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Drawing on Fairclough’s Dialectical-Relational Approach the paper offers a critical discourse analysis of documents relating to the introduction of predictive learning analytics at a UK university. It is concerned with the semiotic realisation of strategies of pathologisation and responsibilisation in Higher Education responses to widening participation. Authority discourses in institutional texts indicate an ambivalent attitude to students that fluctuates between different discourses, two of which are identified as the ‘Here to help’ and ‘Over to you’ discourses. The paper posits a new discursive positioning for students as ‘assets’ rather than learners, partners or clients. At the micro level, the ‘Concerned tutor’ discourse indicates a diminished authority position for academics which parallels the responsibilization of personal tutors in ensuring student success and engagement. The discursive ambivalence suggests that institutions need to maintain ethical vigilance when introducing learning analytics policies in order to maintain stated institutional values of partnership and justice.

Drawing on Fairclough’s Dialectical-Relational Approach the paper offers a critical discourse analysis of documents relating to the introduction of predictive learning analytics at a UK university. It is concerned with the semiotic realisation of strategies of pathologisation and responsibilisation in Higher Education responses to widening participation. Authority discourses in institutional texts indicate an ambivalent attitude to students that fluctuates between different discourses, two of which are identified as the ‘Here to help’ and ‘Over to you’ discourses. The paper posits a new discursive positioning for students as ‘assets’ rather than learners, partners or clients. At the micro level, the ‘Concerned tutor’ discourse indicates a diminished authority position for academics which parallels the responsibilization of personal tutors in ensuring student success and engagement. The discursive ambivalence suggests that institutions need to maintain ethical vigilance when introducing learning analytics policies in order to maintain stated institutional values of partnership and justice.

Autistic individuals with intellectual disability are at greater risk of experiencing anxiety than their non-autistic peers without intellectual disability. Anxiety in this group may present as behaviour that challenges, often leading families to reach out to healthcare or support services. However, many families experience difficulties accessing services and, due to the lack of research into evidence-based anxiety interventions for people with intellectual disability, may not receive individualised support once in a service. This study explored caregivers’ experiences of accessing services for autistic individuals with intellectual disability, and their considerations when developing new interventions for this population. Interviews and focus groups were completed with 16 caregivers of autistic people with intellectual disability. Reflexive thematic analysis was used to develop five themes about service access experiences, and three themes about caregiver considerations for anxiety interventions. Caregivers reported that their experiences of accessing services did not meet their expectations, and considerations for future anxiety interventions were often reflective of this. Interventions being flexible to family circumstances to aid accessibility, the embedding of peer support in services, and skills that can be generalised across the lifespan could be applied when aiming to improve outcomes and develop interventions for this under-served population. Lay Abstract: Many autistic individuals with intellectual disability experience anxiety, and for those who use few or no words, anxiety may present as behaviour that challenges, such as self-injury and avoiding anxiety-provoking situations. Families report difficulty accessing support from services for autistic individuals experiencing anxiety. Moreover, once receiving support, effective interventions for autistic people with intellectual disability are limited. We completed individual and group discussions with 16 car

Autistic individuals with intellectual disability are at greater risk of experiencing anxiety than their non-autistic peers without intellectual disability. Anxiety in this group may present as behaviour that challenges, often leading families to reach out to healthcare or support services. However, many families experience difficulties accessing services and, due to the lack of research into evidence-based anxiety interventions for people with intellectual disability, may not receive individualised support once in a service. This study explored caregivers’ experiences of accessing services for autistic individuals with intellectual disability, and their considerations when developing new interventions for this population. Interviews and focus groups were completed with 16 caregivers of autistic people with intellectual disability. Reflexive thematic analysis was used to develop five themes about service access experiences, and three themes about caregiver considerations for anxiety interventions. Caregivers reported that their experiences of accessing services did not meet their expectations, and considerations for future anxiety interventions were often reflective of this. Interventions being flexible to family circumstances to aid accessibility, the embedding of peer support in services, and skills that can be generalised across the lifespan could be applied when aiming to improve outcomes and develop interventions for this under-served population. Lay Abstract: Many autistic individuals with intellectual disability experience anxiety, and for those who use few or no words, anxiety may present as behaviour that challenges, such as self-injury and avoiding anxiety-provoking situations. Families report difficulty accessing support from services for autistic individuals experiencing anxiety. Moreover, once receiving support, effective interventions for autistic people with intellectual disability are limited. We completed individual and group discussions with 16 car

In 2013, the Global Coalition for Regulatory Science Research (GCRSR) was established with members from over ten countries (www.gcrsr.net). One of the main objectives of GCRSR is to facilitate communication among global regulators on the rise of new technologies with regulatory applications through the annual conference Global Summit on Regulatory Science (GSRS). The 11th annual GSRS conference (GSRS21) focused on "Regulatory Sciences for Food/Drug Safety with Real-World Data (RWD) and Artificial Intelligence (AI)." The conference discussed current advancements in both AI and RWD approaches with a specific emphasis on how they impact regulatory sciences and how regulatory agencies across the globe are pursuing the adaptation and oversight of these technologies. There were presentations from Brazil, Canada, India, Italy, Japan, Germany, Switzerland, Singapore, the United Kingdom, and the United States. These presentations highlighted how various agencies are moving forward with these technologies by either improving the agencies' operation and/or preparing regulatory mechanisms to approve the products containing these innovations. To increase the content and discussion, the GSRS21 hosted two debate sessions on the question of "Is Regulatory Science Ready for AI?" and a workshop to showcase the analytical data tools that global regulatory agencies have been using and/or plan to apply to regulatory science. Several key topics were highlighted and discussed during the conference, such as the capabilities of AI and RWD to assist regulatory science policies for drug and food safety, the readiness of AI and data science to provide solutions for regulatory science. Discussions highlighted the need for a constant effort to evaluate emerging technologies for fit-for-purpose regulatory applications. The annual GSRS conferences offer a unique platform to facilitate discussion and collaboration across regulatory agencies, modernizing regulatory approaches, and harmonizing effort

Background: Mismatch negativity (MMN) and P3a amplitude reductions are robust abnormalities of sensory information processing in schizophrenia, but they are variably present in different profiles of risk (family history vs. clinical high risk) for the disorder. This study aimed to determine whether these abnormalities characterize children presenting replicated risk factors for schizophrenia, using longitudinal assessment over the ages of 9–16 years in children with multiple replicated antecedents of schizophrenia (ASz) and with family history of schizophrenia (FHx), relative to typically developing (TD) peers. Methods: A total of 105 children (52 female) sampled from the community were assessed at ages 9–12 years and approximately 2 and 4 years later. Linear mixed models were fitted to MMN and P3a peak amplitudes and latencies, with intercept and slope estimates from 32 ASz and 28 FHx children compared with those of 45 TD peers. Results: In ASz relative to TD children, MMN amplitude initially increased and then prominently decreased during adolescence. Both ASz and FHx children had greater P3a amplitude than TD children at 11 years, which decreased with age, in contrast to P3a amplitude increasing during adolescence in TD youths. MMN abnormalities were specific to ASz children who continued to present symptoms during follow-up. Conclusions: Age-dependent MMN and P3a abnormalities demarcate adolescent development of ASz and FHx from TD children, with auditory change detection abnormalities specific to ASz children with continuing symptoms and attention-orienting abnormalities characterizing both ASz and FHx risk profiles. Follow-up is required to determine whether these abnormalities index vulnerability for schizophrenia or an illness nonspecific developmental delay.QUT Project 2018001348 (ARC FT170100294)

Premorbid motor dysfunction is one of the earliest of developmental antecedents identified among individuals who develop schizophrenia in adulthood. However, among individuals with schizophrenia, premorbid motor dysfunction is not apparent at all stages of childhood development and may reduce with increasing age. Currently, little is known about the trajectories of motor development during adolescence among youth at-risk for the disorder. One hundred and one participants were assessed repeatedly, at approximately 24-month intervals (time 1, aged 9-12 years; time 2, 11-14 years; and time 3, 13-16 years), on the Purdue Pegboard assessment, comprising four subtests: Dominant Hand (DH), Non-Dominant Hand (NDH), Both Hands (BH), and Assembly. Fine motor and coordination skills development between ages 9-16 years was compared between youth characterised by a triad of developmental antecedents of schizophrenia (ASz, N=32); youth with at least one affected relative with schizophrenia/schizoaffective disorder (FHx; N=26); and typically developing youth without antecedents or family history (TD, N=43). Longitudinal mixed models for repeated measures indicated significant motor skills improvements with age in TD youth on the Assembly subtest only. Relative to TD youth, we found evidence for developmental deficits (i.e., dysfunction that emerged early and remained stable) among ASz youth on DH and BH subtests, and among FHx youth on the Assembly subtest. ASz youth were characterised by a developmental delay on the Assembly subtest (i.e., initial performance decrement in middle childhood that caught up with peers’ performance during adolescence). These divergences from normative motor development may reflect differences in structural and functional neural correlates.

Individuals with established psychosis are characterised by a distinct pattern of hypothalamic-pituitary-adrenal (HPA) axis dysfunctions which include both elevated daytime cortisol levels and a blunted cortisol awakening response (CAR). Whilst these patterns of dysfunction have also been observed among those at elevated risk for the disorder, longitudinal studies are scarce. As such, the relevance of these HPA axis abnormalities for the progression of psychopathology in high-risk populations is unknown. Utilising data from a well-characterised, longitudinal cohort of youth at elevated risk for schizophrenia and their typically-developing peers (The Child Health and Development Study), we aimed to investigate the extent to which HPA axis function determined in childhood is a significant predictor of putative prodromal status and psychopathology in late adolescence/early adulthood.

BACKGROUND: Among adults with schizophrenia, evidence suggests that premorbid deficits in different cognitive domains follow distinct developmental courses during childhood and adolescence. The aim of this study was to delineate trajectories of adolescent cognitive functions prospectively among different groups of youth at-risk for schizophrenia, relative to their typically developing (TD) peers. METHOD: Using linear mixed models adjusted for sex, ethnicity, parental occupation and practice effects, cognitive development between ages 9 and 16 years was compared for youth characterised by a triad of well-replicated developmental antecedents of schizophrenia (ASz; N = 32) and youth with a least one affected relative with schizophrenia or schizoaffective disorder (FHx; N = 29), relative to TD youth (N = 45). Participants completed measures of IQ, scholastic achievement, memory and executive function at three time-points, separated by approximately 24-month intervals. RESULTS: Compared to TD youth, both ASz and FHx youth displayed stable developmental deficits in verbal working memory and inhibition/switching executive functions. ASz youth additionally presented with stable deficits in measures of vocabulary (IQ), word reading, numerical operations, and category fluency executive function, and a slower rate of growth (developmental lag) on spelling from 9 to 16 years than TD peers. Conversely, faster rates of growth relative to TD peers (developmental delay) were observed on visual and verbal memory, and on category fluency executive function (ASz youth only) and on matrix reasoning (IQ) and word reading (FHx youth only). CONCLUSIONS: These differential patterns of deviation from normative adolescent cognitive development among at-risk youth imply potential for cognitive rehabilitation targeting of specific cognitive deficits at different developmental phases.

Background: The hypothalamic-pituitary-adrenal (HPA) axis disturbances observed in psychosis might feasibly contribute to some of the structural brain abnormalities associated with the disorder (i.e., via the potentially toxic effects of elevated glucocorticoid levels on the brain). However, the association between brain structure and cortisol has rarely been investigated. The current study examined relationships between salivary cortisol and regional brain volumes among at-risk children aged 11-14 years, who present multiple antecedents of schizophrenia (ASz=30) or a family history of illness (FHx=22), and typically-developing children (TD=32). Methods: Volumes of specific brain regions known to express glucocorticoid receptors were extracted from structural brain images using FreeSurfer. Diurnal cortisol levels and the cortisol awakening response (CAR) were determined from multiple salivary cortisol samples obtained throughout the day. Results: In the FHx group only, higher diurnal cortisol was correlated with smaller right amygdala and white matter hypointensity volumes (r=-0.51 and -0.62, respectively, p<0.05). In post-hoc analyses, a higher CAR was associated with smaller bilateral cerebellum, bilateral hippocampus, right ventral diencephalon, and total subcortical grey matter volumes among FHx children with a first-degree relative with schizophrenia. In FHx children with an affected second-degree relative, increased diurnal cortisol levels were associated with smaller left hippocampal and white matter hypointensity volumes. Conclusions: Our findings are consistent with the few previous studies examining cortisol and brain structure among adults with established psychosis. These associations may not necessarily reflect a direct effect of cortisol on the developing brain; indeed, abnormal neurodevelopment affecting these brain regions may contribute to HPA-axis dysregulation. Funding: This work was supported by a Sir Henry Well

Aims: Many children and adolescents experiencing mental health problems do not receive appropriate care. Strategies to encourage appropriate access to services might be improved by a more detailed understanding of service use determinants within this group. In view of caregivers’ key role in young people’s pathways to care, this study aimed to advance understanding of caregiver-related characteristics that influence service use among young people. Methods: We interviewed 407 primary caregivers of young people aged 9-18 years, recruited from a Greater London (United Kingdom) community sample. Caregivers reported on young people’s service use in health care sector and/or education settings, and caregivers’ intended stigmatising behaviours, help-seeking attitudes, and personal service use. Logistic regression analyses examined the relationship between these caregiver characteristics and young people’s service use, controlling for young people’s clinical and socio-demographic factors. Results: Caregivers’ intended stigmatising behaviours in particular exerted a strong influence on young people’s service use within each service setting. The impact of this characteristic interacted with caregivers’ service use in influencing young people’s service use across health care and education settings and health care settings specifically. For young people’s service use within education settings, caregivers’ intended stigmatising behaviours score had a main effect. Conclusions: This study highlights the key role caregivers’ attitudes and experiences hold in young people’s service use. The findings indicate that strategies aiming to bridge the gap between young people’s service needs and utilisation might be improved by targeting stigma amongst caregivers.

Background Pituitary volume enlargements have been observed among individuals with first-episode psychosis. These abnormalities are suggestive of hypothalamic–pituitary–adrenal (HPA) axis hyperactivity, which may contribute to the development of psychosis. However, the extent to which these abnormalities characterize individuals at elevated risk for schizophrenia prior to illness onset is currently unclear, as volume increases, decreases and no volume differences have all been reported relative to controls. The current study aimed to determine whether antipsychotic-naive, putatively at-risk children who present multiple antecedents of schizophrenia (ASz) or a family history of illness (FHx) show pituitary volume abnormalities relative to typically developing (TD) children. An additional aim was to explore the association between pituitary volume and experiences of psychosocial stress. Method ASz ( n = 30), FHx ( n = 22) and TD ( n = 32) children were identified at age 9–12 years using a novel community-screening procedure or as relatives of individuals with schizophrenia. Measures of pituitary volume and psychosocial stress were obtained at age 11–14 years. Results Neither ASz nor FHx children showed differences in pituitary volume relative to TD children. Among FHx children only, pituitary volume was negatively associated with current distress relating to negative life events and exposure to physical punishment. Conclusions The lack of pituitary volume abnormalities among ASz and FHx children is consistent with our previous work demonstrating that these children are not characterized by elevated diurnal cortisol levels. The findings imply that these biological markers of HPA axis hyperactivity, observed in some older samples of high-risk individuals, may emerge later, more proximally to disease onset.

Background Psychological stress is implicated in the development of schizophrenia, but little is known about experiences of stress among children at elevated risk for the disorder. Aims To examine stressor exposure and reactivity in children with different vulnerability profiles for schizophrenia: (a) children presenting multiple antecedents of schizophrenia (ASz group), (b) children with a family history of schizophrenia (FHx group) and (c) typically developing low-risk (TD) children. Method Ninety-five children (ASz = 29; FHx = 19; ASz+FHx = 5; TD = 42), identified aged 9–12 years using a community-based screening procedure or as relatives of individuals with schizophrenia, completed questionnaires assessing environmental stressors and psychopathology at age 11–14 years. Results Relative to their typically developing peers, children in the FHx and ASz groups were exposed to a greater number of negative life events and a higher frequency of daily stressors, respectively; and were more distressed by these experiences. Conclusions Stress exposure and reactivity may constitute useful targets of early intervention for psychosis.

Abnormal hypothalamic-pituitary-adrenal (HPA) axis function, as indexed by elevated diurnal cortisol levels and/or a blunted cortisol awakening response (CAR), has been observed among patients with first episode psychosis and associated with neurocognitive deficits in this population. However, the extent to which these features precede illness onset is unclear. The current study aimed to determine whether children who are at putatively elevated risk for psychosis because they present multiple antecedents of schizophrenia (ASz), and high-risk children with a family history of illness (FHx), are characterized by abnormal cortisol levels when compared with their typically developing (TD) peers. A further aim was to investigate the extent to which cortisol levels are associated with psychosocial stress and neurocognitive function. Thirty-three ASz children, 22 FHx children, and 40 TD children were identified at age 9–12 years using a novel community-based screening procedure or as relatives of individuals with schizophrenia. All participants were antipsychotic-naive and not currently seeking treatment for their symptoms. At age 11–14 years, participants provided salivary cortisol samples and completed psychosocial stress measures and tests of memory and executive function. Results indicated that FHx children, but not ASz children, were characterized by a blunted CAR relative to their TD peers (effect size = −0.73, p = 0.01) that was not explained by psychosocial stress exposure or by distress relating to these experiences. Neither FHx nor ASz children were characterized by elevated diurnal cortisol. Among both FHx and ASz children, more pronounced HPA axis function abnormalities (i.e., higher diurnal cortisol levels and greater blunting of the CAR) were associated with poorer performance on tests of verbal memory and executive function. These findings support the notion that at least some HPA axis abnormalities described in psychosis precede illness onset, rather than b

Abnormal hypothalamic-pituitary-adrenal (HPA) axis function, as indexed by elevated diurnal cortisol levels and a blunted cortisol awakening response (CAR), has been observed among patients with first- episode psychosis and also has been associated with neurocognitive deficits in this population . However, the extent to which HPA axis dysfunction precedes illness onset is currently unclear . Whilst elevated diurnal cortisol levels have been reported in samples of youth at ultra high-risk for psychosis, such elevations may relate to distress associated with emerging illness and might also be influenced by psychotropic medication . Further- more, studies of high-risk individuals with a family history of illness have typically included adult relatives who have passed the peak age of illness onset . As yet, no study of high-risk youth has examined the CAR or the extent to which HPA axis dysfunction is associated with neurocognitive performance . The current study aimed to determine whether children at putatively elevated risk for schizophrenia who present psychotic-like experiences and other antecedents of schizophrenia (ASz) and high-risk children with a family history of illness (FHx) are characterised by abnormal HPA axis function relative to their typically-developing (TD) peers . A further aim was to examine associations between HPA axis function and performance on tasks of memory and executive function among ASz and FHx children .

The Salmonella regulatory protein, SlyA is implicated in virulence, survival in macrophages and resistance to oxidative stress and anti-microbial peptides.  SlyA is a member of the MarR family of winged-helix transcription factors. Systematic mutational analysis of the SlyA operator sequence and of the predicted DNA-binding region of SlyA shows that no single base pair in the palindromic SlyA operator sequence is essential for DNA binding, and identifies amino acid residues required to allow SlyA to recognise DNA. Combining the structure-function studies described here and elsewhere with the structures of MarR family proteins suggests a possible model for regulation of SlyA binding to DNA.

The Salmonella regulatory protein, SlyA is implicated in virulence, survival in macrophages and resistance to oxidative stress and anti-microbial peptides.  SlyA is a member of the MarR family of winged-helix transcription factors. Systematic mutational analysis of the SlyA operator sequence and of the predicted DNA-binding region of SlyA shows that no single base pair in the palindromic SlyA operator sequence is essential for DNA binding, and identifies amino acid residues required to allow SlyA to recognise DNA. Combining the structure-function studies described here and elsewhere with the structures of MarR family proteins suggests a possible model for regulation of SlyA binding to DNA.

In today’s schools, building level administrators are faced with a variety of challenges as they strive to provide leadership that promotes successful learning experiences for all students. Promoting the success of all students is also the foundation of current federal legislation with the No Child Left Behind (NCLB) mandates as well as the Individual with Disabilities Education Act (IDEA). Answering the call of these directives and the goal for all students to experience success, building level principals must have fundamental knowledge of special education programs and services. However, research indicates that principal preparation course work may not target special education leadership and responsibilities (DiPaulo and Tschanned-Moran 2003). Further studies, such as work done by Lasky and Karge (2006), examined principal preparation programs and found the need for increased training in the area of special education during the preservice phase. Therefore, with little emphasis during the principal preparation experience in providing leadership at the building level in the area of special education, many beginning principals find themselves challenged on a daily basis. Learning on-the-job becomes the starting point for all fundamental knowledge regarding special education leadership.

In today’s schools, building level administrators are faced with a variety of challenges as they strive to provide leadership that promotes successful learning experiences for all students. Promoting the success of all students is also the foundation of current federal legislation with the No Child Left Behind (NCLB) mandates as well as the Individual with Disabilities Education Act (IDEA). Answering the call of these directives and the goal for all students to experience success, building level principals must have fundamental knowledge of special education programs and services. However, research indicates that principal preparation course work may not target special education leadership and responsibilities (DiPaulo and Tschanned-Moran 2003). Further studies, such as work done by Lasky and Karge (2006), examined principal preparation programs and found the need for increased training in the area of special education during the preservice phase. Therefore, with little emphasis during the principal preparation experience in providing leadership at the building level in the area of special education, many beginning principals find themselves challenged on a daily basis. Learning on-the-job becomes the starting point for all fundamental knowledge regarding special education leadership.

Wiggins and McTighe (2005, 18) challenge educators to think critically about acceptable assessment evidence by asking: “How will we know if students have achieved the desired results? What will we accept as evidence of student understanding and proficiency?” (p 18). Teacher education programs must face these important questions and affirm that answers are both valid and equitable. This article explores the benefits of evaluator training in the scoring of high-stakes work samplings produced by teacher preparation candidates.

Wiggins and McTighe (2005, 18) challenge educators to think critically about acceptable assessment evidence by asking: “How will we know if students have achieved the desired results? What will we accept as evidence of student understanding and proficiency?” (p 18). Teacher education programs must face these important questions and affirm that answers are both valid and equitable. This article explores the benefits of evaluator training in the scoring of high-stakes work samplings produced by teacher preparation candidates.

"The President Song" lists each president in order through President Eisenhower.

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Parthenolide is a natural product that exhibits anti-leukaemic activity, however, its clinical use is limited by its poor bioavailability. It may be extracted from feverfew and protocols for growing, extracting and derivatising it are reported. A novel parthenolide derivative with good bioavailability and pharmacological properties was identified through a screening cascade based on in vitro anti-leukaemic activity and calculated “drug-likeness” properties, in vitro and in vivo pharmacokinetics studies and hERG liability testing. In vitro studies showed the most promising derivative to have comparable anti-leukaemic activity to DMAPT, a previously described parthenolide derivative. The newly identified compound was shown to have pro-oxidant activity and in silico molecular docking studies indicate a prodrug mode of action. A synthesis scheme is presented for the production of amine 7 used in the generation of 5f.

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Theater program of "Bury the Dead" by Irwin Shaw, directed by Earl Billings. This performance ran from January 31-February 2, 1969. Performers include Tom Barkley, Lynette Braithwaite, Nola Briskey, Deborah Chapman, George Gould, Roy Hawkins, Lebron Jackson, Douglas Johnson, Jacqueline Johnson, Anna Kaufman, Aileen Kilburn, Albert Kilburn, Anton Kilburn, Ruth Roberts, Calvin Robinson, Tony Schultz, Samuel Watkins, and Ricky Wilson.