Change is central to critical realism yet there has been little theoretical explication on the temporal dimension. It is shown that this oversight results in Archer's morphogenetic approach employing ...an ontological dualism of cyclical and linear temporalities similar to that contained within Giddens' structuration theory. Consequently, neither Archer nor Giddens is able to explain change and the transition between different epochs in a persuasive manner. In order to minimize these problems, Adam's concept of circadian time is adopted. This allows for a diachronic analysis that synchronically incorporates both continuity and change. Accordingly, it is able to transcend the temporal dualism of repetition and transformation. This temporal conceptualization is then incorporated within a critical realist framework. It is suggested that employing a double helix analogy allows for the integration of the notion of a stratified social ontology with a non-dichotomous temporal conceptualization.
Ethicists often struggle to maintain institution-wide awareness of and commitment to medical ethics. At Beth Israel Deaconess Medical Center (BIDMC), we created the Ethics Liaison Program to address ...that challenge by making ethics part of the moral culture of the institution. Liaisons represent clinical and non-clinical areas throughout the medical centre. The liaison has a four-part role: to spread awareness and understanding of Ethics Programs among their coworkers; share information regarding ethical dilemmas in their work area with the members of the Ethics Support Service; review ethics activities and needs within their area; and undertake ethics-related projects. This paper lists the notable attributes of the Ethics Liaison Program, and describes the purpose and structure of the programme, its advantages and the challenges to implementing it. The Ethics Liaison Program has helped to make ethics part of the everyday culture at BIDMC, and other medical centres might benefit from the establishment of similar programmes.
Examination of the subcellular localization of Dishevelled (Dsh) in fertilized Xenopus eggs revealed that Dsh is associated with vesicle-like organelles that are enriched on the prospective dorsal ...side of the embryo after cortical rotation. Dorsal enrichment of Dsh is blocked by UV irradiation of the vegetal pole, a treatment that inhibits development of dorsal cell fates, linking accumulation of Dsh and specification of dorsal cell fates. Investigation of the dynamics of Dsh localization using Dsh tagged with green fluorescent protein (Dsh-GFP) demonstrated that Dsh-GFP associates with small vesicle-like organelles that are directionally transported along the parallel array of microtubules towards the prospective dorsal side of the embryo during cortical rotation. Perturbing the assembly of the microtubule array with D2 O, a treatment that promotes the random assembly of the array and the dorsalization of embryos, randomizes translocation of Dsh-GFP. Conversely, UV irradiation of the vegetal pole abolishes movement of Dsh-GFP. Finally, we demonstrate that overexpression of Dsh can stabilize β-catenin in Xenopus. These data suggest that the directional translocation of Dsh along microtubules during cortical rotation and its subsequent enrichment on the prospective dorsal side of the embryo play a role in locally activating a maternal Wnt pathway responsible for establishing dorsal cell fates in Xenopus.
Pearson’s correlation is a commonly used descriptive statistic in many published precision agriculture studies, not only in the Precision Agriculture Journal, but also in other journals that publish ...in this domain. Very few of these articles take into consideration auto-correlation in data when performing correlation analysis, despite a statistical solution being available. A brief discussion on the need to consider auto-correlation and the effective sample size when using Pearson’s correlation in precision agriculture research is presented. The discussion is supported by an example using spatial data on vine size and canopy vigour in a juice-grape vineyard. The example data demonstrated that the
p
-value of the correlation between vine size and canopy vigour increased when auto-correlation was accounted for, potentially to a non-significant level depending on the desired α-level. The example data also demonstrated that the method by which data are processed (interpolated) to achieve co-located data will also affect the amount of auto-correlation and the effective sample size. The results showed that for the same variables, with different approaches to data co-location, a lower
r
-value may have a lower
p
-value and potentially hold more statistical significance.
The pulmonary phenotype of Hermansky-Pudlak syndrome (HPS) in adults includes foamy alveolar type 2 cells, inflammation, and lung remodeling, but there is no information about ontogeny or early ...disease mediators.
To establish the ontogeny of HPS lung disease in an animal model, examine disease mediators, and relate them to patients with HPS1.
Mice with mutations in both HPS1/pale ear and HPS2/AP3B1/pearl (EPPE mice) were studied longitudinally. Total lung homogenate, lung tissue sections, and bronchoalveolar lavage (BAL) were examined for phospholipid, collagen, histology, cell counts, chemokines, surfactant protein D (SP-D), and S-nitrosylated SP-D. Isolated alveolar epithelial cells were examined for expression of inflammatory mediators, and chemotaxis assays were used to assess their importance. Pulmonary function test results and BAL from patients with HPS1 and normal volunteers were examined for clinical correlation.
EPPE mice develop increased total lung phospholipid, followed by a macrophage-predominant pulmonary inflammation, and lung remodeling including fibrosis. BAL fluid from EPPE animals exhibited early accumulation of both SP-D and S-nitrosylated SP-D. BAL fluid from patients with HPS1 exhibited similar changes in SP-D that correlated inversely with pulmonary function. Alveolar epithelial cells demonstrated expression of both monocyte chemotactic protein (MCP)-1 and inducible nitric oxide synthase in juvenile EPPE mice. Last, BAL from EPPE mice and patients with HPS1 enhanced migration of RAW267.4 cells, which was attenuated by immunodepletion of SP-D and MCP-1.
Inflammation is initiated from the abnormal alveolar epithelial cells in HPS, and S-nitrosylated SP-D plays a significant role in amplifying pulmonary inflammation.
Aims We used the GUSTO-I and GUSTO-III databases to evaluate our performance in treating cardiogenic shock patients over much of the 1990s. Methods and Results GUSTO-I (1990–1993) and GUSTO-III ...(1995–1997) prospectively identified all patients with cardiogenic shock complicating acute myocardial infarction. Demographics, clinical presentation and outcomes for cardiogenic shock patients in the two trials were compared. Only patients enrolled with cardiogenic shock in countries common to both trials were included in these analysis. The 695 patients with cardiogenic shock in GUSTO-III were compared with the 2814 patients with cardiogenic shock in GUSTO-I. GUSTO-III patients were older (P=0·0001) and more likely to be diabetic (P=0·009) and hypertensive (P=0·025). They had a higher Killip class (P=0·002) and significantly greater index anterior infarction than cardiogenic shock patients enrolled in GUSTO-I. Time to treatment, presentation heart rate, and diastolic blood pressure were similar; however, systolic blood pressure at presentation was higher among GUSTO-III patients (P=0·002). Rates of coronary angiography, pulmonary artery catheterization, and mechanical ventilation declined in GUSTO-III compared with GUSTO-I (P=0·001); rates of angioplasty and bypass surgery were similar. Cardiogenic shock mortality in GUSTO-III was significantly higher than in GUSTO-I (62 vs 54%,P =0·001), as were rates of reinfarction (14 vs 11%, P=0·013) and recurrent ischaemia (35 vs 27%, P=0·00001). Mortality at non-U.S. sites (68 and 64%) was higher than at U.S. sites (53 and 50%) in both GUSTO-I and GUSTO-III studies, respectively. Angioplasty, bypass surgery, and balloon pump rates were lower for non-U.S. patients. Conclusions Cardiogenic shock continues to be associated with high mortality in thrombolytic-treated patients. Lower mortality observed in the U.S.A. supports consideration for percutaneous and surgical revascularization.
Modern reef-building corals sustain a wide range of ecosystem services because of their ability to build calcium carbonate reef systems. The influence of environmental variables on coral ...calcification rates has been extensively studied, but our understanding of their relative importance is limited by the absence of in situ observations and the ability to decouple the interactions between different properties. We show that temperature is the primary driver of coral colony (
and
) and reef-scale calcification rates over a 2-year monitoring period from the Bermuda coral reef. On the basis of multimodel climate simulations (Coupled Model Intercomparison Project Phase 5) and assuming sufficient coral nutrition, our results suggest that
and
coral calcification rates in Bermuda could increase throughout the 21st century as a result of gradual warming predicted under a minimum CO
emissions pathway representative concentration pathway (RCP) 2.6 with positive 21st-century calcification rates potentially maintained under a reduced CO
emissions pathway (RCP 4.5). These results highlight the potential benefits of rapid reductions in global anthropogenic CO
emissions for 21st-century Bermuda coral reefs and the ecosystem services they provide.
Background We aimed to determine the change in treatment strategies and times to treatment over the first 5 years of the Mission: Lifeline program. Methods and Results We assessed pre- and ...in-hospital care and outcomes from 2008 to 2012 for patients with ST -segment-elevation myocardial infarction at US hospitals, using data from the National Cardiovascular Data Registry Acute Coronary Treatment and Intervention Outcomes Network Registry-Get With The Guidelines Registry. In-hospital adjusted mortality was calculated including and excluding cardiac arrest as a reason for primary percutaneous coronary intervention delay. A total of 147 466 patients from 485 hospitals were analyzed. There was a decrease in the proportion of eligible patients not treated with reperfusion (6.2% versus 3.3%) and treated with fibrinolytic therapy (13.4% versus 7.0%). Median time from symptom onset to first medical contact was unchanged (≈50 minutes). Use of prehospital ECGs increased (45% versus 71%). All major reperfusion times improved: median first medical contact-to-device for emergency medical systems transport to percutaneous coronary intervention-capable hospitals (93 to 84 minutes), first door-to-device for transfers for primary percutaneous coronary intervention (130 to 112 minutes), and door-in-door-out at non-percutaneous coronary intervention-capable hospitals (76 to 62 minutes) (all P<0.001 over 5 years). Rates of cardiogenic shock and cardiac arrest, and overall in-hospital mortality increased (5.7% to 6.3%). Adjusted mortality excluding patients with known cardiac arrest decreased by 14% at 3 years and 25% at 5 years ( P<0.001). Conclusions Quality of care for patients with ST -segment-elevation myocardial infarction improved over time in Mission: Lifeline, including increased use of reperfusion therapy and faster times-to-treatment. In-hospital mortality improved for patients without cardiac arrest but did not appear to improve overall as the number of these high-risk patients increased.
Our objective was to determine if increased glycolytic enzyme capacity accommodates rapid glycolysis, which leads to inferior pork color and water-holding capacity. Progeny from HAL-1843 free Duroc (
...n=16) or Pietrain (
n=16) sires were harvested over a 2-week period. Coupled enzyme assays were used to quantify total capacity of pyruvate kinase (PK) and phosphofructokinase (PFK) in the sarcoplasmic fractions and crude homogenates of
longissimus muscle (LM), respectively. Capacity of PK was not correlated with LM pH (20, 45, 180 min or 24 h), purge, drip loss, or CIE
L* (
P > 0.2). However, PFK capacity was inversely related to fluid loss (
P<0.05). This finding was unexpected, but may result from PFK becoming partially denatured and inactivated by 20 min postmortem in samples that undergo a rapid pH decline. These data indicate that lighter pork color and reduced water-holding capacity are not associated with an increase in the capacity of enzymes that catalyze regulated steps of glycolysis.
The osmolyte trimethylamine-
N-oxide (TMAO) is a naturally in vivo occurring “chemical chaperone” that has been shown to stabilise the folding of numerous proteins. Myelin basic protein (MBP) is a ...molecule that has not yet been suitably crystallized either in three dimensions for X-ray crystallography or in two dimensions for electron crystallography. Here, we describe lipid monolayer crystallization experiments of two species of recombinant murine MBP in the presence of TMAO. One protein was unmodified, whereas the other contained six Arg/Lys
→
Gln substitutions to mimic the effects of deimination (i.e., the enzymatic modification of Arg to citrulline), which reduces the net positive charge. Planar arrays of both proteins were formed on binary lipid monolayers containing a nickel-chelating lipid and a phosphoinositide. In the presence of TMAO, the diffraction spots of these arrays became sharper and more distinct than in its absence, indicating some improvement of crystallinity. The osmolyte also induced the formation of epitaxial growth of protein arrays, especially with the mutant protein. However, none of these assemblies was sufficiently ordered to extract high-resolution structural information. Circular dichroic spectroscopy showed that MBP gained no increase in ordered secondary structure in the presence of TMAO in bulk solution, whereas it did in the presence of lipids. Dynamic light-scattering experiments confirmed that the MBP preparations were monomodal under the optimal crystallization conditions determined by electron microscopy trials. The salt and osmolyte concentrations used were shown to result in a largely unassociated population of MBP. The amino acid composition of MBP overwhelmingly favours a disordered state, and a neural-network-based scheme predicted large segments that would be unlikely to adopt a regular conformation. Thus, this protein has an inherently disordered nature, which mitigates strongly against its crystallization for high-resolution structure determination.
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