Comparing primary prevention with secondary prevention to explain decreasing Coronary Heart Disease death rates in Ireland, 1985-2000.

BACKGROUND: To investigate whether primary prevention might be more favourable than secondary prevention (risk factor reduction in patients with coronary heart disease(CHD)). METHODS: The cell-based IMPACT CHD mortality model was used to integrate data for Ireland describing CHD patient numbers, uptake of specific treatments, trends in major cardiovascular risk factors, and the mortality benefits of these specific risk factor changes in CHD patients and in healthy people without recognised CHD. RESULTS: Between 1985 and 2000, approximately 2,530 fewer deaths were attributable to reductions in the three major risk factors in Ireland. Overall smoking prevalence declined by 14% between 1985 and 2000, resulting in about 685 fewer deaths (minimum estimate 330, maximum estimate 1,285) attributable to smoking cessation: about 275 in healthy people and 410 in known CHD patients. Population total cholesterol concentrations fell by 4.6%, resulting in approximately 1,300 (minimum estimate 1,115, maximum estimate 1,660) fewer deaths attributable to dietary changes(1,185 in healthy people and 115 in CHD patients) plus 305 fewer deaths attributable to statin treatment (45 in people without CHD and 260 in CHD patients). Mean population diastolic blood pressure fell by 7.2%, resulting in approximately 170 (minimum estimate 105, maximum estimate 300) fewer deaths attributable to secular falls in blood pressure (140 in healthy people and 30 in CHD patients), plus approximately 70 fewer deaths attributable to antihypertensive treatments in people without CHD. Of all the deaths attributable to risk factor falls, some 1,715 (68%) occurred in people without recognized CHD and 815(32%) in CHD patients. CONCLUSION: Compared with secondary prevention, primary prevention achieved a two-fold larger reduction in CHD deaths. Future national CHD policies should therefore prioritize nationwide interventions to promote healthy diets and reduce smoking

Experimental Evidence for a Metallohydrolase Mechanism in Which the Nucleophile Is Not Delivered by a Metal Ion: EPR Spectrokinetic and Structural Studies of Aminopeptidase from \u3cem\u3eVibrio proteolyticus\u3c/em\u3e

Metallohydrolases catalyse some of the most important reactions in biology and are targets for numerous chemotherapeutic agents designed to combat bacterial infectivity, antibiotic resistance, HIV infectivity, tumour growth, angiogenesis and immune disorders. Rational design of inhibitors of these enzymes with chemotherapeutic potential relies on detailed knowledge of the catalytic mechanism. The roles of the catalytic transition ions in these enzymes have long been assumed to include the activation and delivery of a nucleophilic hydroxy moiety. In the present study, catalytic intermediates in the hydrolysis of L-leucyl-L-leucyl-L-leucine by Vibrio proteolyticus aminopeptidase were characterized in spectrokinetic and structural studies. Rapid-freeze-quench EPR studies of reaction products of L-leucyl-L-leucyl-L-leucine and Co(II)-substituted aminopeptidase, and comparison of the EPR data with those from structurally characterized complexes of aminopeptidase with inhibitors, indicated the formation of a catalytically competent post-Michaelis pre-transition state intermediate with a structure analogous to that of the inhibited complex with bestatin. The X-ray crystal structure of an aminopeptidase–L-leucyl-L-leucyl-L-leucine complex was also analogous to that of the bestatin complex. In these structures, no water/hydroxy group was observed bound to the essential metal ion. However, a water/hydroxy group was clearly identified that was bound to the metal-ligating oxygen atom of Glu152. This water/hydroxy group is proposed as a candidate for the active nucleophile in a novel metallohydrolase mechanism that shares features of the catalytic mechanisms of aspartic proteases and of B2 metallo-b-lactamases. Preliminary studies on site-directed variants are consistent with the proposal. Other features of the structure suggest roles for the dinuclear centre in geometrically and electrophilically activating the substrate

Complete quantum teleportation using nuclear magnetic resonance

Quantum mechanics provides spectacular new information processing abilities (Bennett 1995, Preskill 1998). One of the most unexpected is a procedure called quantum teleportation (Bennett et al 1993) that allows the quantum state of a system to be transported from one location to another, without moving through the intervening space. Partial implementations of teleportation (Bouwmeester et al 1997, Boschi et al 1998) over macroscopic distances have been achieved using optical systems, but omit the final stage of the teleportation procedure. Here we report an experimental implementation of the full quantum teleportation operation over inter-atomic distances using liquid state nuclear magnetic resonance (NMR). The inclusion of the final stage enables for the first time a teleportation implementation which may be used as a subroutine in larger quantum computations, or for quantum communication. Our experiment also demonstrates the use of quantum process tomography, a procedure to completely characterize the dynamics of a quantum system. Finally, we demonstrate a controlled exploitation of decoherence as a tool to assist in the performance of an experiment.Comment: 15 pages, 2 figures. Minor differences between this and the published versio

The Emotional and Practical Experiences of Formula-Feeding Mothers

The majority of infant‐feeding research is focused on identifying mother's reasons for the cessation of breastfeeding. The experience of mothers who choose to use formula is largely overlooked in quantitative designs. This study aimed to describe the emotional and practical experiences of mothers who formula feed in any quantity, and examine whether these experiences would vary among different cohorts of formula‐feeding mothers according to prenatal feeding intention and postnatal feeding method. A total of 890 mothers of infants up to 26 weeks of age, who were currently formula feeding in any quantity, were recruited through relevant international social media sites via advertisements providing a link to an online survey. Predictors of emotional experiences included guilt, stigma, satisfaction, and defense as a result of their infant feeding choices. Practical predictor variables included support received from health professionals, respect displayed by their everyday environment, and main sources of infant feeding information. Descriptive findings from the overall sample highlighted a worryingly high percentage of mother's experienced negative emotions as a result of their decision to use formula. Multinomial logit models revealed that negative emotions such as guilt, dissatisfaction, and stigma were directly associated with feeding intention and method. The evidence suggests that the current approach to infant‐feeding promotion and support may be paradoxically related to significant issues with emotional well‐being. These findings support criticisms of how infant‐feeding recommendations are framed by health care professionals and policy makers, and highlight a need to address formula feeding in a more balanced, woman‐centered manner

Non-steroidal anti-inflammatory drugs (NSAIDs) in cancer pain:A database analysis to determine recruitment feasibility for a clinical trial

BACKGROUND: Insufficient evidence exists to support or refute use of NSAIDs for managing cancer pain. Palliative physicians support a placebo-controlled trial of NSAIDs as strong opioid adjuncts for cancer-induced bone pain as the most pragmatic design to benefit clinical practice. AIM: We aimed to determine patient numbers receiving palliative radiotherapy for cancer-induced bone pain, estimate the suitability of NSAID prescription and determine survival, guiding future trial feasibility. DESIGN: A retrospective observational database analysis was undertaken using 5 years of routinely collected regional radiotherapy and healthcare data, filtered to achieve a cohort with cancer-induced bone pain. Demographics and survival were linked to available serology and co-morbidity data. SETTING/PARTICIPANTS: Data was sourced from the regional Leeds Cancer Centre, a tertiary care setting. Patients who underwent palliative single fraction 8 gray (Gy) radiotherapy treatment for cancer-induced bone pain were included, totalling 2411 over 5 years. RESULTS: A mean of 478 patients received palliative radiotherapy for cancer-induced bone pain annually. Median age (IQR) was 70 (62–77); negatively skewed (−0.69). 65.3% died within 1 year of radiotherapy; 48.0% within 6 months. Age was not associated with survival on univariable analysis (HR 0.999 (95% CI 0.996–1.003)). Serology from 1063 patients (44.2%) were available; eGFR was ⩾60 mL/min/1.73 m(2) in 83.0%. From available data (1352 pts; 51.6% of sample), 20.2% had a coded co-morbidity contra-indicating NSAIDs. Combining serology and co-morbidities, 68.5% could be considered for NSAID prescription. CONCLUSIONS: Patient numbers at a regional radiotherapy centre support the feasibility of trial recruitment. Available serology and co-morbidity data suggest two-thirds may be suitable for NSAID prescription

Population assessment of future trajectories in coronary heart disease mortality.

Background: Coronary heart disease (CHD) mortality rates have been decreasing in Iceland since the 1980s, largely reflecting improvements in cardiovascular risk factors. The purpose of this study was to predict future CHD mortality in Iceland based on potential risk factor trends. Methods and findings: The previously validated IMPACT model was used to predict changes in CHD mortality between 2010 and 2040 among the projected population of Iceland aged 25–74. Calculations were based on combining: i) data on population numbers and projections (Statistics Iceland), ii) population risk factor levels and projections (Refine Reykjavik study), and iii) effectiveness of specific risk factor reductions (published meta-analyses). Projections for three contrasting scenarios were compared: 1) If the historical risk factor trends of past 30 years were to continue, the declining death rates of past decades would level off, reflecting population ageing. 2) If recent trends in risk factors (past 5 years) continue, this would result in a death rate increasing from 49 to 70 per 100,000. This would reflect a recent plateau in previously falling cholesterol levels and recent rapid increases in obesity and diabetes prevalence. 3) Assuming that in 2040 the entire population enjoys optimal risk factor levels observed in low risk cohorts, this would prevent almost all premature CHD deaths before 2040. Conclusions: The potential increase in CHD deaths with recent trends in risk factor levels is alarming both for Iceland and probably for comparable Western populations. However, our results show considerable room for reducing CHD mortality. Achieving the best case scenario could eradicate premature CHD deaths by 2040. Public health policy interventions based on these predictions may provide a cost effective means of reducing CHD mortality in the future

Intermediate Phenotypes Identify Divergent Pathways to Alzheimer's Disease

Background: Recent genetic studies have identified a growing number of loci with suggestive evidence of association with susceptibility to Alzheimer's disease (AD). However, little is known of the role of these candidate genes in influencing intermediate phenotypes associated with a diagnosis of AD, including cognitive decline or AD neuropathologic burden. Methods/Principal Findings: Thirty-two single nucleotide polymorphisms (SNPs) previously implicated in AD susceptibility were genotyped in 414 subjects with both annual clinical evaluation and completed brain autopsies from the Religious Orders Study and the Rush Memory and Aging Project. Regression analyses evaluated the relation of SNP genotypes to continuous measures of AD neuropathology and cognitive function proximate to death. A SNP in the zinc finger protein 224 gene (ZNF224, rs3746319) was associated with both global AD neuropathology (p = 0.009) and global cognition (p = 0.002); whereas, a SNP at the phosphoenolpyruvate carboxykinase locus (PCK1, rs8192708) was selectively associated with global cognition (p = 3.57×10−4). The association of ZNF224 with cognitive impairment was mediated by neurofibrillary tangles, whereas PCK1 largely influenced cognition independent of AD pathology, as well as Lewy bodies and infarcts. Conclusions/Significance: The findings support the association of several loci with AD, and suggest how intermediate phenotypes can enhance analysis of susceptibility loci in this complex genetic disorder

Structure and optical properties of Lu <inf>2</inf>SiO <inf>5</inf>:Ce phosphor thin films

Luminescent, cerium doped Lu 2SiO 5 thin films with C2/c symmetry have been prepared by pulsed laser deposition (PLD) at temperatures much lower than the crystallization temperature (2150°C) of the corresponding bulk crystals. The PLD grown films show the typical luminescence resulting from the Ce 3+ 5d-4f transition. Maximum luminescence efficiency was observed for films prepared at an oxygen partial pressure of 200 mTorr at 600°C. These conditions reflect a balance between Ce 4+/Ce 3+ interconversion and the crystalline quality of the films. The results indicate that PLD offers a low temperature deposition technique for complex oxide phosphor materials. © 2006 American Institute of Physics

Radium ion: A possible candidate for measuring atomic parity violation

Single trapped and laser cooled Radium ion as a possible candidate for measuring the parity violation induced frequency shift has been discussed here. Even though the technique to be used is similar to that proposed by Fortson [1], Radium has its own advantages and disadvantages. The most attractive part of Radium ion as compared to that of Barium ion is its mass which comes along with added complexity of instability as well as other issues which are discussed hereComment: Conference proceedin