Platelet receptors and patient responses: The contributions of Professor Stan Heptinstall to platelet research.

Stan Heptinstall's contributions to platelet research covered organising meetings at the national and European level as well as starting and maintaining the journal "Platelets". The major part of his research addressed problems of inhibition of platelet receptors and the effects of this on patient health. In particular, the effects of P2Y12 inhibitors on patients with acute cardiovascular problems were a major focus. Other studies included the effects of feverfew (Tanacetum parthenium) extracts on platelets, of direct anti-IIb/IIIa receptor (αIIbβ3) inhibitors and of prostanoids on platelet function. Recently, methods for assessing the effectiveness of platelet inhibition were investigated.

Investigation of robotics-assisted tilt table technology for cardiopulmonary exercise testing in stroke patients

Due to the lack of exercise testing devices that can be employed in stroke patients with severe disability, the aim of this PhD research was to investigate the clinical feasibility of using a robotics-assisted tilt table (RATT) as a method for cardiopulmonary exercise testing (CPET) and exercise training in stroke patients. For this purpose, the RATT was augmented with force sensors, a visual feedback system and a work rate calculation algorithm. As the RATT had not been used previously for CPET, the first phase of this project focused on a feasibility study in 11 healthy able-bodied subjects. The results demonstrated substantial cardiopulmonary responses, no complications were found, and the method was deemed feasible. The second phase was to analyse validity and test-retest reliability of the primary CPET parameters obtained from the RATT in 18 healthy able-bodied subjects and to compare the outcomes to those obtained from standard exercise testing devices (a cycle ergometer and a treadmill). The results demonstrated that peak oxygen uptake (V'O2peak) and oxygen uptake at the submaximal exercise thresholds on the RATT were ̴20% lower than for the cycle ergometer and ̴30% lower than on the treadmill. A very high correlation was found between the RATT vs the cycle ergometer V'O2peak and the RATT vs the treadmill V'O2peak. Test-retest reliability of CPET parameters obtained from the RATT were similarly high to those for standard exercise testing devices. These findings suggested that the RATT is a valid and reliable device for CPET and that it has potential to be used in severely impaired patients. Thus, the third phase was to investigate using the RATT for CPET and exercise training in 8 severely disabled stroke patients. The method was technically implementable, well tolerated by the patients, and substantial cardiopulmonary responses were observed. Additionally, all patients could exercise at the recommended training intensity for 10 min bouts. Finally, an investigation of test-retest reliability and four-week changes in cardiopulmonary fitness was carried out in 17 stroke patients with various degrees of disability. Good to excellent test-retest reliability and repeatability were found for the main CPET variables. There was no significant difference in most CPET parameters over four weeks. In conclusion, based on the demonstrated validity, reliability and repeatability, the RATT was found to be a feasible and appropriate alternative exercise testing and training device for patients who have limitations for use of standard devices.

A role for tuned levels of nucleosome remodeler subunit ACF1 during Drosophila oogenesis

The Chromatin Accessibility Complex (CHRAC) consists of the ATPase ISWI, the large ACF1 subunit and a pair of small histone-like proteins, CHRAC-14/16. CHRAC is a prototypical nucleosome sliding factor that mobilizes nucleosomes to improve the regularity and integrity of the chromatin fiber. This may facilitate the formation of repressive chromatin. Expression of the signature subunit ACF1 is restricted during embryonic development, but remains high in primordial germ cells. Therefore, we explored roles for ACF1 during Drosophila oogenesis. ACF1 is expressed in somatic and germline cells, with notable enrichment in germline stem cells and oocytes. The asymmetrical localization of ACF1 to these cells depends on the transport of the Acf1 mRNA by the Bicaudal-D/Egalitarian complex. Loss of ACF1 function in the novel Acf1(7) allele leads to defective egg chambers and their elimination through apoptosis. In addition, we find a variety of unusual 16-cell cyst packaging phenotypes in the previously known Acf1(1) allele, with a striking prevalence of egg chambers with two functional oocytes at opposite poles. Surprisingly, we found that the Acf1(1) deletion - despite disruption of the Acf1 reading frame - expresses low levels of a PHD-bromodomain module from the C-terminus of ACF1 that becomes enriched in oocytes. Expression of this module from the Acf1 genomic locus leads to packaging defects in the absence of functional ACF1, suggesting competitive interactions with unknown target molecules. Remarkably, a two-fold overexpression of CHRAC (ACF1 and CHRAC-16) leads to increased apoptosis and packaging defects. Evidently, finely tuned CHRAC levels are required for proper oogenesis.

Pitfalls of practicing cancer epidemiology in resource-limited settings: the case of survival and loss to follow-up after a diagnosis of Kaposi's sarcoma in five countries across sub-Saharan Africa.

BACKGROUND Survival after diagnosis is a fundamental concern in cancer epidemiology. In resource-rich settings, ambient clinical databases, municipal data and cancer registries make survival estimation in real-world populations relatively straightforward. In resource-poor settings, given the deficiencies in a variety of health-related data systems, it is less clear how well we can determine cancer survival from ambient data. METHODS We addressed this issue in sub-Saharan Africa for Kaposi's sarcoma (KS), a cancer for which incidence has exploded with the HIV epidemic but for which survival in the region may be changing with the recent advent of antiretroviral therapy (ART). From 33 primary care HIV Clinics in Kenya, Uganda, Malawi, Nigeria and Cameroon participating in the International Epidemiologic Databases to Evaluate AIDS (IeDEA) Consortia in 2009-2012, we identified 1328 adults with newly diagnosed KS. Patients were evaluated from KS diagnosis until death, transfer to another facility or database closure. RESULTS Nominally, 22% of patients were estimated to be dead by 2 years, but this estimate was clouded by 45% cumulative lost to follow-up with unknown vital status by 2 years. After adjustment for site and CD4 count, age <30 years and male sex were independently associated with becoming lost. CONCLUSIONS In this community-based sample of patients diagnosed with KS in sub-Saharan Africa, almost half became lost to follow-up by 2 years. This precluded accurate estimation of survival. Until we either generally strengthen data systems or implement cancer-specific enhancements (e.g., tracking of the lost) in the region, insights from cancer epidemiology will be limited.

The Improving Relative Status of Black Men

Using data from the Current Population Survey, we examine recent trends in the relative economic status of black men. Our findings point to gains in the relative wages of black men (compared to whites) during the 1990s, especially among younger workers. In 1989, the average black male worker (experienced or not) earned about 69 percent as much per week as the average white male worker. In 2001, the average younger black worker was earning about 86% percent as much as an equally experienced white male; black males at all experience levels earned 72 percent as much as the average white in 2001. Greater occupational diversity and a reduction in unobserved skill differences and/or labor market discrimination explain much of the trend. For both younger and older workers, general wage inequality tempered the rate of wage convergence between blacks and whites during the 1990s, although the effects were less pronounced than during the 1980s.

Ball Response and Traction of Skinned Infields Amended with Calcine Clay at Varying Soil Moisture Contents

The skinned portions of baseball and softball infields vary widely with respect to soil texture, applied amendments and conditioners, and water management. No studies have been reported that quantify the effects of these varying construction and maintenance practices on the playability of the skinned portions of infields. In Connecticut, USA, skinned infield plots were constructed from five different soils (silt loam, loam, coarse sandy loam, loamy sand, loamy coarse sand) and amended with four rates of calcined clay (0, 4.9, 9.8, 19.6 kg m–2) to determine the effects on surface hardness, traction, and ball-to-surface friction (static and dynamic) at varying soil moisture contents (10, 14, and 18%). Bulk density, saturated hydraulic conductivity, and shear strength of the different soil–calcined clay rate combinations were determined. Increasing the rate of calcined clay decreased bulk density and shear strengths, and increased saturated hydraulic conductivity. Surface hardness increased more with coarse-textured soils and increasing calcined clay rate, but decreased more with fine-textured soils and increasing soil moisture. Increasing the calcined clay rate resulted in decreases in ball-to-surface static friction across all soils and decreased dynamic friction with the fine-textured soils. Increases in soil moisture increased friction in all soils. The fine-textured soils had greater traction than the sandy soils, but no consistent calcined clay or moisture effects on traction were observed. Shear strength of the soils was highly correlated with traction and friction. The results suggest that differences in skinned infield soils are quantifiable, which could lead to the development of playing surface standards.

Does the Federal Reserve Follow a Non-Linear Taylor Rule?

The Taylor rule has become one of the most studied strategies for monetary policy. Yet, little is known whether the Federal Reserve follows a non-linear Taylor rule. This paper employs the smooth transition regression model and asks the question: does the Federal Reserve change its policy-rule according to the level of inflation and/or the output gap? I find that the Federal Reserve does follow a non-linear Taylor rule and, more importantly, that the Federal Reserve followed a non-linear Taylor rule during the golden era of monetary policy, 1985-2005, and a linear Taylor rule throughout the dark age of monetary policy, 1960-1979. Thus, good monetary policy is associated with a non-linear Taylor rule: once inflation approaches a certain threshold, the Federal Reserve adjusts its policy-rule and begins to respond more forcefully to inflation.

Predicting the Fed

Predicting the federal funds rate and beating the federal funds futures market: mission impossible? Not so. We employ a Markov transition process and show that this model outperforms the federal funds futures market in predicting the target federal funds rate. Thus, by using purely historical data we are able to better explain future monetary policy than a forward looking measure like the federal funds futures rate. The fact that the federal funds futures market can be beaten by a statistical model, suggests that the federal funds futures market lacks eciency. The mar- ket allocates too much weight to current Federal Reserve communication and other real-time macro events, and allocates too little weight to past monetary policy behavior.

Job Matching and Wage Growth in the U.S. and Germany

This paper examines the contribution of job matching to wage growth in the U.S. and Germany using data drawn from the Panel Study of Income Dynamics and the German Socio-Economic Panel from 1984 through 1992. Using a symmetrical set of variables and data handling procedures, real wage growth is found to be higher in the U.S. than in Germany during this period. Also, using two different estimators, job matches are found to enhance wage growth in the U.S. and retard it in Germany. The relationship of general skills to employment in each country appears responsible for this result.

Last Hired, First Fired? Black-White Unemployment and the Business Cycle

Past studies have tested the claim that blacks are the last hired during periods of economic growth and the first fired in recessions by examining the movement of relative unemployment rates over the business cycle. Any conclusion drawn from this type of analysis must be viewed as tentative because the cyclical movements in the underlying transitions into and out of unemployment are not examined. Using Current Population Survey data matched across adjacent months from 1989 to 2004, this paper examines labor market transitions for prime age males to test this hypothesis. Considerable evidence is presented that blacks are the first fired as the business cycle weakens. However, no evidence is found that blacks are the last hired. Instead, blacks are initially hired from the ranks of the unemployed early in the business cycle and later are drawn from non-participation. Narrowing of the racial unemployment gap near the peak of the business cycle is driven by a reduction in the rate of job loss for blacks rather than increases in hiring. There is also evidence that residual differences in the racial unemployment gap vary systematically over the business cycle in a manner consistent with discrimination being more evident in the economy at times when its cost is lower.

Income Inequality in the 1990s: Re-Forging a Lost Relationship?

Using data from March Current Population Surveys we find gains from economic growth over the 1990s business cycle (1989-2000) were more equitably distributed than over the 1980s business cycle (1979-1989) using summary inequality measures as well as kernel density estimations. The entire distribution of household size-adjusted income moved upwards in the 1990s with profound improvements for African Americans, single mothers and those living in households receiving welfare. Most gains occurred over the growth period 1993-2000. Improvements in average income and income inequity over the latter period are reminiscent of gains seen in the first three decades after World War II.