Chemistry of pyrrocorphins: methylative opening of the macrocycle between rings A and D, a side reaction in the peripheral C-methylation of a 20-methyl-pyrrocorphinate

One of the minor products from the previously described peripheral -methylation of a magnesium()-20-methyl--pyrrocorphinate is a C-19-methylated 19,20-seco-corphinoid derivative which, on complexation with nickel() acetate, recyclizes to a nickel()-tetradehydro-corrinate.

Cancer's positive flip side: posttraumatic growth after childhood cancer.

BACKGROUND Surviving childhood cancer may result in positive psychological changes called posttraumatic growth (PTG). Knowing about the possibility of positive changes may facilitate survivors' reintegration in daily life. We aimed to (1) describe PTG in Swiss childhood cancer survivors including the most and the least common PTG phenomena on the subscale and item levels and (2) determine factors associated with PTG. METHOD Within the Swiss Childhood Cancer Survivor Study (SCCSS), we sent two questionnaires to childhood cancer survivors registered in the Swiss Childhood Cancer Registry (SCCR). Eligible survivors were diagnosed after 1990 at age ≤16 years, survived ≥5 years, and were aged ≥18 years at the time the second questionnaire was sent. We included the Posttraumatic Growth Inventory (PTGI) to assess five areas of PTG. We investigated the association of PTG with socio-demographic characteristics, self-reported late effects, and psychological distress, which were assessed in the SCCSS and clinical variables extracted from the SCCR. We used descriptive statistics to describe PTG and linear regressions to investigate factors associated with PTG. RESULTS We assessed PTG in 309 childhood cancer survivors. Most individuals reported to have experienced some PTG. The most endorsed change occurred in "relation with others," the least in "spiritual change." PTG was significantly higher in survivors with older age at diagnosis (p = 0.001) and those with a longer duration of treatment (p = 0.042), while it was lower in male survivors (p = 0.003). CONCLUSIONS Supporting experiences of PTG during follow-up may help survivors successfully return to daily life.

After-effects and after-effects and after-effects of after-effects: The multiple side effects of prospective memory

In a prospective memory task responding to a prospective memory target involves switching between ongoing and prospective memory task which can result in a slowing of subsequent ongoing task performance (i.e., an after-effect). Moreover, a slowing can also occur when prospective memory targets occur after the prospective memory task is deactivated (i.e., another after-effect). In this study, we investigated both after-effects within the same study. Moreover, we also tested whether the latter after-effects even occur on subsequent ongoing task trials. The results show, in fact, after-effects of all kinds. Thus, (1) correctly responding to prospective memory targets results in after-effects, a so far neglected cost on ongoing task performance, (2) responding to deactivated prospective memory targets also slows down performance, probably due to the involuntary retrieval of the intention, and (3) this slowing is present even on subsequent ongoing task trials, suggesting that even deactivated intentions are sufficient to induce a conflict that requires subsequent adaptation. Overall, these results indicate that performance slowing in a prospective memory experiment includes various kinds of sources, not only monitoring cost, and these sources may be understood best in terms of conflict adaptation.

The Dark Side of the Moon: Meta-analytical Impact of Recruitment Strategies on Risk Enrichment in the Clinical High Risk State for Psychosis

Background: The individual risk of developing psychosis after being tested for clinical high-risk (CHR) criteria (posttest risk of psychosis) depends on the underlying risk of the disease of the population from which the person is selected (pretest risk of psychosis), and thus on recruitment strategies. Yet, the impact of recruitment strategies on pretest risk of psychosis is unknown. Methods: Meta-analysis of the pretest risk of psychosis in help-seeking patients selected to undergo CHR assessment: total transitions to psychosis over the pool of patients assessed for potential risk and deemed at risk (CHR+) or not at risk (CHR−). Recruitment strategies (number of outreach activities per study, main target of outreach campaign, and proportion of self-referrals) were the moderators examined in meta-regressions. Results: 11 independent studies met the inclusion criteria, for a total of 2519 (CHR+: n = 1359; CHR−: n = 1160) help-seeking patients undergoing CHR assessment (mean follow-up: 38 months). The overall meta-analytical pretest risk for psychosis in help-seeking patients was 15%, with high heterogeneity (95% CI: 9%–24%, I 2 = 96, P < .001). Recruitment strategies were heterogeneous and opportunistic. Heterogeneity was largely explained by intensive (n = 11, β = −.166, Q = 9.441, P = .002) outreach campaigns primarily targeting the general public (n = 11, β = −1.15, Q = 21.35, P < .001) along with higher proportions of self-referrals (n = 10, β = −.029, Q = 4.262, P = .039), which diluted pretest risk for psychosis in patients undergoing CHR assessment. Conclusions: There is meta-analytical evidence for overall risk enrichment (pretest risk for psychosis at 38monhts = 15%) in help-seeking samples selected for CHR assessment as compared to the general population (pretest risk of psychosis at 38monhts=0.1%). Intensive outreach campaigns predominantly targeting the general population and a higher proportion of self-referrals diluted the pretest risk for psychosis.

Nonperturbative results for two-index conformal windows

Via large and small N c relations we derive nonperturbative results about the conformal window of two-index theories. Using Schwinger-Dyson methods as well as four-loops results we estimate subleading corrections and show that naive large number of colors extrapolations are unreliable when N c is less than about six. Nevertheless useful nonper-turbative inequalities for the size of the conformal windows, for any number of colors, can be derived. By further observing that the adjoint conformal window is independent of the number of colors we argue, among other things, that: the large N c two-index conformal window is twice the conformal window of the adjoint representation (which can be determined at small N c) expressed in terms of Dirac fermions; lattice results for adjoint matter can be used to provide independent information on the conformal dynamics of two-index theories such as SU(N c) with two and four symmetric Dirac flavors.

The Hydroxyl Side Chain of a Highly Conserved Serine Residue Is Required for Cation Selectivity and Substrate Transport in the Glial Glutamate Transporter GLT-1/SLC1A2

Glutamate transporters maintain synaptic concentration of the excitatory neurotransmitter below neurotoxic levels. Their transport cycle consists of cotransport of glutamate with three sodium ions and one proton, followed by countertransport of potassium. Structural studies proposed that a highly conserved serine located in the binding pocket of the homologous GltPh coordinates l-aspartate as well as the sodium ion Na1. To experimentally validate these findings, we generated and characterized several mutants of the corresponding serine residue, Ser-364, of human glutamate transporter SLC1A2 (solute carrier family 1 member 2), also known as glutamate transporter GLT-1 and excitatory amino acid transporter EAAT2. S364T, S364A, S364C, S364N, and S364D were expressed in HEK cells and Xenopus laevis oocytes to measure radioactive substrate transport and transport currents, respectively. All mutants exhibited similar plasma membrane expression when compared with WT SLC1A2, but substitutions of serine by aspartate or asparagine completely abolished substrate transport. On the other hand, the threonine mutant, which is a more conservative mutation, exhibited similar substrate selectivity, substrate and sodium affinities as WT but a lower selectivity for Na(+) over Li(+). S364A and S364C exhibited drastically reduced affinities for each substrate and enhanced selectivity for l-aspartate over d-aspartate and l-glutamate, and lost their selectivity for Na(+) over Li(+). Furthermore, we extended the analysis of our experimental observations using molecular dynamics simulations. Altogether, our findings confirm a pivotal role of the serine 364, and more precisely its hydroxyl group, in coupling sodium and substrate fluxes.

On the Dark Side of Therapies with Immunoglobulin Concentrates: The Adverse Events

Therapy by human immunoglobulin G (IgG) concentrates is a success story ongoing for decades with an ever increasing demand for this plasma product. The success of IgG concentrates on a clinical level is documented by the slowly increasing number of registered indication and the more rapid increase of the off-label uses, a topic dealt with in another contribution to this special issue of Frontiers in Immunology. A part of the success is the adverse event (AE) profile of IgG concentrates which is, even at life-long need for therapy, excellent. Transmission of pathogens in the last decade could be entirely controlled through the antecedent introduction by authorities of a regulatory network and installing quality standards by the plasma fractionation industry. The cornerstone of the regulatory network is current good manufacturing practice. Non-infectious AEs occur rarely and mainly are mild to moderate. However, in recent times, the increase in frequency of hemolytic and thrombotic AEs raised worrying questions on the possible background for these AEs. Below, we review elements of non-infectious AEs, and particularly focus on hemolysis and thrombosis. We discuss how the introduction of plasma fractionation by ion-exchange chromatography and polishing by immunoaffinity chromatographic steps might alter repertoire of specificities and influence AE profiles and efficacy of IgG concentrates.

Norm enforcement in the city revisited: An international field experiment of altruistic punishment, norm maintenance, and broken windows

In laboratory experiments, people are willing to sanction norms at a cost—a behavioral tendency called altruistic punishment. However, the degree to which these findings can be generalized to real-world interactions is still debated. Only a small number of field experiments have been conducted, and initial results suggest that punishment is less frequent outside of the lab. This study replicates one of the first field experiments on altruistic punishment and builds ties to research on norm compliance and the broken windows theory. The original study addressed the enforcement of the anti-littering norm in Athens. We replicate this study in Bern, Zurich, and New York City. As an extension, we investigate how the experimental context (clean vs littered) impacts social norm enforcement. As a second extension, we investigate how opportunity structure impacts the maintenance of the anti-littering norm. Findings indicate that norms are universally enforced, although significantly less than in the standard laboratory experiment,and that enforcement is significantly more common in Switzerland than in New York. Moreover, individuals prefer more subtle forms of enforcement to direct punishment. We also find that enforcement is less frequent in littered than in clean contexts, suggesting that broken windows might not only foster deviant behavior but also weaken informal social control. Finally, we find that opportunity structure can encourage people to maintain norms, as indicated by the fact that people are more likely to voluntarily pick up litter when it is closer to a trash bin.

An evaluation of the impact of Inner City Development's Cooperative Home School: An educational alternative program to increase the quality and level of education in San Antonio's West Side community

The research study was intended to evaluate the effectiveness of Inner City Development's (I.C.D.) Cooperative Home School, an educational alternative program to the Title I public schools of San Antonio's West Side community. The study investigated students', parents' and tutors' perception of parental involvement and educational resources. The study also investigated each student's academic achievement. ^ The study found that students progressed toward expected math proficiency at a faster rate than they did in reading proficiency. However, because the target population size was small and a comparison group was not used, the results of this study are only suggestive. This research also indicated that study subjects believed students' quality and level of education increased substantially since program exposure. Study subjects mainly attributed the students' strides in academic performance to the increased amount of individualized attention students received in the small twelve-student class size. Study subjects were more satisfied with the home school's educational resources than those of the Title I public schools. Study subjects also perceived that parental involvement both at home and at school increased since enrollment in the home school program because: (1) there were more opportunities for involvement in the home school; and (2) parents felt closer to the tutors than the teachers in public school. ^ This evaluation also suggested improvements to program operations. With the help of additional volunteers, I.C.D. program operators could improve collection and organization of academic records. Furthermore, as suggested by program participants, science could be added to the curriculum. Lastly, a formal tutor orientation could be implemented to familiarize and train tutors on classroom management procedures. ^

A comparison of worker risk of injury while working on fully automated side loaders and other residential collection trucks at a large solid waste collection company

The study aim was to determine whether using automated side loader (ASL) trucks in higher proportions compared to other types of trucks for residential waste collection results in lower injury rates (from all causes). The primary hypothesis was that the risk of injury to workers was lower for those who work with ASL trucks than for workers who work with other types of trucks used in residential waste collection. To test this hypothesis, data were collected from one of the nation’s largest companies in the solid waste management industry. Different local operating units (i.e. facilities) in the company used different types of trucks to varying degrees, which created a special opportunity to examine refuse collection injuries and illnesses and the risk reduction potential of ASL trucks.^ The study design was ecological and analyzed end-of-year data provided by the company for calendar year 2007. During 2007, there were a total of 345 facilities which provided residential services. Each facility represented one observation.^ The dependent variable – injury and illness rate, was defined as a facility’s total case incidence rate (TCIR) recorded in accordance with federal OSHA requirements for the year 2007. The TCIR is the rate of total recordable injury and illness cases per 100 full-time workers. The independent variable, percent of ASL trucks, was calculated by dividing the number of ASL trucks by the total number of residential trucks at each facility.^ Multiple linear regression models were estimated for the impact of the percent of ASL trucks on TCIR per facility. Adjusted analyses included three covariates: median number of hours worked per week for residential workers; median number of months of work experience for residential workers; and median age of residential workers. All analyses were performed with the statistical software, Stata IC (version 11.0).^ The analyses included three approaches to classifying exposure, percent of ASL trucks. The first approach included two levels of exposure: (1) 0% and (2) >0 - <100%. The second approach included three levels of exposure: (1) 0%, (2) ≥ 1 - < 100%, and (3) 100%. The third approach included six levels of exposure to improve detection of a dose-response relationship: (1) 0%, (2) 1 to <25%, (3) 25 to <50%, (4) 50 to <75%, (5) 75 to <100%, and (6) 100%. None of the relationships between injury and illness rate and percent ASL trucks exposure levels was statistically significant (i.e., p<0.05), even after adjustment for all three covariates.^ In summary, the present study shows that there is some risk reduction impact of ASL trucks but not statistically significant. The covariates demonstrated a varied yet more modest impact on the injury and illness rate but again, none of the relationships between injury and illness rate and the covariates were statistically significant (i.e., p<0.05). However, as an ecological study, the present study also has the limitations inherent in such designs and warrants replication in an individual level cohort design. Any stronger conclusions are not suggested.^