Brain free water alterations in first-episode psychosis: a longitudinal analysis of diagnosis, course of illness, and medication effects.

BACKGROUND: Multiple lines of evidence suggest the presence of altered neuroimmune processes in patients with schizophrenia (Sz) and severe mood disorders. Recent studies using a novel free water diffusion tensor imaging (FW DTI) approach, proposed as a putative biomarker of neuroinflammation, atrophy, or edema, have shown significantly increased FW in patients with Sz. However no studies to date have investigated the longitudinal stability of FW alterations during the early course of psychosis, nor have studies focused separately on FE psychosis patients with Sz or bipolar disorder (BD) with psychotic features. METHODS: The current study included 188 participants who underwent diffusion magnetic resonance imaging scanning at baseline. Sixty-four participants underwent follow-up rescanning after 12 months. DTI-based alterations in patients were calculated using voxelwise tract-based spatial statistics and region of interest analyses. RESULTS: Patients with FE psychosis, both Sz and BD, exhibited increased FW at illness onset which remained unchanged over the 12-month follow-up period. Preliminary analyses suggested that antipsychotic medication exposure was associated with higher FW in gray matter that reached significance in the BD group. Higher FW in white matter correlated with negative symptom severity. CONCLUSIONS: Our results support the presence of elevated FW at the onset of psychosis in both Sz and BD, which remains stable during the early course of the illness, with no evidence of either progression or remission.

Evaluating Practitioner Training to Improve Competencies and Organizational Practices for Engaging Fathers in Parenting Interventions.

Fathers are consistently underrepresented in parenting interventions and practitioners are an important target for change in interventions to enhance father engagement. This research examined the effects of two practitioner training programs in improving practitioner rated competencies and organizational father-inclusive practices. Two studies were conducted, each with a single group, repeated measures (pre, post and 2-month follow-up) design. Study 1 (N = 233) examined the outcomes of face-to-face training in improving practitioner ratings of competencies in engaging fathers, perceived effectiveness and use of father engagement strategies, organizational practices and rates of father engagement. Study 2 (N = 356) examined online training using the same outcome measures. Practitioners in both training formats improved in their competencies, organizational practices and rates of father engagement over time, yet those in the online format deteriorated in three competencies from post-training to follow-up. The implications for delivering practitioner training programs to enhance competencies and rates of father engagement are discussed.

Examining Practitioner Competencies, Organizational Support and Barriers to Engaging Fathers in Parenting Interventions.

Evidence-based parenting interventions have been developed and evaluated largely with mothers. This study examined practitioner reports of rates of father attendance, barriers to engagement, organizational support for father-inclusive practice, participation in training in father engagement, and competencies in working with fathers. It also explored predictors of practitioner competence and rates of father attendance. Practitioners (N = 210) who delivered parenting interventions completed an online survey. Participants reported high levels of confidence in engaging fathers, but only one in three had participated in training and levels of father attendance in parenting interventions were low. Logistic regressions showed that high levels of practitioner competence were predicted by participation in training. Moderate levels of father attendance (vs. low levels) were predicted by greater number of years of experience while high levels of attendance (vs. low levels) were predicted by greater experience, higher levels of competence and higher levels of organizational support. The implications of the findings to informing policy and practice for enhancing father engagement are discussed.

Sex and pubertal variation in reward-related behavior and neural activation in early adolescents.

This study aimed to characterize the role of sex and pubertal markers in reward motivation behavior and neural processing in early adolescence. We used baseline and two-year follow-up data from the Adolescent Brain and Cognitive DevelopmentSM study (15844 observations; 52% from boys; age 9-13). Pubertal development was measured with parent-reported Pubertal Development Scale, and DHEA, testosterone, and estradiol levels. Reward motivation behavior and neural processing at anticipation and feedback stages were assessed with the Monetary Incentive Delay task. Boys had higher reward motivation than girls, demonstrating greater accuracy difference between reward and neutral trials and higher task earnings. Girls had lower neural activation during reward feedback than boys in the nucleus accumbens, caudate, rostral anterior cingulate, medial orbitofrontal cortex, superior frontal gyrus and posterior cingulate. Pubertal stage and testosterone levels were positively associated with reward motivation behavior, although these associations changed when controlling for age. There were no significant associations between pubertal development and neural activation during reward anticipation and feedback. Sex differences in reward-related processing exist in early adolescence, signaling the need to understand their impact on typical and atypical functioning as it unfolds into adulthood.

Sex and pubertal influences on the neurodevelopmental underpinnings of schizophrenia: A case for longitudinal research on adolescents.

Sex is a significant source of heterogeneity in schizophrenia, with more negative symptoms in males and more affective symptoms and internalizing comorbidity in females. In this narrative review, we argue that there are likely sex differences in the pathophysiological mechanisms of schizophrenia-spectrum disorders (SZ) that originate during puberty and relate to the sex-specific impacts of pubertal maturation on brain development. Pubertal maturation might also trigger underlying (genetic or other) vulnerabilities in at-risk individuals, influencing brain development trajectories that contribute to the emergence of SZ. This review is the first to integrate links between pubertal development and neural development with cognitive neuroscience research in SZ to form and evaluate these hypotheses, with a focus on the frontal-striatal and frontal-limbic networks and their hypothesized contribution to negative and mood symptoms respectively. To test these hypotheses, longitudinal research with human adolescents is needed that examines the role of sex and pubertal development using large cohorts or high risk samples. We provide recommendations for such studies, which will integrate the fields of psychiatry, developmental cognitive neuroscience, and developmental endocrinology towards a more nuanced understanding of the role of pubertal factors in the hypothesized sex-specific pathophysiological mechanisms of schizophrenia.

The ENDOCARE questionnaire (ECQ): a valid and reliable instrument to measure the patient-centeredness of endometriosis care in Europe.

BACKGROUND: Endometriosis is prevalent and women need high-quality care, which should be patient-centered. This study aimed to develop a valid and reliable patient-centeredness questionnaire, based on a defined concept of patient-centered endometriosis care (PCEC). METHODS: A literature review, focus groups (FGs) with patients and an expert panel defined PCEC with 10 dimensions. The ENDOCARE questionnaire (ECQ) was developed. FGs resulted in 43 specific statements covering the 10 dimensions of PCEC, for which the ECQ measured 'importance' and 'performance'. Medical and demographic questions and an open question were added. The Dutch ECQ questionnaire was piloted and reciprocally translated into English and Italian. Patients with endometriosis from Belgium, The Netherlands, Italy and the UK were invited to complete the ECQ online. Item analysis, inter-item analysis and confirmatory and exploratory factor analyses (EFA) and reliability analysis were performed. The theory-driven dimensions were adapted. RESULTS: The ECQ was completed by 541 patients. Based on item analysis, five statements were deleted. Factor analysis was performed on 322 questionnaires (only from respondents with a partner). Insights from the data-driven EFA suggested adaptations of the theory-driven dimensions. The reliability statistics of 9/10 adapted theory-driven dimensions were satisfactory and the root mean square error of approximation was good. CONCLUSIONS: This study resulted in a valid and reliable instrument to measure PCEC. For data presentation, the adapted theory-driven dimensions of PCEC are preferred over the data-driven factors. The ECQ may serve to benchmark patient-centeredness, conduct cross-cultural European research and set targets for improvement.

Mothers, Fathers, and Parental Systems: A Conceptual Model of Parental Engagement in Programmes for Child Mental Health-Connect, Attend, Participate, Enact (CAPE).

Parenting programmes are one of the best researched and most effective interventions for reducing child mental health problems. The success of such programmes, however, is largely dependent on their reach and parental engagement. Rates of parental enrolment and attendance are highly variable, and in many cases very low; this is especially true of father involvement in parenting programmes. This paper proposes a conceptual model of parental engagement in parenting programmes-the CAPE model (Connect, Attend, Participate, Enact) that builds on recent models by elaborating on the interdependent stages of engagement, and its interparental or systemic context. That is, we argue that a comprehensive model of parental engagement will best entail a process from connection to enactment of learned strategies in the child's environment, and involve consideration of individual parents (both mothers and fathers) as well as the dynamics of the parenting team. The model provides a framework for considering parent engagement as well as associated facilitators and mechanisms of parenting change such as parenting skills, self-efficacy, attributions, and the implementation context. Empirical investigation of the CAPE model could be used to further our understanding of parental engagement, its importance for programme outcomes, and mechanisms of change. This will guide future intervention refinement and developments as well as change in clinical practice.

The triple P-positive parenting program: a comparison of enhanced, standard, and self-directed behavioral family intervention for parents of children with early onset conduct problems.

Three variants of a behavioral family intervention (BFI) program known as Triple P were compared using 305 preschoolers at high risk of developing conduct problems. Families were randomly assigned to enhanced BFI (EBFI), standard BFI (SBFI), self-directed BFI (SDBFI), or wait list (WL). At postintervention, the 2 practitioner-assisted conditions were associated with lower levels of parent-reported disruptive child behavior, lower levels of dysfunctional parenting, greater parental competence, and higher consumer satisfaction than the SDBFI and WL conditions. Overall, children in EBFI showed greater reliable improvement than children in SBFI, SDBFI, and WL. By 1-year follow-up, children in all 3 conditions achieved similar levels of clinically reliable change in observed disruptive behavior. However, the EBFI and SBFI conditions showed greater reliable improvement on parent-observed disruptive child behavior.

Comparative identity and homogeneity testing of the mtDNA HV1 region using denaturing gradient gel electrophoresis.

A denaturing gradient gel electrophoresis (DGGE) assay has been developed for comparative identity and homogeneity testing of the mtDNA HV1 region. A total of 49 pairs of sequences, each pair differing by a single unique polymorphism, were tested to verify the reliability of the assay. Discrimination between all pairings was achieved as judged by the resolution of the mismatch-containing heteroduplexes from the fully base-paired homoduplexes. In all but two pairings, resolution of the fully base-paired homoduplexes was also obtained. Sequence pairs differing by multiple polymorphisms were also tested and resulted in a greater separation between the homo- and heteroduplexes. Additional information derived from the technique includes the identification of co-amplifying contaminating or heteroplasmic samples in the independent samples lanes. Thirteen heteroplasmic samples, six at positions distinct from those analyzed in the pairwise comparison study, were analyzed and the heteroplasmic positions identified unambiguously by sequencing the excised bands. The technique constitutes a conceptually simple, accurate, and inexpensive test for determining whether two sequences match within the mtDNA HV1 region, while providing a more definitive control for the identification of co-amplifying contaminating or heteroplasmic sequences than is presently available.

Polymorphisms in TNC and COL5A1 genes are associated with risk of superficial digital flexor tendinopathy in National Hunt Thoroughbred racehorses.

REASONS FOR PERFORMING THE STUDY: To explore whether genetic susceptibility is a potential risk factor for superficial digital flexor (SDF) tendinopathy in Thoroughbred (TB) racehorses. OBJECTIVES: To identify informative single nucleotide polymorphisms (SNPs) that capture genetic diversity across a range of candidate genes and to investigate, in a case-control study, their association with SDF tendinopathy in UK National Hunt TB racehorses in training. STUDY DESIGN: Case-control candidate gene association study. METHODS: This study used in silico gene assembly and DNA sequencing to screen candidate genes for SNPs. Seven candidate genes were selected using a hypothesis-driven approach: tenascin-C (TNC), collagen, type 1, α 1 (COL1A1), collagen, type 5, α 1 (COL5A1), matrix metalloproteinase type 3 (MMP3), matrix metalloproteinase type 13 (MMP13), fibromodulin (FMOD) and cartilage oligomeric matrix protein (COMP). The SNPs were validated in DNA isolated from 48 TB racehorses and used to genotype 270 racehorses with SDF tendinopathy and 270 yard-matched controls. Genotyping of cases and controls was performed using SNaPshot™. RESULTS: Racehorses heterozygous for the TNC BIEC2-696469 polymorphism were less likely to have SDF tendinopathy than racehorses homozygous for the wild-type allele (odds ratio [OR] 0.56, 95% confidence interval [CI] 0.36-0.85, P = 0.01). This finding remained significant after adjustment for age and racing background (OR 0.57, 95% CI 0.36-0.92, P = 0.03). Racehorses homozygous for the novel COL5A1 COL5A1_01 variant allele were nearly 3 times more likely to have SDF tendinopathy than those homozygous for the wild-type allele (OR 2.82, 95% CI 1.25-6.35, P = 0.01); this association remained significant after adjustment for age and racing background (OR 2.77, 95% CI 1.18-6.53, P = 0.03). CONCLUSIONS: Results suggest that sequence variants in TNC and COL5A1 genes are associated with SDF tendinopathy in TB racehorses. In future genetic markers may be used to identify horses at risk of SDF tendinopathy.

Compact collimated fiber optic array diagnostic for railgun plasmas.

We developed and tested a compact collimated 16 channel fiber optic array diagnostic for studying the light emission of railgun armature plasmas with approximately millimeter spatial and submicrosecond temporal resolution. The design and operational details of the diagnostic are described. Plasma velocities, oscillation, and dimension data from the diagnostic for the Livermore fixed hybrid armature experiment are presented and compared with one-dimensional simulations. The techniques and principles discussed allow the extension of the diagnostic to other railgun and related dense plasma experiments.

The validity and utility of patients' daily ratings of mood and impairment in clinical trials of bipolar disorder.

OBJECTIVE: Traditional cross-sectional clinician-rated measures have limited use in clinical trials of bipolar disorder. We examine the validity and usefulness of patients' daily ratings of mood and functional impairment during a treatment trial. METHOD: Ten subjects with bipolar II disorder completed daily ratings of depression severity, depression, hypomania and functional impairment over a 9-month trial. Ratings were correlated with clinician-rated measures at nine time points to determine validity. Mood ratings were contrasted with cross-sectional data for one subject to determine usefulness of such fine-grained data. RESULTS: Moderate to large correlations were found between patients' and clinicians' ratings of mood and impairment for most of the nine time points. The utility of the patients' ratings relative to clinician-rated cross-sectional measures was also illustrated. CONCLUSION: Results support the validity and usefulness of patients' daily mood ratings.

Evolution of the uses of ICD-9-CM coding: Medicare risk adjustment methodology for managed care plans.

The health information management (HIM) profession is expanding to new sites and perspectives. The implementation of Medicare managed care has brought changes not only by emphasis on management of the individual's medical care and the cost of that care, but also by creating new uses for coded data. This article examines the evolution of risk adjustment methods in Medicare Managed Care. The current choice for risk adjustment is the Principal Inpatient Diagnostic Cost Groups (PIP-DCG). This article explains the health plan's submission of encounter data and how HIM can play a valuable role in data capture and improvement in data quality and reimbursement.

Characterization of mitochondrial DNA using low-stringency single specific primer amplification analyzed by laser induced fluorescence--capillary electrophoresis.

Polymerase chain reaction (PCR)-based DNA typing is routinely used in forensics for identity testing. Those assays that distinguish single nucleotide polymorphisms (SNPs) require other biochemical reactions in addition to PCR to identify the sequence polymorphisms. Low-stringency sequence-specific PCR (LSSP-PCR) is an example of a recent method that does not require additional biochemical treatments. The analysis of LSSP-PCR by capillary electrophoresis (CE) to discriminate the highly polymorphic mitochondrial DNA (mtDNA) D-loop region is described. The DNA from five individuals were amplified (first step) using sequence-specific primers to produce 1021 bp fragments containing the D-loop region. Each fragment was isolated by electroelution using CE and UV detection, and subjected to a second amplification (second step) using a single primer annealed under low stringency conditions. This generated a range or profile of PCR products for each sample, which were resolved and analyzed by CE with the intercalator TOTO-1 and laser-induced fluorescence (LIF) detection. The LSSP-PCR profiles were unique for each individual, indicating that this technique may be applicable for forensic identity testing.

Mealtime behavior and parent-child interaction: a comparison of children with cystic fibrosis, children with feeding problems, and nonclinic controls.

Examined the role of family interaction factors in dietary compliance problems reported by parents of children with cystic fibrosis (CF). The family mealtime interactions of children with CF, children with feeding problems and nonclinic controls were observed, and parents monitored children's eating behavior at home. Parents of children with CF reported more concern about feeding problems and recorded more disruptive mealtime behavior than parents of nonclinic children. Observational data showed children with CF to display overall rates of disruptive mealtime behavior not significantly different from either comparison group. Mothers of children with CF were observed to engage in higher rates of aversive interaction with their child than did mothers of nonclinic controls. Fathers of children with CF reported lower marital satisfaction than fathers of controls. Both mothers and fathers of children with CF reported lower parenting self-efficacy than non-CF families. Clinical implications are discussed.

A sensitive denaturing gradient-Gel electrophoresis assay reveals a high frequency of heteroplasmy in hypervariable region 1 of the human mtDNA control region.

A population study of heteroplasmy in the hypervariable region 1 (HV1) portion of the human mtDNA control region was performed. Blood samples from 253 randomly chosen individuals were examined using a sensitive denaturing gradient-gel electrophoresis (DGGE) system. This method is capable of detecting heteroplasmic proportions as low as 1% and virtually all heteroplasmy where the minor component is > or = 5%. Heteroplasmy was observed in 35 individuals (13.8%; 95% confidence interval [CI] 9.6-18.0). Of these individuals, 33 were heteroplasmic at one nucleotide position, whereas 2 were heteroplasmic at two different positions (a condition known as "triplasmy"). Although heteroplasmy occurred at a total of 16 different positions throughout HV1, it was most frequently observed at positions 16093 (n=13) and 16129 (n=6). In addition, the majority of heteroplasmic variants occurred at low proportions and could not be detected by direct sequencing of PCR products. This study indicates that low-level heteroplasmy in HV1 is relatively common and that it occurs at a broad spectrum of sites. Our results corroborate those of other recent reports indicating that heteroplasmy in the control region is more common than was previously believed-a finding that is of potential importance to evolutionary studies and forensic applications that are based on mtDNA variation.