Effect of Cristobalite on the Strength of Sintered Fused Silica Above and Below the Cristobalite Transformation

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/111203/1/jace13505.pd

Kinetics of Cristobalite Formation in Sintered Silica

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/107495/1/jace12889.pd

Methotrexate-induced cutaneous ulceration in patients with erythrodermic mycosis fungoides

Methotrexate-induced cutaneous ulceration has rarely been reported in patients with mycosis fungoides. We report 4 patients with mycosis fungoides who developed cutaneous ulceration as an initial manifestation of methotrexate toxicity. Methotrexate dose at the time of ulceration ranged from 10–60 mg. All 4 patients were erythrodermic, which may have predisposed them to this toxic effect. It is important to recognize cutaneous ulceration as an uncommon, but potentially serious, side effect of methotrexate in these patients, and to differentiate it from ulceration due to progressive lymphoma

Analytical and Numerical Models for Wind and Seismic Design and Assessment of Mass Timber Diaphragms

While the use of cross-laminated timber (CLT) panels for building construction has increased over the last several decades, current standards and existing literature provide limited information regarding the design of CLT diaphragms or the prediction of their deflections when subjected to wind and strong earthquake motions. This paper presents the design and assessment of a CLT diaphragm that was part of a full-scale two-story structure subjected to shake-table testing. An analytical model is proposed for diaphragm deflection accounting for in-plane shear and bending stiffness, as well as the stiffness of various connections. Moreover, a refined numerical modeling strategy is proposed in order to consider phenomena such as panel-to-panel gap closure. Results indicate that the analytical model yields conservative results both in terms of deflections and forces when compared to the numerical model that simulates similar sources of strength and stiffness. The analytical model is suitable for the design of symmetric diaphragms with regular shapes, whereas the numerical model can also be used to model asymmetric diaphragms with irregular shapes

Selective Phosphorylation Modulates the PIP2 Sensitivity of the CaM-SK Channel Complex

Phosphatidylinositol bisphosphate (PIP2) regulates the activities of many membrane proteins including ion channels through direct interactions. However, the affinity of PIP2 is so high for some channel proteins that its physiological role as a modulator has been questioned. Here we show that PIP2 is an important cofactor for activation of small conductance Ca2+-activated potassium channels (SK) by Ca2+-bound calmodulin (CaM). Removal of the endogenous PIP2 inhibits SK channels. The PIP2-binding site resides at the interface of CaM and the SK C-terminus. We further demonstrate that the affinity of PIP2 for its target proteins can be regulated by cellular signaling. Phosphorylation of CaM T79, located adjacent to the PIP2-binding site, by Casein Kinase 2 reduces the affinity of PIP2 for the CaM-SK channel complex by altering the dynamic interactions among amino acid residues surrounding the PIP2-binding site. This effect of CaM phosphorylation promotes greater channel inhibition by G-protein-mediated hydrolysis of PIP2

Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p<0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (<1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (<1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

Stress Development and Fracture of Surface Nucleated Cristobalite on Silica Glass

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/109580/1/jace13181.pd

Long-term effects of total skin electron beam therapy for mycosis fungoides on hair and nail loss and regrowth

Objective To better document the risk of permanent hair and nail loss after total skin electron beam therapy (TSEBT) for mycosis fungoides (MF). Methods Interviews and evaluations were conducted in 13 patients with MF treated with TSEBT alone and two patients treated with concomitant TSEBT and chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP). Evaluated parameters included time to hair and nail loss and regrowth, the density of hair regrowth, and quality of hair and nail regrowth. Results Most patients had complete loss of scalp hair during treatment, and new growth appeared about 2 months following treatment completion. After 18 months, most patients felt their hair had regrown to about 70% of baseline thickness without cosmetically obvious alopecia. The patients treated with TSEBT and concomitant chemotherapy had substantially less scalp hair regrowth with persistent cosmetically obvious alopecia. Some lost eyebrows and eyelashes, but complete or near-complete regrowth generally occurred. Most patients lost their nails following TSEBT, with complete regrowth noted by most patients 5 months after treatment. New nails were most often normal, but a few patients developed post-therapy nail dystrophies. Conclusion This data can be used to better inform patients of likely long-term changes of hair and nails following TSEBT

The Children\u27s Oncology Group Radiation Oncology Discipline: 15 Years of Contributions to the Treatment of Childhood Cancer

PURPOSE: Our aim was to review the advances in radiation therapy for the management of pediatric cancers made by the Children\u27s Oncology Group (COG) radiation oncology discipline since its inception in 2000. METHODS AND MATERIALS: The various radiation oncology disease site leaders reviewed the contributions and advances in pediatric oncology made through the work of the COG. They have presented outcomes of relevant studies and summarized current treatment policies developed by consensus from experts in the field. RESULTS: The indications and techniques for pediatric radiation therapy have evolved considerably over the years for virtually all pediatric tumor types, resulting in improved cure rates together with the potential for decreased treatment-related morbidity and mortality. CONCLUSIONS: The COG radiation oncology discipline has made significant contributions toward the treatment of childhood cancer. Our discipline is committed to continuing research to refine and modernize the use of radiation therapy in current and future protocols with the goal of further improving the cure rates and quality of life of children with cancer