Cascade atom in high-Q cavity: The spectrum for non-Markovian decay

The spontaneous emission spectrum for a three level cascade configuration atom in a single mode high-Q cavity coupled to a zero temperature reservoir of continuum external modes is determined from the atom-cavity mode master equation using the quantum regression theorem. Initially the atom is in its upper state and the cavity mode empty of photons. Following Glauber, the spectrum is defined via the response of a detector atom. Spectra are calculated for the detector located inside the cavity (case A), outside the cavity end mirror (Case B-end emission), or placed for emission out the side of the cavity (Case C). The spectra for case A and case B are found to be essentially the same. In all the cases the predicted lineshapes are free of instrumental effects and only due to cavity decay. Spectra are presented for intermediate and strong coupling regime situations (where both atomic transitions are resonant with the cavity frequency), for cases of non-zero cavity detuning, and for cases where the two atomic transition frequencies differ. The spectral features for Cases B(A) and C are qualitatively similar, with six spectral peaks for resonance cases and eight for detuned cases. These general features of the spectra can be understood via the dressed atom model. However, Case B and C spectra differ in detail, with the latter exhibiting a deep spectral hole at the cavity frequency due to quantum interference effects.Comment: 29 pages, 14 figures; v2: very minor correction to two equations, thicker lines in some figure

Using de-identified electronic health records to research mental health supported housing services: A feasibility study

BACKGROUND: Mental health supported housing services are a key component in the rehabilitation of people with severe and complex needs. They are implemented widely in the UK and other deinstitutionalised countries but there have been few empirical studies of their effectiveness due to the logistic challenges and costs of standard research methods. The Clinical Record Interactive Search (CRIS) tool, developed to de-identify and interrogate routinely recorded electronic health records, may provide an alternative to evaluate supported housing services. METHODS: The feasibility of using the Camden and Islington NHS Foundation Trust CRIS database to identify a sample of users of mental health supported accommodation services. Two approaches to data interrogation and case identification were compared; using structured fields indicating individual's accommodation status, and iterative development of free text searches of clinical notes referencing supported housing. The data used were recorded over a 10-year-period (01-January-2008 to 31-December-2017). RESULTS: Both approaches were carried out by one full-time researcher over four weeks (150 hours). Two structured fields indicating accommodation status were found, 2,140 individuals had a value in at least one of the fields representative of supported accommodation. The free text search of clinical notes returned 21,103 records pertaining to 1,105 individuals. A manual review of 10% of the notes indicated an estimated 733 of these individuals had used a supported housing service, a positive predictive value of 66.4%. Over two-thirds of the individuals returned in the free text search (768/1,105, 69.5%) were identified via the structured fields approach. Although the estimated positive predictive value was relatively high, a substantial proportion of the individuals appearing only in the free text search (337/1,105, 30.5%) are likely to be false positives. CONCLUSIONS: It is feasible and requires minimal resources to use de-identified electronic health record search tools to identify large samples of users of mental health supported housing using structured and free text fields. Further work is needed to establish the availability and completion of variables relevant to specific clinical research questions in order to fully assess the utility of electronic health records in evaluating the effectiveness of these services

Heating cancer stem cells to reduce tumor relapse

Tumour relapse is believed to be caused by rare cancer-cells with stem-cell properties (cancer stem cells) that are intrinsically resistant to available treatments. The identification of novel strategies to increase their sensitivity has major clinical implications. Latest clinical trials have shown a positive antitumoral effect of hyperthermia in combination with chemotherapy or radiotherapy. In a recent paper, the combination of increased temperature at the tumour site, generated by laser treatment of intravenously-injected gold nanoshells, and ionizing radiations enhances radiosensitivity of cancer stem cells and tumor response. At the root of the success of hyperthermia in enhancing radio-sensitization of cancer stem cells is the inhibition of their capacity to repair DNA damage, affecting the survival rate of these cells

Dissecting the Active Site of the Collagenolytic Cathepsin L3 Protease of the Invasive Stage of Fasciola hepatica

Background: A family of secreted cathepsin L proteases with differential activities is essential for host colonization and survival in the parasitic flatworm Fasciola hepatica. While the blood feeding adult secretes predominantly FheCL1, an enzyme with a strong preference for Leu at the S2 pocket of the active site, the infective stage produces FheCL3, a unique enzyme with collagenolytic activity that favours Pro at P2. Methodology/Principal Findings: Using a novel unbiased multiplex substrate profiling and mass spectrometry methodology (MSP-MS), we compared the preferences of FheCL1 and FheCL3 along the complete active site cleft and confirm that while the S2 imposes the greatest influence on substrate selectivity, preferences can be indicated on other active site subsites. Notably, we discovered that the activity of FheCL1 and FheCL3 enzymes is very different, sharing only 50% of the cleavage sites, supporting the idea of functional specialization. We generated variants of FheCL1 and FheCL3 with S2 and S3 residues by mutagenesis and evaluated their substrate specificity using positional scanning synthetic combinatorial libraries (PS-SCL). Besides the rare P2 Pro preference, FheCL3 showed a distinctive specificity at the S3 pocket, accommodating preferentially the small Gly residue. Both P2 Pro and P3 Gly preferences were strongly reduced when Trp67 of FheCL3 was replaced by Leu, rendering the enzyme incapable of digesting collagen. In contrast, the inverse Leu67Trp substitution in FheCL1 only slightly reduced its Leu preference and improved Pro acceptance in P2, but greatly increased accommodation of Gly at S3. Conclusions/Significance: These data reveal the significance of S2 and S3 interactions in substrate binding emphasizing the role for residue 67 in modulating both sites, providing a plausible explanation for the FheCL3 collagenolytic activity essential to host invasion. The unique specificity of FheCL3 could be exploited in the design of specific inhibitors selectively directed to specific infective stage parasite proteinases. © 2013 Corvo et al

Structural and functional relationships in the virulence-associated cathepsin L proteases of the parasitic liver fluke, Fasciola hepatica

The helminth parasite Fasciola hepatica secretes cysteine proteases to facilitate tissue invasion, migration, and development within the mammalian host. The major proteases cathepsin L1 (FheCL1) and cathepsin L2 (FheCL2) were recombinantly produced and biochemically characterized. By using site-directed mutagenesis, we show that residues at position 67 and 205, which lie within the S2 pocket of the active site, are critical in determining the substrate and inhibitor specificity. FheCL1 exhibits a broader specificity and a higher substrate turnover rate compared with FheCL2. However, FheCL2 can efficiently cleave substrates with a Pro in the P2 position and degrade collagen within the triple helices at physiological pH, an activity that among cysteine proteases has only been reported forhuman cathepsin K. The 1.4-Å three-dimensional structure of the FheCL1 was determined by x-ray crystallography, and the three-dimensional structure of FheCL2 was constructed via homology-based modeling. Analysis and comparison of these structures and our biochemical data with those of human cathepsins L and Kprovided an interpretation of the substrate-recognition mechanisms of these major parasite proteases. Furthermore, our studies suggest that a configuration involving residue 67 and the "gatekeeper" residues 157 and 158 situated at the entrance of the active site pocket create a topology that endows FheCL2 with its unusual collagenolytic activity. The emergence of a specialized collagenolytic function in Fasciola likely contributes to the success of this tissue-invasive parasite. © 2008 by The American Society for Biochemistry and Molecular Biology, Inc

Nitrous oxide may not increase the risk of cancer recurrence after colorectal surgery: a follow-up of a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Even the best cancer surgery is usually associated with minimal residual disease. Whether these remaining malignant cells develop into clinical recurrence is at least partially determined by adequacy of host defense, especially natural killer cell function. Anesthetics impair immune defenses to varying degrees, but nitrous oxide appears to be especially problematic. We therefore tested the hypothesis that colorectal-cancer recurrence risk is augmented by nitrous oxide administration during colorectal surgery.</p> <p>Methods</p> <p>We conducted a 4- to 8-year follow-up of 204 patients with colorectal cancer who were randomly assigned to 65% nitrous oxide (n = 97) or nitrogen (n = 107), balanced with isoflurane and remifentanil. The primary outcome was the time to cancer recurrence. Our primary analysis was a multivariable Cox-proportional-hazards regression model that included relevant baseline variables. In addition to treatment group, the model considered patient age, tumor grade, dissemination, adjacent organ invasion, vessel invasion, and the number of nodes involved. The study had 80% power to detect a 56% or greater reduction in recurrence rates (i.e., hazard ratio of 0.44 or less) at the 0.05 significance level.</p> <p>Results</p> <p>After adjusting for significant baseline covariables, risk of recurrence did not differ significantly for nitrous oxide and nitrogen, with a hazard ratio estimate (95% CI) of 1.10 (0.66, 1.83), <it>P </it>= 0.72. No two-way interactions with the treatment were statistically significant.</p> <p>Conclusion</p> <p>Colorectal-cancer recurrence risks were not greatly different in patients who were randomly assigned to 65% nitrous oxide or nitrogen during surgery. Our results may not support avoiding nitrous oxide use to prevent recurrence of colorectal cancer.</p> <p>Implications Statement</p> <p>The risk of colorectal cancer recurrence was similar in patients who were randomly assigned to 65% nitrous oxide or nitrogen during colorectal surgery.</p> <p>Trial Registration</p> <p>Current Controlled Clinical Trials NCT00781352 <url>http://www.clinicaltrials.gov</url></p

A Comparison of the Epidemiology and Clinical Presentation of Seasonal Influenza A and 2009 Pandemic Influenza A (H1N1) in Guatemala

A new influenza A (H1N1) virus was first found in April 2009 and proceeded to cause a global pandemic. We compare the epidemiology and clinical presentation of seasonal influenza A (H1N1 and H3N2) and 2009 pandemic influenza A (H1N1) (pH1N1) using a prospective surveillance system for acute respiratory disease in Guatemala.Patients admitted to two public hospitals in Guatemala in 2008-2009 who met a pneumonia case definition, and ambulatory patients with influenza-like illness (ILI) at 10 ambulatory clinics were invited to participate. Data were collected through patient interview, chart abstraction and standardized physical and radiological exams. Nasopharyngeal swabs were taken from all enrolled patients for laboratory diagnosis of influenza A virus infection with real-time reverse transcription polymerase chain reaction. We identified 1,744 eligible, hospitalized pneumonia patients, enrolled 1,666 (96%) and tested samples from 1,601 (96%); 138 (9%) had influenza A virus infection. Surveillance for ILI found 899 eligible patients, enrolled 801 (89%) and tested samples from 793 (99%); influenza A virus infection was identified in 246 (31%). The age distribution of hospitalized pneumonia patients was similar between seasonal H1N1 and pH1N1 (P = 0.21); the proportion of pneumonia patients <1 year old with seasonal H1N1 (39%) and pH1N1 (37%) were similar (P = 0.42). The clinical presentation of pH1N1 and seasonal influenza A was similar for both hospitalized pneumonia and ILI patients. Although signs of severity (admission to an intensive care unit, mechanical ventilation and death) were higher among cases of pH1N1 than seasonal H1N1, none of the differences was statistically significant.Small sample sizes may limit the power of this study to find significant differences between seasonal influenza A and pH1N1. In Guatemala, influenza, whether seasonal or pH1N1, appears to cause severe disease mainly in infants; targeted vaccination of children should be considered

Prognostic value of adenosine stress cardiovascular magnetic resonance in patients with low-risk chest pain

<p>Abstract</p> <p>Background</p> <p>Approximately 5% of patients with an acute coronary syndrome are discharged from the emergency room with an erroneous diagnosis of non-cardiac chest pain. Highly accurate non-invasive stress imaging is valuable for assessment of low-risk chest pain patients to prevent these errors. Adenosine stress cardiovascular magnetic resonance (AS-CMR) is an imaging modality with increasing application. The goal of this study was to evaluate the negative prognostic value of AS-CMR among low-risk acute chest pain patients.</p> <p>Methods</p> <p>We studied 103 patients, mean 56.7 ± 12.3 years of age, with chest pain and no electrocardiographic evidence of ischemia and negative cardiac biomarkers of necrosis, who were admitted to the Cardiac Decision Unit of our institution. All patients underwent AS-CMR. A negative AS-CMR was defined as absence of all the following: regional wall motion abnormalities at rest; perfusion defects during stress (adenosine) and rest; and myocardial scar on late gadolinium enhancement images. The patients were followed for a mean of 277 (range 161-462) days. The primary end point was defined as the combination of cardiac death, nonfatal acute myocardial infarction, re-hospitalization for chest pain, obstructive coronary artery disease (>50% coronary stenosis on invasive angiography) and coronary revascularization.</p> <p>Results</p> <p>In 14 patients (13.6%), AS-CMR was positive. The remaining 89 patients (86.4%), who had negative AS-CMR, were discharged. No patient with negative AS-CMR reached the primary end-point during follow-up. The negative predictive value of AS-CMR was 100%.</p> <p>Conclusion</p> <p>AS-CMR holds promise as a useful tool to rule out significant coronary artery disease in patients with low-risk chest pain. Patients with negative AS-CMR have an excellent short and mid-term prognosis.</p

SmCL3, a Gastrodermal Cysteine Protease of the Human Blood Fluke Schistosoma mansoni

Parasitic infection caused by blood flukes of the genus Schistosoma is a major global health problem. More than 200 million people are infected. Identifying and characterizing the constituent enzymes of the parasite's biochemical pathways should reveal opportunities for developing new therapies (i.e., vaccines, drugs). Schistosomes feed on host blood, and a number of proteolytic enzymes (proteases) contribute to this process. We have identified and characterized a new protease, SmCL3 (for Schistosoma mansoni cathepsin L3), that is found within the gut tissue of the parasite. We have employed various biochemical and molecular biological methods and sequence similarity analyses to characterize SmCL3 and obtain insights into its possible functions in the parasite, as well as its evolutionary position among cathepsin L proteases in general. SmCL3 hydrolyzes major host blood proteins (serum albumin and hemoglobin) and is expressed in parasite life stages infecting the mammalian host. Enzyme substrate specificity detected by positional scanning-synthetic combinatorial library was confirmed by molecular modeling. A sequence analysis placed SmCL3 to the cluster of other cathepsins L in accordance with previous phylogenetic analyses