Re United Steelworkers and Vulcan Containers (Canada) Ltd

Employee Discharge alleging unjust discharge. Determination of quantum of damages. AWARD: In an award dated November 21, 1969, this board ordered the grievor to be reinstated in employment with compensation for loss of income except for wages she would have received in the first two weeks following her discharge by the company. Mr. Wrycraft dissented. The majority award stated that the grievor was subject to a duty to mitigate her losses so that any actual earnings and an amount equal to any earnings that she could have had if she had made a reasonable and prudent effort to find other work during the period of her discharge were to be deducted from her compensation. The working out of the exact amount of compensation was left to the parties, with the board remaining seized of the matter. The parties were unable to agree on the proper amount of compensation and the board reconvened

Machine Learning in Melanoma Diagnosis. Limitations About to be Overcome

[spa] Antecedentes: La clasificación automática de imágenes es una rama prometedora del aprendi-zaje automático (de sus siglas en inglés Machine Learning [ML]), y es una herramienta útil enel diagnóstico de cáncer de piel. Sin embargo, poco se ha estudiado acerca de las limitacionesde su uso en la práctica clínica diaria.Objetivo: Determinar las limitaciones que existen en cuanto a la selección de imágenes usadaspara el análisis por ML de las neoplasias cutáneas, en particular del melanoma.Métodos: Se dise ̃nó un estudio de cohorte retrospectivo, donde se incluyeron de forma conse-cutiva 2.849 imágenes dermatoscópicas de alta calidad de tumores cutáneos para su valoraciónpor un sistema de ML, recogidas entre los a ̃nos 2010 y 2014. Cada imagen dermatoscópica fueclasificada según las características de elegibilidad para el análisis por ML.Resultados: De las 2.849 imágenes elegidas a partir de nuestra base de datos, 968 (34%) cum-plieron los criterios de inclusión. De los 528 melanomas, 335 (63,4%) fueron excluidos. Laausencia de piel normal circundante (40,5% de todos los melanomas de nuestra base de datos)y la ausencia de pigmentación (14,2%) fueron las causas más frecuentes de exclusión para elanálisis por ML.Discusión: Solo el 36,6% de nuestros melanomas se consideraron aceptables para el análisispor sistemas de ML de última generación. Concluimos que los futuros sistemas de ML deberánser entrenados a partir de bases de datos más grandes que incluyan imágenes representativasde la práctica clínica habitual. Afortunadamente, muchas de estas limitaciones están siendosuperadas gracias a los avances realizados recientemente por la comunidad científica, como seha demostrado en trabajos recientes. [eng] Background: Automated image classification is a promising branch of machine learning (ML)useful for skin cancer diagnosis, but little has been determined about its limitations for generalusability in current clinical practice.Objective: To determine limitations in the selection of skin cancer images for ML analysis,particularly in melanoma.Methods: Retrospective cohort study design, including 2,849 consecutive high-quality dermos-copy images of skin tumors from 2010 to 2014, for evaluation by a ML system. Each dermoscopyimage was assorted according to its eligibility for ML analysis.Results: Of the 2,849 images chosen from our database, 968 (34%) met the inclusion criteriafor analysis by the ML system. Only 64.7% of nevi and 36.6% of melanoma met the inclusioncriteria. Of the 528 melanomas, 335 (63.4%) were excluded. An absence of normal surroundingskin (40.5% of all melanomas from our database) and absence of pigmentation (14.2%) were themost common reasons for exclusion from ML analysis.Discussion: Only 36.6% of our melanomas were admissible for analysis by state-of-the-art MLsystems. We conclude that future ML systems should be trained on larger datasets which includerelevant non-ideal images from lesions evaluated in real clinical practice. Fortunately, many ofthese limitations are being overcome by the scientific community as recent works show

Formyl Peptide Receptor as a Novel Therapeutic Target for Anxiety-Related Disorders

Formyl peptide receptors (FPR) belong to a family of sensors of the immune system that detect microbe-associated molecules and inform various cellular and sensorial mechanisms to the presence of pathogens in the host. Here we demonstrate that Fpr2/3-deficient mice show a distinct profile of behaviour characterised by reduced anxiety in the marble burying and light-dark box paradigms, increased exploratory behaviour in an open-field, together with superior performance on a novel object recognition test. Pharmacological blockade with a formyl peptide receptor antagonist, Boc2, in wild type mice reproduced most of the behavioural changes observed in the Fpr2/3(-/-) mice, including a significant improvement in novel object discrimination and reduced anxiety in a light/dark shuttle test. These effects were associated with reduced FPR signalling in the gut as shown by the significant reduction in the levels of p-p38. Collectively, these findings suggest that homeostatic FPR signalling exerts a modulatory effect on anxiety-like behaviours. These findings thus suggest that therapies targeting FPRs may be a novel approach to ameliorate behavioural abnormalities present in neuropsychiatric disorders at the cognitive-emotional interface

Optimization of the Balanced Steady State Free Precession (bSSFP) Pulse Sequence for Magnetic Resonance Imaging of the Mouse Prostate at 3T

INTRODUCTION: MRI can be used to non-invasively monitor tumour growth and response to treatment in mouse models of prostate cancer, particularly for longitudinal studies of orthotopically-implanted models. We have optimized the balanced steady-state free precession (bSSFP) pulse sequence for mouse prostate imaging. METHODS: Phase cycling, excitations, flip angle and receiver bandwidth parameters were optimized for signal to noise ratio and contrast to noise ratio of the prostate. The optimized bSSFP sequence was compared to T1- and T2-weighted spin echo sequences. RESULTS: SNR and CNR increased with flip angle. As bandwidth increased, SNR, CNR and artifacts such as chemical shift decreased. The final optimized sequence was 4 PC, 2 NEX, FA 50°, BW ±62.5 kHz and took 14-26 minutes with 200 µm isotropic resolution. The SNR efficiency of the bSSFP images was higher than for T1WSE and T2WSE. CNR was highest for T1WSE, followed closely by bSSFP, with the T2WSE having the lowest CNR. With the bSSFP images the whole body and organs of interest including renal, iliac, inguinal and popliteal lymph nodes were visible. CONCLUSION: We were able to obtain fast, high-resolution, high CNR images of the healthy mouse prostate with an optimized bSSFP sequence

Dose response of the 16p11.2 distal copy number variant on intracranial volume and basal ganglia.

Carriers of large recurrent copy number variants (CNVs) have a higher risk of developing neurodevelopmental disorders. The 16p11.2 distal CNV predisposes carriers to e.g., autism spectrum disorder and schizophrenia. We compared subcortical brain volumes of 12 16p11.2 distal deletion and 12 duplication carriers to 6882 non-carriers from the large-scale brain Magnetic Resonance Imaging collaboration, ENIGMA-CNV. After stringent CNV calling procedures, and standardized FreeSurfer image analysis, we found negative dose-response associations with copy number on intracranial volume and on regional caudate, pallidum and putamen volumes (β = -0.71 to -1.37; P < 0.0005). In an independent sample, consistent results were obtained, with significant effects in the pallidum (β = -0.95, P = 0.0042). The two data sets combined showed significant negative dose-response for the accumbens, caudate, pallidum, putamen and ICV (P = 0.0032, 8.9 × 10-6, 1.7 × 10-9, 3.5 × 10-12 and 1.0 × 10-4, respectively). Full scale IQ was lower in both deletion and duplication carriers compared to non-carriers. This is the first brain MRI study of the impact of the 16p11.2 distal CNV, and we demonstrate a specific effect on subcortical brain structures, suggesting a neuropathological pattern underlying the neurodevelopmental syndromes

Coordinated Sumoylation and Ubiquitination Modulate EGF Induced EGR1 Expression and Stability

Abstract: Background: Human early growth response-1 (EGR1) is a member of the zing-finger family of transcription factors induced by a range of molecular and environmental stimuli including epidermal growth factor (EGF). In a recently published paper we demonstrated that integrin/EGFR cross-talk was required for Egr1 expression through activation of the Erk1/2 and PI3K/Akt/Forkhead pathways. EGR1 activity and stability can be influenced by many different post-translational modifications such as acetylation, phosphorylation, ubiquitination and the recently discovered sumoylation. The aim of this work was to assess the influence of sumoylation on EGF induced Egr1 expression and/or stability. Methods: We modulated the expression of proteins involved in the sumoylation process in ECV304 cells by transient transfection and evaluated Egr1 expression in response to EGF treatment at mRNA and protein levels. Results: We demonstrated that in ECV304 cells Egr1 was transiently induced upon EGF treatment and a fraction of the endogenous protein was sumoylated. Moreover, SUMO-1/Ubc9 over-expression stabilized EGF induced ERK1/2 phosphorylation and increased Egr1 gene transcription. Conversely, in SUMO-1/Ubc9 transfected cells, EGR1 protein levels were strongly reduced. Data obtained from protein expression and ubiquitination analysis, in the presence of the proteasome inhibitor MG132, suggested that upon EGF stimuli EGR1 sumoylation enhanced its turnover, increasing ubiquitination and proteasome mediated degradation. Conclusions: Here we demonstrate that SUMO-1 modification improving EGR1 ubiquitination is involved in the modulation of its stability upon EGF mediated induction

The Level of Protein in Milk Formula Modifies Ileal Sensitivity to LPS Later in Life in a Piglet Model

Background: Milk formulas have higher protein contents than human milk. This high protein level could modify the development of intestinal microbiota, epithelial barrier and immune functions and have long-term consequences. Methodology/Principal findings: We investigated the effect of a high protein formula on ileal microbiota and physiology during the neonatal period and later in life. Piglets were fed from 2 to 28 days of age either a normoprotein (NP, equivalent to sow milk) or a high protein formula (HP, +40% protein). Then, they received the same solid diet until 160 days. During the formula feeding period ileal microbiota implantation was accelerated in HP piglets with greater concentrations of ileal bacteria at d7 in HP than NP piglets. Epithelial barrier function was altered with a higher permeability to small and large probes in Ussing chambers in HP compared to NP piglets without difference in bacterial translocation. Infiltration of T cells was increased in HP piglets at d28. IL-1b and NF-kappa B sub-units mRNA levels were reduced in HP piglets at d7 and d28 respectively; plasma haptoglobin also tended to be reduced at d7. Later in life, pro-inflammatory cytokines secretion in response to high doses of LPS in explants culture was reduced in HP compared to NP piglets. Levels of mRNA coding the NF-kappa B pathway sub-units were increased by the challenge with LPS in NP piglets, but not HP ones. Conclusions/Significance: A high protein level in formula affects the postnatal development of ileal microbiota, epithelial barrier and immune function in piglets and alters ileal response to inflammatory mediators later in life

Using fish models to investigate the links between microbiome and social behaviour: the next step for translational microbiome research?

Recent research has revealed surprisingly important connections between animals’ microbiome and social behaviour. Social interactions can affect the composition and function of the microbiome; conversely, the microbiome affects social communication by influencing the hosts’ central nervous system and peripheral chemical communication. These discoveries set the stage for novel research focusing on the evolution and physiology of animal social behaviour in relation to microbial transmission strategies. Here, we discuss the emerging roles of teleost fish models and their potential for advancing research fields, linked to sociality and microbial regulation. We argue that fish models, such as the zebrafish (Danio rerio, Cyprinidae), sticklebacks (‎Gasterosteidae), guppies (Poeciliidae) and cleaner–client dyads (e.g., obligate cleaner fish from the Labridae and Gobiidae families and their visiting clientele), will provide valuable insights into the roles of microbiome in shaping social behaviour and vice versa, while also being of direct relevance to the food and ornamental fish trades. The diversity of fish behaviour warrants more interdisciplinary research, including microbiome studies, which should have a strong ecological (field‐derived) approach, together with laboratory‐based cognitive and neurobiological experimentation. The implications of such integrated approaches may be of translational relevance, opening new avenues for future investigation using fish models