Biological-effective versus conventional dose volume histograms correlated with late genitourinary and gastrointestinal toxicity after external beam radiotherapy for prostate cancer: a matched pair analysis

BACKGROUND: To determine whether the dose-volume histograms (DVH's) for the rectum and bladder constructed using biological-effective dose (BED-DVH's) better correlate with late gastrointestinal (GI) and genitourinary (GU) toxicity after treatment with external beam radiotherapy for prostate cancer than conventional DVH's (C-DVH's). METHODS: The charts of 190 patients treated with external beam radiotherapy with a minimum follow-up of 2 years were reviewed. Six patients (3.2%) were found to have RTOG grade 3 GI toxicity, and similarly 6 patients (3.2%) were found to have RTOG grade 3 GU toxicity. Average late C-DVH's and BED-DVH's of the bladder and rectum were computed for these patients as well as for matched-pair control patients. For each matched pair the following measures of normalized difference in the DVH's were computed: (a) δ(AUC )= (Area Under Curve [AUC] in grade 3 patient – AUC in grade 0 patient)/(AUC in grade 0 patient) and (b) δ(V60 )= (Percent volume receiving = 60 Gy [V60] in grade 3 patient – V60 in grade 0 patient)/(V60 in grade 0 patient). RESULTS: As expected, the grade 3 curve is to the right of and above the grade 0 curve for all four sets of average DVH's – suggesting that both the C-DVH and the BED-DVH can be used for predicting late toxicity. δ(AUC )was higher for the BED-DVH's than for the C-DVH's – 0.27 vs 0.23 (p = 0.036) for the rectum and 0.24 vs 0.20 (p = 0.065) for the bladder. δ(V60 )was also higher for the BED-DVH's than for the C-DVH's – 2.73 vs 1.49 for the rectum (p = 0.021) and 1.64 vs 0.71 (p = 0.021) for the bladder. CONCLUSIONS: When considering well-established dosimetric endpoints used in evaluating treatment plans, BED-DVH's for the rectum and bladder correlate better with late toxicity than C-DVH's and should be considered when attempting to minimize late GI and GU toxicity after external beam radiotherapy for prostate cancer

Evaluation of simple rapid HIV assays and development of national rapid HIV test algorithms in Dar es Salaam, Tanzania

BACKGROUND: Suitable algorithms based on a combination of two or more simple rapid HIV assays have been shown to have a diagnostic accuracy comparable to double enzyme-linked immunosorbent assay (ELISA) or double ELISA with Western Blot strategies. The aims of this study were to evaluate the performance of five simple rapid HIV assays using whole blood samples from HIV-infected patients, pregnant women, voluntary counseling and testing attendees and blood donors, and to formulate an alternative confirmatory strategy based on rapid HIV testing algorithms suitable for use in Tanzania. METHODS: Five rapid HIV assays: Determine HIV-1/2 (Inverness Medical), SD Bioline HIV 1/2 3.0 (Standard Diagnostics Inc.), First Response HIV Card 1-2.0 (PMC Medical India Pvt Ltd), HIV1/2 Stat-Pak Dipstick (Chembio Diagnostic System, Inc) and Uni-Gold HIV-1/2 (Trinity Biotech) were evaluated between June and September 2006 using 1433 whole blood samples from hospital patients, pregnant women, voluntary counseling and testing attendees and blood donors. All samples that were reactive on all or any of the five rapid assays and 10% of non-reactive samples were tested on a confirmatory Inno-Lia HIV I/II immunoblot assay (Immunogenetics). RESULTS: Three hundred and ninety samples were confirmed HIV-1 antibody positive, while 1043 were HIV negative. The sensitivity at initial testing of Determine, SD Bioline and Uni-Gold was 100% (95% CI; 99.1-100) while First Response and Stat-Pak had sensitivity of 99.5% (95% CI; 98.2-99.9) and 97.7% (95% CI; 95.7-98.9), respectively, which increased to 100% (95% CI; 99.1-100) on repeat testing. The initial specificity of the Uni-Gold assay was 100% (95% CI; 99.6-100) while specificities were 99.6% (95% CI; 99-99.9), 99.4% (95% CI; 98.8-99.7), 99.6% (95% CI; 99-99.9) and 99.8% (95% CI; 99.3-99.9) for Determine, SD Bioline, First Response and Stat-Pak assays, respectively. There was no any sample which was concordantly false positive in Uni-Gold, Determine and SD Bioline assays. CONCLUSION: An alternative confirmatory HIV testing strategy based on initial testing on either SD Bioline or Determine assays followed by testing of reactive samples on the Determine or SD Bioline gave 100% sensitivity (95% CI; 99.1-100) and 100% specificity (95% CI; 96-99.1) with Uni-Gold as tiebreaker for discordant results

Nanocrystalline hydroxyapatite and zinc-doped hydroxyapatite as carrier material for controlled delivery of ciprofloxacin

In bone disorders infections are common. The concentration of majority of antibiotics is very low in the bone tissue. A high local dose can be obtained from the ciprofloxacin-loaded hydroxyapatite nanoparticles. The present study is aimed at developing the use of hydroxyapatite and zinc-doped hydroxyapatite nanoparticles as a carrier for ciprofloxacin drug delivery system. The ciprofloxacin-loaded hydroxyapatite and zinc-doped hydroxyapatite have a good antibacterial activity against Pseudomonas aeruginosa and Staphylococcus aureus. Hydroxyapatite and zinc-doped hydroxyapatite were prepared and characterized using X-ray diffraction, Transmission electron microscopy and inductively coupled plasma optical emission spectrometry. They were loaded with ciprofloxacin using optimized drug loading parameters. Drug loading, in vitro drug release and antimicrobial activity were analyzed. The influence of zinc on the controlled release of ciprofloxacin was analyzed. The results show that the presence of zinc increases the drug release percentage and that the drug was released in a controlled manner

Mutations at the Subunit Interface of Yeast Proliferating Cell Nuclear Antigen Reveal a Versatile Regulatory Domain

Acknowledgments We thank Szilvia Minorits for technical assistance. I.U. conceived and designed the project and wrote the manuscript. All authors participated in designing and performing the experiments, and analyzing the results. The authors declare no competing financial interests. This work was also supported by a grant from the National Research, Development and Innovation Office GINOP-2.3.2-15-2016-00001. Funding: This work was supported by Hungarian Science Foundation Grant OTKA 109521 and National Research Development and Innovation Office GINOP-2.3.2-15-2016-00001. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

Circular Dichroism Studies of \alpha-Aminoisobutyric Acid-Containing Peptides: Chain Length and Solvent Effects in Alternating Aib-L-Ala and Aib-L-Val Sequences

The CD spectra of the peptides $Boc-X-{(Aib-X)}_n-OMe$ (n = 1,2,3) and $Boc-{(Aib-X)}_5-OMe$, where X = L-Ala or L-Val have been examined in several solvents. The X = Ala and Val peptides behave similarly in all solvents, suggesting that the Aib residues dominate the folding preferences of these peptides. The decapeptides adopt helical conformations in methanol and trifluoroethanol, with characteristic negative CD bands at 222 and 205 nm. In the heptapeptides, similar spectra with reduced intensities are observed. Comparison with nmr studies suggest that estimates of helical content in oligopeptides by CD methods may lead to erroneous conclusions. The pentapeptides yield solvent-dependent spectra indicative of conformational perturbations. Peptide association in dioxane results in an unusual spectrum with a single negative band at 210 nm for the decapeptides. Disaggregation is induced by the addition of methanol or water to dioxane solutions. Aggregation of the heptapeptides is less pronounced in dioxane, suggesting that a critical helix length may be necessary to promote association stabilized by helix dipole-dipole interactions

Cracks emanating from pin-loaded lugs

Pin-loaded lugs were analysed in the presence of cracks emanating from circular holes. The analysis presents a unified treatment of interference, push or clearance fit pins. Both metallic (isotropic) and composite (orthotropic) plates were dealt with. The finite element model used special singular six-noded quadrilateral elements at the crack tip. The non-linear load contact behaviour at the pin-hole interface was dealt with by an inverse technique. A modified crack closure integral (MCCI) technique was used to evaluate the strain energy release rates (SERRs) and stress intensity factors (SIFs) at the crack tips. Numerical results are presented showing the non-linear variation of SIF with applied stress, and the influence of the amount of interference or clearance and the interfacial friction on SIF

Raoultella ornithinolytica: A Case Series of Clinical Presentations and its Role in Various Infections from a Tertiary Care Centre in Tumkur, Karnataka, India

Raoultella ornithinolytica (R. ornithinolytica), a Gram-negative bacillus, has characteristics resembling those of Klebsiella spp. This bacterium is present in soil and aquatic environments and seldom causes Healthcare-Associated Infections (HAIs). However, clinical features and outcomes of human infections caused by R. ornithinolytica have been reported for only a limited number of cases. Here, multiple cases of adult patients with clinical features of community-acquired infections at different body sites are presented. R. ornithinolytica was identified in the laboratory from respective samples sent for culture and sensitivity. These patients were treated with good outcomes. R. ornithinolytica is a saprophyte known to cause secondary infections in patients with risk factors and sometimes exhibits antibiotic resistance. However, all the patients presented to the institution recovered fully from the infections and were discharged

Modified Crack Closure Integral Using Six-Noded Isoparametric Quadrilateral Singular Elements

Six-noded, isoparametric serendipity type quadrilateral regular/singular elements are used for the estimation of stress intensity factors (SIF) in linear elastic fracture mechanics (LEFM) problems involving cracks in two-dimensional structural components. The square root singularity is achieved in the six-noded elements by moving the in-side nodes to the quarter point position. The modified crack closure integral (MCCI) method is adopted which could generate accurate estimates of SIF for a relatively coarse mesh. The equations for strain energy release rate and SIF are derived for mixed mode situations using six-noded quadrilateral elements at the crack tip. The model is validated by numerical studies for a centre crack in a finite plate under uniaxial tension. a single edge notched specimen under uniaxial tension, an inclined crack in a finite rectangular plate and cracks emanating from a pin-loaded lug (or lug attachment). The results compare very well with reference solutions available in the literature