The evaluation of positron emission tomography to assess pharmacodynamics and pahrmacokinetics of anti cancer drugs

Positron emission tomography (PET) is a non-invasive imaging technique that is emerging as a useful tool in the field of cancer medicine particularly in drug development. The purpose of this thesis has been to perform clinical studies using two different radiotracers, 5-[^V]fIuorouracil (5-['^F]FU) and 2-[''C]thymidine, to assess pharmacokinetic and pharmacodynamic parameters respectively, which were derived from PET imaging and to establish the contribution that PET can add to drug development, in vivo, in man. Aims: 1) Quantify the pharmacodynamic effects of cytotoxic agents in tumour and normal tissue using 2-["C]thymidine 2) Measure changes in tumour and normal tissue pharmacokinetics of 5-Fluorouracil in response to the modulating agents carbogen and nicotinamide or interferon 3) Assessment of blood flow change in tumour and normal tissue to carbogen and nicotinamide or interferon 4) Interpretation of PET data using novel analysis methods with modified Patlak and spectral analysis Methods: In the 5-['^]FU study, patients with metastatic gastrointestinal cancer underwent PET scanning at the start of 2 separate chemotherapy cycles. The 2nd scan was performed after the administration of carbogen and nicotinamide or interferon. In the 2-["C]thymidine study patients receiving chemotherapy were scanned before commencing chemotherapy, and 1 week after the 3''' cycle of chemotherapy. Patients also had conventional imaging before the start of and after 3 cycles of treatment. Findings: After carbogen and nicotinamide administration, 5-['^]FU uptake was increased in tumour, but not in normal tissue. Regional perfusion was elevated in tumours but decreased in kidneys after carbogen and nicotinamide. After interferon administration, there was an increase in 5-['^]FU retention in tumours, but no increase in uptake. Regional perfusion in tumour and normal tissue was unaltered by interferon. Retention of 2-["C]thymidine decreased in tumour in keeping with the results of conventional radiology, suggesting a pathological response, assessed in vivo, to chemotherapy

Laparoscopic retrieval of misplaced copper T

Intrauterine contraceptive device is important part of family planning services in India. These can be inserted post menstrually, post abortal, post-delivery or in post puerperal period. Associated complications include bleeding, pain, infection, expulsion and most serious complication as perforation of uterine wall and migration to adjacent organs. We present a case of successful laparoscopic retrieval of a misplaced cuT. A 30-year-old female para 2 live 1 presented in SDMH outpatient department with right sided lower abdominal pain since one year. NCCT scan of pelvis showed IUCD in pelvic cavity anteriorly just above urinary bladder. Laparoscopic removal of cuT was done along with tubal recanalization

Personality Assessment of Officer Cadre of Indian Armed Forces: A De Novo Approach

The present selection system of the officer cadre of the Armed Forces has stood the test of time. However, owing to the transformations and developments in the society, a need was felt to upgrade this system. After a number of interactions and deliberations, a new programme called ‘De Novo system for the Selection of Personnel in the Armed forces’ was initiated. To identify the domains that need to be assessed through this system, job analysis was carried out. Data were collected from the presently employed officers of the Armed Forces, and the officers were asked to fill out survey performa, critical incidents record, task inventory and attribute questionnaire. Job analysis identified 5 domains of assessment, namely, cognition, affect, behaviour, psychomotor, and values. 16 Attributes of military leaders under these 5 domains were also identified. Tests were developed under the three techniques (psychological, group testing, and interview) to assess these 16 attributes and the 5 domains. The prototype of the tests was developed following an assessment centre approach and the trials for the same are due in the coming months

Flow among Scientists A Job Demands Resources Perspective

The study was conducted to investigate the relationship of flow at work of scientists with their job demands, job resources and personal resources. 64 scientists comprised the sample. Personal data sheet, work-related flow inventory, general self-efficacy scale and Copenhagen psychosocial questionnaire (second version) were the instruments used in the study. Descriptive statistics, t-test, ANOVA, correlation analysis and hierarchical regression were the statistical techniques used. The results of the study suggested that scientists of various age-groups and length of service did not differ from each other on job demands, job resources, personal resources and flow at work. It was also found that flow at work was significantly positively related to job resources and personal resources but not significantly related to job demands. Job resources and personal resources were found to be significant positive predictors of flow at work whereas job demands were not found to have a significant impact on flow at work

Affect and its Assessment in Personnel Selection

A sizable amount of literature supports the impact of positive and negative affectivity on organisational effectiveness. Higher positive affectivity is associated with experiencing a preponderance of positive feeling states, while higher levels of negative affectivity are associated with negative feelings. Right person for the right job can be selected if employers consider these emotional dispositions during the selection process. The present study was undertaken with aims to develop a Word Association Test with objective scoring system for assessment of positive and negative affect. A comprehensive list of 120 negative, positive, and neutral words each was prepared after consulting affective lexical resources. Ratings were taken from five SMEs on valence, control and intensity of each word. Two lists of 60 words each were prepared for data collection on 410 male subjects aged 16-18 years. Unanswered or incomprehensible words were deleted, and 45 words were retained. Responses were categorised into positive, negative, neutral categories, and computation of the total number of positive, negative and neutral responses was carried out and objective scoring scheme was prepared. Inter-rater reliability was found to range between 0.46 to 0.85. The concurrent validity was determined against PANAS (-0.273**), and E and N scales of NEO-PI-R (0.20**

An unusual presentation of huge paraovarian cyst as papillary serous cyst adenofibroma: a rare case report

Paraovarian cysts constitute 10-20% of all adnexal masses and are usually less than two centimeter in diameter. Authors reported a 20-year-old unmarried female with vague abdominal discomfort since 1 year. On examination abdomen was uniformly distended with central position of umbilicus. Ultrasonography showed a large cystic mass extending from pelvis to pancreas likely of ovarian origin. Biochemical evaluation was not suggestive of malignant nature of this cystic mass. So, with due care of cosmesis, surgery was planned. After the midline vertical incision, peritoneal washings were collected for oicytological analysis to further exclude malignancy. Then 5mm cannula with trocar was inserted into the cyst to suck out the fluid then shrunken cystic wall was exteriorised. Right ovary was absolutely healthy. Enucleation of the cyst was done with preservation of ovary. Histopathology reported as a papillary serous cyst adenofibroma. Follow up period was uneventful.

Frustrated symmetries in multi-Higgs-doublet models

Within multi-Higgs-doublet models, one can impose symmetries on the Higgs potential, either discrete or continuous, that mix several doublets. In two-Higgs-doublet model any such symmetry can be conserved or spontaneously violated after the electroweak symmetry breaking (EWSB), depending on the coefficients of the potential. With more than two doublets, there exist symmetries which are always spontaneously violated after EWSB. We discuss the origin of this phenomenon and show its similarity to geometric frustration in condensed-matter physics.Comment: 7 pages, no figure

MUTUAL LEARNING IN TREE PARITY MACHINES USING CUCKOO SEARCH ALGORITHM FOR SECURE PUBLIC KEY EXCHANGE

In Neural Cryptography, Artificial Neural Networks are used for the process of key generation and encryption. Tree Parity Machine (TPM) is a single layer neural network that approaches symmetric key exchange using the process of mutual learning. This method is exploited to design a secure key exchange protocol, where the sender and the receiver TPMs are synchronized to obtain an identically tuned weight vectors in both the networks. The synchronized TPMs are then capable of generating a key stream. The time required for synchronization depends on the initial weight vectors which are randomly initialized. In the proposed method, the process of synchronization is expedited using Cuckoo Search (CS) Algorithm used for the generation of optimal weights

MTHFR 677C>T polymorphism and the risk of breast cancer: evidence from an original study and pooled data for 28031 cases and 31880 controls

Background: Methylenetetrahydrofolate Reductase (MTHFR) acts at an important metabolic point in the regulation of cellular methylation reaction. It assists in the conversion of 5, 10-methylenetetrahydrofolate to 5-methyltetrahydrofolate. The latter aids in remethylation of homocysteine to de novo methionine that is required for DNA synthesis. The objective of this study was to examine the effect of MTHFR 677 C>T polymorphism on the risk of breast cancer in the Indian sub-continent. Methods and Results: We genotyped 677 C>T locus in 1096 individuals that were classified into cases (N = 588) and controls (N = 508). Genotype data were analyzed using chi-square test. No significant difference was observed in the distribution of genotypes between cases and controls in north Indian (P = 0.932), south Indian (P = 0.865), and pooled data (P = 0.680). To develop a consensus regarding the impact of 677C>T polymorphism on breast cancer risk, we also conducted a meta-analysis on 28031 cases and 31880 controls that were pooled from sixty one studies. The overall summary estimate upon meta-analysis suggested no significant correlation between the 677C>T substitution and breast cancer in the dominant model (Fixed effect model: OR = 0.97, P = 0.072, Random effects model: OR = 0.96, P = 0.084) or the recessive model (Fixed effect model: OR = 1.05, P = 0.089; Random effects model: OR = 1.08, P = 0.067). Conclusion: 677 C>T substitution does not affect breast cancer risk in the Indo-European and Dravidian populations of India. Analysis on pooled data further ruled out association between the 677 C>T polymorphism and breast cancer. Therefore, 677 C>T substitution does not appear to influence the risk of breast cancer

Oral health status and treatment needs of female beedi factory workers in Mangalore city, India

Purpose: To determine oral health status and treatment needs of female beedi factory workers in Mangalore city, Karnataka. Methods: A cross-sectional study was conducted on 426 female beedi factory workers age 15-70 years in Mangalore city to find out their oral health status and treatment needs. Data collection was done on a structured proforma: regarding demographic data, oral hygiene habits, personal habits, past dental history and data on oral health status and treatment needs was recorded using WHO oral health assessment form (1997). Results: Out of 418 dentate patients only 2 (0.47%) had healthy periodontium, 68 (16.26%) and 348 (83.25%) had gingival disease and periodontal disease respectively. Healthy periodontium and bleeding was seen only in younger age groups (15-24 years and 25-34 years), whereas as age increased score of code 4 (Deep pockets) also increased. The prevalence of dental caries was found to be 82.6%. The total mean DMFT was 5.97±5.78. The mean DT was 4.06±4.03, mean MT was 1.88±3.71 and mean FT was 0.03±0.20. Of the total study population 46 subjects exhibited oral lesions. Conclusions: There are more proportions of unfulfilled treatment needs in this working class as they are not provided with dental treatment, appropriate public health actions at various levels need to be taken like health education and health promotion to curtail the disease in this population