Evaluation of the Homogenous Mobility Shift Assay for Infliximab and Adalimumab Anti-drug Antibody Detection in the Clinical Laboratory.

BACKGROUND: Detecting antidrug antibodies (ADAs) against infliximab or adalimumab is useful for therapeutic drug monitoring. Various ADA detection methods exist, and antibody titer is an output in some algorithms. Homogenous mobility shift assay (HMSA) measures relative ADA concentration and determines drug-ADA complex size in vitro. However, the relevance of complex size determination in drug monitoring remains unclear. Hence, the association between complex size, ADA concentration, and sample detectable neutralizing activity was evaluated. METHODS: Sera from infliximab-treated and adalimumab-treated patients who tested positive for ADA in the National Screening Service were analyzed using 3 ADA assays. HMSA determined the relative ADA concentrations and complex sizes, competitive ligand-binding assay evaluated the sample neutralizing capacity, and enzyme-linked immunosorbent assay detected immunoglobulin (Ig)G4 ADA. RESULTS: Most ADA-positive samples (>80%) formed drug-ADA dimer complexes, whereas 17% had dimer and multimer complexes, and 3% had multimeric complexes. Multimer presence had 100% positive predictive value for detectable neutralizing activity. ADA concentration and detectable neutralizing activity were moderately correlated (r = 0.65) in adalimumab-treated patients and strongly correlated (r = 0.81) in infliximab-treated patients. In adalimumab-treated patients, multimer presence was a stronger predictor of neutralizing activity than ADA concentration was, but not in infliximab-treated patients. However, in infliximab-treated patient samples, multimer presence revealed a distinct subset with high ADA concentrations, neutralizing activity, and IgG4 ADA. CONCLUSIONS: Multimers detected using HMSA had a strong positive predictive value for competitive ligand-binding assay detectable neutralizing activity. Multimeric IgG4-containing ADA-drug complexes revealed a distinct subset of infliximab-treated patient samples, whose clinical relevance merits further investigation.

Mirror self-recognition in gorillas (Gorilla gorilla gorilla): a review and evaluation of mark test replications and variants.

Mirror self-recognition (MSR), widely regarded as an indicator of self-awareness, has not been demonstrated consistently in gorillas. We aimed to examine this issue by setting out a method to evaluate gorilla self-recognition studies that is objective, quantifiable, and easy to replicate. Using Suarez and Gallup's (J Hum Evol 10:175-183, 1981) study as a reference point, we drew up a list of 15 methodological criteria and assigned scores to all published studies of gorilla MSR for both methodology and outcomes. Key features of studies finding both mark-directed and spontaneous self-directed responses included visually inaccessible marks, controls for tactile and olfactory cues, subjects who were at least 5 years old, and clearly distinguishing between responses in front of versus away from the mirror. Additional important criteria include videotaping the tests, having more than one subject, subjects with adequate social rearing, reporting post-marking observations with mirror absent, and giving mirror exposure in a social versus individual setting. Our prediction that MSR studies would obtain progressively higher scores as procedures and behavioural coding practices improved over time was supported for methods, but not for outcomes. These findings illustrate that methodological rigour does not guarantee stronger evidence of self-recognition in gorillas; methodological differences alone do not explain the inconsistent evidence for MSR in gorillas. By implication, it might be suggested that, in general, gorillas do not show compelling evidence of MSR. We advocate that future MSR studies incorporate the same criteria to optimize the quality of attempts to clarify the self-recognition abilities of gorillas as well as other species.

Limb preference and personality in donkeys (Equus asinus).

Interhemispheric laterality has often been linked to different behavioural styles. This study investigates the link between limb preference and personality in donkeys. The sample consisted of 47 donkeys (Equus asinus), 30 males and 17 females. Limb preference was determined using observation of the leading limb in a motionless posture and personality was measured using the Donkey Temperament Questionnaire (French, J. M. (1993). Assessment of donkey temperament and the influence of home environment. Applied Animal Behaviour Science, 36(2), 249-257. doi:10.1016/0168-1591(93)90014-G) completed by the donkeys' keepers. A Principal Component Analysis obtained two components: Agreeableness and Extraversion. Age showed a positive relationship with Agreeableness, echoing trends in humans Donkeys did not show a population-level preference towards either side. Limb preference significantly predicted the trait difficult to handle: donkeys with a preference to keep the right foot forward when motionless were harder to handle. This study presents the first investigation into limb preference and personality in donkeys, although more research is needed to clarify whether there is a population-level limb preference bias in donkeys, and the relationship between limb preference and Agreeableness.

Ape recognition of familiar human faces changed by time and COVID-19 face masks.

Reports of primates being able to recognise familiar humans are rare in the literature and tend to be regarded as anecdotal. The COVID-19 pandemic created two unique conditions facilitating the observation of spontaneous face recognition in zoo apes: i) lengthy gaps in contact with human visitors due to lockdowns and zoo closures, and ii) the wearing of face masks obscuring at least half the face of familiar individuals. Here, I report on the historical context of the familiarity between a primatologist and individual apes of two species, how those apes consistently showed recognition of this particular human over a time span of up to thirty years, how facial recognition was extended to family members, and how recognition persisted even when a significant portion of the face was obscured by a mask. This constitutes, to my knowledge, the first documented cases of recognition of familiar human faces changed by time and COVID-19 face masks in two great ape species. Although based on just two individuals, the documentation of this ability is important because it arose in a more naturalistic and spontaneous context compared to typical face processing research in which primates are tested with experimental stimuli in a laboratory setting. Implications for face processing theory and applications for the therapeutic utility of faces are discussed. These observations provide insight into the evolutionary origins of face recognition and, sitting at the interface of science and society, are of interest to a wide audience.

Design and Implementation of an Opt-Out, End-to-End, Preemptive DPYD Testing Program for Patients Planned for a Systemic Fluoropyrimidine.

PURPOSE: Several allelic variants of the gene DPYD encoding dihydropyrimidine dehydrogenase (DPD) are associated with impaired metabolism of the systemic fluoropyrimidine fluorouracil (5FU) and its oral prodrug, capecitabine, which elevates the risk for severe toxicity. Following a patient death related to capecitabine toxicity in which DPD deficiency was suspected, a multidisciplinary advisory panel was convened to develop an institution-wide approach to future patients planned for a systemic fluoropyrimidine. METHODS: The panel selected an opt-out testing strategy which focused on developing reliable processes to collect and report test results and targeted education. An electronic health record-based automated reminder was designed to activate when a 5FU- or capecitabine-containing chemotherapy regimen was ordered for a patient without prior exposure to either agent and without a prior DPYD sequencing test result. DPYD testing was standardized across all sites of care, and a closed loop reporting system for abnormal test results was created. Before implementation, targeted education was provided to providers, pharmacists, and nurses, and a failure mode and effects analysis was performed. Program rollout was staged over a 6-month period. RESULTS: At 10 months, the rate of preemptive testing increased from a baseline of 26% to a sustained rate of >90%. In the six network sites, the testing rate increased from 9% to 96%. A total of 1,043 patients have been tested preemptively; allelic variants have been identified in 43 (4.1%). Among 25 evaluable patients, dose reduction or change to a non-fluoropyrimidine-based regimen was accomplished in 96%. CONCLUSION: Preemptive DPYD testing is feasible, and high rates of testing can be achieved using an opt-out, reminder-based program. We provide the details of the implementation and encourage others to emulate it.

Facial Expression of TIPI Personality and CHMP-Tri Psychopathy Traits in Chimpanzees (Pan troglodytes) : Evidence for Honest Signalling?

Honest signalling theory suggests that humans and chimpanzees can extract socially relevant information relating to personality from the faces of their conspecifics. Humans are also able to extract information from chimpanzees' faces. Here, we examine whether personality characteristics of chimpanzees, including measures of psychopathy, can be discerned based purely on facial morphology in photographs. Twenty-one chimpanzees were given naïve and expert personality ratings on the Ten Item Personality Inventory (TIPI) and the Chimpanzee Triarchic Model of Psychopathy (CHMP-Tri) before and following behavioural observations. Characteristics relating to openness, conscientiousness, extraversion, and disinhibition could be distinguished from the faces of chimpanzees. Individuals higher on disinhibition have lower scores on conscientiousness and emotional stability and higher scores on extraversion, while those higher on meanness have lower conscientiousness and agreeableness. Facial expressions are linked to personality traits present in the TIPI and CHMP-Tri models: the Relaxed Face and the Grooming Face were displayed more by chimpanzees higher on agreeableness, whereas the Compressed Lips Face was observed more in those individuals higher on boldness, and the Full Open Grin was displayed more by chimpanzees higher on extraversion but lower on emotional stability and conscientiousness. Facial expressions were also found to be associated with particular behavioural contexts, namely the Grooming Face in affiliative contexts and the Relaxed and Relaxed Open Mouth Faces in neutral contexts. Dominant chimpanzees display higher levels of boldness and more Compressed Lips Faces, Relaxed Open Mouth Faces, and Grooming Faces than subordinate individuals. These findings support and extend evidence for an honest signalling system and a personality structure shared between humans and chimpanzees. Future research could further explore how personality is conveyed through the face, perhaps through more than just singular aspects of character, and maybe reflecting what chimpanzees themselves are able to do.

Feasibility and Acceptability of Internet-Based Interpersonal Psychotherapy for Stress, Anxiety, and Depression in Prenatal Women: Thematic Analysis.

BACKGROUND: Prenatal mental health is a global health concern. Despite the far-reaching impact of prenatal mental health issues, many women do not receive the psychological care they require. Women in their childbearing years are frequent users of the internet and smartphone apps. Prenatal women are prime candidates for internet-based support for mental health care. OBJECTIVE: This study aimed to examine the feasibility and acceptability of internet-based interpersonal psychotherapy (IPT) for prenatal women. METHODS: Semistructured interviews were conducted with women who had received internet-based IPT modules with guided support as a component of a randomized controlled trial evaluating the scale-up implementation of a digital mental health platform (The Healthy Outcomes of Pregnancy and Postpartum Experiences digital platform) for pregnant women. Qualitative thematic analysis was used to explore and describe women's experiences. Data were analyzed for emerging themes, which were identified and coded. RESULTS: A total of 15 prenatal women were interviewed to examine their experiences and views on the feasibility and acceptability of internet-based IPT modules. Participants found the content informative and appreciated the ways in which the digital mental health platform made the IPT modules accessible to users. Participants voiced some differing requirements regarding the depth and the way information was presented and accessed on the digital mental health platform. The important areas for improvement that were identified were acknowledging greater depth and clarity of content, the need for sociability and relationships, and refinement of the digital mental health platform to a smartphone app. CONCLUSIONS: This study provides useful evidence regarding treatment format and content preferences, which may inform future development. It also provides research data on the feasibility and acceptability of web-based applications for prenatal mental health care. TRIAL REGISTRATION: ClinicalTrials.gov NCT01901796; https://clinicaltrials.gov/ct2/show/NCT01901796.

Personality and behavioral changes in Asian elephants (Elephas maximus) following the death of herd members.

Elephants are highly social beings with complex individual personalities. We know that elephants have a general interest in death, investigating carcasses, not just limited to kin; however, research does not explore in depth whether individuals change their behavior or personality following traumatic events, such as the death of a conspecific. Within a captive herd of Asian elephants (Elephas maximus) housed at Chester Zoo, UK, we measured social behavior and proximity and personality using the Ten-Item Personality Inventory, and found age-related and relationship-related changes in both behavior and personality following the deaths of herd members. Overall, the herd spent less time socializing and engaging in affiliative behaviors following the death of the adult female when compared to baseline data, yet spent more time engaging in these behaviors after the death of two calves. The death of the central female had a dramatic impact on her infant calf, resulting in increasingly withdrawn behavior, yet had the opposite effect on her adult daughter, who subsequently established a more integrated role within the herd. Emotional Stability fell in the motherless calf but rose in an adult female, who had lost her adult daughter, but had a new calf to care for. We suggest that the greater impact on the behavior and personality of surviving herd members following the deaths of calves, compared to an adult member, attests to the significance of the unifying role played by calves within an elephant herd.

Video-mediated behavior in gorillas (gorilla gorilla gorilla): A stage in the development of self-recognition in a juvenile male?

The anomalous position of gorillas (Gorilla gorilla gorilla) in the capacity for self-recognition remains puzzling. The standard measure of self-recognition is Gallup's (1970) mark test that assesses an individual's ability to recognize its altered image in a mirror following the application of paint marks to visually inaccessible areas. Here, the results of a small-scale pilot study are presented, utilizing video playback through a TV monitor, to examine behavioral differences indicative of developing self-recognition. The behaviors of 4 Western lowland gorillas at Bristol Zoo, United Kingdom, were observed while watching a TV screen during 5 conditions: blank screen, white noise interference, footage of unfamiliar gorillas, self previously recorded, and self-live. Differences were predicted in the frequency of the gorillas' observed behaviors when viewing each of the conditions: specifically, that there would be more visual inspection, contingent body and facial movements, and self-exploration in the self-recorded and self-live conditions compared with the other conditions. These predictions were partially supported. No agonistic or fear responses were observed, and self-exploration was only seen in the self-live condition. During live playback, contingency-checking movements and self-exploration of the mouth were observed, particularly in the youngest gorilla, providing important video evidence of a close parallel to the mouth exploratory behavior witnessed in self-recognizing chimpanzees. On the basis of these preliminary findings of differentiated spontaneous behaviors, a tentative framework is proposed for categorizing gorillas according to levels of developing self-recognition along a continuum. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

There is no other monkey in the mirror for spider monkeys (Ateles geoffroyi).

Mirror self-recognition (MSR), usually considered a marker of self-awareness, occurs in several species and may reflect a capacity that has evolved in small incremental steps. In line with research on human development and building on previous research adopting a gradualist framework, we categorized the initial mirror responses of naïve spider monkeys (Ateles geoffroyi) according to four levels. We compared social, exploratory, contingent and self-exploratory responses to a mirror and faux mirror during three short trials. If spider monkeys respond as most monkey species, we predicted they would perform at level 0, mainly showing social behavior toward their mirror-image. However, because spider monkeys show enhancement of certain cognitive skills comparable to those of great ape species, we predicted that they would perform at level 1a (showing exploratory behavior) or 1b (showing contingent behavior). GLMMs revealed that monkeys looked behind and visually inspected the mirror significantly more in the mirror than the faux mirror condition. Although the monkeys engaged in contingent body movements at the mirror, this trend was not significant. Strikingly, they showed no social behaviors toward their mirror-image. We also measured self-scratching as an indicator of anxiety and found no differences in frequencies of self-scratching between conditions. Therefore, in contrast to most findings on other species, spider monkeys did not treat their image as another monkey during their initial exposure to the mirror. In fact, they reached at least level 1a within minutes of mirror exposure. These responses recommend spider monkeys as good candidates for further explorations into monkey self-recognition. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Concurrent and short-term longitudinal associations between peer victimization and school and recess liking during middle childhood.

BACKGROUND: Prior studies outside of the UK have shown that peer victimization is negatively associated with school adjustment. AIMS: To examine concurrent and short-term longitudinal associations between peer victimization (physical, malicious teasing, deliberate social exclusion, and malicious gossiping) and two measures of school adjustment (school liking and recess liking), and test if these associations were moderated by year and sex. SAMPLE: A UK sample of 429 pupils in Years 4, 5, and 6 (Grades 3, 4, and 5, respectively, in USA) participated in the Autumn/Winter (Time 1) and 189 of these provided follow-up data during the Spring/Summer (Time 2) of the same school year. METHOD: Peer nominations of victimization, and self-reports of school adjustment were collected in individual and small group interviews. RESULTS: At time 2 (but not Time 1), victimization predicted concurrent school liking among year 6 pupils but not among year 4/5 pupils, and victimization predicted recess liking among all pupils. Victimization also predicted changes in School liking among boys (not girls) and among Year 6 (not Year 4/5) pupils, and victimization predicted changes in recess liking among all pupils. CONCLUSIONS: The associations between victimization and poor school adjustment found elsewhere were replicated with this British sample. The implications of these results for children's social adjustment at school were discussed.

Neuroticism and extraversion mediate the relationship between having a sibling with developmental disabilities and anxiety and depression symptoms.

Background Children growing up with a sibling with disabilities report higher levels of depression and anxiety symptoms as adults. Here, we examined whether personality characteristics also play a part in mediating this relationship. Method We tested for differences in personality traits between 132 individuals who have a sibling with developmental disabilities and 132 closely matched comparisons. Results Differences in Big Five factors of personality were demonstrated across the disability groups and between the disability groups and the comparisons, especially in Extraversion, Neuroticism and Openness. Individuals growing up alongside a sibling with developmental disabilities have a higher tendency to experience anxiety and depression symptoms, and this research is the first demonstration that personality traits mediate this relationship. Specifically, Neuroticism is a strong mediator of anxiety while both Neuroticism and Extraversion contribute mediating effects toward the development of depression. Limitations Our study made use of self-report methodology which, although having recognized limitations, is more reliable than parental reports. Given the cross-sectional nature of our design, we were not able to examine pre-existing developmental factors that may have influenced the participant's propensity to particular personality traits and affective disorders. However, we obtained a large sample and closely matched participants to examine differences between those with a sibling with disabilities and those without. Conclusions As such, differences in personality traits have important implications for the understanding and treatment of siblings presenting with anxiety and depression symptoms. We recommend that intervention should target those high in Neuroticism among individuals who have a sibling with disabilities, and that more social support is put in place for siblings to mitigate their tendency towards introversion and buffer them against psychological maladjustment.

Complex Sociality of Wild Chimpanzees Can Emerge from Laterality of Manual Gestures.

Humans are strongly lateralized for manual gestures at both individual and population levels. In contrast, the laterality bias in primates is less strong, leading some to suggest that lateralization evolved after the Pan and Homo lineages diverged. However, laterality in humans is also context-dependent, suggesting that observed differences in lateralization between primates and humans may be related to external factors such as the complexity of the social environment. Here we address this question in wild chimpanzees and examine the extent to which the laterality of manual gestures is associated with social complexity. Right-handed gestures were more strongly associated with goal-directed communication such as repair through elaboration in response to communication failure than left-handed gestures. Right-handed gestures occurred in evolutionarily urgent contexts such as in interactions with central individuals in the network, including grooming reciprocity and mating, whereas left-handed gestures occurred in less-urgent contexts, such as travel and play. Right-handed gestures occurred in smaller parties and in the absence of social competition relative to left-handed gestures. Right-handed gestures increased the rate of activities indicating high physiological arousal in the recipient, whereas left-handed gestures reduced it. This shows that right- and left-handed gestures differ in cognitive and social complexity, with right-handed gestures facilitating more complex interactions in simpler social settings, whereas left-handed gestures facilitate more rewarding interactions in complex social settings. Differences in laterality between other primates and humans are likely to be driven by differences in the complexity of both the cognitive skills underpinning social interactions and the social environment.

Quality of Explanation as an Indicator of Fraction Magnitude Understanding.

Students' explanations of their mathematical thinking and conclusions have become a greater part of the assessment landscape in recent years. With a sample of 71 fourth-grade students at risk for mathematics learning disabilities, we investigated the relation between student accuracy in comparing the magnitude of fractions and the quality of students' explanations of those comparisons, as well as the relation between those measures and scores on a criterion test: released fraction items from the National Assessment of Educational Progress. We also considered the extent to which reasoning and language contribute to the prediction. Results indicated a significant moderate correlation between accuracy and explanation quality. Commonality analyses indicated that explanation quality accounts for little variance in National Assessment of Educational Progress scores beyond what is accounted for by traditional measures of magnitude understanding. Implications for instruction and assessment are discussed.

Internet-based interpersonal psychotherapy for stress, anxiety, and depression in prenatal women: study protocol for a pilot randomized controlled trial.

BACKGROUND: Psychological distress, defined as depression, anxiety and perceived stress, during pregnancy is common, with 15-25% of women experiencing clinically significant levels of such distress. Despite the far-reaching impact of prenatal psychological distress on mothers and their children, and that women are receptive to screening, few providers routinely screen for prenatal psychological distress and less than one in five women will receive the mental health care that they require. There is a lack of certainty regarding the most effective treatments for prenatal psychological distress. No online interpersonal psychotherapy (IPT) trials have been conducted that focus on improving psychological distress in prenatal women. The purpose of this pilot randomized controlled trial is to evaluate the perspectives of pregnant women on the feasibility and acceptability of online IPT (e-IPT) delivered during pregnancy. METHODS: A pilot randomized controlled trial design with repeated measures will evaluate the feasibility and acceptability of e-IPT for pregnant women compared to routine prenatal care. Qualitative interviews with 15-30 individuals in the intervention group will provide further data on the feasibility and acceptability of the intervention. Assessment of feasibility will include the ease of accessing and completing the intervention. Women will also be asked about what barriers there were to starting and completing the e-IPT. Assessment of acceptability will inquire about the perception of women regarding the intervention and its various features. A sample size of 160 consenting pregnant women aged 18 years and older will be enrolled and randomized into the experimental (e-IPT) or control (routine care) condition. The secondary outcome measures include: depression, anxiety and stress symptoms; self-efficacy; self-mastery; self-esteem; relationship quality (spouse, immediate family members); coping; and resilience. All participants will complete the aforementioned measures at baseline during pregnancy (T1), 3 months postrandomization (T2), at 8 months of pregnancy (T3), and 3 months postpartum (T4). DISCUSSION: The results of this pilot randomized controlled trial will provide data on the feasibility and acceptability of the intervention and identify necessary adaptations. This study will allow for optimization of full trial processes and inform the evaluation strategy, including sample size calculations for the full randomized controlled trial. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01901796. Registered on 18 December 2014.

Associations between peer victimization, fear of future victimization and disrupted concentration on class work among junior school pupils.

BACKGROUND: Studies have shown that peer victimization is associated with psychological maladjustment, and have implicated such maladjustment in disrupted ability to concentrate. AIMS: To investigate the levels of, and associations between, physical, verbal, and social exclusion victimization, fear of future victimization, and disrupted classroom concentration. SAMPLE: Participants consisted of 485 pupils aged 10-11 drawn from 11 junior schools in the UK. METHOD: Peer- and self-nominations of physical, verbal, and social exclusion victimization were collected in individual interviews. Self-reports of other variables were collected either individually or in small groups. RESULTS: A substantial minority of pupils reported high levels of fear of future victimization and disrupted concentration on class work, and girls reported higher levels of fear of future victimization than boys. All three types of self-reported victimization, all three types of peer-reported victimization, and fear of all three types of future victimization predicted disrupted concentration on class work. Fear of future social exclusion moderated the association between peer-reported social exclusion and disrupted concentration on class work. CONCLUSIONS: In addition to tackling victimization per se, allaying pupils' fears of it happening to them in the future is called for in order to address a hitherto largely overlooked correlate, and possible source, of disrupted classroom concentration.

What children do on the Internet: domains visited and their relationship to socio-demographic characteristics and academic performance.

HomeNetToo is a longitudinal field study designed to examine the antecedents and consequences of home Internet use in low-income families. Participants included 140 children, mostly 13-year-old African American (83%) boys (58%), living in single-parent households (75%) where the median annual income was $15,000 (USD). This report focuses on children's Internet activities, socio-demographic characteristics related to their Internet activities, and the relationship between academic performance and Internet activities. Overall, findings indicate that low-income children initially use the Internet primarily for entertainment. As home Internet use loses its novelty children become more focused in their Internet activities, reducing the number of websites they visit and visiting more websites targeted to their specific interests. Pornography websites are popular initially, especially among boys, but their popularity decreases dramatically after 3 months. Age, race, and sex have little influence on which websites are most popular. Academic performance predicts subsequent Internet activities, and Internet activities predict subsequent academic performance. Directions for future research to identify mechanisms that mediate the relationship between Internet activities and academic performance and implications for the digital divide are discussed.

Perceived Parenting Styles Fail to Mediate Between Anxiety and Attachment Styles in Adult Siblings of Individuals with Developmental Disabilities.

Adult siblings of individuals with developmental disabilities often experience higher levels of anxiety than individuals in the general population. The present study tested whether perceived parenting could mediate the relationship between attachment styles and anxiety in the sibling group compared to a control group. Little association was found between perceived parenting and attachment styles or anxiety for the siblings but there were robust and expected findings for the control. Adult attachment-related-anxiety was a significant unique predictor of anxiety in the sibling group but there was no mediational role for perceived parenting. Conversely, the majority of parenting styles significantly mediated the relationship between attachment and anxiety in the control. Implications for the atypical findings in the sibling group are discussed.

Anxiety and depression symptomatology in adult siblings of individuals with different developmental disability diagnoses.

Factors predicting the emotional well-being of adult siblings of those with developmental disability (DD) remain under-researched. In this study adult siblings of individuals with Down's syndrome (DS), autism (ASD), Prader-Willi syndrome (PWS) and those with DD but with unknown aetiology (DUA) were compared with each other and a closely-matched control group to ascertain if sibling disability type made a difference to anxiety and/or depression levels. Also considered was the interactive effect of gender, age, parental and sibling educational attainment levels, socio-economic status and birth order on anxiety and depression outcomes. With the exception of siblings of those with DS, adult siblings of those with ASD, PWS and DUA reported significantly higher levels of anxiety and depression than the control group. There were some predictive effects of the demographic variables upon anxiety and depression but none common to all disability types and no moderating effects of demographic factors were found. Consequently other solutions must be found as to why this important group of people have elevated rates of anxiety and depression in comparison to the general population.

The Australasian Clinical Toxicology Investigators Collaboration randomized trial of different loading infusion rates of N-acetylcysteine.

STUDY OBJECTIVE: We determine whether the incidence of adverse events caused by intravenous N -acetylcysteine is significantly less when the initial dose is infused over a 60-minute period compared with the standard infusion period of 15 minutes. A secondary objective is to assess the efficacy of the 2 treatment arms. METHODS: This was a multicenter, randomized, prospective trial of patients who presented with acetaminophen poisoning and who were treated with N -acetylcysteine and had no history of hypersensitivity to N-acetylcysteine. Patients were randomly assigned to receive the initial dose of N-acetylcysteine over a 15-minute or 60-minute period. Baseline signs and symptoms and adverse events were serially evaluated before and during administration of N -acetylcysteine. Tests of liver injury and coagulation were collected at baseline and then at 12-hour intervals. RESULTS: The study was designed with an 80% power to detect a halving of the incidence of adverse events. Of 180 evaluable patients, 109 patients were randomized to the 15-minute group and 71 patients were randomized to the 60-minute group. The incidence of drug-related adverse events was 45% in the 15-minute group and 38% in the 60-minute group (95% confidence interval -8% to 22%). The study did not demonstrate a reduction of drug-related adverse outcomes with the 60-minute infusion. Incidence of maximum alanine aminotransferase levels indicating hepatotoxicity (serum level >1,000 IU/L) was 6.8% (5.6% for 15-minute, 8.7% for 60-minute). The difference did not attain statistical significance. CONCLUSION: This study did not demonstrate a reduction of drug-related adverse outcomes with the 60-minute infusion. The study also confirmed that early treatment with N -acetylcysteine (within 8 hours of ingestion) is more effective than later treatment.