Grain-refining heat treatments to improve cryogenic toughness of high-strength steels

The development of two high Reynolds number wind tunnels at NASA Langley Research Center which operate at cryogenic temperatures with high dynamic pressures has imposed severe requirements on materials for model construction. Existing commercial high strength steels lack sufficient toughness to permit their safe use at temperatures approaching that of liquid nitrogen (-320 F). Therefore, a program to improve the cryogenic toughness of commercial high strength steels was conducted. Significant improvement in the cryogenic toughness of commercial high strength martensitic and maraging steels was demonstrated through the use of grain refining heat treatments. Charpy impact strength at -320 F was increased by 50 to 180 percent for the various alloys without significant loss in tensile strength. The grain sizes of the 9 percent Ni-Co alloys and 200 grade maraging steels were reduced to 1/10 of the original size or smaller, with the added benefit of improved machinability. This grain refining technique should permit these alloys with ultimate strengths of 220 to 270 ksi to receive consideration for cryogenic service

Initial investigation of cryogenic wind tunnel model filler materials

Various filler materials are being investigated for applicability to cryogenic wind tunnel models. The filler materials will be used to fill surface grooves, holes and flaws. The severe test environment of cryogenic models precludes usage of filler materials used on conventional wind tunnel models. Coefficients of thermal expansion, finishing characteristics, adhesion and stability of several candidate filler materials were examined. Promising filler materials are identified

Narcotic administration and fall-related injury in the hospital: Implications for patient safety programs and providers

Objective: Identify factors that predict fall-related injury in hospitalized adults. Design: Retrospective cohort study. Setting: 435-bed university hospital. Participants: Inpatients with reported falls in 2010. Results: Medical records were available for 286/293 (98%) of reported falls in 251 patients. 25% (63/286) of falls were associated with injury, 4% (11/286) with serious injury. Compared to all fallers, patients with injury did not differ by gender or age. In univariate analysis, patients who reported hitting their head, had pre-fall confusion, or who received narcotics within 24 hours before falling were more likely to suffer injury (estimated odds ratios 6.04, 2.00 and 5.1, respectfully). In multivariate analysis, receiving a narcotic prior to falling was the strongest predictor of injury (estimated odds ratio 5.59; 95% confidence intervals 2.14 — 14.65, p \u3c0.001). Conclusions: In this single-institution study, 25% of patients who fell suffered injury and 4% serious injury. Neither age nor gender predicted fall-related injury. Recent narcotic administration was the strongest predictor of injury. Strategies to prevent fall-related injury in the hospital should target patients receiving narcotics. When evaluating inpatients who have fallen, providers should be especially vigilant about injury in patients who have pre-fall confusion, hit their head, or have received recent narcotics

Antigen depot is not required for alum adjuvanticity

Alum adjuvants have been in continuous clinical use for more than 80 yr. While the prevailing theory has been that depot formation and the associated slow release of antigen and/or inflammation are responsible for alum enhancement of antigen presentation and subsequent T- and B-cell responses, this has never been formally proven. To examine antigen persistence, we used the chimeric fluorescent protein EαGFP, which allows assessment of antigen presentation in situ, using the Y-Ae antibody. We demonstrate that alum and/or CpG adjuvants induced similar uptake of antigen, and in all cases, GFP signal did not persist beyond 24 h in draining lymph node antigen-presenting cells. Antigen presentation was first detectable on B cells within 6–12 h of antigen administration, followed by conventional dendritic cells (DCs) at 12–24 h, then finally plasmacytoid DCs at 48 h or later. Again, alum and/or CpG adjuvants did not have an effect on the magnitude or sequence of this response; furthermore, they induced similar antigen-specific T-cell activation in vivo. Notably, removal of the injection site and associated alum depot, as early as 2 h after administration, had no appreciable effect on antigen-specific T- and B-cell responses. This study clearly rules out a role for depot formation in alum adjuvant activity

Aminophobanes:hydrolytic stability, tautomerism and application in Cr-catalysed ethene oligomerisation

The bicyclic aminophobanes have significantly different chemistry from their acyclic analogues Cy2PNHR′.</p

A local infrared perspective to deeper ISO surveys

We present new techniques to produce IRAS 12 micron samples of galaxies andstars. We show that previous IRAS 12 micron samples are incompatible fordetailed comparison with ISO surveys and review their problems. We provide astellar infrared diagnostic diagram to distinguish galaxies from stars withoutusing longer wavelength IRAS colour criteria and produce complete 12 micronsamples of galaxies and stars. This new technique allows us to estimate thecontribution of non-dusty galaxies to the IRAS 12 micron counts and produce atrue local mid-infrared extragalactic sample compatible with ISO surveys. Wepresent our initial analysis and results

Mucosal Application of gp140 Encoding DNA Polyplexes to Different Tissues Results in Altered Immunological Outcomes in Mice

Increasing evidence suggests that mucosally targeted vaccines will enhance local humoral and cellular responses whilst still eliciting systemic immunity. We therefore investigated the capacity of nasal, sublingual or vaginal delivery of DNA-PEI polyplexes to prime immune responses prior to mucosal protein boost vaccination. Using a plasmid expressing the model antigen HIV CN54gp140 we show that each of these mucosal surfaces were permissive for DNA priming and production of antigen-specific antibody responses. The elicitation of systemic immune responses using nasally delivered polyplexed DNA followed by recombinant protein boost vaccination was equivalent to a systemic prime-boost regimen, but the mucosally applied modality had the advantage in that significant levels of antigen-specific IgA were detected in vaginal mucosal secretions. Moreover, mucosal vaccination elicited both local and systemic antigen-specific IgG(+) and IgA(+) antibody secreting cells. Finally, using an Influenza challenge model we found that a nasal or sublingual, but not vaginal, DNA prime/protein boost regimen protected against infectious challenge. These data demonstrate that mucosally applied plasmid DNA complexed to PEI followed by a mucosal protein boost generates sufficient antigen-specific humoral antibody production to protect from mucosal viral challenge

Outcomes of the 2019 Novel Coronavirus in patients with or without a history of cancer - a multi-centre North London experience

© The Author(s) 2020. This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).Background Four months after the first known case of the 2019 novel coronavirus disease (COVID-19), on the 11th March 2020, the WHO declared the outbreak a pandemic and acknowledged the potential to overwhelm national healthcare systems. The high prevalence and associated healthcare, social and economic challenges of COVID-19 suggest this pandemic is likely to have a major impact on cancer management, and has been shown to potentially have worse outcomes in this cohort of vulnerable patients (1). This study aims to compare the outcomes of reverse transcriptase polymerase chain reaction (RT-PCR) confirmed COVID-19 positive disease in patients with or without a history of cancer. Method: We retrospectively collected clinical, pathological and radiological characteristics and outcomes of COVID-19 RT-PCR positive cancer patients treated consecutively in four different North London hospitals (cohort A). Outcomes recorded included morbidity, mortality and length of hospital stay. All clinically relevant outcomes were then compared to consecutively admitted COVID-19 positive patients, without a history of cancer (cohort B), treated at the primary centre during the same time period (12th March- 7th April 2020). Results: A total of 52 electronic patient records during the study time period were reviewed. Cohort A (median age 76 years, 56% males) and cohort B (median age 58 years, 62% male) comprised of 26 patients each. With the exclusion of cancer, both had a median of 2 comorbidities. Within cohort A, the most frequent underlying cancer was colorectal (5/26) and prostate cancer (5/26), and 77% of patients in Cohort A had received previous anti-cancer therapy. The most common presenting symptoms were cough and pyrexia in both cohorts. Frequent laboratory findings included lymphopenia, anaemia and elevated CRP in both cohorts, whilst hypokalaemia, hypoalbuminaemia and hypoproteinaemia was predominantly seen amongst patients with cancer. Median duration of admission was 7 days in both cohorts. The mortality rate was the same in both cohorts (23%), with median age of mortality of 80 years. Of cancer patients who died, all were advanced stage, had been treated with palliative intent and had received anti-cancer therapy within 13 days of admission. Conclusion: Old age, late stage of cancer diagnosis and multiple co-morbidities adversely influence the outcome of patients with COVID-19 positive patients. Whilst extra caution is warranted in the administration of anti-cancer therapies pertaining to the risk of immune-suppression, this data does not demonstrate a higher risk to cancer patients compared to their non-cancer counterparts.Peer reviewedFinal Published versio

Effect of Pimobendan in Dogs with Preclinical Myxomatous Mitral Valve Disease and Cardiomegaly: The EPIC Study - A Randomized Clinical Trial

Background: Pimobendan is effective in treatment of dogs with congestive heart failure (CHF) secondary to myxomatous mitral valve disease (MMVD). Its effect on dogs before the onset of CHF is unknown. Hypothesis/Objectives: Administration of pimobendan (0.4-0.6 mg/kg/d in divided doses) to dogs with increased heart size secondary to preclinical MMVD, not receiving other cardiovascular medications, will delay the onset of signs of CHF, cardiac-related death, or euthanasia. Animals: 360 client-owned dogs with MMVD with left atrial-to-aortic ratio >= 1.6, normalized left ventricular internal diameter in diastole >= 1.7, and vertebral heart sum >10.5. Methods: Prospective, randomized, placebo-controlled, blinded, multicenter clinical trial. Primary outcome variable was time to a composite of the onset of CHF, cardiac-related death, or euthanasia. Results: Median time to primary endpoint was 1228 days (95% CI: 856-NA) in the pimobendan group and 766 days (95% CI: 667-875) in the placebo group (P = .0038). Hazard ratio for the pimobendan group was 0.64 (95% CI: 0.47-0.87) compared with the placebo group. The benefit persisted after adjustment for other variables. Adverse events were not different between treatment groups. Dogs in the pimobendan group lived longer (median survival time was 1059 days (95% CI: 952-NA) in the pimobendan group and 902 days (95% CI: 747-1061) in the placebo group) (P = .012). Conclusions and Clinical Importance: Administration of pimobendan to dogs with MMVD and echocardiographic and radiographic evidence of cardiomegaly results in prolongation of preclinical period and is safe and well tolerated. Prolongation of preclinical period by approximately 15 months represents substantial clinical benefit

Familial Linkage between Neuropsychiatric Disorders and Intellectual Interests

From personality to neuropsychiatric disorders, individual differences in brain function are known to have a strong heritable component. Here we report that between close relatives, a variety of neuropsychiatric disorders covary strongly with intellectual interests. We surveyed an entire class of high-functioning young adults at an elite university for prospective major, familial incidence of neuropsychiatric disorders, and demographic and attitudinal questions. Students aspiring to technical majors (science/mathematics/engineering) were more likely than other students to report a sibling with an autism spectrum disorder (p = 0.037). Conversely, students interested in the humanities were more likely to report a family member with major depressive disorder (p = 8.8×10−4), bipolar disorder (p = 0.027), or substance abuse problems (p = 1.9×10−6). A combined PREdisposition for Subject MattEr (PRESUME) score based on these disorders was strongly predictive of subject matter interests (p = 9.6×10−8). Our results suggest that shared genetic (and perhaps environmental) factors may both predispose for heritable neuropsychiatric disorders and influence the development of intellectual interests