Molecular study of the perforin gene in familial hematological malignancies

Perforin gene (PRF1) mutations have been identified in some patients diagnosed with the familial form of hemophagocytic lymphohistiocytosis (HLH) and in patients with lymphoma. The aim of the present study was to determine whether patients with a familial aggregation of hematological malignancies harbor germline perforin gene mutations. For this purpose, 81 unrelated families from Tunisia and France with aggregated hematological malignancies were investigated. The variants detected in the PRF1 coding region amounted to 3.7% (3/81). Two of the three variants identified were previously described: the p.Ala91Val pathogenic mutation and the p.Asn252Ser polymorphism. A new p.Ala 211Val missense substitution was identified in two related Tunisian patients. In order to assess the pathogenicity of this new variation, bioinformatic tools were used to predict its effects on the perforin protein structure and at the mRNA level. The segregation of the mutant allele was studied in the family of interest and a control population was screened. The fact that this variant was not found to occur in 200 control chromosomes suggests that it may be pathogenic. However, overexpression of mutated PRF1 in rat basophilic leukemia cells did not affect the lytic function of perforin differently from the wild type protein

Albumin and mammalian cell culture: implications for biotechnology applications

Albumin has a long historical involvement in design of media for the successful culture of mammalian cells, in both the research and commercial fields. The potential application of albumins, bovine or human serum albumin, for cell culture is a by-product of the physico-chemical, biochemical and cell-specific properties of the molecule. In this review an analysis of these features of albumin leads to a consideration of the extracellular and intracellular actions of the molecule, and importantly the role of its interactions with numerous ligands or bioactive factors that influence the growth of cells in culture: these include hormones, growth factors, lipids, amino acids, metal ions, reactive oxygen and nitrogen species to name a few. The interaction of albumin with the cell in relation to these co-factors has a potential impact on metabolic and biosynthetic activity, cell proliferation and survival. Application of this knowledge to improve the performance in manufacturing biotechnology and in the emerging uses of cell culture for tissue engineering and stem cell derived therapies is an important prospect

Quantifying sources of variability in infancy research using the infant-directed-speech preference

Psychological scientists have become increasingly concerned with issues related to methodology and replicability, and infancy researchers in particular face specific challenges related to replicability: For example, high-powered studies are difficult to conduct, testing conditions vary across labs, and different labs have access to different infant populations. Addressing these concerns, we report on a large-scale, multisite study aimed at (a) assessing the overall replicability of a single theoretically important phenomenon and (b) examining methodological, cultural, and developmental moderators. We focus on infants’ preference for infant-directed speech (IDS) over adult-directed speech (ADS). Stimuli of mothers speaking to their infants and to an adult in North American English were created using seminaturalistic laboratory-based audio recordings. Infants’ relative preference for IDS and ADS was assessed across 67 laboratories in North America, Europe, Australia, and Asia using the three common methods for measuring infants’ discrimination (head-turn preference, central fixation, and eye tracking). The overall meta-analytic effect size (Cohen’s d) was 0.35, 95% confidence interval = [0.29, 0.42], which was reliably above zero but smaller than the meta-analytic mean computed from previous literature (0.67). The IDS preference was significantly stronger in older children, in those children for whom the stimuli matched their native language and dialect, and in data from labs using the head-turn preference procedure. Together, these findings replicate the IDS preference but suggest that its magnitude is modulated by development, native-language experience, and testing procedure. (This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 798658.

Ovarian cancer molecular pathology.

Peer reviewe

Quantifying Sources of Variability in Infancy Research Using the Infant-Directed-Speech Preference

Psychological scientists have become increasingly concerned with issues related to methodology and replicability, and infancy researchers in particular face specific challenges related to replicability: For example, high-powered studies are difficult to conduct, testing conditions vary across labs, and different labs have access to different infant populations. Addressing these concerns, we report on a large-scale, multisite study aimed at (a) assessing the overall replicability of a single theoretically important phenomenon and (b) examining methodological, cultural, and developmental moderators. We focus on infants’ preference for infant-directed speech (IDS) over adult-directed speech (ADS). Stimuli of mothers speaking to their infants and to an adult in North American English were created using seminaturalistic laboratory-based audio recordings. Infants’ relative preference for IDS and ADS was assessed across 67 laboratories in North America, Europe, Australia, and Asia using the three common methods for measuring infants’ discrimination (head-turn preference, central fixation, and eye tracking). The overall meta-analytic effect size (Cohen’s d) was 0.35, 95% confidence interval = [0.29, 0.42], which was reliably above zero but smaller than the meta-analytic mean computed from previous literature (0.67). The IDS preference was significantly stronger in older children, in those children for whom the stimuli matched their native language and dialect, and in data from labs using the head-turn preference procedure. Together, these findings replicate the IDS preference but suggest that its magnitude is modulated by development, native-language experience, and testing procedure

Safety and efficacy of fluoxetine on functional outcome after acute stroke (AFFINITY): a randomised, double-blind, placebo-controlled trial

Background Trials of fluoxetine for recovery after stroke report conflicting results. The Assessment oF FluoxetINe In sTroke recoverY (AFFINITY) trial aimed to show if daily oral fluoxetine for 6 months after stroke improves functional outcome in an ethnically diverse population. Methods AFFINITY was a randomised, parallel-group, double-blind, placebo-controlled trial done in 43 hospital stroke units in Australia (n=29), New Zealand (four), and Vietnam (ten). Eligible patients were adults (aged ≥18 years) with a clinical diagnosis of acute stroke in the previous 2–15 days, brain imaging consistent with ischaemic or haemorrhagic stroke, and a persisting neurological deficit that produced a modified Rankin Scale (mRS) score of 1 or more. Patients were randomly assigned 1:1 via a web-based system using a minimisation algorithm to once daily, oral fluoxetine 20 mg capsules or matching placebo for 6 months. Patients, carers, investigators, and outcome assessors were masked to the treatment allocation. The primary outcome was functional status, measured by the mRS, at 6 months. The primary analysis was an ordinal logistic regression of the mRS at 6 months, adjusted for minimisation variables. Primary and safety analyses were done according to the patient's treatment allocation. The trial is registered with the Australian New Zealand Clinical Trials Registry, ACTRN12611000774921. Findings Between Jan 11, 2013, and June 30, 2019, 1280 patients were recruited in Australia (n=532), New Zealand (n=42), and Vietnam (n=706), of whom 642 were randomly assigned to fluoxetine and 638 were randomly assigned to placebo. Mean duration of trial treatment was 167 days (SD 48·1). At 6 months, mRS data were available in 624 (97%) patients in the fluoxetine group and 632 (99%) in the placebo group. The distribution of mRS categories was similar in the fluoxetine and placebo groups (adjusted common odds ratio 0·94, 95% CI 0·76–1·15; p=0·53). Compared with patients in the placebo group, patients in the fluoxetine group had more falls (20 [3%] vs seven [1%]; p=0·018), bone fractures (19 [3%] vs six [1%]; p=0·014), and epileptic seizures (ten [2%] vs two [<1%]; p=0·038) at 6 months. Interpretation Oral fluoxetine 20 mg daily for 6 months after acute stroke did not improve functional outcome and increased the risk of falls, bone fractures, and epileptic seizures. These results do not support the use of fluoxetine to improve functional outcome after stroke

Intrapersonal versus peer group predictors of adolescent drug use

In this third report from the Alberta High School study we present data on the predictors of adolescent drug use. Results revealed that conduct disorder and peer pressure were the best predictors of drug-taking across adolescence generally but that significant age x gender differences existed in the strength of these associations. Contrary to expectations, conduct disorder was found to be more closely associated with the illicit drug use of 12&ndash;13 year-old boys than same-age girls. Friends\u27 drug use was also more predictive of the drug use of 12&ndash;13 yearold boys, while overt peer pressure was a better predictor of 12&ndash;13 year-old girls\u27 drug use. Except for friends\u27 drug use, which remained more important for boys than girls throughout adolescence, differences in intrapersonal and peer predictors between males and females ended after the age of 12&ndash;13 years. The implications of these findings for drug prevention programs are considered

New Tools to Enhance Familiar Data: The Micro-computer's Use in Generating Information from Census Material

The purpose of this paper is to describe a current study which utilised micro-computer software as a research tool to generate information from the Australian Bureau of Statistics 1986 Census data. Census material has been an under utilised resource in social work practice but with the arrival of some recent micro-computer software this kind of secondary data can now be processed quickly and easily into descriptive formats to aid in social service planning and delivery. The processed data can also provide an information base for further evaluative and exploratory research. The final part of the reported study demonstrates such an application using Cluster Analysis

Transactional Analysis of AIDS Prevention Advertising

Germane to the production and use of health education advertisements is their effectiveness. MacLachlan, Carr, Fardell, Maffesoni, and Cunningham (1997) proposed that an HIV/AIDS health education message is more effective when the ego state “hooked” by the advertisement is complementary (parallel) to the ego state experienced during sexual interaction. The aim of this study was to test this model further and, through minor modification of the original design, to gather additional salient subsidiary data. One hundred and forty-four sexually active Australian undergraduates viewed two government-sponsored television advertisements (“Reaper” and “Beds”) designed to prevent the spread of acquired immune deficiency syndrome (AIDS). After the viewing, the participants were asked to identify the ego states projected by the advertisements, the ego states they would have preferred to have projected, and their prediction of their own ego state during sexual interaction with both a steady and a casual partner. The participants rated the effectiveness of each of the two advertisements on a categorical scale (poor, satisfactory, good, and excellent) for each of two dimensions (conveying knowledge about HIV/ AIDS and conveying the need for safe sexual practices). Higher ratings for effectiveness on both dimensions were found for parallel transactions represented as matches between projected ego states and preferred ego states at the time of viewing (x 2 (N = 143) = 33.7 p < .001; x 2 (3, N = 143) = 43.1 p < .001; x 2 (3, N = 140) = 36.1 p < .001; and x 2 (N = 141) = 28.1 p < .001), but not for matches (parallel transactions) between advertisement projected ego states and predicted ego states for self during sexual interactions. Analysis of subsidiary data revealed that predicted ego states did not differ according to type of sexual partner (steady, casual); both advertisements were rated as more effective in conveying the need for safe sexual practices than knowledge about HIV/AIDS (z − 6.8, p < .001 & z − 8.9 p < .001); the “Beds” advertisement was rated more effective than the “Reaper” advertisement for both knowledge impact and need for safe practices (z − 2.67, p < .01 & z − 6.0 p < .001); and the majority (63% and 66%) of respondents selected Adult to Adult as their preferred ego states for the advertisements to project. The utility of transactional analysis in the social marketing and evaluation of health education is discussed with reference to overcoming its limitations through the development of a transactional positioning approach