William Zorach

An exhibition made possible by the Maine State Commission on the Arts and the Humanities, together with the exhibiting institutions ... Coordinator of the exhibition - Christopher Huntington. Catalogue of an exhibition held at the Colby College Art Museum Aug. 14-Sept. 22, 1968; Bowdoin College Museum of Art Nov.1-25, 1968.https://digitalcommons.bowdoin.edu/art-museum-exhibition-catalogs/1040/thumbnail.jp

Plethodon sequoyah

Number of Pages: 2Integrative BiologyGeological Science

Writ(h)ing Images: Imagination, the Human Form, and the Divine in William Blake, Salman Rushdie, and Simon Louvish

In this paper, we address issues in segmentation Of remotely sensed LIDAR (LIght Detection And Ranging) data. The LIDAR data, which were captured by airborne laser scanner, contain 2.5 dimensional (2.5D) terrain surface height information, e.g. houses, vegetation, flat field, river, basin, etc. Our aim in this paper is to segment ground (flat field)from non-ground (houses and high vegetation) in hilly urban areas. By projecting the 2.5D data onto a surface, we obtain a texture map as a grey-level image. Based on the image, Gabor wavelet filters are applied to generate Gabor wavelet features. These features are then grouped into various windows. Among these windows, a combination of their first and second order of statistics is used as a measure to determine the surface properties. The test results have shown that ground areas can successfully be segmented from LIDAR data. Most buildings and high vegetation can be detected. In addition, Gabor wavelet transform can partially remove hill or slope effects in the original data by tuning Gabor parameters

Outcomes in participants with failure of initial antibacterial therapy for hospital-acquired/ventilator-associated bacterial pneumonia prior to enrollment in the randomized, controlled phase 3 ASPECT-NP trial of ceftolozane/tazobactam versus meropenem

BACKGROUND: Ceftolozane/tazobactam, a combination antibacterial agent comprising an anti-pseudomonal cephalosporin and β-lactamase inhibitor, is approved for the treatment of hospital-acquired/ventilator-associated bacterial pneumonia (HABP/VABP) in adults. Participants in the ASPECT-NP trial received ceftolozane/tazobactam (3 g [2 g ceftolozane/1 g tazobactam] every 8 h) or meropenem (1 g every 8 h). Participants failing prior antibacterial therapy for the current HABP/VABP episode at study entry had lower 28-day all-cause mortality (ACM) rates with ceftolozane/tazobactam versus meropenem treatment. Here, we report a post hoc analysis examining this result. METHODS: The phase 3, randomized, controlled, double-blind, multicenter, noninferiority trial compared ceftolozane/tazobactam versus meropenem for treatment of adults with ventilated HABP/VABP; eligibility included those failing prior antibacterial therapy for the current HABP/VABP episode at study entry. The primary and key secondary endpoints were 28-day ACM and clinical response at test of cure (TOC), respectively. Participants who were failing prior therapy were a prospectively defined subgroup; however, subgroup analyses were not designed for noninferiority testing. The 95% CIs for treatment differences were calculated as unstratified Newcombe CIs. Post hoc analyses were performed using multivariable logistic regression analysis to determine the impact of baseline characteristics and treatment on clinical outcomes in the subgroup who were failing prior antibacterial therapy. RESULTS: In the ASPECT-NP trial, 12.8% of participants (93/726; ceftolozane/tazobactam, n = 53; meropenem, n = 40) were failing prior antibacterial therapy at study entry. In this subgroup, 28-day ACM was higher in participants who received meropenem versus ceftolozane/tazobactam (18/40 [45.0%] vs 12/53 [22.6%]; percentage difference [95% CI]: 22.4% [3.1 to 40.1]). Rates of clinical response at TOC were 26/53 [49.1%] for ceftolozane/tazobactam versus 15/40 [37.5%] for meropenem (percentage difference [95% CI]: 11.6% [- 8.6 to 30.2]). Multivariable regression analysis determined concomitant vasopressor use and treatment with meropenem were significant factors associated with risk of 28-day ACM. Adjusting for vasopressor use, the risk of dying after treatment with ceftolozane/tazobactam was approximately one-fourth the risk of dying after treatment with meropenem. CONCLUSIONS: This post hoc analysis further supports the previously demonstrated lower ACM rate for ceftolozane/tazobactam versus meropenem among participants who were failing prior therapy, despite the lack of significant differences in clinical cure rates. CLINICALTRIALS: gov registration NCT02070757 . Registered February 25, 2014, clinicaltrials.gov/ct2/show/NCT02070757

Outcomes in participants with ventilated nosocomial pneumonia and organ failure treated with ceftolozane/tazobactam versus meropenem: A subset analysis of the phase 3, randomized, controlled ASPECT-NP trial

BACKGROUND: The pivotal ASPECT-NP trial showed ceftolozane/tazobactam was non-inferior to meropenem for the treatment of ventilated hospital-acquired/ventilator-associated bacterial pneumonia (vHABP/VABP). Here, we evaluated treatment outcomes by degree of respiratory or cardiovascular dysfunction. METHODS: This was a subset analysis of data from ASPECT-NP, a randomized, double-blind, non-inferiority trial (ClinicalTrials.gov NCT02070757). Adults with vHABP/VABP were randomized 1:1 to 3 g ceftolozane/tazobactam or 1 g meropenem every 8 h for 8-14 days. Outcomes in participants with a baseline respiratory component of the Sequential Organ Failure Assessment (SOFA) score (R-SOFA) ≥ 2 (indicative of severe respiratory failure), cardiovascular component of the SOFA score (CV-SOFA) ≥ 2 (indicative of shock), or R-SOFA ≥ 2 plus CV-SOFA ≥ 2 were compared by treatment arm. The efficacy endpoint of primary interest was 28-day all-cause mortality. Clinical response, time to death, and microbiologic response were also evaluated. RESULTS: There were 726 participants in the intention-to-treat population; 633 with R-SOFA ≥ 2 (312 ceftolozane/tazobactam, 321 meropenem), 183 with CV-SOFA ≥ 2 (84 ceftolozane/tazobactam, 99 meropenem), and 160 with R-SOFA ≥ 2 plus CV-SOFA ≥ 2 (69 ceftolozane/tazobactam, 91 meropenem). Baseline characteristics, including causative pathogens, were generally similar in participants with R-SOFA ≥ 2 or CV-SOFA ≥ 2 across treatment arms. The 28-day all-cause mortality rate was 23.7% and 24.0% [difference: 0.3%, 95% confidence interval (CI) - 6.4, 6.9] for R-SOFA ≥ 2, 33.3% and 30.3% (difference: - 3.0%, 95% CI - 16.4, 10.3) for CV-SOFA ≥ 2, and 34.8% and 30.8% (difference: - 4.0%, 95% CI - 18.6, 10.3), respectively, for R-SOFA ≥ 2 plus CV-SOFA ≥ 2. Clinical cure rates were as follows: 55.8% and 54.2% (difference: 1.6%, 95% CI - 6.2, 9.3) for R-SOFA ≥ 2, 53.6% and 55.6% (difference: - 2.0%, 95% CI - 16.1, 12.2) for CV-SOFA ≥ 2, and 53.6% and 56.0% (difference: - 2.4%, 95% CI - 17.6, 12.8), respectively, for R-SOFA ≥ 2 plus CV-SOFA ≥ 2. Time to death was comparable in all SOFA groups across both treatment arms. A higher rate of microbiologic eradication/presumed eradication was observed for CV-SOFA ≥ 2 and R-SOFA ≥ 2 plus CV-SOFA ≥ 2 with ceftolozane/tazobactam compared to meropenem. CONCLUSIONS: The presence of severe respiratory failure or shock did not affect the relative efficacy of ceftolozane/tazobactam versus meropenem; either agent may be used to treat critically ill patients with vHABP/VABP. TRIAL REGISTRATION: ClinicalTrials.gov NCT02070757. Registered 25 February 2014, https://clinicaltrials.gov/ct2/show/NCT02070757

Ceftolozane/tazobactam probability of target attainment and outcomes in participants with augmented renal clearance from the randomized phase 3 ASPECT-NP trial

BACKGROUND: The randomized, double-blind, phase 3 ASPECT-NP trial evaluated the efficacy of 3 g of ceftolozane/tazobactam (C/T) versus 1 g of meropenem infused every 8 h for 8 to 14 days for treatment of adults with hospital-acquired bacterial pneumonia (HABP) or ventilator-associated bacterial pneumonia (VABP). We assessed the probability of target attainment and compared efficacy outcomes from ASPECT-NP in participants with augmented renal clearance (ARC) versus those with normal renal function. METHODS: Baseline renal function was categorized as normal renal function (creatinine clearance 80-130 mL/min) or ARC (creatinine clearance \u3e 130 mL/min). Population pharmacokinetic models informed Monte Carlo simulations to assess probability of target attainment in plasma and pulmonary epithelial lining fluid. Outcomes included 28-day all-cause mortality and clinical cure and per-participant microbiologic cure rates at the test-of-cure visit. RESULTS: A \u3e 99% and \u3e 80% probability of target attainment was demonstrated for ceftolozane and tazobactam, respectively, in simulated plasma and epithelial lining fluid. Within treatment arms, 28-day all-cause mortality rates in participants with normal renal function (C/T, n = 131; meropenem, n = 123) and ARC (C/T, n = 96; meropenem, n = 113) were comparable (data comparisons presented as rate; treatment difference [95% CI]) (C/T: normal renal function, 17.6%; ARC, 17.7%; 0.2 [- 9.6 to 10.6]; meropenem: normal renal function, 20.3%; ARC, 17.7%; - 2.6 [- 12.6 to 7.5]). Clinical cure rates at test-of-cure were also comparable across renal function groups within treatment arms (C/T: normal renal function, 57.3%; ARC, 59.4%; - 2.1 [- 14.8 to 10.8]; meropenem: normal renal function, 59.3%; ARC, 57.5%; 1.8 [- 10.6 to 14.2]). Per-participant microbiologic cure rates at test-of-cure were consistent across renal function groups within treatment arms (C/T: normal renal function, 72.2% [n/N = 70/97]; ARC, 71.4% [n/N = 55/77]; 0.7 [- 12.4 to 14.2]; meropenem: normal renal function, 75.0% [n/N = 66/88]; ARC, 70.0% [n/N = 49/70]; 5.0 [- 8.7 to 19.0]). CONCLUSIONS: C/T and meropenem resulted in 28-day all-cause mortality, clinical cure, and microbiologic cure rates that were comparable between participants with ARC or normal renal function. In conjunction with high probability of target attainment, these results confirm that C/T (3 g) every 8 h is appropriate in patients with HABP/VABP and ARC. Trial registration ClinicalTrials.gov identifier: NCT02070757, registered February 25, 2014; EudraCT: 2012-002862-11

Safety and efficacy of ceftolozane/tazobactam plus metronidazole versus meropenem from a phase 2, randomized clinical trial in pediatric participants with complicated intra-abdominal infection

BACKGROUND: Ceftolozane/tazobactam, a cephalosporin-β-lactamase inhibitor combination, is approved for the treatment of complicated urinary tract infections and complicated intra-abdominal infections (cIAI). The safety and efficacy of ceftolozane/tazobactam in pediatric participants with cIAI were assessed. METHODS: This phase 2 study (NCT03217136) randomized participants to either ceftolozane/tazobactam+metronidazole or meropenem for treatment of cIAI in pediatric participants (\u3c18 years). The primary objective was to assess the safety and tolerability of intravenous ceftolozane/tazobactam+metronidazole. Clinical cure at end of treatment (EOT) and test of cure (TOC) visits were secondary end points. RESULTS: The modified intent-to-treat (MITT) population included 91 participants (ceftolozane/tazobactam+metronidazole, n = 70; meropenem, n = 21). Complicated appendicitis was the most common diagnosis (93.4%); Escherichia coli was the most common pathogen (65.9%). Adverse events (AEs) occurred in 80.0% and 61.9% of participants receiving ceftolozane/tazobactam+metronidazole and meropenem, drug-related AEs occurred in 18.6% and 14.3% and serious AEs occurred in 11.4% and 0% of participants receiving ceftolozane/tazobactam+metronidazole and meropenem, respectively. No drug-related serious AEs or discontinuations due to drug-related AEs occurred. Rates of the clinical cure for ceftolozane/tazobactam+metronidazole and meropenem at EOT were 80.0% and 95.2% (difference: -14.3; 95% confidence interval: -26.67 to 4.93) and at TOC were 80.0% and 100.0% (difference: -19.1; 95% confidence interval: -30.18 to -2.89), respectively; 6 of the 14 clinical failures for ceftolozane/tazobactam+metronidazole at TOC were indeterminate responses imputed as failures per protocol. CONCLUSION: Ceftolozane/tazobactam+metronidazole was well tolerated in pediatric participants with cIAI and had a safety profile similar to the established safety profile in adults. In this descriptive efficacy analysis, ceftolozane/tazobactam+metronidazole appeared efficacious

Ceftolozane/tazobactam versus meropenem in patients with ventilated hospital-acquired bacterial pneumonia: Subset analysis of the ASPECT-NP randomized, controlled phase 3 trial

BACKGROUND: Ceftolozane/tazobactam is approved for treatment of hospital-acquired/ventilator-associated bacterial pneumonia (HABP/VABP) at double the dose approved for other infection sites. Among nosocomial pneumonia subtypes, ventilated HABP (vHABP) is associated with the lowest survival. In the ASPECT-NP randomized, controlled trial, participants with vHABP treated with ceftolozane/tazobactam had lower 28-day all-cause mortality (ACM) than those receiving meropenem. We conducted a series of post hoc analyses to explore the clinical significance of this finding. METHODS: ASPECT-NP was a multinational, phase 3, noninferiority trial comparing ceftolozane/tazobactam with meropenem for treating vHABP and VABP; study design, efficacy, and safety results have been reported previously. The primary endpoint was 28-day ACM. The key secondary endpoint was clinical response at test-of-cure. Participants with vHABP were a prospectively defined subgroup, but subgroup analyses were not powered for noninferiority testing. We compared baseline and treatment factors, efficacy, and safety between ceftolozane/tazobactam and meropenem in participants with vHABP. We also conducted a retrospective multivariable logistic regression analysis in this subgroup to determine the impact of treatment arm on mortality when adjusted for significant prognostic factors. RESULTS: Overall, 99 participants in the ceftolozane/tazobactam and 108 in the meropenem arm had vHABP. 28-day ACM was 24.2% and 37.0%, respectively, in the intention-to-treat population (95% confidence interval [CI] for difference: 0.2, 24.8) and 18.2% and 36.6%, respectively, in the microbiologic intention-to-treat population (95% CI 2.5, 32.5). Clinical cure rates in the intention-to-treat population were 50.5% and 44.4%, respectively (95% CI - 7.4, 19.3). Baseline clinical, baseline microbiologic, and treatment factors were comparable between treatment arms. Multivariable regression identified concomitant vasopressor use and baseline bacteremia as significantly impacting ACM in ASPECT-NP; adjusting for these two factors, the odds of dying by day 28 were 2.3-fold greater when participants received meropenem instead of ceftolozane/tazobactam. CONCLUSIONS: There were no underlying differences between treatment arms expected to have biased the observed survival advantage with ceftolozane/tazobactam in the vHABP subgroup. After adjusting for clinically relevant factors found to impact ACM significantly in this trial, the mortality risk in participants with vHABP was over twice as high when treated with meropenem compared with ceftolozane/tazobactam. TRIAL REGISTRATION: clinicaltrials.gov, NCT02070757. Registered 25 February, 2014, clinicaltrials.gov/ct2/show/NCT02070757