Timing of High-Dose-Rate Brachytherapy With External Beam Radiation Therapy in Patients With Intermediate- and High-Risk Localized Prostate Cancer and Its Effects on Toxicity and Quality of Life: A Randomized Controlled Trial (THEPCA).

PURPOSE: High-dose-rate brachytherapy (HDR-BT) and external beam radiation therapy (EBRT) are effective treatments for prostate cancer but cause genitourinary (GU) and gastrointestinal (GI) toxicities. There is no consensus on the timing of HDR-BT in relation to EBRT and the effect of sequencing on patients. The primary objective was to assess differences, if any, in the incidence of grade (G) 3 or higher GU toxicities from treatment. We also aimed to explore the incidence of G1 to G4 GI toxicities, quality of life (QOL), and patient satisfaction. Suppression of prostate-specific antigen (PSA) and signals for survival differences were also analyzed. METHODS AND MATERIALS: This was a single-center randomized trial in patients with intermediate- and high-risk localized prostate cancer who received HDR-BT before (Arm A) or after (Arm B) EBRT. Toxicities were graded using Common Terminology Criteria for Adverse Events (CTCAE). The International Prostate Symptom Score (IPSS) was used to assess lower urinary tract symptoms. The International Index of Erectile Function scale (IIEF) and Functional Assessment of Cancer Therapy-Prostate (FACT-P) were used to assess erectile dysfunction and QOL at 0, 3, 9, and 12 months. RESULTS: Fifty patients were recruited to each arm, with 48 and 46 patients completing treatment and follow-up in each arm, 81.5% of whom had high-risk disease. There were no G3 or G4 GU or GI toxicities. G1 urinary frequency was the most common adverse event experienced in both arms, peaking in incidence 3 months after treatment commenced (45.7% and 42.2% in Arm A and B, respectively). Up to 11% of patients reported G1 urinary frequency at 12 months. Other G1 GU toxicities experienced by >10% of patients were urinary tract obstruction, tract pain, and urgency. These symptoms also peaked in incidence at 3 months. G2 GU toxicities were uncommon and experienced in a maximum of 2 patients within each arm at any time point. Over 30% of patients had G1 flatulence at baseline, and this remained the most frequently occurring G1 GI toxicity throughout the study, peaking at 12 months (21.4% and 25.6% in Arm A and B, respectively). Other GI toxicities experienced by more than 10% of patients were GI pain, proctitis, and rectal mucositis, most of which demonstrated a peak incidence at 3 or 9 months. G2 GI toxicities were uncommon except for G2 flatulence. No significant difference was found in CTCAE, IPSS, IIEF, FACT-P, and QOL scores between the arms. Median prostate-specific antigen (PSA) follow-up was 5 years. Seven patients had treatment failure in each arm. Disease Free Survival (DFS) was 93.3% and 90.7% at 5 years in Arm A and B, respectively, with median failure time of 60 and 48 months in Arm A and B, respectively. There were no statistically significant differences between arms. CONCLUSIONS: The sequencing of HDR-BT and EBRT did not affect the incidence of G3 or G4 toxicities, and no significant differences were seen in other patient-reported outcomes. Treatment was well tolerated with maintained QOL scores. Treatment failure was low in both arms in a high-risk cohort; however, a larger study with longer follow-up is underway to establish whether the difference in median time to failure between the 2 arms is a signal of superiority.

Investigate the efficacy of size exclusion chromatography for the isolation of extracellular vesicles from C. elegans.

Isolation of Extracellular Vesicles (EVs) has been done extensively in the past using ultracentrifugation, a recent shift has been observed towards precipitation, and exosome isolation kits. These methods often co-elute contaminants of similar size and density which makes their detection and downstream applications quite challenging. As well as the EV yield is also compromised in some methodologies due to aggregate formation. In recent reports, size-exclusion chromatography (SEC) is replacing density gradient-based ultracentrifugation as the gold standard of exosome isolation. It outperforms in yield, purity and does not account for any physical damage to the EVs. We have standardized the methodology for an efficient pure yield of homogenous exosomes of size even smaller than 75 nm in Caenorhabditis elegans homogenate. The paper entails the application and optimization of EV isolation by SEC based on previous studies by optimizing bed size and type of sepharose column employed. We propose that this method is economically feasible in comparison with currently available approaches. A comparative study was conducted to investigate the performance of CL-6B in relation to CL-2B and further, this was combined with ultracentrifugation for higher efficacy. The methodology could be introduced in a clinical setting due to its therapeutic potential and scope. The eluted EVs were studied by flow cytometry, nanotracking and characterized for size and morphology.

Individual Dimensions of Pain Catastrophizing Do Not Mediate the Effect of Sociodemographic and Psychological Factors on Chronic Orofacial Pain Severity, Interference, and Jaw Limitation: A Structural Equation Modeling Approach.

Pain catastrophization (PC), involving rumination, magnification, and helplessness, can be viewed as a coping strategy associated with chronic pain. PC is considered a driving force in mediating pain-related outcomes, but it is still unclear whether PC mediates the relationship between psychological and sociodemographic factors with chronic pain when considered in a single model. Using baseline data from a parent study, this study examined the effect of positive and negative psychological and sociodemographic factors on pain severity, interference, and jaw limitation mediated by the PC dimensions in a sample of 397 temporomandibular disorder (TMD) participants using structural equation modeling (SEM). SEM revealed that pain severity regressed on age, sex, education, and income; interference regressed on positive and negative psychological factors, education, and income; and jaw limitation regressed on age. The PC dimensions did not individually mediate these relationships. Although they jointly mediated the relationships between negative psychological factors and pain severity and between age and pain interference, the effect size was small, suggesting that PC is not a critical factor in mediating TMD pain outcomes. Reducing negative cognitions, not just PC, may be of greatest benefit to the most vulnerable TMD populations. PERSPECTIVE: This study examines sociodemographic and psychological factors that affect orofacial pain, finding that the pain catastrophizing dimensions do not mediate these relationships. Understanding which factors most strongly affect pain outcomes will help identify targets for intervention to produce the greatest benefit for the most vulnerable persons suffering from pain.

How negative and positive constructs and comorbid conditions contribute to disability in chronic orofacial pain.

BACKGROUND: Temporomandibular disorders (TMD) symptoms develop into chronic pain for some patients, but the reasons for this are unclear. Psychosocial factors and chronic overlapping pain conditions are believed to contribute to the development of pain-related disability. We examined the role of jaw function, negative and positive psychological factors and chronic overlapping pain conditions (COPCs) on pain-related disability whilst controlling for demographic variables. METHODS: We collected demographics, medical and psychosocial history and the Graded Chronic Pain Scale, a measure of pain intensity and pain interference from 400 participants with chronic TMD. Structural equation modelling was used to assess a model of COPCs and the latent variables of psychological unease (pain catastrophizing, somatic symptoms and negative affect), positive valence factors (optimism and positive affect), jaw function (chewing, opening and expression limitation) and pain-related disability (pain intensity and pain interference) whilst controlling for demographic variables. RESULTS: We achieved good fit of a parsimonious model (root-mean-square error of approximation = 0.063 [90% CI] [0.051-0.075]), comparative fit index = 0.942, standard root-mean-square residual = 0.067. Jaw function was the strongest latent variable predictor, followed by psychological unease and COPCs suggesting resources focused on improving joint function, psychosocial support and management of COPCs will improve pain-related disability in TMDs. CONCLUSIONS: These findings not only increase the body of knowledge related to TMD clinical phenotypes but also, have a translational impact in further supporting the potential value of targeting physical therapy such as jaw exercise along with psychological interventions as multidisciplinary nonpharmacological therapeutic solutions.

The coping skills and quality of life among rape survivors - A descriptive study from Kerala.

Background: Rape is one of the most heinous of acts. It constitutes a major violation of an individual's basic rights and intensely impacts their mental and physical health. Coping skills used to deal with the trauma could provide information on their quality of life (QOL). Objectives: To assess the coping skills and QOL of rape survivors and to explore its association with their coping skills. Materials and Methods: Data were collected through a questionnaire, and coping skills were assessed using the Brief COPE scale and QOL using the World Health Organization quality of life questionnaire (WHOQOL-BREF). Results were analyzed using the Kruskal-Wallis H test and Spearman rank correlation. Results: Adaptive coping skills such as use of instrumental support, active coping, use of emotional support, self-distraction, and acceptance had higher COPE mean scores. QOL in the domain of physical health (mean = 52.71) had the highest mean score, followed by the domains of environment (mean = 51.35) and psychological health (mean = 48.37). Use of coping skills like active coping, use of emotional support, use of instrumental support, positive reframing, and acceptance had a significant positive correlation with the QOL in the domains of physical health and environment. Active coping and positive reframing were positively correlated with the QOL in the domain of psychological health, while positive reframing and humor were positively correlated with the social relationships domain. Conclusion: Those who employed adaptive coping skills (active coping, use of emotional support, use of instrumental support, positive reframing, acceptance) showed significantly better QOL than those with maladaptive skills.

Prognostic factors for survival and ambulatory status at 8 weeks with metastatic spinal cord compression in the SCORAD randomised trial.

BACKGROUND: Metastatic spinal cord compression (MSCC) carries a poor prognosis and management is based on the likelihood of maintaining mobility and predicted survival. PATIENTS AND METHOD: SCORAD is a randomised trial of 686 patients comparing a single dose of 8 Gy radiotherapy with 20 Gy in 5 fractions. Data was split into a training set (412, 60%) and a validation set (274, 40%). A multivariable Cox regression for overall survival (OS) and a logistic regression for ambulatory status at 8 weeks were performed in the training set using baseline factors and a backward selection regression to identify a parsimonious model with p ≤ 0.10. Receiver Operating Characteristic (ROC) analysis evaluated model prognostic performance in the validation set. Validation of the final survival model was performed in a separate registry dataset (n = 348). RESULTS: The survival Cox model identified male gender, lung, gastrointestinal, and other types of cancer, compression at C1-T12, presence of non-skeletal metastases and poor ambulatory status all significantly associated with worse OS (all p < 0.05). The ROC AUC for the selected model was 75% (95%CI: 69-81) in the SCORAD validation set and 68% (95%CI: 62-74) in the external validation registry data. The logistic model for ambulatory outcome identified primary tumour breast or prostate, ambulatory status grade 1 or 2, bladder function normal and prior chemotherapy all significantly associated with increased odds of ambulation at 8 weeks (all p < 0.05). The ROC AUC for the selected model was 72.3% (95% CI 62.6-82.0) in the validation set. CONCLUSIONS: Primary breast or prostate cancer, and good ambulatory status at presentation, are favourable prognostic factors for both survival and ambulation after treatment.

Cortisol Reactivity and Observed Parenting among Mothers of Children with and without ADHD.

OBJECTIVE: Neurobiological models suggest links between maternal cortisol reactivity and parenting; however, no studies have examined cortisol reactivity and parenting in mothers of school-age children with ADHD. METHOD: We examined the relationship between observed parenting and maternal cortisol reactivity in two laboratory contexts: the Trier Social Stress Task (TSST) and parenting-child interaction (PCI). Mothers of children with (N = 24) and without (N = 36) ADHD participated. RESULTS: During the TSST, greater cortisol output and increase were associated with decreased positive and increased negative parenting. However, during the PCI, cortisol output was associated with increased self-reported and observed positive parenting, and decreased observed negative parenting. Cortisol change during the PCI was associated with decreased observed positive parenting and increased self-reported negative parenting. Among mothers of children with ADHD, cortisol output during the PCI was negatively associated with negative, inconsistent parenting. Change in cortisol predicted more inconsistent discipline and corporal punishment. CONCLUSION: Findings contribute to an integrative biological, psychological, and cognitive process model of parenting in families of children with ADHD.

Pain experience and mood disorders during the lockdown of the COVID-19 pandemic in the United States: an opportunistic study.

INTRODUCTION: The unknown and uncontrollable situation of the coronavirus disease 2019 (COVID-19) pandemic may have triggered changes in pain, anxiety, and depression along with a perception of nonspecific COVID-19 symptoms. OBJECTIVES: We determined how anxiety, depression, and pain outcomes varied during the "Stay-at-Home" order compared with the prepandemic period and whether nonspecific COVID-19 symptoms would occur. METHODS: We conducted an online survey to opportunistically reassess clinical anxiety, depression, pain intensity, and pain interference while controlling for somatic symptom severity during the prepandemic and Stay-at-Home order period. During the Stay-at-Home period, anxiety, depression, pain intensity, and pain interference were reassessed. Coping strategies were assessed as a critical factor influencing pain behaviors. In addition, we explored the occurrence of nonspecific COVID-19 symptoms with an ad hoc survey referencing the Centers for Disease Control and Prevention publicly available COVID-19 symptoms. RESULTS: We observed a significant increase in depression and anxiety levels during the Stay-at-Home period. Coping strategy changes (eg, increased exercise) were linked to lower pain severity and interference which improved overall. Participants who self-reported nonspecific COVID-19 symptoms had higher prepandemic depression. Among the 72 participants not diagnosed with COVID-19, 70.8% of the participants experienced symptoms resembling those associated with COVID-19. CONCLUSION: We suggest the parallel between pain outcome improvement and worsening anxiety and depression during the Stay-at-Home order might reflect a shift in symptoms, indicating that those patients with underlying mood disorders may require more help than they did before the pandemic.

The Unique Effects of Maternal ADHD Symptoms and Emotion Dysregulation on Parenting Behavior.

Objective: Separate literatures have examined the associations between maternal ADHD symptoms and parenting and maternal emotion regulation (ER) and parenting. This study examined the effects of both maternal ADHD symptoms and ER on parenting. Method: This cross-sectional study used a multi-method evaluation of parenting behavior to examine the independent and interactive effects of maternal ADHD symptoms and ER on self-reported and observed parenting among 79 demographically diverse families of 5- to 10-year-old children. Results: There were significant main effects of maternal ER difficulties on negative parenting and of maternal ADHD symptoms on harsh responses to children's negative emotions. Maternal ADHD symptoms and ER were not significantly associated with positive parenting behavior. No interaction effects were observed. Conclusion: Maternal ADHD symptoms and emotion dysregulation may uniquely contribute to parenting difficulties. Maternal ADHD symptoms were associated with difficulties responding to children's negative emotions, whereas maternal ER was associated with difficulties with discipline practices.

Prior Therapeutic Experiences, Not Expectation Ratings, Predict Placebo Effects: An Experimental Study in Chronic Pain and Healthy Participants.

INTRODUCTION: Many clinical trials fail because of placebo responses. Prior therapeutic experiences and patients' expectations may affect the capacity to respond to placebos in chronic disorders. OBJECTIVE: The scope of this study in 763 chronic orofacial pain and healthy study participants was to compare the magnitude and prevalence of placebo effects and determine the putative role of prior therapeutic experiences vs. expectations. METHODS: We tested placebo propensity in a laboratory setting by using 2 distinct levels of individually tailored painful stimulations (high pain and low pain) to reinforce expectations and provide a hypoalgesic experience (conditioning phase). Afterwards, both levels of pain were surreptitiously set at a moderate pain level to test for placebo effects (testing phase). Pain and expectation ratings were assessed as primary outcomes using visual analog scales. RESULTS: In both chronic pain and healthy participants, placebo effects were similar in magnitude, with the larger prevalence of responders in the healthy participants. Although chronic pain participants reported higher pain relief expectations, expectations did not account for the occurrence of placebo effects. Rather, prior experience via conditioning strength mediated placebo effects in both pain and healthy participants. CONCLUSIONS: These findings indicate that participants with chronic pain conditions display robust placebo effects that are not mediated by expectations but are instead directly linked to prior therapeutic experiences. This confirms the importance of assessing the therapeutic history while raising questions about the utility of expectation ratings. Future research is needed to enhance prediction of responses to placebos, which will ultimately improve clinical trial designs.

Effect of Single-Fraction vs Multifraction Radiotherapy on Ambulatory Status Among Patients With Spinal Canal Compression From Metastatic Cancer: The SCORAD Randomized Clinical Trial.

Importance: Malignant spinal canal compression, a major complication of metastatic cancer, is managed with radiotherapy to maintain mobility and relieve pain, although there is no standard radiotherapy regimen. Objective: To evaluate whether single-fraction radiotherapy is noninferior to 5 fractions of radiotherapy. Design, Setting, and Participants: Multicenter noninferiority randomized clinical trial conducted in 42 UK and 5 Australian radiotherapy centers. Eligible patients (n = 686) had metastatic cancer with spinal cord or cauda equina compression, life expectancy greater than 8 weeks, and no previous radiotherapy to the same area. Patients were recruited between February 2008 and April 2016, with final follow-up in September 2017. Interventions: Patients were randomized to receive external beam single-fraction 8-Gy radiotherapy (n = 345) or 20 Gy of radiotherapy in 5 fractions over 5 consecutive days (n = 341). Main Outcomes and Measures: The primary end point was ambulatory status at week 8, based on a 4-point scale and classified as grade 1 (ambulatory without the use of aids and grade 5 of 5 muscle power) or grade 2 (ambulatory using aids or grade 4 of 5 muscle power). The noninferiority margin for the difference in ambulatory status was -11%. Secondary end points included ambulatory status at weeks 1, 4, and 12 and overall survival. Results: Among 686 randomized patients (median [interquartile range] age, 70 [64-77] years; 503 (73%) men; 44% had prostate cancer, 19% had lung cancer, and 12% had breast cancer), 342 (49.8%) were analyzed for the primary end point (255 patients died before the 8-week assessment). Ambulatory status grade 1 or 2 at week 8 was achieved by 115 of 166 (69.3%) patients in the single-fraction group vs 128 of 176 (72.7%) in the multifraction group (difference, -3.5% [1-sided 95% CI, -11.5% to ∞]; P value for noninferiority = .06). The difference in ambulatory status grade 1 or 2 in the single-fraction vs multifraction group was -0.4% (63.9% vs 64.3%; [1-sided 95% CI, -6.9 to ∞]; P value for noninferiority = .004) at week 1, -0.7% (66.8% vs 67.6%; [1-sided 95% CI, -8.1 to ∞]; P value for noninferiority = .01) at week 4, and 4.1% (71.8% vs 67.7%; [1-sided 95% CI, -4.6 to ∞]; P value for noninferiority = .002) at week 12. Overall survival rates at 12 weeks were 50% in the single-fraction group vs 55% in the multifraction group (stratified hazard ratio, 1.02 [95% CI, 0.74-1.41]). Of the 11 other secondary end points that were analyzed, the between-group differences were not statistically significant or did not meet noninferiority criterion. Conclusions and Relevance: Among patients with malignant metastatic solid tumors and spinal canal compression, a single radiotherapy dose, compared with a multifraction dose delivered over 5 days, did not meet the criterion for noninferiority for the primary outcome (ambulatory at 8 weeks). However, the extent to which the lower bound of the CI overlapped with the noninferiority margin should be considered when interpreting the clinical importance of this finding. Trial Registration: ISRCTN Identifiers: ISRCTN97555949 and ISRCTN97108008.

Population Management: A Tool to Improve Timely Care in Pediatric and Young Adult Patients with Inflammatory Bowel Disease.

BACKGROUND: Maintenance of health leads to better outcomes in patients with chronic illness. ImproveCareNow, an international inflammatory bowel disease (IBD) quality improvement (QI) network, recommends maintenance-of-health visits twice a year. We identified a gap in care, with only 64% of IBD patients having documented visits within 200 days. Therefore, we sought to improve our follow-up rate to a goal of 80%. METHODS: Using population management (PM) reports, we identified patient-, data-, and treatment-related reasons for no documented visit within 200 days. We used the Pareto chart, key drivers, and process flow mapping and implemented changes using Plan-Do-Study-Act (PDSA) cycles to improve follow-up visit rates. Outcomes were presented using a control run chart with pre- and post- intervention data. RESULTS: The most common reasons for no visits were patient nonadherence with appointments (50%) and relocation/transition to an adult provider (25%). The median percentage of documented visits within 200 days increased from 64% to 83% (p < 0.0001), and this increase has been sustained for one year. CONCLUSIONS: Using the PM tool and focused QI interventions improved data quality and the percentage of patients with a documented visit within 200 days. The process is simple and can be applied to patients with other chronic illnesses.

Maternal Executive Functioning and Scaffolding in Families of Children with and without Parent-Reported ADHD.

Parental scaffolding robustly predicts child developmental outcomes, including improved self-regulation and peer relationships and fewer externalizing behaviors. However, few studies have examined parental characteristics associated with a parent's ability to scaffold. Executive functioning (EF) may be an important individual difference factor associated with maternal scaffolding that has yet to be examined empirically. Scaffolding may be particularly important for children with attention-deficit/hyperactivity disorder (ADHD) and disruptive behavior disorder (DBD) symptoms due to their core difficulties with inattention, disorganization, EF, and self-regulation, their need for greater parental structure, and higher-than-average rates of parental EF deficits. Yet, little research has examined child ADHD in relation to parental scaffolding. This cross-sectional study examined: (1) the association between maternal EF (as measured by the Hotel Test, Barkley's Deficits in Executive Functioning Scale, and Digit Span) and observed scaffolding, (2) the association between parent-reported child ADHD/DBD symptoms and scaffolding, and (3) the interaction between child ADHD/DBD symptoms and maternal EF in predicting scaffolding. In a sample of 84 mothers and their 5-10 year-old biological children (62% male) with and without parent-reported ADHD, we found that maternal EF, as measured by Digit Span and the Hotel Test, predicted observed maternal scaffolding. However, child ADHD/DBD symptoms did not significantly predict maternal scaffolding controlling for child age, maternal education, and maternal EF, nor did the interaction of maternal EF and parent-reported child ADHD/DBD symptoms. Working memory and task shifting may be key components of parental EF that could be targeted in interventions to improve parental scaffolding.

Timing of High-Dose Rate Brachytherapy With External Beam Radiotherapy in Intermediate and High-Risk Localized Prostate CAncer (THEPCA) Patients and Its Effects on Toxicity and Quality of Life: Protocol of a Randomized Feasibility Trial.

BACKGROUND: Prostate cancer is the most common cancer in males in the UK and affects around 105 men for every 100,000. The role of radiotherapy in the management of prostate cancer significantly changed over the last few decades with developments in brachytherapy, external beam radiotherapy (EBRT), intensity-modulated radiotherapy (IMRT), and image-guided radiotherapy (IGRT). One of the challenging factors of radiotherapy treatment of localized prostate cancer is the development of acute and late genitourinary and gastrointestinal toxicities. The recent European guidelines suggest that there is no consensus regarding the timing of high-dose rate (HDR) brachytherapy and EBRT. The schedules vary in different institutions where an HDR boost can be given either before or after EBRT. Few centers deliver HDR in between the fractions of EBRT. OBJECTIVE: Assessment of acute genitourinary and gastrointestinal toxicities at various time points to better understand if the order in which treatment modality is delivered (ie, HDR brachytherapy or EBRT first) has an effect on the toxicity profile. METHODS: Timing of HDR brachytherapy with EBRT in Prostate CAncer (THEPCA) is a single-center, open, randomized controlled feasibility trial in patients with intermediate and high-risk localized prostate cancer. A group of 50 patients aged 18 years old and over with histological diagnosis of prostate cancer (stages T1b-T3BNOMO), will be randomized to one of two treatment arms (ratio 1:1), following explanation of the study and informed consent. Patients in both arms of the study will be treated with HDR brachytherapy and EBRT, however, the order in which they receive the treatments will vary. In Arm A, patients will receive HDR brachytherapy before EBRT. In Arm B (control arm), patients will receive EBRT before HDR brachytherapy. Study outcomes will look at prospective assessment of genitourinary and gastrointestinal toxicities. The primary endpoint will be grade 3 genitourinary toxicity and the secondary endpoints will be all other grades of genitourinary toxicities (grades 1 and 2), gastrointestinal toxicities (grades 1 to 4), prostate-specific antigen (PSA) recurrence-free survival, overall survival, and quality of life. RESULTS: Results from this feasibility trial will be available in mid-2016. CONCLUSIONS: If the results from this feasibility trial show evidence that the sequence of treatment modality does affect the patients' toxicity profiles, then funding would be sought to conduct a large, multicenter, randomized controlled trial. TRIAL REGISTRATION: International Standard Randomized Controlled Trial Number (ISRCTN): 15835424; http://www.isrctn.com/ISRCTN15835424 (Archived by WebCite at http://www.webcitation.org/6Xz7jfg1u).

Preliminary evaluation of a multimodal early intervention program for behaviorally inhibited preschoolers.

OBJECTIVE: Approximately 15%-20% of young children can be classified as having a behaviorally inhibited (BI) temperament. Stable BI predicts the development of later anxiety disorders (particularly social anxiety), but not all inhibited children develop anxiety. Parenting characterized by inappropriate warmth/sensitivity and/or intrusive control predicts the stability of BI and moderates risk for anxiety among high-BI children. For these reasons, we developed and examined the preliminary efficacy of the Turtle Program: a multimodal early intervention for inhibited preschool-age children. METHOD: Forty inhibited children between the ages of 42-60 months and their parent(s) were randomized to either the Turtle Program (n = 18) or a waitlist control (WLC; n = 22) condition. Participants randomized to the Turtle Program condition received 8 weeks of concurrent parent and child group treatment. Participants were assessed at baseline and posttreatment with multisource assessments, including parent and teacher report measures of child anxiety, diagnostic interviews, and observations of parenting behavior. RESULTS: The Turtle Program resulted in significant beneficial effects relative to the WLC condition on maternal-reported anxiety symptoms of medium to large magnitude; large effects on parent-reported BI; medium to large effects on teacher-rated school anxiety symptoms; and medium effects on observed maternal positive affect/sensitivity. CONCLUSIONS: This study provides encouraging preliminary support for the Turtle Program for young behaviorally inhibited children. Effects of the Turtle Program generalized to the school setting. Future studies should examine whether this early intervention program improves long-term developmental outcomes for this at-risk group.

Maternal Depression History Moderates Parenting Responses to Compliant and Noncompliant Behaviors of Children with ADHD.

Maternal depression and parenting are robust predictors of developmental outcomes for children with attention-deficit/hyperactivity disorder (ADHD). However, methods commonly used to examine parent-child interactions in these families do not account for temporal associations between child and parent behavior that have been theorized to maintain negative child behavior. Moreover, studies examining associations between maternal depression and parenting in families of children with ADHD have not compared mothers who were currently depressed, remitted, and never clinically depressed. This study utilized sequential analysis to examine how maternal reinforcement of compliant and noncompliant child behavior differs as a function of maternal depression history. Within the 82 participating mother-child dyads, 21 mothers were currently depressed, 29 mothers had a lifetime history of depression but were in remission for at least 1 month, and 32 mothers had never been clinically depressed. 24 girls (29.6 %) and 57 boys (70.4 %) between the ages of 6-12 years old (M = 8.7, SD = 2.0) and were diagnosed with ADHD. Results indicated that all mothers were less likely to respond optimally than non-optimally to child compliant and noncompliant behaviors during observed parent-child interactions; however, currently depressed mothers were least likely to reinforce child compliance and responded most coercively to child noncompliance relative to the other groups. Remitted mothers in this sample were more coercive than never clinically depressed mothers, but were more likely to follow through with commands than never clinically depressed mothers. Implications for behavioral parent training programs aimed at skill development for depressed mothers of children with ADHD are discussed.

Sisters unbound is required for meiotic centromeric cohesion in Drosophila melanogaster.

Regular meiotic chromosome segregation requires sister centromeres to mono-orient (orient to the same pole) during the first meiotic division (meiosis I) when homologous chromosomes segregate, and to bi-orient (orient to opposite poles) during the second meiotic division (meiosis II) when sister chromatids segregate. Both orientation patterns require cohesion between sister centromeres, which is established during meiotic DNA replication and persists until anaphase of meiosis II. Meiotic cohesion is mediated by a conserved four-protein complex called cohesin that includes two structural maintenance of chromosomes (SMC) subunits (SMC1 and SMC3) and two non-SMC subunits. In Drosophila melanogaster, however, the meiotic cohesion apparatus has not been fully characterized and the non-SMC subunits have not been identified. We have identified a novel Drosophila gene called sisters unbound (sunn), which is required for stable sister chromatid cohesion throughout meiosis. sunn mutations disrupt centromere cohesion during prophase I and cause high frequencies of non-disjunction (NDJ) at both meiotic divisions in both sexes. SUNN co-localizes at centromeres with the cohesion proteins SMC1 and SOLO in both sexes and is necessary for the recruitment of both proteins to centromeres. Although SUNN lacks sequence homology to cohesins, bioinformatic analysis indicates that SUNN may be a structural homolog of the non-SMC cohesin subunit stromalin (SA), suggesting that SUNN may serve as a meiosis-specific cohesin subunit. In conclusion, our data show that SUNN is an essential meiosis-specific Drosophila cohesion protein.

Development and preliminary evaluation of an integrated treatment targeting parenting and depressive symptoms in mothers of children with attention-deficit/hyperactivity disorder.

OBJECTIVE: More than 50% of mothers of children with attention-deficit/hyperactivity disorder (ADHD) have a lifetime history of major depressive disorder (MDD). Maternal depressive symptoms are associated with impaired parenting and predict adverse developmental and treatment outcomes for children with ADHD. For these reasons, we developed and examined the preliminary efficacy of an integrated treatment targeting parenting and depressive symptoms for mothers of children with ADHD. This integrated intervention incorporated elements of 2 evidence-based treatments: behavioral parent training (BPT) and cognitive behavioral depression treatment. METHOD: Ninety-eight mothers with at least mild depressive symptoms were randomized to receive either standard BPT (n = 51) or the integrated parenting intervention for ADHD (IPI-A; n = 47). Participants were assessed at baseline, posttreatment, and 3- to 6-month follow-up on measures of (a) self-reported maternal depressive symptoms, (b) observed positive and negative parenting, and (c) observed and mother-reported child disruptive behavior and mother-reported child and family impairment. RESULTS: The IPI-A produced effects of small to moderate magnitude relative to BPT on maternal depressive symptoms, observed negative parenting, observed child deviance, and child impairment at posttreatment and on maternal depressive symptoms, child disruptive behavior, child impairment and family functioning at follow-up. Contrary to expectations, the BPT group demonstrated moderate to large effects relative to IPI-A on observed positive parenting at follow-up. CONCLUSIONS: This treatment development study provides encouraging preliminary support for the integrated intervention targeting parenting and depressive symptoms in mothers of children with ADHD. Future studies should examine whether this integrated intervention improves long-term developmental outcomes for children with ADHD. (PsycINFO Database Record (c) 2013 APA, all rights reserved).

When half a face is as good as a whole: effects of simple substantial occlusion on visual and audiovisual speech perception.

The visible movement of a talker's face is an influential component of speech perception. However, the ability of this influence to function when large areas of the face (~50%) are covered by simple substantial occlusions, and so are not visible to the observer, has yet to be fully determined. In Experiment 1, both visual speech identification and the influence of visual speech on identifying congruent and incongruent auditory speech were investigated using displays of a whole (unoccluded) talking face and of the same face occluded vertically so that the entire left or right hemiface was covered. Both the identification of visual speech and its influence on auditory speech perception were identical across all three face displays. Experiment 2 replicated and extended these results, showing that visual and audiovisual speech perception also functioned well with other simple substantial occlusions (horizontal and diagonal). Indeed, displays in which entire upper facial areas were occluded produced performance levels equal to those obtained with unoccluded displays. Occluding entire lower facial areas elicited some impairments in performance, but visual speech perception and visual speech influences on auditory speech perception were still apparent. Finally, implications of these findings for understanding the processes supporting visual and audiovisual speech perception are discussed.

Audiovisual cues and perceptual learning of spectrally distorted speech.

Two experiments investigate the effectiveness of audiovisual (AV) speech cues (cues derived from both seeing and hearing a talker speak) in facilitating perceptual learning of spectrally distorted speech. Speech was distorted through an eight channel noise-vocoder which shifted the spectral envelope of the speech signal to simulate the properties of a cochlear implant with a 6 mm place mismatch: Experiment I found that participants showed significantly greater improvement in perceiving noise-vocoded speech when training gave AV cues than when it gave auditory cues alone. Experiment 2 compared training with AV cues with training which gave written feedback. These two methods did not significantly differ in the pattern of training they produced. Suggestions are made about the types of circumstances in which the two training methods might be found to differ in facilitating auditory perceptual learning of speech.