Radiological staging in breast cancer: which asymptomatic patients to image and how.

BACKGROUND: Approximately 4% of patients diagnosed with early breast cancer have occult metastases at presentation. Current national and international guidelines lack consensus on whom to image and how. METHODS: We assessed practice in baseline radiological staging against local guidelines for asymptomatic newly diagnosed breast cancer patients presenting to the Cambridge Breast Unit over a 9-year period. RESULTS: A total of 2612 patients were eligible for analysis; 91.7% were appropriately investigated. However in the subset of lymph node negative stage II patients, only 269 out of 354 (76.0%) investigations were appropriate. No patients with stage 0 or I disease had metastases; only two patients (0.3%) with stage II and or =4 positive lymph nodes), III and IV disease, respectively. CONCLUSION: These results prompted us to propose new local guidelines for staging asymptomatic breast cancer patients: only clinical stage III or IV patients require baseline investigation. The high specificity and convenience of computed tomography (chest, abdomen and pelvis) led us to recommend this as the investigation of choice in breast cancer patients requiring radiological staging

Eficácia da vacina Sabin em crianças subnutridas da Amazônia

Various hypotheses have been proposed to explain the diminished efficacy of the oral polio vaccine in underdeveloped tropical regions. In this study, the influence of mild to moderate chronic malnutrition on the development of antibodies to the 3 types of polioviruses was investigated in Brazilian Amazonian children. Vaccines were administered to 106 normal and stunted children, between 5 to 14 months of age, who were not suffering from acute malnutrition (wasting), in poor peri-urban slum areas of Manaus (AM) and São Luis (MA) during the National Poliomyelitis Vaccination Campaigns of 1981 and 1982. Two weeks after vaccination, blood was collected by digital puncture and the prevalence of neutralizing antibodies for the 3 types of polioviruses was determined in serum at a dilution of 1:8. In children who had received one dose of the vaccine, 43% of normal children had antibodies to 2 or 3 types of polioviruses, against only 9% of stunted children (p = .04). In children who had received 2 doses of vaccine, 75% of normal children but only 32% of stunted children had formed antibodies to 2 or 3 types of polioviruses (p = .001). These results suggest that mildly to moderately stunted children have an impaired immune response to the oral poliomyelitis vaccine and that more than 2 doses of vaccine are necessary to achieve satisfactory immunity levels in poor tropical communities where such malnutrition is common.A eficácia da vacina Sabin foi determinada em 106 crianças normais e subnutridas da Amazônia, após a administração de uma e duas doses de vacina oral (trivalente). Após a aplicação de uma dose de vacina, verificou-se que apenas 9% das crianças com subnutrição pregressa (crônica) e 43% das crianças normais formaram anticorpos neutralizantes (protetores) contra dois ou três tipos de poliovírus (p = 0,04). Após duas doses de vacina, os níveis de imunidade dos dois grupos de crianças estudadas acusaram, respectivamente, 32% e 75% (p = 0,001). Estes resultados mostram que a resposta imunitária à vacina Sabin foi sensivelmente inferior no grupo das crianças subnutridas, do que no das crianças normais. Em decorrência disto, será necessário administrar um número maior de doses de vacina oral àquelas crianças, a fim de que níveis satisfatórios de imunidade contra a poliomielite sejam atingidos em toda a população infantil

Composable and Finite Computational Security of Quantum Message Transmission

Recent research in quantum cryptography has led to the development of schemes that encrypt and authenticate quantum messages with computational security. The security definitions used so far in the literature are asymptotic, game-based, and not known to be composable. We show how to define finite, composable, computational security for secure quantum message transmission. The new definitions do not involve any games or oracles, they are directly operational: a scheme is secure if it transforms an insecure channel and a shared key into an ideal secure channel from Alice to Bob, i.e., one which only allows Eve to block messages and learn their size, but not change them or read them. By modifying the ideal channel to provide Eve with more or less capabilities, one gets an array of different security notions. By design these transformations are composable, resulting in composable security. Crucially, the new definitions are finite. Security does not rely on the asymptotic hardness of a computational problem. Instead, one proves a finite reduction: if an adversary can distinguish the constructed (real) channel from the ideal one (for some fixed security parameters), then she can solve a finite instance of some computational problem. Such a finite statement is needed to make security claims about concrete implementations. We then prove that (slightly modified versions of) protocols proposed in the literature satisfy these composable definitions. And finally, we study the relations between some game-based definitions and our composable ones. In particular, we look at notions of quantum authenticated encryption and QCCA2, and show that they suffer from the same issues as their classical counterparts: they exclude certain protocols which are arguably secure.Comment: 43+11 pages, 18 figures, v2: minor changes, extended version of the published pape

Ploidy elicits a whole-genome dosage effect: growth of triploid Atlantic salmon is linked to the genetic origin of the second maternal chromosome set

publishedVersio

Precision charging of microparticles in plasma via the Rayleigh instability for evaporating charged liquid droplets

In this paper we describe a novel method for delivering a precise, known amount of electric charge to a micron-sized solid target. Aerosolised microparticles passed through a plasma discharge will acquire significant electric charge. The fluid stability under evaporative stress is a key aspect that is core to the research. Initially stable charged aerosols subject to evaporation (i.e. a continually changing radius) may encounter the Rayleigh stability limit. This limit arises from the electrostatic and surface tension forces and determines the maximum charge a stable droplet can retain, as a function of radius. We demonstrate that even if the droplet charge is initially much less than the Rayleigh limit, the stability limit will be encountered as the droplet evaporates. The instability emission mechanism is strongly linked to the final charge deposited on the target, providing a mechanism that can be used to ensure a predictable charge deposit on a known encapsulated microparticle

Isolation of a small molecule inhibitor of DNA base excision repair

The base excision repair (BER) pathway is essential for the removal of DNA bases damaged by alkylation or oxidation. A key step in BER is the processing of an apurinic/apyrimidinic (AP) site intermediate by an AP endonuclease. The major AP endonuclease in human cells (APE1, also termed HAP1 and Ref-1) accounts for >95% of the total AP endonuclease activity, and is essential for the protection of cells against the toxic effects of several classes of DNA damaging agents. Moreover, APE1 overexpression has been linked to radio- and chemo-resistance in human tumors. Using a newly developed high-throughput screen, several chemical inhibitors of APE1 have been isolated. Amongst these, CRT0044876 was identified as a potent and selective APE1 inhibitor. CRT0044876 inhibits the AP endonuclease, 3′-phosphodiesterase and 3′-phosphatase activities of APE1 at low micromolar concentrations, and is a specific inhibitor of the exonuclease III family of enzymes to which APE1 belongs. At non-cytotoxic concentrations, CRT0044876 potentiates the cytotoxicity of several DNA base-targeting compounds. This enhancement of cytotoxicity is associated with an accumulation of unrepaired AP sites. In silico modeling studies suggest that CRT0044876 binds to the active site of APE1. These studies provide both a novel reagent for probing APE1 function in human cells, and a rational basis for the development of APE1-targeting drugs for antitumor therapy

Treatment costs and priority setting in health care: A qualitative study

The aim of this study is to investigate whether the public believes high cost patients should be a lower priority for public health care than low cost patients, other things being equal, in order to maximise health gains from the health budget. Semi-structured group discussions were used to help participants reflect critically upon their own views and gain exposure to alternative views, and in this way elicit underlying values rather than unreflective preferences. Participants were given two main tasks: first, to select from among three general principles for setting health care priorities the one that comes closest to their own views; second, to allocate a limited hospital budget between two groups of imaginary patients. Forty-one people, varying in age, occupation, income and education level, participated in a total of six group discussions with each group comprising between six and eight people

A quantitative evaluation of aerosol generation during cardiopulmonary resuscitation

Summary: It is unclear if cardiopulmonary resuscitation is an aerosol‐generating procedure and whether this poses a risk of airborne disease transmission to healthcare workers and bystanders. Use of airborne transmission precautions during cardiopulmonary resuscitation may confer rescuer protection but risks patient harm due to delays in commencing treatment. To quantify the risk of respiratory aerosol generation during cardiopulmonary resuscitation in humans, we conducted an aerosol monitoring study during out‐of‐hospital cardiac arrests. Exhaled aerosol was recorded using an optical particle sizer spectrometer connected to the breathing system. Aerosol produced during resuscitation was compared with that produced by control participants under general anaesthesia ventilated with an equivalent respiratory pattern to cardiopulmonary resuscitation. A porcine cardiac arrest model was used to determine the independent contributions of ventilatory breaths, chest compressions and external cardiac defibrillation to aerosol generation. Time‐series analysis of participants with cardiac arrest (n = 18) demonstrated a repeating waveform of respiratory aerosol that mapped to specific components of resuscitation. Very high peak aerosol concentrations were generated during ventilation of participants with cardiac arrest with median (IQR [range]) 17,926 (5546–59,209 [1523–242,648]) particles.l‐1, which were 24‐fold greater than in control participants under general anaesthesia (744 (309–2106 [23–9099]) particles.l‐1, p < 0.001, n = 16). A substantial rise in aerosol also occurred with cardiac defibrillation and chest compressions. In a complimentary porcine model of cardiac arrest, aerosol recordings showed a strikingly similar profile to the human data. Time‐averaged aerosol concentrations during ventilation were approximately 270‐fold higher than before cardiac arrest (19,410 (2307–41,017 [104–136,025]) vs. 72 (41–136 [23–268]) particles.l‐1, p = 0.008). The porcine model also confirmed that both defibrillation and chest compressions generate high concentrations of aerosol independent of, but synergistic with, ventilation. In conclusion, multiple components of cardiopulmonary resuscitation generate high concentrations of respiratory aerosol. We recommend that airborne transmission precautions are warranted in the setting of high‐risk pathogens, until the airway is secured with an airway device and breathing system with a filter

Lymphoid Organ-Resident Dendritic Cells Exhibit Unique Transcriptional Fingerprints Based on Subset and Site

Lymphoid organ-resident DC subsets are thought to play unique roles in determining the fate of T cell responses. Recent studies focusing on a single lymphoid organ identified molecular pathways that are differentially operative in each DC subset and led to the assumption that a given DC subset would more or less exhibit the same genomic and functional profiles throughout the body. Whether the local milieu in different anatomical sites can also influence the transcriptome of DC subsets has remained largely unexplored. Here, we interrogated the transcriptional relationships between lymphoid organ-resident DC subsets from spleen, gut- and skin-draining lymph nodes, and thymus of C57BL/6 mice. For this purpose, major resident DC subsets including CD4 and CD8 DCs were sorted at high purity and gene expression profiles were compared using microarray analysis. This investigation revealed that lymphoid organ-resident DC subsets exhibit divergent genomic programs across lymphoid organs. Interestingly, we also found that transcriptional and biochemical properties of a given DC subset can differ between lymphoid organs for lymphoid organ-resident DC subsets, but not plasmacytoid DCs, suggesting that determinants of the tissue milieu program resident DCs for essential site-specific functions