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Abstract Background Quantitative proteomics technologies have been developed to comprehensively identify and quantify proteins in two or more complex samples. Quantitative proteomics based on differential stable isotope labeling is one of the proteomics quantification technologies. Mass spectrometric data generated for peptide quantification are often noisy, and peak detection and definition require various smoothing filters to remove noise in order to achieve accurate peptide quantification. Many traditional smoothing filters, such as the moving average filter, Savitzky-Golay filter and Gaussian filter, have been used to reduce noise in MS peaks. However, limitations of these filtering approaches often result in inaccurate peptide quantification. Here we present the WaveletQuant program, based on wavelet theory, for better or alternative MS-based proteomic quantification. Results We developed a novel discrete wavelet transform (DWT) and a 'Spatial Adaptive Algorithm' to remove noise and to identify true peaks. We programmed and compiled WaveletQuant using Visual C++ 2005 Express Edition. We then incorporated the WaveletQuant program in the Trans-Proteomic Pipeline (TPP), a commonly used open source proteomics analysis pipeline. Conclusions We showed that WaveletQuant was able to quantify more proteins and to quantify them more accurately than the ASAPRatio, a program that performs quantification in the TPP pipeline, first using known mixed ratios of yeast extracts and then using a data set from ovarian cancer cell lysates. The program and its documentation can be downloaded from our website at http://systemsbiozju.org/data/WaveletQuant.

Abstract Background The objective of this clinical study is to evaluate the safety and effectiveness of the Activ-L Artificial Disc for treatment of single-level degenerative disc disease of the lumbar spine in patients who have been unresponsive to at least six months of prior conservative care. The hypothesis of the study is that the Activ-L Disc is non-inferior to the control (the Charité® Artificial Disc [DePuy Spine] or ProDisc-L® Total Disc Replacement [Synthes Spine]) with respect to the rate of individual subject success at 24 months. Individual subject success is a composite of effectiveness and safety. Methods/Design The study proposed is a prospective, randomized, single-masked, controlled, multi-center clinical trial consisting of an estimated 414 subjects with single-level DDD of the lumbar spine (L4/L5, or L5/S1) who have failed to improve with conservative treatment for at least six months prior to enrollment. After enrollment, subjects will be randomized in a 2:1 ratio to either the Activ-L Disc (investigational device) or the control (Charité or ProDisc-L). Radiographic endpoints will be evaluated by an independent reviewer at an imaging core laboratory. Each subject will be followed for 5 years post-treatment. Discussion The safety and effectiveness of the Activ-L Artificial Disc for treatment of single-level degenerative disc disease of the lumbar spine will be equivalent to Charité® Artificial Disc [DePuy Spine] or ProDisc-L® Total Disc Replacement [Synthes Spine] at 24 months. Trial Registration Current Controlled Trials NCT00589797.

Abstract Background Ecological, biochemical and genetic resemblance as well as clear differences of virulence between L. monocytogenes and L. innocua make this bacterial clade attractive as a model to examine evolution of pathogenicity. This study was attempted to examine the population structure of L. innocua and the microevolution in the L. innocua-L. monocytogenes clade via profiling of 37 internalin genes and multilocus sequence typing based on the sequences of 9 unlinked genes gyrB, sigB, dapE, hisJ, ribC, purM, gap, tuf and betL. Results L. innocua was genetically monophyletic compared to L. monocytogenes, and comprised four subgroups. Subgroups A and B correlated with internalin types 1 and 3 (except the strain 0063 belonging to subgroup C) and internalin types 2 and 4 respectively. The majority of L. innocua strains belonged to these two subgroups. Subgroup A harbored a whole set of L. monocytogenes-L. innocua common and L. innocua-specific internalin genes, and displayed higher recombination rates than those of subgroup B, including the relative frequency of occurrence of recombination versus mutation (ρ/θ) and the relative effect of recombination versus point mutation (r/m). Subgroup A also exhibited a significantly smaller exterior/interior branch length ratio than expected under the coalescent model, suggesting a recent expansion of its population size. The phylogram based on the analysis with correction for recombination revealed that the time to the most recent common ancestor (TMRCA) of L. innocua subgroups A and B were similar. Additionally, subgroup D, which correlated with internalin type 5, branched off from the other three subgroups. All L. innocua strains lacked seventeen virulence genes found in L. monocytogenes (except for the subgroup D strain L43 harboring inlJ and two subgroup B strains bearing bsh) and were nonpathogenic to mice. Conclusions L. innocua represents a young species descending from L. monocytogenes and comprises four subgroups: two major subgroups A and B, and one atypical subgroup D serving as a link between L. monocytogenes and L. innocua in the evolutionary chain. Although subgroups A and B appeared at approximately the same time, subgroup A seems to have experienced a recent expansion of the population size with higher recombination frequency and effect than those of subgroup B, and might represent the possible evolutionary direction towards adaptation to enviroments. The evolutionary history in the L. monocytogenes-L. innocua clade represents a rare example of evolution towards reduced virulence of pathogens.

Abstract Background Alternative splicing is an important gene regulation mechanism. It is estimated that about 74% of multi-exon human genes have alternative splicing. High throughput tandem (MS/MS) mass spectrometry provides valuable information for rapidly identifying potentially novel alternatively-spliced protein products from experimental datasets. However, the ability to identify alternative splicing events through tandem mass spectrometry depends on the database against which the spectra are searched. Results We wrote scripts in perl, Bioperl, mysql and Ensembl API and built a theoretical exon-exon junction protein database to account for all possible combinations of exons for a gene while keeping the frame of translation (i.e., keeping only in-phase exon-exon combinations) from the Ensembl Core Database. Using our liver cancer MS/MS dataset, we identified a total of 488 non-redundant peptides that represent putative exon skipping events. Conclusion Our exon-exon junction database provides the scientific community with an efficient means to identify novel alternatively spliced (exon skipping) protein isoforms using mass spectrometry data. This database will be useful in annotating genome structures using rapidly accumulating proteomics data.

ABSTRACT The need to comply with animal welfare has motivated the research for non-invasive methods that allow the evaluation of poultry and eggs to be painless while providing accurate measurements. In this scenario, bioelectrical impedance was tested as a minimally invasive tool for sexing day-old chicks of two different chicken strains and for evaluating the quality of eggs submitted to different days of storage relative to their hatchability. The resistance and phase angle measured allowed the differentiation between chicken strains, but not between sexes. Eggs stored for seven days showed higher resistance and lower phase angle those stored for only one day. Although the bioimpedance method seems to be a promising method to evaluate egg and chick quality, the results of the present study suggest that further studies are needed to validate its utilization, particularly in terms of electrode type and positioning, as well as for the determination of which electrodes and equipment are best suited for different evaluation purposes.

The revised Functional Assessment of Human Immunodeficiency Virus Infection (FAHI) quality of life (QoL) instrument has been updated and expanded to provide more complete and accurate coverage of human immune deficiency virus/ acquired immune deficiency syndrome (HIV/AIDS)-related QoL. Factor analysis and the Rasch measurement model were used to determine a new subscale structure for the FAHI. The content of these subscales, including physical well-being (ten items, α = 0.91), function and global well-being (13 items, α = 0.86), emotional well-being/living with HIV (10 items, α = 0.82), social well-being (eight items, α = 0.73), and cognitive functioning (three items; α = 0.75), reflect both general illness- and HIV/AIDS-specific QoL concerns: a total QoL score can also be calculated for the FAHI (44 items, α =0.91). Psychometric evaluation revealed good internal consistency reliability for the FAHI and its subscales. In addition, construct validity, known groups validity and sensitivity to change were demonstrated by significant associations between the FAHI and additional indicators of functional status, psychological symptoms, stress and illness severity. In summary, the FAHI is a psychometrically sound instrument that captures multiple important dimensions of HIV/AIDS-related QoL. It is brief, easy to administer and score, has been translated into nine languages other than English and is appropriate for use in clinical trials and clinical practice. [ABSTRACT FROM AUTHOR]

Aluminum foam joints were fabricated via liquid diffusion welding with zinc‐aluminum alloy solder aided with ultrasonic vibration at 520 °C. Zinc‐aluminum alloys with different compositions (10 % aluminum, 20 % aluminum, 30 % aluminum) were used as solder material. The control group was fabricated under the same conditions but without ultrasonic assistance. The microstructure of aluminum foam joints was analyzed by optical microscopy, scanning electron microscopy, and energy dispersive spectroscopy. Among the different soldering alloys, those with the zinc‐20aluminum solder had the widest diffusion area and the most continuous interface. The tensile strength of metallurgic alloy joined aluminum foams was tested. Zn20Al samples had the best performance among all samples, including the low‐density substrate aluminum foam (0.3 g/cm3 and 0.4 g/cm3), but it still showed a lower performance than the high‐density substrate aluminum foam (0.6 g/cm3). Therefore, ultrasonic vibration remarkably improved the tensile strength and impact toughness of joints. Samples with ultrasonic assistance had better tensile strength and impact toughness than high‐density substrate aluminum. [ABSTRACT FROM AUTHOR]

After curative radiotherapy (RT) or chemoradiation (CRT), there is no validated tool to accurately identify patients for adjuvant therapy in nasopharyngeal carcinoma (NPC). Post-RT circulating plasma Epstein–Barr virus (EBV) DNA can detect minimal residual disease and is associated with recurrence and survival independent of TNM (tumor–lymph node–metastasis) stage. We aimed to develop and validate a risk model for stratification of NPC patients after completion of RT/CRT to observation or adjuvant therapy. The prospective multicenter 0502 EBV DNA screening cohort (Hong Kong NPC Study Group 0502 trial) enrolled from 2006 to 2015 (n = 745) was used for model development. For internal validation, we pooled independent patient cohorts from prospective clinical studies enrolled from 1997 to 2006 (n = 340). For external validation, we used retrospective cohort of NPC patients treated at Sun Yat-sen University Cancer Center from 2009 to 2012 (n = 837). Eligible patients had histologically confirmed NPC of Union for International Cancer Control (UICC) 7th Edition stage II–IVB who completed curative RT/CRT with or without neoadjuvant chemotherapy, had post-RT EBV DNA tested within 120 days after RT and received no adjuvant therapy. The primary end point was overall survival (OS). We used recursive-partitioning analysis (RPA) to classify patients into groups of low, intermediate, and high risk of death. Combining post-RT EBV DNA level (0, 1–49, 50–499, and ≥500 copies/ml) and TNM stage (II, III, IVAB), RPA model classified patients into low-, intermediate-, and high-risk groups with 5-year OS of 89.4%, 78.5% and 37.2%, respectively. The RPA low-risk group had comparable OS to TNM stage II (5-year OS 88.5%) but identified more patients (64.8% versus stage II 28.1%) that could potentially be spared adjuvant therapy toxicity. The RPA model (c-index 0.712) showed better risk discrimination than either the TNM stage (0.604) or post-RT EBV DNA alone (0.675) with improved calibration and consistence. These results were validated in both internal and external cohorts. Combining post-RT EBV DNA and TNM stage improved risk stratification in NPC. • Integrating postradiotherapy plasma Epstein–Barr virus (EBV) DNA and tumor–lymph node–metastasis (TNM) stage improves the risk stratification of nasopharyngeal carcinoma. • Postradiotherapy plasma EBV DNA is a better predictor of early death in nasopharyngeal carcinoma than TNM stage. • The low-risk group by recursive partitioning model can spare more patients from unnecessary toxicity of adjuvant therapy. [ABSTRACT FROM AUTHOR]

There was a mistake in the part of OVX rats model and RRP intervention in the original publication. [ABSTRACT FROM AUTHOR]

The article offers a study that reveals the effect of anti-osteoporotic of Rehmanniae Radix Preparata (RRP) in ovariectomized (OVX) rats. Topics discussed include RRP helps to improve bone quality in OVX rats through the regulation of bone homeostasis and suggests for the development of anti-osteoporotic drugs, mentions the treatment of OVX rats with RRP aqueous extract that helps to rebuilt bone homeostasis, and information on the improving trabecular distribution in the femurs of OVX rats.

Aims Almost all patients with epidermal growth factor receptor (EGFR) mutations will develop resistance to first-line EGFR tyrosine kinase inhibitors (TKIs). The management of oligoprogression on EGFR TKI is controversial. Irradiating progressing tumours may potentially eradicate the resistant clone and allow continuation of EGFR TKI, but the clinical data remain sparse. We aimed to assess the effect of radiotherapy on survival outcomes in patients with oligoprogression in a matched-cohort study. Materials and methods This was a retrospective matched-cohort study comparing patients with EGFR mutation-positive stage IV non-small cell lung cancer receiving radiotherapy versus chemotherapy for progression. Patients in the radiotherapy group received radiotherapy (mainly stereotactic ablative radiotherapy) for oligoprogression, whereas the chemotherapy group received only systemic chemotherapy upon progression. Key prognostic factors including gender, age, performance status, time to first progression and mutation subtypes were matched. Results Twenty-five patients with oligoprogression (radiotherapy group) were identified, and a matched chemotherapy group with the same number of patients was generated. The median duration of follow-up was 24.3 and 34 months for the radiotherapy and chemotherapy groups, respectively. The median overall survival of the radiotherapy group was significantly longer than the chemotherapy group, 28.2 versus 14.7 months ( P = 0.026). The median progression-free survival (PFS) was 7.0 and 4.1 months after radiotherapy and chemotherapy, respectively ( P = 0.0017). The use of radiotherapy was an independent predictive factor of overall survival and PFS in multivariate analysis. Only one patient had ≥grade 3 toxicity after radiotherapy. The frequency of secondary T790M mutation and subsequent Osimertinib exposure were similar in both groups. Conclusion Radiotherapy may effectively extend EGFR TKI therapy for patients with oligoprogression on TKI. Improved PFS and overall survival were observed, although potential biases should not be overlooked. Further randomised studies are warranted. [ABSTRACT FROM AUTHOR]

Background: This study investigated the predictive and prognostic significance of assessing early drug response with both positron-emission computerized tomography (PET-CT) and circulating tumor cells (CTCs) in patients receiving first-line chemotherapy for metastatic colorectal cancer. Patients and methods: Eligible patients had PET-CT and CTC analysis at baseline and 4--6 weeks after starting chemotherapy, and then a CT scan at 10--12 weeks to assess the Response Evaluation Criteria In Solid Tumors (RECIST) response. Early response was defined as achieving a dual-endpoint consisting of PET-CT (30% drop in the sum of maximum standard uptake values-- SUVmax--of target lesions) and CTC response (CTC<3 cells/7.5 ml blood) at 4--6 weeks after starting chemotherapy. Results: About 84 patients were enrolled with a median follow-up of 32.9months (95% confidence interval, CI, 24.5months--not reached, NR) and 70 patients (84.3%) completed all assessments. Achieving an early response based on the dual-endpoint was independently associated with progression-free survival (hazard ratio, HR=0.452, 95% CI 0.267--0.765). The median progression-free survival of early responders was 7.41months (95% CI, 6.05--9.11) compared with 5.37 months (95% CI, 4.68--6.24) in non-responders (log-rank, P=0.0167). RECIST response at 10 weeks was independently associated with overall survival (OS) (HR=0.484, 95% CI, 0.275--0.852). Early response based on the dual-endpoint could predict the subsequent RECIST response with a sensitivity, specificity and positive predictive value of 64%, 70% and 74%, respectively. Conclusions: Early response based on both PET-CT and CTC analysis has prognostic and probably predictive significance in patients undergoing first-line chemotherapy for metastatic colorectal cancer. Its utility as a new tool for assessing early drug response should be further validated. [ABSTRACT FROM AUTHOR]

• Classic and modified single-door laminoplasty models were developed and compared, which indicated the latter was superior to the former due to the posterior musculature reconstruction in restoring ROM and limiting the loading responses. All these were well correlated with a review of clinical data on laminoplasty scenarios. • Analysis of the load concentration locations showed that the C2 muscle attachment sustained more tensile loading than the C7 muscle attachment. These tensile damping of the musculature reconstruction retained more postoperative cervical motion. • Motion-sparing is beneficial for the recovery of postoperative neck movement and reducing the risk of eventual kyphosis and axial pain. Clinical relevance of this study indicated that surgeons are encouraged to make every effort to preserve the attachment of the C2 whenever feasible in laminoplasty. The current trend of laminoplasty is developing toward the goal of muscle preservation and minimum tissue damage. Given this, muscle-preserving techniques in cervical single-door laminoplasty have been modified with protecting the spinous processes at the sites of C2 and/or C7 muscle attachment and reconstruct the posterior musculature in recent years. To date, no study has reported the effect of preserving the posterior musculature during the reconstruction. The purpose of this study is to quantitatively evaluate the biomechanical effect of multiple modified single-door laminoplasty procedures for restoring stability and reducing response level on the cervical spine. Different cervical laminoplasty models were established for evaluating kinematics and response simulations based on a detailed finite element (FE) head-neck active model (HNAM), including ① C3 – C7 laminoplasty (LP_C37), ② C3 – C6 laminoplasty with C7 spinous process preservation (LP_C36), ③ C3 laminectomy hybrid decompression with C4 – C6 laminoplasty (LT_C3 + LP_C46) and ④ C3 – C7 laminoplasty with unilateral musculature preservation (LP_C37 + UMP). The laminoplasty model was validated by the global range of motion (ROM) and percentage changes relative to the intact state. The C2 – T1 ROM, axial muscle tensile force, and stress/strain levels of functional spinal units were compared among the different laminoplasty groups. The obtained effects were further analysed by comparison with a review of clinical data on cervical laminoplasty scenarios. Analysis of the locations of concentration of muscle load showed that the C2 muscle attachment sustained more tensile loading than the C7 muscle attachment, primarily in flexion-extension (FE) and in lateral bending (LB) and axial rotation (AR), respectively. Simulated results further quantified that LP_C36 primarily produced 10% decreases in LB and AR modes relative to LP_C37. Compared with LP_C36, LT_C3 + LP_C46 resulted in approximately 30% decreases in FE motion; LP C37 + UMP also showed a similar trend. Additionally, when compared to LP_C37, LT_C3 + LP_C46 and LP C37 + UMP reduced the peak stress level at the intervertebral disc by at most 2-fold as well as the peak strain level of the facet joint capsule by 2–3-fold. All these findings were well correlated with the result of clinical studies comparing modified laminoplasty and classic laminoplasty. Modified muscle-preserving laminoplasty is superior to classic laminoplasty due to the biomechanical effect of the posterior musculature reconstruction, with a retained postoperative ROM and loading response levels of the functional spinal units. More motion-sparing is beneficial for increasing cervical stability, which probably accelerates the recovery of postoperative neck movement and reduces the risk of the complication for eventual kyphosis and axial pain. Surgeons are encouraged to make every effort to preserve the attachment of the C2 whenever feasible in laminoplasty. [ABSTRACT FROM AUTHOR]

To carry out an in-depth analysis of the scientific research on male infertility, we performed the first bibliometric analysis focusing on studies involving male infertility worldwide during the period 1995–2014. Analysis of 6357 articles in the field of male infertility showed a significant increasing trend in the number of publications over the period 1995–2014. Obstetrics and Gynecology was an important subject category and Multidisciplinary Sciences was the newest interest. Authors were mainly from Europe and USA, with researchers from Cleveland Clinic producing the most articles, and those from the Tel Aviv Sourasky Medical Center and the University of Utah having the highest-quality articles. The USA contributed the most independent and international collaborative articles. The Cleveland Clinic and the University of Munster were the most productive institutions. The Cleveland Clinic and the University of Giessen had the most international collaboration publications. Harvard University had the most collaborators. The most common interests were pathogenesis and therapy, and new interests were hypogonadism, obesity, and cryopreservation. In conclusion, rapid development of the male infertility field was observed. Overall, collaborative and multidisciplinary science research has become more popular. The USA and its institutions play a dominant role, followed by European countries. Thanks to the common research focus worldwide, more insight into male fertility has been gained in the scientific literature over the past 20 years. [Correction added on September 21, 2016, after online publication: the term “institute” has been replaced by the term “institution” throughout the text.] [ABSTRACT FROM AUTHOR]

Introduction: Few studies have evaluated the impact of depression in terms of losses to both premature mortality and health-related quality of life (HRQOL) on the overall population. Health-adjusted life expectancy (HALE) is a summary measure of population health that combines both morbidity and mortality into a single summary statistic that describes the current health status of a population. Methods: We estimated HALE for the Canadian adult population according to depression status. National Population Health Survey (NPHS) participants 20 years and older (n = 12 373) were followed for mortality outcomes from 1994 to 2009, based on depression status. Depression was defined as having likely experienced a major depressive episode in the previous year as measured by the Composite International Diagnostic Interview Short Form. Life expectancy was estimated by building period abridged life tables by sex and depression status using the relative risks of mortality from the NPHS and mortality data from the Canadian Chronic Disease Surveillance System (2007-2009). The Canadian Community Health Survey (2009/10) provided estimates of depression prevalence and Health Utilities Index as a measure of HRQOL. Using the combined mortality, depression prevalence and HRQOL estimates, HALE was estimated for the adult population according to depression status and by sex. Results: For the population of women with a recent major depressive episode, HALE at 20 years of age was 42.0 years (95% CI: 40.2-43.8) compared to 57.0 years (95% CI: 56.8-57.2) for women without a recent major depressive episode. For the population of Canadian men, HALE at 20 was 39.0 years (95% CI: 36.5-41.5) for those with a recent major depressive episode compared to 53.8 years (95% CI: 53.6-54.0) for those without. For the 15.0-year difference in HALE between women with and without depression, 12.3 years can be attributed to the HRQOL gap and the remaining 2.7 years to the mortality gap. The 14.8 fewer years of HALE observed for men with depression equated to a 13.0-year HRQOL gap and a 1.8-year mortality gap. Conclusion: The population of adult men and women with depression in Canada had substantially lower healthy life expectancy than those without depression. Much of this gap is explained by lower levels of HRQOL, but premature mortality also plays a role. [ABSTRACT FROM AUTHOR]

Summary: In this study, we found out a previously undefined function of icariin which restored the dynamic balance between osteogenic and adipogenic differentiation of mesenchymal stem cells (MSCs) in patients with osteonecrosis of femoral head (ONFH) via ABCB1-promoter demethylation. These findings provided important information regarding potential implication of icariin targeting epigenetic changes for the treatment of steroid -associated ONFH. Introduction: Here, we investigated whether icariin can also exert a beneficial role in the reactivation of MSCs in the patients with steroid-associated ONFH via ABCB1-promoter demethylation. Methods: Bone marrow was collected from the proximal femur in patients with steroid-associated ONFH ( n = 20) and patients with new femoral neck fractures ( n = 22), and then MSCs were isolated. We investigated cell viability, intracellular reactive oxygen species (ROS) level, mitochondrial membrane potential (MMP), P-glycoprotein (P-gp) activity, the transcript levels of ABCB1 and oxidative stress-related genes, methylation extent at CpG islands of ABCB1 promoter, and osteogenic and adipogenic differentiation ability of MSCs from the femoral neck fractures group and from the steroid-associated ONFH group treated with or without icariin. Results: We observed that MSCs from the steroid-associated ONFH group showed reduced proliferation ability, elevated ROS level, depressed MMP, weakened osteogenesis, and enhanced adipogenesis while low P-gp activity, transcription level of ABCB1, and oxidative stress-related genes as well as aberrant CpG islands hypermethylation of ABCB1 were also noted in steroid-associated ONFH group. Treatment with icariin obviously induced de novo P-gp expression, decreased oxidative stress, and promoted osteogenesis. Conclusion: Icariin may be a potential drug targeting epigenetic changes for the treatment of steroid-associated ONFH. [ABSTRACT FROM AUTHOR]

Unfavorable EBV DNA response at mid-course of radiotherapy/ chemoradiotherapy for nasopharyngeal carcinoma is an adverse prognosticator for treatment outcome, and is linked to majority of failures. The data provides a basis for design of biomarker-driven trials that address alteration of therapy intensity during the latter phase of chemoradiotherapy, and adjuvant therapy.Background To test the hypothesis that prognostication of treatment outcome is feasible by biomarker response at midcourse of chemoradiotherapy (CRT)/radiotherapy (RT), with respect to the plasma load of Epstein–Barr viral (EBV) DNA in nasopharyngeal carcinoma (NPC). Patients and methods One hundred seven patients with stage IIB–IV NPC were prospectively studied. Plasma EBV DNA load was measured by quantitative PCR before therapy (pre-DNA), at completion of 4 weeks of CRT/RT (mid-DNA), and within 3 months of completion of therapy (post-DNA). The end points are post-DNA load, a recognized surrogate of survival, and clinical outcome. Results Ninety-three percent of patients had detectable EBV DNA before therapy (median load = 972 copies/ml). EBV DNA became undetectable in 55 (51%) patients at the end of week 4 of therapy. Detectable mid-DNA was associated with worse clinical outcome (median follow-up time, 6.2 years), for distant failure [hazard ratio (HR) 12.02, 95% confidence interval (CI) 2.78–51.93; P < 0.0001], progression-free survival (PFS; HR 4.05, 95% CI 1.89–8.67, P < 0.0001), and overall survival (OS; HR 3.29, 95% CI 1.37–7.90, P = 0.0077). Seventy-four percent of all failures were associated with detectable mid-DNA, whereas 34% of all failures were associated with detectable post-DNA. Stratification by tumor stage (IIB, III, IV) has no significant prognostic effect. Conclusions Unfavorable EBV DNA response at midcourse of RT/CRT is an adverse prognosticator for treatment outcome, is linked to majority of all failures, and discriminates outcome better than tumor stage. The data could provide a basis for trial design that addresses alteration of therapy intensity during the latter phase of CRT, and adjuvant therapy. Validation studies are awaited. [ABSTRACT FROM PUBLISHER]

Background: Based on our previous work on the clinical activity of cetuximab in recurrent nasopharyngeal carcinoma (NPC), we evaluated the feasibility of adding cetuximab to concurrent cisplatin and intensity-modulated radiotherapy (IMRT) in locoregionally advanced NPC. Patients and methods: Patients with American Joint Committee on Cancer stage III–IVB NPC were given an initial dose of cetuximab (400 mg/m2) 7–10 days before receiving concurrent IMRT, weekly cisplatin (30 mg/m2/week) and cetuximab (250 mg/m2/week). Results: Thirty patients (median age of 45 years) with stage III (67%), IVA (30%) and IVB (3%) nonkeratinizing NPC were enrolled. Grade 3–4 oropharyngeal mucositis occurred in 26 (87%) patients and 10 (33%) patients required short-term nasogastric feeding. Grade 3 radiotherapy-related dermatitis occurred in six patients (20%) and three patients (10%) had grade 3 cetuximab-related acneiform rash. These grade 3–4 skin and mucosal toxic effects were manageable and reversible. At a median follow-up of 31.8 months [95% confidence interval (CI) 26.2–32.1 months], the 2-year progression-free survival was 86.5% (95% CI 74.3% to 98.8%). Conclusions: Concurrent administration of cetuximab, weekly cisplatin and IMRT is a feasible strategy against locoregionally advanced NPC. Preliminary survival data compare favorably with historic data and further follow-up is warranted. [ABSTRACT FROM PUBLISHER]

The technique of explosive powder compaction is used to prepare W-Cu nanocomposites. The nanocrystalline W-Cu powders are produced by mechanical alloying and then analyzed by x-ray diffraction. The compacted specimens are found to have the largest density when the detonation velocity is 5300 m/s. The composition and distribution of the elements in the compacted specimens are uniform and have a Vickers hardness equal to 320 and a density equal to 99.1% of the theoretical density. [ABSTRACT FROM AUTHOR]

Background: We aimed to evaluate the safety and efficacy of single-agent sunitinib in nasopharyngeal carcinoma (NPC).Methods: Eligible patients had progressive disease after prior platinum-based chemotherapy. Sunitinib was given as continuous once-daily dosing of 37.5 mg in 4-week cycles until progression.Results: Thirteen patients were enrolled. Recruitment was stopped after two patients died of hemorrhagic events. All patients had previously received curative radiotherapy (RT) to nasopharynx/neck (including nine patients who had chemoradiotherapy). Patients received a median of three cycles of sunitinib. One patient was still on sunitinib with stable disease after 24 cycles. Hemorrhagic events occurred in nine patients (64%), including epistaxis in six, hemoptyses in three and hematemesis in two patients. Prior RT to thorax was significantly associated with hemoptyses (P = 0.03). Two patients with local tumor invasion into the carotid sheath developed fatal epistaxis/hematemesis within the first cycle of sunitinib, likely due to internal carotid blowout after tumor shrinkage.Conclusions: Sunitinib demonstrated modest clinical activity in heavily pretreated NPC patients. However, the high incidence of hemorrhage from the upper aerodigestive tract in NPC patients who received prior high-dose RT to the region is of concern. Direct vascular invasion by tumors appeared to increase the risk of serious bleeding. [ABSTRACT FROM AUTHOR]

Zhang, L.L., Zhang, J.R., Yu, Z.G., Zhao, J., Mo, F., Jiang, S.X. Effects of ionophores on liver CYP1A and 3A in male broilers. J. vet. Pharmacol. Therap. doi: 10.1111/j.1365-2885.2010.01168.x. The effects of ionophore antibiotics on the enzyme activity, protein and mRNA expression levels of cytochrome P450 (CYP) isoenzymes were investigated in liver from male Arbor Acres (AA) broiler chicks. Monensin, salinomycin and maduramycin at the dosage of 120, 60, and 5 mg/kg were administered in feed for 14 days. CYP1A and CYP3A activities were quantitated using cocktail probe drugs and a high performance liquid chromatographic (HPLC) assay at the 15th day; the protein expressions of CYP1A and CYP3A were detected by Western blot. CYP1A4, CYP1A5 and CYP3A37 mRNA levels were detected by real-time polymerase chain reaction (real-time PCR). Monensin, salinomycin and maduramycin had no effect on caffeine metabolism, protein expression and mRNA expression, but did induce dapsone metabolism, increasing CYP3A protein expression. However, there was no change in CYP3A37 mRNA expression as compared with the control group. It is suggested that ionophore antibiotics may have an induction effect on CYP3A expression and enzyme activity and that such effect might be related to the posttranscriptional regulation of its protein expression. Consideration of the enhanced metabolism of other drugs used simultaneously with ionophores is therefore recommended. [ABSTRACT FROM AUTHOR]

Although previous studies have documented correlations between pretreatment or post-treatment primary tumour volumes and local outcome following definitive concomitant chemoradiotherapy (CCRT) in head and neck squamous cell carcinoma (HNSCC), no study has included and compared tumour volumes during CCRT. We reviewed the MRIs of 69 HNSCC patients treated with a 6 weeks course of CCRT and who underwent successful MRI pre-treatment (n569), 2 weeks intra-treatment (n548) and 6 weeks post-treatment (n561). Primary tumour volumes on MRI at the three time points were calculated and compared for their predictive value for primary site outcome. Volume thresholds optimised to predict failure with the highest accuracy and positive predictive value (PPV) were calculated. The mean pre-treatment volume was 24.6 cm3 (range, 1.1-187.9 cm3) and the mean follow-up interval was 41 months (range, 12-100 months). 23 primary tumours failed treatment (33%). Volumes before, during and after CCRT were positively associatedwith local failure (p50.015, p50.009, p,0.0001). Volume reductions during and after CCRT were negatively associated with local failure (p50.021, p50.001). Pre-treatment and intra-treatment volume thresholds achieved the highest accuracy and produced intermediate PPVs (51-64%) for predicting local failure. Optimised intra-treatment thresholds did not identify any more treatment failures than the pre-treatment thresholds. By comparison, a 6 weeks post-treatment volume reduction (,35%) achieved 100% PPV for failure, albeit with 26% sensitivity. In conclusion, primary tumour volumetry performed early in CCRT provides minimal additional information compared with pre-treatment volumetry, with respect to predicting post-treatment local failures. Therefore, volumetry during CCRT is unlikely to be useful for guiding individual response-based therapeutic modifications. [ABSTRACT FROM AUTHOR]

Carbon-encapsulated metal nanoparticles are synthesized by a detonation method using a home-made water-soluble composite explosive. The results of the study show that detonation products contain face-centered cubic cobalt/nickel nanocrystals approximately 10-25 nm in size, which are encapsulated by thin (3-5 nm) carbon layers. These spherical and ellipsoidal nanoparticles exhibit a good superparamagnetism state at 300 K. [ABSTRACT FROM AUTHOR]

The utility of diffusion-weighted imaging (DWI) in the detection of squamous cell carcinoma (SCC) of the tonsils has not been previously investigated. This preliminary study compared DWI of apparent SCC tonsillar tumours with normal tonsils. DWI of the tonsils was performed in 10 patients with newly diagnosed tonsil SCC that was evident on conventional MRI and in 17 patients undergoing cranial MRI for other indications. Regions of interest (ROI) were drawn around each identifiable tonsil on the apparent diffusion coefficient (ADC) map and the mean ADC value for each tonsil was calculated. ADC values for normal and SCC tonsils were compared using the Mann- Whitney U-test. The median ADC and range (x10-3 mm² s-1) were found to be 0.814 and 0.548-1.312, respectively, for normal tonsils compared with 0.933 and 0.789-1.175, respectively, for SCC tonsils. ADC values were significantly higher for SCC tonsils than for normal tonsils (p50.009). No SCC tonsil had an ADC less than 0.82x10-3 mm² s-1 compared with 58% of normal tonsils. We conclude that there is a difference in the ADC between normal tonsils and SCC tonsils where the cancer is apparent on conventional MRI. These results are promising, although further studies are now required to determine whether DWI can be used to identify or exclude smaller foci of SCC within tonsils where the cancer is not evident on conventional MRI. [ABSTRACT FROM AUTHOR]