One-year mortality,quality of life and predicted life-time cost-utility in critically ill patients with acute respiratory failure

Introduction  

High daily intensive care unit (ICU) costs are associated with the use of mechanical ventilation (MV) to treat acute respiratory failure (ARF), and assessment of quality of life (QOL) after critical illness and cost-effectiveness analyses are warranted.     

Myocardial manganese elevation and proton relaxivity enhancement with manganese dipyridoxyl diphosphate. Ex vivo assessments in normally perfused and ischemic guinea pig hearts.

Manganese (Mn) dipyridoxyl diphosphate (MnDPDP) is the active component of a contrast medium for liver MRI. By being metabolized, MnDPDP releases Mn(2+), which is taken up and retained in hepatocytes. The study examined whether MnDPDP elevates Mn content and enhances proton relaxivity in normal myocardium, but not in ischemic myocardium with reduced coronary flow and impaired metabolism. Isolated guinea pig hearts were perfused at normal flow or low flow, inducing global subtotal ischemia. Ventricular ATP and Mn contents, T(1) and T(2) were measured. At normal flow tissue Mn content increased from the control level of 4.1 to 70.4 micromol/100g dry wt with MnDPDP (3000 microM), while low-flow perfusion with MnDPDP (3000 microM) resulted in a Mn content of 16.6 micromol/100 g dry wt. Prolonged ischemia (35 and 90 min) reduced tissue Mn down to the control level. T(1) shortening closely paralleled myocardial Mn elevations during both normal and low-flow perfusion. The use of a Mn(2+)-releasing contrast agent like MnDPDP may be a promising principle in MRI assessments of myocardial function and viability in coronary heart disease by revealing a differential pattern of changes in T(1) relative to coronary flow, cell Mn uptake and retention, ion channel function and metabolism.     

Acoustic characteristics of /s/ in adolescents.

The goal of the current study was to construct a reference database against which misarticulations of /s/ can be compared. Acoustic data for 26 typically speaking 9- to 15-year-olds were examined to resolve measurement issues in acoustic analyses, including alternative sampling points within the /s/ frication; the informativeness of linear versus Bark transformations of each of the 4 spectral moments of /s/ (Forrest, Weismer, Milenkovic, & Dougall, 1988); and measurement effects associated with linguistic context, age, and sex. Analysis of the reference data set indicates that acoustic characterization of /s/ is appropriately and optimally (a) obtained from the midpoint of /s/, (b) represented in linear scale, (c) reflected in summary statistics for the 1 st and 3rd spectral moments, (d) referenced to individual linguistic-phonetic contexts, (e) collapsed across the age range studied, and (f) described individually by sex.     

Optimized MLC-beam arrangements for tangential breast irradiation.

BACKGROUND AND PURPOSE: Very large numbers of women are treated with tangential breast irradiation after breast-conserving surgery due to mammary carcinoma. The aim of this study was to improve a conventional treatment plan by modifying the dose intensity in the beams to reduce the absorbed dose outside the planning target volume (PTV) and to reduce the absorbed dose variation inside the PTV diotherapy of mammary carcinoma. MATERIALS AND METHODS: Treatment planning was performed both with conventional technique and with a simple intensity modulation technique for 12 consecutive patients. RESULTS: In all cases a higher degree of dose conformity was obtained with the dose intensity modulation technique. The relative gain was found to be similar for all patients irrespective of the size of the target volume or the irradiated lung volume. CONCLUSION: Simple manual intensity modulation can be used to improve the dose distribution in tangential breast irradiation. With modern accelerators the increased time for this technique is less than 2 min per fraction.     

Semiparametric Distributions With Estimated Shape Parameters

Purpose  To investigate the use of adaptive transformations to assess the parameter distributions in population modeling. Methods  The logit, box-cox, and heavy tailed transformations were investigated. Each one was used in conjunction with the standard (exponential) transformation for PK and PD parameters. The shape parameters of these transformations were estimated to allow the parameter distributions to more accurately resemble a wider range of parameter distributions. The transformations were tested both in simulated settings where the true distributions were known and in 30 models developed from real data. Results  In the simulated setting the transformations were better than the standard lognormal distribution at characterizing the true distributions. Improvement could also be seen in objective function value (OFV) and in simulation based diagnostics. In the real datasets, significant model improvement based on OFV could be seen in 22, 18, and 22 out of the 30 models for the three transformations respectively. Conclusion  Transformations with estimated shape parameters are a promising approach to relax the often erroneous assumption of a known shape of the parameter distribution. They offer a simple and straightforward way of handling and characterizing parameter distributions.     

Evaluation of phagocytic activity in human monocyte-derived dendritic cells.

Dendritic cells play a central role in initiation of primary T lymphocyte responses to foreign antigens. Their potency in antigen presentation vis-à-vis reported low or lack of ability to phagocytize particulate matter has limited our understanding of the role that they play in inducing immunity to particulate antigens. One hypothesis is that dendritic cells may possess a high phagocytic capacity when immature and located in peripheral tissues, which they lose on maturation. Our goal was to characterize the phagocytic capacity in human immature dendritic cells. The phagocytic capacity of human monocyte-derived immature dendritic cells was studied by morphological and morphometric means, and compared to that of professional phagocytes, human alveolar macrophages, their progenitors, the peripheral blood monocytes, and mature dendritic cells. Phagocytic index (proportion of phagocytic cells) was decreased by 42.8% (immature dendritic cells) and 74.2% (mature dendritic cells) with respect to monocytes. Similarly, the phagocytic index was decreased by 46.5% (immature dendritic cells) and 75.9% (mature dendritic cells) with respect to macrophages. Volume density of phagocytized particles was decreased by 76.1% (immature dendritic cells) and 96.7% (mature dendritic cells) with respect to the monocytes. However, volume density was decreased by 34.3% (immature dendritic cells) and 91% (mature dendritic cells) with respect to alveolar macrophages. These results show that human monocyte-derived immature dendritic cells possess a phagocytic capacity that is lower than that of peripheral blood monocytes and alveolar macrophages but higher than that of mature dendritic cells.     

Modeling Subpopulations with the $MIXTURE Subroutine in NONMEM: Finding the Individual Probability of Belonging to a Subpopulation for the Use in Model Analysis and Improved Decision Making

In nonlinear mixed effects modeling using NONMEM, mixture models can be used for multimodal distributions of parameters. The fraction of individuals belonging to each of the subpopulations can be estimated, and the most probable subpopulation for each patient is output (MIXEST _k ). The objective function value (OFV) that is minimized is the sum of the OFVs for each patient (OFV _i ), which in turn is the sum across the k subpopulations (OFV _{i ,k} ). The OFV _{i ,k} values can be used together with the total probability in the population of belonging to subpopulation k to calculate the individual probability of belonging to the subpopulation (IP _k ). Our objective was to explore the information gained by using IP _k instead of or in addition to MIXEST _k in the analysis of mixture models. Two real data sets described previously by mixture models as well as simulations were used to explore the use of IP _k and the precision of individual parameter values based on IP _k and MIXEST _k . For both real data-based mixture models, a substantial fraction (11% and 26%) of the patients had IP _k values not close to 0 or 1 (IP _k between 0.25 and 0.75). Simulations of eight different scenarios showed that individual parameter estimates based on MIXEST were less precise than those based on IP _k , as the root mean squared error was reduced for IP _k in all scenarios. A probability estimate such as IP _k provides more detailed information about each individual than the discrete MIXEST _k . Individual parameter estimates based on IP _k should be preferable whenever individual parameter estimates are to be used as study output or for simulations.     

Postpartum depression and mother–offspring conflict over maternal investment

Background and objectivesAs the mother–offspring relationship is central to human reproduction, postpartum depression symptoms are difficult to explain in evolutionary terms. We proposed that postpartum depression might arise as a result of evolutionary mother–offspring conflict over maternal investment, and investigated the association between postpartum depression symptoms, infant night waking, maternal sleep disturbance and breastfeeding frequency.MethodologyWe conducted a cross-sectional analysis using survey responses at 6 months postpartum from 1598 Finnish mothers. We hypothesized that infant night waking at 6 months postpartum would be associated with postpartum depression symptoms, and that this association would be mediated by maternal sleep disturbance and a higher breastfeeding frequency.ResultsInfant night waking was moderately associated with postpartum depression symptoms, and this association was mediated by maternal sleep disturbance (R²=0.09). Contrary to our prediction, we found that increased breastfeeding was associated with less postpartum depression symptoms.Conclusions and implicationsWe conclude that postpartum depression symptoms might partly be the result of increased maternal fatigue stemming from high offspring demands on maternal investment, but that this is not due to the metabolic strain from increased breastfeeding. Studying postpartum depression from the mother–offspring conflict perspective can potentially improve our understanding of the involved behavioral processes of both mother and offspring, and allow interventions designed to benefit the well-being of both parties. Lay Summary: We proposed that postpartum depression is due to an evolutionary conflict between mother and infant, where the infant tires the mother to delay the arrival of a sibling. We found a link between infant night waking and postpartum depression, mediated by the mother’s sleep, but not by breastfeeding frequency.