Associations between fluctuations in lung function and asthma control in two populations with differing asthma severity

Lung function is a major criterion used to assess asthma control. Fluctuation analyses can account for lung function history over time, and may provide an additional dimension to characterise control. The relationships between mean and fluctuations in lung function with asthma control, exacerbation and quality of life were studied in two independent data sets.

Predicting future risk of asthma exacerbations using individual conditional probabilities

Determination of future risk of exacerbations is a key issue in the management of asthma. We previously developed a method to calculate conditional probabilities (π) of future decreases in lung function by using the daily fluctuations in peak expiratory flow (PEF).

General and specific components of depression and anxiety in an adolescent population

Background Depressive and anxiety symptoms often co-occur resulting in a debate about common and distinct features of depression and anxiety. Methods An exploratory factor analysis (EFA) and a bifactor modelling approach were used to separate a general distress continuum from more specific sub-domains of depression and anxiety in an adolescent community sample (n = 1159, age 14). The Mood and Feelings Questionnaire and the Revised Children's Manifest Anxiety Scale were used. Results A three-factor confirmatory factor analysis is reported which identified a) mood and social-cognitive symptoms of depression, b) worrying symptoms, and c) somatic and information-processing symptoms as distinct yet closely related constructs. Subsequent bifactor modelling supported a general distress factor which accounted for the communality of the depression and anxiety items. Specific factors for hopelessness-suicidal thoughts and restlessness-fatigue indicated distinct psychopathological constructs which account for unique information over and above the general distress factor. The general distress factor and the hopelessness-suicidal factor were more severe in females but the restlessness-fatigue factor worse in males. Measurement precision of the general distress factor was higher and spanned a wider range of the population than any of the three first-order factors. Conclusions The general distress factor provides the most reliable target for epidemiological analysis but specific factors may help to refine valid phenotype dimensions for aetiological research and assist in prognostic modelling of future psychiatric episodes.

Outcome in adult patients after arterial switch operation for transposition of the great arteries

BACKGROUND: The arterial switch operation (ASO) is currently the treatment of choice in neonates with transposition of the great arteries (TGA). The outcome in childhood is encouraging but only limited data for long-term outcome into adulthood exist. METHODS AND RESULTS: We studied 145 adult patients (age>16, median 25years) with ASO followed at our institution. Three patients died in adulthood (mortality 2.4/1000-patient-years). Most patients were asymptomatic and had normal left ventricular function. Coronary lesions requiring interventions were rare (3 patients) and in most patients related to previous surgery. There were no acute coronary syndromes. Aortic root dilatation was frequent (56% patients) but rarely significant (>45mm in 3 patients, maximal-diameter 49mm) and appeared not to be progressive. There were no acute aortic events and no patient required elective aortic root surgery. Progressive neo-aortic-valve dysfunction was not observed in our cohort and only 1 patient required neo-aortic-valve replacement. Many patients (42.1%), however, had significant residual lesions or required reintervention in adulthood. Right ventricular outflow tract lesions or dysfunction of the neo-pulmonary-valve were frequent and 8 patients (6%) required neo-pulmonary-valve replacement. Cardiac interventions during childhood (OR 3.0, 95% CI 1.7-5.4, P<0.0001) were strong predictors of outcome (cardiac intervention/significant residual lesion/death) in adulthood. CONCLUSIONS: Adult patients with previous ASO remain free of acute coronary or aortic complications and have low mortality. However, a large proportion of patients require re-interventions or present with significant right sided lesions. Life-long cardiac follow-up is, therefore, warranted. Periodic noninvasive surveillance for coronary complications appears to be safe in adult ASO patients.

Idiomatic Différance: Reflections on Intranslatability in the Works of Gerhard Richter

Translatability of a work of art, according to Walter Benjamin, is an essential ability to allow a translation to take on »a specific significance inherent in the original« so that it will retain a close relationship to the original. In contrast, Gerhard Richter's photo-based paintings show such an auratic significance of the original in its innate deficiency or intranslatability. As Rosemary Hawker puts it, the striking effect of blur in his paintings represents itself at once as a unique photographic idiom and a distinctive shortcoming of photography which impedes the medium from providing viewers with clearly perceivable images; the blur creates a site of différance in which both media come to a common understanding of one another’s idioms by telling what those idioms always fail to achieve. In this short essay, I will examine ways in which Richter’s photographic and pictorial works, including early monochrome paintings and recent abstract works based on microscopic photographs of molecular structures, attempt to untranslate photographic idioms in order to see painting’s (in)abilities simultaneously. In doing so, I intend to observe in the artist’s pictorial practice an actual phenomenon that the image can designate certain facts or truths only through its inherent plurality, faultiness, and partiality.

Idiomatic Différance: Reflections on Intranslatability in the Works of Gerhard Richter

Translatability of a work of art, according to Walter Benjamin, is an essential ability to allow a translation to take on »a specific significance inherent in the original« so that it will retain a close relationship to the original. In contrast, Gerhard Richter's photo-based paintings show such an auratic significance of the original in its innate deficiency or intranslatability. As Rosemary Hawker puts it, the striking effect of blur in his paintings represents itself at once as a unique photographic idiom and a distinctive shortcoming of photography which impedes the medium from providing viewers with clearly perceivable images; the blur creates a site of différance in which both media come to a common understanding of one another’s idioms by telling what those idioms always fail to achieve. In this short essay, I will examine ways in which Richter’s photographic and pictorial works, including early monochrome paintings and recent abstract works based on microscopic photographs of molecular structures, attempt to untranslate photographic idioms in order to see painting’s (in)abilities simultaneously. In doing so, I intend to observe in the artist’s pictorial practice an actual phenomenon that the image can designate certain facts or truths only through its inherent plurality, faultiness, and partiality.

Aggressive vs. conservative phototherapy for infants with extremely low birth weight.

BACKGROUND: It is unclear whether aggressive phototherapy to prevent neurotoxic effects of bilirubin benefits or harms infants with extremely low birth weight (1000 g or less). METHODS: We randomly assigned 1974 infants with extremely low birth weight at 12 to 36 hours of age to undergo either aggressive or conservative phototherapy. The primary outcome was a composite of death or neurodevelopmental impairment determined for 91% of the infants by investigators who were unaware of the treatment assignments. RESULTS: Aggressive phototherapy, as compared with conservative phototherapy, significantly reduced the mean peak serum bilirubin level (7.0 vs. 9.8 mg per deciliter [120 vs. 168 micromol per liter], P<0.01) but not the rate of the primary outcome (52% vs. 55%; relative risk, 0.94; 95% confidence interval [CI], 0.87 to 1.02; P=0.15). Aggressive phototherapy did reduce rates of neurodevelopmental impairment (26%, vs. 30% for conservative phototherapy; relative risk, 0.86; 95% CI, 0.74 to 0.99). Rates of death in the aggressive-phototherapy and conservative-phototherapy groups were 24% and 23%, respectively (relative risk, 1.05; 95% CI, 0.90 to 1.22). In preplanned subgroup analyses, the rates of death were 13% with aggressive phototherapy and 14% with conservative phototherapy for infants with a birth weight of 751 to 1000 g and 39% and 34%, respectively (relative risk, 1.13; 95% CI, 0.96 to 1.34), for infants with a birth weight of 501 to 750 g. CONCLUSIONS: Aggressive phototherapy did not significantly reduce the rate of death or neurodevelopmental impairment. The rate of neurodevelopmental impairment alone was significantly reduced with aggressive phototherapy. This reduction may be offset by an increase in mortality among infants weighing 501 to 750 g at birth. (ClinicalTrials.gov number, NCT00114543.)

Alterations in content and localization of defensins in rat ileum and jejunum following ischemia-reperfusion. Specific peptides, in specific places, for specific jobs?

Objective: To determine alterations in quantities and distributions of natural antimicrobials following ischemia-reperfusion injury. We hypothesized that these compounds would be upregulated in areas of small intestine where changes in permeability and cellular disruption were likely and where protective mechanisms would be initiated. Methods: Rats with ischemia-reperfusion underwent superior mesenteric artery clamping and reperfusion. Shams were subjected to laparotomy but no clamping. Ileum and jejunum were harvested and sectioned, and subjected to fluorescence deconvolution microscopy for determinations of content and localization of rat beta defensins, 1, 2, 3; rat neutrophil protein-1; and cathelicidin LL-37. Modeling was performed to determine cellular location of antimicrobials. Results: Ischemia-reperfusion increased neutrophil defensin alpha (RNP-1) in jejunum; rat beta defensin 1 was increased 2-fold in ileal mucosa and slightly reduced in jejunal mucosa; rat beta defensin 2 was reduced by ischemia-reperfusion in ileum, but slightly increased in jejunum; rat beta defensin 3 was concentrated in the muscularis externa and myenteric plexus of the jejunum; ischemia-reperfusion did not alter cathelicidin LL-37 content in the small intestine, although a greater concentration was seen in jejunum compared with ileum. Conclusion: Ischemia-reperfusion injury caused changes in antimicrobial content in defined areas, and these different regulations might reflect the specific roles of jejunum versus ileum.

Neonatal outcomes of extremely preterm infants from the NICHD Neonatal Research Network.

OBJECTIVE: This report presents data from the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network on care of and morbidity and mortality rates for very low birth weight infants, according to gestational age (GA). METHODS: Perinatal/neonatal data were collected for 9575 infants of extremely low GA (22-28 weeks) and very low birth weight (401-1500 g) who were born at network centers between January 1, 2003, and December 31, 2007. RESULTS: Rates of survival to discharge increased with increasing GA (6% at 22 weeks and 92% at 28 weeks); 1060 infants died at CONCLUSION: Although the majority of infants with GAs of >or=24 weeks survive, high rates of morbidity among survivors continue to be observed.

Outcomes of safety and effectiveness in a multicenter randomized, controlled trial of whole-body hypothermia for neonatal hypoxic-ischemic encephalopathy.

BACKGROUND: Whole-body hypothermia reduced the frequency of death or moderate/severe disabilities in neonates with hypoxic-ischemic encephalopathy in a randomized, controlled multicenter trial. OBJECTIVE: Our goal was to evaluate outcomes of safety and effectiveness of hypothermia in infants up to 18 to 22 months of age. DESIGN/METHODS: A priori outcomes were evaluated between hypothermia (n = 102) and control (n = 106) groups. RESULTS: Encephalopathy attributable to causes other than hypoxia-ischemia at birth was not noted. Inotropic support (hypothermia, 59% of infants; control, 56% of infants) was similar during the 72-hour study intervention period in both groups. Need for blood transfusions (hypothermia, 24%; control, 24%), platelet transfusions (hypothermia, 20%; control, 12%), and volume expanders (hypothermia, 54%; control, 49%) was similar in the 2 groups. Among infants with persistent pulmonary hypertension (hypothermia, 25%; control, 22%), nitric-oxide use (hypothermia, 68%; control, 57%) and placement on extracorporeal membrane oxygenation (hypothermia, 4%; control, 9%) was similar between the 2 groups. Non-central nervous system organ dysfunctions occurred with similar frequency in the hypothermia (74%) and control (73%) groups. Rehospitalization occurred among 27% of the infants in the hypothermia group and 42% of infants in the control group. At 18 months, the hypothermia group had 24 deaths, 19 severe disabilities, and 2 moderate disabilities, whereas the control group had 38 deaths, 25 severe disabilities, and 1 moderate disability. Growth parameters were similar between survivors. No adverse outcomes were noted among infants receiving hypothermia with transient reduction of temperature below a target of 33.5 degrees C at initiation of cooling. There was a trend in reduction of frequency of all outcomes in the hypothermia group compared with the control group in both moderate and severe encephalopathy categories. CONCLUSIONS: Although not powered to test these secondary outcomes, whole-body hypothermia in infants with encephalopathy was safe and was associated with a consistent trend for decreasing frequency of each of the components of disability.

Intensive care for extreme prematurity--moving beyond gestational age.

BACKGROUND: Decisions regarding whether to administer intensive care to extremely premature infants are often based on gestational age alone. However, other factors also affect the prognosis for these patients. METHODS: We prospectively studied a cohort of 4446 infants born at 22 to 25 weeks' gestation (determined on the basis of the best obstetrical estimate) in the Neonatal Research Network of the National Institute of Child Health and Human Development to relate risk factors assessable at or before birth to the likelihood of survival, survival without profound neurodevelopmental impairment, and survival without neurodevelopmental impairment at a corrected age of 18 to 22 months. RESULTS: Among study infants, 3702 (83%) received intensive care in the form of mechanical ventilation. Among the 4192 study infants (94%) for whom outcomes were determined at 18 to 22 months, 49% died, 61% died or had profound impairment, and 73% died or had impairment. In multivariable analyses of infants who received intensive care, exposure to antenatal corticosteroids, female sex, singleton birth, and higher birth weight (per each 100-g increment) were each associated with reductions in the risk of death and the risk of death or profound or any neurodevelopmental impairment; these reductions were similar to those associated with a 1-week increase in gestational age. At the same estimated likelihood of a favorable outcome, girls were less likely than boys to receive intensive care. The outcomes for infants who underwent ventilation were better predicted with the use of the above factors than with use of gestational age alone. CONCLUSIONS: The likelihood of a favorable outcome with intensive care can be better estimated by consideration of four factors in addition to gestational age: sex, exposure or nonexposure to antenatal corticosteroids, whether single or multiple birth, and birth weight. (ClinicalTrials.gov numbers, NCT00063063 [ClinicalTrials.gov] and NCT00009633 [ClinicalTrials.gov].).

The WTO and Food Security: What’s Wrong with the Rules?

The WTO Agreement on Agriculture (AoA) is the predominant multilateral legal framework governing agricultural trade. The objective of the AoA is to liberalise trade in agriculture through reductions in tariffs, domestic support and export subsidies. The AoA has not, however, ‘levelled the playing field’ and has not resulted in the equitable distribution of food, particularly for the poorer developing countries. On the other hand, support for small farmers does not ensure food security for the poor. While food security has no simple solutions such as “free trade is good for you”, reform proposals for trade rules which only address agricultural policy instruments fail to account for consumer and other interests: neither tariff reductions and subsidy disciplines, nor safeguards and other measures of producer protection can automatically increase food security. Rather, what is needed is the full and proper implementation of a number of commitments which the international community has already entered into in various human rights treaties, but which even the envisaged results of the now failed Doha Round negotiations could not ensure without revisiting relevant multilateral trade and investment rules.