The Loss of Pleasure,or Why We Are Still Talking about Oedipus

This article brings psychoanalysis to the fore in grappling with the question: Why does patriarchy persist? It highlights the psychological function of patriarchy as a defense against loss by connecting Gilligan's research on development with Bowlby's studies of attachment. Pathological responses to loss parallel the gender codes of patriarchal masculinity and femininity, which are internalized through an initiation that forces ruptures in relationship and subverts the capacity for repair. This parallel suggests that the gender roles, which uphold a patriarchal order, simultaneously defend against the loss of connection inherent in that order. The loss of pleasure and a change in voice signal the psyche's induction into patriarchy and highlight a potential within psychoanalysis to foster a healthy resistance against losses that otherwise appear necessary or natural.     

A Mechanistic Proof-of-concept Clinical Trial With JX-594, a Targeted Multi-mechanistic Oncolytic Poxvirus,in Patients With Metastatic Melanoma

JX-594 is a targeted and granulocyte macrophage-colony stimulating factor (GM-CSF)-expressing oncolytic poxvirus designed to selectively replicate in and destroy cancer cells through viral oncolysis and tumor-specific immunity. In order to study the mechanisms-of-action (MOA) of JX-594 in humans, a mechanistic proof-of-concept clinical trial was performed at a low dose equivalent to ≤10% of the maximum-tolerated dose (MTD) in other clinical trials. Ten patients with previously treated stage IV melanoma were enrolled. Tumors were injected weekly for up to nine total treatments. Blood samples and tumor biopsies were analyzed for evidence of transgene activity, virus replication, and immune stimulation. The β-galactosidase (β-gal) transgene was expressed in all patients as evidenced by antibody induction. Six patients had significant induction of GM-CSF-responsive white blood cell (WBC) subsets such as neutrophils (25–300% increase). JX-594 replication and subsequent shedding into blood was detectable in five patients after cycles 1–9. Tumor biopsies demonstrated JX-594 replication, perivascular lymphocytic infiltration, and diffuse tumor necrosis. Mild flu-like symptoms were the most common adverse events. In sum, JX-594 replication, oncolysis, and expression of both transgenes were demonstrated; replication was still evident after multiple cycles. These findings have implications for further clinical development of JX-594 and other transgene-armed oncolytic viruses.     

Altered BAFF‐receptor signaling and additional modifier loci contribute to systemic autoimmunity in A/WySnJ mice

Systemic lupus erythematosus pathology reflects autoantibody‐mediated damage due to a failure of B‐lymphocyte tolerance. We previously reported that B‐lymphopenic A/WySnJ mice develop a lupus‐like syndrome and linked this syndrome to the B‐cell maturation defect‐1 (Bcmd‐1) mutant allele of the B‐cell‐activating factor belonging to the TNF family‐receptor (Baffr) gene. Here, we further evaluate the genetic basis for autoimmunity in A/WySnJ mice. We produced B6.Bcmd‐1 and AW.Baffr^?/? congenic mice (N5), and compared them with B6.Baffr^?/? and A/WySnJ mice with respect to B‐lymphocyte development. Bcmd‐1‐expressing mice had more B cells with greater maturity than Baffr^?/? mice regardless of genetic background, indicating that Bcmd‐1 encodes a partially functional BAFF‐R. We also compared these mice for lupus phenotypes to determine whether Bcmd‐1 is necessary and sufficient for disease, or whether the Baffr^?/?‐ allele can also cause autoimmunity. The Baffr^?/? allele did not lead to autoimmunity on either genetic background. In contrast, the Bcmd‐1 allele was necessary and sufficient for development of low levels of IgM autoantibodies in B6.Bcmd‐1 mice. However, Bcmd‐1 plus unidentified A/WySnJ modifier genes were necessary for development of IgG autoantibodies and renal pathology. We propose that in A/WySnJ mice an excess of BAFF per B cell rescues self‐reactive B cells through a partially functional BAFF‐R in a B‐lymphopenic environment.     

Early outgrowth EPCs generation is reduced in patients with Buerger’s disease

Background  

Buerger’s disease often shows poor collateral artery generation (i.e. neovascularization) in the ischemic limbs. However, the etiology has not yet been clarified. Circulating endothelial progenitor cells (EPCs) derived from bone marrow contribute to neovascularization in the multi-step process which includes the following capacities; mobilization, differentiation, adhesion, migration, invasion and secretion.     

Colorectal surgery in octogenarian patients—outcomes and predictors of morbidity

Introduction  Surgery for elderly patients pose a constant challenge. This study aims to review the outcome and find predictors of adverse outcome in octogenarians undergoing major colorectal resection for cancer. Methods  A review of 121 octogenarians who underwent colorectal cancer surgery between September 1992 and May 2008 was performed. Comorbidities were quantified using the weighted Charlson Comorbidity Index and ASA classification. CR-POSSUM scores and ACPGBI scores and the predicted mortality rates were calculated. Outcome measures were morbidity rates and 30-day mortality rates. Results  The patients had a mean age of 83.5 years (range, 80–99). The mean index of comorbidity was 3.1 (2–7) and 12.5% of patients were classified ASA III and above. The mean predicted mortality rate based on CR-POSSUM and ACPGBI scoring models were 11.2% and 5.4% respectively. The overall observed morbidity rate was 30.7% and 30-day mortality was 1.6. Factors found on bivariate analysis to be significantly associated with an increased risk of morbidity were tumor presenting with complication, comorbid coronary heart disease, serum urea levels, ASA classification ≥3 and comorbidity index 3 of 5 ≥ 5. Multivariate analysis revealed the latter two factors to be independent predictors of morbidity. Conclusion  Octogenarians undergoing major colorectal resection have an acceptable perioperative morbidity and mortality rate and survival rate and should not be denied surgery based on age alone. Comorbidity index scores and ASA scores are useful tools to identify poor risk patients.     

Latent profile analysis of healthy schizotypy within the extended psychosis phenotype

Converging evidence suggests that psychosis exists on a continuum, and that even mentally “healthy” individuals may experience subclinical psychotic experiences. However, little research has examined the subjective and psychological well-being of individuals in the putatively healthy end of the continuum. This study explored the latent profile structure of schizotypy in a non-clinical sample and compared subjective and psychological well-being across schizotypy profiles. Latent profile analysis was conducted on participants' responses (N=420) to the Oxford-Liverpool Inventory of Feelings and Experiences. Six latent profiles emerged: Low Schizotypy, Average, High Schizotypy, High Unusual Experiences (UE), High Introvertive Anhedonia, and High Introvertive Anhedonia/Cognitive Disorganization. Individuals in the profile characterized by high UE without negative, disorganized or impulsive features tended to endorse similar levels of well-being as the Average and Low Schizotypy profiles. With some exceptions, all three profiles also demonstrated significantly greater subjective and psychological well-being when compared to negative/disorganized schizotypy profiles. The UE profile most closely aligns with previous conceptualizations of “healthy schizotypy.” Future research should investigate how individuals in this profile make sense of unusual or ambiguous experiences that may lead to distress in clinical populations.     

Validation and comparison of ActiGraph activity monitors

Objective: To compare activity counts from the ActiGraph GT3X to those from the ActiGraph GT1M during treadmill walking/running. A secondary aim was to develop tri-axial vector magnitude (VM3) cut-points to classify physical activity (PA) intensity. Methods: Fifty participants wore the GT3X and the GT1M on the non-dominant hip and exercised at 4 treadmill speeds (4.8, 6.4, 9.7, and 12 km h⁻¹). Vertical (VT) and antero-posterior (AP) activity counts (counts min⁻¹) as well as the vector magnitudes of the two axes (VM2) from both monitors were tested for significant differences using two-way ANOVA's. Bland–Altman plots were used to assess agreement between activity counts from the GT3X and GT1M. Linear regression analysis between VM3 counts min⁻¹ and oxygen consumption data was conducted to develop VM3 cut-points for moderate, hard and very hard PA. Results: There were no significant inter-monitor differences in VT activity counts at any speed. AP and VM2 activity counts from the GT1M were significantly higher (p < 0.01) than those from the GT3X at 4.8, 9.7 and 12 km h⁻¹. High inter-monitor agreement was found for VT activity counts but not for AP and VM2 activity counts. VM3 cut-points for moderate, hard, and very hard PA intensities were 2690–6166, 6167–9642, >9642 counts min⁻¹. Conclusion: Due to the lack of congruence between the AP and VM2 activity counts from the GT1M and the GT3X, comparisons of data obtained with these two monitors should be avoided when using more than just the VT axis. VM3 cut-points may be used to classify PA in future studies.     

Helping the soul: the relationship between connectivity and well‐being within a church community

Although previous research attests to the importance of psychological sense of community (PSOC) to individuals' well‐being, little research has examined this relationship for the four proposed dimensions of PSOC: membership, influence, integration and fulfillment of needs, and shared emotional connection (McMillan & Chavis, 1986). Further, little research has explored multiple aspects of community connectivity in the one study. The current research investigated the relationship between participants' (N=127) religiosity, PSOC, social support, and identification within a church community context and their well‐being. Results indicated that the PSOC dimensions of shared emotional connection and influence were particularly important in the prediction of well‐being in this context. Further, individuals' perception of social support mediated the relationship between PSOC and well‐being and the strength of individuals' identification as a church member enhanced the relationships of both PSOC and religiosity with well‐being. © 2009 Wiley Periodicals, Inc.