Reverse Logistics – Capturing Value in the Extended Supply Chain

Product flows in today’s supply chains do not end once they have reached the customer. Many products lead a second and even third or fourth life after having accomplished their original task at their first customer. Consequently, a product may generate revenues multiple times, rather than a single time. Capturing this value requires a broadening of the supply chain perspective to include new processes, known as ‘reverse logistics’, as well as multiple interrelated usage cycles, linked by specific market interfaces. Coordinating the successive product uses is key to maximizing the value generated. In this chapter, we review the field of reverse logistics. We discuss its opportunities and its challenges and indicate potential ways for companies to master them. We highlight what makes reverse logistics different from ‘conventional’ supply chain processes, but also point out analogies, and explain how both views can be integrated into an extended supply chain concept. We illustrate our discussion with examples of reverse logistics practice at IBM

Boundaries and Prototypes in Categorizing Direction

Projective terms such as left, right, front, back are conceptually interesting due to their flexibility of contextual usage and their central relevance to human spatial cognition. Their default acceptability areas are well known, with prototypical axes representing their most central usage and decreasing acceptability away from the axes. Previous research has shown these axes to be boundaries in certain non-linguistic tasks, indicating an inverse relationship between linguistic and non-linguistic direction concepts under specific circumstances. Given this striking mismatch, our study asks how such inverse non-linguistic concepts are represented in language, as well as how people describe their categorization. Our findings highlight two distinct grouping strategies reminiscent of theories of human categorization: prototype based or boundary based. These lead to different linguistic as well as non-linguistic patterns

Whole exome sequencing identifies genetic variants in inherited thrombocytopenia with secondary qualitative function defects

Inherited thrombocytopenias are a heterogeneous group of disorders characterised by abnormally low platelet counts which can be associated with abnormal bleeding. Next generation sequencing has previously been employed in these disorders for the confirmation of suspected genetic abnormalities, and more recently in the discovery of novel disease causing genes. However its full potential has not previously been utilised. Over the past 6 years we have sequenced the exomes from 55 patients, including 37 index cases and 18 additional family members, all of whom were recruited to the UK Genotyping and Phenotyping of Platelets study. All patients had inherited or sustained thrombocytopenia of unknown aetiology with platelet counts varying from 11-186x109 /L. Of the 51 patients phenotypically tested, 37 (73%), had an additional secondary qualitative platelet defect. Using whole exome sequencing analysis we have identified “pathogenic” or “likely pathogenic” variants in 46% (17/37) of our index patients with thrombocytopenia. In addition, we report variants of uncertain significance in 12 index cases which include novel candidate genetic variants in previously unreported genes in four index cases. These results demonstrate that whole exome sequencing is an efficient method for elucidating potential pathogenic genetic variants in inherited thrombocytopenia. Whole exome sequencing also has the added benefit of discovering potentially pathogenic genetic variants for further study in novel genes not previously implicated in inherited thrombocytopenia

A comprehensive targeted next-generation sequencing panel for genetic diagnosis of patients with suspected inherited thrombocytopenia.

Background: Inherited thrombocytopenias (ITs) are a heterogeneous group of disorders characterized by low platelet counts and often disproportionate bleeding with over 30 genes currently implicated. Previously the UK-GAPP study using whole exome sequencing (WES) identified a pathogenic variant in 19 of 47 (40%) patients of which 71% had variants in genes known to cause IT. Aims: To employ a targeted next-generation sequencing platform to improve efficiency of diagnostic testing and reduce overall costs. Methods: We have developed an IT-specific gene panel as a pre-screen for patients prior to WES using the Agilent SureSelectQXT transposon-based enrichment system. Results: Thirty-one patients were analyzed using the panel-based sequencing, of which; 10% (3/31) were identified with a classified pathogenic variant, 16% (5/31) were identified with a likely pathogenic variant, 51% (16/31) were identified with variants of unknown significance, and 23% (7/31) were identified with either no variant or a benign variant. Discussion and Conclusion: Although requiring further clarification of the impact of the genetic variations, the application of an IT-specific next generation sequencing panel is an viable method of pre-screening patients for variants in known IT-causing genes prior to WES. With an added benefit of distinguishing IT from idiopathic thrombocytopenic purpura (ITP) and the potential to identify variants in genes known to have a predisposition to hematological malignancies, it could become a critical step in improving patient clinical management

Implication of sperm RNAs in transgenerational inheritance of the effects of early trauma in mice.

Small non-coding RNAs (sncRNAs) are potential vectors at the interface between genes and environment. We found that traumatic stress in early life altered mouse microRNA (miRNA) expression, and behavioral and metabolic responses in the progeny. Injection of sperm RNAs from traumatized males into fertilized wild-type oocytes reproduced the behavioral and metabolic alterations in the resulting offspring.We thank M. Rassoulzadegan and V. Grandjean for help with the sperm purification, F. Manuella and H. Hörster for assistance with the MSUS paradigm, H. Welzl for help with behavior, G. Vernaz for help with western blotting, R. Tweedie-Cullen and P. Nanni for help with mass spectrometry, A. Patrignani for advice on DNA and RNA quality assessment, and A. Chen and A. Brunner for constructive discussions. This work was supported by the Austrian Academy of Sciences, the University of Zürich, the Swiss Federal Institute of Technology, Roche, the Swiss National Science Foundation, and The National Center of Competence in Research “Neural Plasticity and Repair”. P.S. was supported by a Gonville and Caius College fellowship.This is the accepted manuscript. The final version is available in Nature Neuroscience 17, 667–669 (2014), doi:10.1038/nn.369

A Close Eye on the Eagle-Eyed Visual Acuity Hypothesis of Autism

Autism spectrum disorders (ASD) have been associated with sensory hypersensitivity. A recent study reported visual acuity (VA) in ASD in the region reported for birds of prey. The validity of the results was subsequently doubted. This study examined VA in 34 individuals with ASD, 16 with schizophrenia (SCH), and 26 typically developing (TYP). Participants with ASD did not show higher VA than those with SCH and TYP. There were no substantial correlations of VA with clinical severity in ASD or SCH. This study could not confirm the eagle-eyed acuity hypothesis of ASD, or find evidence for a connection of VA and clinical phenotypes. Research needs to further address the origins and circumstances associated with altered sensory or perceptual processing in ASD

Long-Term Effects of the Periconception Period on Embryo Epigenetic Profile and Phenotype: The Role of Stress and How This Effect Is Mediated

Stress represents an unavoidable aspect of human life, and pathologies associated with dysregulation of stress mechanisms - particularly psychiatric disorders - represent a significant global health problem. While it has long been observed that levels of stress experienced in the periconception period may greatly affect the offspring's risk of psychiatric disorders, the mechanisms underlying these associations are not yet comprehensively understood. In order to address this question, this chapter will take a 'top-down' approach, by first defining stress and associated concepts, before exploring the mechanistic basis of the stress response in the form of the hypothalamic-pituitary-adrenal (HPA) axis, and how dysregulation of the HPA axis can impede our mental and physical health, primarily via imbalances in glucocorticoids (GCs) and their corresponding receptors (GRs) in the brain. The current extent of knowledge pertaining to the impact of stress on developmental programming and epigenetic inheritance is then extensively discussed, including the role of chromatin remodelling associated with specific HPA axis-related genes and the possible role of regulatory RNAs as messengers of environmental stress both in the intrauterine environment and across the germ line. Furthering our understanding of the role of stress on embryonic development is crucial if we are to increase our predictive power of disease risk and devise-effective treatments and intervention strategies

The sperm factor: paternal impact beyond genes

The fact that sperm carry more than the paternal DNA has only been discovered just over a decade ago. With this discovery, the idea that the paternal condition may have direct implications for the fitness of the offspring had to be revisited. While this idea is still highly debated, empirical evidence for paternal effects is accumulating. Male condition not only affects male fertility but also offspring early development and performance later in life. Several factors have been identified as possible carriers of non-genetic information, but we still know little about their origin and function and even less about their causation. I consider four possible non-mutually exclusive adaptive and non-adaptive explanations for the existence of paternal effects in an evolutionary context. In addition, I provide a brief overview of the main non-genetic components found in sperm including DNA methylation, chromatin modifications, RNAs and proteins. I discuss their putative functions and present currently available examples for their role in transferring non-genetic information from the father to the offspring. Finally, I identify some of the most important open questions and present possible future research avenues