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Arterial pulse waves (PWs) such as blood pressure and photoplethysmogram (PPG) signals contain a wealth of information on the cardiovascular (CV) system that can be exploited to assess vascular age and identify individuals at elevated CV risk. We review the possibilities, limitations, complementarity, and differences of reduced-order, biophysical models of arterial PW propa-gation, as well as theoretical and empirical methods for analyzing PW signals and extracting clinically relevant information for vascular age assessment. We provide detailed mathematical derivations of these models and theoretical methods, showing how they are related to each other. Finally, we outline directions for future research to realize the potential of modeling and analysis of PW signals for accurate assessment of vascular age in both the clinic and in daily life.

Chronic kidney disease (CKD) perturbs the crosstalk with others organs, with the interaction between the kidneys and the heart having been studied most intensively. However, a growing body of data indicates that there is an association between kidney dysfunction and disorders of the central nervous system. In epidemiological studies, CKD is associated with a high prevalence of neurological complications, such as cerebrovascular disorders, movement disorders, cognitive impairment and depression. Along with traditional cardiovascular risk factors (such as diabetes, inflammation, hypertension and dyslipidaemia), non-traditional risk factors related to kidney damage (such as uraemic toxins) may predispose patients with CKD to neurological disorders. There is increasing evidence to show that uraemic toxins, for example indoxyl sulphate, have a neurotoxic effect. A better understanding of factors responsible for the elevated prevalence of neurological disorders among patients with CKD might facilitate the development of novel treatments. Here, we review (i) the potential clinical impact of CKD on cerebrovascular and neurological complications, (ii) the mechanisms underlying the uraemic toxins' putative action (based on pre-clinical and clinical research) and (iii) the potential impact of these findings on patient care.

Neuropeptide Y (NPY) is a 36-amino-acid peptide member of a family also including peptide YY and pancreatic polypeptide, which are all ligands to Gi/Go coupled receptors. NPY regulates several fundamental biologic functions including appetite/satiety, sex and reproduction, learning and memory, cardiovascular and renal function and immune functions. The mesenteric circulation is a major source of NPY in the blood in man and this peptide is considered a key regulator of gut-brain cross talk. A progressive increase in circulating NPY accompanies the progression of chronic kidney disease (CKD) toward kidney failure and NPY robustly predicts cardiovascular events in this population. Furthermore, NPY is suspected as a possible player in accelerated cognitive function decline and dementia in patients with CKD and in dialysis patients. In theory, interfering with the NPY system has relevant potential for the treatment of diverse diseases from cardiovascular and renal diseases to diseases of the central nervous system. Pharmaceutical formulations for effective drug delivery and cost, as well as the complexity of diseases potentially addressable by NPY/NPY antagonists, have been a problem until now. This in part explains the slow progress of knowledge about the NPY system in the clinical arena. There is now renewed research interest in the NPY system in psychopharmacology and in pharmacology in general and new studies and a new breed of clinical trials may eventually bring the expected benefits in human health with drugs interfering with this system., Funding Agencies|COST Action CA19127-Cognitive Decline in Nephro-Neurology: European Cooperative Target (CONNECT)

Neuropeptide Y (NPY) is a 36-amino-acid peptide member of a family also including peptide YY and pancreatic polypeptide, which are all ligands to Gi/Go coupled receptors. NPY regulates several fundamental biologic functions including appetite/satiety, sex and reproduction, learning and memory, cardiovascular and renal function and immune functions. The mesenteric circulation is a major source of NPY in the blood in man and this peptide is considered a key regulator of gut-brain cross talk. A progressive increase in circulating NPY accompanies the progression of chronic kidney disease (CKD) toward kidney failure and NPY robustly predicts cardiovascular events in this population. Furthermore, NPY is suspected as a possible player in accelerated cognitive function decline and dementia in patients with CKD and in dialysis patients. In theory, interfering with the NPY system has relevant potential for the treatment of diverse diseases from cardiovascular and renal diseases to diseases of the central nervous system. Pharmaceutical formulations for effective drug delivery and cost, as well as the complexity of diseases potentially addressable by NPY/NPY antagonists, have been a problem until now. This in part explains the slow progress of knowledge about the NPY system in the clinical arena. There is now renewed research interest in the NPY system in psychopharmacology and in pharmacology in general and new studies and a new breed of clinical trials may eventually bring the expected benefits in human health with drugs interfering with this system., Funding Agencies|COST Action CA19127-Cognitive Decline in Nephro-Neurology: European Cooperative Target (CONNECT)

Neuropeptide Y (NPY) is a 36-amino-acid peptide member of a family also including peptide YY and pancreatic polypeptide, which are all ligands to Gi/Go coupled receptors. NPY regulates several fundamental biologic functions including appetite/satiety, sex and reproduction, learning and memory, cardiovascular and renal function and immune functions. The mesenteric circulation is a major source of NPY in the blood in man and this peptide is considered a key regulator of gut-brain cross talk. A progressive increase in circulating NPY accompanies the progression of chronic kidney disease (CKD) toward kidney failure and NPY robustly predicts cardiovascular events in this population. Furthermore, NPY is suspected as a possible player in accelerated cognitive function decline and dementia in patients with CKD and in dialysis patients. In theory, interfering with the NPY system has relevant potential for the treatment of diverse diseases from cardiovascular and renal diseases to diseases of the central nervous system. Pharmaceutical formulations for effective drug delivery and cost, as well as the complexity of diseases potentially addressable by NPY/NPY antagonists, have been a problem until now. This in part explains the slow progress of knowledge about the NPY system in the clinical arena. There is now renewed research interest in the NPY system in psychopharmacology and in pharmacology in general and new studies and a new breed of clinical trials may eventually bring the expected benefits in human health with drugs interfering with this system., Funding Agencies|COST Action CA19127-Cognitive Decline in Nephro-Neurology: European Cooperative Target (CONNECT)

Neuropeptide Y (NPY) is a 36-amino-acid peptide member of a family also including peptide YY and pancreatic polypeptide, which are all ligands to Gi/Go coupled receptors. NPY regulates several fundamental biologic functions including appetite/satiety, sex and reproduction, learning and memory, cardiovascular and renal function and immune functions. The mesenteric circulation is a major source of NPY in the blood in man and this peptide is considered a key regulator of gut-brain cross talk. A progressive increase in circulating NPY accompanies the progression of chronic kidney disease (CKD) toward kidney failure and NPY robustly predicts cardiovascular events in this population. Furthermore, NPY is suspected as a possible player in accelerated cognitive function decline and dementia in patients with CKD and in dialysis patients. In theory, interfering with the NPY system has relevant potential for the treatment of diverse diseases from cardiovascular and renal diseases to diseases of the central nervous system. Pharmaceutical formulations for effective drug delivery and cost, as well as the complexity of diseases potentially addressable by NPY/NPY antagonists, have been a problem until now. This in part explains the slow progress of knowledge about the NPY system in the clinical arena. There is now renewed research interest in the NPY system in psychopharmacology and in pharmacology in general and new studies and a new breed of clinical trials may eventually bring the expected benefits in human health with drugs interfering with this system., Funding Agencies|COST Action CA19127-Cognitive Decline in Nephro-Neurology: European Cooperative Target (CONNECT)

Neuropeptide Y (NPY) is a 36-amino-acid peptide member of a family also including peptide YY and pancreatic polypeptide, which are all ligands to Gi/Go coupled receptors. NPY regulates several fundamental biologic functions including appetite/satiety, sex and reproduction, learning and memory, cardiovascular and renal function and immune functions. The mesenteric circulation is a major source of NPY in the blood in man and this peptide is considered a key regulator of gut-brain cross talk. A progressive increase in circulating NPY accompanies the progression of chronic kidney disease (CKD) toward kidney failure and NPY robustly predicts cardiovascular events in this population. Furthermore, NPY is suspected as a possible player in accelerated cognitive function decline and dementia in patients with CKD and in dialysis patients. In theory, interfering with the NPY system has relevant potential for the treatment of diverse diseases from cardiovascular and renal diseases to diseases of the central nervous system. Pharmaceutical formulations for effective drug delivery and cost, as well as the complexity of diseases potentially addressable by NPY/NPY antagonists, have been a problem until now. This in part explains the slow progress of knowledge about the NPY system in the clinical arena. There is now renewed research interest in the NPY system in psychopharmacology and in pharmacology in general and new studies and a new breed of clinical trials may eventually bring the expected benefits in human health with drugs interfering with this system., Funding Agencies|COST Action CA19127-Cognitive Decline in Nephro-Neurology: European Cooperative Target (CONNECT)

IntroductionGeographic and transportation barriers are associated with poorer HIV-related health outcomes in sub-Saharan Africa, but data on the impact of these barriers on prevention interventions are limited. We estimated the association between distance to clinic and other transportation-related barriers on pre-exposure prophylaxis (PrEP) uptake and initial clinic visit attendance in a rural community in southwestern Uganda enrolled in the ongoing SEARCH study (NCT01864603).MethodsCommunity-wide HIV testing was conducted and offered to adult (≥15 years) participants in Ruhoko. Participants were eligible for PrEP based on an empiric risk score, having an HIV-discordant partner, or self-referral at either the community health campaign or during home-based testing from March to April 2017. We collected data from PrEP-eligible households on GPS-measured distance to clinic, walking time to clinic and road difficulty. A sample of participants was also asked to identify their primary barriers to PrEP use with a semi-quantitative questionnaire. We used multivariable logistic regression to evaluate the association between transportation barriers and (1) PrEP uptake among PrEP-eligible individuals and (2) four-week clinic visit attendance among PrEP initiators.ResultsOf the 701 PrEP-eligible participants, 272 (39%) started PrEP within four weeks; of these, 45 (17%) were retained at four weeks. Participants with a distance to clinic of ≥2 km were less likely to start PrEP (aOR 0.34; 95% CI 0.15 to 0.79, p = 0.012) and less likely to be retained on PrEP once initiated (aOR 0.29; 95% CI 0.10 to 0.84; p = 0.024). Participants who were deemed eligible during home-based testing and did not have the option of same-day PrEP start were also substantially less likely to initiate PrEP (aOR 0.16, 95% CI 0.07 to 0.37, p < 0.001). Of participants asked to name barriers to PrEP use (N = 98), the most frequently cited were "needing to t

IntroductionGeographic and transportation barriers are associated with poorer HIV-related health outcomes in sub-Saharan Africa, but data on the impact of these barriers on prevention interventions are limited. We estimated the association between distance to clinic and other transportation-related barriers on pre-exposure prophylaxis (PrEP) uptake and initial clinic visit attendance in a rural community in southwestern Uganda enrolled in the ongoing SEARCH study (NCT01864603).MethodsCommunity-wide HIV testing was conducted and offered to adult (≥15 years) participants in Ruhoko. Participants were eligible for PrEP based on an empiric risk score, having an HIV-discordant partner, or self-referral at either the community health campaign or during home-based testing from March to April 2017. We collected data from PrEP-eligible households on GPS-measured distance to clinic, walking time to clinic and road difficulty. A sample of participants was also asked to identify their primary barriers to PrEP use with a semi-quantitative questionnaire. We used multivariable logistic regression to evaluate the association between transportation barriers and (1) PrEP uptake among PrEP-eligible individuals and (2) four-week clinic visit attendance among PrEP initiators.ResultsOf the 701 PrEP-eligible participants, 272 (39%) started PrEP within four weeks; of these, 45 (17%) were retained at four weeks. Participants with a distance to clinic of ≥2 km were less likely to start PrEP (aOR 0.34; 95% CI 0.15 to 0.79, p = 0.012) and less likely to be retained on PrEP once initiated (aOR 0.29; 95% CI 0.10 to 0.84; p = 0.024). Participants who were deemed eligible during home-based testing and did not have the option of same-day PrEP start were also substantially less likely to initiate PrEP (aOR 0.16, 95% CI 0.07 to 0.37, p < 0.001). Of participants asked to name barriers to PrEP use (N = 98), the most frequently cited were "needing to t

Little is understood about the genesis of autoimmune diseases caused by deficiencies in TAM receptors (Tyro3, Axl, Mer). One of the causes of autoimmunity could be defective thymic education. Our goal was to elucidate the localization and role of TAM receptors and their ligands within the thymus. We show that Axl and Mer, but not Tyro3, are expressed within the thymus. Through immunohistochemistry, we identify Axl and Mer expression primarily on macrophages in both the medulla and cortex. Using knockout mice, we show that Axl and Mer perform necessary but redundant roles in the elimination of basally accumulated apoptotic thymocytes. The absence of both receptors leads to immense apoptotic cell accumulation within thymic cortex and medulla.These changes result in minor morphological defects as the weight but not the ratio of medulla to cortex was affected in the Axl-/-Mertk-/- mice. We further use this model to instigate Axl dependence on Gas6 as a ligand in thymus. Additionally, we show that during acute thymocyte apoptosis, Mer but not Axl is critical in cellular clearance.

Little is understood about the genesis of autoimmune diseases caused by deficiencies in TAM receptors (Tyro3, Axl, Mer). One of the causes of autoimmunity could be defective thymic education. Our goal was to elucidate the localization and role of TAM receptors and their ligands within the thymus. We show that Axl and Mer, but not Tyro3, are expressed within the thymus. Through immunohistochemistry, we identify Axl and Mer expression primarily on macrophages in both the medulla and cortex. Using knockout mice, we show that Axl and Mer perform necessary but redundant roles in the elimination of basally accumulated apoptotic thymocytes. The absence of both receptors leads to immense apoptotic cell accumulation within thymic cortex and medulla.These changes result in minor morphological defects as the weight but not the ratio of medulla to cortex was affected in the Axl-/-Mertk-/- mice. We further use this model to instigate Axl dependence on Gas6 as a ligand in thymus. Additionally, we show that during acute thymocyte apoptosis, Mer but not Axl is critical in cellular clearance.

The relative contributions of the JNK subtypes in inflammatory β-cell failure and apoptosis are unclear. The JNK protein family consists of JNK1, JNK2, and JNK3 subtypes, encompassing many different isoforms. INS-1 cells express JNK1α1, JNK1α2, JNK1β1, JNK1β2, JNK2α1, JNK2α2, JNK3α1, and JNK3α2 mRNA isoform transcripts translating into 46 and 54 kDa isoform JNK proteins. Utilizing Lentiviral mediated expression of shRNAs against JNK1, JNK2, or JNK3 in insulin-producing INS-1 cells, we investigated the role of individual JNK subtypes in IL-1β-induced β-cell apoptosis. JNK1 knockdown prevented IL-1β-induced INS-1 cell apoptosis associated with decreased 46 kDa isoform JNK protein phosphorylation and attenuated Myc expression. Transient knockdown of Myc also prevented IL-1β-induced apoptosis as well as caspase 3 cleavage. JNK2 shRNA potentiated IL-1β-induced apoptosis and caspase 3 cleavage, whereas JNK3 shRNA did not affect IL-1β-induced β-cell death compared to nonsense shRNA expressing INS-1 cells. In conclusion, JNK1 mediates INS-1 cell death associated with increased Myc expression. These findings underline the importance of differentiated targeting of JNK subtypes in the development of inflammatory β-cell failure and destruction.

Extensive research in the field of ambient assisted living (AAL) provides profound knowledge about the design of AAL systems. However, more generic design characteristics for user interaction have not been formalized for this domain yet. Thus, we propose to develop a domain specific taxonomy for the design of user interaction in AAL systems. We adopted a systematic taxonomy development approach that combines an empirical and a pseudo-conceptual strategy. Six co-researchers from different disciplines conduct the iterative research process. Next to AAL systems existing taxonomies in the field of human-computer interaction are analyzed following the Delphi method. In this paper we present our research process and preliminary results from the first iteration. The final taxonomy allows classification and should support the analysis of user interaction utilized in AAL systems. Furthermore, it can deal as a practical design guideline.

This century has seen a shift from conventional forms of war and humanitarian interventions to complex contingencies. Combat, humanitarian assistance, and reconstruction operations often occur in parallel. Protection of noncombatant personnel, supplies, and facilities against terrorists, looting, and other lawlessness grows in importance while the availability of military forces cannot meet the demand for these critical, but non-core functions. To address this shortfall, the United States and other international actors have employed armed contractors, or private security companies (PSC). This has led to charges of mercenarism, loss of government monopoly of force, and undermining of the rule of law. This project uses current principles of Stability, Security, Transition, and Reconstruction and the international treaties making up the body of the Law of War to examine the advantages PSCs offer, the risks they bring, and concepts for maximizing the former while mitigating the latter. The employment of armed contractors within the bounds of the Law of War can enhance our ability to respond to complex contingencies. Exceeding these bounds or the failure to exercise appropriate oversight and accountability of armed contractors can undermine policies and mission success. Armed contractors have a valid role to play in the current operational environment, but interagency policies for armed contractors must be changed for maximal effectiveness., USAWC Program Research Project.

Thesis (B.S. and B.M.)--Massachusetts Institute of Technology, Dept. of Electrical Engineering and Computer Science, 1991., Includes bibliographical references (leaves 175-177)., Font and graphics antialiasing are often used methods of enhancing the output quality of video monitors. The same techniques also can enhance the quality of laser printer output. Since the laser printing process and the monitor display process differ radically, the assumptions made for antialiasing on monitors are reexamined. Raster scanning, laser modulation, xerographic transfer, information transfer, and computation are examined in the context of laser printer antialiasing. Past work on antialiasing algorithms is evaluated. A practical method of performing anti-aliasing of text, graphics, and images is developed. Standard antialiasing scan conversion algorithms are adapted to function on two dimensional binary bitmaps of vector data. Computation issues are discussed, and a fast localized scan conversion operation based on statistical models is developed and evaluated. Finally, an architecture for the high bandwidth modulation of the laser by both power and time is developed, implemented, and evaluated., by Christopher M. Mayer., B.S.and B.M.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Economics, 1993., Includes bibliographical references., by Christopher Joseph Mayer., Ph.D.

Multi-century trends in past climate for the middle Rio Grande basin, AD 622-1992

The invention of the Field Programmable Gate Array (FPGA) has led to a number of interesting developments. One is the idea of providing custom hardware support for applications running on a computer. These reconfigurable computers have been shown to decrease the execution time for some applications. Based on past results, attention has subsequently turned to using reconfigurable computing in general-purpose computers (e.g. desktop and workstation environments). This thesis develops a design for just such a computer. The design, FPGADLX, is based on a hypothetical superscalar computer running the DLX instruction set and is generic enough in principle to be adapted to any superscalar or VLIW processor on the market today. This thesis begins by examining FPGA technology and reviewing related reconfigurable computing efforts. Based on this review, requirements for a viable general-purpose reconfigurable computer system were developed. These requirements drove the development of the eventual FPGADLX design which covers hardware organization and operation, as well as modifications to the operating system and compiler. A software simulator which can emulate a significant portion of the design and run actual programs has been built.