A model to assess the impacts of ISO management systems standards

The most widely diffused ISO standards are ISO 9001 and ISO 14001. The main objectives of those are to demonstrate the capability to satisfy the requirements of the customers and to demonstrate the continuous search to reduce the impacts on the environment, respectively. However, these certifications will not necessarily be reflected in the performance of the company. Through the analysis of the literature, mixed results are observed, showing that not all certified companies could achieve benefits and improve the performance of the organization due to the ISO standards certification.Based on a literature review and a questionnaire survey, this paper defines a model where the main critical success factors which will influence the internalization level of the ISO 9001 and ISO 14001 are presented, and consequently their impacts on the organizations. This model could help researchers and practitioners in the process of evaluating the ISO standards impacts and the possible reasons for different outcomes.- This research was funded by FCT-Fundacao para a Ciencia e Tecnologia within the R&D Units Project Scope: UIDB/00319/2020. Monica Cabecinhas is supported by FCT Doctorate Grant Reference SFRH/BD/131932/2017

Multicentric case series of scuba diving fatalities: The role of intracardiac gaseous carbon dioxide in the forensic diagnosis.

Scuba diving fatalities post-mortem diagnosis presents a higher level of forensic complexity because of their occurrence in a non-natural human life environment. Scuba divers are equipped with diving gas to breathe underwater. It is essential for them to be fully trained in order to be able to manage their dive safely despite the varying increase of ambient pressure and temperature decrease. Throughout the dive, the inhaled diving gas is dissolved in the diver's tissues during the descent and if the decompression steps are not respected during the ascent, the balance between the dissolved gas and the tissues (including blood) is disrupted, leading to a gaseous release in the organism. Depending on the magnitude of this gaseous release, free gas can occur in blood and tissue. Venous or arterial gas embolism can also occur as a consequence of decompression sickness or barotraumatism. It can also induce drowsiness that consequently leads to drowning. As a result, the occurrence of gas in dead scuba divers is very complex to interpret, as is the difficulty to distinguish it from resuscitation maneuver artifacts or body decomposition. Although the literature is scarce in this domain, significant work has been done to provide a precise intracadaveric gas sampling method to enlighten the cause and circumstances of death during the dive. The aim of this study is to obtain higher statistical significance by collecting a number of cases to confirm the gas sampling protocol and analysis and gain more information about the cause of death and the events surrounding the fatality through the establishment of clear management guidelines

Steroidogenic Acute Regulatory Protein (StAR): Evidence of Gonadotropin-Induced Steroidogenesis in Alzheimer Disease

BACKGROUND: Alzheimer disease (AD) is clinically characterized by progressive memory loss, impairments in behavior, language and visual-spatial skills and ultimately, death. Epidemiological data reporting the predisposition of women to AD has led to a number of lines of evidence suggesting that age-related changes in hormones of the hypothalamic-pituitary-gonadal (HPG) axis following reproductive senescence, may contribute to the etiology of AD. Recent studies from our group and others have reported not only increases in circulating gonadotropins, namely luteinizing hormone (LH) in individuals with AD compared with control individuals, but also significant elevations of LH in vulnerable neuronal populations in individuals with AD compared to control cases as well as the highest density of gonadotropin receptors in the brain are found within the hippocampus, a region devastated in AD. However, while LH is higher in AD patients, the downstream consequences of this are incompletely understood. To begin to examine this issue, here, we examined the expression levels of steroidogenic acute regulatory (StAR) protein, which regulates the first key event in steroidogenesis, namely, the transport of cholesterol into the mitochondria, and is regulated by LH through the cyclic AMP second messenger pathway, in AD and control brain tissue. RESULTS: Our data revealed that StAR protein was markedly increased in both the cytoplasm of hippocampal pyramidal neurons as well as in the cytoplasm of other non-neuronal cell types from AD brains when compared with age-matched controls. Importantly, and suggestive of a direct mechanistic link, StAR protein expression in AD brains colocalized with LH receptor expression. CONCLUSION: Therefore, our findings suggest that LH is not only able to bind to its receptor and induce potentially pathogenic signaling in AD, but also that steroidogenic pathways regulated by LH may play a role in AD

From Business Model to Business Modelling: Modularity and Manipulation

The concept of modularity has gained considerable traction in technology studies as a way to conceive, describe and innovate complex systems, such as product design or organizational structures. In the recent literature, technological modularity has often been intertwined with business model innovation, and scholarship has started investigating how modularity in technology affects changes in business models, both at the cognitive and activity system levels. Yet we still lack a theoretical definition of what modularity is in the business model domain. Business model innovation also encompasses different possibilities of modeling businesses, which are not clearly understood nor classified. We ask when, how and if modularity theory can be extended to business models in order to enable effective and efficient modeling. We distinguish theoretically between modularity for technology and for business models, and investigate the key processes of modularization and manipulation. We introduce the basic operations of business modeling via modular operators adapted from the technological modularity domain, using iconic examples to develop an analogical reasoning between modularity in technology and in business models. Finally, we discuss opportunities for using modularity theory to foster the understanding of business models and modeling, and develop a challenging research agenda for future investigations

Incumbent Responses to an Entrant with a New Business Model: Resource Co-Deployment and Resource Re-Deployment Strategies

The constructs of re-deployment and co-deployment have been central to discussions of scope economies in diversified firms. We argue however that these constructs are also significant in the context of single business firms. Increasingly, changes in technology and demand preferences have provided opportunities for entrants to attack incumbents with a different business model, one that may neutralize the incumbent’s advantage for at least some set of customers (e.g. Netflix versus Blockbuster). In such a context incumbents often respond by modifying their business model. We note that several of the business model-altering responses of the incumbent can be characterized in terms of co-deployment and re-deployment benefits and costs, where co-deployment benefits/cost apply to the scope economies/diseconomies in running multiple business-models within the same firm and re-deployment benefits/costs apply to the implications of moving assets from one business model to another. We then examine the set of strategic choices faced by the incumbent in competing with an entrant with a different business model. We identify five set of factors that are likely to influence the decision to choose between these alternatives – uncertainty spawned by the new business model, market segment targeted by the new model, the within-business-across-business-model co-deployment and re-deployment benefits and costs, the across-business co-deployment and re-deployment benefits and costs, and the incumbent’s prior performance history. Although some of these choices have seen some work, most remain relatively underexplored in the strategy literature. We highlight the potential for research in this area with a set of propositions that identify key conditions that should hold true for a particular strategic choice to be picked by an incumbent

Phenotypic Variation and Bistable Switching in Bacteria

Microbial research generally focuses on clonal populations. However, bacterial cells with identical genotypes frequently display different phenotypes under identical conditions. This microbial cell individuality is receiving increasing attention in the literature because of its impact on cellular differentiation, survival under selective conditions, and the interaction of pathogens with their hosts. It is becoming clear that stochasticity in gene expression in conjunction with the architecture of the gene network that underlies the cellular processes can generate phenotypic variation. An important regulatory mechanism is the so-called positive feedback, in which a system reinforces its own response, for instance by stimulating the production of an activator. Bistability is an interesting and relevant phenomenon, in which two distinct subpopulations of cells showing discrete levels of gene expression coexist in a single culture. In this chapter, we address techniques and approaches used to establish phenotypic variation, and relate three well-characterized examples of bistability to the molecular mechanisms that govern these processes, with a focus on positive feedback.

Integrated Analysis of Germline and Tumor DNA Identifies New Candidate Genes Involved in Familial Colorectal Cancer

Colorectal cancer (CRC) shows aggregation in some families but no alterations in the known hereditary CRC genes. We aimed to identify new candidate genes which are potentially involved in germline predisposition to familial CRC. An integrated analysis of germline and tumor whole-exome sequencing data was performed in 18 unrelated CRC families. Deleterious single nucleotide variants (SNV), short insertions and deletions (indels), copy number variants (CNVs) and loss of heterozygosity (LOH) were assessed as candidates for first germline or second somatic hits. Candidate tumor suppressor genes were selected when alterations were detected in both germline and somatic DNA, fulfilling Knudson's two-hit hypothesis. Somatic mutational profiling and signature analysis were also performed. A series of germline-somatic variant pairs were detected. In all cases, the first hit was presented as a rare SNV/indel, whereas the second hit was either a different SNV (3 genes) or LOH affecting the same gene (141 genes). BRCA2, BLM, ERCC2, RECQL, REV3L and RIF1 were among the most promising candidate genes for germline CRC predisposition. The identification of new candidate genes involved in familial CRC could be achieved by our integrated analysis. Further functional studies and replication in additional cohorts are required to confirm the selected candidates

Designing sequential transcription logic: a simple genetic circuit for conditional memory

The ability to learn and respond to recurrent events depends on the capacity to remember transient biological signals received in the past. Moreover, it may be desirable to remember or ignore these transient signals conditioned upon other signals that are active at specific points in time or in unique environments. Here, we propose a simple genetic circuit in bacteria that is capable of conditionally memorizing a signal in the form of a transcription factor concentration. The circuit behaves similarly to a "data latch" in an electronic circuit, i.e. it reads and stores an input signal only when conditioned to do so by a "read command". Our circuit is of the same size as the well-known genetic toggle switch (an unconditional latch) which consists of two mutually repressing genes, but is complemented with a "regulatory front end" involving protein heterodimerization as a simple way to implement conditional control. Deterministic and stochastic analysis of the circuit dynamics indicate that an experimental implementation is feasible based on well-characterized genes and proteins. It is not known, to which extent molecular networks are able to conditionally store information in natural contexts for bacteria. However, our results suggest that such sequential logic elements may be readily implemented by cells through the combination of existing protein-protein interactions and simple transcriptional regulation.Comment: 20 pages, 5 figures; supplementary material available upon request from the author