Durvalumab with or without tremelimumab versus the EXTREME regimen as first-line treatment for recurrent or metastatic squamous cell carcinoma of the head and neck: KESTREL, a randomized, open-label, phase III study.

BACKGROUND: Patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) have a poor prognosis. The phase III KESTREL study evaluated the efficacy of durvalumab [programmed death-ligand 1 (PD-L1) antibody] with or without tremelimumab [cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) antibody], versus the EXTREME regimen in patients with R/M HNSCC. PATIENTS AND METHODS: Patients with HNSCC who had not received prior systemic treatment for R/M disease were randomized (2 : 1 : 1) to receive durvalumab 1500 mg every 4 weeks (Q4W) plus tremelimumab 75 mg Q4W (up to four doses), durvalumab monotherapy 1500 mg Q4W, or the EXTREME regimen (platinum, 5-fluorouracil, and cetuximab) until disease progression. Durvalumab efficacy, with or without tremelimumab, versus the EXTREME regimen in patients with PD-L1-high tumors and in all randomized patients was assessed. Safety was also assessed. RESULTS: Durvalumab and durvalumab plus tremelimumab were not superior to EXTREME for overall survival (OS) in patients with PD-L1-high expression [median, 10.9 and 11.2 versus 10.9 months, respectively; hazard ratio (HR) = 0.96; 95% confidence interval (CI) 0.69-1.32; P = 0.787 and HR = 1.05; 95% CI 0.80-1.39, respectively]. Durvalumab and durvalumab plus tremelimumab prolonged duration of response versus EXTREME (49.3% and 48.1% versus 9.8% of patients remaining in response at 12 months), correlating with long-term OS for responding patients; however, median progression-free survival was longer with EXTREME (2.8 and 2.8 versus 5.4 months). Exploratory analyses suggested that subsequent immunotherapy use by 24.3% of patients in the EXTREME regimen arm contributed to the similar OS outcomes between arms. Grade 3/4 treatment-related adverse events (TRAEs) for durvalumab, durvalumab plus tremelimumab, and EXTREME were 8.9%, 19.1%, and 53.1%, respectively. CONCLUSIONS: In patients with PD-L1-high expression, OS was comparable between durvalumab and the EXTREME regimen. Durvalumab alone, and with tremelimumab, demonstrated durable responses and reduced TRAEs versus the EXTREME regimen in R/M HNSCC.

Differential effects of aquatic anaesthetics on the pharmacokinetics of antibiotics: Examples using florfenicol in Nile tilapia (Oreochromis niloticus).

Anaesthetics are commonly applied in pharmacokinetic (PK) studies to assure smooth handling of experimental procedures or to promote animal welfare. However, the influence of anaesthetics on the PK of co-administered drug is generally unknown but assumes ignorable. The goal of the study was to investigate the effect of tricaine methanesulfonate (MS-222), 2-phenoxyethanol (2-PE) and eugenol (EUG) on the PK of florfenicol (FF) in Nile tilapia. Twenty-eight fish were repeatedly exposed to 90 ppm EUG, 300 ppm MS-222 or 900 ppm 2-PE before FF oral administration (15 mg/kg) and each successive blood sampling. The serum concentration-time profiles were analysed by a 2-compartmental model, and the generated parameters in the control (without anaesthetic) and anaesthetic groups were statistically compared. The results demonstrated that the serum concentrations of each anaesthetic were similar at every FF sampling times (70 µg/ml for MS-222; 277 µg/ml for 2-PE; and 61 µg/ml for EUG). In comparison with the control group, the repeated use of MS-222 did not result in a statistical difference in most of the PK parameters. In contrast, the elimination half-lives of the 2-PE and EUG groups were significantly longer whereas the absorption and distribution half-lives of the 2-PE group were significantly shorter than the control, resulting in altered optimal dosages in the simulation modelling. Whether or not the numbers and extent of PK parameters change mitigate subsequent estimations of other PK-derived secondary values such as dosing regimen and withdrawal time remains to be elucidated, but the auxiliary use of anaesthetics in PK studies should not assume uninfluential.

Gaussian Thermal Operations and The Limits of Algorithmic Cooling.

The study of thermal operations allows one to investigate the ultimate possibilities of quantum states and of nanoscale thermal machines. Whilst fairly general, these results typically do not apply to continuous variable systems and do not take into account that, in many practically relevant settings, system-environment interactions are effectively bilinear. Here we tackle these issues by focusing on Gaussian quantum states and channels. We provide a complete characterization of the most general Gaussian thermal operation acting on an arbitrary number of bosonic modes, which turn out to be all embeddable in a Markovian dynamics, and derive necessary and sufficient conditions for state transformations under such operations in the single-mode case, encompassing states with nonzero coherence in the energy eigenbasis (i.e., squeezed states). Our analysis leads to a no-go result for the technologically relevant task of algorithmic cooling: We show that it is impossible to reduce the entropy of a system coupled to a Gaussian environment below its own or the environmental temperature, by means of a sequence of Gaussian thermal operations interspersed by arbitrary (even non-Gaussian) unitaries. These findings establish fundamental constraints on the usefulness of Gaussian resources for quantum thermodynamic processes.

Effective Decision-Making and Decisional Regret in Living Kidney Donors of Taiwan.

BACKGROUND: While most living kidney donors are satisfied with their decision and do not regret donating, few studies have been conducted on the determinants related to the effectiveness and regret of the decision. This study aims to explore the relationship between basic attributes, quality of life, positive affect, negative affect, effectiveness of decision-making, and regret in living kidney donors. METHODS: In this cross-sectional study, living kidney donors were recruited from urology and kidney transplant outpatient services. The structured questionnaire used to collect the data included the Positive and Negative Affect Schedule, Medical Outcomes Study 12-Item Short-Form Health Survey, Decision Conflict Scale, and Decision Regret Scale. RESULTS: The findings indicate that living donors with better health status, 24-hour creatinine clearance, physical health-related quality of life (HRQOL), and positive affect experienced greater feelings of effective decision-making. Moreover, women and donors with better physical HRQOL, positive affect, and decision effectiveness were less regretful about the decision of kidney donation. CONCLUSION: Health status, physical HRQOL, and positive affect are related to decision validity and regret of living donors. Therefore, clinical care providers should regularly assess the mood and health of living kidney donors. Furthermore, activities promoting their health should be encouraged, especially for men.

Positive and Negative Affects in Living Kidney Donors.

OBJECTIVE: This study aimed to identify the factors influencing the positive and negative affects and the health-related quality of life (HRQOL) of living kidney donors. METHODS: With the use of a cross-sectional study design and a structured questionnaire, information on the basic characteristics, positive affect, negative affect, and HRQOL of 41 living kidney donors were compared. RESULTS: The negative affect in living kidney donors was similar to that of the general population, but the positive affect was slightly lower. The physical HRQOL of living kidney donors was slightly higher than that of the general population, and the mental HRQOL was similar. Female donors showed a greater positive affect than male donors. The donors who were siblings of the recipients showed a more negative affect. Donors without chronic disease and with good perceived physical health showed improved positive affect, negative affect, and mental HRQOL. Furthermore, living kidney donors with better positive and negative affects showed improved physical and mental HRQOLs. CONCLUSIONS: Clinical health providers should evaluate and determine the positive affect, negative affect, and quality of life of living kidney donors, especially in men, siblings of the recipients, those with chronic disease, and those with poorer perceived physical health. Moreover, psychosocial interventions should be provided to improve these factors.

Atomic Configuration of Point Defect Clusters in Ion-Irradiated Silicon Carbide.

Silicon Carbide (SiC) is a promising cladding material for accident-tolerant fuel in light water reactors due to its excellent resistance to chemical attacks at high temperatures, which can prevent severe accident-induced environmental disasters. Although it has been known for decades that radiation-induced swelling at low temperatures is driven by the formation of black spot defects with sizes smaller than 2 nm in irradiated SiC, the structure of these defect clusters and the mechanism of lattice expansion have not been clarified and remain as one of the most important scientific issues in nuclear materials research. Here we report the atomic configuration of defect clusters using Cs-corrected transmission electron microscopy and molecular dynamics to determine the mechanism of these defects to radiation swelling. This study also provides compelling evidence that irradiation-induced point defect clusters are vacancy-rich clusters and lattice expansion results from the homogenous distribution of unrecovered interstitials in the material.

Factors Determining Physical and Mental Quality of Life of Living Kidney Donors in Taiwan.

BACKGROUND: Living-donor kidney transplantation has a positive influence on recipients' life expectancy and improves quality of life for patients with end-stage renal disease compared with dialysis patients. Evaluation of the physical and mental quality of life for donors can promote positive perceptions about donation and help potential donors in their decision-making process. The aim of this study was to explore the predictive factors of quality of life for living kidney donors. METHODS: A cross-sectional and descriptive design was used, and the study was conducted from January to July 2013. The donors were a convenience sample of 34 participants who had undergone kidney transplant surgery >1 year earlier. RESULTS: The results showed that kidney donors had a low to moderate physical and mental quality of life. Multiple regression analysis revealed that financial concerns and anxiety explained 27.8% of the total variance of quality of life in the physical component. Anxiety and paid work explained 61.4% of the total variance of quality of life in the mental component. CONCLUSIONS: After renal transplantation, living kidney donors experienced low to moderate quality of life. Because donors are family members (siblings, sons or daughters, spouses, or parents), monthly family income is a significant issue that influences both the decision to donate and quality of life after transplantation. Our findings suggest that pre-transplantation assessment must include social workers as part of the health care team to evaluate the impact of a donor's financial status on post-transplantation quality of life.

The new body mass index system in predicting renal graft outcomes.

BACKGROUND: Obesity has been related to poor renal graft function. The aim of this study was to compare the long-term graft outcomes of living-related kidney recipients regarding donor-to-recipient body mass index (BMI) parameters using the old Quetelet BMI formula and the new Trefethen BMI formula. METHODS: From November 2002 to November 2010, 62 consecutive living-related kidney transplantations were reviewed retrospectively. Four donor-to-recipient BMI parameters were used: (1) BMI difference by the old formula, (2) BMI difference by the new formula, (3) BMI ratio by the old formula, and (4) BMI ratio by the new formula. Long-term outcomes, including graft survival (GS) and rejection-free graft survival (RFGS) either overall or at 5 years post-transplantation, were analysed according to these parameters. RESULTS: The baseline demography was similar among tertiles according to the four BMI parameters tested. Although there is no significant difference in the long-term survivals by the old and new BMI formula, we found that the area under receiver operating characteristic (ROC) curve is larger using the new formula, either by BMI difference (0.584 vs 0.559 in 5-year GS and 0.658 vs 0.636 in 5-year RFGS) or by BMI ratio (0.584 vs 0.561 in 5-year GS and 0.644 vs 0.626 in 5-year RFGS). The same trend was observed in overall survival outcomes. CONCLUSION: The new Trefethen BMI formula seems to predict long-term renal graft outcomes better than the old Quetelet BMI formula.

Association between use of FK506 and prevalence of post-transplantation diabetes mellitus in kidney transplant patients.

BACKGROUND: Tacrolimus (FK506) use has been suggested as a risk factor for post-transplantation diabetes mellitus (PTDM) because it can impair insulin secretion. This association warrants further investigation. This study aimed to examine the prevalence of PTDM and its association with FK506 use in kidney transplant recipients. The study also aimed to examine the relationship of FK506 use and diabetes-related biologic markers. METHODS: A retrospective chart review was used to collect data at a medical center in northern Taiwan from September 2003 to February 2012. PTDM was defined with the use of the criteria of the American Diabetes Association. RESULTS: Among 166 patients included in the analysis, PTDM was reported in 49 patients (29.5%). A total of 93 patients used the FK506 regimen, of whom 34 (36.6%) were PTDM cases. Logistic regression showed that FK506 use (odds ratio [OR], 2.71; 95% confidence interval [CI], 1.20-6.11; P = .016) and older age (OR,1.08; 95% CI, 1.03-1.13; P = .001) were significant risk factors for PTDM. In addition, FK506 use in PTDM cases was associated with a significantly higher hemoglobin A1c level (7.55 vs 5.81; P = .01) and a borderline significantly higher insulin resistance index (3.24 vs 1.92; P = .053) than was FK506 use without the presence of PTDM. CONCLUSIONS: Older age and an FK506 regimen were important predictors of the prevalence of PTDM. Greater early detection and prevention efforts for PTDM are needed for older transplant recipients. PTDM patients with an FK506 regimen had higher hemoglobin A1c levels and insulin resistance index than did patients who did not use FK506. The association of serum indicators with FK506 use in the prevalence of PTDM warrants further investigation.

Optimal dose for stroke thrombolysis in Asians: low dose may have similar safety and efficacy as standard dose.

BACKGROUND: Although intravenous tissue-type plasminogen activator (t-PA) at a standard dose of 0.9 mg kg(-1) is effective for patients with acute ischemic stroke, concerns have been raised regarding Asians. OBJECTIVES: To compare the safety and efficacy between low and standard doses for stroke thrombolysis. PATIENTS/METHODS: Consecutive patients receiving t-PA treatment were recruited according to the prespecified dosing policy from two medical centers in Taiwan: low dose (0.7 mg kg(-1) ) at National Cheng Kung University Hospital (NCKUH) from August 2006 to June 2009, or standard dose (0.9 mg kg(-1) ) at NCKUH from July 2009 to December 2010 and at Changhua Christian Hospital from May 2008 to December 2010. The primary safety outcome was the occurrence of symptomatic intracerebral hemorrhage (SICH). The secondary efficacy outcome was the proportion of patients with a modified Rankin Scale (mRS) grade of ≤ 1 at 3 months. RESULTS: From August 2006 to December 2010, 261 patients were recruited, of whom 105 and 156 received low and standard doses, respectively. The occurrence of SICH was non-significantly lower in the standard-dose group than in the low-dose group (2.6% vs. 4.8%, respectively; P = 0.34). The favorable outcome of mRS grade of ≤ 1 at 3 months was similar (38.4% and 41.1%, respectively; P = 0.676). A review of other case series of low vs. standard doses in Asians also showed similar safety and efficacy. CONCLUSION: Our study, as well as other case series on Asians, revealed that standard-dose thrombolysis for acute ischemic stroke in an Asian population carries no increased risk of symptomatic intracerebral hemorrhage when compared with the low dose.

Urothelial cancer after renal transplantation: an update.

According to the Australian and New Zealand Dialysis and Transplantation (ANZDATA) 2010 Annual Report, cancer is surpassing cardiovascular diseases as the leading cause of posttransplantation death. Skin cancer and posttransplantation lymphoproliferative disorder (PTLD) are 2 cancers in Western countries. However, urothelial cancer happens much more frequently among Chinese people. We reviewed our experience in Congress of the Asian Society of Transplantation (CAST) 2005, including 10 urothelial cancers, among 620 renal transplant recipients. In this report, we have presented our updated data. From July 1981 to May 2011, we performed 770 renal transplantations followed by graft and native kidney sonography annually even among asymptomatic cases using the protocol described in CAST 2005. During this period, 35 urothelial tumors were detected, ie, 25 new cases were identified in 6 years. These 35 cases included 7 cases with bilateral upper tract involvement and 5 of them with bladder tumors. Seven patients had bladder cancer alone. In 19 patients, 22 ureteral cancers included 1 that grew from the graft ureter, 17 (77.3%) patients showed hydronephrosis by sonography. We performed 13 bilateral nephroureterectomies; 2 were known to have bilateral upper tract cancer. Four of the other 11 were found to have insidious tumors. In contrast, 2 of the 15 initial unilateral nephroureterectomy patients underwent a subsequent contralateral nephroureterectomy due to a tumor. The pattern of urethral cancer in renal transplant recipients is thoroughly different, including female predominance, and a higher incidence of upper tract involvement. We emphasize the necessity of routine periodic sonographic survey even among asymptomatic patients for early detection of a urothelial tumor.

Size does matter-donor-to-recipient body mass index difference may affect renal graft outcome.

BACKGROUND: Obesity, in the either kidney donor or the recipient, has been related to worse graft function. The aim of this study was to compare long-term graft outcomes of living-related kidney recipients regarding the donor-to-recipient body mass index (BMI) ratio. METHODS: From November 2002 to November 2010, 62 consecutive living-related kidney transplantations were performed at our center. Donor and recipient BMIs were categorized by Taiwan's national standard using dividing values of 18.5, 24, and 27 kg/m(2) to divide subjects into donor-to-recipient BMI categories. These with the same BMI category as their donors were defined as the same-BMI group (group 0); recipients with a lower BMI category than their donors were defined as the large-to-small group (group 1); and those with a higher BMI category than their donors were defined as the small-to-large group (group 2). Baseline parameters and posttransplantation follow-up data were analyzed according to this grouping. RESULTS: Of the 57 recipients followed regularly at our hospital (mean follow-up 48.9 months), 21 (36.8.1%) were in group 0; 26 (45.6%) in group 1, and 10 (17.6%) in group 2. The baseline parameters were similar among these groups. The overall graft survival rates were 81.0% in group 0, 76.9% in group 1, and 90.0% in group 2. The rejection-free graft survival rates were 81.0%, 65.4%, and 90.0%, respectively. By Kaplan-Meier analysis, group 1 showed worse rejection-free graft survival than group 0 or group 2 (log-rank P = .046). CONCLUSIONS: Living-related recipients of kidneys from donors with a higher BMI showed lower long-term graft survival, which might suggest that petite recipients may need time to compensate adequate blood flow for the relative large graft, thus carrying a higher chance of rejection and worse graft outcomes.

Ensembled artificial neural networks to predict the fitness score for body composition analysis.

OBJECTIVES: To predict the nutrition and health status of staff and students in Yuan Ze University and select the influential variables from the total body composition variables, which should have similar predictive ability with the whole factors. DESIGN: Spontaneous and voluntary physical examination. SETTING: Sanitary and Health Care Section of Yuan Ze University in Taiwan. PARTICIPANTS: 1227 staff and students. MEASUREMENTS: With the help of Inbody720TM, 139 body composition variables were measured and 60 variables were retained after data pre-processing. An ensembled artificial neural networks (EANN) prediction model was established and seven different methods for assessing variables importance were applied. Besides, classical linear and logistic regression models were developed for comparison with EANN prediction results. RESULTS: The prediction performance of EANN model was satisfactory (RMSE (train) = 0.2686, RMSE (validation) = 0.2648, RMSE (test) = 0.3492). Since both the actual and simulation fitness score were at the range of 0 to 100, according to rounding off rule, the simulated value was almost the same with actual value. Besides, 12 important variables were obtained by seven methods for quantifying variable importance in EANN, which had similar predictive capability with 60 variables (RMSE (train) = 0.3263, RMSE (validation) = 0.322, RMSE (test) = 0.3226). The linear and logistic regression models results were both evidently worse than EANN results. CONCLUSION: The results confirm that EANN is appropriate to approximate such a complicated, non-invasive and highly non-linear problem as body composition analysis. It can be helpful for nutritionists to manage and improve the nutrition and health condition of staff and students, by adjusting the 12 most important variables.

Brain metastasis as a late manifestation of ovarian carcinoma.

This paper aims to evaluate the clinical characteristics of ovarian cancer patients with cerebral metastases. Ten ovarian cancer patients with brain metastases were retrospectively identified from a total of 539 ovarian cancer patients. Their characteristics before and at the time of diagnosis of cerebral metastases were analysed. The survival of them was also measured. Ten (1.9%) of the 539 ovarian cancer patients had brain metastases in the study period. Nine had stage III or IV tumours with either moderate or poor histological differentiation. The mean time from diagnosis of ovarian cancer to documentation of central nervous system metastasis was 24.3 months, which was 11.1 months if other sites of metastasis were involved before cerebral relapse. All of the patients with intra-cranial tumours suffered from associated neurological defects and relived by treatments. The median survival time after diagnosis of central nervous system involvement was 3 months. In this study, all ovarian cancer patients with cerebral metastases had clinical neurological symptoms. Physicians should pay more attention to ovarian cancer patients with neurological defects and arrange brain imaging studies for the early diagnosis of brain metastases and prompt management to improve quality of life.

Risk of gynaecological malignancies in cytologically atypical glandular cells: follow-up study of a nationwide screening population.

OBJECTIVE: To investigate the relationship between screening status, clinical characteristics and risk of gynaecological malignancies in women with a cytological diagnosis of atypical glandular cells (AGC). DESIGN: Prospective study of a screened population. POPULATION: Case series from nationwide screening population. METHODS: The 8281 women who were diagnosed with cytological AGC for the first time were divided into screened (5386 women) and unscreened (2895 cases) groups according to their screening status. Follow-up histological reports were analysed. MAIN OUTCOME MEASURES: Diagnosis of cervical, uterine, or ovarian cancers. RESULTS: Of the 323 women who developed gynaecological malignancies, 271 had invasive cervical cancers, 40 had uterine cancers and 12 had ovarian cancers, with a mean follow up of 1.9 years and 50 740 person-years. Previous screening status was a strong risk predictor of gynaecological malignancies (hazard ratio 1.69, P = 0.0027). Compared with the general screening population, women with a first diagnosis of cytological AGC had significantly increased ratios of developing gynaecological malignancies (17.85-fold for cervical cancer, 5.68-fold for uterine cancer, and 2.04-fold for ovarian cancer, P < 0.05). When compared with women aged <35 years, those in other age groups had a significantly higher risk of developing gynaecological cancers (age ≥60 years, hazard ratio 1.99, 95% CI 1.20-2.37, P = 0.016). CONCLUSIONS: Comprehensive evaluation for women with cytological AGC, including pelvic examination, ultrasonography, colposcopy, endocervical curettage, cervical biopsy and endometrial biopsy needs to be considered, especially for those with risk factors (i.e. >60 years old, lower educational status, previous Papanicolaou smear interval longer than 2 years, or no previous Papanicolaou smear).

Morphine-sparing effect by COX-1 inhibitor sustains analgesic function without compromising antigen-specific immunity and antitumor effect of naked DNA vaccine.

Morphine and ketorolac, two analgesics with different mechanisms, have been widely used in controlling cancer pain and postoperative pain in surgery. Our previous study revealed that morphine could suppress the anti-tumor effect of antigen-specific DNA vaccine. In this study, we further evaluated and compared another analgesic drug, ketorolac, with morphine for its analgesic functions and the antitumor immunities of antigen-specific DNA vaccine. We first observed that ketorolac-treated mice did not enhance tumorigenesis nor suppress the anti-tumor effects of antigen-specific (calreticulin linked to HPV16 E7) CRT/E7 DNA vaccine. We then demonstrated that ketorolac was less potent in inducing apoptosis of T lymphocytes and the generation of reactive oxygen species, in reducing mitochondrial membrane potentials, and leading to the activation of caspases 3 and 7 in T lymphocytes than morphine. When CRT/E7 DNA vaccinated mice treated with ketorolac, the declines of frequencies of E7-specific IFN-gamma-secreting CD8+ T cell precursors were slower in the morphine-treated group. CRT/E7 DNA vaccinated mice, treated with a mixture of morphine and ketorolac, could maintain the analgesic function without experiencing a decrease in the anti-tumor effects. CRT/E7 DNA vaccine with the opioid-sparing effect of ketorolac could provide potent anti-tumor effects and good analgesic function.

Effectiveness of national cervical cancer screening programme in Taiwan: 12-year experiences.

BACKGROUND: We examined cervical cancer incidence before and after nationwide cervical cancer screening was initiated in Taiwan in mid-1995. RESULTS: The invasive cancer incidence decreased by 47.8% during 1995-2006. The carcinoma in situ incidence increased 1.7-fold during 1995-2000, and decreased by 19.6% during 2000-2006. CONCLUSION: The Taiwan national programme has significantly decreased invasive cervical cancer.

Noncarrier naked antigen-specific DNA vaccine generates potent antigen-specific immunologic responses and antitumor effects.

Genetic immunization strategies have largely focused on the use of plasmid DNA with a gene gun. However, there remains a clear need to further improve the efficiency, safety, and cost of potential DNA vaccines. The gold particle-coated DNA format delivered through a gene gun is expensive, time and process consuming, and raises aseptic safety concerns. This study aims to determine whether a low-pressured gene gun can deliver noncarrier naked DNA vaccine without any particle coating, and generate similarly strong antigen-specific immunologic responses and potent antitumor effects compared with gold particle-coated DNA vaccine. Our results show that mice vaccinated with noncarrier naked chimeric CRT/E7 DNA lead to dramatic increases in the numbers of E7-specific CD8+ T-cell precursors and markedly raised titers of E7-specific antibodies. Furthermore, noncarrier naked CRT/E7 DNA vaccine generated potent antitumor effects against subcutaneous E7-expressing tumors and pre-established E7-expressing metastatic pulmonary tumors. In addition, mice immunized with noncarrier naked CRT/E7 DNA vaccine had significantly less burning effects on the skin compared with those vaccinated with gold particle-coated CRT/E7 DNA vaccine. We conclude that noncarrier naked CRT/E7 DNA vaccine delivered with a low-pressured gene gun can generate similarly potent immunologic responses and effective antitumor effects has fewer side effects, and is more convenient than conventional gold particle-coated DNA vaccine.

High mesothelin correlates with chemoresistance and poor survival in epithelial ovarian carcinoma.

The objective of this paper is to investigate the mesothelin expression level to the clinicopathological features, chemoresponse, and to the outcome of patients with epithelial ovarian carcinoma (EOC). Mesothelin mRNA was detected by real-time quantitative reverse-transcription PCR in 139 EOC patients. Clinical characteristics, histopathological items, responses to chemotherapy, progression-free survival (PFS), and overall survival (OS) were recorded. Tumours with advanced stages had higher mesothelin than those with early stages. The chemoresistant patients showed significantly higher mesothelin than did chemosensitive patients (2.81 vs 0.43, P<0.001), irrespective of optimal or suboptimal surgery in those with advanced stages. Highly expressed levels of mesothelin were an independent but poor prognostic factor in the PFS (2.03 (1.23-3.37) P=0.006) and OS (3.72 (1.64-8.45), P=0.002) of the 139 EOC patients in multivariate analysis. In addition, patients in advanced stages with highly expressed mesothelin also had significantly worse OS, regardless of whether they had undergone optimal (13.85 (1.76-125.60), P=0.013) or suboptimal (4.47 (1.83-10.88), P=0.001) debulking surgery in multivariate analysis. Out results provide new evidence that mesothelin expression is associated with chemoresistance and with shorter disease-free survival and worse OS of patients with EOC.

Biostabilization assessment of MSW co-disposed with MSWI fly ash in anaerobic bioreactors.

Municipal solid waste incinerator (MSWI) fly ash has been examined for possible use as landfill interim cover. For this aim, three anaerobic bioreactors, 1.2m high and 0.2m in diameter, were used to assess the co-digestion or co-disposal performance of MSW and MSWI fly ash. Two bioreactors contained ratios of 10 and 20 g fly ash per liter of MSW (or 0.2 and 0.4 g g(-1) VS, that is, 0.2 and 0.4 g fly ash per gram volatile solids (VS) of MSW). The remaining bioreactor was used as control, without fly ash addition. The results showed that gas production rate was enhanced by the appropriate addition of MSWI fly ash, with a rate of approximately 6.5l day(-1)kg(-1)VS at peak production in the ash-added bioreactors, compared to approximately 4l day(-1)kg(-1)VS in control. Conductivity, alkali metals and VS in leachate were higher in the fly ash-added bioreactors compared to control. The results show that MSW decomposition was maintained throughout at near-neutral pH and might be improved by release of alkali and trace metals from fly ash. Heavy metals exerted no inhibitory effect on MSW digestion in all three bioreactors. These phenomena indicate that proper amounts of MSWI fly ash, co-disposed or co-digested with MSW, could facilitate bacterial activity, digestion efficiency and gas production rates.