Background One in five deaths in the United States occurs in the ICU, and many of these deaths are experienced as less than optimal by families of dying people. The current study investigated the ...relationship between family satisfaction with ICU care and overall ratings of the quality of dying as a means of identifying targets for improving end-of-life experiences for patients and families. Methods This multisite cross-sectional study surveyed families of patients who died in the ICU in one of 15 hospitals in western Washington State. Measures included the Family Satisfaction in the ICU (FS-ICU) and the Single-Item Quality of Dying (QOD-1) questionnaires. Associations between FS-ICU items and the QOD-1 were examined using multivariate linear regression controlling for patient and family demographics and hospital site. Results Questionnaires were returned for 1,290 of 2,850 decedents (45%). Higher QOD-1 scores were significantly associated (all P < .05) with (1) perceived nursing skill and competence (β = 0.15), (2) support for family as decision-makers (β = 0.10), (3) family control over the patient's care (β = 0.18), and (4) ICU atmosphere (β = 0.12). FS-ICU items that received low ratings and correlated with higher QOD-1 scores (ie, important items with room for improvement) were (1) support of family as decision-maker, (2) family control over patient's care, and (3) ICU atmosphere. Conclusions Increased support for families as decision-makers and for their desired level of control over patient care along with improvements in the ICU atmosphere were identified as aspects of the ICU experience that may be important targets for quality improvement. Trial registry ClinicalTrials.gov ; No.: NCT00685893; URL: www.clinicaltrials.gov.
Pulmonary mycoses are often associated with type-2 helper T (Th2) cell responses. However, mechanisms of Th2 cell accumulation are multifactorial and incompletely known. To investigate Th2 cell ...responses to pulmonary fungal infection, we developed a peptide-MHCII tetramer to track antigen-specific CD4+ T cells produced in response to infection with the fungal pathogen Cryptococcus neoformans. We noted massive accruement of pathologic cryptococcal antigen-specific Th2 cells in the lungs following infection that was coordinated by lung-resident CD11b+ IRF4-dependent conventional dendritic cells. Other researchers have demonstrated that this dendritic cell subset is also capable of priming protective Th17 cell responses to another pulmonary fungal infection, Aspergillus fumigatus. Thus, higher order detection of specific features of fungal infection by these dendritic cells must direct Th2 cell lineage commitment. Since chitin-containing parasites commonly elicit Th2 responses, we hypothesized that recognition of fungal chitin is an important determinant of Th2 cell-mediated mycosis. Using C. neoformans mutants or purified chitin, we found that chitin abundance impacted Th2 cell accumulation and disease. Importantly, we determined Th2 cell induction depended on cleavage of chitin via the mammalian chitinase, chitotriosidase, an enzyme that was also prevalent in humans experiencing overt cryptococcosis. The data presented herein offers a new perspective on fungal disease susceptibility, whereby chitin recognition via chitotriosidase leads to the initiation of harmful Th2 cell differentiation by CD11b+ conventional dendritic cells in response to pulmonary fungal infection.
We evaluated a new technique to characterize resting stage zooplankton assemblages in both riverine slackwater habitats and floodplain wetlands, using coconut fibre mats (CFMs). Results obtained ...using the CFMs were compared with those obtained using the conventional sediment coring technique, over three different mat-setting durations. Presently, there is a paucity of suitable sampling techniques available for characterizing resting stage zooplankton assemblages, particularly for assessing resting stage production and/or use in intervention experiments. Results from this study indicate that, for slackwaters and wetlands, the structure and composition of resting stage communities obtained using mats did not differ from that obtained using the sediment coring technique, irrespective of the mat-setting duration. This suggests that the CFM technique can be used as an effective surrogate for the sediment coring technique to characterize resting stage assemblages in slackwaters and floodplain wetlands. In addition, the CFM technique offers the capacity to measure resting stage production over a known time period, and can be used in intervention experiments. Hence, the mats should prove to be useful in a number of settings, ranging from investigative research to management applications.
Tissue regeneration requires dynamic cellular adaptation to the wound environment. It is currently unclear how this is orchestrated at the cellular level and how cell fate is affected by severe ...tissue damage. Here we dissect cell fate transitions during colonic regeneration in a mouse dextran sulfate sodium (DSS) colitis model, and we demonstrate that the epithelium is transiently reprogrammed into a primitive state. This is characterized by de novo expression of fetal markers as well as suppression of markers for adult stem and differentiated cells. The fate change is orchestrated by remodeling the extracellular matrix (ECM), increased FAK/Src signaling, and ultimately YAP/TAZ activation. In a defined cell culture system recapitulating the extracellular matrix remodeling observed in vivo, we show that a collagen 3D matrix supplemented with Wnt ligands is sufficient to sustain endogenous YAP/TAZ and induce conversion of cell fate. This provides a simple model for tissue regeneration, implicating cellular reprogramming as an essential element.
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•The repairing epithelium can be isolated based on Sca1 expression•Markers upregulated during tissue repair are expressed in the fetal intestine•Mechano-transduction via FAK, Src, and YAP/TAZ facilitate efficient tissue repair•YAP/TAZ activation is required and sufficient to induce cellular reprogramming
The mechanism that governs tissue regeneration following severe damage to the colonic epithelium remains poorly understood. Jensen and colleagues show that the colonic epithelium undergoes a profound reprogramming into a more primitive state with fetal-like properties. Moreover, they demonstrate that YAP and TAZ operate as essential mechano-sensors during tissue reprogramming.
Among the leading causes of death in African children is cerebral malaria caused by the parasitic protozoan
Plasmodium falciparum. Endemic forms of this disease are thought to have originated in ...central Africa 5000–10 000 years ago, coincident with the innovation of slash-and-burn agriculture and the diversification of the
Anopheles gambiae complex of mosquito vectors. Population genetic studies of
P. falciparum have yielded conflicting results. Some evidence suggests that today's population includes multiple ancient lineages pre-dating human speciation. Other evidence suggests that today's population derives from only one, or a small number, of these ancient lineages. Resolution of this issue is important for the evaluation of the long-term efficacy of drug and immunological control strategies.
The magnitude and types of genetic variation observed in different genes of the malaria parasite Plasmodium falciparum give pictures of its ancestry and population history that are completely contradictory
We have discovered a new, near-equal mass, eclipsing M dwarf binary from the Next Generation Transit Survey. This system is only one of 3 field age (\(>\) 1 Gyr), late M dwarf eclipsing binaries ...known, and has a period of 1.74774 days, similar to that of CM~Dra and KOI126. Modelling of the eclipses and radial velocities shows that the component masses are \(M_{\rm pri}\)=0.17391\(^{+0.00153}_{0.00099}\) \(M_{\odot}\), \(M_{\rm sec}\)=0.17418\(^{+0.00193}_{-0.00059}\) \(M_{\odot}\); radii are \(R_{\rm pri}\)=0.2045\(^{+0.0038}_{-0.0058}\) \(R_{\odot}\), \(R_{\rm sec}\)=0.2168\(^{+0.0047}_{-0.0048}\) \(R_{\odot}\). The effective temperatures are \(T_{\rm pri} = 2995\,^{+85}_{-105}\) K and \(T_{\rm sec} = 2997\,^{+66}_{-101}\) K, consistent with M5 dwarfs and broadly consistent with main sequence models. This pair represents a valuable addition which can be used to constrain the mass-radius relation at the low mass end of the stellar sequence.
Generalization of the polymorphism information content (PIC) index to represent marker informativeness (MI) for a three-generation F design requires that two additional sources of non-informativeness ...be added to the PIC formula: the probability of matings between like-heterozygous F individuals, of which one is non-informative; and that of matings between like-heterozygous F individuals, which are both fully informative but where line of origin of the same alleles is reciprocal. Given the dense marker-maps currently available for some species, this F informativeness parameter constitutes the natural criterion for marker selection in F designs, and two computer programs to predict MI from grandparental marker-genotypes were developed for an F population originating from two divergent selection lines of outbred mice (F similar to 0.2). A total of 403 markers had been genotyped for the F grandparents (n=31), and 14 markers had also been genotyped in the complete pedigree including 559 F individuals. One program was based on assumptions of random-mating (RM), while the other (PED) accounted for the pedigreed mating structure. For the 403 markers, the correlation between MI from RM and from PED was 0.95, and the average deviation between the two predictions was 0.005 MI units (MI ranged from 0 to 1). Correlations between predicted and realized MI for the 14 fully genotyped markers were 0.97 for PED and 0.94 for RM, while the corresponding average of deviations between predicted and actual values were 0.01 and 0.04, respectively. Absolute deviations from realized MI never exceeded 0.09 and 0.16 for PED and RM, respectively. Simulated optimization of the mating system to maximize average MI of 28 markers on one chromosome led to improvements in the range of 15-20% average MI (0.07-0.09 MI units). The degree of relative advantage conferred by the F generalization of the PIC index over the traditional index was found to be of minor significance.
We report the discovery of the super-Earth K2-265 b detected with K2 photometry. The planet orbits a bright (V_mag = 11.1) star of spectral type G8V with a period of 2.37 days. We obtained ...high-precision follow-up radial velocity measurements from HARPS, and the joint Bayesian analysis showed that K2-265 b has a radius of 1.71 +/- 0.11 R_earth and a mass of 6.54 +/- 0.84 M_earth, corresponding to a bulk density of 7.1 +/- 1.8 g/cm^3 . Composition analysis of the planet reveals an Earth-like, rocky interior, with a rock mass fraction of 80%. The short orbital period and small radius of the planet puts it below the lower limit of the photoevaporation gap, where the envelope of the planet could have eroded due to strong stellar irradiation, leaving behind an exposed core. Knowledge of the planet core composition allows us to infer the possible formation and evolution mechanism responsible for its current physical parameters.
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