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New surgical procedures can expose patients to harm and should be carefully evaluated before widespread use. The InSpace balloon (Stryker, USA) is an innovative surgical device used to treat people with rotator cuff tears that cannot be repaired. We aimed to determine the effectiveness of the InSpace balloon for people with irreparable rotator cuff tears.We conducted a double-blind, group-sequential, adaptive randomised controlled trial in 24 hospitals in the UK, comparing arthroscopic debridement of the subacromial space with biceps tenotomy (debridement only group) with the same procedure but including insertion of the InSpace balloon (debridement with device group). Participants had an irreparable rotator cuff tear, which had not resolved with conservative treatment, and they had symptoms warranting surgery. Eligibility was confirmed intraoperatively before randomly assigning (1:1) participants to a treatment group using a remote computer system. Participants and assessors were masked to group assignment. Masking was achieved by using identical incisions for both procedures, blinding the operation note, and a consistent rehabilitation programme was offered regardless of group allocation. The primary outcome was the Oxford Shoulder Score at 12 months. Pre-trial simulations using data from early and late timepoints informed stopping boundaries for two interim analyses. The primary analysis was on a modified intention-to-treat basis, adjusted for the planned interim analysis. The trial was registered with ISRCTN, ISRCTN17825590.Between June 1, 2018, and July 30, 2020, we assessed 385 people for eligibility, of which 317 were eligible. 249 (79%) people consented for inclusion in the study. 117 participants were randomly allocated to a treatment group, 61 participants to the debridement only group and 56 to the debridement with device group. A predefined stopping boundary was met at the first interim analysis and recruitment stopped with 117 participants randomised. 43% of participants were female, 57% were male. We obtained primary outcome data for 114 (97%) participants. The mean Oxford Shoulder Score at 12 months was 34·3 (SD 11·1) in the debridement only group and 30·3 (10·9) in the debridement with device group (mean difference adjusted for adaptive design -4·2 [95% CI -8·2 to -0·26];p=0·037) favouring control. There was no difference in adverse events between the two groups.In an efficient, adaptive trial design, our results favoured the debridement only group. We do not recommend the InSpace balloon for the treatment of irreparable rotator cuff tears.Efficacy and Mechanism Evaluation Programme, a Medical Research Council and National Institute for Health and Care Research partnership.

Purpose We investigated Nw-hydroxy l -Arginine (NOHA) predictive response in serous ovarian carcinoma based on estrogen-hormone receptor expression status; and assessed the distinctive NOHA response between estrogen-receptor-negative (ER–) tumor subtypes of ovarian and breast cancer. Materials/methods Three-dimensional (3D) spheroids models of ER– and estrogen-receptor-positive (ER+) from breast and ovarian tumor, cultured for 9 weeks, were assayed for cellular levels of inducible nitric oxide synthase (NOS2), nitric oxide (as total nitrite) and l -Arginine, and compared to NOHA in culture medium. Statistical difference was set at p Results Nine-week in vitro studies showed a progressive NOHA reduction in culture medium by at least 0.4–0.8 fold, and 0.65–0.92 fold only in the ER– breast tumor and ER– ovarian tumor 3D spheroids, respectively; with increases in cellular NOS2 and nitric-oxide levels, by at least 1.0–2.45 fold in both ER– tumor subtype 3D spheroids (p l -Arginine to medium NOHA ratio was higher, and by at least 6.5–22.5 fold in ER– breast tumor 3D-spheroids, and at least 10–70 fold in ER– ovarian tumor 3D spheroids, than in ER+ and control conditions; and was ≥48% higher in ER– ovarian cancer than in ER– breast cancer 3D-spheroids. Conclusions The present study shows NOHA as a sensitive and selective indicator differentiating and distinguishing ER– subtypes based on the tumor grade.

We had shown Nw-hydroxy-l-arginine (NOHA) as a promising blood-based biomarker for estrogen-receptor-negative (ER−) breast cancer (BC) that differentiates ER− BC based on grade and molecular phenotype. In this in vitro study, we assessed the metabolic relevance for ER− BC-specific NOHA modulation and correlated them with NOHA regulatory responses. This study aids future NOHA clinical utility in ER− BC diagnosis and therapy management and would prove useful for potential drug discovery and development process.

In our prior study we identified N w-hydroxy-l-arginine (NOHA) as a simple, yet sensitive indicator for estrogen negative (ER−) breast cancer early-prognosis, but not estrogen positive (ER+), and to offer ethnic selectivity for ER− detection. However, the ability of NOHA to assess ER− breast tumor based on disease progression, and tumor severity needs further delineation. Also, the overall NOHA storage stability needs to be validated. To assess the NOHA predictive capability based on disease progression, ER−/ER+ 3D-spheroids (from breast tumor cell lines of human origin) were cultured for 10 weeks. We found only ER− 3D-spheroid cultured for 10 weeks to show a gradual reduction in NOHA (both in culture medium and 3D-spheroid lysates) that correlated with a progressive increase in cellular NOS2 expression and NOS2 activity (measured as total nitrites). We additionally identified the NOHA-NOS2 correlation to be ethnically selective between ER− African American versus ER− Caucasian groups. Interestingly, such NOHA reduction was observed earlier in ER− culture medium (viz., after week 1) than from ER− 3D-spheroids lysates (viz., at the end of 3 weeks). When categorized based on 3D-spheroid grade, we found a ≥ 68% NOHA reduction in ER− spheroids that were ≤ 3 weeks old, that was categorized as “low-grade” (based on tumor size ≤ 250 µm, and with cellular characteristics identical to healthy cells). A substantial reduction in NOHA of ≥ 87% occurred with ER− 3D-spheroids grown for 6 weeks, which were categorized as “intermediate-grade” (with tumor size of ≥ 400 µm, and with less characteristic similarity to control spheroids). These in vitro findings thus suggest a distinct correlation between NOHA reduction and ER− tumor grade. Such distinctive correlation between NOHA and ER− tumor grade was additionally observed in de-identified clinical samples where a onefold higher reduction in NOHA occurred in grade-2 than with grade-1 de-identified patient plasma (when compared with control), and such correlation offered ethnic selectivity between ER− African American and ER− Caucasian groups. Of additional interest, when NOHA overall storage stability was assessed by incubating patient plasma and culture medium spiked with 75 pg/ml NOHA at multiple incubation temperatures and time-points, we found NOHA to maintain its stability for up to 6 weeks in culture medium and for 7 days in plasma at 4 °C and below. These results thus provide the first evidence of NOHA as a stable indicator to monitor ER− disease progression and tumor severity in ethnically distinctive populations.

The National Science Foundation's Large Facilities are major, multi-user research facilities that operate and manage sophisticated and diverse research instruments and platforms (e.g., large telescopes, interferometers, distributed sensor arrays) that serve a variety of scientific disciplines, from astronomy and physics to geology and biology and beyond. Large Facilities are increasingly dependent on advanced cyberinfrastructure (i.e., computing, data, and software systems; networking; and associated human capital) to enable the broad delivery and analysis of facility-generated data. These cyberinfrastructure tools enable scientists and the public to gain new insights into fundamental questions about the structure and history of the universe, the world we live in today, and how our environment may change in the coming decades. This paper describes a pilot project that aims to develop a model for a Cyberinfrastructure Center of Excellence (CI CoE) that facilitates community building and knowledge sharing and that disseminates and applies best practices and innovative solutions for facility CI.

We found a unit error with our LC-MS lower limit of quantitation (LLOQ) measurement in the Amino Acids Journal.

Common approaches to mapping green infrastructure in urbanised landscapes invariably focus on measures of land use or land cover and associated functional or physical traits. However, such one-dimensional perspectives do not accurately capture the character and complexity of the landscapes in which urban inhabitants live. The new approach presented in this paper demonstrates how open-source, high spatial and temporal resolution data with global coverage can be used to measure and represent the landscape qualities of urban environments. Through going beyond simple metrics of quantity, such as percentage green and blue cover, it is now possible to explore the extent to which landscape quality helps to unpick the mixed evidence presented in the literature on the benefits of urban nature to human well-being. Here we present a landscape approach, employing remote sensing, GIS and data reduction techniques to map urban green infrastructure elements in a large U.K. city region. Comparison with existing urban datasets demonstrates considerable improvement in terms of coverage and thematic detail. The characterisation of landscapes, using census tracts as spatial units, and subsequent exploration of associations with social–ecological attributes highlights the further detail that can be uncovered by the approach. For example, eight urban landscape types identified for the case study city exhibited associations with distinct socioeconomic conditions accountable not only to quantities but also qualities of green and blue space. The identification of individual landscape features through simultaneous measures of land use and land cover demonstrated unique and significant associations between the former and indicators of human health and ecological condition. The approach may therefore provide a promising basis for developing further insight into processes and characteristics that affect human health and well-being in urban areas, both in the United Kingdom and beyond.

In our prior study we identified N

Enadenotucirev (EnAd) is a chimeric group B adenovirus isolated by bioselection from a library of adenovirus serotypes. It replicates selectively in and kills a diverse range of carcinoma cells, shows effective anticancer activity in preclinical systems, and is currently undergoing phase I/II clinical trials. EnAd kills cells more quickly than type 5 adenovirus, and speed of cytotoxicity is dose dependent. The EnAd death pathway does not involve p53, is predominantly caspase independent, and appears to involve a rapid fall in cellular ATP. Infected cells show early loss of membrane integrity; increased exposure of calreticulin; extracellular release of ATP, HSP70, and HMGB1; and influx of calcium. The virus also causes an obvious single membrane blister reminiscent of ischemic cell death by oncosis. In human tumor biopsies maintained in ex vivo culture, EnAd mediated release of pro-inflammatory mediators such as TNF-α, IL-6, and HMGB1. In accordance with this, EnAd-infected tumor cells showed potent stimulation of dendritic cells and CD4(+) T cells in a mixed tumor-leukocyte reaction in vitro. Whereas many viruses have evolved for efficient propagation with minimal inflammation, bioselection of EnAd for rapid killing has yielded a virus with a short life cycle that combines potent cytotoxicity with a proinflammatory mechanism of cell death.

Parmar and colleagues ask an important question about research on the health impact of the 2008 financial crisis in Europe and in answering have devised a new assessment tool for observational studies.1 They spend time on seven aspects of bias: among the 41 studies included (from an original 5670), risk of bias was deemed high in 30, moderate in nine, and low in two. These values do not reflect well on …