Anomaly Detection Methods to Improve Supply Chain Data Quality and Operations

Supply chain operations drive the planning, manufacture, and distribution of billions of semiconductors a year, spanning thousands of products across many supply chain configurations. The customizations span from wafer technology to die stacking and chip feature enablement. Data quality drives efficiency in these processes and anomalies in data can be very disruptive, and at times, consequential. Developing preventative measures that automate the detection of anomalies before they reach downstream execution systems would result in significant efficiency gain for the organization. The purpose of this research is to identify an effective, actionable, and computationally efficient approach to highlight anomalies in a sparse and highly variable supply chain data structure. This research highlights the application of ensemble unsupervised learning algorithms for anomaly detection on supply chain demand data. The outlier detection algorithms explored include Angle-Based Outlier Detection, Isolation Forest, Local Outlier Factor and K-Nearest Neighbors. The application of an ensemble technique on unconstrained forecast signal, which is traditionally a consistent demand line, demonstrated a dramatic decrease in false positives. The application of the ensemble technique to the sales-order netted demand forecast, a signal that is irregular in structure, the algorithm identifies true anomalous observations relative to historical observations across time. The research team concluded that assessing an outlier is not limited to the most recent forecast’s observations but must be considered in the context of historical demand patterns across time

Stress, ageing and their influence on functional, cellular and molecular aspects of the immune system

The immune response is essential for keeping an organism healthy and for defending it from different types of pathogens. It is a complex system that consists of a large number of components performing different functions. The adequate and controlled interaction between these components is necessary for a robust and strong immune response. There are, however, many factors that interfere with the way the immune response functions. Stress and ageing now consistently appear in the literature as factors that act upon the immune system in the way that is often damaging. This review focuses on the role of stress and ageing in altering the robustness of the immune response first separately, and then simultaneously, discussing the effects that emerge from their interplay. The special focus is on the psychological stress and the impact that it has at different levels, from the whole system to the individual molecules, resulting in consequences for physical health

Corroborating indicates nurses’ ethical values in a geriatric ward

The aim of the study was to identify nurses’ ethical values, which become apparent through their behaviour in the interactions with older patients in caring encounters at a geriatric clinic

Selection Mechanisms Underlying High Impact Biomedical Research - A Qualitative Analysis and Causal Model

BACKGROUND: Although scientific innovation has been a long-standing topic of interest for historians, philosophers and cognitive scientists, few studies in biomedical research have examined from researchers' perspectives how high impact publications are developed and why they are consistently produced by a small group of researchers. Our objective was therefore to interview a group of researchers with a track record of high impact publications to explore what mechanism they believe contribute to the generation of high impact publications. METHODOLOGY/PRINCIPAL FINDINGS: Researchers were located in universities all over the globe and interviews were conducted by phone. All interviews were transcribed using standard qualitative methods. A Grounded Theory approach was used to code each transcript, later aggregating concept and categories into overarching explanation model. The model was then translated into a System Dynamics mathematical model to represent its structure and behavior. Five emerging themes were found in our study. First, researchers used heuristics or rules of thumb that came naturally to them. Second, these heuristics were reinforced by positive feedback from their peers and mentors. Third, good communication skills allowed researchers to provide feedback to their peers, thus closing a positive feedback loop. Fourth, researchers exhibited a number of psychological attributes such as curiosity or open-mindedness that constantly motivated them, even when faced with discouraging situations. Fifth, the system is dominated by randomness and serendipity and is far from a linear and predictable environment. Some researchers, however, took advantage of this randomness by incorporating mechanisms that would allow them to benefit from random findings. The aggregation of these themes into a policy model represented the overall expected behavior of publications and their impact achieved by high impact researchers. CONCLUSIONS: The proposed selection mechanism provides insights that can be translated into research coaching programs as well as research policy models to optimize the introduction of high impact research at a broad scale among institutional and governmental agencies

Modulation of hepatic inflammation and energy-sensing pathways in the rat liver by high-fructose diet and chronic stress

Purpose High-fructose consumption and chronic stress are both associated with metabolic inflammation and insulin resistance. Recently, disturbed activity of energy sensor AMP-activated protein kinase (AMPK) was recognized as mediator between nutrient-induced stress and inflammation. Thus, we analyzed the effects of high-fructose diet, alone or in combination with chronic stress, on glucose homeostasis, inflammation and expression of energy sensing proteins in the rat liver. Methods In male Wistar rats exposed to 9-week 20% fructose diet and/or 4-week chronic unpredictable stress we measured plasma and hepatic corticosterone level, indicators of glucose homeostasis and lipid metabolism, hepatic inflammation (pro- and anti-inflammatory cytokine levels, Toll-like receptor 4, NLRP3, activation of NF kappa B, JNK and ERK pathways) and levels of energy-sensing proteins AMPK, SIRT1 and peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1 alpha). Results High-fructose diet led to glucose intolerance, activation of NF kappa B and JNK pathways and increased intrahepatic IL-1 beta, TNF alpha and inhibitory phosphorylation of insulin receptor substrate 1 on Ser(307). It also decreased phospho-AMPK/AMPK ratio and increased SIRT1 expression. Stress alone increased plasma and hepatic corticosterone but did not influence glucose tolerance, nor hepatic inflammatory or energy-sensing proteins. After the combined treatment, hepatic corticosterone was increased, glucose tolerance remained preserved, while hepatic inflammation was partially prevented despite decreased AMPK activity. Conclusion High-fructose diet resulted in glucose intolerance, hepatic inflammation, decreased AMPK activity and reduced insulin sensitivity. Chronic stress alone did not exert such effects, but when applied together with high-fructose diet it could partially prevent fructose-induced inflammation, presumably due to increased hepatic glucocorticoids

The effects of male age on sperm analysis by motile sperm organelle morphology examination (MSOME)

<p>Abstract</p> <p>Background</p> <p>This study aimed to investigate the influence of age on sperm quality, as analysed by motile sperm organelle morphology examination (MSOME).</p> <p>Methods</p> <p>Semen samples were collected from 975 men undergoing evaluation or treatment for infertility. Sperm cells were evaluated at 8400× magnification using an inverted microscope equipped with Nomarski (differential interference contrast) optics. Two forms of spermatozoa were considered: normal spermatozoa and spermatozoa with large nuclear vacuoles (LNV, defined as vacuoles occupying > 50% of the sperm nuclear area). At least 200 spermatozoa per sample were evaluated, and the percentages of normal and LNV spermatozoa were determined. The subjects were divided into three groups according to age: Group I, less than or equal to 35 years; Group II, 36-40 years; and Group III, greater than or equal to 41 years.</p> <p>Results</p> <p>There was no difference in the percentages of normal sperm between the two younger (I and II) groups (<it>P ></it>0.05). The percentage of normal sperm in the older group (III) was significantly lower than that in the younger (I and II) groups (<it>P </it>< 0.05). There was no difference in the percentage of LNV spermatozoa between the younger (I and II) groups (<it>P ></it>0.05). The percentage of LNV spermatozoa was significantly higher in the older group (III) than in the younger (I and II) groups (<it>P </it>< 0.05). Regression analysis demonstrated a significant decrease in the incidence of normal sperm with increasing age (<it>P </it>< 0.05; r = -0.10). However, there was a significant positive correlation between the percentage of spermatozoa with LNV and male age (<it>P </it>< 0.05, r = 0.10).</p> <p>Conclusion</p> <p>The results demonstrated a consistent decline in semen quality, as reflected by morphological evaluation by MSOME, with increased age. Considering the relationship between nuclear vacuoles and DNA damage, these age-related changes predict that increased paternal age should be associated with unsuccessful or abnormal pregnancy as a consequence of fertilisation with damaged spermatozoa. Given that sperm nuclear vacuoles can be evaluated more precisely at high magnification, these results support the routine use of MSOME for ICSI as a criterion for semen analysis.</p

PDE 7 Inhibitors: New Potential Drugs for the Therapy of Spinal Cord Injury

BACKGROUND: Primary traumatic mechanical injury to the spinal cord (SCI) causes the death of a number of neurons that to date can neither be recovered nor regenerated. During the last years our group has been involved in the design, synthesis and evaluation of PDE7 inhibitors as new innovative drugs for several neurological disorders. Our working hypothesis is based on two different facts. Firstly, neuroinflammation is modulated by cAMP levels, thus the key role for phosphodiesterases (PDEs), which hydrolyze cAMP, is undoubtedly demonstrated. On the other hand, PDE7 is expressed simultaneously on leukocytes and on the brain, highlighting the potential crucial role of PDE7 as drug target for neuroinflammation. METHODOLOGY/PRINCIPAL FINDINGS: Here we present two chemically diverse families of PDE7 inhibitors, designed using computational techniques such as virtual screening and neuronal networks. We report their biological profile and their efficacy in an experimental SCI model induced by the application of vascular clips (force of 24 g) to the dura via a four-level T5-T8 laminectomy. We have selected two candidates, namely S14 and VP1.15, as PDE7 inhibitors. These compounds increase cAMP production both in macrophage and neuronal cell lines. Regarding drug-like properties, compounds were able to cross the blood brain barrier using parallel artificial membranes (PAMPA) methodology. SCI in mice resulted in severe trauma characterized by edema, neutrophil infiltration, and production of a range of inflammatory mediators, tissue damage, and apoptosis. Treatment of the mice with S14 and VP1.15, two PDE7 inhibitors, significantly reduced the degree of spinal cord inflammation, tissue injury (histological score), and TNF-α, IL-6, COX-2 and iNOS expression. CONCLUSIONS/SIGNIFICANCE: All these data together led us to propose PDE7 inhibitors, and specifically S14 and VP1.15, as potential drug candidates to be further studied for the treatment of SCI