A controlled evaluation of an enhanced self-directed behavioural family intervention for parents of children with conduct problems in rural and remote areas.

Few studies have examined the impact of parenting interventions for families in rural and isolated areas who have children with conduct problems, where-access to professional services can be difficult. The present investigation compared the effects of three conditions, two levels of self-directed behavioral family intervention: an enhanced self-directed program that combined a self-help program using written materials and a weekly telephone consultation (ESD), a self-help program (SD) and a waitlist control group (WL). At postintervention the ESD group reported significantly lower levels of disruptive behaviour, and lower levels of dysfunctional parenting than the SD and WL controls, and higher levels of consumer satisfaction. At 6 months follow-up the main effects for the ESD group had been maintained. The SD group continued to evidence improvement from postintervention to follow-up such that 65% of children in the ESD condition and 57% of children in the SD condition showed clinical reliable change on measures of disruptive behaviour. Implications of findings and directions for future research are discussed

"Antiscepticism and Easy Justification" - Ch 5 of Seemings and Epistemic Justification

In this chapter I investigate epistemological consequences of the fact that seeming-based justification is elusive, in the sense that the subject can lose this justification simply by reflecting on her seemings. I argue that since seeming-based justification is elusive, the antisceptical bite of phenomenal conservatism is importantly limited. I also contend that since seeming-based justification has this feature, phenomenal conservatism isn’t actually afflicted by easy justification problems

"Cognitive Penetrability" - Ch 3 of Seemings and Epistemic Justification

In this chapter I introduce the thesis that perceptual appearances are cognitively penetrable and analyse cases made against phenomenal conservatism hinging on this thesis. In particular, I focus on objections coming from the externalist reliabilist camp and the internalist inferentialist camp. I conclude that cognitive penetrability doesn’t yield lethal or substantive difficulties for phenomenal conservatism

A multidimensional account of democratic legitimacy: how to make robust decisions in a non-idealized deliberative context

This paper analyses the possibility of granting legitimacy to democratic decisionmaking procedures in a context of deep pluralism. We defend a multidimensional account according to which a legitimate system needs to grant, on the one hand, that citizens should be included on an equal footing and acknowledged as reflexive political agents rather than mere beneficiaries of policies, and, on the other hand, that their decisions have an epistemic quality. While Estlund\u2019s account of imperfect epistemic proceduralism might seem to embody a dualistic conception of democratic legitimacy, we point out that it is not able to recognize citizens as reflexive political agents and is grounded in an idealized model of the circumstances of deliberation. To overcome these ambiguities, we develop an account of democratic legitimacy according to which disagreement is the proper expression of citizens\u2019 reflexive agency and the attribution of epistemic authority does not stem from a major expertise or specific ability, but it comes through the public confrontation among disagreeing agents. Consequently, the epistemic value of deliberation should be derived from the reasons-giving process rather than from the reference to the alleged quality of its outcomes. In this way, we demonstrate the validity of the multidimensional perspective of legitimacy, yet abstain from introducing any outcome-oriented criterion. Finally, we argue that this account of legitimacy is well suited for modeling deliberative democracy as a decision-making procedure that respects the agency of every citizen and grants her opportunity to influence public choices

Mutations in MAP3K7 that Alter the Activity of the TAK1 Signaling Complex Cause Frontometaphyseal Dysplasia.

Frontometaphyseal dysplasia (FMD) is a progressive sclerosing skeletal dysplasia affecting the long bones and skull. The cause of FMD in some individuals is gain-of-function mutations in FLNA, although how these mutations result in a hyperostotic phenotype remains unknown. Approximately one half of individuals with FMD have no identified mutation in FLNA and are phenotypically very similar to individuals with FLNA mutations, except for an increased tendency to form keloid scars. Using whole-exome sequencing and targeted Sanger sequencing in 19 FMD-affected individuals with no identifiable FLNA mutation, we identified mutations in two genes-MAP3K7, encoding transforming growth factor β (TGF-β)-activated kinase (TAK1), and TAB2, encoding TAK1-associated binding protein 2 (TAB2). Four mutations were found in MAP3K7, including one highly recurrent (n = 15) de novo mutation (c.1454C>T [ p.Pro485Leu]) proximal to the coiled-coil domain of TAK1 and three missense mutations affecting the kinase domain (c.208G>C [p.Glu70Gln], c.299T>A [p.Val100Glu], and c.502G>C [p.Gly168Arg]). Notably, the subjects with the latter three mutations had a milder FMD phenotype. An additional de novo mutation was found in TAB2 (c.1705G>A, p.Glu569Lys). The recurrent mutation does not destabilize TAK1, or impair its ability to homodimerize or bind TAB2, but it does increase TAK1 autophosphorylation and alter the activity of more than one signaling pathway regulated by the TAK1 kinase complex. These findings show that dysregulation of the TAK1 complex produces a close phenocopy of FMD caused by FLNA mutations. Furthermore, they suggest that the pathogenesis of some of the filaminopathies caused by FLNA mutations might be mediated by misregulation of signaling coordinated through the TAK1 signaling complex

Missense Pathogenic variants in KIF4A Affect Dental Morphogenesis Resulting in X-linked Taurodontism, Microdontia and Dens-Invaginatus

The etiology of dental anomalies is multifactorial; and genetic and environmental factors that affect the dental lamina have been implicated. We investigated two families of European ancestry in which males were affected by taurodontism, microdontia and dens invaginatus. In both families, males were related to each other via unaffected females. A linkage analysis was conducted in a New Zealand family, followed by exome sequencing and focused analysis of the X-chromosome. In a US family, exome sequencing of the X-chromosome was followed by Sanger sequencing to conduct segregation analyses. We identified two independent missense variants in KIF4A that segregate in affected males and female carriers. The variant in a New Zealand family (p.Asp371His) predicts the substitution of a residue in the motor domain of the protein while the one in a US family (p.Arg771Lys) predicts the substitution of a residue in the domain that interacts with Protein Regulator of Cytokinesis 1 (PRC1). We demonstrated that the gene is expressed in the developing tooth bud during development, and that the p.Arg771Lys variant influences cell migration in an in vitro assay. These data implicate missense variations in KIF4A in a pathogenic mechanism that causes taurodontism, microdontia and dens invaginatus phenotypes

An Outcome Evaluation of the Implementation of the Triple P – Positive Parenting Program in Hong Kong

The present study evaluated the effectiveness of the Positive Parenting Program (Triple P) with a sample of Chinese parents of children with early onset conduct related problems in Hong Kong. The participants consisted of 91 parents whose children attended maternal and child health centers and child assessment centers for service, and were between three to seven years old. Participants were randomly assigned to the intervention (TP) and a waitlist control group (WL. There was no significant difference in pre-intervention measures between the two groups. However, at post intervention, participants in the TP group reported significantly lower levels of child behavior problems, lower dysfunctional parenting styles, and higher parent sense of competence, compared to the WL group. Implications of these findings for the use of Triple P with families of Chinese descent are discussed

"Phenomenal Conservatism" - Ch 2 of Seemings and Epistemic Justification

In this chapter I introduce and analyse the tenets of phenomenal conservatism, and discuss the problem of the nature of appearances. After that, I review the asserted epistemic merits phenomenal conservatism and the principal arguments adduced in support of it. Finally, I survey objections to phenomenal conservatism and responses by its advocates. Some of these objections will be scrutinised and appraised in the next chapters

Hepatitis C infection: eligibility for antiviral therapies

peer reviewedBackground Current treatments of chronic hepatitis C virus (HCV) are effective, but expensive and susceptible to induce significant side effects. Objectives To evaluate the proportion of HCV patients who are eligible for a treatment. Methods In a database comprising 1726 viraemic HCV patients, the files of 299 patients who presented to the same hepatologist for an initial appointment between 1996 and 2003 were reviewed. Results Patients' characteristics were age 43.1 +/- 15.6 years, 53% male and 92% Caucasian. The main risk factors were transfusion (43%) and drug use (22%). Genotypes were mostly genotype 1 (66%), genotype 3 (12%) and genotype 2 (10%). These characteristics were not different from those of the whole series of 1726 patients. A total of 176 patients (59%) were not treated, the reasons for non-treatment being medical contraindications (34%), non-compliance (25%) and normal transaminases (24%). In addition, 17% of patients declined therapy despite being considered as eligible, mainly due to fear of adverse events. Medical contraindications were psychiatric (27%), age (22%), end-stage liver disease (15%), willingness for pregnancy (13%), cardiac contraindication (7%) and others (16%). Only 123 patients (41%) were treated. A sustained viral response was observed in 41%. The treatment was interrupted in 16% for adverse events. Conclusions The majority of HCV patients are not eligible for treatment. This implies that, with current therapies, only 17% of patients referred for chronic HCV become sustained responders. Some modifications of guidelines could extend the rate of treatment (patients with normal transaminases), but an important barrier remains the patients' and the doctors' fear of adverse events

Prevention of child behavior problems through universal implementation of a group behavioral family intervention.

The aim of this mental health promotion initiative was to evaluate the effectiveness of a universally delivered group behavioral family intervention (BFI) in preventing behavior problems in children. This study investigates the transferability of an efficacious clinical program to a universal prevention intervention delivered through child and community health services targeting parents of preschoolers within a metropolitan health region. A quasiexperimental two-group (BFI, n=804 vs. Comparison group, n=806) longitudinal design followed preschool aged children and their parents over a 2-year period. BFI was associated with significant reductions in parent-reported levels of dysfunctional parenting and parent-reported levels of child behavior problems. Effect sizes on child behavior problems ranged from large (.83) to moderate (.47). Positive and significant effects were also observed in parent mental health, marital adjustment, and levels of child rearing conflict. Findings are discussed with respect to their implication for significant population reductions in child behavior problems as well as the pragmatic challenges for prevention science in encouraging both the evaluation and uptake of preventive initiatives in real world settings