Demodulator techniques in satellite communication systems for direct broadcast systems

This thesis is concerned with the FM demodulator techniques used in terrestrial TV receiver designs for Direct Broadcast Systems (DBS) from satellites. The various MAC/Packet schemes intended for DBS applications are described and the international standards that apply to them considered, with particular emphasis on the D2-MAC system. Noise in FM systems is discussed and a suitable threshold noise model is chosen for use in DBS TV demodulator systems. The characteristics of the various types of noise effects are considered in terms of their effect upon the TV picture. The threshold performance of a conventional FM demodulator for differing types of modulation is reviewed and it is shown how the threshold characteristic depends upon the nature of the modulation. The literature review carried out represents a significant component of the thesis and combines material from patent literature with more conventional source materials from professional journals, conferences, textbooks, etc. Some ten existing demodulator concepts that exhibit threshold extension characteristics are examined, and where relevant their potential performance in D2-MAC format systems is assessed. The demodulator characteristics that limit their performance in TV systems are identified. It is concluded that designing a threshold extension demodulator, with reliable operation, for all picture contents and for a wide range of input carrier-to-noise ratios, is a formidable task using existing design techniques. On the basis of this examination an adaptive threshold extension demodulator concept is proposed, that utilises information contained within the signal structure to achieve an improved performance over a wide range of input carrier-to-noise ratios and picture content. It is shown how the relevant signal structures may be derived from conventional (PAL, SECAM and NTSC), MAC format and all-digital television systems. Illustrations are given that show how the adaptive demodulator concept can be applied to certain existing threshold extension demodulators, enhancing their performance for television picture reception. Future trends in all-digital DBS TV systems intended ultimately for DBS applications are briefly discussed together with their demodlilation requirements

An estimate of attributable cases of alzheimer disease and vascular dementia due to modifiable risk factors. the impact of primary prevention in europe and in italy

Background: Up to 53.7% of all cases of dementia are assumed to be due to Alzheimer disease (AD), while 15.8% are considered to be due to vascular dementia (VaD). In Europe, about 3 million cases of AD could be due to 7 potentially modifiable risk factors: diabetes, midlife hypertension and/or obesity, physical inactivity, depression, smoking, and low educational level. Aims: To estimate the number of VaD cases in Europe and the number of AD and VaD cases in Italy attributable to these 7 potentially modifiable risk factors. Methods: Assuming the nonindependence of the 7 risk factors, the adjusted combined population attributable risk (PAR) was estimated for AD and VaD. Results: In Europe, adjusted combined PAR was 31.4% for AD and 37.8% for VaD. The total number of attributable cases was 3,033,000 for AD and 873,000 for VaD. In Italy, assuming a 20% reduction of the prevalence of each risk factor, adjusted combined PAR decreased from 45.2 to 38.9% for AD and from 53.1 to 46.6% for VaD, implying a 6.4 and 6.5% reduction in the prevalence of AD and VaD, respectively. Conclusion: A relevant reduction of AD and VaD cases in Europe and Italy could be obtained through primary prevention

New drugs for non-alcoholic steatohepatitis and HIV infection: great expectations with a great absent?

In recent years, there has been an increasing number of clinical trials for the treatment of non‐alcoholic steatohepatitis (NASH). People living with HIV (PLWH) are commonly excluded from these studies, usually due to concerns over drug‐drug interactions (DDI) associated with antiretroviral therapy (ART). The Steatohepatitis in HIV Emerging Research (SHIVER) Network, a group of international experts in hepatology and infectious diseases, discusses our current understanding on the interaction between HIV and NASH, and the issues related to the inclusion of PLWH in NASH clinical trials. Recent trials addressing NASH treatment in PLWH are discussed. The risk of DDI between ART and aramchol, cenicriviroc, elafibranor, obeticholic acid and resmetirom (MGL‐3196), which are currently in phase III trials for the treatment of NASH, are reviewed. Finally, a model for trial design to include PLWH is proposed, strongly advocating for the scientific community to include this group as a sub‐population within studies

Sequential administration of temozolomide and fotemustine: Depletion of O6-alkyl guanine-DNA transferase in blood lymphocytes and in tumours

Background: The DNA repair protein O6-alkylguanine-DNA alkyl transferase (AT) mediates resistance to chloroethylnitro-soureas. Agents depleting AT such as DTIC and its new analogue temozolomide (TMZ) can reverse resistance to chloro-ethylnitrosoureas. We report the results of a dose finding study of TMZ in association with fotemustine. Patients and methods: Twenty-four patients with metastatic melanoma or recurrent glioma were treated with escalating dose of oral or intravenous TMZ ranging from 300 to 700 mg/m2, divided over two days. Fotemustine 100 mg/m2 was given intravenously on day 2, 4 hours after TMZ. AT depletion was measured in peripheral blood mononuclear cells (PBMCs) and in selected cases in melanoma metastases and was compared to TMZ pharmacokinetics. Results: The maximum tolerated dose (MTD) of TMZ was 400 mg/m2 (200 mg/m2/d) when associated with fotemustine the 2nd day with myelosuppression as dose limiting toxicity. The decrease of AT level in PBMCs was progressive and reached 34% of pretreatment values on day 2. There was however wide interindividual variability. AT reduction was neither dose nor route dependent and did not appear to be related to TMZ systemic exposure (AUC). In the same patients, AT depletion in tumour did not correlate with the decrease of AT observed in PBMCs. Conclusions: PBMCs may not be used as a surrogate of tumour for AT depletion. Further study should concentrate on the pharmacokinetic pharmacodynamic relationship in tumour to provide the basis for individually tailored therap

Meeting Report: Consensus Recommendations for a Research Agenda in Exercise in Solid Organ Transplantation

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/108597/1/ajt12874.pd

Exercise therapy in adults with serious mental illness: a systematic review and meta-analysis

Background: Individuals with serious mental illness are at a higher risk of physical ill health. Mortality rates are at least twice those of the general population with higher levels of cardiovascular disease, metabolic disease, diabetes, and respiratory illness. Although genetics may have a role in the physical health problems of these patients, lifestyle and environmental factors such as levels of smoking, obesity, poor diet, and low levels of physical activity also play a prominent part.<p></p> Objective: To conduct a systematic review and meta-analysis of randomised controlled trials comparing the effect of exercise interventions on individuals with serious mental illness.<p></p> Methods: Searches were made in Ovid MEDLINE, Embase, CINAHL, PsycINFO, Biological Abstracts on Ovid, and The Cochrane Library (January 2009, repeated January 2013) through to February 2013.<p></p> Results: Eight RCTs were identified in the systematic search. Six compared exercise versus usual care. One study assessed the effect of a cycling programme versus muscle strengthening and toning exercises. The final study compared the effect of adding specific exercise advice and motivational skills to a simple walking programme. Exercise programmes were noted by their heterogeneity in terms of the type of exercise intervention, setting, and outcome measures. The review found that exercise improved levels of exercise activity (n=13, standard mean difference [SMD] 1.81, CI 0.44 to 3.18, p = 0.01). No beneficial effect was found on negative (n = 84, SMD = -0.54, CI -1.79 to 0.71, p = 0.40) or positive symptoms of schizophrenia (n = 84, SMD = -1.66, CI -3.78 to 0.45, p = 0.12). No change was found on body mass index compared with usual care (n= 151, SMD = -0.24, CI -0.56 to 0.08, p = 0.14), or body weight (n = 77, SMD = 0.13, CI -0.32 to 0.58, p = 0.57). No beneficial effect was found on anxiety and depressive symptoms (n = 94, SMD = -0.26, CI -0.91 to 0.39, p = 0.43), or quality of life in respect of physical and mental domains. One RCT measured the effect of exercise on exercise intensity, attendance, and persistence at a programme. No significant effect was found on these measures.<p></p> Conclusions: This systematic review showed that exercise therapies can lead to a modest increase in levels of exercise activity but overall there was no noticeable change for symptoms of mental health, body mass index, and body weight.<p></p&gt

Regulatory T Cells Restrain Interleukin-2- and Blimp-1-Dependent Acquisition of Cytotoxic Function by CD4⁺ T Cells

In addition to helper and regulatory potential, CD4+ T cells also acquire cytotoxic activity marked by granzyme B (GzmB) expression and the ability to promote rejection of established tumors. Here, we examined the molecular and cellular mechanisms underpinning the differentiation of cytotoxic CD4+ T cells following immunotherapy. CD4+ transfer into lymphodepleted animals or regulatory T (Treg) cell depletion promoted GzmB expression by tumor-infiltrating CD4+, and this was prevented by interleukin-2 (IL-2) neutralization. Transcriptional analysis revealed a polyfunctional helper and cytotoxic phenotype characterized by the expression of the transcription factors T-bet and Blimp-1. While T-bet ablation restricted interferon-γ (IFN-γ) production, loss of Blimp-1 prevented GzmB expression in response to IL-2, suggesting two independent programs required for polyfunctionality of tumor-reactive CD4+ T cells. Our findings underscore the role of Treg cells, IL-2, and Blimp-1 in controlling the differentiation of cytotoxic CD4+ T cells and offer a pathway to enhancement of anti-tumor activity through their manipulation

Using internet enabled mobile devices and social networking technologies to promote exercise as an intervention for young first episode psychosis patients

<p>Abstract</p> <p>Background</p> <p>Young people with first episode psychosis are at an increased risk for a range of poor health outcomes. In contrast to the growing body of evidence that suggests that exercise therapy may benefit the physical and mental health of people diagnosed with schizophrenia, there are no studies to date that have sought to extend the use of exercise therapy among patients with first episode psychosis. The aim of the study is to test the feasibility and acceptability of an exercise program that will be delivered via internet enabled mobile devices and social networking technologies among young people with first episode psychosis.</p> <p>Methods/Design</p> <p>This study is a qualitative pilot study being conducted at Orygen Youth Health Research Centre in Melbourne, Australia. Participants are young people aged 15-24 who are receiving clinical care at a specialist first episode psychosis treatment centre. Participants will also comprise young people from the general population. The exercise intervention is a 9-week running program, designed to gradually build a person's level of fitness to be able to run 5 kilometres (3 miles) towards the end of the program. The program will be delivered via an internet enabled mobile device. Participants will be asked to post messages about their running experiences on the social networking website, and will also be asked to attend three face-to-face interviews.</p> <p>Discussion</p> <p>This paper describes the development of a qualitative study to pilot a running program coupled with the use of internet enabled mobile devices among young people with first episode psychosis. If the program is found to be feasible and acceptable to patients, it is hoped that further rigorous evaluations will ultimately lead to the introduction of exercise therapy as part of an evidence-based, multidisciplinary approach in routine clinical care.</p

Sequential administration of temozolomide and fotemustine: depletion of O6-alkyl guanine-DNA transferase in blood lymphocytes and in tumours

BACKGROUND: The DNA repair protein O6-alkylguanine-DNA alkyl transferase (AT) mediates resistance to chloroethylnitrosoureas. Agents depleting AT such as DTIC and its new analogue temozolomide (TMZ) can reverse resistance to chloroethylnitrosoureas. We report the results of a dose finding study of TMZ in association with fotemustine. PATIENTS AND METHODS: Twenty-four patients with metastatic melanoma or recurrent glioma were treated with escalating dose of oral or intravenous TMZ ranging from 300 to 700 mg/m2, divided over two days. Fotemustine 100 mg/m2 was given intravenously on day 2, 4 hours after TMZ. AT depletion was measured in peripheral blood mononuclear cells (PBMCs) and in selected cases in melanoma metastases and was compared to TMZ pharmacokinetics. RESULTS: The maximum tolerated dose (MTD) of TMZ was 400 mg/m2 (200 mg/m2/d) when associated with fotemustine the 2nd day with myelosuppression as dose limiting toxicity. The decrease of AT level in PBMCs was progressive and reached 34% of pretreatment values on day 2. There was however wide interindividual variability. AT reduction was neither dose nor route dependent and did not appear to be related to TMZ systemic exposure (AUC). In the same patients, AT depletion in tumour did not correlate with the decrease of AT observed in PBMCs. CONCLUSIONS: PBMCs may not be used as a surrogate of tumour for AT depletion. Further study should concentrate on the pharmacokinetic pharmacodynamic relationship in tumour to provide the basis for individually tailored therapy