Statistical and spatio-temporal analyses of noise pollution level and its health impact.

Due to rapid urbanization and exponential growth in transportation; traffic noise has become a major area of concern. Noise not only disturbs our day-to-day life but also have severe adverse health effects over humans which further may lead to mortality. This paper focuses on the behavior of noise levels of Lucknow city over a decade and establishes its correlation with impact on human health in terms of annoyance and sleep disturbance. Apart from Leq, different noise parameters like L10, L50, L90, Traffic Noise Index (TNI), Noise Pollution Index (NPI), and Noise Climate (NC) have also been analyzed to understand the variation of noise. At all the locations, the noise level has been found exceeding their prescribed standards during day time and night time except at Amausi. Out of nine locations, TNI was found to be exceeding at three locations during day time and NPI exceeding at one location. However, during night time both values of TNI and NPL were observed within the limit at all the locations. From the noise map of the city during day time and night time, among all sampling locations, Charbagh has been found to be worst affected by noise pollution. A strong positive correlation has been observed among the total population, vehicular count, and day and night time noise data, which directly contribute to a higher percentage of sleep disturbance and annoyance among residents. Due to the increase in noise levels over a period of time, almost four times the population get affected by high annoyance and almost double the population get affected by sleep disturbance.

Synbiotics as Supplemental Therapy for the Alleviation of Chemotherapy-Associated Symptoms in Patients with Solid Tumours.

Chemotherapy is still the first line of treatment for most cancer patients. Patients receiving chemotherapy are generally prone to infections, which result in complications, such as sepsis, mucositis, colitis, and diarrhoea. Several nutritional approaches have been trialled to counter the chemotherapy-associated side effects in cancer patients, but none have yet been approved for routine clinical use. One of the approaches to reduce or avoid chemotherapy-associated complications is to restore the gut microbiota. Gut microbiota is essential for the healthy functioning of the immune system, metabolism, and the regulation of other molecular responses in the body. Chemotherapy erodes the mucosal layer of the gastrointestinal tract and results in the loss of gut microbiota. One of the ways to restore the gut microbiota is through the use of probiotics. Probiotics are the 'good' bacteria that may provide health benefits if consumed in appropriate amounts. Some studies have highlighted that the consumption of probiotics in combination with prebiotics, known as synbiotics, may provide better health benefits when compared to probiotics alone. This review discusses the different nutritional approaches that have been studied in an attempt to combat chemotherapy-associated side effects in cancer patients with a particular focus on the use of pre-, pro- and synbiotics.

Retinal defocus in myopes wearing dual-focus zonal contact lenses.

PURPOSE: To evaluate the refractive impact of dual-focus (DF) myopia control contact lenses (CLs) on accommodating young myopic adults. METHODS: Phase 1: accommodative accuracy was assessed in 40 myopic participants. Phase 2: a subset of four subjects who demonstrated accurate accommodation and six who chronically underaccommodated were fitted with single vision (SV, Proclear 1 day) and centre-distance DF myopia control CLs (MiSight 1 day) with approximately +2.00 D of additional power in two surrounding annular zones. While binocularly viewing high contrast characters at 4.00, 1.00, 0.50, 0.33, 0.25 and 0.20 m, aberrometry data were captured across the central ±30° of the horizontal retina. Local refractive errors were pooled for each area of the pupil covered by the central distance or first annular defocus zone of the DF CLs. RESULTS: In the "good" accommodator group fitted with SV CLs, accommodative lags were generally absent except at the closest viewing distance (mean errors: -0.09 ± 0.22 D, -0.12 ± 0.26 D, -0.05 ± 0.37 D and +0.38 ± 0.54 D for -2.00, -3.00, -4.00 and -5.00 D target vergences, respectively) but significantly larger in the "poor" accommodating participants (+0.81 ± 0.21 D, +0.97 ± 0.27 D, +1.18 ± 0.39 D, +1.47 ± 0.55 D). For most viewing distances, hyperopic defocus observed in the region of the pupil covered by the first annular zone was replaced with myopic defocus when fitted with the DF CLs. Myopic defocus created by the first annular region was present across the central 30° of the retina. CONCLUSIONS: Some young adult myopes chronically experience high levels of hyperopic defocus when viewing near targets, which was replaced by myopic defocus in the annular part of the pupil covered by the treatment zones when fitted with a centre-distance myopia control DF CL.

Genomic clustering analysis identifies molecular subtypes of thymic epithelial tumors independent of World Health Organization histologic type.

Further characterization of thymic epithelial tumors (TETs) is needed. Genomic information from 102 evaluable TETs from The Cancer Genome Atlas (TCGA) dataset and from the IU-TAB-1 cell line (type AB thymoma) underwent clustering analysis to identify molecular subtypes of TETs. Six novel molecular subtypes (TH1-TH6) of TETs from the TCGA were identified, and there was no association with WHO histologic subtype. The IU-TAB-1 cell line clustered into the TH4 molecular subtype and in vitro testing of candidate therapeutics was performed. The IU-TAB-1 cell line was noted to be resistant to everolimus (mTORC1 inhibitor) and sensitive to nelfinavir (AKT1 inhibitor) across the endpoints measured. Sensitivity to nelfinavir was due to the IU-TAB-1 cell line's gain-of function (GOF) mutation in PIK3CA and amplification of genes observed from array comparative genomic hybridization (aCGH), including AURKA, ERBB2, KIT, PDGFRA and PDGFB, that are known upregulate AKT, while resistance to everolimus was primarily driven by upregulation of downstream signaling of KIT, PDGFRA and PDGFB in the presence of mTORC1 inhibition. We present a novel molecular classification of TETs independent of WHO histologic subtype, which may be used for preclinical validation studies of potential candidate therapeutics of interest for this rare disease.

Computational Biological Modeling Identifies PD-(L)1 Immunotherapy Sensitivity Among Molecular Subgroups of KRAS-Mutated Non-Small-Cell Lung Cancer.

PURPOSE: KRAS-mutated (KRASMUT) non-small-cell lung cancer (NSCLC) is emerging as a heterogeneous disease defined by comutations, which may confer differential benefit to PD-(L)1 immunotherapy. In this study, we leveraged computational biological modeling (CBM) of tumor genomic data to identify PD-(L)1 immunotherapy sensitivity among KRASMUT NSCLC molecular subgroups. MATERIALS AND METHODS: In this multicohort retrospective analysis, the genotype clustering frequency ranked method was used for molecular clustering of tumor genomic data from 776 patients with KRASMUT NSCLC. These genomic data were input into the CBM, in which customized protein networks were characterized for each tumor. The CBM evaluated sensitivity to PD-(L)1 immunotherapy using three metrics: programmed death-ligand 1 expression, dendritic cell infiltration index (nine chemokine markers), and immunosuppressive biomarker expression index (14 markers). RESULTS: Genotype clustering identified eight molecular subgroups and the CBM characterized their shared cancer pathway characteristics: KRASMUT/TP53MUT, KRASMUT/CDKN2A/B/CMUT, KRASMUT/STK11MUT, KRASMUT/KEAP1MUT, KRASMUT/STK11MUT/KEAP1MUT, KRASMUT/PIK3CAMUT, KRAS MUT/ATMMUT, and KRASMUT without comutation. CBM identified PD-(L)1 immunotherapy sensitivity in the KRASMUT/TP53MUT, KRASMUT/PIK3CAMUT, and KRASMUT alone subgroups and resistance in the KEAP1MUT containing subgroups. There was insufficient genomic information to elucidate PD-(L)1 immunotherapy sensitivity by the CBM in the KRASMUT/CDKN2A/B/CMUT, KRASMUT/STK11MUT, and KRASMUT/ATMMUT subgroups. In an exploratory clinical cohort of 34 patients with advanced KRASMUT NSCLC treated with PD-(L)1 immunotherapy, the CBM-assessed overall survival correlated well with actual overall survival (r = 0.80, P < .001). CONCLUSION: CBM identified distinct PD-(L)1 immunotherapy sensitivity among molecular subgroups of KRASMUT NSCLC, in line with previous literature. These data provide proof-of-concept that computational modeling of tumor genomics could be used to expand on hypotheses from clinical observations of patients receiving PD-(L)1 immunotherapy and suggest mechanisms that underlie PD-(L)1 immunotherapy sensitivity.

Optical and imaging properties of a novel multi-segment spectacle lens designed to slow myopia progression.

PURPOSE: High sampling density optical metrology combined with pupil- and image-plane numerical analyses were applied to evaluate a novel spectacle lens containing multiple small zones designed to slow myopia progression. METHODS: High-resolution aberrometry (ClearWave, www.lumetrics.com) was used to sample wavefront slopes of a novel spectacle lens, Defocus Incorporated Multiple Segments (DIMS) (www.hoya.com), incorporating many small, positive-powered lenslets in its periphery. Using wavefront slope and error maps, custom MATLAB software ('Indiana Wavefront Analyzer') was used to compute image-plane point-spread functions (PSF), modulation transfer functions (MTF), simulated images and power distributions created by the dual-focus optic for different pupil sizes and target vergences. RESULTS: Outside of a central 10 mm zone containing single distance optical power, a hexagonal array of small 1 mm lenslets with nearest-neighbour separations of 0.5 mm were distributed over the lens periphery. Sagittal and curvature-based measures of optical power imperfectly captured the consistent +3.50 D add produced by the lenslets. Image plane simulations revealed multiple PSFs and poor image quality at the lenslet focal plane. Blur at the distance optic focal plane was consistent with a combination of diffraction blur from the distance optic and the approximately +3.50 D of defocus from the 1 mm diameter near optic zones. CONCLUSION: Converging the defocused beams generated by the multiple small (1 mm diameter) lenslets to a blurred image at the distance focal plane produced a blur magnitude determined by the small lenslet diameter and not the overall pupil diameter. The distance optic located in between the near-add lenslets determines the limits of the optical quality achievable by the lens. When compared to the optics of a traditional concentric-zone dual-focus contact lens, the optics of the DIMS lens generates higher-contrast images at low spatial frequencies (<7 cycles per degree), but lower-contrast at high spatial frequencies.

Anti-Heartburn Effects of Sugar Cane Flour: A Double-Blind, Randomized, Placebo-Controlled Study.

Gastroesophageal reflux disease (GERD) affects approximately 20% of Australians. Patients suffer a burning sensation known as heartburn due to the movement of acidic stomach content into the esophagus. There is anecdotal evidence of the effectiveness of prebiotic sugarcane flour in controlling symptoms of GERD. This pilot study aimed to investigate the effectiveness of a prebiotic sugarcane flour in alleviating symptoms in medically-diagnosed GERD patients. This pilot study was a single center, double-blinded, placebo-controlled randomized trial conducted on 43 eligible participants. The intervention group (n = 22) were randomized to receive 3 g of sugarcane flour per day, and the control group (n = 21) received 3 g of cellulose placebo per day. Symptoms of gastroesophageal reflux disease were assessed before and after three weeks treatment using the validated Gastroesophageal Reflux Disease-Health Related Quality of Life questionnaire (GERD-HRQL). After three weeks there were significant differences in symptoms for heartburn, regurgitation, and total symptoms scores (p < 0.05) between the sugarcane flour and placebo. Mean GERD-HRQL scores increased in the placebo group for regurgitation (mean increase 1.7; 95% CI 0.23 to 3.2; p = 0.015) and total symptom scores (2.9; 95% CI 0.26 to 5.7; p = 0.033). In contrast, there were significant reductions in heartburn (mean decrease -2.2; 95% CI -4.2 to -0.14; p = 0.037) and total symptom scores (-3.7; 95% CI -7.2 to -0.11; p = 0.044) in the intervention group. This pilot study has shown significant positive effects of sugarcane flour in the reduction of GERD symptoms, and a larger randomized controlled trial is warranted.

Prediction of Outcomes with a Computational Biology Model in Newly Diagnosed Glioblastoma Patients Treated with Radiation Therapy and Temozolomide.

PURPOSE: Precision medicine has been most successful in targeting single mutations, but personalized medicine using broader genomic tumor profiles for individual patients is less well developed. We evaluate a genomics-informed computational biology model (CBM) to predict outcomes from standard treatments and to suggest novel therapy recommendations in glioblastoma (GBM). METHODS AND MATERIALS: In this retrospective study, 98 patients with newly diagnosed GBM undergoing surgery followed by radiation therapy and temozolomide at a single institution with available genomic data were identified. Incorporating mutational and copy number aberration data, a CBM was used to simulate the response of GBM tumor cells and generate efficacy predictions for radiation therapy (RTeff) and temozolomide (TMZeff). RTeff and TMZeff were evaluated for association with overall survival and progression-free survival in a Cox regression model. To demonstrate a CBM-based individualized therapy strategy, treatment recommendations were generated for each patient by testing a panel of 45 central nervous system-penetrant US Food and Drug Administration-approved agents. RESULTS: High RTeff scores were associated with longer survival on univariable analysis (P < .001), which persisted after controlling for age, extent of resection, performance status, MGMT, and IDH status (P = .017). High RTeff patients had a longer overall survival compared with low RTeff patients (median, 27.7 vs 14.6 months). High TMZeff was also associated with longer survival on univariable analysis (P = .007) but did not hold on multivariable analysis, suggesting an interplay with MGMT status. Among predictions of the 3 most efficacious combination therapies for each patient, only 2.4% (7 of 294) of 2-drug recommendations produced by the CBM included TMZ. CONCLUSIONS: CBM-based predictions of RT and TMZ effectiveness were associated with survival in patients with newly diagnosed GBM treated with those therapies, suggesting a possible predictive utility. Furthermore, the model was able to suggest novel individualized monotherapies and combinations. Prospective evaluation of such a personalized treatment strategy in clinical trials is needed.

Validation of a Clinical Aberrometer Using Pyramidal Wavefront Sensing.

SIGNIFICANCE: Measurement of ocular aberrations is a critical component of many optical corrections. PURPOSE: This study examines the accuracy and repeatability of a newly available high-resolution pyramidal wavefront sensor-based aberrometer (Osiris by Costruzione Strumenti Oftalmici, Firenze, Italy). METHODS: An engineered model eye and a dilated presbyopic eye were used to assess accuracy and repeatability of aberration measurements after systematic introduction of lower- and higher-order aberrations with calibrated trial lenses (sphere +10.00 to -10.00 D, and astigmatic -4.00 and -2.00 D with axis 180, 90, and 45°) and phase plates (-0.57 to 0.60 µm of Seidel spherical aberration defined over a 6-mm pupil diameter). Osiris aberration measurements were compared with those acquired on a previously calibrated COAS-HD aberrometer for foveal and peripheral optics both with and without multizone dual-focus contact lenses. The impact of simulated axial and lateral misalignment was evaluated. RESULTS: Root-mean-square errors for paraxial sphere (corneal plane), cylinder, and axis were, respectively, 0.07, 0.11 D, and 1.8° for the engineered model and 0.15, 0.26 D, and 2.7° for the presbyopic eye. Repeatability estimates (i.e., standard deviation of 10 repeat measures) for the model and presbyopic eyes were 0.026 and 0.039 D for spherical error. Root-mean-square errors of 0.01 and 0.02 µm, respectively, were observed for primary spherical aberration and horizontal coma (model eye). Foveal and peripheral measures of higher- and lower-order aberrations measured with the Osiris closely matched parallel data collected with the COAS-HD aberrometer both with and without dual-focus zonal bifocal contact lenses. Operator errors of focus and alignment introduced changes of 0.018 and 0.02 D/mm in sphere estimates. CONCLUSIONS: The newly available clinical pyramidal aberrometer provided accurate and repeatable measures of lower- and higher-order aberrations, even in the challenging but clinically important cases of peripheral retina and multifocal optics.

Sequential azacitidine and lenalidomide for patients with relapsed and refractory acute myeloid leukemia: Clinical results and predictive modeling using computational analysis.

BACKGROUND: Patients with relapsed and refractory (R/R) acute myeloid leukemia (AML) have limited treatment options. Genomically-defined personalized therapies are only applicable for a minority of patients. Therapies without identifiable targets can be effective but patient selection is challenging. The sequential combination of azacitidine with high-dose lenalidomide has shown activity; we aimed to determine the efficacy of this genomically-agnostic regimen in patients with R/R AML, with the intention of applying sophisticated methods to predict responders. METHODS: Thirty-seven R/R AML/myelodysplastic syndrome patients were enrolled in a phase 2 study of azacitidine with lenalidomide. The primary endpoint was complete remission (CR) and CR with incomplete blood count recovery (CRi) rate. A computational biological modeling (CBM) approach was applied retrospectively to predict outcomes based on the understood mechanisms of azacitidine and lenalidomide in the setting of each patients' disease. FINDINGS: Four of 37 patients (11%) had a CR/CRi; the study failed to meet the alternative hypothesis. Significant toxicity was observed in some cases, with three treatment-related deaths and a 30-day mortality rate of 14%. However, the CBM method predicted responses in 83% of evaluable patients, with a positive and negative predictive value of 80% and 89%, respectively. INTERPRETATION: Sequential azacitidine and high-dose lenalidomide is effective in a minority of R/R AML patients; it may be possible to predict responders at the time of diagnosis using a CBM approach. More efforts to predict responses in non-targeted therapies should be made, to spare toxicity in patients unlikely to respond and maximize treatments for those with limited options.

Predictive simulation approach for designing cancer therapeutic regimens with novel biological mechanisms.

Introduction Ursolic acid (UA) is a pentacyclic triterpene acid present in many plants, including apples, basil, cranberries, and rosemary. UA suppresses proliferation and induces apoptosis in a variety of tumor cells via inhibition of nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB). Given that single agent therapy is a major clinical obstacle to overcome in the treatment of cancer, we sought to enhance the anti-cancer efficacy of UA through rational design of combinatorial therapeutic regimens that target multiple signaling pathways critical to carcinogenesis. Methodology Using a predictive simulation-based approach that models cancer disease physiology by integrating signaling and metabolic networks, we tested the effect of UA alone and in combination with 100 other agents across cell lines from colorectal cancer, non-small cell lung cancer and multiple myeloma. Our predictive results were validated in vitro using standard molecular assays. The MTT assay and flow cytometry were used to assess cellular proliferation. Western blotting was used to monitor the combinatorial effects on apoptotic and cellular signaling pathways. Synergy was analyzed using isobologram plots. Results We predictively identified c-Jun N-terminal kinase (JNK) as a pathway that may synergistically inhibit cancer growth when targeted in combination with NFκB. UA in combination with the pan-JNK inhibitor SP600125 showed maximal reduction in viability across a panel of cancer cell lines, thereby corroborating our predictive simulation assays. In HCT116 colon carcinoma cells, the combination caused a 52% reduction in viability compared with 18% and 27% for UA and SP600125 alone, respectively. In addition, isobologram plot analysis reveals synergy with lowered doses of the drugs in combination. The combination synergistically inhibited proliferation and induced apoptosis as evidenced by an increase in the percentage sub-G1 phase cells and cleavage of caspase 3 and poly ADP ribose polymerase (PARP). Combination treatment resulted in a significant reduction in the expression of cyclin D1 and c-Myc as compared with single agent treatment. Conclusions Our findings underscore the importance of targeting NFκB and JNK signaling in combination in cancer cells. These results also highlight and validate the use of predictive simulation technology to design therapeutics for targeting novel biological mechanisms using existing or novel chemistry.

Table Tilt Versus Pelvic Tilt Position for Intrauterine Resuscitation during Spinal Anaesthesia for Caesarian Section.

BACKGROUND: This study was undertaken to compare the effects on intrauterine resuscitation by table tilt versus pelvic tilt position after spinal anaesthesia for Caesarian Section. PATIENTS #ENTITYSTARTX00026; METHODS: FIFTY ASA I AND II PATIENTS WHO FULFILLED THE ELIGIBILITY CRITERIA WERE ENROLLED IN THE STUDY AND WERE DIVIDED INTO TWO GROUPS: group W (Pelvic tilt with wedge under right hip and group L- (15(0)left lateral table tilt) and received spinal anaesthesia. The following parameters were recorded. Heart rate (HR), mean arterial pressure (MAP) at baseline, 2mins, 5 min and then 5 min thereafter. Mean height of block, Total no. of segments blocked, Onset Time of sensory block (in Minutes), ephedrine doses, incidence of hypotension & bradycardia, APGAR score at 1& 5 Minutes. RESULTS: The decrease in MAP was much more in wedged position as compared to table tilt position also the incidence of hypotension was 40% in wedged position as compared to 12% in table tilt position. Mean height of block, Total no. of segments blocked, and boluses of inj. ephedrine used were more in the wedged position than in table tilt position. CONCLUSION: Wedge placement caused increased incidence of hypotension and higher blockade after spinal anaesthesia as compared to left lateral table tilt position, there was no adverse effects on foetus and patients tolerated wedge better than left lateral table tilt position. Also surgery was easier to perform after wedge placement.

Classification of elderly as fallers and non-fallers using Centre of Pressure velocity.

Falls are a leading cause of death in the elderly. One of the most common methods of predicting falls is to evaluate balance using force plate measurement of the Centre of Pressure (COP) displacement. This signal, known as a stabilogram, can be decomposed into movement in anteroposterior (AP) and mediolateral (ML) directions. It has been suggested that studying the velocity of COP displacement could lead to new insights into fall risk. The aim of this study was to attempt to classify elderly fallers and non-fallers, as well as control subjects based on COP velocity measurements. Three groups of 10 subjects (controls, elderly fallers, and elderly non-fallers) were compared. Discriminant function analysis was able to correctly classify 90% of the subjects based only on COP velocity measurements. Further work is needed to determine whether this parameter might be of use in longitudinal measurement of fall risk in home-dwelling elderly.