Regular whole blood donation and gastrointestinal, breast, colorectal and haematological cancer risk among blood donors in Australia.

BACKGROUND AND OBJECTIVES: Several studies have suggested that blood donors have lower risk of gastrointestinal and breast cancers, whereas some have indicated an increased risk of haematological cancers. We examined these associations by appropriately adjusting the 'healthy donor effect' (HDE). MATERIALS AND METHODS: We examined the risk of gastrointestinal/colorectal, breast and haematological cancers in regular high-frequency whole blood (WB) donors using the Sax Institute's 45 and Up Study data linked with blood donation and other health-related data. We calculated 5-year cancer risks, risk differences and risk ratios. To mitigate HDE, we used 5-year qualification period to select the exposure groups, and applied statistical adjustments using inverse probability weighting, along with other advanced doubly robust g-methods. RESULTS: We identified 2867 (42.4%) as regular high-frequency and 3888 (57.6%) as low-frequency donors. The inverse probability weighted 5-year risk difference between high and low-frequency donors for gastrointestinal/colorectal cancer was 0.2% (95% CI, -0.1% to 0.5%) with a risk ratio of 1.25 (0.83-1.68). For breast cancer, the risk difference was -0.2% (-0.9% to 0.4%), with a risk ratio of 0.87 (0.48-1.26). Regarding haematological cancers, the risk difference was 0.0% (-0.3% to 0.5%) with a risk ratio of 0.97 (0.55-1.40). Our doubly robust estimators targeted minimum loss-based estimator (TMLE) and sequentially doubly robust (SDR) estimator, yielded similar results, but none of the findings were statistically significant. CONCLUSION: After applying methods to mitigate the HDE, we did not find any statistically significant differences in the risk of gastrointestinal/colorectal, breast and haematological cancers between regular high-frequency and low-frequency WB donors

Stellar Cycles in Fully Convective Stars and a New Interpretation of Dynamo Evolution

An $\alpha\Omega$ dynamo, combining shear and cyclonic convection in the tachocline, is believed to generate the solar cycle. However, this model cannot explain cycles in fast rotators (with minimal shear) or in fully convective stars (no tachocline); analysis of such stars could therefore provide key insights into how these cycles work. We reexamine ASAS data for 15 M dwarfs, 11 of which are presumed fully convective; the addition of newer ASAS-SN data confirms cycles in roughly a dozen of them, while presenting new or revised rotation periods for five. The amplitudes and periods of these cycles follow $A_{\rm cyc} \propto P_{\rm cyc}^{0.94 \pm 0.11}$, with $P_{\rm cyc}/P_{\rm rot} \propto {\rm Ro}^{-1.02 \pm 0.06}$ (where Ro is the Rossby number), very similar to $P_{\rm cyc}/P_{\rm rot} \propto {\rm Ro}^{-0.81 \pm 0.17}$ that we find for 40 previously studied FGK stars, although $P_{\rm cyc}/P_{\rm rot}$ and $\alpha$ are a factor of $\sim$20 smaller in the M stars. The very different $P_{\rm cyc}/P_{\rm rot}$-Ro relationship seen here compared to previous work suggests that two types of dynamo, with opposite Ro dependences, operate in cool stars. Initially, a (likely $\alpha^2$ or $\alpha^2\Omega$) dynamo operates throughout the convective zone in mid-late M and fast rotating FGK stars, but once magnetic breaking decouples the core and convective envelope, a tachocline $\alpha\Omega$ dynamo begins and eventually dominates in older FGK stars. A change in $\alpha$ in the tachocline dynamo generates the fundamentally different $P_{\rm cyc}/P_{\rm rot}$-Ro relationship.Comment: 26 pages, 18 figures, submitted to ApJ. Figure sets will be available in the final prin

Aggregates in blood filter chambers used from the plasma donations of anti-D donors: evaluation for monoclonal antibody discovery using phage display.

BACKGROUND: RhD-immunoglobulin (RhIg) prevents anti-D alloimmunisation in D-negative pregnant women when the fetus is D-positive, reducing the incidence of haemolytic disease of the fetus and newborn. Manufacturing RhIg is reliant on the limited supply of plasma donations with anti-D antibodies. Monoclonal antibody (mAb) development platforms such as phage display, require blood samples to be collected from anti-D donors, which may be a complicated process. The blood filter chamber (BFC) discarded after an anti-D donor's donation might provide a source of Ig-encoding RNA. This study aims to evaluate whether used BFCs are a suitable source of Ig-encoding RNA for phage display. MATERIAL AND METHODS: Haemonetics PCS2 BFCs were obtained from 10 anti-D donors for total RNA extraction, cDNA synthesis and amplification of VH and VL IgG sequences for assembly of single-chain variable fragments (scFvs). A scFv-phage display library was constructed and 3 rounds of biopanning were performed using D-positive and D-negative red blood cells (RBCs). Positive phage clones were isolated, Sanger sequenced and, where possible, reformatted into full-length human IgGs to define specificity. The BFC aggregates from 2 anti-D donors underwent a Wright-Giemsa stain and hematological cell count. RESULTS: Of 10 BFCs, a sufficient yield of total RNA for library construction was obtained from BFCs containing cellular aggregates (n=5). Aggregate analysis showed lymphocytes were the cellular source of Ig-encoding RNA. From the 5 samples with aggregates, scFvs were assembled from amplified IgG variable regions. The library constructed from 1 of these samples resulted in the isolation of clones binding to D-positive RBCs with IGHV3 gene usage. Of the 4 reformatted IgG, 3 were anti-D and 1 had undefined specificity. DISCUSSION: BFC aggregates are a new and convenient source of Ig-encoding RNA which can be used to construct Ig gene libraries for mAb isolation and discovery via antibody phage display

Immunomodulation of inflammatory leukocyte markers during intravenous immunoglobulin treatment associated with clinical efficacy in chronic inflammatory demyelinating polyradiculoneuropathy

© 2016 The Authors. Brain and Behavior published by Wiley Periodicals, Inc. Objective: The objective of the study was to profile leukocyte markers modulated during intravenous immunoglobulin (IVIg) treatment, and to identify markers and immune pathways associated with clinical efficacy of IVIg for chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) with potential for monitoring treatment efficacy. Methods: Response to IVIg treatment in newly diagnosed IVIg-naïve and established IVIg-experienced patients was assessed by changes in expression of inflammatory leukocyte markers by flow cytometry. The adjusted INCAT disability and Medical Research Council sum scores defined clinical response. Results: Intravenous immunoglobulin modulated immunopathogenic pathways associated with inflammatory disease in CIDP. Leukocyte markers of clinical efficacy included reduced CD185 + follicular helper T cells, increased regulatory markers (CD23 and CD72) on B cells, and reduction in the circulating inflammatory CD16 + myeloid dendritic cell (mDC) population and concomitant increase in CD62L and CD195 defining a less inflammatory lymphoid homing mDC phenotype. A decline in inflammatory CD16 + dendritic cells was associated with clinical improvement or stability, and correlated with magnitude of improvement in neurological assessment scores, but did not predict relapse. IVIg also induced a nonspecific improvement in regulatory and reduced inflammatory markers not associated with clinical response. Conclusions: Clinically effective IVIg modulated inflammatory and regulatory pathways associated with ongoing control or resolution of CIDP disease. Some of these markers have potential for monitoring outcome

SARS Coronavirus-2 Microneutralisation and Commercial Serological Assays Correlated Closely for Some but Not All Enzyme Immunoassays

Serological testing for SARS-CoV-2-specific antibodies provides important research and diagnostic information relating to COVID-19 prevalence, incidence and host immune response. A greater understanding of the relationship between functionally neutralising antibodies detected using microneutralisation assays and binding antibodies detected using scalable enzyme immunoassays (EIA) is needed in order to address protective immunity post-infection or vaccination, and assess EIA suitability as a surrogate test for screening of convalescent plasma donors. We assessed whether neutralising antibody titres correlated with signal cut-off ratios in five commercially available EIAs, and one in-house assay based on expressed spike protein targets. Sera from recovered patients or convalescent plasma donors who reported laboratory-confirmed SARS-CoV-2 infection (n = 200), and negative control sera collected prior to the COVID-19 pandemic (n = 100), were assessed in parallel. Performance was assessed by calculating EIA sensitivity and specificity with reference to microneutralisation. Neutralising antibodies were detected in 166 (83%) samples. Compared with this, the most sensitive EIAs were the Cobas Elecsys Anti-SARS-CoV-2 (98%) and Vitros Immunodiagnostic Anti-SARS-CoV-2 (100%), which detect total antibody targeting the N and S1 antigens, respectively. The assay with the best quantitative relationship with microneutralisation was the Euroimmun IgG. These results suggest the marker used (total Ab vs. IgG vs. IgA) and the target antigen are important determinants of assay performance. The strong correlation between microneutralisation and some commercially available assays demonstrates their potential for clinical and research use in assessing protection following infection or vaccination, and use as a surrogate test to assess donor suitability for convalescent plasma donation

Rumo à prevenção de acidentes com embarcações na região amazônica. Parte II: as tecnologias 4.0 como alternativas : Towards prevention of ship accidents in the amazon region. Part II: 4.0 technologies as alternatives

As tecnologias da Indústria 4.0 podem ser alternativas para aumentar a eficiência e a segurança em diversas atividades da indústria naval brasileira, incluindo a prevenção de acidentes com embarcações em regiões em desenvolvimento como a região amazônica. Porém, as tecnologias 4.0 são recentes e apesar da sua crescente atenção em diversas áreas da engenharia, ainda há falta de divulgação da informação relacionada com as alternativas de aplicação na Engenharia Naval. O presente artigo apresenta os conceitos básicos de algumas das tecnologias 4.0 que estão sendo aplicadas na indústria naval, incluindo exemplos recentes de aplicação. As seguintes tecnologias foram consideradas: Sistemas Ciberfísicos (CPS, Ciberphysical Systems), Realidade Aumentada (AR, Augmented Reality), Análise de Macrodados (BDA, Big Data Analytics), Computação em Nuvem (CC, Cloud Computing) e Internet das Coisas (IoT, Internet of Things). Foi identificado que as aplicações das tecnologias 4.0 têm bastante potencial de inovação em atividades de construção naval e transporte aquaviário e marítimo, visando a otimização de processos e a prevenção de acidentes. No entanto, projetos de pesquisa e desenvolvimento em vários campos de atuação ainda precisam ser planejados no Brasil. Para implementar estes projetos, as limitações próprias da indústria 4.0 e as barreiras das regiões em desenvolvimento precisam ser consideradas. &nbsp

SARS-CoV-2 neutralizing antibodies: Longevity, breadth, and evasion by emerging viral variants.

The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) antibody neutralization response and its evasion by emerging viral variants and variant of concern (VOC) are unknown, but critical to understand reinfection risk and breakthrough infection following vaccination. Antibody immunoreactivity against SARS-CoV-2 antigens and Spike variants, inhibition of Spike-driven virus-cell fusion, and infectious SARS-CoV-2 neutralization were characterized in 807 serial samples from 233 reverse transcription polymerase chain reaction (RT-PCR)-confirmed Coronavirus Disease 2019 (COVID-19) individuals with detailed demographics and followed up to 7 months. A broad and sustained polyantigenic immunoreactivity against SARS-CoV-2 Spike, Membrane, and Nucleocapsid proteins, along with high viral neutralization, was associated with COVID-19 severity. A subgroup of "high responders" maintained high neutralizing responses over time, representing ideal convalescent plasma donors. Antibodies generated against SARS-CoV-2 during the first COVID-19 wave had reduced immunoreactivity and neutralization potency to emerging Spike variants and VOC. Accurate monitoring of SARS-CoV-2 antibody responses would be essential for selection of optimal responders and vaccine monitoring and design

Cracks in Martensite Plates as Hydrogen Traps in a Bearing Steel

It is demonstrated that a macroscopically homogeneous distribution of tiny cracks introduced into a martensitic bearing steel sample can provide powerful hydrogen traps. The phenomenon has been investigated through thermal desorption spectroscopy and hydrogen permeation measurements using both cracked and integral samples. The e↵ective hydrogen di↵usion coefficient through the cracked sample is found to be far less than in the uncracked one. Similarly, when samples are charged with hydrogen, and then subjected to thermal desorption analysis, the amount of hydrogen liberated from the cracked sample is smaller due to the trapping by the cracks. Theoretical analysis of the data shows that the traps due to cracks are so strong, that any hydrogen within the cracks can never in practice de-trap and cause harm by mechanisms that require the hydrogen to be mobile for the onset of embrittlement.W. Solano-Alvarez is very grateful for support from the Worshipful Company of Ironmongers, CONACyT, the Cambridge Overseas Trust, and the Roberto Rocca Education Programme.This is the accepted manuscript. The final publication is available at Springer via http://dx.doi.org/10.1007/s11661-014-2680-8

Aggravation of allergic airway inflammation by cigarette smoke in mice is CD44-dependent

Background : Although epidemiological studies reveal that cigarette smoke (CS) facilitates the development and exacerbation of allergic asthma, these studies offer limited information on the mechanisms involved. The transmembrane glycoprotein CD44 is involved in cell adhesion and acts as a receptor for hyaluronic acid and osteopontin. We aimed to investigate the role of CD44 in a murine model of CS-facilitated allergic airway inflammation. Methods : Wild type (WT) and CD44 knock-out (KO) mice were exposed simultaneously to house dust mite (HDM) extract and CS. Inflammatory cells, hyaluronic acid (HA) and osteopontin (OPN) levels were measured in bronchoalveolar lavage fluid (BALF). Proinflammatory mediators, goblet cell metaplasia and peribronchial eosinophilia were assessed in lung tissue. T-helper (Th) 1, Th2 and Th17 cytokine production was evaluated in mediastinal lymph node cultures. Results : In WT mice, combined HDM/CS exposure increased the number of inflammatory cells and the levels of HA and OPN in BALF and Th2 cytokine production in mediastinal lymph nodes compared to control groups exposed to phosphate buffered saline (PBS)/CS, HDM/Air or PBS/Air. Furthermore, HDM/CS exposure significantly increased goblet cell metaplasia, peribronchial eosinophilia and inflammatory mediators in the lung. CD44 KO mice exposed to HDM/CS had significantly fewer inflammatory cells in BALF, an attenuated Th2 cytokine production, as well as decreased goblet cells and peribronchial eosinophils compared to WT mice. In contrast, the levels of inflammatory mediators were similar or higher than in WT mice. Conclusion : We demonstrate for the first time that the aggravation of pulmonary inflammation upon combined exposure to allergen and an environmental pollutant is CD44-dependent. Data from this murine model of concomitant exposure to CS and HDM might be of importance for smoking allergic asthmatics