Discordance between resting and hyperemic indices of coronary stenosis severity: the VERIFY 2 study (a comparative study of resting coronary pressure gradient, instantaneous wave-free ratio and fractional flow reserve in an unselected population referred for invasive angiography)

Background—Distal coronary to aortic pressure ratio (Pd/Pa) and instantaneous wave-free ratio (iFR) are indices of functional significance of a coronary stenosis measured without hyperemia. It has been suggested that iFR has superior diagnostic accuracy to Pd/Pa when compared with fractional flow reserve (FFR). We hypothesized that in comparison with FFR, revascularization decisions based on either binary cutoff values for iFR and Pd/Pa or hybrid strategies incorporating iFR or Pd/Pa will result in similar levels of disagreement. Methods and Results—This is a prospective study in consecutive patients undergoing FFR for clinical indications using proprietary software to calculate iFR. We measured Pd/Pa, iFR, FFR, and hyperemic iFR. Diagnostic accuracy versus FFR ≤0.80 was calculated using binary cutoff values of ≤0.90 for iFR and ≤0.92 for Pd/Pa, and adenosine zones for iFR of 0.86 to 0.93 and Pd/Pa of 0.87 to 0.94 in the hybrid strategy. One hundred ninety-seven patients with 257 stenoses (mean diameter stenosis 48%) were studied. Using binary cutoffs, diagnostic accuracy was similar for iFR and resting Pd/Pa with misclassification rates of 21% versus 20.2% (P=0.85). In the hybrid analysis, 54% of iFR cases and 53% of Pd/Pa cases were outside the adenosine zone and rates of misclassification were 9.4% versus 11.9% (P=0.55). Conclusions—Binary cutoff values for iFR and Pd/Pa result in misclassification of 1 in 5 lesions. Using a hybrid strategy, approximately half of the patients do not receive adenosine, but 1 in 10 lesions are still misclassified. The use of nonhyperemic indices of stenosis severity cannot be recommended for decision making in the catheterization laboratory. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT02377310

Property War: Prostitution, Red-Light Districts, and the Transformation of Public Nuisance Law in the Progressive Era

San Francisco, September 14, 1915 As the sun began to set over the Pacific, Bascom Johnson, on leave from the American Social Hygiene Association, left his Berkeley apartment at 2248 Blake Street to make the long trip across the San Francisco Bay. Sometimes he was joined by Thomas D. Eliot, but tonight he was alone. Eliot had told him of a place he should visit - 9 Beckett Street. Upon debarking from the ferry, Johnson made his way along Broadway Street in the direction of Chinatown. By now, the fog had rolled in and the temperatures had begun to drop. Like so many other men of his generation Johnson was headed towards the city\u27s infamous red-light district - the Barbary Coast, which bordered the Chinese Business District. Walking along Broadway, he turned left onto Keamey. The sounds and smells of Chinatown filled the heavy night air. As he took a right onto Pacific Street, he was now in the heart of the Barbary Coast. Throngs of people walked up and down the streets enjoying the district\u27s combustible mixture of sex and other entertainments. Brothels, hot-sheet hotels and gambling dens were intertwined with semi-respectable dance halls, theaters, cabarets and restaurants. As Johnson turned down onto the single block of Beckett Street, passers-by must have assumed that he was either another restless young man looking for sexual pleasure or one of the many middle-class voyeurs who came to the Barbary Coast looking for cheap, visual thrills

Discordance Between Resting and Hyperemic Indices of Coronary Stenosis Severity

Background—Distal coronary to aortic pressure ratio (Pd/Pa) and instantaneous wave-free ratio (iFR) are indices of functional significance of a coronary stenosis measured without hyperemia. It has been suggested that iFR has superior diagnostic accuracy to Pd/Pa when compared with fractional flow reserve (FFR). We hypothesized that in comparison with FFR, revascularization decisions based on either binary cutoff values for iFR and Pd/Pa or hybrid strategies incorporating iFR or Pd/Pa will result in similar levels of disagreement. Methods and Results—This is a prospective study in consecutive patients undergoing FFR for clinical indications using proprietary software to calculate iFR. We measured Pd/Pa, iFR, FFR, and hyperemic iFR. Diagnostic accuracy versus FFR ≤0.80 was calculated using binary cutoff values of ≤0.90 for iFR and ≤0.92 for Pd/Pa, and adenosine zones for iFR of 0.86 to 0.93 and Pd/Pa of 0.87 to 0.94 in the hybrid strategy. One hundred ninety-seven patients with 257 stenoses (mean diameter stenosis 48%) were studied. Using binary cutoffs, diagnostic accuracy was similar for iFR and resting Pd/Pa with misclassification rates of 21% versus 20.2% (P=0.85). In the hybrid analysis, 54% of iFR cases and 53% of Pd/Pa cases were outside the adenosine zone and rates of misclassification were 9.4% versus 11.9% (P=0.55). Conclusions—Binary cutoff values for iFR and Pd/Pa result in misclassification of 1 in 5 lesions. Using a hybrid strategy, approximately half of the patients do not receive adenosine, but 1 in 10 lesions are still misclassified. The use of nonhyperemic indices of stenosis severity cannot be recommended for decision making in the catheterization laboratory. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT02377310

Wills, deeds, acts: women's civic gift-giving in Ottoman Istanbul

The waqf (plural awqaf) is the Islamic pious endowment founded for charitable purposes. The Ottoman waqf, especially between the fifteenth and eighteenth centuries, became a gift-giving practice of solidarity in which women played an active role in founding and maintaining endowments as benefactors. These endowments served almost exclusively civic public services. While there has been considerable research on women and waqf, by moving beyond interpreting the ostensible motives that are always intertwined with women’s role as ‘family caretakers’ or ‘devout Muslims’, we attempt to suggest that, interpreted as acts of piety, awqaf, and especially those that were founded as organized spaces known as külliyes, became institutions by which women were able to cultivate (in themselves and others) civic identities, and articulate civic solidarities as citizens of their cities. This image of women as civic gift-givers recasts them as active citizens of Ottoman cities, especially Istanbul

Rab25 and CLIC3 collaborate to promote integrin recycling from late endosomes/lysosomes and drive cancer progression

Here we show that Rab25 permits the sorting of ligand-occupied, active-conformation α5β1 integrin to late endosomes/lysosomes. Photoactivation and biochemical approaches show that lysosomally targeted integrins are not degraded but are retrogradely transported and recycled to the plasma membrane at the back of invading cells. This requires CLIC3, a protein upregulated in Rab25-expressing cells and tumors, which colocalizes with active α5β1 in late endosomes/lysosomes. CLIC3 is necessary for release of the cell rear during migration on 3D matrices and is required for invasion and maintenance of active Src signaling in organotypic microenvironments. CLIC3 expression predicts lymph node metastasis and poor prognosis in operable cases of pancreatic ductal adenocarcinoma (PDAC). The identification of CLIC3 as a regulator of a recycling pathway and as an independent prognostic indicator in PDAC highlights the importance of active integrin trafficking as a potential drive to cancer progression in vivo