Simultaneous ammonia and organics degradation from municipal landfill leachate by electrochemical oxidation.

The two primary issues for wide implementation of the electrochemical oxidation of wastewater are the significant cost of electrode and high energy consumption. On the other side, conventional biological processes and membrane technology have several drawbacks for recalcitrant landfill leachate (LL) treatment. To address these issues, graphite/PbO2 anode was used to treat medium to mature age (biodegradability index, 5-day biochemical oxygen demand/chemical oxygen demand: 0.25) LL. To reduce the cost of the oxidation process and maximize the efficiency, operating conditions were optimized. The optimum parameter values were obtained as 24.7 mA cm-2, 180 ± 3 rpm, and 1.9 cm of current density, stirring rate, and electrode gap, respectively. Dissolved organic carbon (DOC), chemical oxygen demand (COD), and ammonia-N removal efficiencies of 55 ± 1.4%, 81 ± 1.9%, and 56 ± 3% were obtained after 8 h of degradation at optimum conditions. The decrease in aromatic substances and ultraviolet (UV) quenching materials were evaluated by UV-Visible spectroscopy and Specific UV absorbance. The conversion of aromatic compounds into simpler molecule compounds was also verified by Fourier-transform infrared spectroscopy analysis. The lab-scale anode synthesis cost was evaluated as 0.42 USD.

Idiopathic Intracranial Hypertension and Endoscopic Optic Nerve Sheath Fenestration.

Idiopathic intracranial hypertension (IIH), also called as benign intracranial hypertension is a disorder, which is  considered benign in its course except its' ill effects on vision. Ocular findings in IIH such as papilledema, macular changes, retinal micro haemorrhages, cotton wool spots and tortuosity of vessels are the prominent features in funduscopy examination in these patients. Papilledema is a hallmark feature for evaluation of response to treatment. Ophthalmological rescue is a primary goal of management of idiopathic intracranial hypertension. Among the treatment options described in literature, optic nerve sheath fenestration is a minimally invasive endoscopic technique for the rescue of vision. We present this case-report, which will help ophthalmologists and the surgeons to determine the significance of the funduscopy changes after optic nerve sheath fenestration and help in decision making.

Audiovestibular functioning of post-menopausal females with osteoporosis and osteopenia.

INTRODUCTION: Osteoporosis and osteopenia are progressive disorders characterized by decreased bone mass, especially in postmenopausal women. These can be associated with body pain, fractures, hearing loss and balance disorders. The present study aims to evaluate audio-vestibular function in postmenopausal patients with osteopenia or osteoporosis. METHODS: The study included 48 postmenopausal women (new subjects) diagnosed with osteoporosis (n = 23) or osteopenia (n = 25) in the age range of 50-66 years, as well as 28 normal women as controls. Audiological testing included pure tone audiometry (conventional and extended high-frequency audiometry), speech audiometry, impedance audiometry and otoacoustic emissions, including both transient evoked otoacoustic emissions (TEOAEs) and distortion product otoacoustic emissions (DPOAEs). All subjects also underwent vestibular evoked myogenic potentials testing (both ocular and cervical VEMPs). RESULTS: In the present study, hearing was worse at all frequencies in the osteoporosis group in comparison with the osteopenia and control groups, with worse speech recognition and discrimination scores and OAEs. Vestibular function was affected in 95.65% of women with osteoporosis and 76% of those with osteopenia. CONCLUSION: Osteoporosis and osteopenia are risk factors for vestibular dysfunction and hearing deficits in postmenopausal women. Thus, hearing and vestibular function should be monitored by audiological and vestibular testing periodically in these individuals.

High Prevalence of Anemia and Inherited Hemoglobin Disorders in Tribal Populations of Madhya Pradesh State, India.

Despite estimated high prevalence of inherited hemoglobin (Hb) disorders among tribal populations in Madhya Pradesh State, India, the burden of disease is unknown, leading to high morbidity and associated mortality. Our aim was to screen tribal populations in designated tribal districts of Madhya Pradesh State for various hemoglobinopathies and to estimate the prevalence and plausible cause of anemia. The present study screened a total of 3992 tribal individuals comprised of students of Tribal schools, ashrams of Dindori, Mandla, and Chhindwara districts of Madhya Pradesh State. Screening of hemoglobinopathies was done using Hb electrophoresis and or high performance liquid chromatography (HPLC), α-thalassemia (α-thal) was detected using polymerase chain reaction (PCR). The median age of the studied cohort was 15 years (interquartile range 13-16 years). High prevalence (76.7%) of anemia was observed among the studied cohort. The prevalence of sickle cell trait and sickle cell disease varies from 10.7 to 15.6% and 0.4 to 0.8%, respectively. The allele frequency of sickle cell gene was highest in the Pradhan tribe followed by the Panika tribe. Dindori district had the highest prevalence of sickle cell trait. ß-Thalassemia (ß-thal) trait was observed in only 1.4% of the screened population. α Gene deletions were observed in 84.7% individuals. Significant association of α gene deletion mutations with mean Hb, mean corpuscular volume (MCV), and mean corpuscular Hb (MCH) was observed. The Bharia tribe showed the highest prevalence for α-thal. For comprehensive health care, effective intervention programs are needed to reduce the high prevalence of anemia and hemoglobinopathies among tribes.

Durvalumab alone and durvalumab plus tremelimumab versus chemotherapy in previously untreated patients with unresectable, locally advanced or metastatic urothelial carcinoma (DANUBE): a randomised, open-label, multicentre, phase 3 trial.

BACKGROUND: Survival outcomes are poor for patients with metastatic urothelial carcinoma who receive standard, first-line, platinum-based chemotherapy. We assessed the overall survival of patients who received durvalumab (a PD-L1 inhibitor), with or without tremelimumab (a CTLA-4 inhibitor), as a first-line treatment for metastatic urothelial carcinoma. METHODS: DANUBE is an open-label, randomised, controlled, phase 3 trial in patients with untreated, unresectable, locally advanced or metastatic urothelial carcinoma, conducted at 224 academic research centres, hospitals, and oncology clinics in 23 countries. Eligible patients were aged 18 years or older with an Eastern Cooperative Oncology Group performance status of 0 or 1. We randomly assigned patients (1:1:1) to receive durvalumab monotherapy (1500 mg) administered intravenously every 4 weeks; durvalumab (1500 mg) plus tremelimumab (75 mg) administered intravenously every 4 weeks for up to four doses, followed by durvalumab maintenance (1500 mg) every 4 weeks; or standard-of-care chemotherapy (gemcitabine plus cisplatin or gemcitabine plus carboplatin, depending on cisplatin eligibility) administered intravenously for up to six cycles. Randomisation was done through an interactive voice-web response system, with stratification by cisplatin eligibility, PD-L1 status, and presence or absence of liver metastases, lung metastases, or both. The coprimary endpoints were overall survival compared between the durvalumab monotherapy versus chemotherapy groups in the population of patients with high PD-L1 expression (the high PD-L1 population) and between the durvalumab plus tremelimumab versus chemotherapy groups in the intention-to-treat population (all randomly assigned patients). The study has completed enrolment and the final analysis of overall survival is reported. The trial is registered with ClinicalTrials.gov, NCT02516241, and the EU Clinical Trials Register, EudraCT number 2015-001633-24. FINDINGS: Between Nov 24, 2015, and March 21, 2017, we randomly assigned 1032 patients to receive durvalumab (n=346), durvalumab plus tremelimumab (n=342), or chemotherapy (n=344). At data cutoff (Jan 27, 2020), median follow-up for survival was 41·2 months (IQR 37·9-43·2) for all patients. In the high PD-L1 population, median overall survival was 14·4 months (95% CI 10·4-17·3) in the durvalumab monotherapy group (n=209) versus 12·1 months (10·4-15·0) in the chemotherapy group (n=207; hazard ratio 0·89, 95% CI 0·71-1·11; p=0·30). In the intention-to-treat population, median overall survival was 15·1 months (13·1-18·0) in the durvalumab plus tremelimumab group versus 12·1 months (10·9-14·0) in the chemotherapy group (0·85, 95% CI 0·72-1·02; p=0·075). In the safety population, grade 3 or 4 treatment-related adverse events occurred in 47 (14%) of 345 patients in the durvalumab group, 93 (27%) of 340 patients in the durvalumab plus tremelimumab group, and in 188 (60%) of 313 patients in the chemotherapy group. The most common grade 3 or 4 treatment-related adverse event was increased lipase in the durvalumab group (seven [2%] of 345 patients) and in the durvalumab plus tremelimumab group (16 [5%] of 340 patients), and neutropenia in the chemotherapy group (66 [21%] of 313 patients). Serious treatment-related adverse events occurred in 30 (9%) of 345 patients in the durvalumab group, 78 (23%) of 340 patients in the durvalumab plus tremelimumab group, and 50 (16%) of 313 patients in the chemotherapy group. Deaths due to study drug toxicity were reported in two (1%) patients in the durvalumab group (acute hepatic failure and hepatitis), two (1%) patients in the durvalumab plus tremelimumab group (septic shock and pneumonitis), and one (<1%) patient in the chemotherapy group (acute kidney injury). INTERPRETATION: This study did not meet either of its coprimary endpoints. Further research to identify the patients with previously untreated metastatic urothelial carcinoma who benefit from treatment with immune checkpoint inhibitors, either alone or in combination regimens, is warranted. FUNDING: AstraZeneca.

A review on presence, survival, disinfection/removal methods of coronavirus in wastewater and progress of wastewater-based epidemiology.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused the global pandemic coronavirus 2019 disease (COVID-19). The outbreak of COVID-19 as Public Health Emergency of International Concern is declared by World Health Organization on January 30, 2020. The known route of transmission is due to direct contact or via respiratory droplets. Recently, several studies reported SARS-CoV-2 ribonucleic acid (RNA) in wastewater treatment plant samples. The presence of SARS-CoV-2 RNA in wastewater may predict COVID-19 occurrence qualitatively and quantitatively. The concept is known as wastewater-based epidemiology (WBE) or sewage epidemiology. The present study reviewed the presence of coronavirus in wastewater and investigations relating to WBE development as a tool to detect COVID-19 community transmission. Few articles reported a correlation of SARS-CoV-2 RNA concentration in wastewater with the number of COVID-19 cases, whereas few reported higher prediction by wastewater surveillance than confirmed cases. The application of WBE is still in a preliminary stage but has the potential to indicate an early sign of transmission. The knowledge of persistence of coronavirus in municipal and hospital wastewater is needed for the application of WBE and to understand the chances of transmission. The studies reported more prolonged survival of coronavirus in low-temperature wastewater. Studies relating to the inactivation of coronavirus by disinfectants and removal of coronavirus are also presented. Research on the performance of the commonly adopted disinfection technologies in inactivating SARS-CoV-2 in municipal and hospital wastewater is required to reduce the risk associated with municipal and hospital wastewater.

Optimal PD-L1-high cutoff for association with overall survival in patients with urothelial cancer treated with durvalumab monotherapy.

BACKGROUND: Studies have indicated that programmed death ligand 1 (PD-L1) expression may have utility as a predictive biomarker in patients with advanced/metastatic urothelial carcinoma (UC). Different immunohistochemical (IHC) assays are in development to assess PD-L1 expression on tumor cells (TCs) and tumor-infiltrating immune cells (ICs). METHODS: In this post hoc analysis of the single-arm, phase 1/2 Study 1108 (NCT01693562), PD-L1 expression was evaluated from tumor samples obtained prior to second-line treatment with durvalumab in patients with advanced/metastatic UC using the VENTANA (SP263) IHC Assay. The primary objective was to determine whether the TC ≥ 25%/IC ≥ 25% algorithm (i.e., cutoff of ≥ 25% TC or ≥ 25% IC with PD-L1 staining at any intensity above background) was optimal for predicting response to durvalumab. PD-L1 expression data were available from 188 patients. RESULTS: After a median follow-up of 15.8 and 14.6 months, higher PD-L1 expression was associated with longer overall survival (OS) and progression-free survival (PFS), respectively, with significant separation in survival curves for PD-L1-high and-low expressing patients for the TC ≥ 25%/IC ≥ 25% cutoff (median OS: 19.8 vs 4.8 months; hazard ratio: 0.46; 90% confidence interval: 0.33, 0.639). OS was also prolonged for PD-L1-high compared with-low patients when samples were categorized using TC/IC combined positive score ≥ 10 and IC≥ 5% cutoffs. In multivariate analysis, IC but not TC PD-L1 expression was significantly associated with OS, PFS, and objective response rate (P < 0.001 for each), although interaction analysis showed similar directionality of benefit for ICs and TCs. CONCLUSIONS: These findings support the utility of a combined TC/IC algorithm for predicting response to durvalumab in patients with UC, with the TC≥ 25%/IC≥ 25% cutoff optimal when used with the VENTANA (SP263) IHC Assay.

Patient-reported outcomes and inflammatory biomarkers in patients with locally advanced/metastatic urothelial carcinoma treated with durvalumab in phase 1/2 dose-escalation study 1108.

BACKGROUND: Durvalumab has shown meaningful clinical activity in patients with metastatic urothelial carcinoma (mUC) in Study 1108 (NCT01693562). An important focus in treatment is health-related quality of life (HRQOL). Here, patient-reported outcomes (PROs) from Study 1108 and their relationship with inflammatory biomarkers are explored. METHODS: Disease-related symptoms, functioning, and HRQOL were assessed with the Functional Assessment of Cancer Therapy-Bladder (FACT-Bl) and the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30). Relationships between PRO improvements and the best changes in the tumor size, albumin level, and neutrophil-lymphocyte ratio (NLR) were assessed with Spearman correlation analysis. RESULTS: The mean FACT-Bl total score improved from 107.5 (standard deviation [SD], 23.0) at the baseline to 115.4 (SD, 22.6) on day 113, with similar increases found for the Trial Outcome Index (TOI) and Bladder Cancer Subscale (BLCS) scores. The mean FACT-Bl total scores improved over time, and the FACT-Bl TOI scores significantly improved by day 113 (P < .05). The mean EORTC QLQ-C30 Global Health Status/Quality of Life score improved from 57.1 (SD, 24.8) at the baseline to 69.0 (SD, 21.4) on day 113; the functional scale and symptom scores (day 113) were higher than the baseline scores (P < .05) for EORTC Social Functioning. The FACT-Bl total, BLCS, and TOI scores improved in 32.6%, 34.9%, and 32.6% of the patients by day 113; 26.3% to 37.8% of the patients exhibited improvements in EORTC QLQ-C30 functional scores. The best tumor shrinkage and posttreatment improvements in serum albumin and NLR correlated with increases in FACT-Bl total, TOI, and BLCS scores and in EORTC Physical Functioning and Role Functioning scores (P < .05). CONCLUSIONS: Durvalumab was associated with improvements in disease-related symptoms, functioning, and HRQOL in patients with mUC. Improvements in systemic inflammation may contribute to PRO improvements in these patients.

TTF1-positive Papillary Epithelial Tumor of Pituitary: An Epithelial Variant of Pituicytoma?

Low-grade epithelial tumor of pituitary region with dominant papillary architecture is extremely rare. We describe a case of 20-year female who had a recurrent nonfunctioning pituitary tumor. Histologic examination revealed a low-grade epithelial tumor with predominant papillary architecture, lined by cuboidal to columnar epithelial cells. The tumor cells were immunpositive for cytokeratin (CK), CK7, epithelial membrane antigen, carcinoembryonic antigen and showed diffuse and strong nuclear positivity for thyroid transcription factor 1. They were negative for neuroendocrine markers and pituitary hormones. Ki-67 proliferation index was low (1%). Ultrastructural examination revealed presence of microvilli, intercellular tight junctions, and keratin filaments within the tumor cells and lack of neurosecretory granules. No lesion was identified in thyroid or lung on systemic evaluation. On the basis of the morphology, immunophenotype, ultrastructural findings, and diffuse thyroid transcription factor 1 positivity, this tumor may represent an epithelial variant of pituicytoma with dominant papillary architecture. This type of differentiation is extremely rare, and to the best of our knowledge, has not been described previously in the literature.

Randomised Comparison of Safety Profile and Short Term Response of Itraconazole, Voriconazole and Amphotericin B in the Management of Chronic Invasive Fungal Rhinosinusitis.

Chronic invasive fungal rhino sinusitis (CIFS) is a well described clinical entity characterized by mucosal and sub mucosal infiltration of mycotic organisms and angio-centric extension into orbital and intracranial structures. Itraconazole, Voriconazole and Amphotericin B are commonly used for CIFS. In the present study we have evaluated short term clinical response of these drugs. Thirty diagnosed patients of CIFS who presented to us from January 2011 to December 2015 were divided into three groups randomly. Group A, B and C received Itraconazole, Voriconazole and Amphotericin respectively. Visual Analogue scale (VAS), Lund Mackay (LM) radiological scores and Kupferberg's nasal endoscopic grades were seen and compared in all patients before treatment, after primary surgical debridement and biopsy and after post biopsy antifungal drug treatment. We assessed the serum drug levels using HPLC assay at 4 and 8 weeks of therapy and correlated them for efficacy and safety. All the groups had significant improvement after treatment compared to beginning of study. Inter group comparison showed that mean LM, NE and VAS scores were significantly better in Voriconazole group compared to Itraconazole and amphotericin B therapy. The reduction of these objective parameters with treatment was also significantly high in Voriconazole group compared to the other two groups. Voriconazole has shown to be the most effective treatment modality for chronic invasive fungal sinusitis compared to other commonly used drugs such as Itraconazole and Amphotericin B.

Clinical Activity, Tolerability, and Long-Term Follow-Up of Durvalumab in Patients With Advanced NSCLC.

INTRODUCTION: Durvalumab is a selective, high-affinity human immunoglobulin G1 monoclonal antibody that blocks programmed cell death ligand 1 (PD-L1) binding to programmed death 1. Here we report safety and clinical activity in the NSCLC cohort of a phase I/II trial that included multiple tumor types (Study 1108; NCT01693562). METHODS: Patients with stage IIIB-IV NSCLC (squamous or nonsquamous) received durvalumab 10 mg/kg every 2 weeks for 12 months or until confirmed progressive disease or unacceptable toxicity. Primary objectives were safety and antitumor activity. Tumoral PD-L1 expression was assessed using the VENTANA SP263 Assay. Responses were assessed by blinded independent central review (Response Evaluation Criteria in Solid Tumors v1.1). Adverse events were graded according to National Cancer Institute's Common Terminology Criteria for Adverse Events (v4.03). RESULTS: Of 304 patients, 79.0% were previously treated. Confirmed objective response rate was 21.8% in patients with greater than or equal to 25% PD-L1 expression and 6.4% in those with less than 25%; 25.9% in first-line patients and 12.7% in previously treated patients; and 14.0% in squamous and 16.7% in nonsquamous disease. Median overall survival was 12.4 months and median progression-free survival was 1.7 months; both were numerically longer in the PD-L1 greater than or equal to 25% group than in the PD-L1 less than 25% group (overall survival 16.4 versus 7.6 months, respectively; progression-free survival 2.6 versus 1.4 months, respectively). Treatment-related adverse events occurred in 57.2%, were grade 3/4 in 10.2%, and led to discontinuation in 5.6%. One patient (0.3%) died of treatment-related pneumonia with underlying pneumonitis. CONCLUSIONS: Durvalumab was clinically active irrespective of histology in this mostly pretreated population, with a manageable safety profile. Response rates and survival appeared to be enhanced in patients with greater tumoral PD-L1 expression.

A novel framework of multivariate modeling of water distribution network through 33 factorial design and artificial neural network.

The water distribution network is largely affected by the change in the influencing factors, such as input pressure, demand and supply duration. The change in each parameter requires the extensive design of the network and the interactive effect of the influencing parameters are hardly explored. The main hurdles for the water providers lie in the absence of a prediction model, which can be used as a decision tool to assess the effect of the change in parameter and estimating the cost for the changed scenario. The present study developed a novel framework based on the artificial neural network for multivariate prediction modeling taking the response as the cost of the pipe network. The application of the 33 factorial design was used for the selection of the influencing parameters and outcome was taken as the input to the neural network model. The adequacy of the model was tested through error functions and analysis of variance. The low values of the error functions (0.0004-0.228) and high F value (162,442) and R2 (0.999) established the significance of the model. The model can be used for predicting the cost of the changed scenarios and assessment of the optimal solution for the system variables.

Sorptive equilibrium profile of fluoride onto aluminum olivine [(FexMg1-x)2SiO4] composite (AOC): Physicochemical insights and isotherm modeling by non-linear least squares regression and a novel neural-network-based method.

A novel aluminum/olivine composite (AOC) was prepared by wet impregnation followed by calcination and was introduced as an efficient adsorbent for defluoridation. The adsorption of fluoride was modeled with one-, two- and three-parameter isotherm equations by non-linear regression to demonstrate the adsorption equilibrium. The FI was the best-fitted model among the two-parameter isotherms with a R2 value of 0.995. The three-parameter models were found to have better performance with low values of the error functions and high F values. The neural-network-based model was applied for the first time in the isotherm study. The optimized model was framed with eight neurons in hidden layer with a mean square of error of 0.0481 and correlation coefficient greater than 0.999. The neural-based model has the better predictability with a higher F value of 9484 and R2 value of 0.998 compared to regression models, exhibiting the F value and the R2 in the range of 86-3572 and 0.835-0.995, respectively. The material characterization established the formation of the aluminum oxide, silicate, etc. onto the olivine which is conducive of the removal of fluoride by the formation of aluminum fluoride compounds, such as AlF3 in the spent material after defluoridation.

Adsorptive removal of arsenic by novel iron/olivine composite: Insights into preparation and adsorption process by response surface methodology and artificial neural network.

Olivine, a low-cost natural material, impregnated with iron is introduced in the adsorptive removal of arsenic. A wet impregnation method and subsequent calcination were employed for the preparation of iron/olivine composite. The major preparation process parameter, viz., iron loading and calcination temperature were optimized through the response surface methodology coupled with a factorial design. A significant variation of adsorption capacity of arsenic (measured as total arsenic), i.e., 63.15 to 310.85 mg/kg for arsenite [As(III)T] and 76.46 to 329.72 mg/kg for arsenate [As(V)T] was observed, which exhibited the significant effect of the preparation process parameters on the adsorption potential. The iron loading delineated the optima at central points, whereas a monotonous decreasing trend of adsorption capacity for both the As(III)T and As(V)T was observed with the increasing calcination temperature. The variation of adsorption capacity with the increased iron loading is more at lower calcination temperature showing the interactive effect between the factors. The adsorbent prepared at the optimized condition of iron loading and calcination temperature, i.e., 10% and 200 °C, effectively removed the As(III)T and As(V)T by more than 96 and 99%, respectively. The material characterization of the adsorbent showed the formation of the iron compound in the olivine and increase in specific surface area to the tune of 10 multifold compared to the base material, which is conducive to the enhancement of the adsorption capacity. An artificial neural network was applied for the multivariate optimization of the adsorption process from the experimental data of the univariate optimization study and the optimized model showed low values of error functions and high R2 values of more than 0.99 for As(III)T and As(V)T. The adsorption isotherm and kinetics followed Langmuir model and pseudo second order model, respectively demonstrating the chemisorption in this study.

Review on landfill leachate treatment by electrochemical oxidation: Drawbacks, challenges and future scope.

Various studies on landfill leachate treatment by electrochemical oxidation have indicated that this process can effectively reduce two major pollutants present in landfill leachate; organic matter and ammonium nitrogen. In addition, the process is able to enhance the biodegradability index (BOD/COD) of landfill leachate, which make mature or stabilized landfill leachate suitable for biological treatment. The elevated concentration of ammonium nitrogen especially observed in bioreactor landfill leachate can also be reduced by electrochemical oxidation. The pollutant removal efficiency of the system depends upon the mechanism of oxidation (direct or indirect oxidation) which depends upon the property of anode material. Applied current density, pH, type and concentration of electrolyte, inter-electrode gap, mass transfer mode, total anode area to volume of effluent to be treated ratio, temperature, flow rate or flow velocity, reactor geometry, cathode material and lamp power during photoelectrochemical oxidation may also influence the system performance. In this review paper, past and present scenarios of landfill leachate treatment efficiencies and costs of various lab scale, pilot scale electrochemical oxidation studies asa standalone system or integrated with biological and physicochemical processes have been reviewed with the conclusion that electrochemical oxidation can be employed asa complementary treatment system with biological process for conventional landfill leachate treatment as well asa standalone system for ammonium nitrogen removal from bioreactor landfill leachate. Furthermore, present drawbacks of electrochemical oxidation process asa landfill leachate treatment system and relevance of incorporating life cycle assessment into the decision-making process besides process efficiency and cost, have been discussed.

Efficacy and Safety of Durvalumab in Locally Advanced or Metastatic Urothelial Carcinoma: Updated Results From a Phase 1/2 Open-label Study.

IMPORTANCE: The data reported herein were accepted for assessment by the US Food and Drug Administration for Biologics License Application under priority review to establish the clinical benefit of durvalumab as second-line therapy for locally advanced or metastatic urothelial carcinoma (UC), resulting in its recent US approval. OBJECTIVE: To report a planned update of the safety and efficacy of durvalumab in patients with locally advanced/metastatic UC. DESIGN, SETTING, AND PARTICIPANTS: This is an ongoing phase 1/2 open-label study of 191 adult patients with histologically or cytologically confirmed locally advanced/metastatic UC whose disease had progressed on, were ineligible for, or refused prior chemotherapy from 60 sites in 9 countries as reported herein. INTERVENTION: Patients were administered durvalumab intravenous infusion, 10 mg/kg every 2 weeks, for up to 12 months or until progression, starting another anticancer therapy, or unacceptable toxic effects. MAIN OUTCOMES AND MEASURES: Primary end points were safety and confirmed objective response rate (ORR) per blinded independent central review (Response Evaluation Criteria In Solid Tumors [RECIST], version 1.1). RESULTS: A total of 191 patients with UC had received treatment. As of October 24, 2016 (90-day update), the median follow-up was 5.78 months (range, 0.4-25.9 months). The median age of patients was 67.0 years and most were male (136 [71.2%]) and white (123 [71.1%]). All patients had stage 4 disease, and 190 (99.5%) had prior anticancer therapy (182 [95.3%] postplatinum). The ORR was 17.8% (34 of 191; 95% CI, 12.7%-24.0%), including 7 complete responses. Responses were early (median time to response, 1.41 months), durable (median duration of response not reached), and observed regardless of programmed cell death ligand-1 (PD-L1) expression (ORR, 27.6% [n = 27; 95% CI, 19.0%-37.5%] and 5.1% [n = 4; 95% CI, 1.4%-12.5%] in patients with high and low or negative expression of PD-L1, respectively). Median progression-free survival and overall survival were 1.5 months (95% CI, 1.4-1.9 months) and 18.2 months (95% CI, 8.1 months to not estimable), respectively; the 1-year overall survival rate was 55% (95% CI, 44%-65%), as estimated by Kaplan-Meier method. Grade 3/4 treatment-related adverse events (AEs) occurred in 13 patients (6.8%); grade 3/4 immune-mediated AEs occurred in 4 patients (2.1%); and treatment-related AEs led to discontinuation of 3 patients (1.6%), 2 of whom had immune-mediated AEs that led to death (autoimmune hepatitis and pneumonitis). CONCLUSIONS AND RELEVANCE: Durvalumab, 10 mg/kg every 2 weeks, demonstrates favorable clinical activity and an encouraging and manageable safety profile in patients with locally advanced/metastatic UC. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01693562.

Voice Quality Following Unilateral Vocal Fold Paralysis: A Randomized Comparison of Therapeutic Modalities.

In this work, a study on the efficacy of different therapeutic modalities in patients with unilateral vocal fold paralysis (UVFP) was carried out. The study included 20 patients with UVFP, divided into two groups. The objective of this work is to evaluate the voice quality in these patients and to compare the voice following surgery and voice therapy. Group I received voice therapy and group II underwent thyroplasty type I and type IV. The voice was assessed pretreatment and 1 and 3 months posttreatment. Different parameters, such as habitual fundamental frequency (F0), signal-to-noise ratio, jitter, shimmer, maximum phonation duration, s/z ratio, and objective and subjective ratings of dysphonia, were analyzed. It was observed that in group I, all the parameters in seven out of ten patients improved significantly, except for shimmer. In group II, voice quality improved in 70% of the patients with all the parameters. As per previous studies, jitter and shimmer improved after a rehabilitation procedure. However, in this work, it is observed that shimmer did not improve in patients receiving voice therapy. The present study is the first of its type documenting and comparing the efficacy of voice therapy and thyroplasty type I and type IV in patients with UVFP.

Performance analysis of a continuous serpentine flow reactor for electrochemical oxidation of synthetic and real textile wastewater: Energy consumption, mass transfer coefficient and economic analysis.

A continuous flow electrochemical reactor was developed, and its application was tested for the treatment of textile wastewater. A parallel plate configuration with serpentine flow was chosen for the continuous flow reactor. Uniparameter optimization was carried out for electrochemical oxidation of synthetic and real textile wastewater (collected from the inlet of the effluent treatment plant). Chemical Oxygen Demand (COD) removal efficiency of 90% was achieved for synthetic textile wastewater (initial COD - 780 mg L-1) at a flow rate of 500 mL h-1 (retention time of 6 h) and a current density of 1.15 mA cm-2 and the energy consumption for the degradation was 9.2 kWh (kg COD)-1. The complete degradation of real textile wastewater (initial COD of 368 mg L-1) was obtained at a current density of 1.15 mA cm-2, NaCl concentration of 1 g L-1 and retention time of 6 h. Energy consumption and mass transfer coefficient of the reactions were calculated. The continuous flow reactor performed better than batch reactor with reference to energy consumption and economy. The overall treatment cost for complete COD removal of real textile wastewater was 5.83 USD m-3.

Electrochemical degradation of malachite green: Multivariate optimization, pathway identification and toxicity analysis.

Application of a newly developed electrode material, PbO2 coated on mild steel plate (MS-PbO2), for the degradation of malachite green (MG) by photocatalytic oxidation (PCO), electrochemical oxidation (ECO) and photoelectrochemical oxidation (PEC) was explored. PEC performed marginally better at lower current density. However, the performances of PEC and ECO were equally good at higher current densities. One variable at a time optimization was carried out to identify the major parameters influencing ECO. Multivariate optimization was carried out with NaCl concentration, current density and pH as the variables and chemical oxygen demand (COD) removal efficiency and current efficiency (CE) as the responses. Increasing the current density aided the COD removal efficiency, but decreased the CE. Low NaCl concentration and acidic pH were beneficial for both. The optimum condition for maximizing the COD removal efficiency and CE of MG (50 mg L(-1)) was obtained as NaCl concentration of 1.56 g L(-1), a current density of 1.91 mA cm(-2) and pH 5. The maximum predicted and experimental COD removal efficiencies were 89.41% and 90.8%, and CEs were 21.52% and 21.1%, respectively. Degradation intermediates were identified and a possible pathway of degradation was proposed. Disc inhibition study showed that the degraded samples are non-toxic. The efficacy of the method was tested for treating wastewater collected from dyebath having a COD of about 2000 mg L(-1). COD removal efficiency of greater than 90% was achieved within 12 h at a current density of 7.2 mA cm(-2).

p53 codon 72 polymorphism and its overexpression in patients with laryngeal carcinoma: Prognostic implications.

Abnormalities in the p53 gene are the most common genetic alterations seen in laryngeal carcinoma. No data exist regarding the association between laryngeal carcinoma and a distinct codon 72 variant and its expression. We conducted a prospective study (1) to analyze the p53 codon 72 polymorphic variants in patients with laryngeal carcinoma, (2) to analyze the expression of p53 mRNA in tissues of patients with laryngeal carcinoma using the reverse transcriptase-polymerase chain reaction (RT-PCR) assay, and (3) to detect p53 antibodies in the plasma of patients with laryngeal carcinoma before and after treatment. Tissue and blood samples were taken from 40 patients with laryngeal carcinoma-36 men and 4 women, aged 40 to 65 years (mean: 56)-and 20 age-matched controls with laryngeal conditions other than carcinoma. RT-PCR was used to measure p53 mRNA expression, and PCR-restriction fragment length polymorphism was used to determine p53 polymorphism. In addition, p53 antibodies were detected in plasma by Western blot testing. The 40 patients were treated with either surgery (total laryngectomy or conservation surgery) or radiotherapy. Tissue and blood samples were analyzed before treatment and 4 weeks after treatment. The findings were compared with those of the 20 controls. The results revealed that (1) homozygosity of the Pro72 variant of p53 was present in 26 laryngeal carcinoma patients (65%), (2) heterozygosity for the Pro/Arg genotype was present in 13 patients (32.5%), and (3) the Arg72 variant of the p53 allele was present in 1 patient (2.5%) before treatment. Overexpression of p53 mRNA was found in all patients with laryngeal carcinoma and in none of the controls before treatment; the difference was approximately 3.3 folds higher in the carcinoma group. However, p53 expression was not related to the biologic aggressiveness of these tumors. It is interesting that 4 weeks after definitive therapy, the expression levels of p53 mRNA in the 40 patients were comparable to those of the controls. The p53 antibodies were detected in the plasma of all patients with laryngeal carcinoma prior to definitive therapy and in none of them afterward, indicating that these antibodies represent a prognostic marker in laryngeal carcinoma. Our findings suggest that there is a correlation between p53 overexpression and the development of laryngeal carcinoma. Anti-p53 antibodies can be used as a prognostic marker in laryngeal carcinoma, and they can be exploited in the future to control the response to therapy and to monitor for certain early recurrences before they become clinically detectable.