Establishing the sensitivity and specificity of the gynaecological cancer distress screen.

OBJECTIVE: Nuanced distress screening tools can help cancer care services manage specific cancer groups' concerns more efficiently. This study examines the sensitivity and specificity of a tool specifically for women with gynaecological cancers (called the Gynaecological Cancer Distress Screen or DT-Gyn). METHODS: This paper presents cross-sectional data from individuals recently treated for gynaecological cancer recruited through Australian cancer care services, partner organisations, and support/advocacy services. Receiver operating characteristics analyses were used to evaluate the diagnostic accuracy of the DT-Gyn against criterion measures for anxiety (GAD-7), depression (patient health questionnaire), and distress (IES-R and K10). RESULTS: Overall, 373 individuals aged 19-91 provided complete data for the study. Using the recognised distress thermometer (DT) cut-off of 4, 47% of participants were classified as distressed, while a cut-off of 5 suggested that 40% had clinically relevant distress. The DT-Gyn showed good discriminant ability across all measures (IES-R: area under the curve (AUC) = 0.86, 95% CI = 0.82-0.90; GAD-7: AUC = 0.89, 95% CI = 0.85-0.93; K10: AUC = 0.88, 95% CI = 0.85-0.92; PHQ-9: AUC = 0.85, 95% CI = 0.81-0.89) and the Youden Index suggested an optimum DT cut-point of 5. CONCLUSIONS: This study established the psychometric properties of the DT-Gyn, a tool designed to identify and manage the common sources of distress in women with gynaecological cancers. We suggest a DT cut point ≥5 is optimal in detecting 'clinically relevant' distress, anxiety, and depression in this population.

A role for enjoyment for encouraging fruit consumption.

This work investigated the value of highlighting the enjoyment conferred by fruit for encouraging fruit consumption. Study 1 investigated the effects on fruit consumption of visualizing eating fruit that was either enjoyable, not enjoyable, or was unassociated with enjoyment. Study 2 investigated the effects on fruit consumption of health promotion posters that featured either enjoyable or less enjoyable fruit. Both studies used an independent-groups design, where young adults (Study 1, N = 142; Study 2, N = 221) were randomized to conditions, and outcomes: intentions to consume fruit, attitudes towards fruit, immediate fruit selection, subsequent fruit consumption; and a range of characteristics likely to be associated with fruit and vegetable consumption were assessed. In Study 1, higher intentions to consume fruit and more positive attitudes towards fruit were associated with higher likely enjoyment of the fruit visualized, higher fruit liking in general and higher fruit-related self-efficacy (smallest Beta = 0.270, p = 0.02). In Study 2, similar effects were found for likely enjoyment of the fruit featured on a poster; higher likely enjoyment also predicted greater immediate fruit selection (smallest Beta = 0.122, p = 0.03). These outcomes were also associated with variables often associated with fruit and vegetable consumption. Subsequent fruit consumption was only associated with past fruit consumption (smallest Beta = 0.340, p = 0.05). These two studies (Study 1 using visualisation, Study 2 using health promotion posters) highlight a role for enjoyment for encouraging fruit consumption. The value of enjoyment and the simplicity of the poster intervention particularly should be noted.

The impact of subtle language and communication difficulties on the daily lives of autistic children without intellectual disability: Parent perspectives.

BACKGROUND: Autistic children without intellectual disability will likely experience higher level language and communication difficulties. These may appear subtle, in that they are not immediately evident to those who do not know the child well and may not manifest in all environments. Because of this, the impact of such difficulties may be underestimated. This phenomenon has similarly attracted little research attention, meaning the extent to which subtle language and communication difficulties contribute to the needs of autistic individuals without intellectual disability may be underspecified in clinical services. AIMS: To offer a detailed exploration of how relatively subtle language and communication difficulties impact on autistic children without intellectual disability and what strategies parents recognize can mediate those negative effects. METHODS & PROCEDURES: Twelve parents of autistic children from the target group (aged 8-14 years, attending mainstream school) were interviewed about how subtle language and communication difficulties impact their autistic child. Rich accounts were derived then analysed using thematic analysis. Eight of the children discussed had previously been interviewed independently in a parallel study. Comparisons are discussed in this paper. OUTCOMES & RESULTS: Parents reported heterogeneous but pervasive higher level language and communication difficulties which universally impacted key areas of the children's function: peer relationships, developing independence and performance in education. Communication difficulties were also universally associated with negative emotional responses, social withdrawal and/or negative self-perceptions. While parents identified a range of ad hoc strategies and naturally occurring opportunities that improved outcomes, there was little mention of the means to address primary language and communication difficulties. The current study showed a number of parallels with child accounts, demonstrating the benefits of collecting data from both sources in clinical and research investigations. However, parents were more concerned about longer term implications of language and communication difficulties and highlighted their impact on the child developing functional independence. CONCLUSIONS & IMPLICATIONS: Subtle language and communication difficulties, typically identified in this higher ability autistic group, can impact significantly on key areas of childhood function. Support strategies seem to be parent generated and inconsistently applied across individuals, without the benefit of coherent specialist services. Dedicated provision and resources targeting areas of functional need may be beneficial to the group. In addition, the commonly reported association between subtle language and communication difficulties and emotional well-being indicates the need for greater exploration using empirical methods, and joined-up clinical working between speech and language therapy and mental health services. WHAT THIS PAPER ADDS: What is already known on the subject There is now a wide understanding of how language and communication difficulties can impact the individual. However, where those difficulties are relatively subtle, for example, in children without intellectual disability and where difficulties are not immediately evident, less is known. Research has often speculated on how identified differences in higher level structural language and pragmatic difficulties might impact on the function of autistic children. However, to date dedicated exploration of this phenomenon is limited. The current author group explored first-hand accounts of children. Corroborative evidence from parents of the same children would add further weight to understanding this phenomenon. What this paper adds to the existing knowledge This study provides a detailed exploration of parents' perspective relating to the impact of language and communication difficulties on autistic children without intellectual disability. It provides corroborative detail that support child accounts of the same phenomenon, indicating the impact on peer relationships, school outcomes and emotional well-being. Parents also report functional concerns around the child's ability to develop independence and this paper demonstrates how parents and children might deviate in their accounts, with parents reporting increased concerns around the longer term implications of early language and communication difficulties. What are the potential or actual clinical implications of this work? Relatively subtle language and communication difficulties can have a significant impact on the lives of autistic children without intellectual disability. Greater service provision for this group is therefore indicated. Interventions could focus on areas of functional concern where language is implicated, for example, peer relationships, developing independence and school success. Additionally, the relationship between language and emotional well-being points to further integration between speech and language therapy and mental health services. Differences found between parental and child reports highlight the need to collect data from both parties during clinical investigations. Parental strategies may offer benefits for the wider population.

Factors associated with provision of smoking cessation support to pregnant women - a cross-sectional survey of midwives in New South Wales, Australia.

BACKGROUND: Smoking is the most important preventable cause of adverse pregnancy outcomes, but provision of smoking cessation support (SCS) to pregnant women is poor. We examined the association between midwives' implementation of SCS (5As - Ask, Advise, Assess, Assist, Arrange follow-up) and reported barriers/enablers to implementation. METHODS: On-line anonymous survey of midwives providing antenatal care in New South Wales (NSW), Australia, assessing provision of the 5As and barriers/enablers to their implementation, using the Theoretical Domains Framework (TDF). Factor analyses identified constructs underlying the 5As; and barriers/enablers. Multivariate general linear models examined relationships between the barrier/enabler factors and the 5As factors. RESULTS: Of 750 midwives invited, 150 (20%) participated. Respondents more commonly reported Asking and Assessing than Advising, Assisting, or Arranging follow-up (e.g. 77% always Ask smoking status; 17% always Arrange follow-up). Three 5As factors were identified- 'Helping', 'Assessing quitting' and 'Assessing dependence'. Responses to barrier/enabler items showed greater knowledge, skills, intentions, and confidence with Assessment than Assisting; endorsement for SCS as a priority and part of midwives' professional role; and gaps in training and organisational support for SCS. Nine barrier/enabler factors were identified. Of these, the factors of 'Capability' (knowledge, skills, confidence); 'Work Environment' (service has resources, capacity, champions and values SCS) and 'Personal priority' (part of role and a priority) predicted 'Helping'. CONCLUSION: The TDF enabled systematic identification of barriers to providing SCS, and the multivariate models identified key contributors to poor implementation. Combined with qualitative data, these results have been mapped to intervention components to develop a comprehensive intervention to improve SCS.

Metacognition in speech and language therapy for children with social (pragmatic) communication disorders: implications for a theory of therapy.

BACKGROUND: Metacognition is a significant component of complex interventions for children who have developmental language disorders. Research into how metacognition operates in the content or process of developmental language therapy delivery is limited. Identification and description of proposed active therapy components, such as metacognition, may contribute to our understanding of how to deliver complex communication interventions in an optimal manner. AIMS: To analyse aspects of metacognition during therapy derived from a manualized speech and language intervention (the Social Communication Intervention Programme-SCIP) as delivered to children who have social (pragmatic) communication disorder (SPCD) and to examine the dynamic process of delivering therapy. METHODS & PROCEDURES: A purposive sample of eight filmed therapy sessions was selected from the video data corpus of intervention-arm participants within a randomized controlled trial. The child-therapist interactions during therapy sessions from five children (aged between 5;11 and 10;3) in the SCIP trial were transcribed. Filmed sessions represented a variety of communication profiles and SCIP therapy content. Starting from existing theory on metacognition, cycles of iterative analysis were performed using a mixed inductive-deductive qualitative analysis. A preliminary list of metacognitive content embedded in the intervention was developed into a metacognitive coding framework (MCF). A thematic analysis of the identified metacognitive content of the intervention was then carried out across the whole sample. OUTCOMES & RESULTS: Thematic analysis revealed the presence of metacognition in the content and delivery of SCIP intervention. Four main themes of metacognitive person, task and strategy knowledge, and monitoring/control were identified. Metacognition was a feature of how children's ability to monitor language, pragmatic and social interaction skills, in themselves and other people, was developed. Task design and delivery methods were found to play a particular role in adjusting the metacognitive content of the therapy activities. CONCLUSIONS & IMPLICATIONS: This study makes explicit the metacognitive content and delivery within a complex developmental communication intervention. Discussion of the findings about metacognitive content provides an explanation of how the skilled speech and language therapist manipulates task demands, person knowledge and therapy methods towards the therapy goal. Clinical applications of the metacognitive framework are discussed. We suggest that the process of making the tacit knowledge of the therapist explicit can contribute to the implementation of complex evidence-based interventions.

Teaching Phenomenological Research and Writing.

In this article, we describe our approach and philosophical methodology of teaching and doing phenomenology. The human science seminar that we offer involves participants in the primary phenomenological literature as well as in a variety of carefully engaged writing exercises. Each seminar participant selects a personal phenomenological project that aims at producing a publishable research paper. We show how the qualitative methodology of hermeneutic phenomenology requires of its practitioner a sensitivity and attitudinal disposition that has to be internalized and that cannot be captured in a procedural or step-by-step program. Our experience is that seminar participants become highly motivated and committed to their phenomenological project while involved in the rather intense progression of lectures, workshop activities, readings, and discussions.

Mental health problems in people living with HIV: changes in the last two decades: the London experience 1990-2014.

Mental health problems continue to be a significant comorbidity for people with HIV infection, even in the era of effective antiretroviral therapy. Here, we report on the changes in the mental health diagnoses based on clinical case reports amongst people with HIV referred to a specialist psychological medicine department over a 24-year period, which include the relative increase in depressive and anxiety disorders, often of a chronic nature, together with a decline in acute mental health syndromes, mania, and organic brain disorders. In addition, new challenges, like the presence of HIV and Hepatitis C co-infection, and the new problems created by recreational drugs, confirm the need for mental health services to be closely involved with the general medical services. A substantial proportion of people with HIV referred to specialist services suffer complex difficulties, which often require the collaboration of both psychiatrists and psychologists to deal effectively with their difficulties.

Do children with social communication disorder have explicit knowledge of pragmatic rules they break? A comparison of conversational pragmatic ability and metapragmatic awareness.

BACKGROUND: Children who have social communication disorder (CwSCD) demonstrate persistent difficulties with language pragmatics in conversations and other verbal interactions. Speech-language interventions for these children often include promotion of metapragmatic awareness (MPA); that is, the ability to identify explicitly and reflect upon pragmatic rules (MP explicitation). Improved MPA is assumed to support increased self-monitoring and generalization of pragmatic knowledge. Evidence to support this as a mechanism of intervention depends upon the identification of a systematic relationship between MPA and use of pragmatic rules in conversational behaviour. AIMS: To explore whether there is a relationship between MPA and conversational pragmatic ability in CwSCD. Further, it is asked whether CwSCD can demonstrate MPA for the pragmatic rules they themselves violate in conversation. METHODS & PROCEDURES: Thirty-nine CwSCD (aged 6;1-10;7 years), recruited from NHS speech and language therapy caseloads across the North West of England and South East Scotland, completed (1) a novel task, the Assessment of Metapragmatics (AMP), in which they identified and described a series of pragmatic errors depicted in scripted films; responses on this task were categorized into levels of MP explicitation; and (2) the Targeted Observation of Pragmatics in Children's Conversations (TOPICC), a semi-structured conversation-elicitation task from which 12 aspects of pragmatics were coded for presence of impairment. Regression analysis was used to explore the interaction between scores on the two tasks. OUTCOMES & RESULTS: Expressive language score was a significant predictor of TOPICC score. However, AMP score, when added into the regression model, did not explain a significant amount of unique variance in TOPICC score. Over half of CwSCD demonstrated moderate or marked impairment in one or two pragmatic behaviours on TOPICC. For just over half of the occasions where a child showed moderate/marked impairment of a pragmatic rule on TOPICC did the same child demonstrate MPA for the same pragmatic rule on AMP. On 25% of occasions they demonstrated the most sophisticated level of MP explicitation. CONCLUSIONS & IMPLICATIONS: Findings indicate that some CwSCD have an awareness of the pragmatic rules they themselves violate in conversation. This finding suggests that, for some CwSCD, it may be beneficial for speech and language therapy to focus on improving motivation for use and better understanding of the impact of one's own pragmatic performance on others, rather than solely teaching awareness of pragmatic rules that are already understood but not used.

The interaction between maternal immune activation and alpha 7 nicotinic acetylcholine receptor in regulating behaviors in the offspring.

Mutation of human chromosome 15q13.3 increases the risk for autism and schizophrenia. One of the noteworthy genes in 15q13.3 is CHRNA7, which encodes the nicotinic acetylcholine receptor alpha 7 subunit (α7nAChR) associated with schizophrenia in clinical studies and rodent models. This study investigates the role of α7nAChR in maternal immune activation (MIA) mice model, a murine model of environmental risk factor for autism and schizophrenia. We provided choline, a selective α7nAChR agonist among its several developmental roles, in the diet of C57BL/6N wild-type dams throughout the gestation and lactation period and induced MIA at mid-gestation. The adult offspring behavior and gene expression profile in the maternal-placental-fetal axis at mid-gestation were investigated. We found that choline supplementation prevented several MIA-induced behavioral abnormalities in the wild-type offspring. Pro-inflammatory cytokine interleukin-6 (Il6) and Chrna7 gene expression in the wild-type fetal brain were elevated by poly(I:C) injection and were suppressed by gestational choline supplementation. We further investigated the gene expression level of Il6 in Chrna7 mutant mice. We found that the basal level of Il6 was higher in Chrna7 mutant fetal brain, which suggests that α7nAChR may serve an anti-inflammatory role in the fetal brain during development. Lastly, we induced MIA in Chrna7(+/-) offspring. The Chrna7(+/-) offspring were more vulnerable to MIA, with increased behavioral abnormalities. Our study shows that α7nAChR modulates inflammatory response affecting the fetal brain and demonstrates its effects on offspring behavior development after MIA.

Insights into preferences for psycho-oncology services among women with gynecologic cancer following distress screening.

Much attention has been given to implementing routine screening programs in cancer care to improve the management of distress following diagnosis. Although patients might screen positive for distress, several studies have found that most then refuse additional psychosocial support. To inform the development of successful models of distress screening, this qualitative study explored preferences for psychosocial care among 18 women diagnosed with a gynecologic cancer who scored at least 4 on the Distress Thermometer (DT). Participants were recruited from a gynecologic oncology outpatient clinic in Newcastle, Australia, and interviewed. Unanimously, participants felt that completing the DT was an integral part of their cancer care. However, half then refused the referral to see a psychologist. These women typically reported that a referral was not needed, because their rating on the DT reflected transient stressors or physical distress. Many also spoke about their need to cope with the challenges they were facing on their own and the extensive social support they already had in place to help them overcome these challenges. In contrast, women who accepted referral to the psychologist often struggled to cope with several losses they felt had existential and long-term effects. Commonly, these women reported not having the social support they needed, managing several concurrent life stressors, and/or not having the repertoire of coping skills they required to "remain afloat." Findings from this study begin to bridge the gap between clinicians' and patients' expectations of how psychosocial services should be used in response to distress screening.

Postmortem computed tomography age assessment of juvenile dentition: comparison against traditional OPT assessment.

Age estimation is one of the primary demographic features used in the identification of juvenile remains. Determining the accuracy and repeatability of age estimations based on postmortem computed tomography (PMCT) data compared with those using conventional orthopantomography (OPT) images is important to validate the use of PMCT as a single imaging technique in forensic and disaster victim identification (DVI). In this study, 19 juvenile mandibles and maxilla of known age underwent both OPT and PMCT. Three raters then estimated dental age using the resulting images and 3D reconstructions. This assessment showed excellent agreement between the age estimations using the two techniques for all three observers. PMCT also offers a greater range of measurements for both the dentition and the whole human skeleton using a single image acquisition and therefore has the potential to improve both the speed and accuracy of age estimation.

A minimum data set approach to post-mortem computed tomography reporting for anthropological biological profiling.

Anthropological examination of bones is routinely undertaken in medico-legal investigations to establish an individual's biological profile, particularly their age. This often requires the removal of soft tissue from bone (de-fleshing), which, especially when dealing with the recently deceased, is a time consuming and invasive procedure. Recent advances in multi-detector computed tomography have made it practical to rapidly acquire high-resolution morphological skeletal information from images of "fleshed" remains. The aim of this study was to develop a short standard form, created from post-mortem computed tomography images, that contains the minimum image-set required to anthropologically assess an individual. The proposed standard forms were created for 31 juvenile forensic cases with known age-at-death, spanning the full age range of the developing human. Five observers independently used this form to estimate age-at-death. All observers estimated age in all cases, and all estimations were within the accepted ranges for traditional anthropological and odontological assessment. This study supports the implementation of this approach in forensic radiological practice.

A Case Report of Pulmonary Vein Stenosis Within the Labyrinth of Fibrosing Mediastinitis.

This case centers on a 76-year-old male experiencing exertional dyspnea and hemoptysis, with a medical history marked by recurrent pulmonary embolism and chronic obstructive pulmonary disease (COPD). Notably, he resides in a histoplasmosis-endemic area. A computed tomography (CT) pulmonary embolism scan revealed notable findings, including an enlarged right lower pulmonary artery, vascular congestion, atelectasis, and a mass exerting pressure on the right lower pulmonary vein. Biopsy results identified the mass as fibrosing mediastinitis, likely attributed to histoplasmosis. A transthoracic echocardiogram indicated right ventricular dilatation, impaired function, and a right ventricular systolic pressure of 63 mm Hg. During right heart catheterization, the patient displayed disparate pulmonary artery wedge pressures (PAWPs) between the right and left sides. This discrepancy was linked to a blunted back wave from the left atrium to the catheter, induced by pulmonary vein compression. Although an infrequent phenomenon, the recorded asymmetry in PAWPs played a crucial role in guiding accurate patient management. The absence of subsequent evaluation of PAWP on the left side could have altered the treatment plan, potentially delaying appropriate patient care. This case emphasizes the necessity of thorough exploration with right heart catheterization when clinical symptoms warrant, highlighting the importance of standardized practices in such procedures.

Protocol for the process evaluation of an intervention to improve antenatal smoking cessation support (MOHMQuit) in maternity services in New South Wales, Australia.

INTRODUCTION: Smoking cessation in pregnancy remains a public health priority. Our team used the Behaviour Change Wheel to develop the Midwives and Obstetricians Helping Mothers to Quit smoking (MOHMQuit) intervention with health system, leader (including managers and educators) and clinician components. MOHMQuit addresses a critical evidence to practice gap in the provision of smoking cessation support in antenatal care. It involves nine maternity services in New South Wales in a cluster randomised stepped-wedge controlled trial of effectiveness. This paper describes the design and rationale for the process evaluation of MOHMQuit. The process evaluation aims to assess to what extent and how MOHMQuit is being implemented (acceptability; adoption/uptake; appropriateness; feasibility; fidelity; penetration and sustainability), and the context in which it is implemented, in order to support further refinement of MOHMQuit throughout the trial, and aid understanding and interpretation of the results of the trial. METHODS AND ANALYSIS: The process evaluation is an integral part of the stepped-wedge trial. Its design is underpinned by implementation science frameworks and adopts a mixed methods approach. Quantitative evidence from participating leaders and clinicians in our study will be used to produce individual and site-level descriptive statistics. Qualitative evidence of leaders' perceptions about the implementation will be collected using semistructured interviews and will be analysed descriptively within-site and thematically across the dataset. The process evaluation will also use publicly available data and observations from the research team implementing MOHMQuit, for example, training logs. These data will be synthesised to provide site-level as well as individual-level implementation outcomes. ETHICS AND DISSEMINATION: The study received ethical approval from the Population Health Services Research Ethics Committee for NSW, Australia (Reference 2021/ETH00887). Results will be communicated via the study's steering committee and will also be published in peer-reviewed journals and presented at conferences. TRIAL REGISTRATION NUMBER: Australian New Zealand Trials Registry ACTRN12622000167763. https://www.australianclinicaltrials.gov.au/anzctr/trial/ACTRN12622000167763.

Expression of immune genes on chromosome 6p21.3-22.1 in schizophrenia.

Schizophrenia is a common mental illness with a large genetic component. Three genome-wide association studies have implicated the major histocompatibility complex gene region on chromosome 6p21.3-22.1 in schizophrenia. In addition, nicotine, which is commonly abused in schizophrenia, affects the expression of central nervous system immune genes. Messenger RNA levels for genes in the 6p21.3-22.1 region were measured in human postmortem hippocampus of 89 subjects. The effects of schizophrenia diagnosis, smoking and systemic inflammatory illness were compared. Cell-specific expression patterns for the class I major histocompatibility complex gene HLA-A were explored utilizing in situ hybridization. Expression of five genes was altered in schizophrenic subjects. Messenger RNA levels for the class I major histocompatibility complex antigen HLA-B were increased in schizophrenic nonsmokers, while levels for smokers were indistinguishable from those of controls. ß2 microglobulin, HLA-A and Notch4 were all expressed in a pattern where inflammatory illness was associated with increased expression in controls but not in subjects with schizophrenia. Schizophrenia was also associated with increased expression of Butyrophilin 2A2. HLA-A was expressed in glutamatergic and GABAergic neurons in the dentate gyrus, hilus, and the stratum pyramidale of the CA1-CA4 regions of the hippocampus, but not in astrocytes. In conclusion, the expression of genes from the major histocompatibility complex region of chromosome 6 with likely roles in synaptic development is altered in schizophrenia. There were also significant interactions between schizophrenia diagnosis and both inflammatory illness and smoking.

Social communication disorder outside autism? A diagnostic classification approach to delineating pragmatic language impairment, high functioning autism and specific language impairment.

BACKGROUND: Developmental disorders of language and communication present considerable diagnostic challenges due to overlapping of symptomatology and uncertain aetiology. We aimed to further elucidate the behavioural and linguistic profile associated with impairments of social communication occurring outside of an autism diagnosis. METHODS: Six to eleven year olds diagnosed with pragmatic language impairment (PLI), high functioning autism (HFA) or specific language impairment (SLI) were compared on measures of social interaction with peers (PI), restricted and repetitive behaviours/interests (RRBIs) and language ability. Odds ratios (OR) from a multinomial logistic regression were used to determine the importance of each measure to diagnostic grouping. MANOVA was used to investigate differences in subscale scores for the PI measure. RESULTS: Greater degrees of PI difficulties (OR = 1.22, 95% CI = 1.05-1.41), RRBI (OR = 1.23, 95% CI = 1.06-1.42) and expressive language ability (OR = 1.16, 95% CI = 1.03-1.30) discriminated HFA from PLI. PLI was differentiated from SLI by elevated PI difficulties (OR = 0.82, 95% CI = 0.70-0.96) and higher expressive language ability (OR = 0.88, 95% CI = 0.77-0.98), but indistinguishable from SLI using RRBI (OR = 1.01, 95% CI=0.94-1.09). A significant effect of group on PI subscales was observed (θ = 1.38, F(4, 56) = 19.26, p < .01) and PLI and HFA groups shared a similar PI subscale profile. CONCLUSIONS: Results provide empirical support for a conceptualisation of PLI as a developmental impairment distinguishable from HFA by absence of RRBIs and by the presence of expressive language difficulties. PI difficulties appear elevated in PLI compared with SLI, but may be less pervasive than in HFA. Findings are discussed with reference to the proposed new category of 'social communication disorder' in DSM-5.

Natural but not inducible regulatory T cells require TNF-alpha signaling for in vivo function.

TNF-α has a multifunctional role in autoimmune diseases as reflected in the variable responses of different human diseases to anti-TNF-α therapy. Recent studies have suggested that TNF-α modulates autoimmunity partially via effects on regulatory T cells (Tregs) and that these effects are mediated through the type II TNFR (TNFR2). We have investigated the requirement for TNFR2-expression on murine natural Tregs (nTregs) and induced Tregs (iTregs) in mediating suppression of colitis. Surprisingly, we find that TNFR2-expression is required for both spleen- and thymus-derived nTreg-mediated suppression, but is not required for iTreg-mediated suppression. Abnormal TNFR2(-/-) nTreg function was not associated with an in vivo decrease in accumulation, stability, or expression of markers known to be relevant in Treg function. Because iTregs are generated in the presence of TGF-ß, we investigated whether activation in the presence of TGF-ß could overcome the functional defect in TNFR2(-/-) nTregs. Although preactivation alone did not restore suppressive function of nTregs, preactivation in the presence of TGF-ß did. These results identify potentially critical differences in activation requirements for nTregs versus iTregs. Furthermore, our findings are consistent with reports suggesting that nTregs are activated in sites of inflammation while iTregs are activated in lymph nodes. Finally, by demonstrating that nTregs require TNF-α for optimal function whereas iTregs do not, our results suggest that the enigma of variable responses of different human diseases to anti-TNF-α therapy may relate to whether nTregs or iTregs have the predominant regulatory role in a given disease.

Peroxisome proliferator-activated receptor gamma is required for CD4+ T cell-mediated lymphopenia-associated autoimmunity.

The nuclear hormone receptor peroxisome proliferator-activated receptor γ (PPARγ) was shown to play an immunoregulatory role in many immune-related cell types, and activation of PPARγ was reported to be an effective therapeutic approach in murine and human autoimmune disease. However, despite an association between lymphopenia and autoimmunity, there has been no study on the role of T cell PPARγ in lymphopenia-associated autoimmunity. In the present studies, we examined the role of PPARγ in CD4(+) T cells in two murine models of lymphopenia-associated autoimmunity. Surprisingly, we found that PPARγ expression in CD4(+) CD25(-) T cells (T effector cells [Teffs]) is actually required for development of autoimmunity under lymphopenic conditions. Mechanistically, the inability of PPARγ-deficient (T-PPAR) Teffs to mediate lymphopenic autoimmunity is associated with a significant decrease in accumulation of Teffs in the spleen, lymph nodes, and tissues after adoptive transfer. This abnormal accumulation of T-PPAR Teffs was associated with defects in both in vivo proliferation and survival. Additionally, T-PPAR Teffs demonstrated decreased cytokine production in inflammatory sites and decreased expression of the homing receptor α4ß7. Finally, these abnormalities in T-PPAR Teff function were not elicited by lymphopenia alone but also required the additional activation involved in the mediation of autoimmunity. Thus, in contrast to its documented immunosuppressive role, we identified an unexpected function for PPARγ in Teffs: a role in Teff proliferation and survival in lymphopenia-associated autoimmunity. These findings highlight both the multifunctional role of PPARγ in T cells and the complexity of PPARγ as a potential therapeutic target in autoimmunity.

Outcomes of pseudo-severe aortic stenosis under conservative treatment.

AIMS: In the setting of low-flow/low-gradient aortic stenosis (LF/LGAS), outcomes of pseudo-severe aortic stenosis (AS) remain poorly described. This study was aimed to assess the outcome of patients with pseudo-severe AS under conservative treatment. METHODS AND RESULTS: Among 305 patients from the European Registry of LF/LGAS, the outcomes of the 107 patients followed under conservative treatment were analysed. Based on the results of dobutamine echocardiography, patients were divided into group IA [left ventricular (LV) contractile reserve present with true-severe AS, n = 43], group IB [pseudo-severe AS (n = 29) defined as LV contractile reserve with a final aortic valve area ≥1.2 cm(2) and a mean transaortic pressure gradient <40 mmHg at peak dobutamine infusion], or group II (exhausted LV contractile reserve, n = 35). The rate of death within 5 years was significantly lower in the group IB (43 ± 11%, n = 10), when compared with the group IA (91 ± 6%, n = 33; P = 0.001) and the group II (100%, n = 23; P < 0.001). The Cox proportional hazard model analysis demonstrated that the hazard ratio for death in the group IB remained significantly lower than in the other groups, even after adjustment for currently established risk factors. Furthermore, the 5-year survival of pseudo-severe AS patients was comparable with that of propensity-matched patients with systolic heart failure and no evidence of valve disease. CONCLUSION: In patients with pseudo-severe AS, the 5-year survival under conservative treatment is better than in true-severe AS and comparable with that of propensity-matched patients with LV systolic dysfunction and no evidence of valve disease. Further studies are needed to define optimal therapeutic management in these patients.

Parent and teacher perceptions of participation and outcomes in an intensive communication intervention for children with pragmatic language impairment.

BACKGROUND: Treatment trials that enquire into parents' and teachers' views on speech-language interventions and outcomes for primary school-age children are relatively rare. The current study sought perceptions of the process of intervention and value placed on outcomes resulting from a trial of intervention, the Social Communication Intervention Project (SCIP), for children with communication disorders characterized by persistent needs in pragmatics and social use of language. AIMS: To describe parent and teacher views around the process and experience of participating in SCIP intervention, including aspects of collaborative practice; and to gain understanding of parents' and teachers' perceptions of communication outcomes for children who had received intervention. METHODS & PROCEDURES: Parents and teachers of eight children in the intervention arm of the SCIP study participated in semi-structured interviews with a researcher within 2 months of completion of SCIP intervention. The framework method of analysis was used to explore predetermined themes based around a list of topics informed by previous thinking and experience of the research. OUTCOMES & RESULTS: Parents and teachers perceived liaison with the SCIP speech and language therapist as being an important element of the intervention. Indirect approaches to liaison with parents were perceived as effective in transferring information as were brief meetings with teachers. Teachers and parents were able to make explicit links between therapy actions and perceived changes in the child. Work on comprehension monitoring and emotional vocabulary was perceived to be particularly effective with respect to communication outcomes. Parents also reflected that they had adopted different strategies towards communication and behaviour in the home as a result of intervention. The limits of potential change in terms of child communication in areas such as non-verbal communication and pragmatic skills were discussed by parents. CONCLUSIONS & IMPLICATIONS: This analysis has contributed essential information to the evaluation of SCIP by describing the experience of the intervention as delivered, exploring processes of effective implementation and change in the school setting and by describing the value placed on different outcomes by parents and teachers. These findings can inform planning for collaborations between speech and language therapists and teachers and provide useful information about mechanisms of change in different components of the SCIP intervention which have not been individually evaluated before. Information on changes in children's communication skills which were perceived as meaningful to those living and working with the children daily is crucial to the acceptance and translation of the SCIP intervention into practice.