The role of BNP testing in heart failure

Brain natriuretic peptide (BNP) levels are simple and objective measures of cardiac function. These measurements can be used to diagnose heart failure, including diastolic dysfunction, and using them has been shown to save money in the emergency department setting. The high negative predictive value of BNP tests is particularly helpful for ruling out heart failure. Treatment with angiotensin-converting enzyme inhibitors, angiotensin-II receptor blockers, spironolactone, and diuretics reduces BNP levels, suggesting that BNP testing may have a role in monitoring patients with heart failure. However, patients with treated chronic stable heart failure may have levels in the normal range (i.e., BNP less than 100 pg per mL and N-terminal proBNP less than 125 pg per mL in patients younger than 75 years). Increases in BNP levels may be caused by intrinsic cardiac dysfunction or may be secondary to other causes such as pulmonary or renal diseases (e.g., chronic hypoxia). BNP tests are correlated with other measures of cardiac status such as New York Heart Association classification. BNP level is a strong predictor of risk of death and cardiovascular events in patients previously diagnosed with heart failure or cardiac dysfunction.

A comparison of road accidents in developing countries with special reference to Jamaica

This research was originally undertaken to aid the Jamaican government and the World Bank in making funding decisions relative to improvement of road systems and traffic control in Jamaica. An investigation of the frequency and causes of road accidents and an evaluation of their impact on the Jamaican economy were carried out, and a model system which might be applied was developed. It is believed that the importance of road accident economic and manpower losses to the survival of developing countries, such as Jamaica, cannot be overemphasized. It is suggested that the World Bank, in cooperation with national governments, has a role to play in alleviating this serious problem. Data was collected from such organizations as the Jamaica Ministry of Construction, Police Department, the World Bank, and the World Health Organization. A variety of methodologies were utilized to organize this data in useful and understandable forms. The most important conclusion of this research is that solvable problems in road systems and in traffic control result in the unnecessary loss of useful citizens, in both developed and developing countries. However, a lack of information and understanding regarding the impact of high rates of road accident death and injury on the national economy and stability of a country results in an apparent lack of concern. Having little internal expertise in the field of road accident prevention, developing countries usually hire consultants to help them address this problem. In the case of Jamaica, this practice has resulted in distrust and hard feelings between the Jamaican authorities and major organizations involved in the field. Jamaican officials have found confusing the recommendations of most experts contracted to study traffic safety. The attempts of foreign consultants to utilize a technological approach (the use of coding systems and computers), methods which do not appear cost-effective for Jamaica, have resulted in the expenditure of limited funds for studies which offer no feasible approach to the problem. This funding limitation, which hampers research and road improvement, could be alleviated by such organizations as the World Bank. The causes of high accident rates are many, it was found. Formulation of a plan to address this serious problem must take into account the current failure to appreciate the impact of a high level of road accidents on national economy and stability, inability to find a feasible approach to the problem, and inadequate funding. Such a plan is discussed in detail in the main text of this research.

The pathogenesis of Alzheimer's disease: a reevaluation of the "amyloid cascade hypothesis"

The most influential theory to explain the pathogenesis of Alzheimer's disease (AD) has been the "Amyloid Cascade Hypothesis" (ACH) first formulated in 1992. The ACH proposes that the deposition of ß-amyloid (Aß) is the initial pathological event in AD leading to the formation of senile plaques (SPs) and then to neurofibrillary tangles (NFTs) death of neurons, and ultimately dementia. This paper examines two questions regarding the ACH: (1) is there a relationship between the pathogenesis of SPs and NFTs, and (2) what is the relationship of these lesions to disease pathogenesis? These questions are examined in relation to studies of the morphology and molecular determinants of SPs and NFTs, the effects of gene mutation, degeneration induced by head injury, the effects of experimentally induced brain lesions, transgenic studies, and the degeneration of anatomical pathways. It was concluded that SPs and NFTs develop independently and may be the products rather than the causes of neurodegeneration in AD. A modification to the ACH is proposed which may better explain the pathogenesis of AD, especially of late-onset cases of the disease.

The effect of innate compliance on the performance of a counterpulsation device

Cardiovascular disease (CVD) continues to be one of the top causes of mortality in the world. World Heart Organization (WHO) reported that in 2004, CVD contributed to almost 30% of death from estimated worldwide death figures of 58 million[1]. Heart failure treatment varies from lifestyle adjustment to heart transplantation; its aims are to reduce HF symptoms, prolong patient survival and minimize risk [2]. One alternative available in the market for HF treatment is Left Ventricular Assist Device (LVAD). Chronic Intermittent Mechanical Support (CIMS) device is a novel (LVAD) heart failure treatment using counterpulsation similar to Intra Aortic Balloon Pumps (IABP). However, the implantation site of the CIMS balloon is in the ascending aorta just distal to aortic valve contrasted with IABP in the descending aorta. Counterpulsation coupled with implantation close to the aortic valve enables comparable flow augmentation with reduced balloon volume. Two prototypes of the CIMS balloon were constructed using rapid prototyping: the straight-body model is a cylindrical tube with a silicone membrane lining with zero expansive compliance. The compliant-body model had a bulging structure that allowed the membrane to expand under native systolic pressure increasing the device’s static compliance to 1.5 mL/mmHg. This study examined the effect of device compliance and vascular compliance on counterpulsating flow augmentation. Both prototypes were tested on a two-element Windkessel model human mock circulatory loop (MCL). The devices were placed just distal to aortic valve and left coronary artery. The MCL mimicked HF with cardiac output of 3 L/min, left ventricular pressure of 85/15 mmHg, aortic pressure of 70/50 mmHg and left coronary artery flow rate of 66 mL/min. The mean arterial pressure (MAP) was calculated to be 57 mmHg. Arterial compliance was set to be1.25 mL/mmHg and 2.5 mL/mmHg. Inflation of the balloon was triggered at the dicrotic notch while deflation was at minimum aortic pressure prior to systole. Important haemodynamics parameters such as left ventricular pressure (LVP), aortic pressure (AoP), cardiac output (CO), left coronary artery flowrate (QcorMean), and dP (Peak aortic diastolic augmentation pressure – AoPmax ) were simultaneously recorded for both non-assisted mode and assisted mode. ANOVA was used to analyse the effect of both factors (balloon and arterial compliance) to flow augmentation. The results showed that for cardiac output and left coronary artery flowrate, there were significant difference between balloon and arterial compliance at p < 0.001. Cardiac output recorded maximum output at 18% for compliant body and stiff arterial compliance. Left coronary artery flowrate also recorded around 20% increase due to compliant body and stiffer arterial compliance. Resistance to blood ejection recorded highest difference for combination of straight body and stiffer arterial compliance. From these results it is clear that both balloon and arterial compliance are statistically significant factors for flow augmentation on peripheral artery and reduction of resistance. Although the result for resistance reduction was different from flow augmentation, these results serves as an important aspect which will influence the future design of the CIMS balloon and its control strategy. References: 1. Mathers C, Boerma T, Fat DM. The Global Burden of disease:2004 update. Geneva: World Heatlh Organization; 2008. 2. Jessup M, Brozena S. Heart Failure. N Engl J Med 2003;348:2007-18.

‘Death talk’, ‘loss talk’ and identification in the process of ageing

In this paper, we examine the injunction issued by the prominent politician, broadcaster and older people's advocate, Baroness Joan Bakewell, to engage in ‘death talk’. We see positive ethical potential in this injunction, insofar as it serves as a call to confront more directly the prospects of death and dying, thereby releasing creative energies with which to change our outlook on life and ageing more generally. However, when set against a culture that valorises choice, independence and control, the positive ethical potential of such injunctions is invariably thwarted. We illustrate this with reference to one of Bakewell's interventions in a debate on scientific innovation and population ageing. In examining the context of her intervention, we affirm her intuition about its positive ethical potential, but we also point to an ambivalence that accompanies the formulation of the injunction – one that ultimately blunts the force and significance of her intuition. We suggest that Gilleard and Higgs' idea of the third age/fourth age dialectic, combined with the psycho-analytic concepts of fantasy and mourning, allow us to express this intuition better. In particular, we argue that the expression ‘loss talk’ (rather than ‘death talk’) better captures the ethical negotiations that should ultimately underpin the transformation processes associated with ageing, and that our theoretical contextualisation of her remarks can help us see this more clearly. In this view, deteriorations in our physical and mental capacities are best understood as involving changes in how we see ourselves, i.e. in our identifications, and so what is at stake are losses of identity and the conditions under which we can engage in new processes of identification.

Sugar and coffee: A history of settler agriculture in nineteenth-century Liberia

This dissertation is about commercial agriculture in nineteenth-century Liberia. Based primarily on the archives of the American Colonization Society (founder of Liberia), it examines the impact of environmental and demographic constraints on an agrarian settler society from 1822 to the 1890s. Contrary to the standard interpretation, which linked the poor state of commercial agriculture to the settlers' disdain for cultivation, this dissertation argues that the scarcity of labor and capital impeded the growth of commercial agriculture. The causes of the scarcity were high mortality, low immigration and the poverty of the American “Negroes” who began to settle Liberia in 1822. ^ Emigration to Liberia meant almost certain death and affliction for many immigrants because they encountered a new set of diseases. Mortality was particularly high during the early decades of colonization. From 1822 to 1843, about 48 percent of all immigrants died of various causes, usually within their first year. The bulk of the deaths is attributed to malaria. There was no natural increase in the population for this early period and because American “Negroes” were unenthusiastic about relocation to Liberia, immigration remained sparse throughout the century. Low immigration, combined with the high death rate, deprived the fledgling colony of its potential human resource, especially for the cultivation of labor-intensive crops, like sugar cane and coffee. Moreover, even though females constituted approximately half of the settlers, they seldom performed agricultural labor. ^ The problem of labor was compounded by the scarcity of draft animals. Liberia is in the region where trypanosomiasis occurs. The disease is fatal to large livestock. Therefore, animal-drawn plows, common in the United States, were never successfully transplanted in Liberia. Besides, the dearth of livestock obstructed the development of the sugar industry since many planters depended on oxen-powered mills because they could not afford to buy the more expensive steam engine mills. ^ Finally, nearly half of the immigrants were newly emancipated slaves. Usually these former bondsmen arrived in Liberia penniless. Consequently, they lacked the capital to invest in large-scale plantations. The other categories of immigrants (e.g., those who purchased their freedom), were hardly better off than the emancipated slaves. ^

Stable carbon and oxygen isotope record of foraminifera from DSDP Hole 30-289

Sediments accumulate on the sea floor far from land with rates of a few millimetres to a few centimetres per thousand years. Sediments have been accumulating under broadly similar conditions, subject to similar controls, for the past 10 8 years and more. In principle we should be able to study the distribution of climatic variance with frequencies over the range 10**-3 to 10**-7 cycles per year with comparative ease. In fact, nearly all our data are heavily weighted towards the youngest part of the geological record. We study frequencies higher than 10**-4 cycles per year in the special case of a Pleistocene interglacial (the present one), and frequencies in the range 10**-4 to 10**-5 cycles per year in the special case of an ice-age. Although these may be of more direct interest to mankind than earlier periods, it may well be that we will understand the causes of climatic variability better if we can examine their operation over a longer time scale and under different boundary conditions. Rather than review the available data, I have collected some new data to show the feasibility of gathering a data base for examining climatic variability without this usual bias toward the recent. The most widely applicable tool for extracting climatic information from deep-sea sediments is oxygen isotope analysis of calcium carbonate microfossils. It is generally possible to select from the sediment both specimens of benthonic Foraminifera (that is, those that lived in ocean deep water at the sediment-water interface) and specimens of planktonic Foraminifera (that is, those that lived and formed their shells near the ocean surface, and fell to the sediment after death). Thus one is able to monitor conditions at the surface and at depth at simultaneous moments in the geological past. The necessity to analyse calcareous microfossils restricts investigation to calcareous sediments, but even with this restriction in sediment type there are many factors governing the rate of sediment accumulation. On a global scale, sediment accumulates so as to balance the input to the oceans from continental erosion. Even when averaged globally, long-term accumulation rates have varied by almost a factor of ten (Davies et al., 1977, doi:10.1126/science.197.4298.53). At the regional scale, surface productivity and deep-water physical and chemical conditions also affect the sediment accumulation rate. Since all these are susceptible to variation and may well vary in response to climatic change as well as other factors, it is extremely hazardous to attempt to express any climatic variable as a function of time on the basis of measurements originally made as a function of depth in sediment. Although time has been used as a basis for plotting Figs. i-8, these should be regarded as freehand sketches of climatic history rather than as time-series plots.

Determination of 210Po content of vietnamese tobacco samples

Smoking is one of the leading causes of preventable death. In recent years, numerous countries have initiated the prohibition of smoking in restaurants, workplaces and public spaces. The Vietnamese government intends to follow the precautions against public smoking as well. Over and above the number of some hazardous chemical components found in tobacco, ²¹⁰Po isotope content could enhance the probability of the development of lung cancer. In this study 14 Vietnamese tobacco products (commercial cigarettes and pipe tobacco) ²¹⁰Po activity concentration were determined using PIPS semiconductor alpha spectrometry. The results showed that the 210Po activity concentration of the investigated samples varied between 7.40 ± 1.09 - 128.64 ± 11.22 mBq g^-1. The average ²¹⁰Po content of commercial cigarettes was 15.5 mBq g^-1, whilst the average of pipe tobacco was 20.4 mBq g^-1. To estimate the risk of inhalation of ²¹⁰Po isotopes originating as a result of smoking, dose estimations were carried out. © Versita Sp. z o.o.

The effectiveness of community-based interventions to improve maternal and infant health in the Northeast of Brazil

EMOND, Alan et al. The effectiveness of community-based interventions to improve maternal and infant health in the Northeast of Brazil. Revista Panamericana de Salud Pública/ Pan American Journal of Public Health , v.12, n.2, p.101-110, 2002

Project Pró-Natal: population-based study of perinatal and infant mortality in Natal, Northeast Brazil

RAMOS, Ana Maria de Oliveira et al. Project Pró-Natal: population-based study of perinatal and infant mortality in Natal, Northeast Brazil. Pediatric and Developmental Pathology, v.3, n.1, p.29-35, 2000

Estimates of global, regional, and national incidence, prevalence, and mortality of HIV, 1980-2015 : the Global Burden of Disease Study 2015

Background Timely assessment of the burden of HIV/AIDS is essential for policy setting and programme evaluation. In this report from the Global Burden of Disease Study 2015 (GBD 2015), we provide national estimates of levels and trends of HIV/AIDS incidence, prevalence, coverage of antiretroviral therapy (ART), and mortality for 195 countries and territories from 1980 to 2015. Methods For countries without high-quality vital registration data, we estimated prevalence and incidence with data from antenatal care clinics and population-based seroprevalence surveys, and with assumptions by age and sex on initial CD4 distribution at infection, CD4 progression rates (probability of progression from higher to lower CD4 cell-count category), on and off antiretroviral therapy (ART) mortality, and mortality from all other causes. Our estimation strategy links the GBD 2015 assessment of all-cause mortality and estimation of incidence and prevalence so that for each draw from the uncertainty distribution all assumptions used in each step are internally consistent. We estimated incidence, prevalence, and death with GBD versions of the Estimation and Projection Package (EPP) and Spectrum software originally developed by the Joint United Nations Programme on HIV/AIDS (UNAIDS). We used an open-source version of EPP and recoded Spectrum for speed, and used updated assumptions from systematic reviews of the literature and GBD demographic data. For countries with high-quality vital registration data, we developed the cohort incidence bias adjustment model to estimate HIV incidence and prevalence largely from the number of deaths caused by HIV recorded in cause-of-death statistics. We corrected these statistics for garbage coding and HIV misclassifi cation. Findings Global HIV incidence reached its peak in 1997, at 3·3 million new infections (95% uncertainty interval [UI] 3·1–3·4 million). Annual incidence has stayed relatively constant at about 2·6 million per year (range 2·5–2·8 million) since 2005, after a period of fast decline between 1997 and 2005. The number of people living with HIV/AIDS has been steadily increasing and reached 38·8 million (95% UI 37·6–40·4 million) in 2015. At the same time, HIV/AIDS mortality has been declining at a steady pace, from a peak of 1·8 million deaths (95% UI 1·7–1·9 million) in 2005, to 1·2 million deaths (1·1–1·3 million) in 2015. We recorded substantial heterogeneity in the levels and trends of HIV/AIDS across countries. Although many countries have experienced decreases in HIV/AIDS mortality and in annual new infections, other countries have had slowdowns or increases in rates of change in annual new infections. Interpretation Scale-up of ART and prevention of mother-to-child transmission has been one of the great successes of global health in the past two decades. However, in the past decade, progress in reducing new infections has been slow, development assistance for health devoted to HIV has stagnated, and resources for health in low-income countries have grown slowly. Achievement of the new ambitious goals for HIV enshrined in Sustainable Development Goal 3 and the 90-90-90 UNAIDS targets will be challenging, and will need continued eff orts from governments and international agencies in the next 15 years to end AIDS by 2030.

The effectiveness of community-based interventions to improve maternal and infant health in the Northeast of Brazil

EMOND, Alan et al. The effectiveness of community-based interventions to improve maternal and infant health in the Northeast of Brazil. Revista Panamericana de Salud Pública/ Pan American Journal of Public Health , v.12, n.2, p.101-110, 2002

Project Pró-Natal: population-based study of perinatal and infant mortality in Natal, Northeast Brazil

RAMOS, Ana Maria de Oliveira et al. Project Pró-Natal: population-based study of perinatal and infant mortality in Natal, Northeast Brazil. Pediatric and Developmental Pathology, v.3, n.1, p.29-35, 2000

Quasispecies dynamics and treatment outcome during early hepatitis C infection in a cohort of HIV-infected men

Hepatitis C virus (HCV) is emerging as one of the leading causes of morbidity and mortality in individuals infected with HIV and has overtaken AIDS-defining illnesses as a cause of death in HIV patient populations who have access to highly active antiretroviral therapy. For many years, the clonal analysis was the reference method for investigating viral diversity. In this thesis, a next generation sequencing (NGS) approach was developed using 454 pyrosequencing and Illumina-based technology. A sequencing pipeline was developed using two different NGS approaches, nested PCR, and metagenomics. The pipeline was used to study the viral populations in the sera of HCV-infected patients from a unique cohort of 160 HIV-positive patients with early HCV infection. These pipelines resulted in an improved understanding of HCV quasispecies dynamics, especially regarding studying response to treatment. Low viral diversity at baseline correlated with sustained virological response (SVR) while high viral diversity at baseline was associated with treatment failure. The emergence of new viral strains following treatment failure was most commonly associated with emerging dominance of pre-existing minority variants rather than re-infection. In the new era of direct-acting antivirals, next generation sequencing technologies are the most promising tool for identifying minority variants present in the HCV quasispecies populations at baseline. In this cohort, several mutations conferring resistance were detected in genotype 1a treatment-naïve patients. Further research into the impact of baseline HCV variants on SVR rates should be carried out in this population. A clearer understanding of the properties of viral quasispecies would enable clinicians to make improved treatment choices for their patients.

Benefits of targeting each risk factor for cardiovascular death

Globally cardiovascular diseases are the main cause of death. In clinical practice we are able to advise an control several risk factors that might benefit our patients. But we know that trying to reach all goals we might chew more than we can swallow