Background
Understanding the factors influencing nodal status in breast cancer is vital for axillary staging, therapy, and patient survival. The nodal stage remains a crucial factor in ...prognostication indices. This study investigates the relationship between tumour-to-skin distance (in T1–T3 tumours where the skin is not clinically involved) and the risk of nodal metastasis.
Methods
We retrospectively reviewed data from 100 patients who underwent neoadjuvant chemotherapy (NACT). Besides patient demographics and tumour variables, a radiologist retrospectively reviewed pre-operative MRI to measure tumour-to-skin distance. R core packages were used for univariate (χ2 and T-Wilcoxon tests) and bivariate logistic regression statistical analysis.
Results
Of 95 analysable datasets, patients’ median age was 51 years (IQR: 42–61), 97% were symptomatic (rest screen detected), and the median tumour size was 43 mm (IQR, 26–52). On multivariate analysis, increasing invasive tumour size (
p
= 0.02), ER positivity (
p
= 0.007) and shorter tumour-to-skin distance (
p
= 0.05) correlated with nodal metastasis. HER2 was not included in multivariate analysis as there was no association with nodal status on univariate analysis. In node-positive tumours, as tumour size increased, the tumour-to-skin distance decreased (
r
= − 0.34,
p
= 0.026). In node-negative tumours, there was no correlation (
r
= + 0.18,
p
= 0.23).
Conclusion
This study shows that non-locally advanced cancers closer to the skin (and consequent proximity to subdermal lymphatics) are associated with a greater risk of nodal metastasis. Pre-operative identification of those more likely to be node positive may suggest the need for a second-look USS since a higher nodal stage may lead to a change in therapeutic strategies, such as upfront systemic therapy, node marking, and axillary clearance without the need to return to theatre following sentinel node biopsy.
Reversible logic finds many applications, especially in the area of quantum computing. A completely specified n-input, n-output Boolean function is called reversible if it maps each input assignment ...to a unique output assignment and vice versa. Logic synthesis for reversible functions differs substantially from traditional logic synthesis and is currently an active area of research. The authors present an algorithm and tool for the synthesis of reversible functions. The algorithm uses the positive-polarity Reed-Muller expansion of a reversible function to synthesize the function as a network of Toffoli gates. At each stage, candidate factors, which represent subexpressions common between the Reed-Muller expansions of multiple outputs, are explored in the order of their attractiveness. The algorithm utilizes a priority-based search tree, and heuristics are used to rapidly prune the search space. The synthesis algorithm currently targets the generalized n-bit Toffoli gate library. However, other algorithms exist that can convert an n-bit Toffoli gate into a cascade of smaller Toffoli gates. Experimental results indicate that the authors' algorithm quickly synthesizes circuits when tested on the set of all reversible functions of three variables. Furthermore, it is able to quickly synthesize all four-variable and most five-variable reversible functions that were in the test suite. The authors also present results for some benchmark functions widely discussed in literature and some new benchmarks that the authors have developed. The algorithm is shown to synthesize many, but not all, randomly generated reversible functions of as many as 16 variables with a maximum gate count of 25
Broad-scale geographical gradients in the abiotic environment and interspecific interactions should select for clinal adaptation. How trait clines evolve has recently received increased attention ...because of anticipated climate change and the importance of rapid evolution in invasive species. This issue is particularly relevant for clines in growth and defense of plants, because both sets of traits are closely tied to fitness and because such sessile organisms experience strong local selection. Yet despite widespread recognition that growth and defense traits are intertwined, the general issue of their joint clinal evolution is not well resolved.
To address heritable clinal variation and adaptation of growth and defense traits of common milkweed (
Asclepias syriaca
), we planted seed from 22 populations encompassing the species' latitudinal range in common gardens near the range center (New York) and toward the range edges (New Brunswick and North Carolina). Populations were differentiated in 13 traits, and six traits showed genetically based latitudinal clines. Higher-latitude populations had earlier phenology, lower shoot biomass, more root buds and clonal growth, higher root-to-shoot ratio, and greater latex production. The cline in shoot biomass was consistent in all three locations. Selection on phenology was reversed in New Brunswick and North Carolina, with early genotypes favored in the north but not the south. We found no clines in foliar trichomes or toxic cardenolides. Annual precipitation of source populations explained variation in phenology, clonal growth, root-to-shoot ratio, and latex. Across four traits measured in New Brunswick and North Carolina, we found garden-by-latitude (and garden-by-precipitation) interactions, indicating plasticity in genetically based trait clines.
In the two gardens with substantial herbivory (New York and North Carolina), northern populations showed higher resistance to insects. Resistance to aphids was driven by trichomes and water content, while resistance to monarch caterpillars was driven by latex. However, surveys of natural populations indicated that leaf damage and insect diversity on milkweed are low at the geographical extremes (New Brunswick and North Carolina) and higher toward the range center. We speculate that milkweed plants evolved clines in growth traits in response to climate, and that this set the template for tolerance to herbivory, which subsequently shaped the evolution of defensive traits.
Background Low social support has been associated with several disorders. We test the relationship between perceived interpersonal social support (ISS) and aspects of mental and physical health. ...Methods We used data from National Epidemiological Survey on Alcohol and Related Conditions in which 34 653 individuals aged 20–99 years were interviewed twice (2001–02 and 2004–05), with the second interview including the interpersonal support evaluation list. The association of perceived ISS with lifetime DSM-IV psychopathology and physical health from the past 12 months was investigated. We also tested whether this association changes as a function of number of traumatic events in accordance with the buffering hypothesis. Results Low perceived ISS correlated with increased prevalence of major depressive disorder, generalized anxiety, social phobia and several physical health problems. There was a strong association between excellent self-perceived physical health and high social support. Conclusions There was evidence for both the main, beneficial effects of high perceived ISS and buffering, whereby increased perceived ISS ameliorated the pathogenic influence of exposure to traumatic life events on psychopathology. Current findings highlight the importance of perceived ISS in individuals' general mental and physical well-being, both in daily life and upon exposure to negative life events.
Inducible defenses, which provide enhanced resistance after initial attack, are nearly universal in plants. This defense signaling cascade is mediated by the synthesis, movement, and perception of ...jasmonic acid and related plant metabolites. To characterize the long-term persistence of plant immunity, we challenged Arabidopsis (Arabidopsis thaliana) and tomato (Solanum lycopersicum) with caterpillar herbivory, application of methyl jasmonate, or mechanical damage during vegetative growth and assessed plant resistance in subsequent generations. Here, we show that induced resistance was associated with transgenerational priming of jasmonic acid-dependent defense responses in both species, caused caterpillars to grow up to 50% smaller than on control plants, and persisted for two generations in Arabidopsis. Arabidopsis mutants that are deficient in jasmonate perception (coronatine insensitive1) or in the biogenesis of small interfering RNA (dicer-like2 dicer-like3 dicer-like4 and RNA polymerase d2a nuclear RNA polymerase d2b) do not exhibit inherited resistance. The observation of inherited resistance both the Brassicaceae and Solanaceae suggests that this trait may be more widely distributed in plants. Epigenetic resistance to herbivory thus represents a phenotypically plastic mechanism for enhanced defense across generations.
The quest for ultrahigh-Qnanomechanical resonators has driven intense study of strain-induced dissipation dilution, an effect whereby vibrations of a tensioned plate are effectively trapped in a ...lossless potential. Here, we show for the first time that torsion modes of nanostructures can experience dissipation dilution, yielding a new class of ultrahigh-Qnanomechanical resonators with broad applications to quantum experiments and precision measurement. Specifically, we show that torsion modes of strained nanoribbons haveQfactors scaling as their width-to-thickness ratio squared (characteristic of “soft clamping”), yieldingQfactors as high as108andQ-frequency products as high as1013Hzfor devices made ofSi3N4. Using an optical lever, we show that the rotation of one such nanoribbon can be resolved with an imprecision 100 times smaller than the zero-point motion of its fundamental torsion mode, without the use of a cavity or interferometric stability. We also show that a strained nanoribbon can be mass loaded without changing its torsionalQ. We use this strategy to engineer a chip-scale torsion pendulum with an ultralow damping rate of7μHzand show how it can be used to sense micro-gfluctuations of the local gravitational field. Our findings signal the potential for a new field of imaging-based quantum optomechanics, demonstrate that the utility of strained nanomechanics extends beyond force microscopy to inertial sensing, and hint that the landscape for dissipation dilution remains largely unexplored.
Heterozygous somatic mutations affecting the spliceosome gene SF3B1 drive age-related clonal hematopoiesis, myelodysplastic syndromes (MDS) and other neoplasms. To study their role in such disorders, ...we generated knock-in mice with hematopoietic-specific expression of Sf3b1-K700E, the commonest type of SF3B1 mutation in MDS. Sf3b1
animals had impaired erythropoiesis and progressive anemia without ringed sideroblasts, as well as reduced hematopoietic stem cell numbers and host-repopulating fitness. To understand the molecular basis of these observations, we analyzed global RNA splicing in Sf3b1
hematopoietic cells. Aberrant splicing was associated with the usage of cryptic 3' splice and branchpoint sites, as described for human SF3B1 mutants. However, we found a little overlap between aberrantly spliced mRNAs in mouse versus human, suggesting that anemia may be a consequence of globally disrupted splicing. Furthermore, the murine orthologues of genes associated with ring sideroblasts in human MDS, including Abcb7 and Tmem14c, were not aberrantly spliced in Sf3b1
mice. Our findings demonstrate that, despite significant differences in affected transcripts, there is overlap in the phenotypes associated with SF3B1-K700E between human and mouse. Future studies should focus on understanding the basis of these similarities and differences as a means of deciphering the consequences of spliceosome gene mutations in MDS.
Plants employ hormone-mediated signaling pathways to defend against pathogens and insects. We tested predictions about the relative effect of jasmonate and salicylate pathways and how they mediate ...interactions between pathogens and herbivores. We employed two pathogens of tomato,
Pseudomonas syringae
(
Pst
) and tobacco mosaic virus (TMV), that are known to elicit distinct components of the two pathways, and we address the consequences of their induction for resistance in wild-type and salicylate-deficient transgenic plants in field experiments. We report that
Pst
infection induced jasmonic acid and proteinase inhibitors (PIs), and reduced the growth of
Spodoptera exigua
caterpillars on wild-type and salicylate-deficient plants.
Pst
and TMV both induced salicylic acid in wild-type but not salicylate-deficient plants. Although TMV did not affect jasmonic acid or PIs, infection increased caterpillar growth on wild-type plants, but not on salicylate-deficient plants. Aphid population growth was higher on salicylate-deficient compared to wild-type plants, and lower on salicylate-induced plants compared to controls. Natural aphid colonization was reduced on TMV-infected wild types, but not on salicylate-deficient plants. In sum, jasmonate-mediated resistance is induced by some pathogens, independent of salicylate, and salicylate-mediated induction by other pathogens results in induced susceptibility to a chewer and resistance to an aphid. We conclude with a predictive model for the expression of defense pathways and their consequences.
Summary
A report on a prospective trial on the reuse of tissue expander is presented, to determine the feasibility of reusing these implants, the risks involved and the incidence of complications. ...Four tissue expanders of different capacities were repeatedly used in 17 patients for different indications, after explaining the possible risks to all of them. Two patients encountered complications while reusing the expanders, but this did not compromise the final result. We feel that like refurbished cardiac pacemakers, the reuse of these expanders has no untoward effect on the patient as well as on the reconstructive procedure. A protocol for expander removal, resterilization and testing has been described.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Predators are potent agents of natural selection in biological communites. Experimental studies have shown that the introduction of predators can cause rapid evolution of defensive morphologies and ...behaviours in prey and chemical defences in plants. Such defences may be constitutively expressed (phenotypically fixed) or induced when predators initially attack. Here we show that non-lethal exposure of an animal to carnivores, and a plant to a herbivore, not only induces a defence, but causes the attacked organisms to produce offspring that are better defended than offspring from unthreatened parents. This transgenerational effect, referred to as a maternally induced defence, is in contrast to the more common defences induced in single individuals within a generation. Transgenerational induction of defences is a new level of phenotypic plasticity across generations that may be an important component of predator-prey interactions.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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