To assess the effectiveness of tailored food recipe in attenuating the progression of cancer cachexia to refractory cachexia in adult female patients undergoing palliative care in India

Cancer cachexia negatively impacts patients’ capability to undergo chemotherapy and fight infection. Increased energy expenditure and anorexia are key clinical features among cachexia patients leading to body weight loss. Therefore, it is imperative to assess all cancer patients for early signs of undernourishment. Nutrition intervention with counseling may ameliorate undernutrition and metabolic alterations. The aim of this study was to attenuate the progression to refractory cachexia, improve nutritional status and quality of life of female palliative care patients by providing nutrient rich natural food along with counseling. Female cancer patients with symptoms of cachexia were randomly distributed into control and intervention group. Patients were recruited from the Palliative clinic, Oncology department in AIIMS, New Delhi, India; control/placebo groups (for pilot n= 30 and scale-up n=75) and intervention groups (for pilot n= 33 and scale-up n=75). In addition to nutritional and physical activity counseling, intervention patients were instructed to consume 100g nutritional supplement (IAtta) on a daily basis with their normal dietary intake for a six month period, during the pilot study. Moreover, during the scale-up study, the intervention group received 100g of IAtta while the placebo group received 100g of whole wheat flour for daily consumption. Anthropometric measurements, physical activity level (PAL), dietary intake, quality of life (QoL) and biochemical indices were assessed at baseline, three-month and after six-month period. Study variables were analysed using repeated-measures ANOVA and the Friedman test for multi–comparisons to determine the changes within the groups at different time points (i.e. baseline, mid-intervention and post-intervention). Student t-test/ Wilcoxon ranksum tests were performed on the variables to assess the difference between the intervention and control/placebo groups at baseline (P- value ≤0.05; 95% confidence interval). After six months, patients in intervention group (IAtta group) had significant improvement in PAL (p<0.001) and QoL domain (global health status, p<0.001 and fatigue, p=0.001). Conversely, the QoL in the placebo group did not improve (global health status, p=0.74) nor did PAL (p=0.49). Body mass index was maintained in both groups (IAtta, p-value 0.121; Placebo, p-value 0.35). Serum albumin levels were significantly reduced (p = 0.005) in placebo group patients after six months of intervention. Nutrition sensitive intervention (IAtta meal) along with counseling (tailored nutrition and physical activity) improves quality of life and nutritional status as well as delays progression of cachexia among female palliative care patients. These findings highlight the need to ascertain the nutritional status of cancer patients and underpin the pivotal role of IAtta as intervention tool to compensate for deficient nutrients. It is therefore suggested to embed IAtta into the Indian palliative care framework to modulate cancer progression

Characterising citizenship: race, criminalisation and the extension of internal borders

Citizenship in the UK has in recent times been explicitly framed as a privilege not a right, granted selectively and withdrawn from some. There are several criteria that assist the government in distinguishing those deserving of British citizenship from those undeserving, one of the key ones being ‘character’. The ‘bad character’ criterion can apply for multiple reasons from inconsistencies in immigration paperwork to direct or indirect political associations with a range of disavowed political groups. Although not new, ‘bad character’ has become a principle reason for citizenship refusals in recent years, though has received little academic scrutiny. By bringing together quantitative and qualitative data on citizenship refusals, the article maps the scale of this measure, outlining what it means and to whom it applies. It argues that the ‘bad character’ criterion operates as a racialised exclusionary mechanism that constitutes a new set of amorphous restrictions upon the lives of non-white denizens

Unmaking citizens: passport removals, pre-emptive policing and the reimagining of colonial governmentalities

With the intensifying securitization of Western borders in the global War on Terror citizenship rights are increasingly fragile. Measures introduced by the British government to deal with the terrorist threat at home include citizenship deprivation, temporary exclusion orders as well as passport removals. Whilst citizenship deprivation has provoked critique for its potential violations of international human rights conventions on statelessness, cancellations of passports have not been subjected to the same kind of critique. Drawing on recent debates and interview data we demonstrate the alignment of citizenship deprivation and passport removals and conclude that these measures serve the same goal: of unmaking citizens. In this paper, we discuss findings from novel empirical research with individuals who have been removed of their British passports to illuminate the racialized dynamics of this process and the reconfiguration of racial governmentalities

Tissue-dependent T Cell Apoptosis and Transcriptional Regulation of Memory CD8+T Cell Differentiation During Viral Infections: A Dissertation

Activation and proliferation of antigen-specific T cells is the hallmark of an anti-viral immune response. Effector T cells generated during an immune response are heterogeneous in regards to their ability to populate the memory pool once the immune response has resolved. Initial T cell activation takes place in the lymphoid organs, after which T cells migrate into the non-lymphoid tissues. The presence of memory T cells at non-lymphoid tissue sites has been shown to be critical for protection against secondary virus challenge. Our lab has previously demonstrated that during and after the resolution of the immune response to Lymphocytic choriomeningitis virus (LCMV) CD8+T cells in the nonlymphoid tissues are more resistant to apoptosis than those in the lymphoid organs. This stability of T cells in the non-lymphoid tissues may be critical in ensuring protection against a secondary virus challenge. Mechanisms regulating tissue-dependent differences in CD8+T cell apoptosis were studied in an acute LCMV infection model. Virus-specific CD8+T cells from lymphoid (spleen, mesenteric lymph nodes (MLN), inguinal lymph nodes (ILN)) and non-lymphoid tissues (peritoneal exudate cells (PEC), fat-pads) were compared for expression of surface antigenic markers known to correlate with a memory phenotype. Non-lymphoid tissues were enriched in IL-7Rhi, KLRG-1lo, CD27hi and CXCR3hi virus-specific CD8+ T cells, and the presence of these antigenic markers correlated with increased memory potential and survival. Transcription factors in addition to cell surface antigens were assessed as correlates of resistance to apoptosis. Virus-specific CD8+T cells in the nonlymphoid tissues were enriched in cells expressing T cell factor-1 (TCF-1), which correlated with increased memory potential and survival. CD8+T cells in the peritoneum of TCF-1-deficient mice had decreased survival during resolution of the immune response to LCMV, suggesting a role for TCF-1 in promoting survival in the non-lymphoid tissues. As an additional mechanism, I investigated whether apoptosis-resistant CD8+T cells migrate to non-lymphoid tissues and contribute to tissue-dependent apoptotic differences. CXCR3+ CD8+T cells resisted apoptosis and accumulated in the lymph nodes of mice treated with FTY720, which blocks the export of lymph node cells into the peripheral tissues. The PECs expressed increased amounts of CXCR3 ligands, CXCL9 and CXCL10, which may have recruited the non-apoptotic cells from the lymph nodes. By adoptively transferring splenic T cells into the spleen or PEC environment I showed that the peritoneal environment through a yet undefined factor promoted survival of CD8+T cells. In this study I have elucidated the mechanisms by which CD8+T cells preferentially survive in the non-lymphoid tissues. I found that non-lymphoid tissues were enriched in memory-phenotype CD8+T cells which were intrinsically resistant to apoptosis irrespective of the tissue environment. Furthermore, apoptosisresistant CD8+T cells may preferentially migrate into the non-lymphoid tissues where the availability of tissue-specific factors may enhance memory cell survival. Few transcription factors have been identified that regulate CD8+T cell effector-memory differentiation during an immune response. In this thesis, I have also studied the mechanism by which the transcription factor Blimp-1 regulates the generation of effector and memory CD8+T cells. Blimp-1 is known to repress a large number of target genes, and ChIP (chromatin immunoprecipitation) sequencing analysis done by Dr. HyunMu Shin in the lab of Dr. Leslie J. Berg identified CD25 (IL-2Rα) and CD27 as potential targets of Blimp-1. I found that Blimp-1-deficient CD8+T cells had sustained expression of CD25 (IL-2Rα) and CD27 during peak and resolution of the immune response to LCMV. By performing adoptive transfers of CD25hi and CD27hi CD8+T cells I showed that CD25 and CD27 expression on CD8+T cells during resolution of the immune response correlates with enhanced survival. Silencing Il2rα and Cd27 expression reduced the Blimp-1-deficient CD8+T cell response, suggesting that sustained expression of CD25 and CD27 was in part responsible for the enhanced CD8+T cell response seen in the Blimp-1-deficient mice. Furthermore, our collaborator Dr. HyunMu Shin showed that CD25 and CD27 are direct targets of Blimp-1, and that Blimp-1 recruits histone modifying enzymes to Il2rα and Cd27 loci to suppress their expression during the peak of the anti-viral immune response. This study identifies one of the mechanisms by which Blimp-1 regulates the balance between generation of effector and memory CD8+T cells. In this thesis work I also studied the function of the transcription factor ROG (Repressor of GATA-3) in regulating in vivo T cell responses during both acute and chronic LCMV infection. ROG-deficient mice had increased CD8+T cell responses during an acute LCMV infection. ROG deficiency also led to the generation of memory T cells with an enhanced recall response compared to WT controls. By using LCMV-specific P14+ TCR transgenic ROG-deficient CD8+T cells these defects were shown to be T cell intrinsic. ROG-deficient mice had enhanced CD8+T cell responses and viral clearance during a persistent high dose LCMV Clone 13 infection. During chronic LCMV infection ROG-deficient mice also had increased lung pathology and mortality. The results indicate that ROG negatively regulates T cell responses and memory generation during both acute and chronic LCMV infection. The studies highlighted in this thesis elucidate the mechanisms promoting CD8+T cell survival in non-lymphoid tissues as well as transcription factormediated regulation of memory CD8+T cell differentiation. Knowledge of this will help us better understand T cell immunity after infections and may eventually help develop better vaccines

Determination and Correlation of Anticardiolipin Antibody with High Sensitivity C- reactive Proteins and its Role in Predicting Short Term Outcome in Patients with Acute Coronary Syndrome

Anticardiolipin antibody (aCL) is considered to be an independent risk factor while high sensitivity C reactive protein (hsCRP) is an established marker for coronary artery disease. This study was conducted to determine levels of aCL antibodies and hsCRP, their correlation and role in predicting recurrence of events in patients presenting with Acute Coronary Syndrome (ACS). Sixty patients admitted with Acute Coronary Syndrome were followed up for 7 days or until discharge. Patients were classified into two groups as those having experienced an ischemic event needing intervention within 7 days (Group I) and other having an event free recovery (Group II). aCL antibody and hsCRP levels were estimated and compared in these two groups. Twenty age and sex matched disease free persons served as controls. The levels of aCL were significantly higher in patients with ACS as compared to the controls (p=0.020). However the levels of aCL in Group I (13.39±9.46 GPL-U/ml) and Group II (13.51±9.93 GPL-U/ml) were not significantly different (p =0.838). The mean hsCRP levels were higher in cases with an event (23.30±10.68 mg/dl) than in cases without an event (20.60±11.45mg/dl) though it was not significant statistically (p=0.389). aCL and CRP were not found to be significantly correlated in causing the recurrence of events(p=0.178). Therefore anticardiolipin antibody is an independent risk factor which could be implicated in the pathogenesis of ACS. However it is not significantly associated with recurrence of short-term events in patients with ACS. Also, aCL antibody does not have significant correlation with hSCRP in causing recurrence of events in the patients of acute coronary syndrome

Measures of Performance for a Flexible Manufacturing System

A number of measures of performance of flexible manufacturing system, represented by a closed queueing network model are given and the relationships among them have been developed

An Algorithm for Calculating Expected Production Function and other Similar Functions for a Flexible Manufacturing System

The fact that for the case when the number of machines in each group is the same, the expected production function is a symmetric function of scaled workloads, is exploited to express this function in terms of the, basic symmetric functions of the loads. The same technique is suggested for calculating the probability of all the machines being found busy and the variance of the proportion of busy machines in the system