Characterizing HMX/AP Cocrystal Propellant Through Planar Laser Induced Fluorescence

Energetic cocrystals, or energetic materials that consist of two or more components that form a unique crystalline structure with unique properties, are currently being investigated as a possible method for decreasing the sensitivity of high energy density explosives for use in powerful solid composite propellants. Fuels more powerful than those in current use have not been practical because of their increased safety hazard due to higher sensitivity to being ignited. This has been one of the barriers that has prevented solid composite propellants from seeing significant improvements in performance. This study is an attempt to characterize a cocrystal of HMX and ammonium perchlorate (AP) of 2:3 molar mass ratio. The cocrystal was compared to the equivalent physical mix and baseline propellants of HMX and AP. Planar laser induced fluorescence (PLIF) was performed to measure hydroxyl (OH) concentrations in the propellants’ flames. It appeared that the flame structure of the cocrystal was very similar to that of HMX, as well as the distribution of OH concentrations around the flame. The results were inconclusive, and it is believed that the cocrystal’s constituents were not sufficiently bonded at the molecular level; thus, the cocrystal was instead more a mixture of smaller individual crystals of HMX and AP. Future research could include cocrystals created by varying methods, and perform cyano (CN) PLIF to characterize these cocrystals, which may display a better defined region of interest in the flame that can be more closely studied and answer more questions

Olanzapine for the Prevention of Chemotherapy-Induced Nausea and Vomiting

BACKGROUND We examined the efficacy of olanzapine for the prevention of nausea and vomiting in patients receiving highly emetogenic chemotherapy. METHODS In a randomized, double-blind, phase 3 trial, we compared olanzapine with placebo, in combination with dexamethasone, aprepitant or fosaprepitant, and a 5-hydroxytryptamine type 3–receptor antagonist, in patients with no previous chemotherapy who were receiving cisplatin (≥70 mg per square meter of body-surface area) or cyclophosphamide–doxorubicin. The doses of the three concomitant drugs administered before and after chemotherapy were similar in the two groups. The two groups received either 10 mg of olanzapine orally or matching placebo daily on days 1 through 4. Nausea prevention was the primary end point; a complete response (no emesis and no use of rescue medication) was a secondary end point. RESULTS In the analysis, we included 380 patients who could be evaluated (192 assigned to olanzapine, and 188 to placebo). The proportion of patients with no chemotherapy-induced nausea was significantly greater with olanzapine than with placebo in the first 24 hours after chemotherapy (74% vs. 45%, P = 0.002), the period from 25 to 120 hours after chemotherapy (42% vs. 25%, P = 0.002), and the overall 120-hour period (37% vs. 22%, P = 0.002). The complete-response rate was also significantly increased with olanzapine during the three periods: 86% versus 65% (P<0.001), 67% versus 52% (P = 0.007), and 64% versus 41% (P<0.001), respectively. Although there were no grade 5 toxic effects, some patients receiving olanzapine had increased sedation (severe in 5%) on day 2. CONCLUSIONS Olanzapine, as compared with placebo, significantly improved nausea prevention, as well as the complete-response rate, among previously untreated patients who were receiving highly emetogenic chemotherapy. (Funded by the National Cancer Institute; ClinicalTrials.gov number, NCT02116530.

Australian forested wetlands under climate change:Collapse or proliferation?

Climatically driven perturbations (e.g. intense drought, fire, sea surface temperature rise) can bring ecosystems that are already stressed by long-term climate change and other anthropogenic impacts to a point of collapse. Recent reviews of the responses of Australian ecosystems to climate change and associated stressors have suggested widespread ecosystem collapse is occurring across multiple biomes. Two commonly cited case studies concern forested wetland ecosystems: mangrove forest dieback in northern Australia (2015-16) and riverine forest dieback in the south-east of the continent (2002-09). We present an alternative interpretation that emphasises the dominant signal of climate change effects, rather than the interdecadal signal of climate variability that drives wetland forest dynamics. For both the south-east Australian riverine forests and mangroves of northern Australia, aerial extent remains greater after dieback than in the early 1990s. We interpret dieback and defoliation in both systems as a dry phase response and provide evidence of a current and near-future climate change trajectory of increased areal extent and cover (i.e. tree colonisation and range infilling). In both case studies, climate change-driven increases in tree cover and extent are occurring at the expense of wetland grasslands and the important ecosystem functions they support

New directions in cellular therapy of cancer: a summary of the summit on cellular therapy for cancer

A summit on cellular therapy for cancer discussed and presented advances related to the use of adoptive cellular therapy for melanoma and other cancers. The summit revealed that this field is advancing rapidly. Conventional cellular therapies, such as tumor infiltrating lymphocytes (TIL), are becoming more effective and more available. Gene therapy is becoming an important tool in adoptive cell therapy. Lymphocytes are being engineered to express high affinity T cell receptors (TCRs), chimeric antibody-T cell receptors (CARs) and cytokines. T cell subsets with more naïve and stem cell-like characteristics have been shown in pre-clinical models to be more effective than unselected populations and it is now possible to reprogram T cells and to produce T cells with stem cell characteristics. In the future, combinations of adoptive transfer of T cells and specific vaccination against the cognate antigen can be envisaged to further enhance the effectiveness of these therapies

A General Framework of Bound States in the Continuum in an Open Acoustic Resonator

Bound states in the continuum (BICs) provide a viable way of achieving high-Q resonances in both photonics and acoustics. In this work, we proposed a general method of constructing Friedrich-Wintgen (FW) BICs and accidental BICs in a coupled acoustic waveguide-resonator system. We demonstrated that FW BICs can be achieved with arbitrary two degenerate resonances in a closed resonator regardless of whether they have the same or opposite parity. Moreover, their eigenmode profiles can be arbitrarily engineered by adjusting the position of attached waveguide. That suggests an effective way of continuous switching the nature of BIC from FW BIC to symmetry-protected BIC or accidental BICs. Also, such BICs are sustained in the coupled waveguide-resonator system with shapes such as rectangle, ellipse, and rhomboid. These interesting phenomena are well explained by the two-level effective non Hermitian Hamiltonian, where two strongly coupled degenerate modes play a major role in forming such FW BICs. Besides, we found that such an open system also supports accidental BICs in geometry space instead of momentum space via tuning the position of attached waveguide, which are attributed to the quenched coupling between the waveguide and eigenmodes of the closed cavity. Finally, we fabricated a series of 3D coupled-resonator-waveguide and experimentally verified the existence of FW BICs and accidental BICs by measuring the transmission spectra. Our results complement the current BIC library in acoustics and provide new routes for designing novel acoustic devices, such as in acoustic absorbers, filters and sensors.Comment: 20 pages, 6 figure

24-Month Overall Survival from KEYNOTE-021 Cohort G: Pemetrexed and Carboplatin with or without Pembrolizumab as First-Line Therapy for Advanced Nonsquamous Non–Small Cell Lung Cancer

Introduction Cohort G of KEYNOTE-021 (NCT02039674) evaluated the efficacy and safety of pembrolizumab plus pemetrexed-carboplatin (PC) versus PC alone as first-line therapy for advanced nonsquamous NSCLC. At the primary analysis (median follow-up time 10.6 months), pembrolizumab significantly improved objective response rate (ORR) and progression-free survival (PFS); the hazard ratio (HR) for overall survival (OS) was 0.90 (95% confidence interval [CI]: 0.42‒1.91). Herein, we present an updated analysis. Methods A total of 123 patients with previously untreated stage IIIB/IV nonsquamous NSCLC without EGFR and/or ALK receptor tyrosine kinase gene (ALK) aberrations were randomized 1:1 to four cycles of PC with or without pembrolizumab, 200 mg every 3 weeks. Pembrolizumab treatment continued for 2 years; maintenance pemetrexed was permitted in both groups. Eligible patients in the PC-alone group with radiologic progression could cross over to pembrolizumab monotherapy. p Values are nominal (one-sided p < 0.025). Results As of December 1, 2017, the median follow-up time was 23.9 months. The ORR was 56.7% with pembrolizumab plus PC versus 30.2% with PC alone (estimated difference 26.4% [95% CI: 8.9%‒42.4%, p = 0.0016]). PFS was significantly improved with pembrolizumab plus PC versus PC alone (HR = 0.53, 95% CI: 0.33‒0.86, p = 0.0049). A total of 41 patients in the PC-alone group received subsequent anti‒programmed death 1/anti‒programmed death ligand 1 therapy. The HR for OS was 0.56 (95% CI: 0.32‒0.95, p = 0.0151). Forty-one percent of patients in the pembrolizumab plus PC group and 27% in the PC-alone group had grade 3 to 5 treatment-related adverse events. Conclusions The significant improvements in PFS and ORR with pembrolizumab plus PC versus PC alone observed in the primary analysis were maintained, and the HR for OS with a 24-month median follow-up was 0.56, favoring pembrolizumab plus PC

Systematic review of communication technologies to promote access and engagement of young people with diabetes into healthcare

Background: Research has investigated whether communication technologies (e.g. mobile telephony, forums, email) can be used to transfer digital information between healthcare professionals and young people who live with diabetes. The systematic review evaluates the effectiveness and impact of these technologies on communication. Methods: Nine electronic databases were searched. Technologies were described and a narrative synthesis of all studies was undertaken. Results: Of 20,925 publications identified, 19 met the inclusion criteria, with 18 technologies assessed. Five categories of communication technologies were identified: video-and tele-conferencing (n = 2); mobile telephony (n = 3); telephone support (n = 3); novel electronic communication devices for transferring clinical information (n = 10); and web-based discussion boards (n = 1). Ten studies showed a positive improvement in HbA1c following the intervention with four studies reporting detrimental increases in HbA1c levels. In fifteen studies communication technologies increased the frequency of contact between patient and healthcare professional. Findings were inconsistent of an association between improvements in HbA1c and increased contact. Limited evidence was available concerning behavioural and care coordination outcomes, although improvement in quality of life, patientcaregiver interaction, self-care and metabolic transmission were reported for some communication technologies. Conclusions: The breadth of study design and types of technologies reported make the magnitude of benefit and their effects on health difficult to determine. While communication technologies may increase the frequency of contact between patient and health care professional, it remains unclear whether this results in improved outcomes and is often the basis of the intervention itself. Further research is needed to explore the effectiveness and cost effectiveness of increasing the use of communication technologies between young people and healthcare professionals

Protocol for the Foot in Juvenile Idiopathic Arthritis trial (FiJIA): a randomised controlled trial of an integrated foot care programme for foot problems in JIA

&lt;b&gt;Background&lt;/b&gt;: Foot and ankle problems are a common but relatively neglected manifestation of juvenile idiopathic arthritis. Studies of medical and non-medical interventions have shown that clinical outcome measures can be improved. However existing data has been drawn from small non-randomised clinical studies of single interventions that appear to under-represent the adult population suffering from juvenile idiopathic arthritis. To date, no evidence of combined therapies or integrated care for juvenile idiopathic arthritis patients with foot and ankle problems exists. &lt;b&gt;Methods/design&lt;/b&gt;: An exploratory phase II non-pharmacological randomised controlled trial where patients including young children, adolescents and adults with juvenile idiopathic arthritis and associated foot/ankle problems will be randomised to receive integrated podiatric care via a new foot care programme, or to receive standard podiatry care. Sixty patients (30 in each arm) including children, adolescents and adults diagnosed with juvenile idiopathic arthritis who satisfy the inclusion and exclusion criteria will be recruited from 2 outpatient centres of paediatric and adult rheumatology respectively. Participants will be randomised by process of minimisation using the Minim software package. The primary outcome measure is the foot related impairment measured by the Juvenile Arthritis Disability Index questionnaire's impairment domain at 6 and 12 months, with secondary outcomes including disease activity score, foot deformity score, active/limited foot joint counts, spatio-temporal and plantar-pressure gait parameters, health related quality of life and semi-quantitative ultrasonography score for inflammatory foot lesions. The new foot care programme will comprise rapid assessment and investigation, targeted treatment, with detailed outcome assessment and follow-up at minimum intervals of 3 months. Data will be collected at baseline, 6 months and 12 months from baseline. Intention to treat data analysis will be conducted. A full health economic evaluation will be conducted alongside the trial and will evaluate the cost effectiveness of the intervention. This will consider the cost per improvement in Juvenile Arthritis Disability Index, and cost per quality adjusted life year gained. In addition, a discrete choice experiment will elicit willingness to pay values and a cost benefit analysis will also be undertaken

Surgical-pathological findings in type 1 and 2 endometrial cancer: An NRG Oncology/Gynecologic Oncology Group study on GOG-210 protocol

To report clinical and pathologic relationships with disease spread in endometrial cancer patients

Red clover (Trifolium pratense L.) draft genome provides a platform for trait improvement

Red clover (Trifolium pratense L.) is a globally significant forage legume in pastoral livestock farming systems. It is an attractive component of grassland farming, because of its high yield and protein content, nutritional value and ability to fix atmospheric nitrogen. Enhancing its role further in sustainable agriculture requires genetic improvement of persistency, disease resistance, and tolerance to grazing. To help address these challenges, we have assembled a chromosome-scale reference genome for red clover. We observed large blocks of conserved synteny with Medicago truncatula and estimated that the two species diverged ~23 million years ago. Among the 40,868 annotated genes, we identified gene clusters involved in biochemical pathways of importance for forage quality and livestock nutrition. Genotyping by sequencing of a synthetic population of 86 genotypes show that the number of markers required for genomics-based breeding approaches is tractable, making red clover a suitable candidate for association studies and genomic selection