Optimization of treatment planning workflow and tumor coverage during daily adaptive magnetic resonance image guided radiation therapy (MR-IGRT) of pancreatic cancer

Abstract Background To simplify the adaptive treatment planning workflow while achieving the optimal tumor-dose coverage in pancreatic cancer patients undergoing daily adaptive magnetic resonance image guided radiation therapy (MR-IGRT). Methods In daily adaptive MR-IGRT, the plan objective function constructed during simulation is used for plan re-optimization throughout the course of treatment. In this study, we have constructed the initial objective functions using two methods for 16 pancreatic cancer patients treated with the ViewRay™ MR-IGRT system: 1) the conventional method that handles the stomach, duodenum, small bowel, and large bowel as separate organs at risk (OARs) and 2) the OAR grouping method. Using OAR grouping, a combined OAR structure that encompasses the portions of these four primary OARs within 3 cm of the planning target volume (PTV) is created. OAR grouping simulation plans were optimized such that the target coverage was comparable to the clinical simulation plan constructed in the conventional manner. In both cases, the initial objective function was then applied to each successive treatment fraction and the plan was re-optimized based on the patient’s daily anatomy. OAR grouping plans were compared to conventional plans at each fraction in terms of coverage of the PTV and the optimized PTV (PTV OPT), which is the result of the subtraction of overlapping OAR volumes with an additional margin from the PTV. Results Plan performance was enhanced across a majority of fractions using OAR grouping. The percentage of the volume of the PTV covered by 95% of the prescribed dose (D95) was improved by an average of 3.87 ± 4.29% while D95 coverage of the PTV OPT increased by 3.98 ± 4.97%. Finally, D100 coverage of the PTV demonstrated an average increase of 6.47 ± 7.16% and a maximum improvement of 20.19%. Conclusions In this study, our proposed OAR grouping plans generally outperformed conventional plans, especially when the conventional simulation plan favored or disregarded an OAR through the assignment of distinct weighting parameters relative to the other critical structures. OAR grouping simplifies the MR-IGRT adaptive treatment planning workflow at simulation while demonstrating improved coverage compared to delivered pancreatic cancer treatment plans in daily adaptive radiation therapy

Antibiotic prophylaxis for selected gynecologic surgeries

BackgroundAntibiotic prophylaxis for surgery is commonly used and is recommended by multiple organizations.ObjectiveTo critically review gynecology‐specific data regarding surgical antibiotic prophylaxis in selected benign gynecologic surgeries.Search strategyMEDLINE and Cochrane databases were searched from inception to July 2010.Selection criteriaRandomized controlled trials of benign vaginal, cervical, transcervical, abdominal, or laparoscopic procedures other than hysterectomy comparing prophylactic antibiotic use with placebo or with another antibiotic. Outcomes of interest were postoperative infections, additional treatments, and adverse events.Data collection and analysisIn total, 19 trials met the inclusion criteria. Studies were individually assessed for methodologic quality, then grouped by procedure and evaluated for evidence quality.Main resultsThere was no difference in infectious outcome for loop electrosurgical excision, hysteroscopic ablation, or laparoscopy, although evidence quality was poor. Fair evidence supports antibiotic prophylaxis for suction curettage or laparotomy. There were insufficient data regarding vaginal surgery prophylaxis.ConclusionAntibiotic prophylaxis may be beneficial in first‐trimester suction curettage and laparotomy. No advantage was found for loop electrosurgical excision, hysteroscopy, or laparoscopic gynecologic surgery. Newer procedures and vaginal surgery lack research and merit study.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/135267/1/ijgo10.pd

Hα Reverberation Mapping of the Intermediate-mass Active Galactic Nucleus in NGC 4395

We present the results of a high-cadence spectroscopic and imaging monitoring campaign of the active galactic nucleus (AGN) of NGC 4395. High signal-to-noise-ratio spectra were obtained at the Gemini-N 8 m telescope using the GMOS integral field spectrograph (IFS) on 2019 March 7 and at the Keck I 10 m telescope using the Low-Resolution Imaging Spectrometer with slit masks on 2019 March 3 and April 2. Photometric data were obtained with a number of 1 m-class telescopes during the same nights. The narrow-line region (NLR) is spatially resolved; therefore, its variable contributions to the slit spectra make the standard procedure of relative flux calibration impractical. We demonstrate that spatially resolved data from the IFS can be effectively used to correct the slit-mask spectral light curves. While we obtained no reliable lag owing to the lack of a strong variability pattern in the light curves, we constrain the broad-line time lag to be less than 3 hr, consistent with the photometric lag of ∼80 minutes reported by Woo et al. By exploiting the high-quality spectra, we measure the second moment of the broad component of the Hα emission line to be 586 ± 19 km s−1, superseding the lower value reported by Woo et al. Combining the revised line dispersion and the photometric time lag, we update the black hole mass to (1.7 ± 0.3) × 104 M⊙

The Seoul National University AGN Monitoring Project. IV. Hα Reverberation Mapping of Six AGNs and the Hα Size–Luminosity Relation

The broad-line region (BLR) size–luminosity relation has paramount importance for estimating the mass of black holes in active galactic nuclei (AGNs). Traditionally, the size of the Hβ BLR is often estimated from the optical continuum luminosity at 5100 Å, while the size of the Hα BLR and its correlation with the luminosity is much less constrained. As a part of the Seoul National University AGN Monitoring Project, which provides 6 yr photometric and spectroscopic monitoring data, we present our measurements of the Hα lags of high-luminosity AGNs. Combined with the measurements for 42 AGNs from the literature, we derive the size–luminosity relations of the Hα BLR against the broad Hα and 5100 Å continuum luminosities. We find the slope of the relations to be 0.61 ± 0.04 and 0.59 ± 0.04, respectively, which are consistent with the Hβ size–luminosity relation. Moreover, we find a linear relation between the 5100 Å continuum luminosity and the broad Hα luminosity across 7 orders of magnitude. Using these results, we propose a new virial mass estimator based on the Hα broad emission line, finding that the previous mass estimates based on scaling relations in the literature are overestimated by up to 0.7 dex at masses lower than 107M⊙

The Seoul National University AGN Monitoring Project III: Hβ\beta lag measurements of 32 luminous AGNs and the high-luminosity end of the size--luminosity relation

We present the main results from a long-term reverberation mapping campaign carried out for the Seoul National University Active Galactic Nuclei (AGN) Monitoring Project. High-quality data were obtained during 2015-2021 for 32 luminous AGNs (i.e., continuum luminosity in the range of $10^{44-46}$ erg s$^{-1}$) at a regular cadence, of 20-30 days for spectroscopy and 3-5 days for photometry. We obtain time lag measurements between the variability in the H$\beta$ emission and the continuum for 32 AGNs; twenty-five of those have the best lag measurements based on our quality assessment, examining correlation strength, and the posterior lag distribution. Our study significantly increases the current sample of reverberation-mapped AGNs, particularly at the moderate to high luminosity end. Combining our results with literature measurements, we derive a H$\beta$ broad line region size--luminosity relation with a shallower slope than reported in the literature. For a given luminosity, most of our measured lags are shorter than the expectation, implying that single-epoch black hole mass estimators based on previous calibrations could suffer large systematic uncertainties.Comment: Accepted by ApJ; 39 pages, 22 figure

Controlling anal incontinence in women by performing anal exercises with biofeedback or loperamide (CAPABLe) trial: Design and methods

The goals of this trial are to determine the efficacy and safety of two treatments for women experiencing fecal incontinence. First, we aim to compare the use of loperamide to placebo and second, to compare the use of anal sphincter exercises with biofeedback to usual care. The primary outcome is the change from baseline in the St. Mark's (Vaizey) Score 24 weeks after treatment initiation. As a Pelvic Floor Disorders Network (PFDN) trial, subjects are enrolling from eight PFDN clinical centers across the United States. A centralized data coordinating center supervises data collection and analysis. These two first-line treatments for fecal incontinence are being investigated simultaneously using a two-by-two randomized factorial design: a medication intervention (loperamide versus placebo) and a pelvic floor strength and sensory training intervention (anal sphincter exercises with manometry-assisted biofeedback versus usual care using an educational pamphlet). Interventionists providing the anal sphincter exercise training with biofeedback have received standardized training and assessment. Symptom severity, diary, standardized anorectal manometry and health-related quality of life outcomes are assessed using validated instruments administered by researchers masked to randomized interventions. Cost effectiveness analyses will be performed using prospectively collected data on care costs and resource utilization. This article describes the rationale and design of this randomized trial, focusing on specific research concepts of interest to researchers in the field of female pelvic floor disorders and all other providers who care for patients with fecal incontinence

The Seoul National University AGN Monitoring Project IV: Hα\alpha reverberation mapping of 6 AGNs and the Hα\alpha Size-Luminosity Relation

The broad line region (BLR) size-luminosity relation has paramount importance for estimating the mass of black holes in active galactic nuclei (AGNs). Traditionally, the size of the H$\beta$ BLR is often estimated from the optical continuum luminosity at 5100\angstrom{} , while the size of the H$\alpha$ BLR and its correlation with the luminosity is much less constrained. As a part of the Seoul National University AGN Monitoring Project (SAMP) which provides six-year photometric and spectroscopic monitoring data, we present our measurements of the H$\alpha$ lags of 6 high-luminosity AGNs. Combined with the measurements for 42 AGNs from the literature, we derive the size-luminosity relations of H$\alpha$ BLR against broad H$\alpha$ and 5100\angstrom{} continuum luminosities. We find the slope of the relations to be $0.61\pm0.04$ and $0.59\pm0.04$, respectively, which are consistent with the \hb{} size-luminosity relation. Moreover, we find a linear relation between the 5100\angstrom{} continuum luminosity and the broad H$\alpha$ luminosity across 7 orders of magnitude. Using these results, we propose a new virial mass estimator based on the H$\alpha$ broad emission line, finding that the previous mass estimates based on the scaling relations in the literature are overestimated by up to 0.7 dex at masses lower than $10^7$~M$_{\odot}$.Comment: Accepted for publication in ApJ (Jun. 25th, 2023). 21 pages, 12 figure

Genetic effects on gene expression across human tissues

Characterization of the molecular function of the human genome and its variation across individuals is essential for identifying the cellular mechanisms that underlie human genetic traits and diseases. The Genotype-Tissue Expression (GTEx) project aims to characterize variation in gene expression levels across individuals and diverse tissues of the human body, many of which are not easily accessible. Here we describe genetic effects on gene expression levels across 44 human tissues. We find that local genetic variation affects gene expression levels for the majority of genes, and we further identify inter-chromosomal genetic effects for 93 genes and 112 loci. On the basis of the identified genetic effects, we characterize patterns of tissue specificity, compare local and distal effects, and evaluate the functional properties of the genetic effects. We also demonstrate that multi-tissue, multi-individual data can be used to identify genes and pathways affected by human disease-associated variation, enabling a mechanistic interpretation of gene regulation and the genetic basis of diseas

Multi-ancestry study of blood lipid levels identifies four loci interacting with physical activity.

Many genetic loci affect circulating lipid levels, but it remains unknown whether lifestyle factors, such as physical activity, modify these genetic effects. To identify lipid loci interacting with physical activity, we performed genome-wide analyses of circulating HDL cholesterol, LDL cholesterol, and triglyceride levels in up to 120,979 individuals of European, African, Asian, Hispanic, and Brazilian ancestry, with follow-up of suggestive associations in an additional 131,012 individuals. We find four loci, in/near CLASP1, LHX1, SNTA1, and CNTNAP2, that are associated with circulating lipid levels through interaction with physical activity; higher levels of physical activity enhance the HDL cholesterol-increasing effects of the CLASP1, LHX1, and SNTA1 loci and attenuate the LDL cholesterol-increasing effect of the CNTNAP2 locus. The CLASP1, LHX1, and SNTA1 regions harbor genes linked to muscle function and lipid metabolism. Our results elucidate the role of physical activity interactions in the genetic contribution to blood lipid levels