The addition of breast magnetic resonance imaging (MRI) to screening mammography for women with BRCA mutations significantly increases sensitivity, but there is little data on clinical outcomes. We ...report screening performance, cancer stage, distant recurrence rate, and breast cancer-specific mortality in our screening study.
From 1997 to 2009, 496 women aged 25 to 65 years with a known BRCA1/2 mutation, of whom 380 had no previous cancer history, were enrolled in a prospective screening trial that included annual MRI and mammography.
In 1847 screening rounds, 57 cancers were identified (53 screen-detected, 1 interval, and 3 incidental at prophylactic mastectomy), of which 37 (65%) were invasive. Sensitivity of MRI vs mammography was 86% vs 19% over the entire study period (P<0.0001), but was 74% vs 35% from 1997 to 2002 (P=0.02) and 94% vs 9% from 2003 to 2009 (P<0.0001), respectively. The relative sensitivities of MRI and mammography did not differ by mutation, age, or invasive vs non-invasive disease. Of the incident cancers, 97% were Stage 0 or 1. Of 28 previously unaffected women diagnosed with invasive cancer, 1 BRCA1 mutation carrier died following relapse of a 3 cm, node-positive breast cancer diagnosed on her first screen at age 48 (annual breast cancer mortality rate=0.5%). Three patients died of other causes. None of the 24 survivors has had a distant recurrence at a median follow-up of 8.4 years since diagnosis.
Magnetic resonance imaging surveillance of women with BRCA1/2 mutations will detect the majority of breast cancers at a very early stage. The absence of distant recurrences of incident cancers to date is encouraging. However, longer follow-up is needed to confirm the safety of breast surveillance.
Type IV pili are cell surface organelles found on many Gram-negative bacteria. They mediate a variety of functions, including adhesion, twitching motility, and competence for DNA uptake. The type IV ...pilus is a helical polymer of pilin protein subunits and is capable of rapid polymerization or depolymerization, generating large motor forces in the process. Here we show that a specific interaction between the outer membrane secretin PilQ and the type IV pilus fiber can be detected by far-Western analysis and sucrose density gradient centrifugation. Transmission electron microscopy of preparations of purified pili, to which the purified PilQ oligomer had been added, showed that PilQ was uniquely located at one end of the pilus fiber, effectively forming a “mallet-type” structure. Determination of the three-dimensional structure of the PilQ-type IV pilus complex at 26-Å resolution showed that the cavity within the protein complex was filled. Comparison with a previously determined structure of PilQ at 12-Å resolution indicated that binding of the pilus fiber induced a dissociation of the “cap” feature and lateral movement of the “arms” of the PilQ oligomer. The results demonstrate that the PilQ structure exhibits a dynamic response to the binding of its transported substrate and suggest that the secretin could play an active role in type IV pilus assembly as well as secretion.
Type IV pili are long, thin fibres, which extend from the surface of the bacterial pathogen Neisseria meningitidis; they play a key role in adhesion and colonisation of host cells. PilP is a ...lipoprotein, suggested to be involved in the assembly and stabilization of an outer membrane protein, PilQ, which is required for pilus formation. Here we describe the expression of a recombinant fragment of PilP, spanning residues 20 to 181, and determination of the solution structure of a folded domain, spanning residues 85 to 163, by NMR. The N-terminal third of the protein, from residues 20 to 84, is apparently unfolded. Protease digestion yielded a 113 residue fragment that contained the folded domain. The domain adopts a simple β-sandwich type fold, consisting of a three-stranded β-sheet packed against a four-stranded β-sheet. There is also a short segment of 310 helix at the N-terminal part of the folded domain. We were unable to identify any other proteins that are closely related in structure to the PilP domain, although the fold appears to be distantly related to the lipocalin family. Over 40 homologues of PilP have been identified in Gram-negative bacteria and the majority of conserved residues lie within the folded domain. The fourth β-strand and adjacent loop regions contain a high proportion of conserved residues, including three glycine residues, which seem to play a role in linking the two β-sheets. The two β-sheets pack together to form a crevice, lined with conserved hydrophobic residues: we suggest that this feature could act as a binding site for a small ligand. The results show that PilP and its homologues have a conserved, folded domain at the C-terminal end of the protein that may be involved in mediating binding to hydrophobic ligands.
Catamenial pneumothorax Balasingham, S; Arulkumaran, S; Nadarajah, K ...
Australian & New Zealand journal of obstetrics & gynaecology,
February 1986, Letnik:
26, Številka:
1
Journal Article
Recenzirano
Catamenial or menses related pneumothorax is a rare clinical manifestation of pulmonary endometriosis. We document a case where the clinical history was the key to diagnosis, and evidence of ...endometriosis elsewhere was scanty. Prolonged medical therapy was not preferred in our patient in view of her age and parity. Surgical pleural ablation was carried out to prevent further episodes of life threatening pneumothoraces. The investigations that may be useful in such a patient are discussed and the clinical profile of our patient is compared with those of the few cases reported in the literature.
Disease-affected nervous systems exhibit anatomical or physiological impairments that degrade processing, transfer, storage, and retrieval of neural information, leading to physical or intellectual ...disabilities. Brain implants may potentially promote clinical means for detecting and treating neurological symptoms by establishing direct communication between the nervous and artificial systems. Current technology can modify the neural function at the supracellular level as in Parkinson's disease, epilepsy, and depression. However, recent advances in nanotechnology, nanomaterials, and molecular communications have the potential to enable brain implants to preserve the neural function at the subcellular level, which could increase effectiveness, decrease energy consumption, and make the leadless devices chargeable from outside the body or by utilizing the body's own energy sources. In this paper, we focus on understanding the principles of elemental processes in synapses to enable diagnosis and treatment of brain diseases with pathological conditions using biomimetic synaptically interactive brain-machine interfaces (BMIs). First, we provide an overview of the synaptic communication system, followed by an outline of brain diseases that promote dysfunction in the synaptic communication system. Then, we discuss the technologies for brain implants and propose future directions for the design and fabrication of cognitive BMIs. The overarching goal of this paper is to summarize the status of engineering research at the interface between the technology and the nervous system and direct the ongoing research toward the point where synaptically interactive BMIs can be embedded in the nervous system.
We examine the role of carbon risk in dividend policy, and how its effect varies between imputation (paying franked dividends) and classical (paying unfranked dividends) tax environments in the ...unique experimental setting in Australia. We find that the probability of paying dividend and dividend payout ratio is lower for firms in the highest-emitting industries (polluters) relative to non-polluters, subsequent to ratification of the Kyoto Protocol. While the post-Kyoto reduction in the likelihood of paying dividend is not significantly different, the reduction in payout ratio is smaller in the imputation environment than classical tax system, highlighting the significance of imputation tax environment only on the impact of carbon risk on dividend payout rather than decision to pay. We further document that the post-Kyoto reduction in dividend payout of polluters is driven by their relative increase in earnings uncertainty. The evidence suggests a causal influence of carbon risk on firm dividend policy.
Information theory provides maximum possible information transfer over communication channels, including neural channels recently emerged as remarkable for disruptive nano-networking applications. ...Information theory was successfully applied to quantify the ability of biological sensory neurons to transfer the information from dynamic stimuli. However, a little of information theory has been subjected to quantify the reliability of neuro-transmission between synaptically coupled neurons. Neuro-transmission, regarded as molecular synaptic communication, relays information between neurons and significantly affects the overall brain processing performance. In this study, we use concepts from information theory to provide the framework based on closed-form expressions that quantify the information rate allowing assessment of neuro-transmission when the parameters are provided for any type of neurons. Considering Poissonian statistics and the rate coding model of neural communication, we show how the information transferred between cortical neurons depend on the molecular, physiological and morphological diversity of cells, the firing rate, and the synaptic wiring. With synaptic redundancy, we infer the ability of an isolated post-synaptic neuron to reliably convey information encoded in the spike train from a pre-synaptic neuron. Estimating information rate between neurons primarily serves in the evaluation of the overall performance of biological neural nano-networks and the development of artificial nano-networks.
Exclusionary innovation poses a bigger threat to competition in digital platform markets than in other innovation markets given the relevance of data-driven network effects as well as the strong ...incentive and ability of digital platforms to pursue an envelopment strategy. This paper advocates a theory of harm called "platform-wide exclusionary innovation" which applies to conduct that plausibly creates short-term consumer benefit but is more likely to foreclose rivals and therefore reduce technological progress in the long run. This theory of harm can help to explain Google's conduct that the European Commission condemned in its three decisions against Google between 2017 and 2019. Due to interconnections between Google's practices in the three cases this article assesses whether they may be considered jointly for the purpose of finding of an infringement of Article 102 TFEU or under the proposed Digital Markets Act.
The extraction and characterization of DNA from aquatic environmental samples offers an alternative, noninvasive approach for the detection of rare species. Environmental DNA, coupled with PCR and ...next‐generation sequencing (“metabarcoding”), has proven to be very sensitive for the detection of rare aquatic species. Our study used a custom‐designed group‐specific primer set and next‐generation sequencing for the detection of three species at risk (Eastern Sand Darter, Ammocrypta pellucida; Northern Madtom, Noturus stigmosus; and Silver Shiner, Notropis photogenis), one invasive species (Round Goby, Neogobius melanostomus) and an additional 78 native species from two large Great Lakes tributary rivers in southern Ontario, Canada: the Grand River and the Sydenham River. Of 82 fish species detected in both rivers using capture‐based and eDNA methods, our eDNA method detected 86.2% and 72.0% of the fish species in the Grand River and the Sydenham River, respectively, which included our four target species. Our analyses also identified significant positive and negative species co‐occurrence patterns between our target species and other identified species. Our results demonstrate that eDNA metabarcoding that targets the fish community as well as individual species of interest provides a better understanding of factors affecting the target species spatial distribution in an ecosystem than possible with only target species data. Additionally, eDNA is easily implemented as an initial survey tool, or alongside capture‐based methods, for improved mapping of species distribution patterns.
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