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In quantum mechanics, the precision achieved in parameter estimation using a quantum state as a probe is determined by the measurement strategy employed. The quantum limit of precision is bounded by a value set by the state and its dynamics. Theoretical results have revealed that in interference measurements with two possible outcomes, this limit can be reached under ideal conditions of perfect visibility and zero losses. However, in practice, these conditions cannot be achieved, so precision never reaches the quantum limit. But how do experimental setups approach precision limits under realistic circumstances? In this Letter, we provide a model for precision limits in two-photon Hong-Ou-Mandel interferometry using coincidence statistics for nonperfect visibility and temporally unresolved measurements. We show that the scaling of precision with visibility depends on the effective area in time-frequency phase space occupied by the state used as a probe, and we find that an optimal scaling exists. We demonstrate our results experimentally for different states in a setup where the visibility can be controlled and reaches up to 99.5%. In the optimal scenario, a ratio of 0.97 is observed between the experimental precision and the quantum limit, establishing a new benchmark in the field.
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Humans use a family of more than 400 olfactory receptors (ORs) to detect odors, but there is currently no model that can predict olfactory perception from receptor activity patterns. Genetic variation in human ORs is abundant and alters receptor function, allowing us to examine the relationship between receptor function and perception. We sequenced the OR repertoire in 332 individuals and examined how genetic variation affected 276 olfactory phenotypes, including the perceived intensity and pleasantness of 68 odorants at two concentrations, detection thresholds of three odorants, and general olfactory acuity. Genetic variation in a single OR was frequently associated with changes in odorant perception, and we validated 10 cases in which in vitro OR function correlated with in vivo odorant perception using a functional assay. In 8 of these 10 cases, reduced receptor function was associated with reduced intensity perception. In addition, we used participant genotypes to quantify genetic ancestry and found that, in combination with single OR genotype, age, and gender, we can explain between 10% and 20% of the perceptual variation in 15 olfactory phenotypes, highlighting the importance of single OR genotype, ancestry, and demographic factors in the variation of olfactory perception.
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Variação Genética , Genótipo , Percepção Olfatória/genética , Receptores Odorantes/genética , Feminino , Humanos , MasculinoRESUMO
Quantum critical systems derive their finite-temperature properties from the influence of a zero-temperature quantum phase transition. The paradigm is essential for understanding unconventional high-Tc superconductors and the non-Fermi liquid properties of heavy fermion compounds. However, the microscopic origins of quantum phase transitions in complex materials are often debated. Here we demonstrate experimentally, with support from numerical renormalization group calculations, a universal crossover from quantum critical non-Fermi liquid behaviour to distinct Fermi liquid ground states in a highly controllable quantum dot device. Our device realizes the non-Fermi liquid two-channel Kondo state, based on a spin-1/2 impurity exchange-coupled equally to two independent electronic reservoirs. On detuning the exchange couplings we observe the Fermi liquid scale T*, at energies below which the spin is screened conventionally by the more strongly coupled channel. We extract a quadratic dependence of T* on gate voltage close to criticality, and validate an asymptotically exact description of the universal crossover between strongly correlated non-Fermi liquid and Fermi liquid states.
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BACKGROUND: In recent years studies have provided increasing evidence suggesting an association between the (gut) microbiome and idiopathic Parkinson's disease (IPD). OBJECTIVE: The aim of this article is to summarize and evaluate existing evidence with respect to the relevance of the (gut) microbiome for IPD. MATERIAL AND METHODS: An analysis and critical review of studies in the field of IPD and (gut) microbiome were carried out. The resulting potential perspectives and therapeutic strategies are discussed. RESULTS: Despite partially divergent results between different studies (potentially due to the applied methods and variance in the composition of the investigated cohorts), there is an overlap between studies indicating an association between IPD, the microbiome and microbial metabolites. Nevertheless, the cause-effect relationship between IPD and the microbiome has still not been clarified. Taken together, existing evidence supports a potentially relevant role for the microbiome with respect to typical disease symptoms and pathogenesis of the disease. CONCLUSION: Over the past 5 years there has been an enormous increase in the evidence with respect to the relevance of the microbiome for IPD. While early work in this field was mainly descriptive, new diagnostic methods provide evidence for the underlying mechanisms and the complex interactions between man as the host, the human immune system, the enteric nervous system, gut microbiota and microbial metabolites. A relatively novel and clinically relevant field of research is how the gut microbiome can influence the success of oral pharmacotherapy and whether substitution of specific microbiome components might be used either for future therapeutic or prophylactic strategies.
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Microbioma Gastrointestinal , Microbiota , Doença de Parkinson , Humanos , MasculinoRESUMO
Asthma is a chronic disease with impacts on public health. It affects the airways causing pulmonary inflammation mediated by CD4 T cells type Th2, eosinophilia, mucus hypersecretion, and elevated IgE. The unbalance between cytokines and transcription factors is an important feature in asthma. Probiotics has gaining highlight as a therapy for chronic diseases. Thus, we investigate the Lactobacillus bulgaricus (Lb) effect in murine allergic asthma. BALB/c-mice were sensitized to ovalbumin (OA) on days 0 and 7 and were challenged from day 14-28 with OA. Mice received Lb seven days prior to sensitization and it was kept until day 28. The Lb attenuated the eosinophils infiltration, mucus and collagen secretion, IgE production, pro-inflammatory cytokines, TLR4 expression, GATA3, STAT6 and RORγt in lung. Otherwise, Lb increased the anti-inflammatory cytokines, the T-bet and foxp3. Finally, Lb attenuated the allergic asthma-induced inflammation and airway remodeling by interfering on Th1/Th2 cytokines and STAT6/T-bet transcription factors.
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Remodelação das Vias Aéreas/efeitos dos fármacos , Asma/prevenção & controle , Lactobacillus delbrueckii/imunologia , Pneumonia/prevenção & controle , Probióticos/farmacologia , Fator de Transcrição STAT6/imunologia , Proteínas com Domínio T/imunologia , Remodelação das Vias Aéreas/imunologia , Animais , Asma/induzido quimicamente , Asma/imunologia , Asma/microbiologia , Citocinas/genética , Citocinas/imunologia , Modelos Animais de Doenças , Eosinófilos/efeitos dos fármacos , Eosinófilos/imunologia , Eosinófilos/patologia , Fator de Transcrição GATA3/genética , Fator de Transcrição GATA3/imunologia , Regulação da Expressão Gênica , Imunoglobulina E/genética , Imunoglobulina E/imunologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/genética , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/imunologia , Ovalbumina/administração & dosagem , Pneumonia/induzido quimicamente , Pneumonia/imunologia , Pneumonia/microbiologia , Fator de Transcrição STAT6/genética , Transdução de Sinais , Proteínas com Domínio T/genética , Células Th1/efeitos dos fármacos , Células Th1/imunologia , Células Th1/patologia , Equilíbrio Th1-Th2/efeitos dos fármacos , Células Th2/efeitos dos fármacos , Células Th2/imunologia , Células Th2/patologia , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/imunologiaRESUMO
OBJECTIVE: To perform a genome-wide characterization of changes in microRNA (miRNA) expression during the course of venom immunotherapy (VIT). METHODS: miRNA was isolated from the whole-blood of 13 allergic patients and 14 controls, who experienced no allergic reaction upon stings by honeybees and wasps. We analyzed 2549 miRNAs from the whole blood of these patients prior to VIT and 12 months after the start of VIT. The results for differential expression obtained on a microarray platform were confirmed by quantitative real-time PCR. Out of the 13 patients, 8 had a negative allergic reaction with VIT, thus indicating that this approach was successful. RESULTS: By comparing time points before and 12 months after ultrarush VIT, correlation analysis and principal component analysis both indicated a limited effect of VIT on the overall miRNA expression pattern. Volcano plot analysis based on raw P values revealed few deregulated miRNAs, most of which were increasingly expressed after VIT as compared with before VIT. Based on the 50 most altered miRNAs, no clear clustering was observed before or after VIT. CONCLUSIONS: Our results indicate an overall reduced effect of VIT on the miRNA expression pattern in whole blood.
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Alérgenos/imunologia , Venenos de Abelha/imunologia , Células Sanguíneas/fisiologia , Dessensibilização Imunológica/métodos , Hipersensibilidade Imediata/terapia , MicroRNAs/genética , Venenos de Vespas/imunologia , Animais , Abelhas , Análise por Conglomerados , Estudo de Associação Genômica Ampla , Humanos , Hipersensibilidade Imediata/genética , Tolerância Imunológica/genética , Análise de Componente Principal , Transcriptoma , Resultado do Tratamento , VespasRESUMO
Background: Bispecific antibody MEDI3902, targeting the Pseudomonas aeruginosa type 3 secretion system (PcrV) and Psl exopolysaccharide, is currently in phase 2b development for prevention of nosocomial pneumonia in patients undergoing mechanical ventilation. We surveyed a diverse collection of isolates to study MEDI3902 epitope conservation and protective activity. Methods: P. aeruginosa clinical isolates (n = 913) were collected from diverse patients and geographic locations during 2003-2014. We conducted whole-genome sequencing; performed PcrV and Psl expression analyses via immunoblotting and enzyme-linked immunosorbent assay, respectively; performed crystallography to determine the MEDI3902 PcrV epitope, using anti-PcrV Fab and PcrV components (resolved at 2.8 Å); and evaluated MEDI3902 protective activity against select isolates in vitro and in vivo. Results: Intact psl operon and pcrV genes were present in 94% and 99% of isolates, respectively, and 99.9% of isolates contained at least one of the genetic elements. Anti-Psl binding was confirmed in tested isolates harboring a complete Psl operon or lacking nonessential psl genes. We identified 46 PcrV variant sequences, and MEDI3902-PcrV contact residues were preserved. MEDI3902 maintained potent in vivo activity against various strains, including strains expressing only a single target. Conclusions: Psl and PcrV are highly prevalent in global clinical isolates, suggesting MEDI3902 can mediate broad coverage against P. aeruginosa.
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Anticorpos Antibacterianos/imunologia , Anticorpos Monoclonais/imunologia , Antígenos de Bactérias/genética , Proteínas de Bactérias/genética , Sequência Conservada , Pseudomonas aeruginosa/metabolismo , Anticorpos Biespecíficos , Antígenos de Bactérias/imunologia , Proteínas de Bactérias/imunologia , Epitopos , Humanos , Modelos Moleculares , Óperon , Conformação Proteica , Infecções por Pseudomonas/microbiologia , Pseudomonas aeruginosa/genética , Pseudomonas aeruginosa/imunologia , Sequenciamento Completo do GenomaRESUMO
BACKGROUND AND OBJECTIVES: Australia introduced bacterial contamination screening (BCS) for platelet components in April 2008. This study presents analysis performed to assess the efficacy of testing. MATERIALS AND METHODS: Seven-day aerobic and anaerobic culture is performed using the BacT/ALERT 3D system. Following an initial machine positive (IMP) flag, all associated components are recalled, and/or clinicians treating already transfused patients are notified. IMPs are categorized as 'machine false positive', 'confirmed positive' or 'indeterminate' depending on culture results of initial and repeat samples. RESULTS: Between 2010 and 2012, 1·1% of platelet donations tested IMP; since 2013, this rate has fallen to 0·6% through improved instrument management, reducing false-positive IMPs but maintaining sensitivity for cultures yielding bacterial growth. On average, 66% of confirmed positive and indeterminate platelet units had been transfused at the time of detection. The majority (95%) of these grew Propionibacterium sp., a slow-growing organism that rarely causes sepsis in the transfusion setting. The incidence of reported transfuion-transmitted bacterial infection (TTBI) has fallen since the introduction of BCS, with a 4·2-fold [0·5, 28·2] lower rate from platelets. CONCLUSION: BCS has been successful in detecting platelet units containing pathogenic bacteria. The incidence of TTBI from platelets has fallen since the introduction of BCS, but the risk has not been eliminated due to rare false-negative results. In the absence of a pathogen inactivation system for red blood cells, BCS provides 'surrogate' testing of red blood cells from which platelets have been manufactured.
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Infecções Bacterianas/prevenção & controle , Plaquetas/microbiologia , Austrália/epidemiologia , Infecções Bacterianas/epidemiologia , Infecções Bacterianas/transmissão , Segurança do Sangue , Técnicas de Cultura , Humanos , Incidência , Transfusão de Plaquetas/efeitos adversosRESUMO
Progressive muscle relaxation (PMR) after Jacobson has been used for migraine prophylaxis since the early 1970s. Migraine patients are assumed to have an enhanced autonomic arousal which can be counterbalanced by systematic relaxation. Relaxation techniques are thought to reduce the activation level, to alter cortical pain processing and to enhance activation in pain-reducing cortical structures in the periaqueductal grey matter. Meta-analyses could show PMR to be just as efficacious as pharmacological treatment options. A beneficial effect can only arise if regular daily exercises of 5-25â¯min are performed and the exercises are transferred into the daily routine. This review critically summarizes the empirical findings concerning the effects of PMR on migraine. A lack of recent research on this topic was determined. In a study by this group 50 migraine patients and 46 healthy controls were examined. It could be shown that in addition to the clinical efficacy on migraine frequency, changes in cortical information processing, measured by means of the evoked potential contingent negative variation (CNV) could also be determined. The initially increased CNV amplitude became normalized after regular PMR training in migraine patients. With the review of PMR studies on migraine prophylaxis and the results of our own study it could be shown that PMR is an efficacious non-pharmacological treatment option for migraine prophylaxis. In addition to its clinical effects, alterations in cortical stimulation processing in terms of a normalization of the CNV could be documented.
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Treinamento Autógeno , Transtornos de Enxaqueca , Variação Contingente Negativa , Potenciais Evocados , Humanos , Resultado do TratamentoRESUMO
BACKGROUND AND OBJECTIVES: We previously published a model to estimate the residual risk (RR) for occult hepatitis B infection (OBI) in the absence of universal anti-HBc testing. To incorporate new information on the epidemiology of OBI, we describe model refinements and estimate a more accurate HBV RR due to OBI in Australia. MATERIALS AND METHODS: In our original model, the OBI risk, p(OBI), was defined by the rate of 'non-detection' by the HBV DNA screening test in use, p(NAT non-detection), and the average infectivity of blood components from OBI donors, p(transmission). We revised the model by integrating three refinements: that donations with anti-HBs levels of >10 IU/l, or donations solely for manufactured plasma products, be excluded from the risk calculation, and an updated estimate of p(transmission). RESULTS: Refining our OBI RR model resulted in a more than 10-fold reduction in the reported RR risk to recipients from OBI in our donor population. Based on the use of a common data set, the mean OBI RR risk decreased from 1 in 374 354 donations (95% CI: 1 in 191 940-1 072 681) to 1 in 3 984 033 (95% CI: 1 in 1 146 188-65 268 257) for the refined model. CONCLUSION: Our model refinements provide a more realistic measure of the HBV RR in the donor population. Unlike the previous model, the new model demonstrates that the risk of HBV due to OBI in the Australian blood donor population is negligible, and further potentially cost-ineffective risk management strategies are not currently warranted.
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Transfusão de Sangue , Hepatite B/transmissão , Modelos Teóricos , Doadores de Sangue , DNA Viral/sangue , Hepatite B/epidemiologia , Hepatite B/virologia , Anticorpos Anti-Hepatite B/sangue , Antígenos do Núcleo do Vírus da Hepatite B/imunologia , Vírus da Hepatite B/genética , Vírus da Hepatite B/isolamento & purificação , Humanos , Análise de Sequência com Séries de Oligonucleotídeos , RiscoRESUMO
BACKGROUND AND OBJECTIVES: Universal testing of blood donations for human T-cell lymphotropic virus (HTLV) in Australia may no longer be appropriate given the low prevalence of HTLV infection and the mitigating effect of universal leucodepletion for cellular components. This study aimed to determine the most appropriate HTLV testing strategy using the Risk-Based Decision-Making Framework for Blood Safety. MATERIALS AND METHODS: The risk of HTLV transfusion-transmission using three testing strategies (universal, new-donor and no testing) and cost-effectiveness of the first two strategies were assessed using adaptations of published mathematical models. RESULTS: The overall prevalence for 2004-2014 was three HTLV-positives per million donations. It was estimated that annually, universal testing incurred a cost of approximately AUD $3 million and prevented 83 HTLV-positive cellular components from being issued, and new-donor testing cost approximately $225 000 and prevented 81 components. The number of cases of transfusion-transmitted HTLV and HTLV-associated disease prevented per year by universal and new-donor testing was essentially equivalent. According to preset risk thresholds, the risk of transfusion-transmission was negligible for universal and new-donor testing, and minimal without testing. CONCLUSION: Transfusion-transmission of HTLV is a minimal risk in Australia even without testing. However, any revision of testing strategy must consider not only risk and cost-effectiveness, but also stakeholder, ethical and regulatory perspectives. Considering all relevant criteria, new-donor testing is judged the optimal strategy because it is able to achieve almost the same outcomes as universal testing, at a fraction of the cost.
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Segurança do Sangue/economia , Infecções por HTLV-I/sangue , Anticorpos Antivirais/sangue , Austrália/epidemiologia , Doadores de Sangue , Transfusão de Sangue , Análise Custo-Benefício , Infecções por HTLV-I/epidemiologia , Infecções por HTLV-I/prevenção & controle , Testes Hematológicos , Vírus Linfotrópico T Tipo 1 Humano/imunologia , Humanos , Imunoensaio/economia , Prevalência , Medição de RiscoRESUMO
In Coulomb drag, a current flowing in one conductor can induce a voltage across an adjacent conductor via the Coulomb interaction. The mechanisms yielding drag effects are not always understood, even though drag effects are sufficiently general to be seen in many low-dimensional systems. In this Letter, we observe Coulomb drag in a Coulomb-coupled double quantum dot and, through both experimental and theoretical arguments, identify cotunneling as essential to obtaining a correct qualitative understanding of the drag behavior.
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BACKGROUND AND OBJECTIVES: Ross River virus (RRV) is an enveloped, RNA alphavirus in the same antigenic group as chikungunya virus. Australia records an annual average of 5000 laboratory-confirmed RRV infections. While RRV is currently geographically restricted to the Western Pacific, the capacity of arboviruses for rapid expansion is well established. The first case of RRV transfusion-transmission was recently described prompting a comprehensive risk assessment. MATERIALS AND METHODS: To estimate the RRV residual risk, we applied laboratory-confirmed RRV notifications to two published models. This modelling generated point estimates for the risk of viraemia in the donor population, the risk of collecting a viraemic donation and the predicted number of infected components. RESULTS: The EUFRAT model estimated the risk of infection in donors as one in 95 039 (one in 311 328 to one in 32 399) to one in 14 943 (one in 48 593 to one in 5094). The point estimate for collecting a RRV viraemic donation varied from one in 166 486 (one in 659 078 to one in 49 158) (annualized national risk) to one in 26 117 (one in 103 628 to one in 7729) (area of high transmission). The modelling predicted 8-11 RRV-infected labile blood components issued in Australia during a 1-year period. CONCLUSION: Considering the uncertainty in the modelled estimates, the unknown rate of RRV donor viraemia and the low severity of any recipient RRV infection, additional risk management for RRV in Australia will initially be restricted to strengthening the messaging to donors regarding prompt reporting of any postdonation illnesses.
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Infecções por Alphavirus/transmissão , Ross River virus/isolamento & purificação , Infecções por Alphavirus/epidemiologia , Infecções por Alphavirus/virologia , Austrália/epidemiologia , Doadores de Sangue , Transfusão de Sangue , Humanos , Medição de RiscoRESUMO
BACKGROUND AND OBJECTIVES: Cytomegalovirus poses a risk to transfusion safety as its transmission to an immunocompromised recipient may lead to significant clinical sequelae. Once infection is established, it is lifelong and generally asymptomatic. Strategies to reduce the risk of transfusion-transmitted CMV (TT-CMV) include donor serological testing and blood component leucodepletion to deplete the transmissible reservoir. We estimate the residual risk for non-CMV antibody screened, leucodepleted (LD-only) fresh blood components. MATERIALS AND METHODS: We established an approach to estimate the risk of TT-CMV under various scenarios. We estimated the probability of an infectious component, for both red cells and platelets, as a function of the observed WBC filter failure rate and the probability that such a unit was also contaminated with infectious virus. RESULTS: Using this model, the estimated combined residual risk of LD-only red cell and platelet units was very low, 1 in 13 575 000 (95%CI:1 in 1 344 167 000-1 in 1 730 000) as was the individual residual risk estimate for LD-only red cells, 1 in 7 790 000 (95%CI: 1 in 771 307 000-1 in 993 000) and LD-only platelets, where a zero risk was estimated (95%CI: 0-1 in 1 074 000). CONCLUSION: We describe a novel approach to assess the residual risk of LD-only components. This can be applied generally using local data. Our risk estimate for LD-only blood components in Australia is below the threshold of 1 in 1 million, generally considered negligible. This provides a useful indicator of the relative safety of LD-only components to assist clinical decisions when serologically screened inventory is unavailable.
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Transfusão de Componentes Sanguíneos , Infecções por Citomegalovirus/transmissão , Animais , Doadores de Sangue , Plaquetas/citologia , Citomegalovirus/imunologia , Eritrócitos/citologia , Humanos , Leucócitos/citologia , Camundongos , RiscoRESUMO
BACKGROUND AND OBJECTIVES: Previous studies have demonstrated that transfused blood components from donors with occult hepatitis B virus infection (OBI) are potentially infectious. This study reports the results of an Australian lookback programme for the period subsequent to the commencement of individual donation HBV NAT in July 2010 and estimates the HBV transmission rate for components from two categories of donors, confirmed OBI and HBV inconclusive (anti-HBc reactive with non-discriminated NAT result). MATERIALS AND METHODS: Using the results of lookback investigations, we estimated HBV transmission rates by donor category and type of component transfused based on the prevalence of antibodies to HBV core antigen (anti-HBc) in recipients adjusted for the estimated prevalence in the general population. RESULTS: After subtracting the background anti-HBc rate, we derived an adjusted transmission rate (all components) with lower and upper bounds as follows: 0·85% (0·00-2·35%) for OBI donors, 2·83% (1·23-4·33%) for inconclusive donors and 1·81% (0·21-3·31%) for total (OBI and inconclusive) donors. The median adjusted transmission rate for total donors was higher (but not statistically) for plasma (3·01%) than RCCs (2·86%), but there was no evidence of transmission for cryoprecipitate or platelets (0% for both components). CONCLUSION: Our lookback study suggests a low (0·2-3·3%) but measurable rate of HBV transmission in Australia associated with donors with OBI and supports published evidence that at least some blood component types from OBI donors, including a proportion undetectable by ID-NAT can transmit HBV by transfusion.
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Doadores de Sangue , DNA Viral/sangue , Hepatite B/transmissão , Reação Transfusional , Austrália , Hepatite B/sangue , Anticorpos Anti-Hepatite B/sangue , Antígenos de Superfície da Hepatite B/sangue , Vírus da Hepatite B/genética , Humanos , Pessoa de Meia-Idade , PrevalênciaRESUMO
Alpha-toxin (AT) is a major virulence factor in the disease pathogenesis of Staphylococcus aureus. We previously identified a monoclonal antibody (MAb) against AT that reduced disease severity in a mouse dermonecrosis model. Here, we evaluate the activity of an affinity-optimized variant, LC10, in a mouse model of S. aureus pneumonia. Passive immunization with LC10 increased survival and reduced bacterial numbers in the lungs and kidneys of infected mice and showed protection against diverse S. aureus clinical isolates. The lungs of S. aureus-infected mice exhibited bacterial pneumonia, including widespread inflammation, whereas the lungs of mice that received LC10 exhibited minimal inflammation and retained healthy architecture. Consistent with reduced immune cell infiltration, LC10-treated animals had significantly lower (P < 0.05) proinflammatory cytokine and chemokine levels in the bronchoalveolar lavage fluid than did those of the control animals. This reduction in inflammation and damage to the LC10-treated animals resulted in reduced vascular protein leakage and CO2 levels in the blood. LC10 was also assessed for its therapeutic activity in combination with vancomycin or linezolid. Treatment with a combination of LC10 and vancomycin or linezolid resulted in a significant increase (P < 0.05) in survival relative to the monotherapies and was deemed additive to synergistic by isobologram analysis. Consistent with improved survival, the lungs of animals treated with antibiotic plus LC10 exhibited less inflammatory tissue damage than those that received monotherapy. These data provide insight into the mechanisms of protection provided by AT inhibition and support AT as a promising target for immunoprophylaxis or adjunctive therapy against S. aureus pneumonia.
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Antibacterianos/farmacologia , Anticorpos Monoclonais/farmacologia , Toxinas Bacterianas/antagonistas & inibidores , Proteínas Hemolisinas/antagonistas & inibidores , Pulmão/efeitos dos fármacos , Pneumonia Estafilocócica/tratamento farmacológico , Acetamidas/farmacologia , Animais , Toxinas Bacterianas/imunologia , Líquido da Lavagem Broncoalveolar/química , Quimiocinas/antagonistas & inibidores , Quimiocinas/biossíntese , Sinergismo Farmacológico , Quimioterapia Combinada , Feminino , Proteínas Hemolisinas/imunologia , Imunização Passiva , Rim/efeitos dos fármacos , Rim/imunologia , Rim/microbiologia , Linezolida , Pulmão/imunologia , Pulmão/microbiologia , Camundongos , Camundongos Endogâmicos C57BL , Oxazolidinonas/farmacologia , Pneumonia Estafilocócica/imunologia , Pneumonia Estafilocócica/microbiologia , Pneumonia Estafilocócica/mortalidade , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/metabolismo , Análise de Sobrevida , Vancomicina/farmacologiaRESUMO
BACKGROUND AND OBJECTIVES: In Australia since 2000, donors are deferred for 12 months since last male-to-male sexual contact. There is no estimate of the prevalence of non-compliance (i.e. failure to disclose a risk during the predonation interview which would lead to deferral) with the policy in Australia; however, published studies elsewhere indicate a range of 0·8-2.3% [corrected]. We investigated the rate of, timing and motivation for non-compliance. MATERIALS AND METHODS: A nationally representative sample of donors who had made a recent donation negative for transfusion-transmissible infection testing was surveyed using an anonymous, online instrument. Non-compliance was considered as a 'yes' response to the current screening question. Non-compliers were requested to define the timing of the last sexual contact relevant to their most recent donation. Univariate and multivariate regression analyses were used to define factors associated with non-compliance. RESULTS: Of 14 476 responses from male donors, 34 (0·23%, 95% CI: 0·16-0·33%) were non-compliant of whom 24 (0·17%, 95% CI: 0·11-0·25%) had contact within 6 months of donation. Factors significantly associated with non-compliance included: multiple sexual partners, history of injecting drug use, perception of a lack of privacy during interview and preference for a computer-based questionnaire. CONCLUSION: Our study confirms high compliance (>99·7%) to the 12-month deferral for male-to-male sex in Australia providing reassuring evidence for the efficacy of the screening question. Issues of 'privacy' and 'discomfort' associated with disclosure suggest the use of validated audio computer-assisted structured interview as a possible option for improving compliance with the donor questionnaire.
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Doadores de Sangue/psicologia , Fidelidade a Diretrizes/estatística & dados numéricos , Infecções por HIV/prevenção & controle , Hepatite B/prevenção & controle , Homossexualidade Masculina , Abstinência Sexual/estatística & dados numéricos , Reação Transfusional , Adolescente , Adulto , Austrália , Feminino , Infecções por HIV/transmissão , Hepatite B/transmissão , Humanos , Masculino , Pessoa de Meia-Idade , Motivação , Risco , Inquéritos e Questionários , Fatores de Tempo , Adulto JovemRESUMO
BACKGROUND: The number of elderly patients diagnosed with idiopathic pulmonary arterial hypertension (IPAH) is increasing. A 6-min walk distance (6MWD) > 380 m on therapy is associated with improved survival in IPAH. As exercise capacity is naturally decreasing with age, treatment goals for elderly patients might be different from those established for younger patients. METHODS: Consecutive adult patients diagnosed with IPAH between 1/2005 and 7/2012 were retrospectively included. We analysed the prognostic value of 6MWD targets (in metres and % predicted) with respect to age at diagnosis. RESULTS: The mean (± SD) 6MWD in 23 patients aged > 65 years at diagnosis compared with 22 younger patients was significantly lower at baseline (262 ± 69 vs. 356 ± 128 m; p = 0.011) and first follow up (310 ± 75 vs. 377 ± 137 m; p = 0.045), while the corresponding % predicted values were similar (62 ± 16% vs. 63 ± 21%; p = 0.854, and 74 ± 16% vs. 68 ± 21%; p = 0.267). The established treatment target of > 380 m 6MWD was met by only 13% of elderly compared with 46% of younger patients (p = 0.016), while the corresponding 6MWD of 78% predicted was exceeded by similar proportions (48% and 46%, respectively; p = 0.873). Survival of patients walking > 380 m or 78% predicted on first follow up was significantly better compared with patients not exceeding the respective threshold (100% vs. 72% and 95% vs. 67% at the end of follow up, respectively; p < 0.05 each). CONCLUSION: Expression of the 6MWD target as % predicted equalises age-related differences and has similar prognostic power compared with absolute values in patients with IPAH. As elderly patients are less likely to reach the absolute 6MWD threshold, the use of % predicted could be helpful in their individual assessment and adaption of targeted therapy.
Assuntos
Teste de Esforço/métodos , Hipertensão Pulmonar/diagnóstico , Caminhada/fisiologia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Teste de Esforço/estatística & dados numéricos , Feminino , Humanos , Hipertensão Pulmonar/mortalidade , Hipertensão Pulmonar/fisiopatologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Análise de SobrevidaRESUMO
PURPOSE: Thymoma is a rare tumour. The most common treatment for thymoma is surgical resection, while the use of radiotherapy and chemotherapy remains controversial. PATIENTS AND METHODS: We conducted a monocentric observational study of 31 patients diagnosed with thymoma from June 2004 to July 2020 at cancer centre in Strasbourg, France. We analysed the outcomes of the patients. RESULTS: The 2- and 5- year locoregional relapse-free survival rates were 96.3% (95% confidence interval [CI]: 76.5-99.5%) and 68.0% (95% CI: 43.8-83.5%), respectively. Radiotherapy and chemotherapy significantly improved local tumour control (P=0.0008 and 0.04, respectively), while a larger initial tumour size significantly worsened local control rates (P=0.04). The 5- and 10-year overall survival rates were 87.1% (95% CI: 69.2-95%) and 81.7% (95% CI: 60.3-92.2%), respectively. The median overall survival was not reached, and no favourable factor was retrieved. For relapsed patients, the median overall survival after relapse was 115 months. CONCLUSION: Despite the inherent limitations of retrospective studies with a limited patient sample size, we demonstrated that chemotherapy and radiotherapy in addition to surgery were effective in achieving local control and contributed to improving patient outcomes in thymoma. Notably, an aggressive treatment strategy at the time of relapse resulted in favourable outcomes for retreated patients.
Assuntos
Timoma , Neoplasias do Timo , Humanos , Timoma/radioterapia , Radioterapia Adjuvante , Estudos Retrospectivos , Recidiva Local de Neoplasia/patologia , Neoplasias do Timo/terapia , Neoplasias do Timo/patologia , Recidiva , Quimioterapia Adjuvante , Estadiamento de Neoplasias , Intervalo Livre de DoençaRESUMO
We report measurements of the Kondo effect in a double quantum dot, where the orbital states act as pseudospin states whose degeneracy contributes to Kondo screening. Standard transport spectroscopy as a function of the bias voltage on both dots shows a zero-bias peak in conductance, analogous to that observed for spin Kondo in single dots. Breaking the orbital degeneracy splits the Kondo resonance in the tunneling density of states above and below the Fermi energy of the leads, with the resonances having different pseudospin character. Using pseudospin-resolved spectroscopy, we demonstrate the pseudospin character by observing a Kondo peak at only one sign of the bias voltage. We show that even when the pseudospin states have very different tunnel rates to the leads, a Kondo temperature can be consistently defined for the double quantum dot system.