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Working memory (WM) develops rapidly during early childhood. In the present study, visual WM (VSM) was measured using the well-established Spin the Pots task (Hughes & Ensor, 2005), a complex non-verbal eight-location object occlusion task. A self-ordered hiding procedure was adopted to allow for an examination of children's strategy use during a VWM task. Participants (N = 640) between the ages of 2 and 4 years were tested under semi-naturalistic conditions, in the home or in a museum. Computational modeling was used to estimate an expected value for the total trials to complete Spin the Pots via a random search and child performance was compared to expected values. Based on this approach, we determined that children who found six stickers retrieved them in significantly fewer trials than the expected value, excluding chance performance and implicating VWM. Results also showed age-related and sex-related changes in VWM. Between 2 and 4 years of age, 4-year-olds performed significantly better than younger children and girls out-performed the boys. Spontaneous use of a color matching hiding strategy was associated with a higher success rate on the task. Implications of these findings for early development of VWM are discussed.

This paper uses daily hotel occupancy data to examine the effects of a wide variety of political and sporting events on the hotel room market of Charlotte, North Carolina from 2005 to 2014. Two political conventions and NASCAR auto races are associated with large increases in hotel occupancy, prices, and revenue, but many other events have no discernable effect on Charlotte's hotel market. The results also indicate that occupancy effects before or after most events are modest at best. Back‐of‐the‐envelope calculations show incremental hotel‐tax receipts fall short of the debt service incurred in constructing and maintaining the city's sports venues. (JEL H71, Z23, Z28)

Discovery of novel drug delivery systems to transport therapeutics to the brain remains a key task for successful treatment of neurodegenerative disorders. In this regard, living cells, immunocytes, and immunocyte derived extracellular vesicles (EVs) have unique features to avoid rapid clearance by the reticuloendothelial system, cross biological barriers, target disease tissues with inflammation, and deliver their cargo. Herein, we investigated biodistribution of immunocyte-based carriers, peripheral blood mononuclear cells (PBMCs) and monocyte derived EVs in adult rhesus macaques using longitudinal PET/MRI imaging. (64)Cu-labeled drug carriers were introduced via different routes of administration: intraperitoneal (IP), intravenous (IV), or intrathecal (IT) injection. Whole body PET/MRI (or PET/CT) images were acquired at 1h, 24h, and 48h post injection of (64)Cu-labeled drug carriers, and standardized uptake values (SUV(mean) and SUV(max)) in the main organs were estimated. The brain retention for both types of carriers increased based on route of administration: IP < IV < IT. Importantly, a single IT injection of PBMCs produced higher brain retention compared to IT injection of EVs. Accordingly, SUV(max) brain values at 48h post IT injection were 71.5 ± 7.9 and 25.5 ± 6.9 for PBMCs and EVs, respectively. In contrast, EVs showed superior brain accumulation compared to the cells when administered via IP and IV routes, respectively. Finally, a comprehensive chemistry panel of blood samples demonstrated no cytotoxic effects of either carrier. Together, these preliminary results suggest that living cells and EVs have a great potential to be used for drug delivery to the brain. When identifying the ideal drug carrier, the route of administration could make big differences in CNS drug delivery and should be considered as an important factor.

We use daily hotel occupancy, price, and revenue data to analyze the economic impact of the 2008 and 2012 Democratic and Republican National Conventions. We find that political conventions generate approximately 29,000 room nights of lodging, though this figure is offset by lower hotel occupancy during the week before and, to a lesser extent, after conventions. Conventions increase hotel revenue by approximately $20 million on average, a figure which suggests that host cities’ claims of economic impacts of $150 million or more may be implausible.

The nifH gene is a widely used molecular proxy for studying nitrogen fixation. Phylogenetic classification of nifH gene sequences is an essential step in diazotroph community analysis that requires a fast automated solution due to increasing size of environmental sequence libraries and increasing yield of nifH sequences from high-throughput technologies. A novel approach to rapidly classify nifH amino acid sequences into well-defined phylogenetic clusters that provides a common platform for comparative analysis across studies is presented. Phylogenetic group membership can be accurately predicted with decision tree-type statistical models that identify and utilize signature residues in the amino acid sequences. Our classification models were trained and evaluated with a publicly available and manually curated nifH gene database containing cluster annotations. Model-independent sequence sets from diverse ecosystems were used for further assessment of the models' prediction accuracy. The utility of this novel sequence binning approach was demonstrated in a comparative study where joint treatment of diazotroph assemblages from a wide range of habitats identified habitat-specific and widely-distributed diazotrophs and revealed a marine - terrestrial distinction in community composition. Our rapid and automated phylogenetic cluster assignment circumvents extensive phylogenetic analysis of nifH sequences; hence, it saves substantial time and resources in nitrogen fixation studies.

Objective The goal of this study was to explore the association of timing of and frequency of meals with markers of cardiometabolic risk in patients with bipolar disorder in out-patient maintenance treatment. Methods We used Pittsburgh Sleep Diary and actigraphy measures for individuals with bipolar I disorder. Linear and logistic regression analyses were used to determine whether dinnertime, instability of dinnertime, and/or interval between meals were associated with metabolic syndrome and its components. Results Later dinnertime was associated with greater waist circumference (β = 0.25, P = 0.02) after adjusting for age, sex, dinner-to-bed interval, and sleep duration. Longer breakfast-to-lunch intervals were also associated with greater waist circumferences (β =−.35, P = .002) after adjusting for age, sex, and sleep duration. Neither instability of dinnertime nor number of meals per day was associated with the metabolic syndrome or its components. Conclusion Weight gain is often perceived as inevitable side-effect of medications. While patients often need to be on medication to function, a more careful lifestyle assessment with attention to social rhythms and timing of activities may be critical not only for mood stability, but also to reduce cardiovascular risk.

Crocosphaera watsonii is a unicellular nitrogen (N2)-fixing cyanobacterium with ecological importance in oligotrophic oceans. In cultivated strains there are two phenotypes of C. watsonii (large and small cells) with differences that could differentially impact biogeochemical processes. Recent work has shown the phenotypes diverged through loss or addition of type-specific genes in a fraction of their genomes, whereas the rest of the genomes were maintained at 99-100% DNA identity. Previous molecular assays for C. watsonii abundances targeted the conserved regions and therefore could not differentiate between phenotypes, so their relative distributions in natural communities were unknown. To determine phenotype distributions, this study developed and applied type-specific quantitative polymerase chain reaction assays to samples from the North and South Pacific. Abundances of both Crocosphaera types declined sharply with depth between 45 and 75 m in both sites. In surface water small cells were 10-100 times more abundant than large cells in the N. Pacific, whereas in the S. Pacific the two phenotypes were nearly equal. Evidence for large cell aggregation was only found in N. Pacific samples. The differences in C. watsonii sub-populations in the North and South Pacific have direct implications for biogeochemistry and carbon export in oligotrophic gyres.

Flood damage modelling is becoming an essential component in flood risk management. However damage assessments are affected by large uncertainty, mainly related to the use of depth–damage functions. In some countries, where no site-specific curves are available, a transfer of damage models developed from other areas is required, adding extra uncertainty in the modelling process. This paper discusses the transferability in space of damage curves from literature, with a focus on ‘function uncertainty’, pointing out, especially for mesoscale ones, the lack of detailed information in terms of flood and/or building characteristics that can allow to identify the conditions of applicability of the models. New site-specific depth–damage functions are then developed for the residential sector, at meso- and microscale, based on damage data from the 2010 flood in Veneto, Italy. The application of the new curves reveals a better performance of the mesoscale model compared with the more detailed microscale one, probably due to the small extent of the inundated area.

A dataset of 87 020 nifH reads and 16 782 unique nifH protein sequences obtained over 2 years from four locations across a gradient of agricultural soil types in Argentina were analysed to provide a detailed and comprehensive picture of the diversity, abundance and responses of the N2 -fixing community in relation to differences in soil chemistry and agricultural practices. Phylogenetic analysis revealed an expected high proportion of Alphaproteobacteria, Betaproteobacteria and Deltaproteobacteria, mainly relatives to Bradyrhizobium and Methylosinus/Methylocystis, but a surprising paucity of Gammaproteobacteria. Analysis of variance and stepwise regression modelling suggested location and treatment-specific influences of soil type on diazotrophic community composition and organic carbon concentrations on nifH diversity. nifH gene abundance, determined by quantitative real-time polymerase chain reaction, was higher in agricultural soils than in non-agricultural soils, and was influenced by soil chemistry under intensive crop rotation but not under monoculture. At some locations, sustainable increased crop yields might be possible through the management of soil chemistry to improve the abundance and diversity of N2 -fixing bacteria.

Multiple imputation methods properly account for the uncertainty of missing data. One of those methods for creating multiple imputations is predictive mean matching (PMM), a general purpose method. Little is known about the performance of PMM in imputing non-normal semicontinuous data (skewed data with a point mass at a certain value and otherwise continuously distributed). We investigate the performance of PMM as well as dedicated methods for imputing semicontinuous data by performing simulation studies under univariate and multivariate missingness mechanisms. We also investigate the performance on real-life datasets. We conclude that PMM performance is at least as good as the investigated dedicated methods for imputing semicontinuous data and, in contrast to other methods, is the only method that yields plausible imputations and preserves the original data distributions. © 2014 The Authors.

I. INTRODUCTION Labor market conditions are one of the most politically salient dimensions of public policy. For example, the change in the unemployment rate is strongly related to presidential election outcomes (Fair 1978). That such a relationship exists is not particularly surprising--people out of work or anxious about being able to find or retain a job are, ceteris paribus, probably less inclined to think existing policies should be continued. Beyond the electoral fortunes of politicians, U.S. labor market conditions are especially prominent in current public discourse because unemployment reached levels not seen for three decades during the sharp recession of 2007-2009 and has receded only lethargically. The attention placed on national labor market aggregates, however, obscures the disparate labor conditions that exist across states. For example, in December 2012 (the most recent month available at the time of writing), state unemployment rates ranged from 3.2% in North Dakota to 10.2% in Nevada and Rhode Island. This variation in labor market conditions across states is the topic of our article. We posit that the variation in labor market conditions across states is related to interstate differences in economic freedom. There are a number of channels through which economic freedom might be associated with labor market outcomes. The most direct is through labor market regulations. For example, there is an extensive, although not unanimous, literature finding a negative relationship between the minimum wage and employment (Neumark and Wascher 2007). Consistent with the possibility that labor market regulations stifle labor market outcomes, Garrett and Rhine (2011) find that less labor market regulation (as well as more economic freedom in general) is associated with higher rates of employment growth among U.S. states over the period 1980-2005. Beyond a direct link between labor market regulation and employment conditions, there are other channels through which economic freedom might also be associated with favorable labor market outcomes. There is an extensive literature 'finding that economic freedom is positively related to economic growth (Dawson 2003; Doucouliagos and Ulubasoglu 2006; Gwartney, Lawson, and Holcombe 1999; Heller 2009). Increases in economic output presumably increase the demand for labor (and other inputs) unless the entire increase in output arises solely from productivity gains. Entrepreneurship is another channel through which economic freedom might foster robust labor market outcomes. Using different measures of new firm creation, Kreft and Sobel (2005), Campbell, Rogers, and Heriot (2007-2008), and Campbell and Rogers (2007) find that economic freedom is positively related to interstate differences in new firm formation. If such entrepreneurial activity leads to job creation, then there would be a positive relationship between economic freedom and favorable labor market outcomes. Another channel through which economic freedom could be associated with more favorable labor market outcomes is net immigration. Ashby (2007) finds that economic freedom is positively related to net immigration among U.S. states. If the decision to migrate is based, at least in part, on seeking out better labor market possibilities then net immigration would be related to job creation in states attracting immigrants. In addition to the theoretical reasons why interstate variation in economic freedom should be associated with cross-state differences in unemployment and other labor market outcomes, extensive international comparisons support such a conclusion. Cross-country studies by Feldmann (2006, 2007, 2010) find that economic freedom is associated with lower unemployment. Our article extends this line of research to the U.S. states. II. EMPIRICAL FRAMEWORK We use annual state-level data to examine state labor market conditions over the period 1981-2009. …

Due to photobleaching and phototoxicity induced by high-intensity excitation light the number of fluorescence images that can be obtained in live cells is always limited. This limitation becomes particularly prominent in multi-dimensional recordings when multiple Z-planes are captured at every time point. Here we present a simple technique, termed Predictive-Focus Illumination (PFI), which helps to minimize cells’ exposure to light by decreasing the number of Z-planes that need to be captured in live-cell 3-D time lapse recordings. PFI utilizes computer tracking to predict positions of objects-of-interest (OOIs) and restricts image acquisition to small dynamic Z-regions centered on each OOI. Importantly, PFI does not require hardware modifications and it can be easily implemented on standard wide-field and spinning-disk confocal microscopes.

Colposcopy is used to evaluate women with genital tract abnormalities and abnormal cervical cytology. It is an office-based procedure during which the cervix is examined under illumination and magnification before and after application of dilute acetic acid. Colposcopy may include a biopsy of lesions with characteristics of malignancy and premalignancy, such as acetowhite changes, abnormal vascular patterns, and failure to uptake iodine stain. Endocervical sampling may accompany colposcopy, particularly in the evaluation of nonpregnant women with cytology results of atypical glandular cells and adenocarcinoma in situ. Satisfactory colposcopy requires visualization of the entire squamocolumnar junction and margins of any visible lesions. While most midwives do not perform colposcopy, they will provide the pre- and postprocedure education, counseling, and evaluation of patients undergoing the procedure. This paper reviews essential information and gives special consideration to colposcopic examination in adolescent women, pregnant women, and postmenopausal women.

POPULATION: Population: Illinois Caucasian (n=117), Illinois African American (n=218), and Illinois Hispanic (n=68).

1. Hyperlipidemic effects of HIV-1-protease inhibitors (PI) are associated with increased hepatic production of triglyceride (TG)-rich lipoproteins, rather than lipoprotein clearance. PI are known to increase apolipoprotein B (apoB) secretion, apoC-III mRNA expression and decrease apoA-1 secretion. Nutritional therapy remains an important strategy to manage PI-associated hyperlipidemia. 2. This study investigated the in vitro efficacy of Asian vegetable, Momordica charantia or bitter melon (BM) to ameliorate PI-associated apoB and lipid abnormalities in HepG2 cells. 3. Our study demonstrates that bitter melon juice (BMJ) significantly reduced apoB secretion and apoC-III mRNA expression and normalized apoA-I expression in PI-treated HepG2 cells. BMJ also significantly reduced cellular TG and microsomal TG transfer protein, suggesting that lipid bioavailability and lipidation of apoB assembly may play a role in decreased apoB secretion. 4. Identifying molecular targets of BM may offer alternative dietary strategies to decrease PI-associated hyperlipidemia and improve quality of life among HIV-1-infected patients.

Dramatic changes in wintering distributions of Canada geese (Branta canadensis) have occurred over the past 50 years in eastern North America. Declines in numbers of subarctic-nesting geese wintering in southern states, and increases in numbers wintering in northern regions, have resulted in a northern shift in winter distributions. In contrast, numbers of temperate-nesting geese have increased throughout eastern North America. Management efforts to control overabundant temperate-nesting flocks have included the establishment of special early harvest seasons in September. However, the effect of early seasons on survival and harvest of subarctic-nesting populations has not been documented. Understanding the timing of migration movements and the fidelity of subarctic-nesting flocks to terminal winter refuges in the Southeast also is necessary to design early harvest seasons that target temperate-nesting flocks and protect subarctic-nesting populations. We used recoveries of marked geese to estimate...

Objective: To investigate the relationship between lifetime mood and psychotic spectrum features in patients with borderline personality disorder (BPD). Method: The study sample consisted of BPD patients with (n = 39, BPD-M) or without (n = 21, BPD-noM) lifetime mood disorders. The diagnostic assessment was conducted with the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I). The diagnosis of BPD was made clinically and then confirmed by Gunderson's diagnostic interview for borderlines. Subjects were also administered the Structured Clinical Interview for Psychotic Spectrum (SCI-PSY) and the Mood Spectrum self-report questionnaire (MOODS-SR). Results: BPD-M had significantly higher scores than BPD-noM on the ‘lifetime’ mood spectrum subdomains ‘depressive mood’ and ‘depressive cognition’. The two groups did not differ on the scores of psychotic spectrum except for higher ‘hypertrophic self-esteem’ scores in BPD-noM. In BPD-noM both the depressive and the manic-hypomanic component of mood spectrum were significantly correlated with the ‘delusion’ subdomain of the psychotic spectrum. The depressive component was correlated with ‘depersonalization/derealization’ and the manic-hypomanic component was correlated with ‘hypertrophic self-esteem’. In BPD-M, the manic-hypomanic component of mood spectrum was correlated with different subdomains of the psychotic spectrum: ‘hypertrophic self-esteem’, ‘self-reference’, ‘interpretive attitude’, ‘anger/overreactivity, ‘unusual and odd thoughts’, ‘illusions’, ‘delusions’, ‘hallucinations’ and ‘catatonia’. The depressive component of mood spectrum was ‘uncorrelated’ with the subdomains of the psychotic spectrum. Conclusions: Our data support the hypothesis that ‘lifetime’ manic-hypomanic mood dysregulations are correlated with psychotic spectrum features in borderline patients. The assessment of these spectrum features in borderline patients may be useful to inform treatment choices.

This collection of essays tackles thorny questions related to critical incidents in teaching. By using different pedagogical methods and techniques, each author provokes creative thinking about how to address specific concerns common to teaching. The authors demonstrate that the teaching and learning process must make room for – if not celebrate – the surprises that happen not only to the students, but to the teachers as well. The discussion of critical incidents helps to promote reflection on teaching practice and prompt insights into the intricate dynamics shaping the increasingly diverse learning community. Each individual essay is accompanied by reflection questions that can be used to spark conversation among colleagues and/or prompt further personal reflection on teaching and learning.

How can poetry be a resource for effective teaching of congregational life and leadership? Drawing on poetry from an array of sources, the author weaves a narrative to discuss specific strategies employed for using poetry in the classroom. Recognizing the capacity of poems to awaken latent imaginations and evoke new insights about church leadership among his students, the author provides details about particular methods that can serve as alternative approaches for learning about a subject.

This paper reports on the acceptability, reliability and validity of the Structured Clinical Interview for the Spectrum of Substance Use (SCI‐SUBS), a new instrument exploring the interactive pathway between substance abuse and psychiatric disorders. Psychiatric outpatients with (n = 21) and without (n = 32) substance abuse comorbidity according to the DSM‐IV, non‐psychiatric subjects with opioid dependence (OD, n = 14) and normal controls (n = 33) were assessed with the SCI‐SUBS. The presence or absence of psychiatric disorders was determined with the Structured Clinical Interview for DSM IV (SCID). The SCI‐SUBS was well accepted by participants. The internal consistency of the domains was satisfactory (between 0.64 and 0.93). Domain scores of OD subjects were significantly higher than those of controls and of psychiatric patients without substance abuse. The cut‐off point on the SCI‐SUBS total score at which there was optimal discrimination between the presence and the absence of a DSM‐IV diagnosis of substance abuse was 45. The pilot version of the SCI‐SUBS has satisfactory internal consistency and construct validity. Copyright © 2003 Whurr Publishers Ltd.

Pneumonia caused by Pasteurella (Mannheimia) haemolytica was induced in weaned beef heifer calves, approximately 6 months of age. Calves were treated at 20 h after challenge with therapeutic doses of danofloxacin or tilmicosin. Peripheral blood neutrophils were collected at 3, 24 and 48 h after treatment. The ex vivo effects on neutrophil function, neutrophil apoptosis, and hematological parameters were examined, as was the effect on percentage lung consolidation. Neutrophil function assays included random migration under agarose, cytochrome C reduction, iodination, Staphylococcus aureus ingestion, chemotaxis, and antibody-dependent and antibody-independent cell-mediated cytotoxicity. Apoptosis was determined using a cell death detection kit. Killing was performed at 72 h after treatment. Statistical comparisons were made among the three groups of challenged-treated animals: saline, danofloxacin, and tilmicosin. Comparisons were also made between nonchallenged nontreated animals (NCH) and challenged saline-treated animals. There were no significant differences for any of the neutrophil function assays or neutrophil apoptosis among the challenged-treated groups. This suggests that danofloxacin and tilmicosin have no clinically significant effects on neutrophil function or apoptosis. There were also no significant differences in percentage lung consolidation among the challenged-treated groups. Significant differences were found between the NCH calves and the challenged saline-treated calves in several neutrophil assays, which were attributed to effects of P. haemolytica infection.

The clinical course of inflammatory bowel disease (IBD) in dogs is characterized by spontaneous exacerbations and remissions, which makes assessment of disease burden difficult. The objectives of this study were to develop a scoring system for evaluation of canine IBD activity and to validate this scoring method by correlating it to objective laboratory and histologic indices of intestinal inflammation. Fifty-eight dogs with IBD were evaluated prospectively and compared to 9 disease-free control dogs. Clinical disease activity was quantified by a simple scoring system, the canine IBD activity index (CIBDAI), and compared to serum concentrations of C-reactive protein (CRP), haptoglobin (HAP), alpha-acid glycoprotein (AGP), and serum amyloid A (SAA), as well as histology scores derived from endoscopic biopsy specimens. Forty-six dogs were available for a reevaluation of the CIBDAI, CRP HAP, and AGP, and 34 dogs had repeat analysis of SAA performed after medical therapy. Serum concentrations of CRP were significantly (P.02) increased in dogs with CIBDAI scoresor = 5 (mild disease activity or greater) compared to controls. Among IBD dogs, the CIBDAI showed good correlation (r = 0.82, P.0001) to both histology and HAP scores, but CRP also was a strong co-correlate of disease activity. The IBD dogs showed significantly (P.0001) decreased CIBDAI and CRP values but significantly (P.0001) increased HAP concentrations after medical therapy compared to pretreatment values. We conclude that the CIBDAI is a reliable measure of inflammatory activity in canine IBD and that CRP is suitable for laboratory evaluation of the effect of therapy in these patients.

Petroleum waste sludges are treated in a continuous flow multistage slurry bioreactor system that operates at relatively short residence times with minimal loss of volatile constituents. The paper presents data for both pilot- and commercial-scale versions of the process applied to the treatment of petroleum industry wastes of the classifications primary separation sludge (F037), API separator sludge (K051), dissolved gas flotation float (K048), and slop-oil emulsion solids (K049). The process is shown to meet the EPA Universal Treatment Standards (UTS). The pilot-scale system treated petrochemical-based tarry wastes that contained volatile and semi-volatile petroleum hydrocarbons in combination with a variety of chlorinated compounds, including polychlorinated biphenyls. The commercial-scale system included centrifugation to recover recyclable oil and reduce sludge volume; slurry-phase biotreatment to degrade hazardous organic constituents and convert these to carbon dioxide, water, and less toxic intermediates; and, finally, dewatering of the residual, biotreated sludge before off-site disposal. These petroleum waste sludges are initially treated to recover oil and generate solid cake at approximately 50 wt % moisture. The solids are slurried with active cultures of facultative anaerobic bacteria, and treated in tank-based slurry bioreactors before being disposed of in a hazardous waste landfill. The process is shown to meet UTS criteria for volatile organics (i.e., benzene through xylenes); polycyclic aromatic hydrocarbons (PAHs), including naphthalene through benzo(a)pyrene; and phenolics. The most challenging treatment targets were the PAHs, which were present at concentrations significantly above the regulatory criteria. The higher molecular weight PAHs, including the four-ring compounds of pyrene, benzo(a)anthracene, and chrysene, were effectively treated at destruction efficiencies greater than 90%.

Objectives: Current guidelines provide little practical information on the clinical characteristics of bipolar I patients who are likely to benefit from the combination of a mood stabilizer and an antidepressant. Rather, guidelines simply state that an adjunctive antidepressant is recommended in cases of ‘severe’ depression. Our objective was to evaluate the clinical and demographic differences between patients who remitted on a mood stabilizer alone and patients who subsequently required an adjunctive antidepressant to achieve stabilization. Methods: We retrospectively compared the pharmacological treatment strategies of 39 patients with bipolar I disorder who were in a current depressive episode. Patients who did not respond to mood stabilizer monotherapy were prescribed an adjunctive antidepressant. We evaluated the clinical differences at baseline and week 1, 2 and 3 of treatment between patients stabilizing on a mood stabilizer alone and patients that did not remit until they subsequently received an adjunctive antidepressant. Results: Patients who required an adjunctive antidepressant had significantly higher total Hamilton Depression Rating (HRS-D) scores at week 1, 2 and 3 of treatment, but not at baseline. Patients who remitted on mood stabilizer monotherapy were more likely to be married, achieved stabilization in less time, presented with higher Young Mania Rating Scale (YMRS) scores, and experienced the previous episode of depression more recently than patients who required an antidepressant. Conclusions: Our findings suggest that rapid improvement after achieving a therapeutic dose of a mood stabilizer is clinically significant and represents a surrogate endpoint in the treatment of bipolar I depression. Larger, prospective, and controlled studies are needed to verify our results and to identify additional indicators for a mood stabilizer and antidepressant combination treatment strategy.

False Vampires (Megaderma lyra) are gleaning bats which emit brief (1 ms) and faint echolocation signals consisting of four harmonics of a shallow frequency downward modulated fundamental (27-19 kHz). The complete signal spans a frequency range from 100 to 19 kHz. In sound recordings from three experimental animals we show that Megaderma lyra shifts the dominant frequency in the echolocation signals in relation to the type of prey offered and to flight style. During roaming flights the mean peak frequency was 63.2 ± 9 kHz (third harmonic). In prey catching flights, peak frequencies were shifted into the fourth harmonic. In flights towards a dish of crawling mealworms, mean peak frequency was raised to 91.2 ± 3.3 kHz. When the bats flew towards living mice the dominant frequency was further increased to 99.8 ± 5.2 kHz, and the second and third harmonic were at least 10 dB fainter or no longer recordable. The additional frequency shift when flying towards mice was not only a consequence of the dominance of the fourth harmonic but also of an additional rise of the fundamental harmonic by nearly 2 kHz. These prey-correlated frequency shifts in echolocation calls showed little variation between the three experimental animals and were reproducible over time. They occurred at or even before take-off of the bats. This is the first report of target-correlated transient adaptations in echolocation calls of any bat species.

Data quality in the Penn World Tables varies systematically across countries that have different growth rates and at different stages of economic development, thus introducing measurement error correlated with variables of economic interest. We explore the seriousness of this problem with three examples from the literature, showing that the problem appears to be minor in growth convergence regressions but serious in estimating the effect of growth volatility on the average growth rate and in a cross-country test of the Permanent Income Hypothesis. The results suggest, at the very least, a need for performing appropriate sensitivity tests before drawing conclusions from analyses based on available cross-country data.

In this paper we examine divisive corporate restructurings in which a firm takes a subsidiary public. Using a sample of 64 spin-off and 76 carve-out firms during 1991–1997, we find firms carve-out subsidiaries with higher market demand. These subsidiaries are more frequently in related industries than spin-offs. The carve-out firms are also more likely to be cash constrained and have lower marginal tax rates, but are not likely to be considering financial reporting synergies when structuring the divestiture. These results provide evidence that factors impacting the divestiture choice related to Master Limited partnerships, as studied previously, differ when divesting a corporate subsidiary.

Objective To determine whether human chorionic gonadotropin (HCG) contributes to pregnancy-associated immunosuppression, as observed clinically by an amelioration of symptoms in human autoimmune diseases, including rheumatoid arthritis, during pregnancy. Methods Administration of HCG was initiated 2 days prior to an arthritogenic dose of streptococcal cell wall (SCW) in nonpregnant female rats, and the development and severity of SCW-induced arthritis was monitored. Inflammatory mediators, including plasma nitrite/nitrate and cytokine levels, were measured. Inducible nitric oxide synthase (iNOS) protein and cytokine messenger RNA expression in joint tissue were compared between treated and untreated arthritic animals. Results Systemic administration of HCG resulted in a dose-dependent reduction in the clinical arthritis index. Consistent with the amelioration of clinical symptoms, HCG significantly reduced the inflammatory cell infiltration, pannus formation, and bone and cartilage degradation. Mechanistically, HCG therapy was associated with suppression of the overzealous production of tumor necrosis factor α, interleukin-6 (IL-6), and IL-1β, which contribute to synovial pathology in animals with SCW-induced arthritis. Circulating nitric oxide and the amount of iNOS protein were also reduced. Furthermore, circulating transforming growth factor β levels were elevated by the HCG, all of which suggest monocytes/macrophages as a potential target. Conclusion These findings indicate that HCG exerts a protective effect in this experimental arthritis model, through modulation of inflammatory mediators.

In this study we evaluated the psychometric properties of the Structured Clinical Interview for the Anorexic-Bulimic Spectrum (SCI-ABS), including internal consistency, concurrent validity, discriminant validity and test–retest reliability. We also determine acceptability and feasibility of administration of the interview. The SCI-ABS was designed to assess typical and atypical symptoms, behaviours and temperament traits pertaining to eating disorders. The interview included 134 items grouped into nine domains, four of which were divided into subdomains. Data were collected from 372 subjects: 55 psychiatric patients with any eating disorder according to DSM-IV criteria, 118 university students, 141 subjects working out in a gym, and 65 obstetrical patients. Concurrent validity of the instrument was assessed against the Eating Attitude Test (EAT) and the Eating Disorder Inventory (EDI). Thirty-five subjects were also recruited to study the test–retest reliability and 25 women with any eating disorder were administered both the self-report and the interview formats of the SCI-ABS. Internal consistency of domains and subdomains was good. Mean domain and subdomain scores were significantly higher in patients with eating disorders, supporting the discriminant validity of the instrument. Correlation with EAT and EDI indicated good concurrent validity. Test–retest reliability was excellent and the agreement between the interview and self-report formats was satisfactory. Copyright © 2000 Whurr Publishers Ltd.

Categorical classifications of mental disorders do not take into account the subthreshold, atypical and often enduring symptoms that accompany the core manifestations of full-blown mental disorders. However, this often neglected spectrum of symptoms may be as distressing and debilitating as the full-blown disorder and may have unrecognized importance in treatment selection and response. To this end, a spectrum approach to mental disorders, such as bipolar, obsessive-compulsive, eating, and panic disorder has been developed, which has been extensively used and proven effective in clinical practice. The need for a systematic identification and assessment of a broad array of symptoms and behavioural features led, as a first step, to the conceptualization of the panic-agoraphobic spectrum model and to the development of a structured interview (SCI-PAS). This model has been constructed by identifying different psychopathological and clinical domains incorporating and extending Panic Disorder as described in DSM-IV. The rationale, clinical usefulness, and heuristic significance of the panic-agoraphobic spectrum model will be discussed. Copyright © 1999 John Wiley & Sons, Ltd.

Burning mouth syndrome (BMS) is an oral pain disorder of uncertain origin. Central or peripheral pain mechanisms may play a role in the oral burning of BMS. We tested the effect of a topical anesthetic (dyclonine HCl) on patients' intensity ratings for oral burning, taste dysgeusia and the taste of two chemical stimuli (1.0 M NaCl and 1.0 M sucrose). A total of 33 patients (9 male and 24 female, average age: 60 yr) are included in this analysis. The anesthetic reduced the perceptual intensity of both chemicals in these patients on four out of five postanesthesia trials (p < 0.01). The BMS cohort included 12 patients whose burning increased (p < 0.001), 14 patients whose burning did not change, and 7 patients whose burning decreased (p < 0.001) after anesthesia. Baseline dysgeusias (n = 13) decreased in intensity (p < 0.001) after anesthesia, suggesting BMS dysgeusia is related to the activation of peripheral taste mechanisms. The results also suggest that BMS oral burning may be a disorder of peripheral pain pathways in some patients.

n-Pentane (CAS no. 109-6-0) is a hydrocarbon solvent with an estimated production volume of 50000 metric tons in Europe. The present work was carried out to strengthen the toxicological information available for regulatory decision-making, particularly product classification, occupational exposure limits and risk assessment. The work described in this report was sponsored either by the Pentane Special Interest Group under the auspices of the Hydrocarbon Solvent Producers Association of CEFIC (European Chemical Industry Council) or by Exxon Chemical Europe. The following results were obtained: n-pentane was not acutely toxic by oral or inhalation routes, it was not a skin or eye irritant and did not induce skin sensitization. It did not exhibit cumulative toxicity at levels up to 20000 mg m(-3), which is approximately one-half of the lower explosive limit and the highest level considered safe to test. It did not induce developmental toxicity and was not mutagenic. From this and other existing information, it is concluded that n-pentane does not require classification for potential toxic hazards (as defined by Annex VI of the EU Dangerous Substance Directive, 1993), although the physical properties indicate that it would be appropriate to warn for the potential for aspiration. Further, there is no reason to reduce the current occupational exposure recommendations. Finally, although there are some safety issues relating to the flammability of n-pentane, the absence of any demonstrable toxicity at high treatment levels indicates that the risk of adverse health effects is minimal for all segments of the population.

The literature of combinatorial chemistry is reviewed with particular attention paid to considerations of absorption, distribution, metabolism and excretion in the design and evaluation of libraries containing drug-like molecules. Published libraries are evaluated in particular for the likelihood that the products would possess oral bioavailability. © 1998 John Wiley & Sons, Inc. Med. Res. Rev., 18, No. 3, 149–185, 1998.

OBJECTIVES The purpose of this study was to test the hypothesis that low circulating thyroxine concentrations characteristic of very low birth weight (VLBW) neonates (

A double-blind, placebo-controlled study was performed in order to confirm the safety, suitability, and efficacy of an alum-adsorbed Parietaria judaica-pollen allergoid, Allergovit, for allergen-specific immunotherapy. Parietaria pollen is an important cause of pollinosis, particularly in the Mediterranean zone, where it may be encountered for up to 8-9 months of the year. It is an aggressive allergen, and the doses tolerated during immunotherapy are less than those achieved with grass pollen. This factor increases the desirability of using therapeutic preparations with minimal IgE-binding activity, such as allergoids, in order to reduce the risk of side-effects and enable patients to tolerate a higher dose of allergen, thereby increasing the chances of successful specific immunotherapy. Forty patients with rhinitis and/or asthma were allocated at random to active- or placebo-treatment groups at the beginning of the study. All patients received the active preparation during the second year of the study. Immunotherapy was well tolerated by all patients and the incidence of side-effects was low. Treatment resulted in significant reductions in specific cutaneous reactivity and increases in nasal tolerance. A progressive improvement in nasal inspiratory peak flow in association with the immunotherapy indicated a reduction in nasal inflammation. These objective assessments of efficacy endorsed the results from the patients' diary cards, which indicated significant improvements in symptoms and reductions in the use of medication. The immunologic activity of the therapeutic preparation was demonstrated by the induction of a significant specific-IgG antibody response, with increases in IgG4 during the second year of treatment. We conclude that the safety and efficacy of immunotherapy with the Parietaria allergoid make it suitable for consideration in the treatment of patients with Parietaria-pollen-induced rhinitis or asthma.

Studies on the use of performance enhancing drugs (PED) in fitness centres rely predominately on conventional survey methods using direct questioning. However, research indicates that direct questioning of sensitive information is characterized by under-reporting. The aim of the present study was to contrast direct questioning of different types of PED use by Dutch fitness centre members with results obtained with the Randomized Response Technique (RRT). Questionnaires were conducted among members of fitness centres. PED were classified into the following categories: anabolic steroids, prohormones, substances to counteract side-effects, growth hormone and/or insulin, stimulants (to reduce weight), and miscellaneous substances. A total of 718 athletes from 92 fitness centres completed the questionnaire. The conventional method resulted in prevalences varying between 0% and 0.4% for the different types of PED with an overall prevalence of 0.4%. RRT resulted in prevalences varying between 0.8% and 4.8% for the different types of PED with an overall prevalence of 8.2%. The overall prevalence of the two survey methods differed significantly. The current study showed that the conventional survey method using direct questioning led to an underestimation of the prevalence. Based on the RRT results, the percentage of users of PED among members of fitness centres is approximately 8.2%. Stimulants to lose weight had the highest prevalence, even higher than anabolic steroids. The key task for future preventive health work is to not only focus on anabolic steroid use, but also include interventions focusing on the use of stimulants to lose weight.

The effects of wheat pentosans on protein digestibility and endogenous amino acid losses in precision-fed chickens was investigated using the homo-arginine marker technique. Addition of pentosans equivalent to 15 g and 35 g of wheat arabinoxylans per kg diet significantly depressed (P < 005) the overall digestibility of amino acids and increased (P < 0-05) endogenous losses of amino acids, but the inclusion of cellulose or polyethylene polymer (92 g per kg diet) had no measurable effects.