Twistable mold for helicopter blades

Design is described of mold for fabrication of blades composed of sets of aerodynamic shells having same airfoil section characteristics but different distributions. Mold consists of opposing stacks of thin templates held together by long bolts. When bolts are loosened, templates can be set at different positions with respect to each other and then locked in place

Mapping the interaction of B cell Leukemia 3 (BCL-3) and nuclear factor κB (NF-κB) p50 identifies a BCL-3-mimetic anti-inflammatory peptide

The NF-κB transcriptional response is tightly regulated by a number of processes including the phosphorylation, ubiquitination, and subsequent proteasomal degradation of NF-κB subunits. The IκB family protein BCL-3 stabilizes a NF-κB p50 homodimer·DNA complex through inhibition of p50 ubiquitination. This complex inhibits the binding of the transcriptionally active NF-κB subunits p65 and c-Rel on the promoters of NF-κB target genes and functions to suppress inflammatory gene expression. We have previously shown that the direct interaction between p50 and BCL-3 is required for BCL-3-mediated inhibition of pro-inflammatory gene expression. In this study we have used immobilized peptide array technology to define regions of BCl-3 that mediate interaction with p50 homodimers. Our data show that BCL-3 makes extensive contacts with p50 homodimers and in particular with ankyrin repeats (ANK) 1, 6, and 7, and the N-terminal region of Bcl-3. Using these data we have designed a BCL-3 mimetic peptide based on a region of the ANK1 of BCL-3 that interacts with p50 and shares low sequence similarity with other IκB proteins. When fused to a cargo carrying peptide sequence this BCL-3-derived peptide, but not a mutated peptide, inhibited Toll-like receptor-induced cytokine expression in vitro. The BCL-3 mimetic peptide was also effective in preventing inflammation in vivo in the carrageenan-induced paw edema mouse model. This study demonstrates that therapeutic strategies aimed at mimicking the functional activity of BCL-3 may be effective in the treatment of inflammatory disease

Adherence to prescribing restrictions for HER2-positive metastatic breast cancer in Australia: A national population-based observational study (2001-2016)

Background: Targeted cancer therapy is often complex, involving multiple agents and chemotherapeutic partners. In Australia, prescribing restrictions are put in place to reflect existing evidence of cost-effectiveness of these medicines. As therapeutic options continue to expand, these restrictions may not be perceived to align with best practice and it is not known if their use in the real-world clinic adheres to these restrictions. We examined the treatment of women receiving trastuzumab for HER2-positive metastatic breast cancer (HER2+MBC) to determine the extent to which treatment adhered to national prescribing restrictions. Patients and methods: Our population-based, retrospective cohort study used dispensing records for every Australian woman initiating publicly-subsidised trastuzumab for HER2+MBC between 2001±2013, followed through 2016. We used group-based trajectory models (GBTMs) to cluster patients, first on their patterns of trastuzumab exposure, and then on their patterns of lapatinib and chemotherapy exposure. We described the characteristics of patients within each cluster, and examined their treatments and combinations of treatments to determine restriction adherence. Results: Of 5,052 patients initiating trastuzumab, 1,795 (36%) received at least one non-adherent HER2-targeted treatment. The most common non-adherent treatments were trastuzumab combinations involving vinorelbine (24% of non-adherent treatments); capecitabine (24%); and anthracyclines (10%). Non-adherent lapatinib use was observed in 4% of patients. GBTM identified three trastuzumab exposure clusters, each containing three further subclusters. The largest proportions of non-adherent treatments were in sub-clusters with longer trastuzumab exposure and more non-taxane chemotherapy. Patients in these sub-clusters were younger than those in sub-clusters with less non-adherent treatment. Conclusions: Our study highlights that, even during the relatively simpler treatment era of our study period, a substantial amount of treatment did not adhere to prescribing restrictions. As more trials are conducted exploring pertuzumab and T-DM1 in combination with different chemotherapies and other HER2-targeted therapies, the regulation and funding of HER2-targeted treatment will become more challenging

Stasis disguised as motion: Waiting, endurance and the camouflaging of austerity in mental health services

This paper develops an account of the camouflaging of austerity as an institutional strategy. In doing so it brings together and advances geographical literatures on mental health, waiting, and austerity. Where geographers have tended to focus on moments when austerity surfaces in everyday life, this paper addresses those moments where austerity is made to recede. Presenting evidence from interviews with mental health service users/survivors, I argue that stasis is a central feature of encounters with the austere state. Such periods of durative waiting can make austerity apparent, so institutions are incentivised to camouflage them, in order to legitimate their claims of providing care. I advance the concept of the “holding pattern” to capture the mobile cycles of waiting that service users/survivors endure, arguing that these circulations inculcate cruelly optimistic affects by exploiting the immanent potentiality of waiting. These affects engender a belief that the time of care and of progress is imminent. For those held within it, the holding pattern is experienced as a form of stasis disguised as motion. The paper then analyses how people endure this travel without a destination. I demonstrate that, like the holding pattern, these practices of endurance make use of potentiality. Some cast themselves as responsibilised neoliberal subjects, to blame for the lack of meaningful care they receive; others reclaim the potentiality that fuels the holding pattern, engaging in ongoing practices that are sustaining despite their seeming uneventfulness. The paper highlights the centrality of austerity to contemporary mental health geographies; develops a critical account of the politics of stasis and waiting; and argues that the camouflaging of austerity will prove increasingly important to the legitimation of beleaguered “universalist” social services. I conclude with some reflections on the potentiality of a grinding politics of resistance to austerity

Remission vs low disease activity: function, quality of life and structural outcomes in the Early Rheumatoid Arthritis Study and Network

Objectives To examine associations between function, quality of life and structural outcomes in patients achieving remission vs low disease activity in early RA. Methods Demographic, clinical and radiographic variables were collected at baseline and then annually from the Early Rheumatoid Arthritis Study (ERAS) and Early Rheumatoid Arthritis Network (ERAN) inception cohorts in routine care from 1986 to 2012. Disease activity was categorized: mean DAS28 score between years 1 and 5: remission [mean remission DAS (mRDAS) <2.6] or low [mean low DAS (mLDAS) 2.6–3.2]; sustained low/remission DAS28 (sLDAS/sRDAS) at years 1 and 2; and sustained Boolean remission (sBR) at years 1 and 2. Changes in HAQ and Short Form 36 Health Survey Questionnaire [SF-36; physical (PCS) and mental (MCS) component score]) and total Sharp van der Heijde (SvdH) scores for each disease activity category were modelled using multi-level models. Covariates included year of onset, age, gender and DMARD use at first visit. Results Of 2701 patients, 562 (21%) were categorized mRDAS, 330 (12%) mLDAS, 279 (10%) sRDAS, 203 (7.5%) sLDAS and 93 (3%) sBR. Patients categorized as mRDAS had increasingly divergent improved HAQ, SF-36 PCS, MCS and total SvdH scores compared with mLDAS (P-values 0.001 to <0.0001, all time points). Patients categorized as sRDAS had better HAQ, SF-36 PCS and MCS scores (P-values 0.05 to <0.0001, all time points) and SvdH scores (P = 0.05, years 3–5) over sLDAS. sBR was associated with better HAQ, and SF-36 PCS and MCS scores over sLDAS (P-values 0.002 to <0.0001, all time points). Conclusion These findings from routine care support ACR/EULAR guidelines that remission is a preferable goal over low disease activity in early RA.Peer reviewedFinal Published versio