The specification of a construct of social anxiety, the subsequent development of two scales, and validational studies are reported. The two scales are the Fear of Negative Evaluation scale (FNE) and the Social Avoidance and Distress scale (SAD). The scales had very high indexes of homogeneity and possessed sufficient reliability. Three experiments and other correlational data are presented. People high in SAD tended to avoid social interactions, preferred to work alone, reported that they talked less, were more worried and less confident about social relationships, but were more likely to appear for appointments. Those high in FNE tended to become nervous in evaluative situations, and worked hard either to avoid disapproval or gain approval. Certain convergent and discriminant relationships had been part of the construct of social anxiety, and the correlational data supported these differentiations.

Background: Glucagon-like peptide 1 agonists differ in chemical structure, duration of action and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. Methods: We randomly assigned patients with type 2 diabetes and cardiovascular disease to the addition of once-weekly subcutaneous injection of albiglutide (30 mg to 50 mg) or matching placebo to standard care. We hypothesized that albiglutide would be noninferior to placebo for the primary outcome of first occurrence of cardiovascular death, myocardial infarction, or stroke. If noninferiority was confirmed by an upper limit of the 95% confidence interval for the hazard ratio of less than 1.30, closed-testing for superiority was prespecified. Findings: Overall, 9463 participants were followed for a median of 1.6 years. The primary composite outcome occurred in 338 of 4731 patients (7.1%; 4.6 events per 100 person-years) in the albiglutide group and in 428 of 4732 patients (9.0%; 5.9 events per 100 person-years) in the placebo group (hazard ratio, 0.78; 95% confidence interval [CI ], 0.68 to 0.90), indicating that albiglutide, was superior to placebo (P<0.0001 for noninferiority, P=0.0006 for superiority). The incidence of acute pancreatitis (albiglutide 10 patients and placebo 7 patients), pancreatic cancer (6 and 5), medullary thyroid carcinoma (0 and 0), and other serious adverse events did not differ significantly between the two groups. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. (Funded by GlaxoSmithKline; Harmony Outcomes ClinicalTrials.gov number, NCT02465515.) noninferiority; P = 0.06 for superiority). There seems to be variation in the results of existing trials with GLP-1 receptor agonists, which if correct, might reflect drug structure or duration of action, patients studied, duration of follow-up or other factors.

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We describe a new self-report instrument, the Inventory of Depression and Anxiety Symptoms (IDAS), which was designed to assess specific symptom dimensions related to major depression and related anxiety disorders. We created the IDAS by conducting principal factor analyses in three large samples (college students, psychiatric patients, community adults); we also examined the robustness of its psychometric properties in five additional samples (high school students, college students, young adults, postpartum women, psychiatric patients) that were not involved in the scale development process. The IDAS contains 10 specific symptom scales: Suicidality, Lassitude, Insomnia, Appetite Loss, Appetite Gain, Ill Temper, Well-Being, Panic, Social Anxiety, and Traumatic Intrusions. It also includes two broader scales: General Depression (which contains items overlapping with several other IDAS scales) and Dysphoria (which does not). The scales (a) are internally consistent, (b) capture the target dimensions well, and (c) define a single underlying factor. They show strong short-term stability, and display excellent convergent validity and good discriminant validity in relation to other self-report and interview-based measures of depression and anxiety.

The phenazine pigments pyocyanin and 1-hydroxyphenazine were resolved by high-pressure liquid chromatography from the sputum sol phase from 9 of 13 patients with cystic fibrosis or bronchiectasis colonized by Pseudomonas aeruginosa. The concentrations measured were each sufficient to inhibit ciliary beating in vitro and contributed a significant proportion of sol phase toxicity for respiratory epithelium.Pseudomonas aeruginosa colonizes the lungs of patients with cystic fibrosis (CF) and other forms of severe bronchiectasis. We have recently demonstrated that pyocyanin and 1-hydroxyphenazine, phenazine redox pigments generated by P. aeruginosa, disrupt human ciliary beating in vitro (15). Pyocyanin also inhibits epidermal cell growth (4) and lymphocyte proliferation (7), has antibiotic properties against other microorganisms (9), and influences the acquisition of iron by pseudomonads (3). 1-Hydroxyphenazine inhibits mammalian cell respiration (1).Sputum was collected from 12 patients who were colonized by P. aeruginosa; 8 had bronchiectasis and 4 had CF. Pulmonary secretions, from which P. aeruginosa was cultured, were aspirated directly from the large airways of a CF lung removed at transplantation. Sputum was also collected from five patients who had bronchiectasis and who had never been colonized by P. aeruginosa. Each sputum sample was centrifuged (50,000 x g for 90 min at 4°C), the watery sol phase was retained, and the gel phase was discarded. Each sol phase sample (1 ml) was loaded in 5% acetic acid on a C18 Sep Pak column (Waters Associates, Inc.) and eluted with 40% propan-2-ol in aqueous acetic acid. The eluant was fractionated by high-pressure liquid chromatography (HPLC) at 2 ml/min on a p,Bondapak Cl8 column (30 by 0.8 cm) with a 20-min linear gradient from 0 to 40% propan-2-ol in 5% aqueous acetic acid, with monitoring at 280 and 254 nm in UV light (14). Pyocyanin and 1-hydroxyphenazine were identified by their HPLC-UV profiles (14). All pyocyanin concentrations in each sol sample and 1hydroxyphenazine concentrations in sol samples 1, 2, and 7 were calculated after extraction and full UV analysis; 1hydroxyphenazine concentrations in other sol samples were calculated from the HPLC-UV peak height.Human nasal ciliated epithelium was obtained from the inferior turbinate of normal volunteers (8). The sol phase pH was variable (5.5 to 9.5) and was adjusted to 7.4 to ensure that changes in ciliary beat frequency (CBF) were not pH related. A sol phase sample was added to ciliated epithelium, a sealed microscope cover slip slide preparation was constructed, and controls were suspended in phosphate-buffered saline (PBS). Ten epithelium strips were identified, and their positions were marked. CBF was measured in each * Corresponding author. epithelial strip by a photometric technique at 1-h intervals for 4 h (8, 15), and a mean was calculated. Any change in beating pattern, ciliary stasis (previously beating cilia subsequently observed to be static), or change in epithelium structure was noted. Results are sho...

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Pseudomonas aeruginosa culture filtrates varied in their ability to slow human ciliary beat frequency (7-71%). This activity did not correlate with known virulence factors. However, a close correlation (r = 0.97) existed between ciliary slowing and pigment content. In a prolonged culture, the increase in activity correlated (r = 0.94) with pigment accumulation. Gel filtration of lyophilized filtrate yielded a single peak of activity corresponding to the pigment fraction. Pyocyanin extracted from an active strain, and 1-hydroxyphenazine were purified by high performance liquid chromatography, and characterized by ultraviolet absorbance spectra and mass spectrometry. Both slowed cilia in a dose-dependent manner, and were synthesized and shown to be indistinguishable from the biological compounds. Pyocyanin caused gradual onset of slowing and ultimate widespread ciliostasis with epithelial disruption. 1-hydroxyphenazine caused rapid onset of ciliary slowing associated with dyskinesia and ciliostasis. Pyocyanin assayed within filtrates accounted for a significant proportion of the bioactivity present.

Much current psychopathology research is framed by categorical constructs. Limitations of categorical constructs have been articulated, and dimensional constructs are often proposed as viable alternatives to categories of psychopathology. The purpose of this Special Section is to articulate and discuss diverse issues that arise in contemplating dimensional constructs as targets for psychopathology research.The goal of this special section is to synthesize recent advances in the development of dimensional models and approaches to research on psychopathology. Much current psychopathology research is framed by what are basically categorical conceptions of psychopathology, such as the prototypical categories described in the Diagnostic and