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1.
Cancer ; 2019 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-31581306

RESUMO

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.

2.
Surg Radiol Anat ; 2019 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-31549199

RESUMO

PURPOSE: The purpose of the study is to study the details of dimensions and shape of oval window in different age groups, sides and genders and their clinical implications. The oval window is a key structure while performing surgeries in relation to stapes. An intricate knowledge of the shape and size of the oval window is important for the reconstruction and fitting of cartilage compatible with the native shape of the oval window. METHODS: Sixty normal wet cadaveric temporal bones of known age; gender and side were micro-dissected. The maximum height and width of the oval window was measured. The shape of the oval window was noticed. RESULTS: The mean value for maximum height and width of the oval window was 1.31 ± 0.28 mm and 2.67 ± 0.42 mm, respectively. The height and width of the oval window ranged between 1 mm and 1.5 mm and 2 mm and 3 mm in majority of the cases. he oval window was found to be oval shaped in 53.3% cases, other shapes such as kidney, D shape, rectangular or trapezoidal were also observed. CONCLUSIONS: The refined morphometric information of the oval window will help in preoperative assessment and surgical planning of various oval window-related surgical procedures. The knowledge may also help in designing and selecting proper cartilage shoe for the best outcome. Narrow oval window may cause procedural complications and surgeon discomfort in various stapes surgeries.

3.
Environ Res ; 176: 108542, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31387068

RESUMO

Pharmaceutically active compounds (PhACs) have pernicious effects on all kinds of life forms because of their toxicological effects and are found profoundly in various wastewater treatment plant influents, hospital effluents, and surface waters. The concentrations of different pharmaceuticals were found in alarmingly high concentrations in various parts of the globe, and it was also observed that the concentration of PhACs present in the water could be eventually related to the socio-economic conditions and climate of the region. Drinking water equivalent limit for each PhAC has been calculated and compared with the occurrence data from various continents. Since these compounds are recalcitrant towards conventional treatment methods, while advanced oxidation processes (AOPs) have shown better efficiency in degrading these PhACs. The performance of the AOPs have been evaluated based on percentage removal, time, and electrical energy consumed to degrade different classes of PhACs. Ozone based AOPs were found to be favorable because of their low treatment time, low cost, and high efficiency. However, complete degradation cannot be achieved by these processes, and various transformation products are formed, which may be more toxic than the parent compounds. The various transformation products formed from various PhACs during treatment have been highlighted. Significant stress has been given on the role of various process parameters, water matrix, oxidizing radicals, and the mechanism of degradation. Presence of organic compounds, nitrate, and phosphate usually hinders the degradation process, while chlorine and sulfate showed a positive effect. The role of individual oxidizing radicals, interfering ions, and pH demonstrated dissimilar effects on different groups of PhACs.

4.
Artigo em Inglês | MEDLINE | ID: mdl-31397623

RESUMO

The kinetic, isotherm and thermodynamic modeling of the adsorption of arsenite by layered double hydroxide have been performed to analyze the feasibility, efficacy and mechanism of the system. The fast uptake was observed during the initial phase of the process, which reached equilibrium at 240 min following Elovich model. The diffusion kinetic model exhibited that the rate-limiting step of adsorption was controlled by film diffusion as well as intraparticle diffusion. The isotherm modeling revealed the applicability of the Freundlich equation with the Kf values as 8.19-13.99 (mg g-1)(L mg-1)1/n at 283-323 K showing the increasing trend of adsorption capacity, which was further confirmed by the positive value of ΔH0 (9.49 kJ mol-1) demonstrating the endothermic nature of the adsorption process. The spontaneous nature of the adsorption reaction was established by the negative values of ΔG0. Application of the calcined Mg-Fe-LDH adsorbent for the removal of arsenic from real arsenic contaminated groundwater was also successfully performed. The effect of process parameters of the adsorption system was modeled by an artificial neural network (ANN) for adsorption capacity and removal efficiency. The optimized model exhibited high R2, F-value and low values of error functions, establishing the significant applicability of the ANN model.

5.
Clin Lung Cancer ; 2019 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-31327642

RESUMO

INTRODUCTION: Two clinical studies (Study 1108 and ATLANTIC) were analyzed to evaluate the prognostic value of baseline liver metastases (LMs) in advanced/metastatic non-small-cell lung cancer patients treated with durvalumab 10 mg/kg every 2 weeks. PATIENTS AND METHODS: A multivariate Cox proportional hazards analysis was conducted; covariates included performance status, tumor stage, histology, sex, age, smoking status, and programmed cell death ligand 1 (PD-L1) status. RESULTS: In all, 569 patients were included. LMs were present in 31.6% (96/304) of Study 1108 patients and 17.9% (47/263) of ATLANTIC patients. Median overall survival (OS) was shorter in patients with LMs than in those without in both studies. In both studies, LMs were an independent negative prognostic factor for OS and progression-free survival. Objective response rates were also significantly lower. PD-L1 independently predicted benefit across all patients. CONCLUSION: Liver metastases were associated with worse outcomes irrespective of PD-L1 status, but PD-L1 status predicted benefit from durvalumab irrespective of LMs.

6.
J Thorac Oncol ; 14(10): 1794-1806, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31228626

RESUMO

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.

7.
PLoS One ; 14(4): e0215717, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31002695

RESUMO

The present study provides first evidence on the role of plasma gelsolin in protecting pulmonary thromboembolism and thrombosis in a mouse model. Gelsolin is the most abundant actin depolymerizing protein in plasma and its significantly depleted values have been reported in metabolic disorders including cardiovascular diseases and myocardial infarction. Though gelsolin replacement therapy (GRT) has been shown to be effective in some animal models, no such study has been reported for thrombotic diseases that are acutely in need of bio-therapeutics for immediate and lasting relief. Here, using mice model and recombinant human gelsolin (rhuGSN), we demonstrate the antithrombotic effect of gelsolin in ferric chloride induced thrombosis in carotid artery and thrombin induced acute pulmonary thromboembolism. In thrombosis model, arterial occlusion time was significantly enhanced upon subcutaneous (SC) treatment with 8 mg of gelsolin per mice viz. 15.83 minutes vs. 8 minutes in the placebo group. Pertinently, histopathological examination showed channel formation within the thrombi in the carotid artery following injection of gelsolin. Fluorescence molecular tomography imaging further confirmed that administration of gelsolin reduced thrombus formation following carotid artery injury. In thrombin-induced acute pulmonary thromboembolism, mice pretreated with aspirin or gelsolin showed 100 and 83.33% recovery, respectively. In contrast, complete mortality of mice was observed in vehicle treated group within 5 minutes of thrombin injection. Overall, our studies provide conclusive evidence on the thrombo-protective role of plasma gelsolin in mice model of pulmonary thromboembolism and thrombosis.

8.
Health Qual Life Outcomes ; 17(1): 53, 2019 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-30922346

RESUMO

BACKGROUND: This study was aimed to assess the impact of quality of life using WHOQOL-BREF in patients with Visceral leishmaniasis (VL). METHODS: A total of 95 VL cases and 95 healthy participants filled out the questionnaires. Data on socio-demographic aspects along with disease duration were collected. Data were compared using a t-test, analysis of variance and chi-square test. RESULTS: VL patients experienced very high impact on their quality of life. Study cohort had male preponderance (72.63%). Majority (64.21%) were aged < 40 years. Longer disease duration was found to have significantly poor quality of life (p < 0.05). The physical domain was found to be most affected domains of quality of life (QOL). QOL was affected most in illiterate, married, housewife, rural population and patients with longer disease duration (p < 0.05). The psychological and environmental domains were significantly affected in > 40 years of age group married patients (p < 0.05). CONCLUSIONS: VL significantly impaired the patients' (QOL) in all four domains (physical, psychological, social relationship and environmental). Physical domain was significantly the most affected domain.


Assuntos
Leishmaniose Visceral/psicologia , Qualidade de Vida , Inquéritos e Questionários/normas , Adulto , Idoso , Estudos de Casos e Controles , Estudos Transversais , Feminino , Humanos , Leishmaniose Visceral/terapia , Masculino , Pessoa de Meia-Idade , População Rural/estatística & dados numéricos , Adulto Jovem
9.
Artigo em Inglês | MEDLINE | ID: mdl-30795730

RESUMO

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.


Assuntos
Modelos Teóricos , Redes Neurais (Computação) , Projetos de Pesquisa , Abastecimento de Água/métodos , Algoritmos , Abastecimento de Água/economia
10.
Childs Nerv Syst ; 2019 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-30659354

RESUMO

PURPOSE: A preliminary survey of pediatric neurosurgeons working at different centers around the world suggested differences in clinical practice resulting in variation in the risk of pediatric cerebellar mutism (CM) and cerebellar mutism syndrome (CMS) after posterior fossa (PF) tumor resection. The purposes of this study were (1) to determine the incidence and severity of CM and CMS after midline PF tumor resection in children treated at these centers and (2) to identify potentially modifiable factors related to surgical management (rather than tumor biology) that correlate with the incidence of CM/CMS. METHODS: Attending pediatric neurosurgeons at British Columbia's Children's Hospital (BCCH) and neurosurgeons who completed a pediatric neurosurgery fellowship at BCCH were invited to provide data from the center where they currently practiced. Children aged from birth to less than 18 years who underwent initial midline PF tumor resection within a contemporary, center-selected 2-year period were included. Data was obtained by retrospective chart and imaging review. Modifiable surgical factors that were assessed included pre-resection surgical hydrocephalus treatment, surgical positioning, ultrasonic aspirator use, intraoperative external ventricular drain (EVD) use, surgical access route to the tumor, and extent of resection. CM was defined as decreased or absent speech output postoperatively and CMS as CM plus new or worsened irritability. RESULTS: There were 263 patients from 11 centers in 6 countries (Canada, Germany, the Netherlands, India, Indonesia, and the USA). Median age at surgery was 6 years (range < 1 to 17 years). The overall incidence of postoperative CM was 23.5% (range 14.7-47.6% for centers with data on ≥ 20 patients). The overall incidence of CMS was 6.5% (range 0-10.3% for centers contributing data on ≥ 20 patients). A multivariate logistic regression on the full data set showed no significant association between pre-resection surgical hydrocephalus treatment, prone position, ultrasonic aspirator use, EVD use, telovelar approach, complete or near total resection, or treating center and either postoperative CM or CMS. CONCLUSIONS: While there was variation in surgical management of midline PF tumors among centers participating in this study, the factors in management that were examined did not predict postoperative CM or CMS.

11.
Arch Pathol Lab Med ; 2018 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-30457897

RESUMO

CONTEXT.­: Clinical responses to anti-programmed death receptor-1 and anti-programmed death ligand-1 (PD-L1) agents are generally improved in patients with high PD-L1 expression compared with those with low/negative expression across several tumor types, including urothelial carcinoma. OBJECTIVE.­: To validate a PD-L1 immunohistochemical diagnostic test in urothelial carcinoma patients treated with the anti-PD-L1 monoclonal antibody durvalumab. DESIGN.­: The Ventana PD-L1 (SP263) assay was validated for intended use in urothelial carcinoma formalin-fixed, paraffin-embedded samples in studies addressing sensitivity, specificity, robustness, and precision, and implemented in study CD-ON-MEDI4736-1108 (NCT01693562). Efficacy was analyzed in patients classified according to prespecified PD-L1 expression cutoffs: PD-L1 high (if >1% of the tumor area contained tumor-associated immune cells, ≥25% of tumor cells or ≥25% of immune cells stained for PD-L1; if ≤1% of the tumor area contained immune cells, ≥25% of tumor cells or 100% of immune cells stained for PD-L1) and PD-L1 low/negative (did not meet criteria for PD-L1 high). RESULTS.­: The assay met all predefined acceptance criteria for sensitivity, specificity, and precision. Interreader and intrareader precision overall agreement were 93.0% and 92.4%, respectively. For intraday reproducibility and interday precision, overall agreement was 99.2% and 100%, respectively. Interlaboratory overall agreement was 92.6%. In study CD-ON-MEDI4736-1108, durvalumab demonstrated clinical activity and durable responses in both PD-L1-high and PD-L1-low/negative subgroups, although objective response rates tended to be higher in the PD-L1-high subgroup than in the PD-L1-low/negative subgroup. CONCLUSIONS.­: Determination of PD-L1 expression in urothelial carcinoma patients using the Ventana PD-L1 (SP263) assay was precise, highly reproducible, and clinically relevant.

12.
Asian J Neurosurg ; 13(3): 636-639, 2018 Jul-Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30283517

RESUMO

Background: Traumatic brain injury (TBI) is the leading cause of deaths worldwide. The morbidity and mortality due to TBI are related to both primary as well as secondary insults. The patients who survive from the primary insults, some may still have long-term disabilities. Most of these outcomes are related to the high incidence of prehospital secondary brain insults. Knowledge of these variables and timely management of the disease at the prehospital level can significantly improve the outcome and decrease the mortality. Aims: The present study is aimed to evaluate the current status of prehospital care, prehospital factors, epidemiological characteristics, and outcome of TBI patients at a Level 1 trauma center. Material and Methods: It is a prospective observational study of 830 cases of TBI, done from November 15, 2015, to March 15, 2016, in the Department of Neurosurgery, Institute of Traumatology, SMS Medical College, Jaipur, Rajasthan, India. Results: Analysis of data revealed that the incidence of TBI in males is four times higher than females. Most patients are in the age group of 21-30 years (30.24%) followed by 31-40 years (18.55%). Road traffic injury (69.52%) is the most common mode of injury in the age group of 21-30 years followed by injury due to fall (22.77%) which mostly affects the age group of 0-10 years (72.64%) and 61-70 years (38.6%). Analysis of different factors revealed that age is significantly correlated with the outcome having P = 0.016. Glasgow Coma Scale, saturation of peripheral oxygen, systolic blood pressure at admission are also significantly correlated with the outcome having P < 0.001, P < 0.001, and P < 0.001, respectively. Conclusion: It is evident from the study that the factors which affect the outcome of a TBI are influenced by prehospital care, and thus prehospital management of the TBIs can definitely improve the outcomes.

13.
Asian J Neurosurg ; 13(3): 867-869, 2018 Jul-Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30283569

RESUMO

Noncompressive myelopathy of lower dorsal spine secondary to trauma is a rare event. We report a case of delayed paraplegia in a patient with a history of road traffic accident. The X-ray of dorsolumbar spine did not show any abnormality. Magnetic resonance imaging of dorsolumbar spine was performed which showed the presence of central T2-weighted hyperintensities from D10-D11 to D12-L1 level. No associated bony injury was documented, and the integrity of the spinal canal was maintained. The patient was managed conservatively with bed rest, and steroids were given. However, the patient did not show any signs of improvement after 1 month of follow-up.

14.
Indian J Pediatr ; 2018 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-30209734

RESUMO

Schmid type metaphyseal chondrodysplasia (SMCD) is a rare skeletal dysplasia, characterized by short stature, short limbs, bowing of the legs, and radiographic features of metaphyseal irregularities with fraying and splaying, more severe at the knee. It is caused by mutations of the COL10A1 gene. The authors present an Indian patient with a novel COL10A1 gene mutation.

15.
Indian J Otolaryngol Head Neck Surg ; 70(3): 366-373, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30211091

RESUMO

To evaluate the outcome and initial hurdles of transaxillary robotic thyroidectomy in the Indian subcontinent. A total of seven (n = 7) patients were operated from August 2016 to February 2017. Ultrasonography was used as a tool to decide the size of thyroid lobe and fine needle aspiration cytology for the type of lesion. All patients underwent ipsilateral brachial plexus nerve conduction studies preoperatively. Two arm positions were evaluated. The robot was docked at the contralateral side of the surgical field. Before discharge from hospital, all patients were given a questionnaire evaluate outcome. Set 1 was answered on the day of discharge and Set 2 at one-month follow up. The most common pathology in our case series was colloid goiter (n = 4) followed by follicular lesion (n = 3). The mean console time was 167 min, with initial two cases taking more than 200 min. The maximum and minimum length of the axillary tunnel was 16 and 27 cm respectively. There was no difference with regard to complication rate with either arm position. None of the patients developed brachial plexus injury and was confirmed by normal nerve conduction study done on postoperative day three. In our experience with transaxillary robotic thyroidectomy, the problems we faced in our population were unique considering the varied physical parameters. Use of malleable retractors comes handy in these situation and we recommend the use of these over the rigid ones. Though both the arm positions had similar outcomes, the one with sideways position was more favorable.

16.
Clin Cancer Res ; 2018 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-30093454

RESUMO

Purpose: Immunotherapy has transformed the treatment of many solid tumors, with some patients deriving long-term benefit, but how to identify such patients remains unclear. Somatic mutations detected in circulating tumor DNA (ctDNA) from plasma can be an indicator of disease progression, response to therapy, and clonality of primary and metastatic lesions. Hence, ctDNA analysis can provide a valuable noninvasive and tumor-specific marker for longitudinal monitoring of tumor burden. We explored the use of ctDNA to predict survival on durvalumab, an anti-PD-L1 therapy.Experimental Design: Variant allele frequencies (VAF) of somatic mutations in 73 genes were assessed in ctDNA using targeted sequencing in a discovery cohort consisting of 28 patients with non-small cell lung cancer (NSCLC) and two validation NSCLC and urothelial cancer (UC) cohorts of 72 and 29 patients, respectively, to correlate ctDNA changes with clinical outcomes.Results: Somatic variants were detected in 96% of patients. Changes in VAF preceded radiographic responses, and patients with reduction in VAF at 6 weeks had significantly greater reduction in tumor volume, with longer progression-free and overall survival.Conclusions: ctDNA VAF changes are strongly correlated with duration of treatment, antitumor activity, and clinical outcomes in NSCLC and UC. Early on-treatment reduction in ctDNA VAF may be a useful predictor of long-term benefit from immunotherapy. Prospective studies should validate these findings and the value of utilizing early changes in ctDNA for therapeutic decision making by identifying nonresponders to checkpoint inhibitor monotherapies and guiding combination therapies. Clin Cancer Res; 1-11. ©2018 AACR.

17.
Allergy Rhinol (Providence) ; 9: 2152656718764199, 2018 Jan-Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29977653

RESUMO

Background: Ever since its characterization in the 1970s, allergic fungal rhinosinusitis (AFRS) has been the subject of much controversy, especially regarding its pathogenesis. In this study, we analyzed the differential expression of genes that encode protease-activated receptors (PAR) in patients with AFRS and patients with chronic rhinosinusitis, and tried to understand the pathogenic basis of this disease. Objective: To analyze the differential expression of PAR genes in patients with AFRS and in patients with chronic rhinosinusitis. Methods: Mucosa from ethmoid sinuses of 51 patients (tests and controls) was biopsied and evaluated for messenger RNA expression of PAR genes by using reverse transcriptase-polymerase chain reaction. Each of the four PAR genes, i.e., par1, par2, par3 and par4 was amplified, the final gene products were run on 1.8% agarose gel and analyzed by densitometry to calculate differential expression. The significance level was determined as p ≤ 0.05. Results: It was observed that the expressions of all four par genes were higher in the test samples compared with the controls, but statistical significance was achieved only for par1 (p=0.004) and par2 (p=0.05). Comparative expression of the four PAR genes was also performed within the test and control groups, and a statistically significant difference was seen between par1 and par2 (p=0.007), par1 and par3 (p=0.029), par1 and par4 (p=0.0001), par2 and par4 (p=0.002), and par3 and par4 (p=0.009) in the test group. In the control group as well, par1, par2, and par3 exhibited a higher expression compared with par4 but the difference was significant between par3 and par4 genes only. Conclusion: Patients with AFRS expressed increased levels of PAR genes in their nasal mucosa, and, of the four PAR genes, a higher expression of par1, par2, and par3 was observed in both the groups compared with par4. This information contributes toward our understanding of pathogenesis and possibly treatment of AFRS.

18.
Artigo em Inglês | MEDLINE | ID: mdl-29869925

RESUMO

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.

19.
Clin Cancer Res ; 24(16): 3857-3866, 2018 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-29716923

RESUMO

Purpose: To identify a predictive biomarker for durvalumab, an anti-programmed death ligand 1 (PD-L1) mAb.Experimental Design: RNA sequencing of 97 advanced-stage non-small cell lung carcinoma (NSCLC) biopsies from a nonrandomized phase Ib/II clinical trial (1108/NCT01693562) were profiled to identify a predictive signature; 62 locally advanced or metastatic urothelial cancer tumors from the same study were profiled to confirm predictive utility of the signature. Thirty NSCLC patients provided pre- and posttreatment tumors for messenger RNA (mRNA) analysis. NSCLC with ≥25% tumor cells and urothelial cancer with ≥25% tumor or immune cells stained for PD-L1 at any intensity were scored PD-L1 positive (PD-L1+). Kaplan-Meier and Cox proportional hazards analyses were used to adjust for gender, age, prior therapies, histology, ECOG status, liver metastasis, and smoking. Tumor mutation burden (TMB) was calculated using data from The Cancer Genome Atlas (TCGA).Results: In the NSCLC discovery set, a four-gene IFNγ-positive (IFNγ+) signature comprising IFNγ, CD274, LAG3, and CXCL9 was associated with higher overall response rates, longer median progression-free survival, and overall survival compared with signature-low patients. IFNγ+-signature NSCLC patients had improved survival regardless of IHC PD-L1 status. These associations were replicated in a urothelial cancer cohort. The IFNγ+ signature was induced 2-fold (P = 0.003) by durvalumab after 8 weeks of therapy in patients with NSCLC, and baseline signature was associated with TMB but not survival in TCGA data.Conclusions: The IFNγ+ mRNA signature may assist in identifying patients with improved outcomes with durvalumab, independent of PD-L1 assessed by IHC. Clin Cancer Res; 24(16); 3857-66. ©2018 AACR.

20.
J Indian Assoc Pediatr Surg ; 23(2): 106-108, 2018 Apr-Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29681705

RESUMO

Cloacal malformation is a rare entity and is invariably referred only to females. We are reporting a very rare case of cloacal malformation variant in a 6-day-old male neonate who presented with absent anal opening along with passage of urine and meconium from an abnormal opening in the perineum.

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