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The International Classification of Diseases–11th revision (ICD-11) classification of personality disorders is the official diagnostic system that is used all over the world, and it has recently been renewed. However, as yet very few data are available on its performance. This study examines the Personality Inventory for ICD-11 (PiCD), which assesses the personality domains of the system, and the Standardized Assessment of Severity of Personality Disorder (SASPD), which determines severity. The Spanish versions of the questionnaires were administered to a community (n = 2,522) and a clinical sample (n = 797). Internal consistency was adequate in the PiCD (α =.75 to.84) but less so in the SASPD (α =.64 and.73). Factor analyses suggested a unidimensional or bidimensional structure for severity, while revealing that the personality trait qualifiers are organized into four factors: negative affectivity, detachment, dissociality, and a bipolar domain of disinhibition–anankastia. The mutual relationships between traits and severity were analyzed, as well as the ability of the whole system to identify clinical subjects. Although further improvements are required, the results generally support the use of the PiCD and the SASPD and help substantiate the new ICD-11 taxonomy that underlies them., This work was supported by project PI15/00536, part of the Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016, financed by the ISCIII Subdirección General de Evaluación and the cofinanced by the European Regional Development Fund (ERDF, “A way to build Europe”; PI: F. Gutiérrez)

The 11Mit der 11. Version der International Statistical Classification of Diseases and Related Health Problems (ICD-11) erfolgt ein Paradigmenwechsel in der Diagnostik von Persönlichkeitsstörungen: Deren Klassifikation erfolgt künftig nicht mehr kategorial, sondern dimensional entlang der Schweregrade von Persönlichkeitsbeeinträchtigungen und optional der Präsenz maladaptiver Persönlichkeitsmerkmale. Diese Studie untersucht die Reliabilität und Validität der deutschen Version des Personality Inventory for ICD-11 (PiCD), ein Fragebogen zur Erfassung der ICD-11 Persönlichkeitsdomänen, in einer klinischen und nicht-klinischen Stichprobe (N=939). Die Faktorstruktur des PiCD wurde mit Hilfe einer explorativen Faktorenanalyse (EFA) untersucht und zeigte eine Tendenz für ein Vier-Faktoren Modell (Negative Affektivität, Dissozialität, Distanziertheit und ein bipolarer Faktor Enthemmung-Anankasmus). Die Subskalen des PiCD wiesen akzeptable bis exzellente Reliabilitätskoeffizienten mit Cronbach‘s α=0,79 – 0,89 und McDonald‘s ω=0,76 – 0,90 auf. Die konvergente und diskriminante Validität wurde anhand weiterer Selbsteinschätzungsinstrumente untersucht und erwies sich als zufriedenstellend. Die Ergebnisse legen nahe, dass es sich bei der deutschen Version des PiCD um ein reliables und einigermaßen valides Messinstrument zur Erfassung der maladaptiven Persönlichkeitsmerkmale gemäß ICD-11 handelt. Es ist jedoch weitere Forschung zur Faktorenstruktur, geeigneten Cut-Off- sowie Normwerten notwendig.

Dissertation, RWTH Aachen University, 2018; Dissertation, RWTH Aachen University, 2018, Neonates are highly susceptible to microbial infections, resulting in nearly 1 million neonatal deaths per year. This predisposition is particularly referable to distinct differences between the immune system of adults and neonates. The process of inflammation is usually triggered as a protective response to infection or tissue injury. The accurate resolution of the inflammatory response is essential to return to tissue homeostasis since a prolonged inflammation with ongoing cytokine release can result in tissue damage, organ dysfunctions and mortality. This is of particular importance for newborns, since various neonatal diseases, including periventricular leukomalacia, necrotizing enterocolitis or bronchopulmonary dysplasia, are characterized by sustained inflammation. One factor known to control length and extent of the inflammatory response, is the regulation of effector cell apoptosis. A special type of apoptosis is the phagocytosis-induced cell death (PICD) of phagocytic immune cells. Previous studies demonstrated that PICD is less frequently triggered in neonatal monocytes than in adult monocytes. Hence, a rescue of monocyte PICD could be a potential therapeutic approach to target the sustained inflammation in neonates. The EGF receptor is capable of blocking the initiation of apoptosis upon activation by its specific ligands. One ligand is the cytokine amphiregulin (AREG), which is increasingly shedded in response to bacterial infection and was shown to mediate apoptosis resistance. Therefore, it was hypothesized that AREG might contribute to the reduced PICD of neonatal monocytes by affecting the apoptosis signaling of monocytes. In this study, a well-established in vitro E. coli infection model was used to analyze PICD in primary monocytes from peripheral (PBMO) or cord blood (CBMO). The results indicate that CBMO show remarkably higher AREG surface expression as well as soluble levels in response to infection which could function as anti-apoptotic stimulus. Flow cytometry experiments were conducted to analyze intrinsic and extrinsic apoptosis signaling in dependence on AREG. Strikingly, AREG was proven to affect both pathways through EGFR downstream trafficking. With regard to extrinsic apoptosis, AREG increases intracellular MMP-2 and MMP-9 levels through EGFR activation, whereby inducing cleavage of membrane-bound FasL. Intrinsic apoptosis signaling is supressed by AREG function via EGFR-mediated phosphorylation of ERK1/2, Akt and BAD, resulting in increased intracellular Bcl-2 and Bcl-XL levels and decreased cleavage of pro-caspase-9 and -3. Furthermore, the results indicate that AREG may have regulatory function on T cells, which are of special importance for the immune response as they perform key effector functions during inflammation. AREG potentially reduces T cell proliferation through the suppressed costimulatory capacity of monocytes, since surface expression of CD80, CD86 und HLA-DR was found downregulated. The temporary presence during the newborn period might identify AREG as endogenous immune regulator. Targeting inflammatory diseases in neonates is of central clinical relevance and a better understanding of the regulatory elements involved in PICD could be essential to find new therapeutic strategies. Inhibition of AREG rescued the PICD of neonatal monocytes, thereby identifying AREG as potential target to reduce sustained inflammation in neonates.

Background Clarithromycin (CL) is a macrolide antibiotic with anti-MM activity when combined with dexamethasone (dex), and imids. Immunomodulatory activity and altered dex metabolism are proposed mechanisms of CL activity, though concerns over toxicity remain. We designed a phase I/II study of pomalidomide (pom), ixazomib (ix), CL and dex (PICd) to assess the tolerability and efficacy of CL in RRMM. Methods The primary endpoints were the maximal tolerated and recommended phase 2 dose of PICd. Secondary endpoints were overall response rate (ORR)(≥ PR), disease control rate (DCR)(≥ SD), duration of response (DOR) and progression free (PFS) and overall survival (OS). Cycles were 28 days. CL 250 mg PO BID was given c1 d15-21 and d1-21 subsequently. Pom 4 mg PO daily for 21 days, ix 4 mg d1, 8, 15 and dex 40 mg (20 mg if age >75 years) d1, 8, 15 and 22 were given for 6 cycles. After C6, maintenance until unacceptable toxicity or PD consisted of reduced pom, ix, dex and CL doses at 2, 2.3, 20 and 250 mg respectively. CL was held during weeks 1-2 of cycle 1 to facilitate correlative studies. Results A total of 32 patients consented to study. Of these, 4 were unevaluable for response/survival due to rapid disease progression (n=2), late screen failure (n=1), and withdrawn consent (n=1). Of these, 3 were included in toxicity data. Median follow up was 20 months (mo). Median age was 68.5 (range 54 – 82), 74% were male. Median number of prior therapies was 2 (1 – 5). All patients had prior lenalidomide and proteasome inhibitor exposure. Of the 26 patients with FISH data, 15 (57%) had high risk cytogenetics. Of these, 9 (35%) had del(17p), 10 (38%) had + 1q and 2 (8%) had t(4;14). Four had del(17p) and +1q; 1 each had t(4;14) and del(17p) or +1q. At least 1 grade 3-4 adverse event (AE) was experienced by 17 (55%) patients. Grade 3-4 hematologic AEs were seen in 8 (26%), of which 5 (16%) had neutropenia. Ten (31%) experienced grade 3-4 non-hematologic AEs, of which infections were the most common [4 (13%) patients]. Grade 3-4 neuropathy was not seen. ORR was 75%, DCR was 100%; 13 patients (56%) achieved ≥VGPR while 4 (14%) achieved CR/sCR. High risk cytogenetics were not associated with ORR (Fisher exact test P=1) or ≥VGPR rates (Fisher exact test P=0.42). Median DOR was 23.2 mo (95% Confidence interval: 12.2 – not reached); median PFS was 24.7 mo (13.4 – NR). There was no difference in median PFS in patients with or without del(17p): 24.7 mo (7.5 – NR) vs 22.2 mo (11.0 – NR) respectively (log rank P=0.4). Patients with + 1q had a median PFS of 13.4 mo (11 – NR) vs to 39.6 mo (25 – NR) in those without +1q (log rank P=0.09). Median OS was 37.3 mo (21.5 – NR). Correlative studies examining immune effector subsets before and after the addition of CL will be presented at the meeting. Conclusions Overall, PICd is a promising all PO regimen which combines convenient administration, tolerable side effect profile, and long duration of disease control.

To assess the psychometric properties of the Personality Inventory for ICD-11 (PiCD, where ICD-11 is the International Classification of Diseases, 11th Revision), a sample of Italian community-dwelling adult participants (N = 1,122) was administered the PiCD, the Five-Factor Model Rating Form, the Big Five Inventory, the Personality Inventory for DSM-5 Short Form (where DSM-5 is the Diagnostic and Statistical Manual of Mental Disorders, fifth edition), and the Measure of Disordered Personality Functioning. Our findings supported the unidimensionality hypothesis for the PiCD Negative Affectivity, Detachment, and Dissocial scale items, whereas adequate fit indices were observed for the bifactor model of the PiCD Disinhibition and Anankastic item joint polychoric correlation matrix. The PiCD scales showed adequate internal consistency, test-retest reliability (n = 262), and meaningful relationships with five-factor model domains and their maladaptive variants. A four-factor model of the joint correlation matrix of the PiCD, Personality Inventory for DSM-5 Short Form, and the five-factor model composite score was provided with adequate fit. All PiCD scales were significantly associated with the impairment in personality functioning. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Supplemental material, Suppl.Mat._-_PiCD_and_SASPD_revision for Personality Disorders in the ICD-11: Spanish Validation of the PiCD and the SASPD in a Mixed Community and Clinical Sample by Fernando Gutiérrez, Anton Aluja, José Ruiz, Luis F. García, Miguel Gárriz, Alfonso Gutiérrez-Zotes, David Gallardo-Pujol, Maria V. Navarro-Haro, Miquel Alabèrnia-Segura, Joan Ignasi Mestre-Pintó, Marta Torrens, Josep M. Peri, Bárbara Sureda, Joaquim Soler, Juan Carlos Pascual, Gemma Vall, Natalia Calvo, Marc Ferrer, Joshua R. Oltmanns and Thomas A. Widiger in Assessment

Supplemental material, Figure_S1_Hierarchical_Structure_of_the_PiCD for Personality Disorders in the ICD-11: Spanish Validation of the PiCD and the SASPD in a Mixed Community and Clinical Sample by Fernando Gutiérrez, Anton Aluja, José Ruiz, Luis F. García, Miguel Gárriz, Alfonso Gutiérrez-Zotes, David Gallardo-Pujol, Maria V. Navarro-Haro, Miquel Alabèrnia-Segura, Joan Ignasi Mestre-Pintó, Marta Torrens, Josep M. Peri, Bárbara Sureda, Joaquim Soler, Juan Carlos Pascual, Gemma Vall, Natalia Calvo, Marc Ferrer, Joshua R. Oltmanns and Thomas A. Widiger in Assessment

Dig Dis Sci DOI 10.1007/s10620-016-4248-5 EDITORIAL Prevention of the Paracentesis-Induced Circulatory Dysfunction (PICD) in Cirrhosis: Is the SPA Treatment Worthwhile? John Carl Hoefs 1 Received: 3 July 2016 / Accepted: 5 July 2016 O Springer Science+Business Media New York 2016 The older leading concept concerning ascites formation postulates an imbalance of oncotic and hydrostatic forces, with portal pressure pushing fluid into the peritoneal cavity opposed by the serum colloid osmotic pressure generated by albumin. When hydrostatic exceed oncotic forces, the abdominal cavity fills with fluid until a counterbalancing increase in abdominal pressure prevents further ascites formation. Furthermore, patients with ascites are almost perfectly separated from those without ascites on the basis of portal pressure (relative to the cardiac pressure) and serum albumin concentration [1] seeming to support this concept. According to this model, decreased intra-abdom- inal pressure due to fluid removal by paracentesis promotes fluid movement into the peritoneal cavity at the expense of the intravascular compartment, potentially resulting in catastrophic hypotension and renal failure. Since these events were thought to occur soon after paracentesis, the prevailing recommendation was for \2 L to be removed at any one time. Harmful effects from paracentesis were considered likely despite a large global clinical experience that had not identified a high incidence of hypotension or renal failure due to a common and routine clinical procedure. Two factors changed this view. The first was the description of oncotic-hydrostatic balance between serum and ascites [2–7] documenting an ‘‘abnormal balance’’ between colloid osmotic and hydrostatic pressure rather than an outright imbalance. In this model, the portal pres- sure gradient (portal pressure relative to intra-abdominal & John Carl Hoefs jchoefs@uci.edu Emeritus Professor, University of California, Irvine, Irvine, CA, USA pressure) was the major cause of ascites, as reflected in the serum to ascites albumin gradient (SAAG) both of which are unchanged after removing peritoneal fluid, during diuresis, or following albumin infusions [4, 5]. Thus, rapid formation of ascitic fluid was an unlikely consequence of paracentesis in this model although a fragile system sen- sitive to changes in intravascular volume might be pre- dicted. Furthermore, the model predicted the importance of the SAAG in the differential diagnosis of ascites, a widely accepted finding [4, 5] supporting the validity of this model. The second was data obtained from controlled trials that failed to document a major decrease in systemic blood pressure or an increased incidence of renal failure follow- ing paracentesis [7]. Indeed, control of ascites with para- centesis appeared safer than with diuretics [7]. Nevertheless, carefully controlled trials using sensitive hemodynamic measures did document statistically signifi- cant mild subclinical abnormalities such as alterations in plasma renin activity (PRA) and creatinine in some patients with tense ascites following complete fluid drainage or ‘‘total’’ paracentesis, usually days after the procedure and this is termed paracentesis-induced circulatory dysfunction (PICD) [8, 9]. Progressive renal failure or vascular collapse was not reported in these studies. Nonetheless, the concept of PICD became firmly established, with data supporting the concept that PICD could be prevented by salt-poor albumin (SPA) infusions [9]. The concern remained that some patients with PICD would deteriorate to the point that severe adverse clinical events occurred, justifying the expense of SPA infusions in all patients undergoing para- centesis. Furthermore, similar, but more pronounced alterations were present in the context of this fragile hemodynamic system such as spontaneous bacterial peri- tonitis, with hemodynamic improvement and increased survival attributed to concurrent SPA infusions [10]. Thus

An imbalance in apoptosis or survival of immune cells plays an essential role in the pathophysiology of sepsis. Phagocytosis-induced cell death (PICD) is a common result of the pathogen-host cell interaction mediated by reactive oxygen species (ROS). Neonatal sepsis is frequently characterized by hyperinflammation. Cord blood monocytes (CBMO) are equivalent to monocytes of adults [peripheral blood monocytes (PBMO)], both in terms of phagocytosis and killing of Escherichia coli. We investigated whether CBMO are less sensitive toward PICD compared with PBMO. Monocytes were infected with green fluorescent protein (GFP)-labeled E. coli. Phagocytic activity, cell-count, Annexin V staining, hypoploid DNA content, CD95 and CD95L expression, and caspase-8 and -9 activities were analyzed by flow cytometry, ROS production by chemiluminescence, and CD95L mRNA expression by reverse-transcriptase polymerase chain reaction. With equal phagocytic activity and ROS production, PBMO cell count was decreased by 82 +/- 6% versus 28 +/- 8% for CBMO after infection. Annexin V binding was enhanced fivefold on PBMO; 56 +/- 15% of PBMO showed a hypodiploid DNA content compared with 9 +/- 6% of CBMO. Caspases CD95L and CD95L mRNA were up-regulated in PBMO. Our results indicate that CBMO are less sensitive toward E. coli-mediated PICD than PBMO. Modifying monocyte apoptosis may be a target for future interventions in sepsis.

Passive Inflow Control Devices (PICD) are a common completion method for horizontal wells. A PICD completion can not only equalize the fluid influx along the length of the horizontal well but also can delay breakthrough of unwanted fluids and solve the challenges associated with uneven reservoir heterogeneities. Saudi Aramco is now the world leader in the use of PICD technology. Since the first installation of PICD in 2002, Saudi Aramco utilized various types of PICD for their sandstone and carbonate oil fields. Among these fields, one particular carbonate field was selected to study the performance of PICD completion and assess its effectiveness over barefoot completion. Production logs from 22 post-installation horizontal wells with PICD from the subject were analyzed. A near-wellbore simulator was used to match the actual fluid influx in PICD completion obtained from production logs. The matched model was used to simulate the flux profile for the openhole case and well performance was compared with PICD case. As part of the evaluation, production history of the PICD installed wells was also studied. Time-to-water breakthrough and increase in water-cut trends for PICD-installed wells were investigated to find how PICD design can improve fluid flux along the horizontal well and delay unwanted fluid. This exsercise helped identify optimization design guidelines with regards to number of compartments, PICDs per compartment and the process of dealing with uncertain changing well conditions in naturally fractured carbonate field. Dynamic modeling was also performed to evaluate the suggested PICD design recommendations with respect cumulative oil production and water breakthrough deferment. This paper describes the detailed evaluation methodology, analysis results for the selected field and subsequent recommendations for design practice to maximize the value of PICD.

Hintergrund: Apoptose-induzierendeMoleküle der TNF-Superfamilie (TNF-alpha, CD95) sind unmittelbar nach ihrer Synthese in der Membran verankert. Durch gleichzeitige, benachbarte Expression von Metalloproteasen können o.g. Moleküle vom Membrananker abgelöst und in die zellnahe [zum vollständigen Text gelangen Sie über die oben angegebene URL], 24. Jahrestagung der Deutschen Gesellschaft für Pädiatrische Infektiologie (DGPI)