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This article focuses on French author Didier Daeninckx’s 1986 crime novel Le Bourreau et son double[‘The Hangman and His Double’]. Daeninckx’s novel challenged official narratives that minimized the use of torture during the Algerian War and highlighted the brutalization of conscripted soldiers, the conflict’s hidden victims. Firstly, this article investigates Daeninckx’s use of what Max Silverman (2013) terms palimpsestic memory to highlight the interconnections between France’s process of decolonization throughout the 1960s, and 1980s France, which saw a rise in urban poverty and racism and a severe decline in left-leaning politics. Secondly, palimpsestic memory is closely associated with intertextuality and this article examines Daeninckx’s allusions to Georges Perec’s W ou le souvenir d’enfance(1975) [W, or the Memory of Childhood(1988)], which shares a similar structure and the themes of haunting and repressed memories with Le Bourreau et son double. Finally, the article emphasizes the value of popular culture, such as crime fiction, in the remembrance of hidden conflicts.

Early warning signs monitoring by service users with schizophrenia has shown promise in preventing relapse but the quality of evidence is low. We aimed to establish the feasibility of undertaking a definitive randomised controlled trial to determine the effectiveness of a blended digital intervention for relapse prevention in schizophrenia.

Judge Eugene H. Nickerson of the US District Court for the Eastern District of New York is memorialized.

A major challenge in cartilage tissue engineering (TE) is the development of instructive and biomimetic scaffolds capable of driving effective mesenchymal stem cell (MSC) chondrogenic differentiation and robust de novomatrix formation. Type I collagen-based scaffolds are one of the most commonly selected materials given collagen's intrinsic ability to act as an instructive and active biomaterial. However, the chondrogenic potential of these scaffolds does not offer significant improvement over traditional treatments. We propose that taking a biomimetic approach to scaffold development might lead to an improved outcome for enhanced cartilage repair. Therefore, this study aimed to develop innovative type II collagen (CII)-containing scaffolds for enhanced cartilage repair, by incorporating CII and/or hyaluronic acid (HyA) into a type I collagen (CI) framework. Moreover, focus was placed on understanding the potential synergistic effects played by CII in combination with HyA, in terms of MSC chondrogenesis and cartilage-like formation, when both molecules are incorporated into scaffold biomaterials. The newly developed CII-containing scaffold exhibited a highly porous interconnected structure with 99% porosity and similar mechanical properties to previously optimised collagen-based scaffolds. Although all scaffold variants sustained early cartilaginous matrix deposition, the CII-containing scaffolds in the presence of HyA performed best, offering enhanced deposition and distribution of sulphated glycosaminoglycans (sGAG) in vitroby day 28. Taken together, the combination of CII and HyA resulted in the development of a biomimetic scaffold with improved chondrogenic benefits. These simple “off-the-shelf” implants hold great promise to direct enhanced tissue regeneration for the treatment of focal cartilage defects.

The president’s power to grant clemency is but one feature of a sentence-correction ecosystem. But the abolition of federal parole in the 1980s left the clemency power as the only way to correct lawfully imposed sentences for the simple reason that they are too damn long. This article is about another way to correct sentences for that simple reason, one that has been right there all along but was moribund for decades, and about a 2018 statute and a Debevoise & Plimpton pro bono project that breathed life into it. And it is a critical Article III complement to the Article II clemency power. For the past five years, the Holloway Project at Debevoise has advocated for federal prisoners, overwhelmingly men of color, who were given bone-crushing sentences pursuant to the cruelest mandatory sentencing law the federal system had to offer. The typical Holloway Project client is a middle-aged man who was sentenced decades ago for robbery sprees in which a firearm was used but no one was hurt and little was stolen. In almost all of their cases, the indefensible sentences—often as not the equivalent of life without parole—had nothing to do with their culpability and everything to do with their refusals to cooperate and/or plead guilty. This article describes the Holloway Project and how it has used what has become known colloquially as the “compassionate release” statute, 18 U.S.C. § 3582(c)(1)(A), and 2018’s First Step Act to persuade federal judges to undertake holistic, compassionate reevaluations of the men these incarcerated individuals have become after all their years in prison, and inject some humanity and justice into a sentencing regime that is still in desperate need of both.

This study aimed to determine whether, following two years of specialized support for first‐episode psychosis, the addition of a new digital intervention (Horyzons) to treatment as usual (TAU) for 18 months was more effective than 18 months of TAU alone. We conducted a single‐blind randomized controlled trial. Participants were people with first‐episode psychosis (N=170), aged 16‐27 years, in clinical remission and nearing discharge from a specialized service. They were randomly assigned (1:1) to receive Horyzons plus TAU (N=86) or TAU alone (N=84) between October 2013 and January 2017. Horyzons is a novel, comprehensive digital platform merging: peer‐to‐peer social networking; theory‐driven and evidence‐informed therapeutic interventions targeting social functioning, vocational recovery and relapse prevention; expert clinician and vocational support; and peer support and moderation. TAU involved transfer to primary or tertiary community mental health services. The primary outcome was social functioning at 18 months as measured by the Personal and Social Performance Scale (PSP). Forty‐seven participants (55.5%) in the Horyzons plus TAU group logged on for at least 6 months, and 40 (47.0%) for at least 9 months. Social functioning remained high and stable in both groups from baseline to 18‐month follow‐up, with no evidence of significant between‐group differences (PSP mean difference: –0.29, 95% CI: –4.20 to 3.63, p=0.77). Participants in the Horyzons group had a 5.5 times greater increase in their odds to find employment or enroll in education compared with those in TAU (odds ratio, OR=5.55, 95% CI: 1.09‐28.23, p=0.04), with evidence of a dose‐response effect. Moreover, participants in TAU were twice as likely to visit emergency services compared to those in the Horyzons group (39% vs. 19%; OR=0.31, 95% CI: 0.11‐0.86, p=0.03, number needed to treat, NNT=5). There was a non‐significant trend for lower hospitalizations due to psychosis in the Horyzons group vs. TAU (13% vs. 27%; OR=0.36, 95% CI: 0.11‐1.08, p=0.07, NNT=7). So, although we did not find a significant effect of Horyzons on social functioning compared with TAU, the intervention was effective in improving vocational or educational attainment, a core component of social recovery, and in reducing usage of hospital emergency services, a key aim of specialized first‐episode psychosis services. Horyzons holds significant promise as an engaging and sustainable intervention to provide effective vocational and relapse prevention support for young people with first‐episode psychosis beyond specialist services.

The 10 Commandments Of Toxic Tort Defense Two recent court cases suggest a need to stress right and wrong ways to approach legal and scientific issues in toxic tort litigation. [...]

Oral delivery of potent peptide drugs provides key formulation challenges in the pharmaceutical industry: stability, solubility, and permeability. Intestinal permeation enhancers (PEs) can overcome the low oral bioavailability by improving the drug permeability. Conventional in vitroand ex vivomodels for assessing PEs fail to predict efficacy in vivo. Here, we compared Caco-2 cells cultured in the conventional static Transwell model to a commercially available continuous flow microfluidic Gut-on-a-Chip model. We determined baseline permeability of FITC-Dextan 3 kDa (FD3) in Transwell (5.3 ± 0.8 × 10–8cm/s) vs Chip (3.2 ± 1.8 × 10–7cm/s). We screened the concentration impact of two established PEs sodium caprate and sucrose monolaurate and indicated a requirement for higher enhancer concentration in the Chip model to elicit equivalent efficacy e.g., 10 mM sodium caprate in Transwells vs 25 mM in Chips. Fasted and fed state simulated intestinal fluids (FaSSIF/FeSSIF) were introduced into the Chip and increased basal FD3 permeability by 3-fold and 20-fold, respectively, compared to 4-fold and 4000-fold in Transwells. We assessed the utility of this model to peptides (Insulin and Octreotide) with PEs and observed much more modest permeability enhancement in the Chip model in line with observations in ex vivoand in vivopreclinical models. These data indicate that microfluidic Chip models are well suited to bridge the gap between conventional in vitroand in vivomodels.

DNA damage occurs as a result of environmental insults and aging and, if unrepaired, may lead to chromosomal instability and tumorigenesis. Because GH suppresses ataxia-telangiectasia mutated kinase phosphorylation, decreases DNA repair, and increases DNA damage accumulation, we elucidated whether GH effects on DNA damage are mediated through induced IGF-1. In nontumorous human colon cells, GH, but not IGF-1, increased DNA damage. Stably disrupted IGF-1 receptor (IGF-1R) by lentivirus-expressing short hairpin RNA in vitro or treatment with the IGF-1R phosphorylation inhibitor picropodophyllotoxin (PPP) in vitro and in vivo led to markedly induced GH receptor (GHR) abundance, rendering cells more responsive to GH actions. Suppressing IGF-1R triggered DNA damage in both normal human colon cells and three-dimensional human intestinal organoids. DNA damage was further increased when cells with disrupted IGF-1R were treated with GH. Because GH induction of DNA damage accumulation appeared to be mediated not by IGF-1R but probably by more abundant GH receptor expression, we injected athymic mice with GH-secreting xenografts and then treated them with PPP. In these mice, high circulating GH levels were associated with increased colon DNA damage despite disrupted IGF-1R activity (P < 0.01), whereas GHR levels were also induced. Further confirming that GH effects on DNA damage are directly mediated by GHR signaling, GHR-/- mice injected with PPP did not show increased DNA damage, whereas wild-type mice with intact GHR exhibited increased colon DNA damage in the face of IGF-1 signaling suppression. The results indicate that GH directly induces DNA damage independent of IGF-1.

The impact of the Internet across multiple aspects of modern society is clear. However, the influence that it may have on our brain structure and functioning remains a central topic of investigation. Here we draw on recent psychological, psychiatric and neuroimaging findings to examine several key hypotheses on how the Internet may be changing our cognition. Specifically, we explore how unique features of the online world may be influencing: a) attentional capacities, as the constantly evolving stream of online information encourages our divided attention across multiple media sources, at the expense of sustained concentration; b) memory processes, as this vast and ubiquitous source of online information begins to shift the way we retrieve, store, and even value knowledge; and c) social cognition, as the ability for online social settings to resemble and evoke real‐world social processes creates a new interplay between the Internet and our social lives, including our self‐concepts and self‐esteem. Overall, the available evidence indicates that the Internet can produce both acute and sustained alterations in each of these areas of cognition, which may be reflected in changes in the brain. However, an emerging priority for future research is to determine the effects of extensive online media usage on cognitive development in youth, and examine how this may differ from cognitive outcomes and brain impact of uses of Internet in the elderly. We conclude by proposing how Internet research could be integrated into broader research settings to study how this unprecedented new facet of society can affect our cognition and the brain across the life course.

In this tribute to the Honorable Jack B. Weinstein, his judicial successor highlights Judge Weinstein’s virtues and shares some of his wisdom. Included among these pearls are the conclusions that judges are obligated to confront injustices and that they are equal governmental partners with their executive and legislative colleagues. The essay also chronicles Judge Weinstein’s approach to sentencing and commitment to procedural justice.

The lack of success associated with the use of bone grafts has motivated the development of tissue engineering approaches for bone defect repair. However, the traditional tissue engineering approach of direct osteogenesis, mimicking the process of intramembranous ossification (IMO), leads to poor vascularization. In this study, we speculate that mimicking an endochondral ossification (ECO) approach may offer a solution by harnessing the potential of hypertrophic chondrocytes to secrete angiogenic signals that support vasculogenesis and enhance bone repair. We hypothesized that stimulation of mesenchymal stem cell (MSC) chondrogenesis and subsequent hypertrophy within collagen-based scaffolds would lead to improved vascularization and bone formation when implanted within a critical-sized bone defect in vivo.To produce ECO-based constructs, two distinct scaffolds, collagen–hyaluronic acid (CHyA) and collagen–hydroxyapatite (CHA), with proven potential for cartilage and bone repair, respectively, were cultured with MSCs initially in the presence of chondrogenic factors and subsequently supplemented with hypertrophic factors. To produce IMO-based constructs, CHA scaffolds were cultured with MSCs in the presence of osteogenic factors. These constructs were subsequently implanted into 7 mm calvarial defects on Fischer male rats for up to 8 weeks in vivo. The results demonstrated that IMO- and ECO-based constructs were capable of supporting enhanced bone repair compared to empty defects. However, it was clear that the scaffolds, which were previously shown to support the greatest cartilage formation in vitro(CHyA), led to the highest new bone formation (p< 0.05) within critical-sized bone defects 8 weeks postimplantation. We speculate this to be associated with the secretion of angiogenic signals as demonstrated by the higher VEGF protein production in the ECO-based constructs before implantation leading to the greater blood vessel ingrowth. This study thus demonstrates the ability of recapitulating a developmental process of bone formation to develop tissue-engineered constructs that manifest appreciable promise for bone defect repair.

Recent investigations into micro-architecture of scaffolds has revealed that mean pore sizes are cell-type specific and influence cellular shape, differentiation, and extracellular matrix secretion. In this context, the overall goal of this study was to investigate whether scaffold mean pore sizes affect mesenchymal stem cell initial attachment, chondrogenic gene expression, and cartilage-like matrix deposition. Collagen-hyaluronic acid (CHyA) scaffolds, recently developed in our laboratory for in vitrochondrogenesis, were fabricated with three distinct mean pore sizes (94, 130, and 300 μm) by altering the freeze-drying technique used. It was evident that scaffolds with the largest mean pore sizes (300 μm) stimulated significantly higher cell proliferation, chondrogenic gene expression, cartilage-like matrix deposition, and resulting bulk compressive modulus after in vitroculture, relative to scaffolds with smaller mean pore sizes (94, 130 μm). Taken together, these findings demonstrate the importance of scaffold micro-architecture in the development of advanced tissue engineering strategies for articular cartilage defect repair.

'As long as Wal-Mart doesn't buy them, I think we are okay.' --John Gleeson, vp, treasurer, Walgreens, commenting on impending sale of Eckerd Drugs by JCPenney, at Banc of America [...]

The jumping-to-conclusions bias has not been examined in a new religious movement (NRM) group. Twenty-seven delusion-prone NRM individuals were compared with 25 individuals with psychotic disorders and 63 non–delusion-prone individuals on four probabilistic inference tasks, together with measures of psychotic symptoms and delusion proneness. The NRM individuals requested significantly less evidence when compared with the control individuals on both meaningful and nonmeaningful tasks. The NRM individuals requested significantly more evidence on a difficult meaningful task when compared with the individuals with psychotic disorders. A specific reasoning style but not a general reasoning style differentiates the NRM individuals from the individuals with psychotic disorders. These findings may be specific to NRM individuals and may not be generalized to other delusion-prone groups.

The study examined the selective attention to threat bias in delusion-prone individuals recruited from New Religious Movements (NRMs). Twenty-seven delusion-prone NRM individuals were compared with 25 individuals with psychotic disorders and 63 non-delusion-prone individuals on a Stroop task, together with psychotic and delusion proneness measures. NRM individuals showed significantly lower levels of selective attention to threat bias compared with individuals with psychotic disorders but not with non-delusion-prone individuals. Selective attention to threat bias was also not correlated with distress associated with delusional ideation. These findings may be specific to delusion-prone NRM individuals. The absence of the selective attention to threat bias may be related to levels of safety and security among members of NRMs.

Objective: To investigate predictors of adherence with a cognitive-behavioural intervention in first-episode psychosis (FEP) patients.Method: Predictors of adherence to cognitive-behavioural therapy (CBT) were longitudinally investigated in the experimental arm of a randomized controlled trial designed to evaluate the effectiveness of a CBT intervention for relapse prevention early in the course of psychosis when compared with treatment as usual within 2 high quality, youth oriented, specialist FEP programs (the EPISODE II trial).Results: Longer duration of untreated psychosis (DUP) and poorer level of insight predicted poor adherence to CBT. This association remained significant after controlling for potential confounders.Conclusions: Treatment delay may decrease adherence with CBT in FEP patients. Reducing DUP and promoting insight early in the course of psychosis are likely to enhance adherence with CBT.

Semantic processing abnormalities are predicted to underlie thought disorder in schizophrenia. This study investigated semantic processing in relation to cognitive disorganization in schizotypy, a thought disorder analog. Schizotypy was measured in 53 healthy university students using the Oxford-Liverpool Inventory of Feelings and Experiences questionnaire. All participants completed 2 semantic priming tasks; direct and indirect (referring to the degree of association between word pair stimuli) and within each task, half of the stimuli were presented with a short time interval between prime and target presentation and half with a long time interval. Correlational analyses suggested that increasing cognitive disorganization was significantly associated with greater priming on the indirect tasks only. Separate analyses of the male and female data also revealed that men scoring highly on cognitive disorganization exhibited more indirect priming and less direct priming, whereas the female schizotypy data showed no significant correlations with either priming task. These findings are indicative of abnormal indirect priming in schizotypy, which was more pronounced in the male participant group. The findings of the present study further support the proposal that semantic processing is abnormal in schizophrenia, without the presence of potentially confounding factors that have limited research with clinical populations.

Langer–Giedion syndrome results from a microdeletion at 8q24.1 encompassing the EXT1and the adjacent TRPS1gene. We report on a boy with an oligo arraycgh characterized small microdeletion involving EXT1alone but with some features of Langer–Giedion syndrome suggesting a functional disturbance of TRPS1. This boy, in addition to a mild Langer–Giedion like phenotype, also had some unusual features including prominent toe pads and fat pads on the soles of his feet similar to those described in Pierpont syndrome. © 2008 WileyLiss, Inc.

There is increasing evidence that cognitive behavioural therapy (CBT) is efficacious in treating psychosis. However, very little attention has been paid to the nature of the control treatments used in studies of this. Befriending has been used as a control treatment in several randomized control trials (RCTs) of CBT for psychosis as it is simple to learn and administer. The aim of the present study was to examine whether Befriending controlled for important non-specific aspects of therapy when compared to CBT in a RCT for acute first episode psychosis (FEP). These non-specific factors included time in, expectancy created by, and acceptability of therapy. Expectations and enjoyment of therapy were measured by questionnaire. Time in therapy and the number of drop-outs were also recorded. Results showed that Befriending was comparable to CBT on measures of expectancy, enjoyment of therapy and drop-out rate, but significantly different with regard to time in therapy. This suggests that Befriending is a credible and acceptable control therapy for FEP with modification to increase time in therapy sessions. Methodological issues are raised, and suggestions for future research are made regarding control treatments.

Cross-sectional investigations, using the five-factor model of personality have evinced relationships among neuroticism, agreeableness, and psychotic symptoms. The current study examined these relationships via a prospective follow-up study with remitted first-episode psychosis patients. Baseline five-factor model personality profiles, diagnoses, symptom ratings, and premorbid adjustment ratings were followed by nine monthly ratings on Brief Psychiatric Rating Scale psychosis items in 60 first-episode patients. Valid baseline personality profiles were completed by 40 patients. Patients who had a return of symptoms scored higher on baseline neuroticism and agreeableness than those who remained in remission. Premorbid adjustment also predicted return of symptoms. After premorbid adjustment was controlled for, the agreeableness differences remained significant, but the neuroticism scores were no longer significantly different. It is concluded that lower agreeableness acts as a mediating variable in relapse. Further studies should clarify whether agreeableness is associated with specific biases in processing interpersonal information, and interpersonal behaviors.

AbstractThis article aims to overview a broad range of psychosocial treatments for first-episode psychosis, and for the prodromal phase (or so-called at-risk mental state)— the period preceding the first acute episode (Yung and McGorry, 1996). Firstly, an introduction to the empirically based rationale for early intervention in first-episode psychosis is provided. This is followed by a selective review of individual psychotherapies for early psychosis, which then proceeds to a discussion of family-based interventions for first-episode families and the role of group programs. Next, the role of psychological interventions within the newly emerging indicated preventiveapproach (Mrazek and Haggerty, 1994) for at-risk mental state is examined before some illustrative case material is presented. It is concluded that integrated psychosocial interventions for first-episode psychosis and for prodrome are newly emerging, innovative fields that offer some preventive opportunities. These opportunities, combined with some initial outcome data, warrant continuing research and clinical innovation.

Several letters to the editor are presented in response to articles published in earlier issues including "The dollars and cents of working abroad" in December 19, 1970 issue, one related to Christmas Corp. in December 5 issue and "They found newspapers best after all" again in the same issue.

Objective: The increasing focus on adolescent personality disorder has tended to ignore evidence of the developmental continuity of the period from puberty to young adulthood. This study aims to: (1) describe the characteristics of a sample of young people with borderline personality disorder (BPD) who had no previous history of evidence-based treatment for the disorder and (2) compare their characteristics by participant age group.Methods: One hundred and thirty-nine young people (15 to 25 years) with BPD, newly enrolled in the Monitoring Outcomes of BPD in Youth randomized controlled trial, completed semi-structured interview and self-report measures assessing demographic, clinical, and functional characteristics. Younger (aged 15 to 17 years; n= 64) and older (aged 18 to 25 years; n= 75) participants were compared on these same variables using t-tests, chi-square tests, and logistic regression.Results: Young outpatients with BPD had extensive and severe psychopathology and were functioning poorly. Adolescents and young adults with BPD showed substantial similarities on 20 key aspects of their presentation. Significant between-groups differences were observed in household makeup, treatment history, antisocial personality disorder, emotion dysregulation, substance use, age of commencement and extent of self-harm, and achievement of age-appropriate educational milestones. Adolescent BPD group membership was predicted by family composition and self-harm, whereas young adult BPD group membership was predicted by not achieving age-appropriate milestones, vocational disengagement, and emotion dysregulation. The final model explained 54% of the variance and correctly classified 80.2% of the sample by age.Conclusions: Both adolescents and young adults with early stage BPD present with severe and often similar problems to one another, supporting developmental continuity across this age range. However, there are also meaningful differences in presentation, suggesting that pathways to care might differ by age and/or developmental stage. Detection and intervention for personality disorder should not be delayed until individuals reach 18 years of age.

ABSTRACTIntestinal permeation enhancers (PEs) are key components in ∼12 oral peptide formulations in clinical trials for a range of molecules, primarily insulin and glucagon-like-peptide 1 (GLP-1) analogs. The main PEs comprise medium chain fatty acid-based systems (sodium caprate, sodium caprylate, and N-[8-(2-hydroxybenzoyl) amino] caprylate (SNAC)), bile salts, acyl carnitines, and EDTA. Their mechanism of action is complex with subtle differences between the different molecules. With the exception of SNAC and EDTA, most PEs fluidize the plasma membrane causing plasma membrane perturbation, as well as enzymatic and intracellular mediator changes that lead to alteration of intestinal epithelial tight junction protein expression. The question arises as to whether PEs can cause irreversible epithelial damage and tight junction openings sufficient to permit co-absorption of payloads with bystander pathogens, lipopolysaccharides and its fragment, or exo- and endotoxins that may be associated with sepsis, inflammation and autoimmune conditions. Most PEs seem to cause membrane perturbation to varying extents that is rapidly reversible, and overall evidence of pathogen co-absorption is generally lacking. It is unknown however, whether the intestinal epithelial damage-repair cycle is sustained during repeat-dosing regimens for chronic therapy.

The article reports on the implication of ruling by Canada Supreme Court for shíshálh (Sechelt) Nation and aboriginal people. It discusses the views of Chief Calvin Craigan regarding court's judgement. Also mentioned the role of Aboriginal people for Canadian provinces and the importance of the government policies on Aboriginal rights.

TO THE EDITOR:— The value of the electrocardiogram in spontaneous pneumothorax to date rests largely with the negative information gained, usually the exclusion of an acute cardiac event as a cause for sudden chest pain or dyspnea. Positive information is available, though this is largely of academic interest, particularly where radiographic study is available. Under rare circumstances the ECG may be of some practical value.In the tracings of a large number of cases of pneumothorax, the most prominent feature noted (by F.L.G.) was localized diminution of the QRS amplitude, particularly with a pneumothorax on the left.1 Modest shifts in axis were sometimes noted which usually returned to the previous state with expansion. The changes cited were most likely due to loss of potential transmitted to the chest wall because of the insulating effect of air interposed between thoracic structures and chest wall. The loss of "proximity" potentials may