Enhancing the shelf life of chevon Seekh Kabab using chitosan edible film and Cinnamomum zeylanicum essential oil.

Chevon Seekh Kabab is a popular meat product of India. However, due to high protein and moisture content it undergoes quick microbial spoilage and oxidative reactions leading to lower shelf life. The combination of chitosan edible film and cinnamon essential oil (CEO) was chosen to remediate this problem because of its antimicrobial and antioxidative effect. Control and chitosan edible film with CEO coated chevon Seekh Kabab samples were stored at 4 °C. The physicochemical (pH, TBARS, TVBN, moisture, colour), microbiological (APC, psychrophilic, coliform and Staphylococcal count) and sensory attributes were evaluated over a 30 days period. The maximum shelf life of 27 days was observed when 2% chitosan edible film with 0.3% CEO was coated over samples. A reduction in moisture, L* value, a* value and sensory scores along with an increase in pH, TVBN, TBARS, b* value and microbiological parameters were observed during the storage period. Reaction kinetics for the physicochemical and microbiological parameters was also established. The physicochemical, microbiological and sensory parameters were within prescribed limits till spoilage in the treated sample. This investigation may aid researchers working on scaling up of processing and preservation of Seekh Kabab.

Triploid genetic algorithm for convolutional neural network-based diagnosis of mild cognitive impairment.

The diagnosis of mild cognitive impairment (MCI), which is deemed a formative phase of dementia, may greatly assist clinicians in delaying its headway toward dementia. This article proposes a deep learning approach based on a triploid genetic algorithm, a proposed variant of genetic algorithms, for classifying MCI converts and non-converts using structural magnetic resonance imaging data. It also explores the effect of the choice of activation functions and that of the selection of hyper-parameters on the performance of the model. The proposed work is a step toward automated convolutional neural networks. The performance of the proposed method is measured in terms of accuracy and empirical studies exhibit the preeminence of our proposed method over the existing ones. The proposed model results in a maximum accuracy of 0.97961. Thus, it may contribute to the effective diagnosis of MCI and may prove important in clinical settings.

Development and application of a triplex-PCR assay for rapid detection of methicillin-resistant Staphylococcus aureus from pigs.

A triplex-PCR assay was developed and evaluated for rapid detection of methicillin-resistant Staphylococcus aureus (MRSA) recovered from various biological samples of pig. Three sets of primers were designed to target mecA, 16S rRNA and nuc genes of MRSA. The specific amplification generated three bands on agarose gel, with sizes 280 bp for mecA, 654 bp for 16S rRNA and 481 bp for nuc, respectively. A potential advantage of the PCR assay is its sensitivity with a detection limit of 102  CFU per ml of bacteria. In all, 79 MRSA isolates recovered from various samples of pigs were subjected to the amplification by the triplex-PCR assay and all the isolates yielded three bands corresponding to the three genes under this study. No false-positive amplification was observed, indicating the high specificity of the developed triplex-PCR assay. This assay will be a useful and powerful method for differentiation of MRSA from methicillin-sensitive S. aureus, coagulase-negative methicillin-resistant staphylococci and coagulase-negative methicillin-sensitive staphylococci.

Jamun fruit (Syzgium cumini) skin extract based indicator for monitoring chicken patties quality during storage.

Natural plant pigment, anthocyanins have the capability to change its color with the change of its structure influenced by changing pH. This feature of anthocyanin has been harnessed to design a meat products quality indicator. In the present experiment anthocyanin rich Jamun fruit (Syzgium cumini) skin extract was used to develop quality indicator by immobilizing on filter paper strips with the purpose of application in chicken patties packets stored at refrigeration temperature (4 ± 1 °C). The indicator changed its color from violet to yellow due to changed pH in it when it was attached inside packet of chicken patties during storage, due to reaction with volatile basic compounds generated from meat. During storage for 21 days, various changes in quality attributes of chicken patties viz., pH, Total volatile basic nitrogen (TVBN), ammonia level, color value, sensory attributes and microbial evaluation were estimated. The pH decreased (P < 0.5) from 6.22 to 6.04. TVBN and ammonia and level increased significantly (P < 0.5) throughout storage. Redness, yellowness, hue and chroma value gradually changed during storage. Sensory scores also decreased significantly (P < 0.5). Microbial count also increased (P < 0.5) during this time. The experiment showed that, during storage, the color changing pattern of quality indicator was well correlated with the changes in quality attributes of chicken meat patties. Therefore, it is expected that the developed quality indicator can provide a convenient, non destructive, visual mean to monitor the meat products quality during refrigerated storage.

Experimental bovine rotavirus-A (RV-A)infection causes intestinal and extra-intestinal pathology in suckling mice.

We describe here the intestinal and extra-intestinal spread of the species A rotavirus (RV-A) and associated lesions thereof in Swiss albino suckling mice pups, inoculated with a bovine-origin RV-A strain. In total, 35 suckling pups were used, wherein 20 pups received cell culture isolated RV-A @ 160 µL (TCID50/ml, 5 × 106.5) per pup [oral 80 µL and intra peritoneal (IP) 80 µL] and served as an infected group, while 15 pups were kept in the control group and inoculated the same volume of phosphate buffered saline (PBS) of neutral pH orally and IP. Four pups from the infected group and 3 from control group were sacrificed at 3, 5, 7, 9 and 12 day post infection (DPI). Of note, infected pups exhibited signs of dullness and restlessness till 5DPI, but none showed diarrhea at any point of time. No appreciable gross lesions were evident in any of the organs, except for mild congestion of the small intestine and yellowish catarrhal smearing over the luminal surface. However, light microscopic lesions in hematoxylin and eosin (H&E) stained sections of jejunum and ileum revealed vacuolation and pyknosis of nuclei of the mature enterocytes, their lysis and detachment, constriction and detachment of villi, mild mononuclear cells (MNCs) infiltration in the lamina propria and mildcell depletion of Peyer's patches and mesenteric lymph nodes (MLN). The extra-intestinal lesions of the cellular degeneration and mild MNCs infiltration were identified in the liver and kidneys from 3 to 7 DPI, but no lesion was seen in the brain. Interstitial thickening with MNCs of lung parenchyma was visible from 3 to 7 DPI. The lesions in the intestine, lymphoid tissues and lungs resolved after 7 DPI. The presence of viral nucleic acid was seen in the intestinal contents from 3 to 5 DPI by using a RV-A specific reverse-transcription polymerase chain reaction (RT-PCR), while in the MLNs and the lungs it could be detected till 5 DPI by both the RT-PCR and direct fluorescent antigen test (dFAT). However, liver, spleen and brain were tested negative for the presence of RV-A by any of these tests. Nonetheless, the persistence of the RV-A was seen in the MLNs even after the absence of virus from the small intestines. Findings here conclusively indicates that heterologous host origin RV-A has an affinity not only to the intestine but also to extra-intestinal tissues like MLNs and lung tissues.

Rapid visual isothermal nucleic acid-based detection assay of Brucella species by polymerase spiral reaction.

AIM: The aim of this study was to develop polymerase spiral reaction (PSR) for rapid, sensitive and specific detection of Brucella sp. METHODS AND RESULTS: Polymerase spiral reaction assay was developed using specifically designed primers targeting the conserved multicopy IS711 gene of Brucella sp. The assay could be performed within 60 min at an isothermal temperature of 64°C. The lower limit of detection of PSR was 11·8 fg and conventional PCR was 1·18 pg of Brucella abortus genomic DNA. Thus, PSR was found to be 100-fold more sensitive than conventional PCR and was comparable to real-time PCR. The specificity of PSR was tested with other non-Brucella bacteria and also with some bacterial and viral pathogens causing abortions. The assay was found to be specific as it did not detect any putative pathogens other than Brucella sp. Fifty-six clinical samples suspected for brucellosis (aborted fetal stomach content) were screened with PSR to validate the applicability of the test to detect Brucella DNA. The same samples were also screened with conventional PCR and real-time PCR. Of 56 samples, 25 samples were found to be positive with both PSR as well as real-time PCR, whereas only 20 samples were found positive with conventional PCR. CONCLUSIONS: The results of this study indicated that the PSR assay is a simple, rapid, sensitive and specific method for the detection of Brucella sp. that may improve diagnostic potential in clinical laboratories or can be used at diagnostic laboratories with minimal infrastructure. SIGNIFICANCE AND IMPACT OF THE STUDY: The PSR assay, because of its simplicity and low cost, can be preferred to other molecular methods in the diagnosis of infectious diseases.

Relevant Feature Selection from a Combination of Spectral-Temporal and Spatial Features for Classification of Motor Imagery EEG.

This paper presents a novel algorithm (CVSTSCSP) for determining discriminative features from an optimal combination of temporal, spectral and spatial information for motor imagery brain computer interfaces. The proposed method involves four phases. In the first phase, EEG signal is segmented into overlapping time segments and bandpass filtered through frequency filter bank of variable size subbands. In the next phase, features are extracted from the segmented and filtered data using stationary common spatial pattern technique (SCSP) that can handle the non- stationarity and artifacts of EEG signal. The univariate feature selection method is used to obtain a relevant subset of features in the third phase. In the final phase, the classifier is used to build adecision model. In this paper, four univariate feature selection methods such as Euclidean distance, correlation, mutual information and Fisher discriminant ratio and two well-known classifiers (LDA and SVM) are investigated. The proposed method has been validated using the publicly available BCI competition IV dataset Ia and BCI Competition III dataset IVa. Experimental results demonstrate that the proposed method significantly outperforms the existing methods in terms of classification error. A reduction of 76.98%, 75.65%, 73.90% and 72.21% in classification error over both datasets and both classifiers can be observed using the proposed CVSTSCSP method in comparison to CSP, SBCSP, FBCSP and CVSCSP respectively.

Comparison of RECIST and iRECIST criteria in patients with advanced lung cancer treated with nivolumab.

Background: Systemic therapy in lung cancer is mainstay of treatment as most patients present in advanced stages, with rising importance of new immunotherapy agents. Purpose: To compare the RECIST 1.1 and the immunotherapy Response Evaluation Criteria in Solid Tumors (iRECISTs) criteria for response assessment in lung cancer patients on immunotherapy. To find the incidence of pseudoprogression and associated imaging patterns. Material and Methods: Retrospective study in 28 patients treated with immunotherapy for advanced metastatic NSCLC. End points were progression-free survival (PFS) and overall survival (OS). Response assessments were separately tabulated according to RECIST 1.1 and iRECIST and classified into dichotomous groups of responders and nonresponders. Agreement in assessments between RECIST 1.0 and iRECIST examined using Cohen kappa (κ) coefficient with 95% confidence intervals. Kaplan-Meier survival analysis was done for PFS and OS. Differences between RECIST 1.1 and iRECIST for both responder and nonresponder were evaluated by the log rank test, Breslow (Generalized Wilcoxon) test, and Tarone-Ware test. Results: Incidence of pseudoprogression was 7% (2/28). The RECIST1.1 and iRECIST were in disagreement in two patients. The agreement between RECIST and iRECIST was almost perfect. The PFS and the OS are significantly longer in duration for responders in comparison to nonresponders for both RECIST and iRECIST and the difference between two assessment criteria is not significant. Conclusion: Although iRECIST aims to monitor treatment more precisely than conventional response criteria, this must be weighed against how infrequent pseudoprogression is and the cost of this therapy, both financially and in the potential delay in changing to a more effective treatment.

Detailed Sub-study Analysis of the SECRAB Trial: Quality of Life, Cosmesis and Chemotherapy Dose Intensity.

AIMS: SECRAB was a prospective, open-label, multicentre, randomised phase III trial comparing synchronous to sequential chemoradiotherapy (CRT). Conducted in 48 UK centres, it recruited 2297 patients (1150 synchronous and 1146 sequential) between 2 July 1998 and 25 March 2004. SECRAB reported a positive therapeutic benefit of using adjuvant synchronous CRT in the management of breast cancer; 10-year local recurrence rates reduced from 7.1% to 4.6% (P = 0.012). The greatest benefit was seen in patients treated with anthracycline-cyclophosphamide, methotrexate, 5-fluorouracil (CMF) rather than CMF. The aim of its sub-studies reported here was to assess whether quality of life (QoL), cosmesis or chemotherapy dose intensity differed between the two CRT regimens. MATERIALS AND METHODS: The QoL sub-study used EORTC QLQ-C30, EORTC QLQ-BR23 and the Women's Health Questionnaire. Cosmesis was assessed: (i) by the treating clinician, (ii) by a validated independent consensus scoring method and (iii) from the patients' perspective by analysing four cosmesis-related QoL questions within the QLQ-BR23. Chemotherapy doses were captured from pharmacy records. The sub-studies were not formally powered; rather, the aim was that at least 300 patients (150 in each arm) were recruited and differences in QoL, cosmesis and dose intensity of chemotherapy assessed. The analysis, therefore, is exploratory in nature. RESULTS: No differences were observed in the change from baseline in QoL between the two arms assessed up to 2 years post-surgery (Global Health Status: -0.05; 95% confidence interval -2.16, 2.06; P = 0.963). No differences in cosmesis were observed (via independent and patient assessment) up to 5 years post-surgery. The percentage of patients receiving the optimal course-delivered dose intensity (≥85%) was not significantly different between the arms (synchronous 88% versus sequential 90%; P = 0.503). CONCLUSIONS: Synchronous CRT is tolerable, deliverable and significantly more effective than sequential, with no serious disadvantages identified when assessing 2-year QoL or 5-year cosmetic differences.

Enhanced depression detection from speech using Quantum Whale Optimization Algorithm for feature selection.

There is an urgent need to detect depression using a non-intrusive approach that is reliable and accurate. In this paper, a simple and efficient unimodal depression detection approach based on speech is proposed, which is non-invasive, cost-effective and computationally inexpensive. A set of spectral, temporal and spectro-temporal features is derived from the speech signal of healthy and depressed subjects. To select a minimal subset of the relevant and non-redundant speech features to detect depression, a two-phase approach based on the nature-inspired wrapper-based feature selection Quantum-based Whale Optimization Algorithm (QWOA) is proposed. Experiments are performed on the publicly available Distress Analysis Interview Corpus Wizard-of-Oz (DAICWOZ) dataset and compared with three established univariate filtering techniques for feature selection and four well-known evolutionary algorithms. The proposed model outperforms all the univariate filter feature selection techniques and the evolutionary algorithms. It has low computational complexity in comparison to traditional wrapper-based evolutionary methods. The performance of the proposed approach is superior in comparison to existing unimodal and multimodal automated depression detection models. The combination of spectral, temporal and spectro-temporal speech features gave the best result with the LDA classifier. The performance achieved with the proposed approach, in terms of F1-score for the depressed class and the non-depressed class and error is 0.846, 0.932 and 0.094 respectively. Statistical tests demonstrate that the acoustic features selected using the proposed approach are non-redundant and discriminatory. Statistical tests also establish that the performance of the proposed approach is significantly better than that of the traditional wrapper-based evolutionary methods.

Natural infection of Delta mutant of SARS-CoV-2 in Asiatic lions of India.

The current pandemic caused by a novel coronavirus (SARS-CoV-2) has underlined the importance of emerging diseases of zoonotic importance. Along with human beings, several species of wild and pet animals have been demonstrated to be infected by SARS-CoV-2, both naturally and experimentally. In addition, with constant emergence of new variants, the species susceptibility might further change which warrants intensified screening efforts. India is a vast and second most populated country, with a habitat of a very diverse range of animal species. In this study we place on record of SARS-CoV-2 infections in three captive Asiatic lions. Detailed genomic characterization revealed involvement of Delta mutant (Pango lineage B.1.617.2) of SARS-CoV-2 at two different locations. Interestingly, no other feline species enclosed in the zoo/park were found infected. The epidemiological and molecular analysis will contribute to the understanding of the emerging mutants of SARS-CoV-2 in wild and domestic animals.

Prediction of HIV-1 protease inhibitory activity of 4-hydroxy-5,6-dihydropyran-2-ones: QSAR study.

Inhibition of human immunodeficiency virus 1 (HIV-1) protease is an important strategy for the treatment of HIV and acquired immune deficiency syndrome (AIDS). Therefore, HIV-1 protease inhibitory activity of dihydropyranone derivatives has been analyzed with different physico-chemical parameters. In the present work, QSAR studies were performed on a series of 4-hydroxy-5,6-dihydropyran-2-ones to explore the physico-chemical parameters responsible for their HIV-1 protease inhibitory activity. Physico-chemical parameters were calculated using WIN CAChe 6.1. Stepwise multiple linear regression analysis was performed to derive QSAR models which were further evaluated for statistical significance and predictive power by internal and external validation. The selected best QSAR model was having correlation coefficient (R) = 0.875 and cross-validated squared correlation coefficient (Q²) = 0.707. The developed significant QSAR model indicates that hydrophobicity of whole molecule and the substituent present at sixth position of dihydropyranones play an important role in the HIV-1 protease inhibitory activities of 4-hydroxy-5,6-dihydropyran-2-ones.

The UK Standardisation of Breast Radiotherapy (START) Trial B of radiotherapy hypofractionation for treatment of early breast cancer: a randomised trial.

BACKGROUND: The international standard radiotherapy schedule for early breast cancer delivers 50 Gy in 25 fractions of 2.0 Gy over 5 weeks, but there is a long history of non-standard regimens delivering a lower total dose using fewer, larger fractions (hypofractionation). We aimed to test the benefits of radiotherapy schedules using fraction sizes larger than 2.0 Gy in terms of local-regional tumour control, normal tissue responses, quality of life, and economic consequences in women prescribed post-operative radiotherapy. METHODS: Between 1999 and 2001, 2215 women with early breast cancer (pT1-3a pN0-1 M0) at 23 centres in the UK were randomly assigned after primary surgery to receive 50 Gy in 25 fractions of 2.0 Gy over 5 weeks or 40 Gy in 15 fractions of 2.67 Gy over 3 weeks. Women were eligible for the trial if they were aged over 18 years, did not have an immediate reconstruction, and were available for follow-up. Randomisation method was computer generated and was not blinded. The protocol-specified principal endpoints were local-regional tumour relapse, defined as reappearance of cancer at irradiated sites, late normal tissue effects, and quality of life. Analysis was by intention to treat. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN59368779. FINDINGS: 1105 women were assigned to the 50 Gy group and 1110 to the 40 Gy group. After a median follow up of 6.0 years (IQR 5.0-6.2) the rate of local-regional tumour relapse at 5 years was 2.2% (95% CI 1.3-3.1) in the 40 Gy group and 3.3% (95% CI 2.2 to 4.5) in the 50 Gy group, representing an absolute difference of -0.7% (95% CI -1.7% to 0.9%)--ie, the absolute difference in local-regional relapse could be up to 1.7% better and at most 1% worse after 40 Gy than after 50 Gy. Photographic and patient self-assessments indicated lower rates of late adverse effects after 40 Gy than after 50 Gy. INTERPRETATION: A radiation schedule delivering 40 Gy in 15 fractions seems to offer rates of local-regional tumour relapse and late adverse effects at least as favourable as the standard schedule of 50 Gy in 25 fractions.

Visualization of tRNA movements on the Escherichia coli 70S ribosome during the elongation cycle.

Three-dimensional cryomaps have been reconstructed for tRNA-ribosome complexes in pre- and posttranslocational states at 17-A resolution. The positions of tRNAs in the A and P sites in the pretranslocational complexes and in the P and E sites in the posttranslocational complexes have been determined. Of these, the P-site tRNA position is the same as seen earlier in the initiation-like fMet-tRNA(f)(Met)-ribosome complex, where it was visualized with high accuracy. Now, the positions of the A- and E-site tRNAs are determined with similar accuracy. The positions of the CCA end of the tRNAs at the A site are different before and after peptide bond formation. The relative positions of anticodons of P- and E-site tRNAs in the posttranslocational state are such that a codon-anticodon interaction at the E site appears feasible.

Direct visualization of A-, P-, and E-site transfer RNAs in the Escherichia coli ribosome.

Transfer RNA (tRNA) molecules play a crucial role in protein biosynthesis in all organisms. Their interactions with ribosomes mediate the translation of genetic messages into polypeptides. Three tRNAs bound to the Escherichia coli 70S ribosome were visualized directly with cryoelectron microscopy and three-dimensional reconstruction. The detailed arrangement of A- and P-site tRNAs inferred from this study allows localization of the sites for anticodon interaction and peptide bond formation on the ribosome.

Incidence of end stage renal disease on renal replacement therapy in Nepal.

BACKGROUND: End stage renal disease patients are treated with dialysis in Nepal. But there is no renal registry to indicate the burden of disease in the country. OBJECTIVES: The objective of this study is to find out the incidence of ESRD on renal replacement therapy and their out come. MATERIALS AND METHODS: It is a retrospective analysis (audit) of all ESRD patients who had received dialysis inside Nepal and had under gone transplantation from 1990 to 1999. The haemodialysis (HD) registry, HD patients file, intermittent peritoneal dialysis (IPD) registry of Bir Hospital, Shree Birendra Hospital, Tribhuwan University Teaching hospital and National Kidney Center were reviewed. Acute renal failure and acute on chronic renal failure were excluded and the demographic profile, dialysis session, dialysis duration and outcome of all ESRD patients were computed. One patient was counted only once in spite of attending more than one center for dialysis. SPSS package was used for analysis. RESULTS: Total number of 1393 ESRD patients received renal replacement therapy (RRT) in the decade. Mean age of patients were 46.7 +/- 16.7 with 70% of ESRD were between 20-60 years age with male: female ratio of 1.8:1. Initial mode of RRT was IPD in 58.2%, HD in 41.7% and pre-emptive transplantation in 0.1% patients. Records of 189 patients could not be found and out of remaining 1208 patients, 85.8% received dialysis for < 3 months, 6% received dialysis for more than a year and 9.5% had undergone kidney transplantation. The incidence of ESRD had increased gradually with 3.4 per million populations (pmp) in 1990 to 11.89 pmp in 1999 with an average annual incidence of 6 pmp and only 0.31% of expected ESRD patients received RRT. CONCLUSION: The incidence of ESRD is increasing but majority discontinue or die within 3 months. Dialysis centers needs to be expanded to different parts of country and prospective studies have to be carried out to fi nd out of cause of ESRD and to institute preventive measures.

The UK Standardisation of Breast Radiotherapy (START) Trial A of radiotherapy hypofractionation for treatment of early breast cancer: a randomised trial.

BACKGROUND: The international standard radiotherapy schedule for breast cancer treatment delivers a high total dose in 25 small daily doses (fractions). However, a lower total dose delivered in fewer, larger fractions (hypofractionation) is hypothesised to be at least as safe and effective as the standard treatment. We tested two dose levels of a 13-fraction schedule against the standard regimen with the aim of measuring the sensitivity of normal and malignant tissues to fraction size. METHODS: Between 1998 and 2002, 2236 women with early breast cancer (pT1-3a pN0-1 M0) at 17 centres in the UK were randomly assigned after primary surgery to receive 50 Gy in 25 fractions of 2.0 Gy versus 41.6 Gy or 39 Gy in 13 fractions of 3.2 Gy or 3.0 Gy over 5 weeks. Women were eligible if they were aged over 18 years, did not have an immediate surgical reconstruction, and were available for follow-up. Randomisation method was computer generated and was not blinded. The protocol-specified principal endpoints were local-regional tumour relapse, defined as reappearance of cancer at irradiated sites, late normal tissue effects, and quality of life. Analysis was by intention to treat. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN59368779. FINDINGS: 749 women were assigned to the 50 Gy group, 750 to the 41.6 Gy group, and 737 to the 39 Gy group. After a median follow up of 5.1 years (IQR 4.4-6.0) the rate of local-regional tumour relapse at 5 years was 3.6% (95% CI 2.2-5.1) after 50 Gy, 3.5% (95% CI 2.1-4.3) after 41.6 Gy, and 5.2% (95% CI 3.5-6.9) after 39 Gy. The estimated absolute differences in 5-year local-regional relapse rates compared with 50 Gy were 0.2% (95% CI -1.3% to 2.6%) after 41.6 Gy and 0.9% (95% CI -0.8% to 3.7%) after 39 Gy. Photographic and patient self-assessments suggested lower rates of late adverse effects after 39 Gy than with 50 Gy, with an HR for late change in breast appearance (photographic) of 0.69 (95% CI 0.52-0.91, p=0.01). From a planned meta-analysis with the pilot trial, the adjusted estimates of alpha/beta value for tumour control was 4.6 Gy (95% CI 1.1-8.1) and for late change in breast appearance (photographic) was 3.4 Gy (95% CI 2.3-4.5). INTERPRETATION: The data are consistent with the hypothesis that breast cancer and the dose-limiting normal tissues respond similarly to change in radiotherapy fraction size. 41.6 Gy in 13 fractions was similar to the control regimen of 50 Gy in 25 fractions in terms of local-regional tumour control and late normal tissue effects, a result consistent with the result of START Trial B. A lower total dose in a smaller number of fractions could offer similar rates of tumour control and normal tissue damage as the international standard fractionation schedule of 50 Gy in 25 fractions.

NEAT: National Epirubicin Adjuvant Trial--toxicity, delivered dose intensity and quality of life.

The NEAT trial reported considerable benefit for ECMF (epirubicin followed by cyclophosphamide, methotrexate and 5-fluorouracil) of 28% for relapse-free survival (RFS) and 30% for overall survival (OS), when compared with classical CMF in early breast cancer. To assess tolerability, toxicity, dose intensity and quality of life (QoL) analyses were undertaken. All 2021 eligible patients had common toxicity criteria (CTC), delivered chemotherapy and supportive treatments details and long-term morbidities recorded. The QoL substudy used multiple validated measures. ECMF produced low CTC scores, although higher than CMF for nausea, vomiting, alopecia, constipation, stomatitis (P<0.001), infection (P=0.001) and fatigue (P=0.03). Supportive treatments required, however, were similar across randomised treatments. On-treatment deaths were more common with CMF (13) than ECMF(5). Optimal course-delivered dose intensity (CDDI > or =85%) was received more often by ECMF patients (83 vs 76%: P=0.0002), and was associated with better RFS (P=0.0006). QoL over 2 years was equivalent across treatments, despite minimally worse side effects for ECMF during treatment. ECMF benefit spanned all levels of toxicity, CDDI and QoL. There are no reported acute myeloid leukaemias or cardiac dysfunctions. ECMF is tolerable, deliverable, and significantly more effective than CMF, with no serious long-term toxicity or QoL detriment.

Prediction of caspase-3 inhibitory activity of 1,3-dioxo-4-methyl-2,3-dihydro-1h-pyrrolo[3,4-c] quinolines: QSAR study.

Neurodegenerative disorders are consequences of progressive and irreversible loss of neurons due to unwanted apoptosis which involves caspases, a group of cysteine proteases that cleave other proteins and inactivate them. Among several different groups of caspase enzymes, caspases-3 plays a key role in apoptosis and are a therapeutic target for their inhibition. In pursuit of better caspase-3 inhibitors, a quantitative structure-activity relationship (QSAR) analysis was performed on a series of 1,3-dioxo-4-methyl-2,3-dihydro-1H-pyrrolo[3,4-c] quinolines as caspase-3 inhibitors using WIN CAChe 6.1 and Medicinal Chemistry Regression Machine. The best QSAR model was selected and validated by internal and external validation method. The values of statistical data are r = 0.955, F = 72.95, SEE = 0.397, q(2) = 0.885, S(PRESS) = 0.44. The present study reveals that when the conformational minimum energy is increased, and lowest unoccupied molecular orbital energy and highest occupied molecular orbital energy are decreased the biological activity can be increased. On the basis of a selected QSAR model, we designed a new series of 1,3-dioxo-4-methyl-2,3-dihydro-1H-pyrrolo[3,4-c]quinolines compounds, calculated their caspases inhibitory activity and found that the designed compounds were more potent than the existing compounds.

A novel fuzzy rough selection of non-linearly extracted features for schizophrenia diagnosis using fMRI.

BACKGROUND AND OBJECTIVES: Schizophrenia is a severe brain disorder primarily diagnosed through externally observed behavioural symptoms due to the dearth of established clinical tests. Functional magnetic resonance imaging (fMRI) can capture the distortions caused by schizophrenia in the brain activation. Hence, it can be useful for developing a decision model that performs computer-aided diagnosis of schizophrenia. But, fMRI data is huge in dimension. Therefore dimension reduction is indispensable. It is additionally required to identify the discriminative brain regions. Hence, we aim to build an effective decision model that incorporates suitable dimension reduction and also identifies discriminative brain regions. METHODS: We propose a three-phase dimension reduction. First phase involves spatially-constrained fuzzy clustering of 3-dimensional spatial maps (obtained from general linear model and independent component analysis). In the second phase, non-linear features are extracted from each cluster using a generalized discriminant analysis. In the third phase, a novel fuzzy rough feature selection is proposed. The features obtained after the third phase are used for learning a decision model by the help of support vector machine classifier. This complete method is implemented within leave-one-out cross-validation on two balanced datasets (respectively acquired on 1.5Tesla and 3Tesla scanners). Both these datasets are created using Function Biomedical Informatics Research Network multisite data and contain fMRI data acquired during auditory oddball task performed by age-matched schizophrenia patients and healthy subjects. A permutation test is also carried out to ensure that no bias is involved in the learning. RESULTS: The results indicate that the proposed method achieves maximum classification accuracy of 97.1% and 98.0% for the two datasets respectively. The proposed method outperforms the state-of-the-art methods. The results of the permutation test show that p-values are lesser than the significance level i.e. 0.05. Therefore, the classifier has found a significant class structure and does not involve any bias. Further, discriminative brain regions are identified and are in agreement with the findings in related literature. CONCLUSION: The proposed method is able to derive suitable non-linear features and the related brain regions for effective computer-aided diagnosis. The fuzzy and rough set based approaches help in handling uncertainty and ambiguity in real data.