Subclinical thyroid dysfunction, cardiac function, and the risk of heart failure. The Cardiovascular Health study.

OBJECTIVES: The goal of this study was to determine whether subclinical thyroid dysfunction was associated with incident heart failure (HF) and echocardiogram abnormalities. BACKGROUND: Subclinical hypothyroidism and hyperthyroidism have been associated with cardiac dysfunction. However, long-term data on the risk of HF are limited. METHODS: We studied 3,044 adults>or=65 years of age who initially were free of HF in the Cardiovascular Health Study. We compared adjudicated HF events over a mean 12-year follow-up and changes in cardiac function over the course of 5 years among euthyroid participants, those with subclinical hypothyroidism (subdivided by thyroid-stimulating hormone [TSH] levels: 4.5 to 9.9, >or=10.0 mU/l), and those with subclinical hyperthyroidism. RESULTS: Over the course of 12 years, 736 participants developed HF events. Participants with TSH>or=10.0 mU/l had a greater incidence of HF compared with euthyroid participants (41.7 vs. 22.9 per 1,000 person years, p=0.01; adjusted hazard ratio: 1.88; 95% confidence interval: 1.05 to 3.34). Baseline peak E velocity, which is an echocardiographic measurement of diastolic function associated with incident HF in the CHS cohort, was greater in those patients with TSH>or=10.0 mU/l compared with euthyroid participants (0.80 m/s vs. 0.72 m/s, p=0.002). Over the course of 5 years, left ventricular mass increased among those with TSH>or=10.0 mU/l, but other echocardiographic measurements were unchanged. Those patients with TSH 4.5 to 9.9 mU/l or with subclinical hyperthyroidism had no increase in risk of HF. CONCLUSIONS: Compared with euthyroid older adults, those adults with TSH>or=10.0 mU/l have a moderately increased risk of HF and alterations in cardiac function but not older adults with TSH<10.0 mU/l. Clinical trials should assess whether the risk of HF might be ameliorated by thyroxine replacement in individuals with TSH>or=10.0 mU/l.

IL1B and DEFB1 Polymorphisms Increase Susceptibility to Invasive Mold Infection After Solid-Organ Transplantation.

BACKGROUND: Single-nucleotide polymorphisms (SNPs) in immune genes have been associated with susceptibility to invasive mold infection (IMI) among hematopoietic stem cell but not solid-organ transplant (SOT) recipients. METHODS: Twenty-four SNPs from systematically selected genes were genotyped among 1101 SOT recipients (715 kidney transplant recipients, 190 liver transplant recipients, 102 lung transplant recipients, 79 heart transplant recipients, and 15 recipients of other transplants) from the Swiss Transplant Cohort Study. Association between SNPs and the end point were assessed by log-rank test and Cox regression models. Cytokine production upon Aspergillus stimulation was measured by enzyme-linked immunosorbent assay in peripheral blood mononuclear cells (PBMCs) from healthy volunteers and correlated with relevant genotypes. RESULTS: Mold colonization (n = 45) and proven/probable IMI (n = 26) were associated with polymorphisms in the genes encoding interleukin 1β (IL1B; rs16944; recessive mode, P = .001 for colonization and P = .00005 for IMI, by the log-rank test), interleukin 1 receptor antagonist (IL1RN; rs419598; P = .01 and P = .02, respectively), and β-defensin 1 (DEFB1; rs1800972; P = .001 and P = .0002, respectively). The associations with IL1B and DEFB1 remained significant in a multivariate regression model (P = .002 for IL1B rs16944; P = .01 for DEFB1 rs1800972). The presence of 2 copies of the rare allele of rs16944 or rs419598 was associated with reduced Aspergillus-induced interleukin 1β and tumor necrosis factor α secretion by PBMCs. CONCLUSIONS: Functional polymorphisms in IL1B and DEFB1 influence susceptibility to mold infection in SOT recipients. This observation may contribute to individual risk stratification.

PTX3 Polymorphisms and Invasive Mold Infections After Solid Organ Transplant.

Donor PTX3 polymorphisms were shown to influence the risk of invasive aspergillosis among hematopoietic stem cell transplant recipients. Here, we show that PTX3 polymorphisms are independent risk factors for invasive mold infections among 1101 solid organ transplant recipients, thereby strengthening their role in mold infection pathogenesis and patients' risk stratification.

Mechanical circulatory support for destination therapy.

Patients with chronic heart failure who are not eligible for heart transplant and whose life expectancy depends mainly on the heart disease may benefit from mechanical circulatory support. Mechanical circulatory support restores adequate cardiac output and organ perfusion and eventually improves patients' clinical condition, quality of life and life expectancy. This treatment is called destination therapy (DT) and we estimate that in Switzerland more than 120 patients per year could benefit from it. In the last 10 years, design of the devices, implantation techniques and prognoses have changed dramatically. The key to successful therapy with a left ventricular assist device is appropriate patient selection, although we are still working on the definition of reliable inclusion and exclusion criteria and optimal timing for surgical implantation. Devices providing best long-term results are continuous flow, rotary or axial blood pumps implanted using minimally invasive techniques on a beating heart. These new devices (Thoratec HeartMate II and HeartWare HVAD) have only a single moving part, and have improved durability with virtually 10 years freedom from mechanical failure. In selected patients, the overall actuarial survival of DT patients is 75% at 1 year and 62% at 2 years, with a clear improvement in quality of life compared with medical management only. Complications include bleeding and infections; their overall incidence is significantly lower than with previous devices and their management is well defined. DT is evolving into an effective and reasonably cost-effective treatment option for a growing population of patients not eligible for heart transplant, showing encouraging survival rates at 2 years and providing clear improvement in quality of life. The future is bright for people suffering from chronic heart failure.

Armourstone revetments : will standard design criteria prevent failure? /

Bank stabilization structures are used to prevent the loss of valuable land within the urban environment and the decision for the type of structure used depends on the properties of the stream. In the urban areas of Southern Ontario there is a preference for the use of armourstone blocks as bank stabilization. The armourstone revetment is a free standing stone structure with large blocks of stone layered vertically and offset from one another. During fieldwork at Forty Mile Creek in Grimsby, Ontario armourstone failure was identified by the removal of two stones within one column from the wall. Since the footer stones were still in place, toe scour was eliminated as a cause of failure. Through theoretical, field, and experimental work the process of suction has been identified as a mode of failure for the armourstone wall and the process of suction works similarly to quarrying large blocks of rock off bedrock streambeds. The theory of lateral suction has previously not been taken into consideration for the design of these walls. The physical and hydraulic evidence found in the field and studied during experimental work indicate that the armourstone wall is vulnerable to the process of suction. The forces exerted by the flow and the resistance of the block determine the stability of the armourstone block within the wall. The design of the armourstone wall, high surface velocities, and short pulses of faster flowing water within the profile could contribute to armourstone failure by providing the forces needed for suction to occur, therefore adjustments to the design of the wall should be made in order to limit the effect.

Analysis of the late correspondence between our administration and Great Britain & France, with an attempt to show what are the real causes of the failure of the negotiation.

Ten pieces originally published in the Columbian Centinel. A later edition with imprint New York, Printed for E. Sargeant, 1809, contains two additional pieces.

Frederick Swann at Memorial Hall pipe organ, Chapman College, Orange, California

Dedication of new Schant 37-rank pipe organ in the auditorium of Memorial Hall, Chapman College, Orange, California, April 18, 1974. Frederick Swann, director of music and organist of the Riverside Church in New York City, is playing.

Evaporative respiratory cooling augments pit organ thermal detection in rattlesnakes

Rattlesnakes use their facial pit organs to sense external thermal fluctuations. A temperature decrease in the heat-sensing membrane of the pit organ has the potential to enhance heat flux between their endothermic prey and the thermal sensors, affect the optimal functioning of thermal sensors in the pit membrane and reduce the formation of thermal ‘‘afterimages’’, improving thermal detection. We examined the potential for respiratory cooling to improve strike behaviour, capture, and consumption of endothermic prey in the South American rattlesnake, as behavioural indicators of thermal detection. Snakes with a higher degree of rostral cooling were more accurate during the strike, attacking warmer regions of their prey, and relocated and consumed their prey faster. These findings reveal that by cooling their pit organs, rattlesnakes increase their ability to detect endothermic prey; disabling the pit organs caused these differences to disappear. Rattlesnakes also modify the degree of rostral cooling by altering their breathing pattern in response to biologically relevant stimuli, such as a mouse odour. Our findings reveal that low humidity increases their ability to detect endothermic prey, suggesting that habitat and ambush sites election in the wild may be influenced by external humidity levels as well as temperature.

Score PELOD : indice précoce de mortalité pédiatrique des transplantations hépatiques pour hépatite fulminante

La transplantation hépatique est le seul traitement définitif des enfants ayant une hépatite fulminante sans résolution spontanée. L’évolution de cette maladie dans la population pédiatrique diffère de celle adulte, particulièrement en regard de l’encéphalopathie. Pour définir les indications de transplantation hépatique, plusieurs indicateurs précoces de pronostic furent étudiés chez les adultes. Ces indicateurs n’ont pu être transposés à la population pédiatrique. Objectif primaire : Déterminer les marqueurs de risque de mortalité des enfants recevant une transplantation hépatique pour une hépatite fulminante, se définissant par une insuffisance hépatique sévère sans antécédent au cours des huit semaines précédentes. Méthode : Il s’agit d’une étude rétrospective incluant tous les enfants ayant reçu une transplantation hépatique pour une hépatite fulminante à l’hôpital Sainte-Justine entre 1985 et 2005. Le score PELOD (Pediatric Logistic Organ Dysfunction) est une mesure de sévérité clinique d’un enfant aux soins intensifs. Il fut calculé à l’admission et avant la transplantation hépatique. Résultats : Quatorze enfants (cinq mois à seize ans) reçurent une transplantation hépatique pour une hépatite fulminante. Neuf enfants (64%) survécurent et cinq (36%) décédèrent. L’utilisation de la ventilation mécanique fut associée à un mauvais pronostic (p = 0,027). Entre l’admission et la transplantation hépatique, 88% des enfants ayant eu une variation du score PELOD inférieure à cinq survécurent. Tous ceux ayant eu une variation supérieure à cinq décédèrent. (p = 0,027) Conclusion : La variation du score PELOD pourrait aider à définir un indicateur précoce de l’évolution d’un enfant après une transplantation hépatique pour une hépatite fulminante.

Market failure, inequality and redistribution

We consider the following question: does market failure justify redistribution? We argue that the general answer to this question is no, in the sense that policies for correcting market failures do not aim at producing a "desirable" income distribution. This follows from the fact that, by construction, market failure is a deviation from "efficiency" that does not involve any notion of a desirable distribution of welfare (or income). However, there are special cases where a "corrective measure" involving redistribution can offset a market failure, so this can provide a form of efficiency- based justification for redistribution.