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Neoadjuvant intratumoral cisplatin has the potential to generate substantial cytotoxicity and immune priming within the tumor environment, while minimizing systemic, off-target, adverse events. We initiated a phase 1A, 3+3 dose-ranging study of neoadjuvant, intratumoral cisplatin, delivered through endobronchial ultrasound bronchoscopy, in the same procedure as the initial diagnosis. There were no dose-limiting toxicity identified at the 20mg level

Abstract Water‐use efficiency (WUE) is an under‐researched but very important drought tolerance trait in forage breeding. This research estimated quantitative genetic parameters of morpho‐physiological traits linked to agronomic water‐use efficiency (WUEA) and its proxy measures based on δ13C (WUEi) or gas exchange (evapotranspiration, WUEAET, or stomatal conductance WUEASC) of genotypes from half‐sib families of Lolium perenne L. (PRG) in a simulated summer drought cycle. Principal component analysis (PCA) of trait data distinguished a group of PRG genotypes where high WUEA and dry matter yield was associated with deep rooting, leaf hydration at more negative leaf osmotic and water potential, and reduced soil moisture depletion. Plants with this trait association sustained net assimilation and postdefoliation regrowth in drought. However, WUEi, WUEASC, and WUEAET were poorly correlated with most traits of interest at p 0.7;p

The addition of intravenous (i.v.) chemotherapy to i.v. immunotherapy for patients with lung cancer results in improved overall survival but is limited by synergistic side effects and an unknown, highly variable final cytotoxic dose within the tumor. The synergy between i.v. chemo- and immunotherapies is hypothesized to occur as a result of cell injury caused by chemotherapy, a mechanism demonstrated to drive antigen presentation within the tumor microenvironment. Intratumoral delivery of chemotherapy may thus be optimized to maximize tumor cell injury. To assess the balance between the damage versus the death of tumor cells, we developed a computational model of intratumoral dynamics within a lung cancer tumor for three different chemotherapy agents following direct injection as a function of location and number of injection sites. We based the model on the morphology of a lung tumor obtained from a thoracic CT scan. We found no meaningful difference in the extent of tumor cell damage between a centrally injected versus peripherally injected agent, but there were significant differences between a single injection versus when the total dose was apportioned between multiple injection sites. Importantly, we also found that the standard chemotherapeutic concentrations used for intravenous administration were effective at causing cell death but were too high to generate significant cell injury. This suggests that to induce maximal tumor cell injury, the optimal concentration should be several orders of magnitude lower than those typically used for intravenous therapy.

Objective:. To determine baseline quality of life characteristics in patients with low-flow head and neck vascular malformations. Study Design:. Retrospective review of prospectively collected data. Setting:. Tertiary Pediatric Hospital. Methods:. Patients with low-flow head and neck vascular malformations (age 0–18 years) evaluated through our vascular anomalies clinic from 2016 to 2019 were reviewed. Patients with completed PedsQL surveys using parent-proxy reports for children 2–7 years old and both patient and parent-proxy data for patients ≥8 years old were included. Results:. In total 94 consecutive patients were included, with a mean age of 9.2 ± 4.7 years. Diagnoses included lymphatic malformations (n = 50), venous malformations (n = 41), and combined venolymphatic malformations (n = 3). Total parental quality of life scores were lower than their children’s (84.23 vs 87.45; P = .037), with lower emotional scores as age at presentation increased (d = −0.60; P < .01). Lower parental scores were also noted across multiple domains for submandibular/sublingual, oropharyngeal, hypopharyngeal, and orbital involvement. (g = −0.68 to −1.10; P < .05). Increasing subsite number involvement affected parents and children similarly (−0.30 vs −0.35; P ≤ .02). Higher physical function scores were noted in venous versus lymphatic malformations (d =−1.07; P = .01). The child-reported school function scores were lower in African-American versus Caucasian children (P = .04). Prior treatment was associated with lower parental scores (d = 0.59; P = .04). Conclusion:. The parent and patient’s quality of life is reduced across multiple domains for low-flow head and neck vascular malformations based on age, lesion location and type, disease burden, race, and prior treatment.

BACKGROUND: Polycystic ovarian syndrome and endometriosis are 2 of the most common reproductive disorders among women but are thought to be unrelated. OBJECTIVE: This study aimed to examine the overlap and common symptoms of polycystic ovarian syndrome and endometriosis. STUDY DESIGN: The study population included the Endometriosis, Natural History, Diagnosis, and Outcomes Study (2007–2009) operative cohort: 473 women, aged 18 to 44 years, who underwent a diagnostic and/or therapeutic laparoscopy or laparotomy at 1 of 14 surgical centers located in Salt Lake City, Utah, or San Francisco, California, in addition to a population cohort composed of 127 women from the surgical centers’ catchment areas. Age and site-adjusted multinomial regression models were used to estimate adjusted prevalence ratios and 95% confidence intervals of reproductive history characteristics among women with endometriosis only, women with polycystic ovarian syndrome only, and women with both endometriosis and polycystic ovarian syndrome. RESULTS: Among the operative cohort, 35% had endometriosis only, 9% had polycystic ovarian syndrome only, and 5% had endometriosis and polycystic ovarian syndrome. Among the population cohort, 10% had endometriosis only, 8% had polycystic ovarian syndrome only, and 2% had endometriosis and polycystic ovarian syndrome. In the operative cohort, a history of subfertility was associated with a higher adjusted probability of having both conditions (adjusted prevalence ratio, 10.33; 95% confidence interval, 3.94–27.08), followed by having endometriosis only (adjusted prevalence ratio, 2.45; 95% confidence interval, 1.56–3.84) or polycystic ovarian syndrome only (adjusted prevalence ratio, 1.15; 95% confidence interval, 0.51–2.61), than having neither condition. In addition, experiencing chronic pelvic pain within the past 12 months was associated with a higher probability of having both conditions (adjusted prevalence ratio, 2.53; 95% confidence interval, 1.07–6.00) than having neither condition. CONCLUSION: Among a cohort of women undergoing gynecologic laparoscopy or laparotomy, our study found that nearly 1 in 20 women had both an incident endometriosis diagnosis and symptoms consistent with polycystic ovarian syndrome. Among a population cohort of women not seeking gynecologic care, polycystic ovarian syndrome and endometriosis overlap prevalence was approximately 1 in 50 women.

Abstract Background In developing countries where both high rates of smoking and endemic tuberculosis (TB) are often present, identification of early lung cancer can be significantly confounded by the presence of nodules such as those due to latent TB (LTB). It is very challenging to distinguish lung cancer and LTB without invasive procedures, which have their own risks of morbidity and even mortality. Methods Our method uses a customized VGG16-based 15-layer 2-dimensional deep convolutional neural network (DNN) architecture with transfer learning. The DNN was trained and tested on sets of CT images set extracted from the National Lung Screening Trial and the National Institute of Allergy and Infectious Disease TB Portals. Performance of the DNN was evaluated under locked and step-wise unlocked pretrained weight conditions. Results The DNN with unlocked pretrained weights achieved an accuracy of 90.4% with an F score of 90.1%. Conclusions Our findings support the potential for a DNN to serve as a noninvasive screening tool capable of reliably detecting and distinguishing between lung cancer and LTB.

Abstract We recently developed a computational model of cisplatin pharmacodynamics in an endobronchial lung tumor following ultrasound-guided transbronchial needle injection (EBUS-TBNI). The model suggests that it is more efficacious to apportion the cisplatin dose between injections at different sites rather than giving it all in a single central injection, but the model was calibrated only on blood cisplatin data from a single patient. Accordingly, we applied a modified version of our original model in a set of 32 patients undergoing EBUS-TBNI for non-small cell lung cancer (NSCLC). We used the model to predict clinical responses and compared them retrospectively to actual patient outcomes. The model correctly predicted the clinical response in 72% of cases, with 80% accuracy for adenocarcinomas and 62.5% accuracy for squamous-cell lung cancer. We also found a power-law relationship between tumor volume and the minimal dose needed to induce a response, with the power-law exponent depending on the number of injections administered. Our results suggest that current injection strategies may be significantly over- or under-dosing the agent depending on tumor size, and that computational modeling can be a useful planning tool for EBUS-TBNI of cisplatin in lung cancer.

Abstract Objectives To identify trends in timing of pediatric cochlear implant (CI) care during COVID‐19. Study Design Retrospective cohort. Setting Tertiary care center. Methods Patients under 18 years of age who underwent CI between 1/1/2016 and 2/29/2020 were included in the pre‐COVID‐19 group, and patients implanted between 3/1/2020 and 12/31/2021 comprised the COVID‐19 group. Revision and sequential surgeries were excluded. Time intervals between care milestones including severe‐to‐profound hearing loss diagnosis, initial CI candidacy evaluation, and surgery were compared among groups, as were the number and type of postoperative visits. Results A total of 98 patients met criteria; 70 were implanted pre‐COVID‐19 and 28 during COVID‐19. A significant increase in the interval between CI candidacy evaluation and surgery was seen among patients with prelingual deafness during COVID‐19 compared with pre‐COVID‐19 (µ = 47.3 weeks, 95% confidence interval [CI]: 34.8‐59.9 vs µ = 20.5 weeks, 95% CI: 13.1‐27.9; p

Abstract Background To review the safety and efficacy of percutaneous cryoablation for the treatment of chondroblastoma and osteoblastoma in the pediatric and adolescent population. Materials and methods A retrospective review from 2016 to 2020 was performed to evaluate clinical and imaging response to percutaneous cryoablation in 11 symptomatic patients with diagnosis of chondroblastoma and osteoblastoma treated from two pediatric hospitals with at least 12-month follow-up. Technical success (correct needle placement and potential full coverage of the tumor with the planned ablation zone) and clinical success (relief of the symptoms) were evaluated. The primary objective was to alleviate pain related to the lesion(s). Immediate and late complications were recorded. Patients were followed in clinic and with imaging studies such as MRI or CT for a minimum of 6 months. Results A total of 11 patients were included (mean 14 years, age range 9–17; male n = 8). Diagnoses were osteoblastoma (n = 4) and chondroblastoma (n = 7). Locations were proximal humerus (n = 1), femur condyle (n = 1), and proximal femur (n = 1) tibia (n = 3), acetabulum (n = 3), thoracic vertebra (n = 1) and lumbar vertebra (n = 1). Cryoablation was technically successful in all patients. Clinical success (cessation of pain) was achieved in all patients. No signs of recurrence were observed on imaging follow-up in any of the patients. One of the patients developed periprocedural right L2–L3 transient radiculopathy as major immediate complication. Conclusions Percutaneous image-guided cryoablation can be considered potentially safe and effective treatment for chondroblastoma and osteoblastoma in children and adolescents.

Facial nerve tumors within the temporal bone present several surgical challenges due to the tortuous course of the facial nerve and the nerve’s close relationship to other important structures. Surgical approaches often have either sacrificed hearing/vestibular function or involved brain retraction. We present a case of a patient who was diagnosed with a facial nerve schwannoma (House-Brackmann IV/VI). Magnetic resonance imaging (MRI) showed the tumor was limited to the middle ear. The patient had already undergone facial reanimation procedures and elected to have the tumor removed. A transmastoid trans-facial canal surgical approach was used to remove the tumor without disturbing the ossicular chain. The patient’s hearing and vestibular function remained intact. Operating from within the facial canal provides the surgeon additional room to dissect facial nerve tumors from the middle ear to the geniculate ganglion when using a transmastoid approach. This surgical approach is similar to the previously described transmastoid/supralabyrinthine approach to excise facial nerve tumors within the temporal bone but modified to keep the ossicles intact. While the described approach has a limited application, in certain cases of facial nerve tumors within the temporal bone when surgery is warranted, a transmastoid trans-facial canal approach may have advantages over previously-described approaches.

In some lower rainfall regions of the world (300–750 mm), common vetch (Vicia sativa L., hereafter referred to as vetch) has been shown to have yields competitive with alternate crops and provide high-quality hay for ruminant diets, but there are few studies of vetch performance as a livestock feed, or of vetch varietal differences in livestock feeding value. This study evaluated vetch varietal differences in hay nutritive value, ruminal fermentation properties, nutrient digestibility, nitrogen retention and animal performance in fattening lambs consuming a diet comprising 20% vetch. Fifty male Hu lambs with an initial BW of 17.7 ± 0.27 kg and 2–3 months of age were assigned randomly into five groups of 10 lambs, and each allocated one of five dietary treatments for 67 days (10 days of adaptation and a 57 day experimental period). All diets contained 30% maize stover, 50% concentrate, and with a different forage source (on an as-fed basis): 20% alfalfa hay (Control), 20% vetch 333A (C333A) hay, 20% vetch Lanjian No. 1 (CLJ1) hay, 20% vetch Lanjian No. 2 (CLJ2) hay, or 20% vetch Lanjian No. 3 (CLJ3) hay. Hay CLJ3 had greater contents of ash, CP, ether extract, in vitro organic matter digestibility and metabolizable energy, and lower cell wall contents (P 0.05). Compared to the Control diet, the CLJ2 and CLJ3 diets resulted in greater (P 0.05) from the Control diet. No differences (P > 0.05) were observed between dietary treatments with respect to average daily feed intake, ruminal pH, total volatile fatty acid contents and molar proportions of acetate, butyrate, valerate, isobutyrate, and isovalerate, or total tract apparent digestibility of DM, organic matter, and ADF. The feed efficiency of tested feeds ranked CLJ3 = CLJ2 > CLJ1 > Control with C333A intermediate between CLJ1 and Control. In summary, considering hay quality, nutrient digestibility and animal weight gain, performance as a ruminant feed of hays from recently released vetch cultivars Lanjian No. 2 and Lanjian No. 3 was superior to the older cultivar C333A and the alfalfa control.

The American Opportunity Study is an ongoing initiative to build the country’s capacity to access and analyze linked administrative data. It is best viewed as a population-level scaffolding on which other administrative data can then be hung. This scaffolding, if used as a stand-alone resource, will allow for long-run analyses of fundamental population and labor market processes. If combined with data from other sources, it will allow for long-run program evaluation and other experimental and quasi-experimental analyses. We discuss the current status of the American Opportunity Study, its potential to advance the field, remaining obstacles that must be overcome to build it, and how it can work within the guidelines suggested by the Commission on Evidence-Based Policymaking.

There is a growing consumer preference for regional or "terroir" based products (Guy 2011). The designation of American Viticultural Area (AVA) status has the potential to increase the development of consumer identification with regional wine products. The presence of a distinguishing terroir is one of the prerequisites for the establishment of a federally recognized AVA. The Tobacco Tax and Trade Bureau (TTB) granted the Shawnee Hills, located in southern Illinois, this designation at their request in 2006 (MKF 2005). The goal of the present research is to determine the key factors enhancing or constraining the competitive performance of wine businesses in the Shawnee Hills AVA. A winery competitiveness survey was administered to all owner/operators in the Shawnee Hills to determine whether the infrastructure was in place to sustain a regional wine quality program. The specific aim of this survey was to understand key factors influencing the competitive performance of wine businesses in the Shawnee Hills AVA. Shawnee Hill׳s AVA winery owner/operators regard increases in regional tourism, growth in the US wine market continuous innovation, unique services and processes, and flow of information from customers to have the most enhancing effects on their businesses, and that confidence/trust in Illinois state political systems, tax systems, and administrative/bureaucratic regulations were the most constraining factors. Furthermore the Shawnee Hills AVA has growing competition, yet consists of innovative winery owners. It may currently lack external financial support, but with a community focus on product differentiation, the Shawnee Hills AVA has a chance, owners believe, to capture a portion of the growing market for regional products.

American music history textbooks have traditionally covered the entire history of Western music in a single volume. This approach reflects the now dominant teaching methodology at American universities of a multiple-semester survey that covers the breadth of music history from Ancient Greece to modern times. An obvious problem with a broad survey is the lack of depth on issues relevant to current musicological scholarship such as music in society, feminism, archival research, or patronage. As new approaches to teaching music history become more popular in US colleges, in part due to the “pedagogy movement” in American musicology, the canonical status of single-volume history of music is under increased scrutiny and review.

Corn producers frequently have been told that the sugar program provides an important stimulus to corn demand through its positive influence on the high fructose corn syrup sector. In this article we qualify the extent of this support and find it to be very small- not more than 3 cents per bushel, and probably less. Previous studies have overstated this effect due a lack of attention to the interindustry linkages in the sweetener complex.

The American Opportunity Study is an ongoing initiative to build the country's capacity to access and analyze linked administrative data. It is best viewed as a population-level scaffolding on which other administrative data can then be hung. This scaffolding, if used as a stand-alone resource, will allow for long-run analyses of fundamental population and labor market processes. If combined with data from other sources, it will allow for long-run program evaluation and other experimental and quasi-experimental analyses. We discuss the current status of the American Opportunity Study, its potential to advance the field, remaining obstacles that must be overcome to build it, and how it can work within the guidelines suggested by the Commission on Evidence-Based Policymaking.