DCE-MRI biomarkers of tumour heterogeneity predict CRC liver metastasis shrinkage following bevacizumab and FOLFOX-6

Background: There is limited evidence that imaging biomarkers can predict subsequent response to therapy. Such prognostic and/or predictive biomarkers would facilitate development of personalised medicine. We hypothesised that pre-treatment measurement of the heterogeneity of tumour vascular enhancement could predict clinical outcome following combination anti-angiogenic and cytotoxic chemotherapy in colorectal cancer (CRC) liver metastases. Methods: Ten patients with 26 CRC liver metastases had two dynamic contrast-enhanced MRI (DCE-MRI) examinations before starting first-line bevacizumab and FOLFOX-6. Pre-treatment biomarkers of tumour microvasculature were computed and a regression analysis was performed against the post-treatment change in tumour volume after five cycles of therapy. The ability of the resulting linear model to predict tumour shrinkage was evaluated using leave-one-out validation. Robustness to inter-visit variation was investigated using data from a second baseline scan. Results: In all, 86% of the variance in post-treatment tumour shrinkage was explained by the median extravascular extracellular volume (ve), tumour enhancing fraction (EF), and microvascular uniformity (assessed with the fractal measure box dimension, d0) (R2=0.86, P<0.00005). Other variables, including baseline volume were not statistically significant. Median prediction error was 12%. Equivalent results were obtained from the second scan. Conclusion: Traditional image analyses may over-simplify tumour biology. Measuring microvascular heterogeneity may yield important prognostic and/or predictive biomarkers

GLIPR1L1 is an IZUMO-binding protein required for optimal fertilization in the mouse

Background: The sperm protein IZUMO1 (Izumo sperm-egg fusion 1) and its recently identified binding partner on the oolemma, IZUMO1R, are among the first ligand-receptor pairs shown to be essential for gamete recognition and adhesion. However, the IZUMO1-IZUMO1R interaction does not appear to be directly responsible for promoting the fusion of the gamete membranes, suggesting that this critical phase of the fertilization cascade requires the concerted action of alternative fusogenic machinery. It has therefore been proposed that IZUMO1 may play a secondary role in the organization and/or stabilization of higher-order heteromeric complexes in spermatozoa that are required for membrane fusion. Results: Here, we show that fertilization-competent (acrosome reacted) mouse spermatozoa harbor several high molecular weight protein complexes, a subset of which are readily able to adhere to solubilized oolemmal proteins. At least two of these complexes contain IZUMO1 in partnership with GLI pathogenesis-related 1 like 1 (GLIPR1L1). This interaction is associated with lipid rafts and is dynamically remodeled upon the induction of acrosomal exocytosis in preparation for sperm adhesion to the oolemma. Accordingly, the selective ablation of GLIPR1L1 leads to compromised sperm function characterized by a reduced ability to undergo the acrosome reaction and a failure of IZUMO1 redistribution. Conclusions: Collectively, this study characterizes multimeric protein complexes on the sperm surface and identifies GLIPRL1L1 as a physiologically relevant regulator of IZUMO1 function and the fertilization process.Avinash S. Gaikwad, Amanda L. Anderson, D. Jo Merriner, Anne E. O’Connor, Brendan J. Houston, R. John Aitken, Moira K. O’Bryan, and Brett Nixo

The longitudinal association of actigraphy-estimated sleep with grief in middle-aged and elderly persons

Most people experience grief after a loss, about 10% develop complicated grief, often accompanied by sleep complaints. Yet, the role of objectively estimated poor sleep remains unclear. Therefore, we assessed the cross-sectional and longitudinal association of actigraphy-estimated sleep with grief. We included 1,776 participants (mean age: 61.8 ± 8.9 years, 55% women) of a prospective population-based cohort. Of 1,471 participants (83%) repeated measures of grief were available (median follow-up 6 years, inter quartile range 5.6–6.3). At baseline, sleep was objectively estimated using actigraphy (mean duration 6.0 ± 0.8days). At baseline and follow-up, participants were asked about significant losses and completed the Dutch Inventory of Complicated Grief (17 items, cut-off ≥22). At baseline 1,521 (86%) participants experienced no grief, 44 (2%) acute grief (<6 months, any grief score), 158 (9%) non-complicated grief (≥6 months, grief score<22), and 53 (3%) complicated grief (≥6 months, grief score≥22). In those indicating any grief (n = 255), low sleep efficiency (B = −0.16, 95%CI = −0.30;-0.02), long sleep onset latency (B = 0.07, 95%CI = 0.01; 0.14), and long wake after sleep onset (B = 0.06, 95%CI = 0.01; 0.10) were cross-sectionally associated with more grief symptoms. Over time, those with a short total sleep time (OR = 0.59, 95%CI = 0.39; 0.91), low sleep efficiency (OR = 0.95, 95%CI = 0.91; 0.99), long sleep onset latency (OR = 1.02, 95%CI = 1.00; 1.04), and long wake after sleep onset (OR = 1.02, 95%CI = 1.00; 1.03) at baseline more often experienced complicated grief than non-complicated grief at follow-up. This study suggests that objectively estimated poor sleep is associated with grief over time. Poor sleep might not only accompany grief, but also be a risk factor for developing complicated grief after a loss

Eureka and beyond: mining's impact on African urbanisation

This collection brings separate literatures on mining and urbanisation together at a time when both artisanal and large-scale mining are expanding in many African economies. While much has been written about contestation over land and mineral rights, the impact of mining on settlement, notably its catalytic and fluctuating effects on migration and urban growth, has been largely ignored. African nation-states’ urbanisation trends have shown considerable variation over the past half century. The current surge in ‘new’ mining countries and the slow-down in ‘old’ mining countries are generating some remarkable settlement patterns and welfare outcomes. Presently, the African continent is a laboratory of national mining experiences. This special issue on African mining and urbanisation encompasses a wide cross-section of country case studies: beginning with the historical experiences of mining in Southern Africa (South Africa, Zambia, Zimbabwe), followed by more recent mineralizing trends in comparatively new mineral-producing countries (Tanzania) and an established West African gold producer (Ghana), before turning to the influence of conflict minerals (Angola, the Democratic Republic of Congo and Sierra Leone)

Paleobiology of titanosaurs: reproduction, development, histology, pneumaticity, locomotion and neuroanatomy from the South American fossil record

Fil: García, Rodolfo A.. Instituto de Investigación en Paleobiología y Geología. Museo Provincial Carlos Ameghino. Cipolletti; ArgentinaFil: Salgado, Leonardo. Instituto de Investigación en Paleobiología y Geología. General Roca. Río Negro; ArgentinaFil: Fernández, Mariela. Inibioma-Centro Regional Universitario Bariloche. Bariloche. Río Negro; ArgentinaFil: Cerda, Ignacio A.. Instituto de Investigación en Paleobiología y Geología. Museo Provincial Carlos Ameghino. Cipolletti; ArgentinaFil: Carabajal, Ariana Paulina. Museo Carmen Funes. Plaza Huincul. Neuquén; ArgentinaFil: Otero, Alejandro. Museo de La Plata. Universidad Nacional de La Plata; ArgentinaFil: Coria, Rodolfo A.. Instituto de Paleobiología y Geología. Universidad Nacional de Río Negro. Neuquén; ArgentinaFil: Fiorelli, Lucas E.. Centro Regional de Investigaciones Científicas y Transferencia Tecnológica. Anillaco. La Rioja; Argentin

Integrated motor drives: state of the art and future trends

With increased need for high power density, high efficiency and high temperature capabilities in Aerospace and Automotive applications, Integrated Motor Drives (IMD) offers a potential solution. However, close physical integration of the converter and the machine may also lead to an increase in components temperature. This requires careful mechanical, structural and thermal analysis; and design of the IMD system. This paper reviews existing IMD technologies and their thermal effects on the IMD system. The effects of the power electronics (PE) position on the IMD system and its respective thermal management concepts are also investigated. The challenges faced in designing and manufacturing of an IMD along with the mechanical and structural impacts of close physical integration is also discussed and potential solutions are provided. Potential converter topologies for an IMD like the Matrix converter, 2-level Bridge, 3-level NPC and Multiphase full bridge converters are also reviewed. Wide band gap devices like SiC and GaN and their packaging in power modules for IMDs are also discussed. Power modules components and packaging technologies are also presented

Controle associado de Alphitobius diaperinuse efeito de microrganismos eficazes no desenvolvimento de Beauveria bassiana

O objetivo deste trabalho foi avaliar a eficiência de Beauveria bassiana (Bb), terra diatomácea (TD) e microrganismos eficazes (EM-4), associados ou não, no controle de Alphitobius diaperinus, e o efeito de EM-4 no desenvolvimento de B. bassiana. Os agentes de controle (Bb, TD e EM-4), em diferentes concentrações e combinações, foram aplicados em uma mistura de cama-de-frango e ração, em que os insetos foram acondicionados por dez dias. Avaliaram-se, in vitro: a germinação, as unidades formadoras de colônia (UFC), o crescimento vegetativo e a produtividade de conídios de Bb em contato com suspensão aquosa de EM-4 (1%) não filtrada e filtrada. Os maiores índices de mortalidade foram observados nos tratamentos TD + Bb + EM-4 e TD + Bb, nas maiores concentrações. Verificou-se efeito não-aditivo sinérgico para TD + Bb nas três concentrações. Nos testes com EM-4 filtrado, não houve diferença em relação à testemunha quanto à germinação e às UFC, entretanto, o crescimento vegetativo e a produtividade de conídios foram negativamente afetados. O uso conjunto de B. bassiana e terra diatomácea, para o manejo de populações de A. diaperinus, pode reduzir o uso de produtos químicos

Measurement of the cross section for isolated-photon plus jet production in pp collisions at √s=13 TeV using the ATLAS detector

The dynamics of isolated-photon production in association with a jet in proton–proton collisions at a centre-of-mass energy of 13 TeV are studied with the ATLAS detector at the LHC using a dataset with an integrated luminosity of 3.2 fb−1. Photons are required to have transverse energies above 125 GeV. Jets are identified using the anti- algorithm with radius parameter and required to have transverse momenta above 100 GeV. Measurements of isolated-photon plus jet cross sections are presented as functions of the leading-photon transverse energy, the leading-jet transverse momentum, the azimuthal angular separation between the photon and the jet, the photon–jet invariant mass and the scattering angle in the photon–jet centre-of-mass system. Tree-level plus parton-shower predictions from Sherpa and Pythia as well as next-to-leading-order QCD predictions from Jetphox and Sherpa are compared to the measurements