The concept of system resilience is important and popular—in fact, hyper-popular over the last few years. Clarifying the technical meanings and foundations of the concept of resilience would appear ...to be necessary. Proposals for defining resilience are flourishing as well. This paper organizes the different technical approaches to the question of what is resilience and how to engineer it in complex adaptive systems. This paper groups the different uses of the label ‘resilience’ around four basic concepts: (1) resilience as rebound from trauma and return to equilibrium; (2) resilience as a synonym for robustness; (3) resilience as the opposite of brittleness, i.e., as graceful extensibility when surprise challenges boundaries; (4) resilience as network architectures that can sustain the ability to adapt to future surprises as conditions evolve.
•There continues to be a wide diversity of definitions of the label resilience.•Research progress points to 4 basic concepts underneath diverse uses of.•Each of the four core concepts defines different research agendas.•The 4 concepts provide guides on how to engineer resilience for safety.
D. D. Raphael provides a critical account of the moral philosophy of Adam Smith, presented in his first book, The Theory of Moral Sentiments. Whilst it does not have the same prominence in its field ...as his work on economics, The Wealth of Nations, Smith's writing on ethics is of continuing importance and interest today, especially for its theory of conscience. Smith sees the origin of conscience in the sympathetic and antipathetic feelings of spectators. As spectators of the actions of other people, we can imagine how we would feel in their situation. If we would share their motives, we approve of their action. If not, we disapprove. When we ourselves take an action, we know from experience what spectators would feel, approval or disapproval. That knowledge forms conscience, an imagined impartial spectator who tells us whether an action is right or wrong. In describing the content of moral judgement, Smith is much influenced by Stoic ethics, with an emphasis on self-command, but he voices criticism as well as praise. His own position is a combination of Stoic and Christian values. There is a substantial difference between the first five editions of the Moral Sentiments and the sixth. Failure to take account of this has led some commentators to mistaken views about the supposed youthful idealism of the Moral Sentiments as contrasted with the mature realism of The Wealth of Nations. A further source of error has been the supposition that Smith treats sympathy as the motive of moral action, as contrasted with the supposedly universal motive of self-interest in The Wealth of Nations. Available in OSO: http://www.oxfordscholarship.com/oso/public/content/philosophy/019921333X/toc.html
The Sensory Neurons of Touch Abraira, Victoria E.; Ginty, David D.
Neuron (Cambridge, Mass.),
08/2013, Letnik:
79, Številka:
4
Journal Article
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The somatosensory system decodes a wide range of tactile stimuli and thus endows us with a remarkable capacity for object recognition, texture discrimination, sensory-motor feedback and social ...exchange. The first step leading to perception of innocuous touch is activation of cutaneous sensory neurons called low-threshold mechanoreceptors (LTMRs). Here, we review the properties and functions of LTMRs, emphasizing the unique tuning properties of LTMR subtypes and the organizational logic of their peripheral and central axonal projections. We discuss the spinal cord neurophysiological representation of complex mechanical forces acting upon the skin and current views of how tactile information is processed and conveyed from the spinal cord to the brain. An integrative model in which ensembles of impulses arising from physiologically distinct LTMRs are integrated and processed in somatotopically aligned mechanosensory columns of the spinal cord dorsal horn underlies the nervous system’s enormous capacity for perceiving the richness of the tactile world.
Low-threshold mechanoreceptors (LTMRs) are critical for touch perception. Here, Abraira and Ginty review LTMR structure and function, emphasizing their unique tuning properties and the organizational logic of their axonal projections, which underlie our capacity for perceiving the richness of the tactile world.
Summary Background Patients with locally advanced rectal cancer who achieve a pathological complete response to neoadjuvant chemoradiation have an improved prognosis. The need for surgery in these ...patients has been questioned, but the proportion of patients achieving a pathological complete response is small. We aimed to assess whether adding cycles of mFOLFOX6 between chemoradiation and surgery increased the proportion of patients achieving a pathological complete response. Methods We did a phase 2, non-randomised trial consisting of four sequential study groups of patients with stage II–III locally advanced rectal cancer at 17 institutions in the USA and Canada. All patients received chemoradiation (fluorouracil 225 mg/m2 per day by continuous infusion throughout radiotherapy, and 45·0 Gy in 25 fractions, 5 days per week for 5 weeks, followed by a minimum boost of 5·4 Gy). Patients in group 1 had total mesorectal excision 6–8 weeks after chemoradiation. Patients in groups 2–4 received two, four, or six cycles of mFOLFOX6, respectively, between chemoradiation and total mesorectal excision. Each cycle of mFOLFOX6 consisted of racemic leucovorin 200 mg/m2 or 400 mg/m2 , according to the discretion of the treating investigator, oxaliplatin 85 mg/m2 in a 2-h infusion, bolus fluorouracil 400 mg/m2 on day 1, and a 46-h infusion of fluorouracil 2400 mg/m2 . The primary endpoint was the proportion of patients who achieved a pathological complete response, analysed by intention to treat. This trial is registered with ClinicalTrials.gov , number NCT00335816. Findings Between March 24, 2004, and Nov 16, 2012, 292 patients were registered, 259 of whom (60 in group 1, 67 in group 2, 67 in group 3, and 65 in group 4) met criteria for analysis. 11 (18%, 95% CI 10–30) of 60 patients in group 1, 17 (25%, 16–37) of 67 in group 2, 20 (30%, 19–42) of 67 in group 3, and 25 (38%, 27–51) of 65 in group 4 achieved a pathological complete response (p=0·0036). Study group was independently associated with pathological complete response (group 4 compared with group 1 odds ratio 3·49, 95% CI 1·39–8·75; p=0·011). In group 2, two (3%) of 67 patients had grade 3 adverse events associated with the neoadjuvant administration of mFOLFOX6 and one (1%) had a grade 4 adverse event; in group 3, 12 (18%) of 67 patients had grade 3 adverse events; in group 4, 18 (28%) of 65 patients had grade 3 adverse events and five (8%) had grade 4 adverse events. The most common grade 3 or higher adverse events associated with the neoadjuvant administration of mFOLFOX6 across groups 2–4 were neutropenia (five in group 3 and six in group 4) and lymphopenia (three in group 3 and four in group 4). Across all study groups, 25 grade 3 or worse surgery-related complications occurred (ten in group 1, five in group 2, three in group 3, and seven in group 4); the most common were pelvic abscesses (seven patients) and anastomotic leaks (seven patients). Interpretation Delivery of mFOLFOX6 after chemoradiation and before total mesorectal excision has the potential to increase the proportion of patients eligible for less invasive treatment strategies; this strategy is being tested in phase 3 clinical trials. Funding National Institutes of Health National Cancer Institute.
Germline mutation in either BRCA1 or BRCA2 is associated with an increased risk of ovarian cancer, particularly the most common invasive histotype - serous carcinoma. In addition, serous ovarian ...cancers have an unusually high frequency of other molecular events involving BRCA pathway dysfunction. Recent findings show a high frequency of TP53 mutation, chromosomal instability, distinct molecular subtypes and DNA copy number-driven changes in gene expression. These findings suggest a model in which homologous recombination repair deficiency initiates a cascade of molecular events that sculpt the evolution of high-grade serous ovarian cancer and dictate its response to therapy.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Our sense of touch emerges from an array of mechanosensory structures residing within the fabric of our skin. These tactile end organ structures convert innocuous forces acting on the skin into ...electrical signals that propagate to the CNS via the axons of low-threshold mechanoreceptors (LTMRs). Our rich capacity for tactile discrimination arises from the dissimilar intrinsic properties of the LTMR subtypes that innervate different regions of the skin and the structurally distinct end organ complexes with which they associate. These end organ structures comprise a range of non-neuronal cell types, which may themselves actively contribute to the transformation of tactile forces into neural impulses within the LTMR afferents. Although the mechanism and the site of transduction across end organs remain unclear, PIEZO2 has emerged as the principal mechanosensitive channel involved in light touch of the skin. Here we review the physiological properties of LTMR subtypes and discuss how features of their cutaneous end organ complexes shape subtype-specific tuning.
Coffee is a rich source of dietary antioxidants, and this property, coupled with the fact that coffee is one of the world's most popular beverages, has led to the understanding that coffee is a major ...contributor to dietary antioxidant intake. Brewed coffee is a complex food matrix with numerous phytochemical components that have antioxidant activity capable of scavenging free radicals, donating hydrogen and electrons, providing reducing activity and also acting as metal ion pro-oxidant chelators. More recent studies have shown that coffee components can trigger tissue antioxidant gene expression and protect against gastrointestinal oxidative stress. This paper will describe different in vitro, cell-free and cell-based assays that both characterize and compare the antioxidant capacity and mechanism of action of coffee and its bioactive constituents. Moreover, evidence of cellular antioxidant activity and correlated specific genomic events induced by coffee components, which are relevant to antioxidant function in both animal and human studies, will be discussed.
Chlorogenic acids (CGAs) are esters formed between caffeic and quinic acids, and represent an abundant group of plant polyphenols present in the human diet. CGAs have different subgroups that include ...caffeoylquinic, p-coumaroylquinic, and feruloyquinic acids. Results of epidemiological studies suggest that the consumption of beverages such as coffee, tea, wine, different herbal infusions, and also some fruit juices is linked to reduced risks of developing different chronic diseases. These beverages contain CGAs present in different concentrations and isomeric mixtures. The underlying mechanism(s) for specific health benefits attributed to CGAs involves mitigating oxidative stress, and hence the related adverse effects associated with an unbalanced intracellular redox state. There is also evidence to show that CGAs exhibit anti-inflammatory activities by modulating a number of important metabolic pathways. This review will focus on three specific aspects of the relevance of CGAs in coffee beverages; namely: (1) the relative composition of different CGA isomers present in coffee beverages; (2) analysis of in vitro and in vivo evidence that CGAs and individual isomers can mitigate oxidative and inflammatory stresses; and (3) description of the molecular mechanisms that have a key role in the cell signaling activity that underlines important functions.
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