A study of nurses' judgement of and participation in decision-making for nursing home placement for the elderly

This study investigated the effects of patient variables (physical and cognitive disability, significant others' preference and social support) on nurses' nursing home placement decision-making and explored nurses' participation in the decision-making process.^ The study was conducted in a hospital in Texas. A sample of registered nurses on units that refer patients for nursing home placement were asked to review a series of vignettes describing elderly patients that differed in terms of the study variables and indicate the extent to which they agreed with nursing home placement on a five-point Likert scale. The vignettes were judged to have good content validity by a group of five colleagues (expert consultants) and test-retest reliability based on the Pearson correlation coefficient was satisfactory (average of.75) across all vignettes.^ The study tested the following hypotheses: Nurses have more of a propensity to recommend placement when (1) patients have severe physical disabilities; (2) patients have severe cognitive disabilities; (3) it is the significant others' preference; and (4) patients have no social support nor alternative services. Other hypotheses were that (5) a nurse's characteristics and extent of participation will not have a significant effect on their placement decision; and (6) a patient's social support is the most important, single factor, and the combination of factors of severe physical and cognitive disability, significant others' preference, and no social support nor alternative services will be the most important set of predictors of a nurse's placement decision.^ Analysis of Variance (ANOVA) was used to analyze the relationships implied in the hypothesis. A series of one-way ANOVA (bivariate analyses) of the main effects supported hypotheses one-five.^ Overall, the n-way ANOVA (multivariate analyses) of the main effects confirmed that social support was the most important single factor controlling for other variables. The 4-way interaction model confirmed that the most predictive combination of patient characteristics were severe physical and cognitive disability, no social support and the significant others did not desire placement. These analyses provided an understanding of the importance of the influence of specific patient variables on nurses' recommendations regarding placement. ^

The molecular and genetic characterization of the MADS box transcription factor {\it Drosophila\/} MEF2

The myocyte enhancer factor (MEF)-2 family of transcription factors has been implicated in the regulation of muscle transcription in vertebrates, but the precise position of these regulators within the genetic hierarchy leading to myogenesis is unclear. The MEF2 proteins bind to a conserved A/T-rich DNA sequence present in numerous muscle-specific genes, and they are expressed in the cells of the developing somites and in the embryonic heart at the onset of muscle formation in mammals. The MEF2 genes belong to the MADS box family of transcription factors, which control specific programs of gene expression in species ranging from yeast to humans. Each MEF2 family member contains two highly conserved protein motifs, the MADS domain and the MEF2-specific domain, which together provide the MEF2 factors with their unique DNA binding and dimerization properties. In an effort to further define the function of the MEF2 proteins, and to evaluate the degree of conservation shared among these factors and the phylogenetic pathways that they regulate, we sought to identify MEF2 family members in other species. In Drosophila, a homolog of the vertebrate MEF2 genes was identified and termed D-mef2. The D-MEF2 protein binds to the consensus MEF2 element and can activate transcription through tandem copies of that site. During Drosophila embryogenesis, D-MEF2 is specific to the mesoderm germ layer of the developing embryo and becomes expressed in all muscle cell types within the embryo. The role of D-mef2 in Drosophila embryogenesis was examined by generating a loss-of-function mutation in the D-mef2 gene. In embryos homozygous for this mutant allele, somatic, cardiac, and visceral muscles fail to differentiate, but precursors of these myogenic lineages are normally specified and positioned. These results demonstrate that different muscle cell types share a common myogenic differentiation program controlled by MEF2 and suggest that this program has been conserved from Drosophila to mammals. ^

The differential expression of the $\beta\sb2$-adrenergic receptor modifies agonist-dependent adenylylcyclase activation

There have been multiple reports which indicate that variations in $\beta$AR expression affect the V$\sb{\rm max}$ observed for the agonist-dependent activation of adenylylcyclase. This observation has been ignored by most researchers when V$\sb{\rm max}$ values obtained for wild type and mutant receptors are compared. Such an imprecise analysis may lead to erroneous conclusions concerning the ability of a receptor to activate adenylylcyclase. Equations were derived from the Cassel-Selinger model of GTPase activity and Tolkovsky and Levitzki's Collision Coupling model which predict that the EC$\sb{50}$ and V$\sb{\rm max}$ for the activation of adenylylcyclase are a function of receptor number. Experimental results for L cell clones in which either hamster or human $\beta$AR were transfected at varying levels showed that EC$\sb{50}$ decreases and V$\sb{\rm max}$ increases as receptor number increases. Comparison of these results with simulations obtained from the equations describing EC$\sb{50}$ and V$\sb{\rm max}$ showed a close correlation. This documents that the kinetic parameters of adenylylcyclase activation change with the level of receptor expression and relates this phenomenon to a theoretical framework concerning the mechanisms involved in $\beta$AR signal transduction.^ One of the terms used in the equations which expressed the EC$\sb{50}$ and V$\sb{\rm max}$ as a function of receptor number is coupling efficiency, defined as $\rm k\sb1/k\sb{-1}$. Calculation of $\rm k\sb1/k\sb{-1}$ can be accomplished for wild type receptors with the easily measured experimental values of agonist K$\sb{\rm d}$, EC$\sb{50}$ and receptor number. This was demonstrated for hamster $\beta$AR which yielded a coupling efficiency of 0.15 $\pm$ 0.003 and human $\beta$AR which yielded a coupling efficiency of 0.90 $\pm$ 0.031. $\rm k\sb1/k\sb{-1}$ replaces the traditional qualitative evaluation of the ability to activate adenylylcyclase, which utilizes V$\sb{\rm max}$ without correction for variation in receptor number, with a quantitative definition that more accurately describes the ability of $\beta$AR to couple to G$\sb{\rm s}$.^ The equations which express the EC$\sb{50}$ and V$\sb{\rm max}$ for adenylylcyclase activation as a function of receptor number and coupling efficiency were tested to determine whether they could accurately simulate the changes seen in these parameters during desensitization. Data from original desensitization experiments and data from the literature (24,25,52,54,83) were compared to simulated changes in EC$\sb{50}$ and V$\sb{\rm max}$. In a variety of systems the predictions of the equations were consistent with the changes observed in EC$\sb{50}$ and V$\sb{\rm max}$. In addition reductions in the calculated value of $\rm k\sb1/k\sb{-1}$ was shown to correlate well with $\beta$AR phosphorylation and to be minimally affected by sequestration and down-regulation. ^

The Most Extensive Holocene Advance in the Stauning Alper, East Greenland, Occurred in the Little Ice Age

We present glacial geologic and chronologic data concerning the Holocene ice extent in the Stauning Alper of East Greenland. The retreat of ice from the late-glacial position back into the mountains was accomplished by at least 11 000 cal years B.P. The only recorded advance after this time occurred during the past few centuries (the Little Ice Age). Therefore, we postulate that the Little Ice Age event represents the maximum Holocene ice extent in this part of East Greenland.

Variations in Ice Rafted Detritus on Beaches in the South Shetland Islands: A Possible Climate Proxy

Raised beach ridges on Livingston Island of the South Shetland Islands display variations in both quantity and source of ice rafted detritus (IRD) received over time. Whereas the modem beach exhibits little IRD, all of which is of local origin, the next highest beach (similar to250 C-14 yr BP) has large amounts, some of which comes from as far away as the Antarctic Peninsula. Significant quantities of IRD also were deposited similar to 1750 C-14 yr BP. Both time periods coincide with generally cooler regional conditions and, at least in the case of the similar to250 yr old beach, local glacial advance. We suggest that the increases in ice rafting may reflect periods of greater glacial activity, altered ocean circulation, and/or greater iceberg preservation during the late Holocene. Limited IRD and lack of far-travelled erratics on the modem beach are both consistent with the ongoing warming trend in the Antarctic Peninsula region.

Pliocene Paleoenvironment and Antarctic Ice Sheet Behavior: Evidence from Wright Valley

Investigations in Wright Valley, adjacent to the Transantarctic Mountains in East Antarctica, shed light on the question of whether high-latitude Pliocene climate was warm enough to cause widespread deglaciation of the East Antarctic craton with a concurrent Magellanic moorland-like environment. If Pliocene age diatoms, presently in glaciogenic deposits high in the Transantarctic Mountains, had come from seaways on the East Antarctic craton, an expanding Late Pliocene ice sheet must have first eroded them from marine sediments and then deposited the diatoms at their present high-altitude locations. This hypothetical expanding glacier would have had to have come through Wright Valley. Glacial drift sediments from the central Wright Valley were mapped, sampled, analyzed, and Ar-40/Ar-39 whole rock dated. Our evidence indicates that an East Antarctic outlet glacier has not expanded through Wright Valley, and hence cannot have overridden the Dry Valleys sector of the Transantarctic Mountains, any time in the past 3.8 myr. Rather, there was only moderate Pliocene expansion of local cola-based alpine glaciers and continuous cold-desert conditions in Wright Valley. Persistence of a cold-desert paleoenvironment implies that the sector of the East Antarctic Ice Sheet adjacent to Wright Valley has remained relatively stable without melting ablation zones since at least 3.8 Ma, in Early Pliocene time. A further implication is that Antarctic Ice Sheet behavior in the Pliocene was much like that in the Quaternary, when the ice sheet consisted of a stable, terrestrial core in East Antarctica and a dynamic, marine-based appendage in West Antarctica.

Antarctic Glacial History Since the Last Glacial Maximum: An Overview of the Record on Land

This overview examines available circum-Antarctic glacial history archives on land, related to developments after the Last Glacial Maximum (LGM). It considers the glacial-stratigraphic and morphologic records and also biostratigraphical information from moss banks, lake sediments and penguin rookeries, with some reference to relevant glacial marine records. It is concluded that Holocene environmental development in Antarctica differed from that in the Northern Hemisphere. The initial deglaciation of the shelf areas surrounding Antarctica took place before 10000 C-14 yrs before present(sp), and was controlled by rising global sea level. This was followed by the deglaciation of some presently ice-free inner shelf and land areas between 10000 and 8000 yr sp. Continued deglaciation occurred gradually between 8000 yr sp and 5000 yr sp. Mid-Holocene glacial readvances are recorded from various sites around Antarctica. There are strong indications of a circum-Antarctic climate warmer than today 4700-2000 yr sp. The best dated records from the Antarctic Peninsula and coastal Victoria Land suggest climatic optimums there from 4000-3000 yr sp and 3600-2600 yr sp, respectively. Thereafter Neoglacial readvances are recorded. Relatively limited glacial expansions in Antarctica during the past few hundred years correlate with the Little Ice Age in the Northern Hemisphere.

Glacial Lake Wright, a High-Level Antarctic Lake During the LGM and Early Holocene

We report evidence of a large proglacial lake (Glacial Lake Wright) that existed in Wright Valley in the McMurdo Dry Valleys region of Antarctica at the last glacial maximum (LGM) and in the early Holocene. At its highstands, Glacial Lake Wright would have stretched 50 km and covered c. 210 km(2). Chronology for lake-level changes comes from 30 AMS radiocarbon dates of lacustrine algae preserved in deltas, shorelines, and glaciolacustrine deposits that extend up to 480 m above present-day lakes. Emerging evidence suggests that Glacial Lake Wright was only one of a series of large lakes to occupy the McMurdo Dry Valleys and the valleys fronting the Royal Society Range at the LGM. Although the cause of such high lake levels is not well understood, it is believed to relate to cool, dry conditions which produced fewer clouds, less snowfall, and greater amounts of absorbed radiation, leading to increased meltwater production.

Circum-Antarctic Coastal Environmental Shifts During the Late Quaternary Reflected by Emerged Marine Deposits

This review assesses the circumpolar occurrence of emerged marine macrofossils and sediments from Antarctic coastal areas in relation to Late Quaternary climate changes. Radiocarbon ages of the macrofossils, which are interpreted in view of the complexities of the Antarctic marine radiocarbon reservoir and resolution of this dating technique, show a bimodal distribution. The data indicate that marine species inhabited coastal environments from at least 35000 to 20000 yr sp, during Marine Isotope Stage 3 when extensive iceberg calving created a 'meltwater lid' over the Southern Ocean. The general absence of these marine species from 20000 to 8500 yr sp coincides with the subsequent advance of the Antarctic ice sheets during the Last Glacial Maximum. Synchronous re-appearance of the Antarctic marine fossils in emerged beaches around the continent, all of wh ich have Holocene marine-limit elevations an order of magnitude lower than those in the Arctic, reflect minimal isostatic rebound as relative sea-level rise decelerated. Antarctic coastal marine habitat changes around the continent also coincided with increasing sea-ice extent and outlet glacial advances during the mid-Holocene. in view of the diverse environmental changes that occurred around the Earth during this period, it is suggested that Antarctic coastal areas were responding to a mid-Holocene climatic shift associated with the hydrological cycle. This synthesis of Late Quaternary emerged marine deposits demonstrates the application of evaluating circum-Antarctic phenomena from the glacial-terrestrial-marine transition zone.

FOXC2 and fluid shear stress stabilize postnatal lymphatic vasculature

Biomechanical forces, such as fluid shear stress, govern multiple aspects of endothelial cell biology. In blood vessels, disturbed flow is associated with vascular diseases, such as atherosclerosis, and promotes endothelial cell proliferation and apoptosis. Here, we identified an important role for disturbed flow in lymphatic vessels, in which it cooperates with the transcription factor FOXC2 to ensure lifelong stability of the lymphatic vasculature. In cultured lymphatic endothelial cells, FOXC2 inactivation conferred abnormal shear stress sensing, promoting junction disassembly and entry into the cell cycle. Loss of FOXC2-dependent quiescence was mediated by the Hippo pathway transcriptional coactivator TAZ and, ultimately, led to cell death. In murine models, inducible deletion of Foxc2 within the lymphatic vasculature led to cell-cell junction defects, regression of valves, and focal vascular lumen collapse, which triggered generalized lymphatic vascular dysfunction and lethality. Together, our work describes a fundamental mechanism by which FOXC2 and oscillatory shear stress maintain lymphatic endothelial cell quiescence through intercellular junction and cytoskeleton stabilization and provides an essential link between biomechanical forces and endothelial cell identity that is necessary for postnatal vessel homeostasis. As FOXC2 is mutated in lymphedema-distichiasis syndrome, our data also underscore the role of impaired mechanotransduction in the pathology of this hereditary human disease.

Similar outcome of upfront-unrelated and matched sibling stem cell transplantation in idiopathic paediatric aplastic anaemia. A study on behalf of the UK Paediatric BMT Working Party, Paediatric Diseases Working Party and Severe Aplastic Anaemia Working Party of EBMT

Abstract We explored the feasibility of unrelated donor haematopoietic stem cell transplant (HSCT) upfront without prior immunosuppressive therapy (IST) in paediatric idiopathic severe aplastic anaemia (SAA). This cohort was then compared to matched historical controls who had undergone first-line therapy with a matched sibling/family donor (MSD) HSCT (n = 87) or IST with horse antithymocyte globulin and ciclosporin (n = 58) or second-line therapy with unrelated donor HSCT post-failed IST (n = 24). The 2-year overall survival in the upfront cohort was 96 ± 4% compared to 91 ± 3% in the MSD controls (P = 0·30) and 94 ± 3% in the IST controls (P = 0·68) and 74 ± 9% in the unrelated donor HSCT post-IST failure controls (P = 0·02).The 2-year event-free survival in the upfront cohort was 92 ± 5% compared to 87 ± 4% in MSD controls (P = 0·37), 40 ± 7% in IST controls (P = 0·0001) and 74 ± 9% in the unrelated donor HSCT post-IST failure controls (n = 24) (P = 0·02). Outcomes for upfront-unrelated donor HSCT in paediatric idiopathic SAA were similar to MSD HSCT and superior to IST and unrelated donor HSCT post-IST failure. Front-line therapy with matched unrelated donor HSCT is a novel treatment approach and could be considered as first-line therapy in selected paediatric patients who lack a MSD. © 2015 John Wiley & Sons Ltd.

Outcomes after early administration of plasma exchange in pediatric central nervous system inflammatory demyelination.

The use of plasma exchange has been described in steroid-refractory central nervous system inflammatory demyelination in adults, but less has been published regarding its use in children and adolescents. We describe 12 children treated with plasma exchange for acute severe central nervous system inflammatory demyelination. The clinical attack leading to plasma exchange included symptomatic spinal cord lesions in 10 and symptomatic brainstem lesions in 2 children. Diagnosis was acute transverse myelitis in 6, relapsing-remitting multiple sclerosis in 5, and acute disseminated encephalomyelitis in 1 child. Adverse events related to plasma exchange necessitating intervention were observed in 3 children. Median Expanded Disability Status Scale score at plasma exchange start was 7.5 (range 4-9.5). At 3 months, 7 children were ambulatory without aid (Expanded Disability Status Scale score of ≤4). This retrospective study suggests that plasma exchange can be effective in ameliorating symptoms in severe pediatric central nervous system inflammatory demyelination, although lack of randomization or control group limits the ability to attribute this outcome entirely to plasma exchange.

Perceived risk and outcome expectancy on the practice of home infusion technique in a hemophilia population

This study described home infusion techniques and practices, measured the perceived risk of HIV and hepatitis transmission to self and others, and measured the outcome expectancy of following risk reduction guidelines for 90 hemophilia patients and/or their infusion assistants. It also assessed general knowledge of HIV and hepatitis information for the same population.^ The study subjects were hemophilia patients or their infusion assistants from the Gulf States Hemophilia Center in Houston, the El Paso Satellite Hemophilia Clinic in El Paso, or Texas members of the Women Outreach Network of the National Hemophilia Foundation (WONN) group. Each subject was interviewed either by telephone or in person. The questionnaire used was developed for the study and consisted of 60 items. These items assessed general demographics for the patients and assistants, including questions about their training to do infusions as well as the actual practices, measured perceived personal risk for the transmission of HIV or hepatitis to the assistants, perceived risk of transmission of HIV or hepatitis to others for assistants and self-infusers, and the outcome expectancy for following recommended risk reduction guidelines also for both groups.^ The theoretical framework used assumed that perceived risk and outcome expectancy would be predictive of behavior. The findings did not support this theory. Instead, the findings suggest that infusion behavior is habitual in nature; most respondents perform exactly the same behavior for every infusion. Since none of the variables selected were predictive of the compliance behavior for home infusion the teaching method should be directed towards mastery learning, or learning that will incorporate the correct behavior into a habitual pattern of home infusion. ^

A Bayesian analysis for spatial processes with application to mapping

In geographical epidemiology, maps of disease rates and disease risk provide a spatial perspective for researching disease etiology. For rare diseases or when the population base is small, the rate and risk estimates may be unstable. Empirical Bayesian (EB) methods have been used to spatially smooth the estimates by permitting an area estimate to "borrow strength" from its neighbors. Such EB methods include the use of a Gamma model, of a James-Stein estimator, and of a conditional autoregressive (CAR) process. A fully Bayesian analysis of the CAR process is proposed. One advantage of this fully Bayesian analysis is that it can be implemented simply by using repeated sampling from the posterior densities. Use of a Markov chain Monte Carlo technique such as Gibbs sampler was not necessary. Direct resampling from the posterior densities provides exact small sample inferences instead of the approximate asymptotic analyses of maximum likelihood methods (Clayton & Kaldor, 1987). Further, the proposed CAR model provides for covariates to be included in the model. A simulation demonstrates the effect of sample size on the fully Bayesian analysis of the CAR process. The methods are applied to lip cancer data from Scotland, and the results are compared. ^