retrievable macroencapsulated devices small enough for clinical use and provide a firm basis for design of devices for testing in large animals and humans