The Montreal Criteria for the Ethical Feasibility of Uterine Transplantation

Absolute uterine factor infertility (UFI) refers to the refractory causes of female infertility stemming from the anatomical or physiological inability of a uterus to sustain gestation. Today, uterine factor infertility affects 3-5% of the population. Traditionally, although surrogacy and adoption have been the only viable options for females affected by this condition, the uterine transplant is currently under investigation as a potential medical alternative for women who desire to go through the experience of pregnancy. Although animal models have shown promising results, human transplantation cases have only been described in case reports and a successful transplant leading to gestation is yet to occur in humans. Notwithstanding the intricate medical and scientific complexities that a uterine transplant places on the medical minds of our time, ethical questions on this matter pose a similar, if not greater, challenge. In light of these facts, this article attempts to present the ethical issues in the context of experimentation and standard practice which surround this controversial and potentially paradigm-altering procedure; and given these, introduces "The Montreal Criteria for the Ethical Feasibility of Uterine Transplantation", a set of proposed criteria required for a woman to be ethically considered a candidate for uterine transplantation.     

Can Dialysis Patients Be Accurately Identified Using Healthcare Claims Data?

♦ Background: While health insurance claims data are often used to estimate the costs of renal replacement therapy in patients with end-stage renal disease (ESRD), the accuracy of methods used to identify patients receiving dialysis — especially peritoneal dialysis (PD) and hemodialysis (HD) — in these data is unknown.♦ Methods: The study population consisted of all persons aged 18 - 63 years in a large US integrated health plan with ESRD and dialysis-related billing codes (i.e., diagnosis, procedures) on healthcare encounters between January 1, 2005, and December 31, 2008. Using billing codes for all healthcare encounters within 30 days of each patient’s first dialysis-related claim (“index encounter”), we attempted to designate each study subject as either a “PD patient” or “HD patient.” Using alternative windows of ± 30 days, ± 90 days, and ± 180 days around the index encounter, we reviewed patients’ medical records to determine the dialysis modality actually received. We calculated the positive predictive value (PPV) for each dialysis-related billing code, using information in patients’ medical records as the “gold standard.”♦ Results: We identified a total of 233 patients with evidence of ESRD and receipt of dialysis in healthcare claims data. Based on examination of billing codes, 43 and 173 study subjects were designated PD patients and HD patients, respectively (14 patients had evidence of PD and HD, and modality could not be ascertained for 31 patients). The PPV of codes used to identify PD patients was low based on a ± 30-day medical record review window (34.9%), and increased with use of ± 90-day and ± 180-day windows (both 67.4%). The PPV for codes used to identify HD patients was uniformly high — 86.7% based on ± 30-day review, 90.8% based on ± 90-day review, and 93.1% based on ± 180-day review.♦ Conclusions: While HD patients could be accurately identified using billing codes in healthcare claims data, case identification was much more problematic for patients receiving PD.     

Are Different Individuals Sensitive to Different Environments? Individual Differences in Sensitivity to the Effects of the Parent,Peer and School Environment on Externalizing Behavior and its Genetic and Environmental Etiology

Behavior Genetics - Externalizing behavior is substantially affected by genetic effects, which are moderated by environmental exposures. However, little is known about whether these moderation...     

Do what you say and say what you are going to do: A preliminary meta-analysis of client change and sustain talk subtypes in motivational interviewing

Abstract

Objective: This meta-analysis examines the predictive validity of client change language subtypes in motivational interviewing (MI) sessions addressing addictive behavior change. Method: A systematic review identified k?=?13 primary studies, contributing 16 MI conditions (N?=?1556). The pooled correlation coefficient was used to assess the significance, direction, and strength of seven language subtypes (i.e., reason, desire, need, ability, commitment, taking steps, and other) by three valences (i.e., frequency positive or change talk, frequency negative or sustain talk, and proportion change talk) and their relationship to subsequent engagement in addictive behavior. Results: For frequency measures, more sustain talk related to reason, desire, ability, and other were associated with more addictive behavior at follow up. Other change talk was associated with MI outcomes but in an unexpected direction (i.e., more addictive behavior). Proportion measures showed more proportion change talk-reason and -other statements were associated with less addictive behavior at follow up. Sensitivity analyses indicated some heterogeneity and instability of effect sizes, but no evidence of publication bias. Conclusions: This preliminary meta-analysis suggests that aggregate measures of change and sustain talk are comprised of statement subtypes that are not equally meaningful in predicting outcome following MI for addictive behavior change.     

Incentive motivation deficits in schizophrenia reflect effort computation impairments during cost-benefit decision-making

Background

Motivational impairments are a core feature of schizophrenia and although there are numerous reports studying this feature using clinical rating scales, objective behavioural assessments are lacking. Here, we use a translational paradigm to measure incentive motivation in individuals with schizophrenia.

Methods

Sixteen stable outpatients with schizophrenia and sixteen matched healthy controls completed a modified version of the Effort Expenditure for Rewards Task that accounts for differences in motoric ability. Briefly, subjects were presented with a series of trials where they may choose to expend a greater amount of effort for a larger monetary reward versus less effort for a smaller reward. Additionally, the probability of receiving money for a given trial was varied at 12%, 50% and 88%. Clinical and other reward-related variables were also evaluated.

Results

Patients opted to expend greater effort significantly less than controls for trials of high, but uncertain (i.e. 50% and 88% probability) incentive value, which was related to amotivation and neurocognitive deficits. Other abnormalities were also noted but were related to different clinical variables such as impulsivity (low reward and 12% probability). These motivational deficits were not due to group differences in reward learning, reward valuation or hedonic capacity.

Conclusions

Our findings offer novel support for incentive motivation deficits in schizophrenia. Clinical amotivation is associated with impairments in the computation of effort during cost-benefit decision-making. This objective translational paradigm may guide future investigations of the neural circuitry underlying these motivational impairments.     

Phosphoantigens and butyrophilin 3A1 induce similar intracellular activation signaling in human TCRVγ9 γδ T lymphocytes

Human γδ cells expressing TCRVγ9 are T lymphocytes with great potential for cancer immunotherapy and unconventional pattern of antigen specificity. These HLA-unrestricted lymphocytes are specifically reactive to non-peptide metabolites (phosphoantigens) and to the butyrophilin 3A (BTN3A/CD277) protein. Whether recognition of such highly different structures trigger the same activation signaling pathway remains unclear, however. Here we combined fluorescent cell barcoding and phosphoflow analysis of TCRVγ9⁺ T lymphocytes to compare simultaneously the level of several signaling phosphoproteins after activation by phosphoantigen (BrHPP) or by anti-BTN3A (monoclonal antibody 20.1). This approach shows that the same pathways involving ZAP70, PLCγ2, Akt, NFκB p65, MAPK p38 and Erk1, were induced by either of these stimuli. These data strongly suggest the TCRVγ9⁺ T lymphocytes detect phosphoantigens and butyrophilin A3 by the same recognition process.