Comparison of a Multi-Component Physical Function Battery to Usual Walking Speed for Assessing Lower Extremity Function and Mobility Limitation in Older Adults.

OBJECTIVES: To compare a composite measure of physical function that comprises locomotor and non-locomotor tests (i.e., the Mobility Battery Assessment (MBA)) with traditional measures of mobility (4-m usual gait speed (UGS), six-minute walk (6MW) gait speed, and short physical performance battery (SPPB) score) for assessing lower extremity function and discriminating community dwelling older adults with and without mobility limitations. DESIGN: Cross-sectional, observational study. SETTING: Laboratory-based. PARTICIPANTS: 89 community-dwelling older adults (74.9±6.7). MEASUREMENTS: Using principal component analysis we derived an MBA score for 89 community-dwelling older adults, and quantified 4-m UGS, 6MW gait speed, and SPPB score. The MBA score was based on five lab-based tests. We also quantified self-reported lower extremity function/mobility using the Neuro-QOL Lower Extremity Function-Mobility instrument. Based on this data a continuous score was derived and subjects were classified as "mobility limited" or "non-mobility limited". Correlations between the mobility measures and the Neuro-QOL score were calculated, and ROC curves were constructed to determine the AUC for the mobility measures ability to predict mobility limitations. RESULTS: The MBA had the largest AUC (0.92) for discriminating mobility limitations and exhibited the strongest correlation (0.73) with the Neuro-QOL Lower Extremity Function-Mobility Scale. The worst performing predictors were the 4-meter UGS and stair climb power both with an AUC of 0.8 for discriminating mobility limitations, and a low correlation with Neuro-QOL Lower Extremity Function Scale of 0.39 and 0.46, respectively. CONCLUSION: The MBA score moderately improves the magnitude of correlation and discrimination of mobility limitation in older adults than singular, standard tests of mobility.

Cost-effectiveness of angiotensin-converting enzyme inhibitors versus angiotensin II receptor blockers as first-line treatment in autosomal dominant polycystic kidney disease.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is a rare kidney disorder impacting ∼1:2,500 individuals among the general US population. Hypertension is a significant predictor of ADPKD progression, and a risk factor for development of cardiovascular disease (CVD), the most common cause for mortality among ADPKD patients. Angiotensin-converting enzymes inhibitors (ACE-I) are widely used as first-line treatment in ADPKD for the management of hypertension. However, their cost-effectiveness relative to other hypertensive medications, such as angiotensin II receptor blockers (ARB), has never been assessed. OBJECTIVE: To determine if ARB are more cost-effective than ACE-Is as first-line treatment in ADPKD. METHODS: A Markov-state decision model was constructed for estimation of cost and outcome benefits in hypertensive ADPKD patients. Transition probabilities were extrapolated from a retrospective cohort study comparing chronic kidney disease (CKD) stage transitions in ADPKD patients. Annual pharmaceutical costs per average daily dose per CKD stage were extracted from a US healthcare claims database. Median total healthcare costs per CKD stage or transplant were extracted from the published literature. The time horizon was set to 30 years, with 1-year duration to cycle shift. A cost-effectiveness analysis was conducted to estimate the incremental cost-effectiveness ratio (ICER) of ACE-I vs ARB per additional year of prevented transplant and/or death. A one-way probabilistic sensitivity analysis was conducted, with 10% variation in probabilities and cost. RESULTS: Total annual healthcare costs accrued after 30 years among ADPKD patients taking ACE-Is was estimated to be $3,505,028.41, compared to ARB at $3,644,327.65. Life expectancy was increased by 1.39 years among patients taking ACE-I. Approximate 10-year survival in patients taking ACE-Is was 47% compared to ARB at 34%. CONCLUSIONS: ACE-I dominated ARB and displayed greater cost-effectiveness due to lower cost and increased capacity to prolong years of life without transplant or death among hypertensive ADPKD patients. This model strengthens the value of ACE-I over ARB as first-line treatment for hypertension management in ADPKD patients.

Association of DLA-DQB1 alleles with exocrine pancreatic insufficiency in Pembroke Welsh Corgis.

Exocrine pancreatic insufficiency (EPI) is a digestive disorder resulting from the insufficient secretion of enzymes from the pancreas. In dogs, this condition is often attributed to pancreatic acinar atrophy, wherein the enzyme-producing acinar cells are believed to be destroyed through an autoimmune process. Although EPI affects many diverse breeds, to date, molecular studies have been limited to the German Shepherd dog. A recent study of major histocompatibility genes in diseased and healthy German Shepherd dogs identified both risk and protective haplotypes. Herein, we genotyped DLA-DQB1 in Pembroke Welsh Corgis to determine whether dog leukocyte antigen alleles contribute to the pathogenesis of EPI across dog breeds. We evaluated 14 affected and 43 control Pembroke Welsh Corgis, which were selected based on an age of onset similar to German Shepherd dogs. We identified one protective allele (odds ratio = 0.13, P-value = 0.044) and one risk allele (odds ratio = 3.8, P-value = 0.047). As in German Shepherd dogs, the risk allele is a duplication of DLA-DQB1 (alleles DQB1*013:03 and 017:01); however, Pembroke Welsh Corgis have acquired a single polymorphism on DQB1*017:01. Thus, the DLA-DQB1 duplication is a risk allele for EPI in at least two breeds.

Improved cognitive content endures for 2 years among unstable responders to acute-phase cognitive therapy for recurrent major depressive disorder.

BACKGROUND: The cognitive model of depression suggests that cognitive therapy (CT) improves major depressive disorder (MDD) in part by changing depressive cognitive content (e.g. dysfunctional attitudes, hopelessness). The current analyses clarified: (1) the durability of improvements in cognitive content made by acute-phase CT responders; (2) whether continuation-phase CT (C-CT) or fluoxetine (FLX) further improves cognitive content; and (3) the extent to which cognitive content mediates continuation treatments' effects on depressive symptoms and major depressive relapse/recurrence. METHOD: Out-patients with recurrent MDD who responded to acute-phase CT (n = 241) were randomized to 8 months of C-CT, FLX or pill placebo (PBO) and followed for an 24 additional months. Cognitive content was assessed approximately every 4 months using five standard patient-report measures. RESULTS: Large improvements in cognitive content made during acute-phase CT were maintained for 32 months, with 78-90% of patients scoring in normal ranges, on average. Cognitive content varied little between C-CT, FLX and PBO arms, overall. Small, transient improvements in cognitive content in C-CT or FLX compared with PBO patients did not clearly mediate the treatments' effects on depressive symptoms or on major depressive relapse/recurrence. CONCLUSIONS: Outpatients with recurrent MDD who respond to acute-phase CT show durable improvements in cognitive content. C-CT or FLX may not continue to improve patient-reported cognitive content substantively, and thus may treat recurrent MDD by other paths.

Change in psychosocial functioning and depressive symptoms during acute-phase cognitive therapy for depression.

BACKGROUND: Major depressive disorder (MDD) is highly prevalent, is recurrent, and impairs people's work, relationships and leisure. Acute-phase treatments improve psychosocial impairment associated with MDD, but how these improvements occur is unclear. In this study, we tested the hypotheses that reductions in depressive symptoms exceed, precede and predict improvements in psychosocial functioning. METHOD: Patients with recurrent MDD (n=523; 68% women, 81% Caucasian, mean age 42 years) received acute-phase cognitive therapy (CT). We measured functioning and symptom severity with the Social Adjustment Scale - Self-Report (SAS-SR), Range of Impaired Functioning Tool (RIFT), Beck Depression Inventory (BDI), Hamilton Rating Scale for Depression (HAMD) and Inventory for Depressive Symptomatology - Self-Report (IDS-SR). We tested cross-lagged correlations between functioning and symptoms measured at baseline and the beginning, middle and end of acute-phase CT. RESULTS: Pre- to post-treatment improvement in psychosocial functioning and depressive symptoms was large and intercorrelated. Depressive symptoms improved more and sooner than did psychosocial functioning. However, among four assessments across the course of treatment, improvements in functioning more strongly predicted later improvement in symptoms than vice versa. CONCLUSIONS: Improvements in psychosocial functioning and depressive symptoms correlate substantially during acute-phase CT, and improvements in functioning may play a role in subsequent symptom reduction during acute-phase CT.

Age-group differences in facets of positive and negative affect.

OBJECTIVES: The higher order structure of Positive Affect (PA) and Negative Affect (NA) is comparable in self-report affect data from younger and older adults. The current study advances this work by comparing the factor structure of facets of PA and NA in older and younger adults using exploratory and confirmatory factor analyses. METHOD: Older (N = 203; M age = 73.5 years, range 65-92) and younger (N = 349; M age = 19.1 years, range 18-30) adults completed the Positive and Negative Affect Schedule-Expanded Form (PANAS-X) (Watson, D., & Clark, L.A. (1999). Manual for the Positive and Negative Affect Schedule -- Expanded Form. Iowa City, IA: The University of Iowa), which measures General PA and NA as well as three facets of PA (Joviality, Self-Assurance, and Attentiveness) and four facets of NA (Fear, Sadness, Guilt, and Hostility). RESULTS: Item-level exploratory factor analyses of the facet scales revealed structures that were similar in older and younger adults; however, older adult solutions were more diffuse and diverged more from the PANAS-X scale structure. The facet of Sadness exhibited the largest age-group difference, relating more to guilt and anxiety in older than younger adults. CONCLUSION: Older adults may discriminate less amongst specific affect terms or may experience greater affective heterogeneity. Further, Sadness may manifest in age-specific ways. The construct variance of Sadness, and how this issue might be related to the assessment of depression in older adults, is discussed.

Contrasting prototypes and dimensions in the classification of personality pathology: evidence that dimensions, but not prototypes, are robust.

BACKGROUND: DSM-5 may mark the shift from a categorical classification of personality pathology to a dimensional system. Although dimensional and categorical conceptualizations of personality pathology are often viewed as competing, it is possible to develop categories (prototypes) from combinations of dimensions. Robust prototypes could bridge dimensions and categories within a single classification system. METHOD: To explore prototype structure and robustness, we used finite mixture modeling to identify empirically derived personality pathology prototypes within a large sample (n=8690) of individuals from four settings (clinical, college, community, and military), assessed using a dimensional measure of normal and abnormal personality traits, the Schedule for Nonadaptive and Adaptive Personality (SNAP). We then examined patterns of convergent and discriminant external validity for prototypes. Finally, we investigated the robustness of the dimensional structure of personality pathology. RESULTS: The resulting prototypes were meaningful (externally valid) but non-robust (sample dependent). By contrast, factor analysis revealed that the dimensional structures underlying specific traits were highly robust across samples. CONCLUSIONS: We interpret these results as further evidence of the fundamentally dimensional nature of an empirically based classification of personality pathology.

Prevalence of deafness in dogs heterozygous or homozygous for the merle allele.

BACKGROUND: Deafness in dogs is frequently associated with the pigment genes piebald and merle. Little is known about the prevalence of deafness in dogs carrying the merle allele. OBJECTIVE: To determine the prevalence of deafness in dogs heterozygous and homozygous for the merle allele of the mouse Silver pigment locus homolog (SILV) gene. ANIMALS: One hundred and fifty-three privately owned merle dogs of different breeds and both sexes. METHODS: Hearing was tested by brainstem auditory-evoked response and classified as bilaterally hearing, unilaterally deaf, or bilaterally deaf. DNA from buccal cells was genotyped as either heterozygous or homozygous for the merle allele. Deafness association tests among merle genotype, eye color, and sex were performed by the chi(2) test. RESULTS: Deafness prevalence in merles overall was 4.6% unilaterally deaf and 4.6% bilaterally deaf. There was a significant association between hearing status and heterozygous versus homozygous merle genotype. For single merles (Mm), 2.7% were unilaterally deaf and 0.9% were bilaterally deaf. For double merles (MM), 10% were unilaterally deaf and 15% were bilaterally deaf. There was no significant association with eye color or sex. CONCLUSIONS: Deafness prevalence in merle dogs was greater than that in some dog breeds homozygous for the piebald gene, such as the English Cocker Spaniel, but comparable to, or lower than, that in the Dalmatian and white Bull Terrier. Dogs homozygous for the merle allele were significantly more likely to be deaf than heterozygotes.

Improvement in social-interpersonal functioning after cognitive therapy for recurrent depression.

BACKGROUND: Cognitive therapy reduces depressive symptoms of major depressive disorder, but little is known about concomitant reduction in social-interpersonal dysfunction. METHOD: We evaluated social-interpersonal functioning (self-reported social adjustment, interpersonal problems and dyadic adjustment) and depressive symptoms (two self-report and two clinician scales) in adult outpatients (n=156) with recurrent major depressive disorder at several points during a 20-session course of acute phase cognitive therapy. Consenting acute phase responders (n=84) entered a 2-year follow-up phase, which included an 8-month experimental trial comparing continuation phase cognitive therapy to assessment-only control. RESULTS: Social-interpersonal functioning improved after acute phase cognitive therapy (dyadic adjustment d=0.47; interpersonal problems d=0.91; social adjustment d=1.19), but less so than depressive symptoms (d=1.55). Improvement in depressive symptoms and social-interpersonal functioning were moderately to highly correlated (r=0.39-0.72). Improvement in depressive symptoms was partly independent of social-interpersonal functioning (r=0.55-0.81), but improvement in social-interpersonal functioning independent of change in depressive symptoms was not significant (r=0.01-0.06). In acute phase responders, continuation phase therapy did not further enhance social-interpersonal functioning, but improvements in social-interpersonal functioning were maintained through the follow-up. CONCLUSIONS: Social-interpersonal functioning is improved after acute phase cognitive therapy and maintained in responders over 2 years. Improvement in social-interpersonal functioning is largely accounted for by decreases in depressive symptoms.

Digging up the canine genome--a tale to wag about.

There is incredible morphological and behavioral diversity among the hundreds of breeds of the domestic dog, CANIS FAMILIARIS. Many of these breeds have come into existence within the last few hundred years. While there are obvious phenotypic differences among breeds, there is marked interbreed genetic homogeneity. Thus, study of canine genetics and genomics is of importance to comparative genomics, evolutionary biology and study of human hereditary diseases. The most recent version of the map of the canine genome is comprised of 3,270 markers mapped to 3,021 unique positions with an average intermarker distance of approximately 1 Mb. The markers include approximately 1,600 microsatellite markers, about 1,000 gene-based markers, and almost 700 bacterial artificial chromosome-end markers. Importantly, integration of radiation hybrid and linkage maps has greatly enhanced the utility of the map. Additionally, mapping the genome has led directly to characterization of microsatellite markers ideal for whole genome linkage scans. Thus, workers are now able to exploit the canine genome for a wide variety of genetic studies. Finally, the decision to sequence the canine genome highlights the dog's evolutionary and physiologic position between the mouse and human and its importance as a model for study of mammalian genetics and human hereditary diseases.

Detection of deception on the Schedule for Nonadaptive and Adaptive Personality: validation of the validity scales.

This study used a simulation design to investigate the validity scales of the Schedule for Nonadaptive and Adaptive Personality (SNAP). Undergraduates (N=192) were randomly assigned to two positive distortion (PD) groups, two negative distortion (ND) groups, and a control group. Controls responded normally, whereas the deception groups responded according to assigned characters. Preliminary analyses indicated no significant differences within distortion valence; thus, the groups were collapsed into single PD (n=76), ND (n=79), and control groups (n=37). Mean-level analyses revealed that, consistent with previous studies, ND profiles are easier to detect than PD profiles. Cutoff scores were suggested, and the classification accuracy of these scores converged with the results of several discriminant function analyses to indicate that Rare Virtues and Deviance predict group membership at least as well as MMPI-2 validity scales. Structural analyses revealed that two moderately correlated factors-positive distortion and negative distortion-underlie scores on these validity scales.

Predicting dimensions of personality disorder from domains and facets of the Five-Factor Model.

We compared the utility of several trait models for describing personality disorder in a heterogeneous clinical sample (N = 94). Participants completed the Schedule for Nonadaptive and Adaptive Personality (SNAP; Clark, 1993b), a self-report measure that assesses traits relevant to personality disorder, and two measures of the Five-Factor Model: the Revised NEO Personality Inventory (NEO-PI-R; Costa and McCrae, 1992) and the Big Five Inventory (BFI; John, Donahue, & Kentle, 1991). Regression analyses indicated substantial overlap between the SNAP scales and the NEO-PI-R facets. In addition, use of the NEO-PI-R facets afforded substantial improvement over the Five-Factor Model domains in predicting interview-based ratings of DSM-IV personality disorder (American Psychiatric Association, 1994), such that the NEO facets and the SNAP scales demonstrated roughly equivalent levels of predictive power. Results support assessment of the full range of NEO-PI-R facets over the Five-Factor Model domains for both research and clinical use.

Toward DSM-V and the classification of psychopathology.

The Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) developed by the American Psychiatric Association (1994) is a compelling effort at a best approximation to date of a scientifically based nomenclature, but even its authors have acknowledged that its diagnoses and criterion sets are highly debatable. Well-meaning clinicians, theorists, and researchers could find some basis for fault in virtually every sentence, due in part to the absence of adequate research to guide its construction. Some points of disagreement, however, are more fundamental than others. The authors discuss issues that cut across individual diagnostic categories and that should receive particular attention in DSM-V: (a) the process by which the diagnostic manual is developed, (b) the differentiation from normal psychological functioning, (c) the differentiation among diagnostic categories, (d) cross-sectional vs. longitudinal diagnoses, and (e) the role of laboratory instruments.

Universal newborn hearing screening.

BACKGROUND: New technology has made universal newborn hearing screening possible. Our goal was to investigate the feasibility of universal newborn screening using distortion product otoacoustic emissions (DPOAE) on infants in a community hospital in a normal newborn nursery. METHODS: We used DPOAE to screen newborn infants from February 1997 to March 1999. RESULTS: Of 1002 infants, 111 failed the initial screen (11.1%). When screening was repeated, only 2 infants failed. One infant failed the second screen and a tympanogram. He was treated and he passed a third use of DPOAE. An additional infant failed the repeat screen but passed the tympanogram. That infant was referred on for auditory brain response testing. CONCLUSIONS: DPOAE testing can be accomplished easily in a normal newborn nursery with an acceptable false-positive rate when a two-stage approach is used. The cost for each test was $19.88. The cost to find the 1 infant with sensory neural hearing loss was $22,114.

Growth factor enhanced retroviral gene transfer to the adult central nervous system.

The use of viral vectors for gene delivery into mammalian cells provides a new approach in the treatment of many human diseases. The first viral vector approved for human clinical trials was murine leukemia virus (MLV), which remains the most commonly used vector in clinical trials to date. However, the application of MLV vectors is limited since MLV requires cells to be actively dividing in order for transduction and therefore gene delivery to occur. This limitation precludes the use of MLV for delivering genes to the adult CNS, where very little cell division is occurring. However, we speculated that this inherent limitation of ML V may be overcome by utilizing the known mitogenic effect of growth factors on cells of the CNS. Specifically, an in vivo application of growth factor to the adult brain, if able to induce cell division, could enhance MLV-based gene transfer to the adult brain. We now show that an exogenous application of basic fibroblast growth factor induces cell division in vivo. Under these conditions, where cells of the adult brain are stimulated to divide, MLV-based gene transfer is significantly enhanced. This novel approach precludes any vector modifications and provides a simple and effective way of delivering genes to cells of the adult brain utilizing MLV-based retroviral vectors.

Mothers' personality and its interaction with child temperament as predictors of parenting behavior.

In this longitudinal, multimethod investigation, the authors examined mothers' personality and its interaction with infants' negative emotionality as predictors of parenting behavior. When infants were 8-10 months old (N = 112), mothers completed personality self-reports, and the authors observed infants' negative emotionality in both standard procedures and naturalistic daily contexts. When infants were 13-15 months old (N = 108), the authors observed two aspects of parenting, power assertion and maternal responsiveness, in mother-child interactive contexts. Maternal personality alone and also in interaction with child emotionality predicted future parenting behaviors. The longitudinal links established between personality and parenting behaviors indicate the predictive utility of personality. Findings also highlight the bidirectionality of the early parent-child relationship.

Introduction to the special section on the concept of disorder.

Despite the absence of a consensual definition of disorder, considerable research and clinical work is based on the categorization and diagnosis of mental disorder. This article introduces a special section of the Journal of Abnormal Psychology that expands the debate between J. C. Wakefield (1999), who has proposed a "harmful dysfunction" analysis of disorder and S. O. Lilienfeld and L. Marino (1995, 1999), who offer an alternative "Roschian" or prototype analysis. This introduction summarizes the main arguments of Wakefield's target article and 8 critiques and discusses the conceptual value of the debate, especially an integration of diverse viewpoints and stimulation to further consideration of this important topic.