Thermal Studies of Butadiene-Acrylonitrile Copolymers

Abstract Not Provided

Medical treatment of Cushing’s disease: Overview and recent findings

Cushing’s disease, due to pituitary adrenocorticotropic hormone (ACTH) hypersecretion, is the most common etiology of spontaneous excess cortisol production. The majority of pituitary tumors causing Cushing’s disease measure <1 cm and the excess morbidity associated with these tumors is mostly due to the effects of elevated, nonsuppressible, ACTH levels leading to adrenal steroid hypersecretion. Elevated circulating cortisol levels lead to abnormal fat deposition, hypertension, diabetes, coronary artery disease, osteoporosis, muscle weakness and psychological disturbances. At experienced centers, initial surgical remission rate via transnasal, transphenoidal resection approaches 80% for tumors less than 1 cm, but may be as low as 30% for larger lesions and long-term recurrence in all groups approaches 25%. Residual disease may be managed with more radical surgery, pituitary-directed radiation, bilateral adrenalectomy, or medical therapy. This paper addresses current and novel therapies in various stages of development for Cushing’s disease

Modulation of interleukin 2 high affinity binding to human T cells by a pyrimidodiazepine insect metabolite

AbstractAn insect metabolite containing the little known pyrimido[4,5-b][l,4]diazepine ring system has been found to act as an effective mimic of tetrahydrobiopterin in its ability to modulate the affinity of interleukin 2 (IL-2) for its receptors on human T cells. Semi-empirical molecular orbital calculations reveal that while tetrahydrobiopterin has considerable flexibility, the pyrimidodiazepine has rather few conformational options and offers a useful model for exploring the nature of the pterin binding site

Residual Tumor Confers a 10-Fold Increased Risk of Regrowth in Clinically Nonfunctioning Pituitary Tumors.

ObjectiveWe evaluated tumor recurrence and regrowth rates following endoscopic transnasal transsphenoidal (TNTS) surgical removal in a consecutive series of clinically nonfunctioning pituitary adenomas (CNFTs).DesignRetrospective chart review of clinical, biochemical, and sellar MRI findings in all TNTS surgeries in patients with CNFT, performed by a single surgeon, between 2008 and 2015 (n = 280).PatientsNinety-three patients met eligibility criteria, with complete clinical, biochemical, and imaging follow-up for a 3-year minimum.ResultsOf 85 patients who were not irradiated, 3-month postsurgical MRI demonstrated no residual tumor in 58 of 85 (68.2%), equivocal findings in 12 of 85 (14.1%), and definite residual tumor in 15 of 85 (17.6%) patients. Six of 85 (7.1%) demonstrated tumor regrowth by 3 years, and 2 further patients demonstrated true tumor recurrence at 3 and 6 years after surgery, respectively, for a total recurrence rate of 9.4% (8 of 85). Eight of the 93 patients were irradiated between 3 months and 4 years after pituitary surgery. In 3 patients with tumor regrowth, 2 exhibited residual tumor and 1 had no residual findings at the 3-month postoperative imaging. Overall, Ki-67 labeling index or Knosp grading did not predict recurrence.ConclusionTumor recurrence at 3 years was low (1 of 58; 1.7%) if the 3-month postoperative MRI showed no residual tumor. The findings support a less frequent imaging schedule for this group. Patients with definite residual tumor visible at 3 months harbor the greatest risk for tumor growth, but regrowth does not occur in all patients (6 of 15; 40%)

Fructose impairs glucose-induced hepatic triglyceride synthesis

Obesity, type 2 diabetes and hyperlipidemia frequently coexist and are associated with significantly increased morbidity and mortality. Consumption of refined carbohydrate and particularly fructose has increased significantly in recent years and has paralled the increased incidence of obesity and diabetes. Human and animal studies have demonstrated that high dietary fructose intake positively correlates with increased dyslipidemia, insulin resistance, and hypertension. Metabolism of fructose occurs primarily in the liver and high fructose flux leads to enhanced hepatic triglyceride accumulation (hepatic steatosis). This results in impaired glucose and lipid metabolism and increased proinflammatory cytokine expression. Here we demonstrate that fructose alters glucose-stimulated expression of activated acetyl CoA carboxylase (ACC), pSer hormone sensitive lipase (pSerHSL) and adipose triglyceride lipase (ATGL) in hepatic HepG2 or primary hepatic cell cultures in vitro. This was associated with increased de novo triglyceride synthesis in vitro and hepatic steatosis in vivo in fructose- versus glucose-fed and standard-diet fed mice. These studies provide novel insight into the mechanisms involved in fructose-mediated hepatic hypertriglyceridemia and identify fructose-uptake as a new potential therapeutic target for lipid-associated diseases

Overview of Game and Content Design for a Mobile Game that Will Prepare Students in Calculus and Physics Prerequisites to the Engineering Curriculum

As part of a research project which assists veterans as they exit the military, complete engineering degrees, and enter the workforce as engineering professionals, a range of serious games for Science, Technology, Engineering, and Mathematics (STEM) education is under development. The current focus of this development is CAPTIVATE, a serious game to assist student veterans in mastering the calculus and physics skills that are necessary prerequisites to the main engineering curriculum. Building on the development and lessons learned from MAVEN, a game developed previously to help student veterans master precalculus skills, the design and initial implementation for CAPTIVATE involves careful consideration regarding game and instructional design. Many of the positive aspects from the design of MAVEN will be implemented in CAPTIVATE. First, the overall framework developed for MAVEN will be reused in CAPTIVATE. This modular framework involves both a model and process that combine game, instructional, and software design in a way that supports adaptability throughout the design and development cycle. Additionally by embedding concepts in game play similar to well-known board games such as Battleship, computer games such as Minesweeper, and console or mobile games such as Guitar Hero, students will use their calculus and physics skills to complete tasks in a familiar environment. In addition, the game itself will consist of a series of sub-games each focusing on a topic that students traditionally struggle to understand. Furthermore, students will be offered access to learning resources and assessed regularly as they progress through the game. CAPTIVATE will also overcome some shortcomings from the previous development. While MAVEN was developed for desktop deployment, CAPTIVATE is targeted for deployment on a variety of mobile device including Apple and Android phones and tablets to engage students in interactive games that support their endeavor to build a solid foundation in mathematics and science topics. Additionally by creating games that are short and easily accessible, students will be able to engage with the material at a time and place convenient for them. The development of CAPTIVATE supports student veterans as they transition from the military to engineering degree programs and helps to accelerate them through their STEM prerequisite courses

A Pilot Program For The Recruitment and Education of Navy Veterans Based on System-Level Technical Expertise and Leadership Maturation Developed During Service

The project, Stern2STEM, aims to advance STEM (Science, Technology, Engineering, and Mathematics) education through the preparation of student veterans to pursue baccalaureate STEM degrees and support the re-employment of these veterans into the Department of Defense (DoD) and the wider defense support industry. The program builds on the training that veterans have received in highly skilled technical areas, both in the classroom and “on-the-job”, to develop system level expertise in their respective technical disciplines. Key components of the program include: (1) establishing a mechanism for outreach and recruitment; (2) providing leveling, tutoring, mentoring, and support for students; (3) teaching and learning through proven pedagogical practices and through sound academic advising; (4) partnering with the DoD community to facilitate student career placement in the DoD STEM workforce; (5) providing workforce development for DoD STEM professionals. This paper will discuss the academic challenges that student veterans face while in higher education and the current STEM pipelines as students move through their college to professional careers. The early impact of academic tutoring, professional advising, mentorship, career placement, and recruitment of current service members into STEM disciplines through involvement with Stern2STEM will be discussed. Through Stern2STEM’s systematic interventions, the project has the potential to have a significant impact on the broader STEM education community as many of the principles, lessons learned, and tools developed will prove valuable for institutions which have a large population of student veterans

Response comparison of multiple myeloma and monoclonal gammopathy of undetermined significance to the same anti-myeloma therapy: a retrospective cohort study

BackgroundMultiple myeloma is consistently preceded by monoclonal gammopathy of undetermined significance (MGUS), which is usually only treated by a form of anti-multiple myeloma therapy if it is causing substantial disease through deposition of secreted M proteins. However, studies comparing how MGUS and multiple myeloma plasma cell clones respond to these therapies are scarce. Biclonal gammopathy multiple myeloma is characterised by the coexistence of an active multiple myeloma clone and a benign MGUS clone, and thus provides a unique model to assess the responses of separate clones to the same anti-multiple myeloma therapy, in the same patient, at the same time. We aimed to identify how MGUS and multiple myeloma plasma cell clones responded to anti-multiple myeloma therapy in patients newly diagnosed with biclonal gammopathy multiple myeloma.MethodsIn this retrospective cohort study, we identified patients with biclonal gammopathy multiple myeloma by central laboratory analysis of 6399 newly diagnosed patients with multiple myeloma enrolled in three UK clinical trials (Myeloma IX, Myeloma XI, and TEAMM) between July 7, 2004, and June 2, 2015. In addition to the inclusion criteria of these trials, our study necessitated at trial entry the presence of two distinct M proteins in immunofixation electrophoresis. The primary endpoint was difference in response achieved with anti-multiple myeloma therapy on MGUS (which we defined as M2) and multiple myeloma (M1) clones—overall, within patients, and between therapy types—with international therapy response criteria assessed with χ2 analyses. We analysed by intention to treat.Findings44 patients with biclonal gammopathy multiple myeloma with IgG or IgA MGUS clones were subsequently identified from the three trials and then longitudinally monitored. 41 (93%) of M1 clones had a response to therapy (either complete response, very good partial response, partial response, or minor response) compared with only 28 (64%) of M2 clones (p=0·0010). For the 20 patients who received intensive therapy, there was no difference between the proportion of responding clones in M1 (19 [95%]) and M2 (15 [75%], p=0·13). However, for the 17 patients who received non-intensive therapy, 16 (94%) of M1 clones had a response compared with ten [59%] of M2 clones (p=0·031). When examining clones within the same patient, 30 (68%) of 44 individual patients had different levels of responses within the M1 and M2 clones. One patient exhibited M2 progression to myeloma and subsequently died.InterpretationThese results show that, in patients with biclonal gammopathy multiple myeloma, anti-multiple myeloma therapies exert a greater depth of response against multiple myeloma plasma cell clones than MGUS plasma cell clones. Although some MGUS clones exhibited a complete response, many did not respond, which suggests that the underlying features that render multiple myeloma plasma cells susceptible to therapy are present in only some MGUS plasma cell clones. To determine MGUS clone susceptibly to therapy, future studies might seek to identify, with biclonal gammopathy multiple myeloma as an investigative model, the genetic and epigenetic alterations that affect whether MGUS plasma cell clones are responsive to anti-multiple myeloma therapy