The pulsed laser deposition (PLD) technique is used for the direct fabrication of nanohybrid heterojunctions (NH‐HJs) solar cells exhibiting high PCE and excellent stability in air without any ...encapsulation and/or resorting to any surface treatment, ligand engineering and/or post‐synthesis processing. The NH‐HJs are achieved through the PLD‐based decoration of hydrothermally‐grown one‐dimensional TiO2 nanorods (TiO2‐NRs) by PbS quantum dots (PbS‐QDs). By optimizing both the amount of PbS‐QDs (via the number of laser ablation pulses) and the length of the TiO2‐NRs, it is possible to achieve optimal NH‐HJs based PV devices with high power conversion efficiency (PCE) of 4.85%. This high PCE is found to occur for an optimal length of the NRs (≈290 nm) which coincides with the average penetration depth of PbS‐QDs into the porous TiO2‐NRs matrix, leading thereby to the formation of the largest extent of NH‐HJs. Most importantly, the PCE of these novel devices is found to be fairly stable for several months under ambient air. The addition of single‐wall carbon nanotubes (SWCNTs) onto the TiO2‐NRs prior to their decoration by PbS‐QDs is shown to further enhance their PCE to a value as high as 5.3%, because of additional light absorption and improved charge collection ensured by SWCNTs.
Pulsed laser deposition (PLD) is advantageously used to decorate TiO2‐nano rods (TiO2‐NRs) with PbS‐quantum dots (PbS‐QDs) to achieve highly efficient nanohybrid‐heterojunctions (NH‐HJ) solar cells. By optimizing the characteristics of both PLD‐deposited PbS‐QDs and TiO2‐NRs, while introducing MoO3 hole extracting layer and single‐wall carbon nanotubes efficient charge carrier, NH‐HJ PV‐devices exhibit power conversion efficiencies as high as 5.3% (under AM1.5 solar illumination).
The oncogenic PI3K/Akt/mTOR pathway is frequently activated in HCC. Data on the mTOR inhibitor, temsirolimus, is limited in HCC patients with concomitant chronic liver disease. The objectives of this ...study were: (1) In phase I, to determine DLTs and MTD of temsirolimus in HCC patients with chronic liver disease; (2) In phase II, to assess activity of temsirolimus in HCC, and (3) to explore potential biomarkers for response.
Major eligibility criteria included histologically confirmed advanced HCC and adequate organ function. In Phase I part of the study, temsirolimus was given weekly in 3-weekly cycle; dose levels were 20 mg (level 1), 25 mg (level 2) and 30 mg (level 3). The MTD was used in the subsequent phase II part; the primary endpoint was PFS and secondary endpoints were response and OS. In addition, exploratory analysis was conducted on pre-treatment tumour tissues to determine stathmin, pS6, pMTOR or p-AKT expressions as potential biomarkers for response. Overall survival and PFS were calculated using the Kaplan-Meier method. Reassessment CT scans were done every 6 weeks. All adverse events were reported using CTCAE v3.
The Phase I part consisted of 19 patients, 2 of 6 patients at level 3 experienced DLT; dose level 2 was determined to be the MTD. The phase II part consisted of 36 patients. Amongst 35 assessable patients, there were 1 PR, 20 SD and 14 PD. Overall, the median PFS was 2.83 months (95% C.I. 1.63-5.24). The median OS was 8.89 months (95% C.I. 5.89-13.30). Grade ≥ 3 that occurred in > 10% of patients included thrombocytopenia (4) and hyponatraemia (4). Exploratory analysis revealed that disease stabilization (defined as CR + PR + SD > 12 weeks) in tumours having high and low pMTOR H-scores to be 70% and 29% respectively (OR 5.667, 95% CI 1.129-28.454, p = 0.035).
In HCC patients with chronic liver disease, the MTD of temsirolimus was 25 mg weekly in a 3-week cycle. The targeted PFS endpoint was not reached. However, further studies to identify appropriate patient subgroup are warranted.
This study has been registered in ClinicalTrials.gov (Id: NCT00321594) on 1 December 2010.
We sequenced the genomes of 3,615 strains of serotype Emm protein 1 (M1) group A Streptococcus to unravel the nature and timing of molecular events contributing to the emergence, dissemination, and ...genetic diversification of an unusually virulent clone that now causes epidemic human infections worldwide. We discovered that the contemporary epidemic clone emerged in stepwise fashion from a precursor cell that first contained the phage encoding an extracellular DNase virulence factor (streptococcal DNase D2, SdaD2) and subsequently acquired the phage encoding the SpeA1 variant of the streptococcal pyrogenic exotoxin A superantigen. The SpeA2 toxin variant evolved from SpeA1 by a single-nucleotide change in the M1 progenitor strain before acquisition by horizontal gene transfer of a large chromosomal region encoding secreted toxins NAD ⁺-glycohydrolase and streptolysin O. Acquisition of this 36-kb region in the early 1980s into just one cell containing the phage-encoded sdaD2 and speA2 genes was the final major molecular event preceding the emergence and rapid intercontinental spread of the contemporary epidemic clone. Thus, we resolve a decades-old controversy about the type and sequence of genomic alterations that produced this explosive epidemic. Analysis of comprehensive, population-based contemporary invasive strains from seven countries identified strong patterns of temporal population structure. Compared with a preepidemic reference strain, the contemporary clone is significantly more virulent in nonhuman primate models of pharyngitis and necrotizing fasciitis. A key finding is that the molecular evolutionary events transpiring in just one bacterial cell ultimately have produced millions of human infections worldwide.
Post-traumatic arthritis (PTA) is a rapidly progressive form of arthritis that develops due to joint injury, including articular fracture. Current treatments are limited to surgical restoration and ...stabilization of the joint; however, evidence suggests that PTA progression is mediated by the upregulation of pro-inflammatory cytokines, such as interleukin-1 (IL-1) or tumor necrosis factor-α (TNF-α). Although these cytokines provide potential therapeutic targets for PTA, intra-articular injections of anti-cytokine therapies have proven difficult due to rapid clearance from the joint space. In this study, we examined the ability of a cross-linked elastin-like polypeptide (xELP) drug depot to provide sustained intra-articular delivery of IL-1 and TNF-α inhibitors as a beneficial therapy. Mice sustained a closed intra-articular tibial plateau fracture; treatment groups received a single intra-articular injection of drug encapsulated in xELP. Arthritic changes were assessed 4 and 8 weeks after fracture. Inhibition of IL-1 significantly reduced the severity of cartilage degeneration and synovitis. Inhibition of TNF-α alone or with IL-1 led to deleterious effects in bone morphology, articular cartilage degeneration, and synovitis. These findings suggest that IL-1 plays a critical role in the pathogenesis of PTA following articular fracture, and sustained intra-articular cytokine inhibition may provide a therapeutic approach for reducing or preventing joint degeneration following trauma.
As more clinically-relevant genomic features of myeloid malignancies are revealed, it has become clear that targeted clinical genetic testing is inadequate for risk stratification. Here, we develop ...and validate a clinical transcriptome-based assay for stratification of acute myeloid leukemia (AML). Comparison of ribonucleic acid sequencing (RNA-Seq) to whole genome and exome sequencing reveals that a standalone RNA-Seq assay offers the greatest diagnostic return, enabling identification of expressed gene fusions, single nucleotide and short insertion/deletion variants, and whole-transcriptome expression information. Expression data from 154 AML patients are used to develop a novel AML prognostic score, which is strongly associated with patient outcomes across 620 patients from three independent cohorts, and 42 patients from a prospective cohort. When combined with molecular risk guidelines, the risk score allows for the re-stratification of 22.1 to 25.3% of AML patients from three independent cohorts into correct risk groups. Within the adverse-risk subgroup, we identify a subset of patients characterized by dysregulated integrin signaling and RUNX1 or TP53 mutation. We show that these patients may benefit from therapy with inhibitors of focal adhesion kinase, encoded by PTK2, demonstrating additional utility of transcriptome-based testing for therapy selection in myeloid malignancy.
Abstract Background Eradication of Helicobacter pylori has become part of the standard therapy for peptic ulcer. However, the role of H pylori eradication in perforation of peptic ulcers remains ...controversial. It is unclear whether eradication of the bacterium confers prolonged ulcer remission after simple repair of perforated peptic ulcer. Methods A systematic review and meta-analysis of randomized controlled trials was performed to evaluate the effects of H pylori eradication on prevention of ulcer recurrence after simple closure of perforated peptic ulcers. The primary outcome to evaluate these effects was the incidence of postoperative ulcers; the secondary outcome was the rate of H pylori elimination. Results The meta-analysis included five randomized controlled trials and 401 patients. A high prevalence of H pylori infection occurred in patients with perforated peptic ulcers. Eradication of H pylori significantly reduced the incidence of ulcer recurrence at 8 wk (risk ratio 2.97; 95% confidence interval: 1.06–8.29) and 1 y (risk ratio 1.49; 95% confidence interval: 1.10–2.03) postoperation. The rate of H pylori eradication was significantly higher in the treatment group than in the nontreatment group. Conclusions Eradication therapy should be provided to patients with H pylori infection after simple closure of perforated gastroduodenal ulcers.
Chronic obstructive pulmonary disease (COPD) results from a progressive decline in lung function, which is thought to be the consequence of airway inflammation. We hypothesized that antiinflammatory ...therapy with inhaled corticosteroids would slow this decline.
We enrolled 1116 persons with COPD whose forced expiratory volume in one second (FEV1) was 30 to 90 percent of the predicted value in a 10-center, placebo-controlled, randomized trial of inhaled triamcinolone acetonide administered at a dose of 600 microg twice daily. The primary outcome measure was the rate of decline in FEV1 after the administration of a bronchodilator. The secondary outcome measures included respiratory symptoms, use of health care services, and airway reactivity. In a substudy of 412 participants, we measured bone density in the lumbar spine and femur at base line and one and three years after the beginning of treatment.
The mean duration of follow-up was 40 months. The rate of decline in the FEV1 after bronchodilator use was similar in the 559 participants in the triamcinolone group and the 557 participants in the placebo group (44.2+/-2.9 vs. 47.0+/-3.0 ml per year, P= 0.50). Members of the triamcinolone group had fewer respiratory symptoms during the course of the study (21.1 per 100 person-years vs. 28.2 per 100 person-years, P=0.005) and had fewer visits to a physician because of a respiratory illness (1.2 per 100 person-years vs. 2.1 per 100 person-years, P=0.03). Those taking triamcinolone also had lower airway reactivity in response to methacholine challenge at 9 months and 33 months (P=0.02 for both comparisons). After three years, the bone density of the lumbar spine and the femur was significantly lower in the triamcinolone group (P < or = 0.007).
Inhaled triamcinolone does not slow the rate of decline in lung function in people with COPD, but it improves airway reactivity and respiratory symptoms and decreases the use of health care services for respiratory problems. These benefits should be weighed against the potential long-term adverse effects of triamcinolone on bone mineral density.
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•We model thermodynamic stabilization of nanocrystalline metals via solute additions.•Our model calculations for FeZr are in agreement with experimental observations.•Thermodynamic ...stability maps are presented as a guide for solute selection.•Thermodynamic stability maps show systems that mitigate nanocrystalline grain growth.•Applied to >1000 nanocrystalline systems to show boundary and interior concentrations.
Mitigating grain growth at high temperatures in binary nanocrystalline alloys is important for processing nanocrystalline alloy systems. The objective of this research is to develop a methodical design-based approach for selecting solutes in binary nanocrystalline alloys by revisiting grain boundary thermodynamics and the internal processes of grain growth and solute segregation in a closed system. In this work, the grain boundary energy is derived and systematically studied in terms of temperature, grain size, concentration, and solute segregation for binary systems of 44 solvents and 52 solutes, using readily-available elemental data, such as moduli and liquid enthalpy of mixing. It is shown that through solute segregation, the grain boundary energies of some binary systems can be reduced, resulting in thermodynamically stable grain structures and successful prediction of solutes that inhibit grain growth in some nanocrystalline alloys. Parametric studies reveal trends between equilibrium grain size, solute distribution and temperature for various binary systems culminating in the generation of nanocrystalline thermodynamic stability maps as a tool for solute selection in binary nanocrystalline alloys.
Background. Candidemia remains a major cause of morbidity and mortality in the health care setting, and the epidemiology of Candida infection is changing. Methods. Clinical data from patients with ...candidemia were extracted from the Prospective Antifungal Therapy (PATH) Alliance database, a comprehensive registry that collects information regarding invasive fungal infections. A total of 2019 patients, enrolled from 1 July 2004 through 5 March 2008, were identified. Data regarding the candidemia episode were analyzed, including the specific fungal species and patient survival at 12 weeks after diagnosis. Results. The incidence of candidemia caused by non–Candida albicans Candida species (54.4%) was higher than the incidence of candidemia caused by C. albicans (45.6%). The overall, crude 12-week mortality rate was 35.2%. Patients with Candida parapsilosis candidemia had the lowest mortality rate (23.7%; P<.001) and were less likely to be neutropenic (5.1%; P<.001) and to receive corticosteroids (33.5%; P<.001) or other immunosuppressive drugs (7.9%; P=.002), compared with patients infected with other Candida species. Candida krusei candidemia was most commonly associated with prior use of antifungal agents (70.6%; P<.001), hematologic malignancy (52.9%; P<.001) or stem cell transplantation (17.7%; P<.001), neutropenia (45.1%; P<.001), and corticosteroid treatment (60.8%; P<.001). Patients with C. krusei candidemia had the highest crude 12-week mortality in this series (52.9%; P<.001). Fluconazole was the most commonly administered antimicrobial, followed by the echinocandins, and amphotericin B products were infrequently administered. Conclusions. The epidemiology and choice of therapy for candidemia are rapidly changing. Additional study is warranted to differentiate host factors and differences in virulence among Candida species and to determine the best therapeutic regimen.
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