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Prevalence of Human Papillomavirus Genotypes among African Women with Normal Cervical Cytology and Neoplasia: A Systematic Review and Meta-Analysis

Wed, 07/22/2015 - 12:27pm

BACKGROUND: Several meta-analyses confirmed the five most prevalent human papillomavirus (HPV) strains in women with and without cervical neoplastic diseases are HPV16, 18, 31, 52, and 58. HPV16/18 are the predominant oncogenic genotypes, causing approximately 70% of global cervical cancer cases. The vast majority of the women studied in previous analyses were from Europe, North America, Asia, and most recently Latin America and the Caribbean. Despite the high burden of cervical cancer morbidity and mortality in Africa, a robust meta-analysis of HPV genotype prevalence and distribution in African women is lacking.

METHODS AND FINDINGS: We systematically searched 14 major databases from inception to August 2013 without language restriction, following the Meta-Analysis of Observational Studies in Epidemiology and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Seventy-one studies from 23 African countries were identified after screening 1162 citations and data abstracted and study quality appraised from 195 articles. HPV type-specific prevalence and distribution was estimated from 17,273 cases of women with normal cervical cytology; 1019 women with atypical squamous cells of undetermined significance (ASCUS); 1444 women with low-grade squamous intraepithelial lesion (LSIL); 1571 women with high-grade squamous intraepithelial lesion (HSIL); and 4,067 cases of invasive cervical carcinoma (ICC). Overall prevalence of HPV16/18 were 4.4% and 2.8% of women with normal cytology, 12.0% and 4.4% with ASCUS, 14.5% and 10.0% with LSIL, 31.2% and 13.9% with HSIL, and 49.7% and 18.0% with ICC, respectively. Study limitations include the lack of adequate data from Middle and Northern African regions, and variations in the HPV type-specific sensitivity of different genotyping protocols.

CONCLUSIONS: To our knowledge, this study is the most comprehensive assessment of the overall prevalence and distribution of HPV genotypes in African women with and without different cervical neoplasias. We have established that HPV16/18 account for 67.7% of ICC cases among African women. Based on our findings, we highly recommend the administration of existing prophylactic vaccines to younger women not infected with HPV16/18 and an increase in HPV screening efforts for high-risk genotypes to prevent cervical cancer.

REVIEW REGISTRATION: International Prospective Register of Systematic Reviews CRD42013006558.

The p53R172H Mutant Does Not Enhance Hepatocellular Carcinoma Development and Progression

Wed, 07/22/2015 - 12:27pm

Hepatocellular carcinoma is a highly deadly malignancy, accounting for approximately 800,000 deaths worldwide every year. Mutation of the p53 tumor suppressor gene is a common genetic change in HCC, present in 30% of cases. p53R175H (corresponding to p53R172H in mice) is a hotspot for mutation that demonstrates "prometastatic" gain-of-function in other cancer models. Since the frequency of p53 mutation increases with tumor grade in HCC, we hypothesized that p53R172H is a gain-of-function mutation in HCC that contributes to a decrease in tumor-free survival and an increase in metastasis. In an HCC mouse model, we found that p53R172H/flox mice do not have decreased survival, increased tumor incidence, or increased metastasis, relative to p53flox/flox littermates. Analysis of cell lines derived from both genotypes indicated that there are no differences in anchorage-independent growth and cell migration. However, shRNA-mediated knockdown of mutant p53 in p53R172H-expressing HCC cell lines resulted in decreased cell migration and anchorage-independent growth. Thus, although p53 mutant-expressing cells and tumors do not have enhanced properties relative to their p53 null counterparts, p53R172H-expressing HCC cells depend on this mutant for their transformation. p53 mutants have been previously shown to bind and inhibit the p53 family proteins p63 and p73. Interestingly, we find that the levels of p63 and p73 target genes are similar in p53 mutant and p53 null HCC cells. These data suggest that pathways regulated by these p53 family members are similarly impacted by p53R172H in mutant expressing cells, and by alternate mechanisms in p53 null cells, resulting in equivalent phenotypes. Consistent with this, we find that p53 null HCC cell lines display lower levels of the TA isoforms of p63 and p73 and higher levels of DeltaNp63. Taken together these data point to the importance of p63 and p73 in constraining HCC progression.

Genomic and clinical effects associated with a relaxation response mind-body intervention in patients with irritable bowel syndrome and inflammatory bowel disease

Wed, 07/22/2015 - 12:27pm

INTRODUCTION: Irritable Bowel Syndrome (IBS) and Inflammatory Bowel Disease (IBD) can profoundly affect quality of life and are influenced by stress and resiliency. The impact of mind-body interventions (MBIs) on IBS and IBD patients has not previously been examined.

METHODS: Nineteen IBS and 29 IBD patients were enrolled in a 9-week relaxation response based mind-body group intervention (RR-MBI), focusing on elicitation of the RR and cognitive skill building. Symptom questionnaires and inflammatory markers were assessed pre- and post-intervention, and at short-term follow-up. Peripheral blood transcriptome analysis was performed to identify genomic correlates of the RR-MBI.

RESULTS: Pain Catastrophizing Scale scores improved significantly post-intervention for IBD and at short-term follow-up for IBS and IBD. Trait Anxiety scores, IBS Quality of Life, IBS Symptom Severity Index, and IBD Questionnaire scores improved significantly post-intervention and at short-term follow-up for IBS and IBD, respectively. RR-MBI altered expression of more genes in IBD (1059 genes) than in IBS (119 genes). In IBD, reduced expression of RR-MBI response genes was most significantly linked to inflammatory response, cell growth, proliferation, and oxidative stress-related pathways. In IBS, cell cycle regulation and DNA damage related gene sets were significantly upregulated after RR-MBI. Interactive network analysis of RR-affected pathways identified TNF, AKT and NF-kappaB as top focus molecules in IBS, while in IBD kinases (e.g. MAPK, P38 MAPK), inflammation (e.g. VEGF-C, NF-kappaB) and cell cycle and proliferation (e.g. UBC, APP) related genes emerged as top focus molecules.

CONCLUSIONS: In this uncontrolled pilot study, participation in an RR-MBI was associated with improvements in disease-specific measures, trait anxiety, and pain catastrophizing in IBS and IBD patients. Moreover, observed gene expression changes suggest that NF-kappaB is a target focus molecule in both IBS and IBD-and that its regulation may contribute to counteracting the harmful effects of stress in both diseases. Larger, controlled studies are needed to confirm this preliminary finding.

TRIAL REGISTRATION: ClinicalTrials.Gov NCT02136745.

OXPHOS-Mediated Induction of NAD+ Promotes Complete Oxidation of Fatty Acids and Interdicts Non-Alcoholic Fatty Liver Disease

Wed, 07/22/2015 - 12:27pm

OXPHOS is believed to play an important role in non-alcoholic fatty liver disease (NAFLD), however, precise mechanisms whereby OXPHOS influences lipid homeostasis are incompletely understood. We previously reported that ectopic expression of LRPPRC, a protein that increases cristae density and OXPHOS, promoted fatty acid oxidation in cultured primary hepatocytes. To determine the biological significance of that observation and define underlying mechanisms, we have ectopically expressed LRPPRC in mouse liver in the setting of NAFLD. Interestingly, ectopic expression of LRPPRC in mouse liver completely interdicted NAFLD, including inflammation. Consistent with mitigation of NAFLD, two markers of hepatic insulin resistance-ROS and PKCepsilon activity-were both modestly reduced. As reported by others, improvement of NAFLD was associated with improved whole-body insulin sensitivity. Regarding hepatic lipid homeostasis, the ratio of NAD+ to NADH was dramatically increased in mouse liver replete with LRPPRC. Pharmacological activators and inhibitors of the cellular respiration respectively increased and decreased the [NAD+]/[NADH] ratio, indicating respiration-mediated control of the [NAD+]/[NADH] ratio. Supporting a prominent role for NAD+, increasing the concentration of NAD+ stimulated complete oxidation of fatty acids. Importantly, NAD+ rescued impaired fatty acid oxidation in hepatocytes deficient for either OXPHOS or SIRT3. These data are consistent with a model whereby augmented hepatic OXPHOS increases NAD+, which in turn promotes complete oxidation of fatty acids and protects against NAFLD.

Chitin recognition via chitotriosidase promotes pathologic type-2 helper T cell responses to cryptococcal infection

Wed, 07/22/2015 - 12:27pm

Pulmonary mycoses are often associated with type-2 helper T (Th2) cell responses. However, mechanisms of Th2 cell accumulation are multifactorial and incompletely known. To investigate Th2 cell responses to pulmonary fungal infection, we developed a peptide-MHCII tetramer to track antigen-specific CD4+ T cells produced in response to infection with the fungal pathogen Cryptococcus neoformans. We noted massive accruement of pathologic cryptococcal antigen-specific Th2 cells in the lungs following infection that was coordinated by lung-resident CD11b+ IRF4-dependent conventional dendritic cells. Other researchers have demonstrated that this dendritic cell subset is also capable of priming protective Th17 cell responses to another pulmonary fungal infection, Aspergillus fumigatus. Thus, higher order detection of specific features of fungal infection by these dendritic cells must direct Th2 cell lineage commitment. Since chitin-containing parasites commonly elicit Th2 responses, we hypothesized that recognition of fungal chitin is an important determinant of Th2 cell-mediated mycosis. Using C. neoformans mutants or purified chitin, we found that chitin abundance impacted Th2 cell accumulation and disease. Importantly, we determined Th2 cell induction depended on cleavage of chitin via the mammalian chitinase, chitotriosidase, an enzyme that was also prevalent in humans experiencing overt cryptococcosis. The data presented herein offers a new perspective on fungal disease susceptibility, whereby chitin recognition via chitotriosidase leads to the initiation of harmful Th2 cell differentiation by CD11b+ conventional dendritic cells in response to pulmonary fungal infection.

Osteopetrorickets due to Snx10 deficiency in mice results from both failed osteoclast activity and loss of gastric acid-dependent calcium absorption

Wed, 07/22/2015 - 12:27pm

Mutations in sorting nexin 10 (Snx10) have recently been found to account for roughly 4% of all human malignant osteopetrosis, some of them fatal. To study the disease pathogenesis, we investigated the expression of Snx10 and created mouse models in which Snx10 was knocked down globally or knocked out in osteoclasts. Endocytosis is severely defective in Snx10-deficient osteoclasts, as is extracellular acidification, ruffled border formation, and bone resorption. We also discovered that Snx10 is highly expressed in stomach epithelium, with mutations leading to high stomach pH and low calcium solubilization. Global Snx10-deficiency in mice results in a combined phenotype: osteopetrosis (due to osteoclast defect) and rickets (due to high stomach pH and low calcium availability, resulting in impaired bone mineralization). Osteopetrorickets, the paradoxical association of insufficient mineralization in the context of a positive total body calcium balance, is thought to occur due to the inability of the osteoclasts to maintain normal calcium-phosphorus homeostasis. However, osteoclast-specific Snx10 knockout had no effect on calcium balance, and therefore led to severe osteopetrosis without rickets. Moreover, supplementation with calcium gluconate rescued mice from the rachitic phenotype and dramatically extended life span in global Snx10-deficient mice, suggesting that this may be a life-saving component of the clinical approach to Snx10-dependent human osteopetrosis that has previously gone unrecognized. We conclude that tissue-specific effects of Snx10 mutation need to be considered in clinical approaches to this disease entity. Reliance solely on hematopoietic stem cell transplantation can leave hypocalcemia uncorrected with sometimes fatal consequences. These studies established an essential role for Snx10 in bone homeostasis and underscore the importance of gastric acidification in calcium uptake.

Dissecting cis and trans Determinants of Nucleosome Positioning: A Dissertation

Tue, 07/21/2015 - 12:55pm

Eukaryotic DNA is packaged in chromatin, whose repeating subunit, the nucleosome, consists of an octamer of histone proteins wrapped by about 147bp of DNA. This packaging affects the accessibility of DNA and hence any process that occurs on DNA, such as replication, repair, and transcription. An early observation from genome-wide nucleosome mapping in yeast was that genes had a surprisingly characteristic structure, which has motivated studies to understand what determines this architecture. Both sequence and trans acting factors are known to influence chromatin packaging, but the relative contributions of cis and trans determinants of nucleosome positioning is debated. Here we present data using genetic approaches to examine the contributions of cis and trans acting factors on nucleosome positioning in budding yeast.

We developed the use of yeast artificial chromosomes to exploit quantitative differences in the chromatin structures of different yeast species. This allows us to place approximately 150kb of sequence from any species into the S.cerevisiae cellular environment and compare the nucleosome positions on this same sequence in different environments to discover what features are variant and hence regulated by trans acting factors. This method allowed us to conclusively show that the great preponderance of nucleosomes are positioned by trans acting factors. We observe the maintenance of nucleosome depletion over some promoter sequences, but partial fill-in of NDRs in some of the YAC v promoters indicates that even this feature is regulated to varying extents by trans acting factors.

We are able to extend our use of evolutionary divergence in order to search for specific trans regulators whose effects vary between the species. We find that a subset of transcription factors can compete with histones to help generate some NDRs, with clear effects documented in a cbf1 deletion mutant. In addition, we find that Chd1p acts as a potential “molecular ruler” involved in defining the nucleosome repeat length differences between S.cerevisiae and K.lactis. The mechanism of this measurement is unclear as the alteration in activity is partially attributable to the N-terminal portion of the protein, for which there is no structural data. Our observations of a specialized chromatin structure at de novo transcriptional units along with results from nucleosome mapping in the absence of active transcription indicate that transcription plays a role in engineering genic nucleosome architecture. This work strongly supports the role of trans acting factors in setting up a dynamic, regulated chromatin structure that allows for robustness and fine-tuning of gene expression.

Chromatin Regulators and DNA Repair: A Dissertation

Tue, 07/21/2015 - 12:55pm

DNA double-strand break (DSB) repair is essential for maintenance of genome stability. However, the compaction of the eukaryotic genome into chromatin creates an inherent barrier to any DNA-mediated event, such as during DNA repair. This demands that there be mechanisms to modify the chromatin structure and thus access DNA. Recent work has implicated a host of chromatin regulators in the DNA damage response and several functional roles have been defined. Yet the mechanisms that control their recruitment to DNA lesions, and their relationship with concurrent histone modifications, remain unclear. We find that efficient DSB recruitment of many yeast chromatin regulators is cell-cycle dependent. Furthering this, we find recruitment of the INO80, SWR-C, NuA4, SWI/SNF, and RSC enzymes is inhibited by the non-homologous end joining machinery, and that their recruitment is controlled by early steps of homologous recombination. Strikingly, we find no significant role for H2A.X phosphorylation (γH2AX) in the recruitment of chromatin regulators, but rather that their recruitment coincides with reduced levels of γH2AX. We go on to determine the chromatin remodeling enzyme Fun30 functions in histone dynamics surround a DSB, but does not significantly affect γH2AX dynamics. Additionally, we describe a conserved functional interaction among the chromatin remodeling enzyme, SWI/SNF, the NuA4 and Gcn5 histone acetyltransferases, and phosphorylation of histone H2A.X. Specifically, we find that the NuA4 and Gcn5 enzymes are both required for the robust recruitment of SWI/SNF to a DSB, which in turn promotes the phosphorylation of H2A.X.

Language Proficiency, Citizenship, and Food Insecurity among Predominantly Immigrant Caribbean Latinos in Massachusetts: A Masters Thesis

Tue, 07/21/2015 - 12:55pm

BACKGROUND: Latinos report higher food insecurity than the national average, and food insecurity has been associated with adverse health outcomes wherein Latinos experience disparities. This study quantified the independent effects of language-speaking proficiency and citizenship on increased food insecurity among a predominantly immigrant Caribbean Latino sample in Lawrence, Massachusetts.

METHODS: The analytic sample comprised 574 participants aged 21-83 who visited a community health center in 2011-2013. Food insecurity was assessed via the 6-item US Household Food Security Survey. Multivariable logistic modeling (adjusted for self-reported age group, gender, education, and marital status) examined the independent associations between language proficiency and citizenship on increased food insecurity.

RESULTS: One-third of participants were classified as food insecure. Most respondents were citizens (59.5%), foreign-born (92.4%; 70.3% from the Dominican Republic), and spoke monolingual Spanish (72.8%). Monolingual Spanish-speakers had marginally increased odds of food insecurity (odds ratio (OR) = 1.50, 95% confidence interval (CI): 1.00 to 2.26), compared to bilingual participants; however after adjustment this relationship was attenuated (OR = 1.25, 95% CI: 0.79 to 2.00). Non-citizenship was not associated with increased odds of food insecurity (OR=1.18, 95% CI: 0.82 to 1.68).

CONCLUSION: Food insecurity in this predominantly immigrant Caribbean Latino sample was higher than the national average for Latinos. Future research on food insecurity among different Latino ethnicities is needed in order to inform targeted interventions that promote food security.

Depression and anxiety among high-risk obstetric inpatients

Tue, 07/21/2015 - 9:14am

OBJECTIVE: To assess the following among women hospitalized antenatally due to high-risk pregnancies: (1) rates of depression symptoms and anxiety symptoms, (2) changes in depression symptoms and anxiety symptoms and, (3) rates of mental health treatment.

METHODS: Sixty-two participants hospitalized for high-risk obstetrical complications completed the Edinburgh Postnatal Depression Scale (EPDS), Generalized Anxiety Disorder 7-item scale (GAD-7) and Short-Form 12 weekly until delivery or discharge, and once postpartum.

RESULTS: Average length of total hospital stay was 8.3 +/- 7.6 days for women who completed an initial admission survey (n = 62) and 16.3 +/- 8.9 (n = 34), 25.4 +/- 10.2 (n = 17) and 35 +/- 10.9 days (n = 9) for those who completed 2, 3 and 4 surveys, respectively. EPDS was > /= 10 in 27% (n=17) and GAD-7 was > /= 10 in 13% (n = 8) of participants at initial survey. Mean anxiety (4.2 +/- 6.5 vs. 5.2 +/- 5.1, p = .011) and depression (4.4 +/- 5.6 vs. 6.9 +/- 4.8, p = .011) scores were lower postpartum compared to initial survey. Past mental health diagnosis predicted depression symptoms [odds ratio (OR) = 4.54; 95% confidence interval (CI) 1.91-7.17] and anxiety symptoms (OR = 5.95; 95% CI 3.04-8.86) at initial survey; however, 21% (n = 10) with no diagnostic history had EPDS > /= 10. Five percent (n = 3) received mental health treatment during pregnancy.

CONCLUSION: Hospitalized high-risk obstetrical patients may commonly experience depression symptoms and/or anxiety symptoms and not receive treatment. A history of mental health treatment or diagnosis was associated with depression symptoms or anxiety symptoms in pregnancy. Of women with an EPDS > /= 10, > 50% did not report a past mental health diagnosis.

Mental health care use in relation to depressive symptoms among pregnant women in the USA

Tue, 07/21/2015 - 9:14am

We examined mental health care use in relation to depressive symptoms (Patient Health Questionnaire (PHQ-9) >/=10) among a nationally representative sample of pregnant women using data from the National Health and Nutrition Examination Survey 2005-2012. Logistic regression models estimated crude and adjusted odds ratios for mental health care use in the past year in relation to depressive symptoms. While 8.2 % (95 % CI 4.6-11.8) of pregnant women were depressed, only 12 % (95 % CI 1.8-22.1) of these women reported mental health care use in the past year.

Vitamin D3 Supplemental Treatment for Mania in Youth with Bipolar Spectrum Disorders

Sun, 07/19/2015 - 10:29pm

OBJECTIVE: We aimed to determine the effect of an open-label 8 week Vitamin D3 supplementation on manic symptoms, anterior cingulate cortex (ACC) glutamate, and γ-aminobutyric acid (GABA) in youth exhibiting symptoms of mania; that is, patients with bipolar spectrum disorders (BSD). We hypothesized that an 8 week Vitamin D3 supplementation would improve symptoms of mania, decrease ACC glutamate, and increase ACC GABA in BSD patients. Single time point metabolite levels were also evaluated in typically developing children (TD).

METHODS: The BSD group included patients not only diagnosed with BD but also those exhibiting bipolar symptomology, including BD not otherwise specified (BD-NOS) and subthreshold mood ratings (Young Mania Rating Scale [YMRS] ≥8 and Clinical Global Impressions - Severity [CGI-S] ≥3). Inclusion criteria were: male or female participants, 6-17 years old. Sixteen youth with BSD exhibiting manic symptoms and 19 TD were included. BSD patients were asked to a take daily dose (2000 IU) of Vitamin D3 (for 8 weeks) as a supplement. Neuroimaging data were acquired in both groups at baseline, and also for the BSD group at the end of 8 week Vitamin D3 supplementation.

RESULTS: Baseline ACC GABA/creatine (Cr) was lower in BSD than in TD (F[1,31]=8.91, p=0.007). Following an 8 week Vitamin D3 supplementation, in BSD patients, there was a significant decrease in YMRS scores (t=-3.66, p=0.002, df=15) and Children's Depression Rating Scale (CDRS) scores (t=-2.93, p=0.01, df=15); and a significant increase in ACC GABA (t=3.18, p=0.007, df=14).

CONCLUSIONS: Following an 8 week open label trial with Vitamin D3, BSD patients exhibited improvement in their mood symptoms in conjunction with their brain neurochemistry.

Diving into Data: Planning a Research Data Management Event

Thu, 07/16/2015 - 2:46pm

The George T. Harrell Health Sciences Library at Penn State Hershey initiated its participation in institutional research data management activities by coordinating and hosting a well-attended data management symposium. To maximize relevance to clinical and basic sciences researchers, a planning committee of faculty and administrators assisted in defining important topics for the event. This article describes the symposium development and outcomes. The goal is to share this information with librarians who are seeking ways to become more involved with data management in their institutions.

Assessment of Data Management Services at New England Region Resource Libraries

Thu, 07/16/2015 - 2:20pm

Objective: To understand how New England medical libraries are addressing scientific research data management and providing services to their communities.

Setting: The National Network of Libraries of Medicine, New England Region (NN/LM NER) contains 17 Resource Libraries. The University of Massachusetts Medical School serves as the New England Regional Medical Library (RML). Sixteen of the NER Resource Libraries completed this survey.

Methods: A 40-question online survey assessed libraries’ services and programs for providing research data management education and support. Libraries shared their current plans and institutional challenges associated with developing data services.

Results: This study shows few NER Resource Libraries currently integrate scientific research data management into their services and programs, and highlights the region’s use of resources provided by the NN/LM NER RML at the University of Massachusetts Medical School.

Conclusions: Understanding the types of data services being delivered at NER libraries helps to inform the NN/LM NER about the eScience learning needs of New England medical librarians and helps in the planning of professional development programs that foster effective biomedical research data services.

Food Selectivity, Mealtime Behavior Problems, Spousal Stress, and Family Food Choices in Children with and without Autism Spectrum Disorder

Wed, 07/15/2015 - 2:15pm

Mealtime behavior problems and family stress occur frequently among families of children with autism spectrum disorder (ASD). However, it is unknown whether food selectivity is an associated factor. The associations of high food selectivity with mealtime behavior problems, spousal stress, and influence on family members were assessed among 53 children with ASD and 58 typically developing (TD) children ages 3-11 years. Compared to TD children, children with ASD were more likely to have high food selectivity, and their parents reported more mealtime behavior problems, higher spousal stress, and influence on what other family members ate. High food selectivity was associated with mealtime behavior problems in both groups. Interventions to reduce food selectivity may lead to decreases in mealtime behavior problems.

Including Youth with Intellectual Disabilities in Health Promotion Research: Development and Reliability of a Structured Interview to Assess the Correlates of Physical Activity among Youth

Wed, 07/15/2015 - 2:15pm

BACKGROUND: The input of youth with intellectual disabilities in health promotion and health disparities research is essential for understanding their needs and preferences. Regular physical activity (PA) is vital for health and well-being, but levels are low in youth generally, including those with intellectual disabilities. Understanding the perceptions of and barriers to PA as reported by youth with intellectual disabilities themselves is important for designing effective interventions.

MATERIALS AND METHODS: We developed a structured interview that queried youth with intellectual disabilities and typically developing youth (ages 13-21 years) about their enjoyment, preferences and perceived barriers to PA. We describe the development of this interview and present its test-retest reliability on 15 youth with intellectual disabilities and 20 typically developing youth.

RESULTS: Twenty-three of 33 questions were reliable in both groups. The results suggest that youth with intellectual disabilities can reliably report activities that they do or do not enjoy, as well as their beliefs and perceived benefits of PA.

CONCLUSIONS: Self-reported information on the experiences, preferences, beliefs and perceptions about among youth with intellectual disabilities is key for research efforts in health promotion and health disparities.

Functional analysis of problem behavior: A systematic approach for identifying idiosyncratic variables

Wed, 07/15/2015 - 2:15pm

When inconclusive functional analysis (FA) outcomes occur, a number of modifications have been made to enhance the putative establishing operation or consequence associated with behavioral maintenance. However, a systematic method for identifying relevant events to test during modified FAs has not been evaluated. The purpose of this study was to develop and evaluate a technology for systematically identifying events to test in a modified FA after an initial FA led to inconclusive outcomes. Six individuals, whose initial FA showed little or no responding or high levels only in the control condition, participated. An indirect assessment (IA) questionnaire developed for identifying idiosyncratic variables was administered, and a descriptive analysis (DA) was conducted. Results from the IA only or a combination of the IA and DA were used to inform modified FA test and control conditions. Conclusive FA outcomes were obtained with 5 of the 6 participants during the modified FA phase.

Stimulus Fading and Response Elaboration in Differential Reinforcement for Alternative Behavior

Wed, 07/15/2015 - 2:15pm

A hallmark of applied behavior analysis is the development of function-based interventions for problem behavior. A widely recommended function-based intervention is differential reinforcement of alternative behavior (DRA), in which reinforcement is contingent upon socially acceptable alternatives to problem behavior (e.g., teaching communication skills). Typically, DRA is introduced under rich schedules of reinforcement. Although effective for initiating behavior change, rich schedules are often impractical in the natural setting. In this study, we evaluated the extent to which a stimulus fading program could be employed to elaborate alternative behavior (mands) in two individuals diagnosed with an Autism Spectrum Disorder. For both participants, problem behavior was reduced substantially upon implementation of the DRA procedure. Further, problem behavior rates remained low and mand rates decreased to more practical levels as the DRA behavioral requirements increased during the fading program. The fading approach demonstrated in this paper may be a useful component of intervention packages for clinicians.

Stimulus control in a go/no-go procedure with compound stimuli with pigeons

Wed, 07/15/2015 - 2:15pm

Our previous study using a go/no-go procedure with compound stimuli taught pigeons to peck at two-component compounds A1B1, A2B2, B1C1, B2C2 and refrain from pecking at A1B2, A2B1, B1C2, B2C1. Subjects showed training-consistent responding in tests presenting compounds rotated 180 degrees (BA and CB relations) but not recombined (AC and CA relations). It is unclear whether the responses to BA and CB stimuli were controlled by the relation between the components (conditional discrimination) or by the compounds functioning as a unitary stimulus (simple discrimination). The present study assessed whether the four pigeons from our previous study would show maintained discrimination when the positions of the components of each compound were changed relative to the training stimuli. Training components were rotated 90 degrees to the right and left (Tests 1 and 2, respectively), presented with a 1cm separation (Test 3), and presented with a 1cm separation and rotated 180 degrees (Test 4). Subject P11 maintained discriminations in all tests. Maintained discriminations were only observed in Tests 1 and 2 for P21, 1-3 for P10, and 1, 2, and 4 for P9. Results indicate that pigeons may not maintain discrimination when stimulus elements are presented further apart and/or rotated 180 degrees relative to training.

Impact of COPD on the mortality and treatment of patients hospitalized with acute decompensated heart failure: the Worcester Heart Failure Study

Tue, 07/14/2015 - 4:04pm

BACKGROUND: COPD is a common comorbidity in patients with heart failure, yet little is known about the impact of this condition in patients with acute decompensated heart failure (ADHF), especially from a more generalizable, community-based perspective. The primary objective of this study was to describe the in-hospital and postdischarge mortality and treatment of patients hospitalized with ADHF according to COPD status.

METHODS: The study population consisted of patients hospitalized with ADHF at all 11 medical centers in central Massachusetts during four study years: 1995, 2000, 2002, and 2004. Patients were followed through 2010 for determination of their vital status.

RESULTS: Of the 9,748 patients hospitalized with ADHF during the years under study, 35.9% had a history of COPD. The average age of this population was 76.1 years, 43.9% were men, and 93.3% were white. At the time of hospital discharge, patients with COPD were less likely to have received evidence-based heart failure medications, including beta-blockers and angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, than patients without COPD. Multivariable, adjusted in-hospital death rates were similar for patients with and without COPD. However, among patients who survived to hospital discharge, patients with COPD had a significantly higher risk of dying at 1 year (adjusted relative risk [RR], 1.10; 95% CI, 1.06-1.14) and 5 years (adjusted RR, 1.40; 95% CI, 1.28-1.52) after hospital discharge than patients who were not previously diagnosed with COPD.

CONCLUSIONS: COPD is a common comorbidity in patients hospitalized with ADHF and is associated with a worse long-term prognosis. Further research is required to understand the complex interactions of these diseases and ensure that patients with ADHF and COPD receive optimal treatment modalities.