Experimental Analysis of Energy Transfers between a Quantum Emitter and Light Fields.

Energy can be transferred between two quantum systems in two forms: unitary energy-that can be used to drive another system-and correlation energy-that reflects past correlations. We propose and implement experimental protocols to access these energy transfers in interactions between a quantum emitter and light fields. Upon spontaneous emission, we measure the unitary energy transfer from the emitter to the light field and show that it never exceeds half the total energy transfer and is reduced when introducing decoherence. We then study the interference of the emitted field and a coherent laser field at a beam splitter and show that the nature of the energy transfer quantitatively depends on the quantum purity of the emitted field.

Drug Survival, Safety, and Effectiveness of Biologics in Older Patients with Psoriasis: A Comparison with Younger Patients-A BioCAPTURE Registry Study.

BACKGROUND: Psoriasis is a common inflammatory disease in any age group, but also in older patients (≥ 65 years of age). Since older patients are often excluded from clinical trials, limited data specifically on this growing population are available, e.g. regarding the safety and performance of biological treatment. AIMS: We aimed to give insight into this specific population by comparing the drug survival and safety of biologics in older patients with that in younger patients. METHODS: In this real-world observational study, data from 3 academic and 15 non-academic centers in The Netherlands were extracted from the prospective BioCAPTURE registry. Biologics included in this study were tumor necrosis factor (TNF)-α, interleukin (IL)-17, IL-12/23, and IL-23 inhibitors. Patients were divided into two age groups: ≥ 65 years and < 65 years. The Charlson Comorbidity Index (CCI) was used to measure comorbid disease status, and all adverse events (AEs) that led to treatment discontinuation were classified according to the Medical Dictionary for Regulatory Activities (MedDRA) classification. All AEs that led to treatment discontinuation were studied to check whether they could be classified as serious AEs (SAEs). Kaplan-Meier survival curves for overall 5-year drug survival and split according to reasons of discontinuation (ineffectiveness or AEs) were constructed. Cox regression models were used to correct for possible confounders and to investigate associations with drug survival in both age groups separately. Psoriasis Area and Severity Index (PASI) scores during the first 2 years of treatment and at the time of treatment discontinuation were assessed and compared between age groups. RESULTS: A total of 890 patients were included, of whom 102 (11.4%) were aged ≥ 65 years. Body mass index, sex, and distribution of biologic classes (e.g. TNFα, IL12/23) were not significantly different between the two age groups. A significantly higher CCI score was found in older patients, indicative of more comorbidity (p < 0.001). The 5-year ineffectiveness-related drug survival was lower for older patients (44.5% vs. 60.5%; p = 0.006), and the 5-year overall (≥ 65 years: 32.4% vs. < 65 years: 42.1%; p = 0.144) and AE-related (≥ 65 years: 82.1% vs. < 65 years: 79.5%; p = 0.913) drug survival was comparable between age groups. Of all AEs (n = 155) that led to discontinuation, 16 (10.3%) were reported as SAEs but these only occurred in younger patients. After correcting for confounders, the same trends were observed in the drug survival outcomes. Linear regression analyses on PASI scores showed no statistical differences at 6, 12, 18, and 24 months of treatment between age groups. CONCLUSIONS: This study in a substantial, well-defined, prospective cohort provides further support that the use of biologics in older patients seems well-tolerated and effective. Biologic discontinuation due to AEs did not occur more frequently in older patients. Older patients discontinued biologic treatment more often due to ineffectiveness, although no clear difference in PASI scores was observed. More real-world studies on physician- and patient-related factors in older patients are warranted.

Bright Polarized Single-Photon Source Based on a Linear Dipole.

Semiconductor quantum dots in cavities are promising single-photon sources. Here, we present a path to deterministic operation, by harnessing the intrinsic linear dipole in a neutral quantum dot via phonon-assisted excitation. This enables emission of fully polarized single photons, with a measured degree of linear polarization up to 0.994±0.007, and high population inversion-85% as high as resonant excitation. We demonstrate a single-photon source with a polarized first lens brightness of 0.50±0.01, a single-photon purity of 0.954±0.001, and single-photon indistinguishability of 0.909±0.004.

Hong-Ou-Mandel Interference with Imperfect Single Photon Sources.

Hong-Ou-Mandel interference is a cornerstone of optical quantum technologies. We explore both theoretically and experimentally how unwanted multiphoton components of single-photon sources affect the interference visibility, and find that the overlap between the single photons and the noise photons significantly impacts the interference. We apply our approach to quantum dot single-photon sources to access the mean wave packet overlap of the single-photon component. This study provides a consistent platform with which to diagnose the limitations of current single-photon sources on the route towards the ideal device.

Optimal Coherent Filtering for Single Noisy Photons.

We introduce a filter using a noise-free quantum buffer with large optical bandwidth that can both filter temporal-spectral modes as well as interconvert them and change their frequency. We theoretically show that such quantum buffers optimally filter out temporal-spectral noise, producing identical single photons from many distinguishable noisy single-photon sources with the minimum required reduction in brightness. We then experimentally demonstrate a noise-free quantum buffer in a warm atomic system that is well matched to quantum dots. Based on these experiments, simulations show that our buffer can outperform all intensity (incoherent) filtering schemes for increasing indistinguishability.

On incorporating osmotic prestretch/prestress in image-driven finite element simulations of cartilage.

Medical imaging performed in vivo captures geometries under Donnan osmotic loading, even when the articulating joint is otherwise mechanically unloaded. Hence patient-specific finite element (FE) models constructed from such medical images of cartilage represent osmotically induced prestretched/prestressed states. When applying classical modeling approaches to patient-specific simulations of cartilage a theoretical inconsistency arises: the in-vivo imaged geometry (used to construct the model) is not an unloaded, stress-free reference configuration. Furthermore when fitting nonlinear constitutive models that include osmotic swelling (to obtain material parameters), if one assumes that experimental data-generated from osmotically loaded cartilage-begin from a stress-free reference configuration the fitted stress-stretch relationship (parameters) obtained will actually describe a different behavior. In this study we: (1) establish a practical computational method to include osmotically induced prestretch/prestress in image-driven simulations of cartilage; and (2) investigate the influence of considering the prestretched/prestressed state both when fitting fiber-reinforced, biphasic constitutive models of cartilage that include osmotic swelling and when simulating cartilage responses. Our results highlight the importance of determining the prestretched/prestressed state within cartilage induced by osmotic loading in the imaged configuration prior to solving boundary value problems of interest. With our new constitutive model and modeling methods, we aim to improve the fidelity of FE-based, patient-specific biomechanical simulations of joints and cartilage. Improved simulations can provide medical researchers with new information often unavailable in a clinical setting, information that may contribute to better insight into the pathophysiology of cartilage diseases.

Growth Description for Vessel Wall Adaptation: A Thick-Walled Mixture Model of Abdominal Aortic Aneurysm Evolution.

(1) Background: Vascular tissue seems to adapt towards stable homeostatic mechanical conditions, however, failure of reaching homeostasis may result in pathologies. Current vascular tissue adaptation models use many ad hoc assumptions, the implications of which are far from being fully understood; (2) Methods: The present study investigates the plausibility of different growth kinematics in modeling Abdominal Aortic Aneurysm (AAA) evolution in time. A structurally motivated constitutive description for the vessel wall is coupled to multi-constituent tissue growth descriptions; Constituent deposition preserved either the constituent's density or its volume, and Isotropic Volume Growth (IVG), in-Plane Volume Growth (PVG), in-Thickness Volume Growth (TVG) and No Volume Growth (NVG) describe the kinematics of the growing vessel wall. The sensitivity of key modeling parameters is explored, and predictions are assessed for their plausibility; (3) Results: AAA development based on TVG and NVG kinematics provided not only quantitatively, but also qualitatively different results compared to IVG and PVG kinematics. Specifically, for IVG and PVG kinematics, increasing collagen mass production accelerated AAA expansion which seems counterintuitive. In addition, TVG and NVG kinematics showed less sensitivity to the initial constituent volume fractions, than predictions based on IVG and PVG; (4) Conclusions: The choice of tissue growth kinematics is of crucial importance when modeling AAA growth. Much more interdisciplinary experimental work is required to develop and validate vascular tissue adaption models, before such models can be of any practical use.

The role of azithromycin in healthcare-associated pneumonia treatment.

WHAT IS KNOWN AND OBJECTIVE: Healthcare-associated pneumonia (HCAP) is an important presentation among hospitalized patients. Standardized definitions of this entity are almost a decade old, and practice patterns have shifted from published guidelines to include empiric coverage with a macrolide, such as azithromycin. Azithromycin is oftentimes included in the empiric treatment regimen for HCAP because of the importance of appropriate empiric antimicrobial coverage, the perceived concern regarding atypical organisms, potential anti-inflammatory effects of the medication, and positive clinical data among patients with Streptococcal bacteremia. METHODS: In this review, we systematically investigate data for each of these topics along with clinical data examining the role of azithromycin in HCAP. RESULTS AND DISCUSSION: Our findings indicate that atypical organisms are rare in HCAP, that the anti-inflammatory actions of azithromycin - although promising - have not produced consistently positive effects in many chronic or acute conditions, and that the data available for azithromycin use in bacteremia are of low quality. A single-centre cohort indicated that the clinical benefits of azithromycin did not extend to HCAP compared to community-acquired pneumonia. WHAT IS NEW AND CONCLUSION: Additionally, there are newer data emphasizing the potential cardiotoxicity of azithromycin, particularly among patients at high risk. All of these data indicate that azithromycin should not be part of the standard empiric treatment for HCAP.

A district general hospital experience of palliative biliary stenting.

BACKGROUND: Palliative management of malignant pancreaticobiliary (PB) disease typically takes the form of endoscopic biliary stenting with a covered metal stent. We set out to assess outcomes from endoscopic biliary stenting (endoscopic retrograde cholangiopancreatography, ERCP) for malignant disease in our district general hospital (DGH). METHODS: We identified patients with malignant PB disease who underwent primary ERCP between 2011 and 2012. Case notes were reviewed for clinical outcomes and involvement of palliative care. RESULTS: 38 patients underwent biliary stenting in this period. Median age was 75.6 years (53.6-99.8 years). 35 stents were placed for primary PB malignancy. 31 of these stents were covered metal stents and 6 were uncovered. Bilirubin decreased from a median of 218 to 112 µmol/L (median decrease 55 µmol/L). Complications occurred in the following 13 cases: 7 blocked stents (18.9%), 2 of which were associated with sepsis; 2 cases of stent migration (8.1%); 3 cases of biliary sepsis (8.1%) and 1 episode of pancreatitis (2.7%). Subsequently, 12 patients underwent a single repeat ERCP and 1 patient underwent 3 further ERCPs. Median survival following ERCP and stent was 78 days (10-806). 28 patients (76%) were known to the hospital palliative care team. CONCLUSIONS: Our DGH provides local service with complication rates comparable to those described in the literature. This allows care of patients with limited prognosis to be treated close to home. The majority of stent complications and mortality occur within 3 months. Input from the palliative care team is useful when considering whether a patient has a prognosis long enough to benefit from the procedure.

Modeling the dispersion in electromechanically coupled myocardium.

We present an approach to model the dispersion of fiber and sheet orientations in the myocardium. By utilizing structure parameters, an existing orthotropic and invariant-based constitutive model developed to describe the passive behavior of the myocardium is augmented. Two dispersion parameters are fitted to experimentally observed angular dispersion data of the myocardial tissue. Computations are performed on a unit myocardium tissue cube and on a slice of the left ventricle indicating that the dispersion parameter has an effect on the myocardial deformation and stress development. The use of fiber dispersions relating to a pathological myocardium had a rather big effect. The final example represents an ellipsoidal model of the left ventricle indicating the influence of fiber and sheet dispersions upon contraction over a cardiac cycle. Although only a minor shift in the pressure-volume (PV) loops between the cases with no dispersions and with fiber and sheet dispersions for a healthy myocardium was observed, a remarkably different behavior is obtained with a fiber dispersion relating to a diseased myocardium. In future simulations, this dispersion model for myocardial tissue may advantageously be used together with models of, for example, growth and remodeling of various cardiac diseases.

Pharmacokinetics of oral valganciclovir solution and intravenous ganciclovir in pediatric renal and liver transplant recipients.

In an open-label, prospective, pharmacokinetic assessment, we evaluated total drug exposure (area under the curve [AUC]) of intravenous (IV) ganciclovir (GCV) and oral (p.o.) valganciclovir when normalized for body surface area (BSA) in pediatric liver (n=20) and renal (n=26) transplant patients Reference doses for IV GCV (200 mg/m(2)) and p.o. valganciclovir (520 mg/m(2)) were based on adult doses, and adjusted for BSA initially, and BSA and renal function (estimated via creatinine clearance [CrCL]) thereafter. Renal transplant patients received GCV on days 1-2, valganciclovir 260 mg/m(2) on day 3, and valganciclovir 520 mg/m(2) on day 4. Liver transplant patients received twice daily GCV from enrollment to day 12, and then valganciclovir twice daily on days 13-14. GCV pharmacokinetics were described using a population pharmacokinetic approach. Type of solid organ transplant (kidney or liver) had no effect on GCV pharmacokinetics. Median GCV exposure following valganciclovir 520 mg/m(2) was similar to that with IV GCV, and to that reported in adults. Patients <5 years of age had AUC values approximately 50% of those compared with older age ranges; dosing based on both BSA and CrCL increased drug exposure in younger patients. A dosing algorithm based on BSA and CrCL should be tested in future studies.

Fungal and plant gene expression during the colonization of cacao seedlings by endophytic isolates of four Trichoderma species.

Endophytic isolates of Trichoderma species are being considered as biocontrol agents for diseases of Theobroma cacao (cacao). Gene expression was studied during the interaction between cacao seedlings and four endophytic Trichoderma isolates, T. ovalisporum-DIS 70a, T. hamatum-DIS 219b, T. harzianum-DIS 219f, and Trichoderma sp.-DIS 172ai. Isolates DIS 70a, DIS 219b, and DIS 219f were mycoparasitic on the pathogen Moniliophthora roreri, and DIS 172ai produced metabolites that inhibited growth of M. roreri in culture. ESTs (116) responsive to endophytic colonization of cacao were identified using differential display and their expression analyzed using macroarrays. Nineteen cacao ESTs and 17 Trichoderma ESTs were chosen for real-time quantitative PCR analysis. Seven cacao ESTs were induced during colonization by the Trichoderma isolates. These included putative genes for ornithine decarboxylase (P1), GST-like proteins (P4), zinc finger protein (P13), wound-induced protein (P26), EF-calcium-binding protein (P29), carbohydrate oxidase (P59), and an unknown protein (U4). Two plant ESTs, extensin-like protein (P12) and major intrinsic protein (P31), were repressed due to colonization. The plant gene expression profile was dependent on the Trichoderma isolate colonizing the cacao seedling. The fungal ESTs induced in colonized cacao seedlings also varied with the Trichoderma isolate used. The most highly induced fungal ESTs were putative glucosyl hydrolase family 2 (F3), glucosyl hydrolase family 7 (F7), serine protease (F11), and alcohol oxidase (F19). The pattern of altered gene expression suggests a complex system of genetic cross talk occurs between the cacao tree and Trichoderma isolates during the establishment of the endophytic association.

Paroxetine for social anxiety and alcohol use in dual-diagnosed patients.

The objective of this study was to compare the efficacy and tolerability of paroxetine to matched placebo in adults with co-occurring social anxiety disorder and alcohol use disorder. Outcome measures included standardized indices of social anxiety and alcohol use. Fifteen individuals meeting DSM-IV criteria for both social anxiety disorder and alcohol use disorder were randomized to treatment. Paroxetine (n = 6) or placebo (n = 9) was given in a double-blind format for 8 weeks using a flexible dosing schedule. Dosing began at 20 mg/d and increased to a target dose of 60 mg/d. There was a significant effect of treatment group on social anxiety symptoms, where patients treated with paroxetine improved more than those treated with placebo on both the Clinical Global Index (CGI) and the Liebowitz Social Anxiety Scale (Ps < or = 0.05). On alcohol use, there was not a significant effect of treatment on quantity/frequency measures of drinking, but there was for the CGI ratings (50% paroxetine patients versus 11% placebo patients were improvers on drinking, P < or = 0.05). This pilot study suggests that paroxetine is an effective treatment for social anxiety disorder in individuals with comorbid alcohol problems, and positive treatment effects can be seen in as little as 8 weeks. Further study is warranted to investigate its utility in helping affected individuals reduce alcohol use.

An overview of controlled studies of adolescent substance abuse treatment.

Although several treatments for adolescents with substance use disorders are available, there are few well-controlled studies in the extant literature that compare these treatments for efficacy. This paper provides an overview of controlled treatment studies for adolescents with substance use disorders. It focuses specifically on five main treatment modalities: family-based and multi-systemic interventions, behavioral therapy, cognitive behavioral therapy, pharmacotherapy, and twelve step approaches. Examples of adolescent-specific standardized assessment instruments are also provided, the inclusion of which may improve future treatment comparison studies. While the results look especially promising for cognitive behavioral therapy and family-based/multi-systemic therapies for adolescents with SUDs, most of the relevant studies fail to utilize validated outcome measures, making it difficult to conclude that one treatment approach is more effective than another.

Comparison of polyclonal induction agents in pediatric renal transplantation.

Collective pediatric data suggest that anti-T-cell induction therapy with polyclonal antibodies improves the outcome of both short- and long-term renal allograft survival. Polyclonal agents, including thymoglobulin (Thy), a rabbit anti-thymocyte globulin; Minnesota (horse) anti-lymphoblast globulin (ALG); and ATGAM, a horse anti-thymocyte globulin (ATG), all suppress B and T cells. While no specific T-cell subset marker exists to measure the adequacy of immunosuppression with polyclonal induction, flow cytometric analysis has been used to evaluate the suppression of CD3, CD4, and CD8 cells. Thy is currently undergoing pediatric trials at our center, and we have utilized ATG and ALG in previous pediatric induction protocols. ALG (20 mg/kg/day) and ATG (15 mg/kg/day) were administered over 10 days, whereas Thy (2 mg/kg/day) was given over 5 days. All inductions were accompanied by preoperative intravenous solumedrol (10 mg/kg) followed by oral prednisone (2 mg/kg/day) with taper. Preoperative (1.5 mg/kg/day) and post-operative (2 mg/kg/day) azathioprine was administered to patients receiving ALG or ATG. Mycophenolate mofetil (MMF) (1200 mg/m2/day) was given to the patients receiving Thy. Post-operative cyclosporin A (CsA) (14 mg/kg/day) was started (for all groups) once renal function permitted (creatinine < 50% of baseline with brisk urine output) (trough goal 150-250 ng/mL via HPLC). Values for CD3, CD4, and CD8 T cells were determined by flow cytometry in 2-18-yr-old renal transplant recipients, comparing the polyclonal induction agent utilized [Thy (n = 8), mean age 9.7 +/- 2.3 yr; ATG (n = 13), mean age 10.1 +/- 4.1 yr; and ALG (n = 9), mean age 9.3 +/- 3.7 yr] over days 2-10 post-induction. Data were expressed as the average percentage of cells remaining relative to the baseline T-cell subsets (day 1 = 100%), because of the large age variation present in basal T-cell subset values. The flow cytometric data suggest that 5 days of Thy appears to give an equal or greater peripheral blood T-cell suppression by day 10 than a 10-day course of either ATG or ALG.

Gender comparison in alcoholics with concurrent social phobia: implications for alcoholism treatment.

The present study compares male and female alcoholics with concurrent social phobia (N = 110) enrolled in an alcohol treatment study. Groups were compared using demographics, social phobia symptoms and severity, and psychiatric variables. Results showed that females reported higher fear ratings than males on some social phobia measures, although for the most part, the genders were more similar than different on social phobia symptoms and severity. There was a high occurrence of psychiatric comorbidity, especially for females. Females also reported more distress than males in family and social functioning. The results are discussed in terms of their implications for treatment for individuals with concurrent alcoholism and social phobia.