A service evaluation of measuring fluid responsiveness in acutely unwell hypotensive patients outside of critical care.

INTRODUCTION: Early recognition and prompt, appropriate management may reduce mortality in patients with sepsis. The Surviving Sepsis Campaign's guidelines suggest the use of dynamic measurements to guide fluid resuscitation in sepsis; although these methods are rarely employed to monitor cardiac output in response to fluid administration outside intensive care units. This service evaluation investigated the introduction of a nurse led protocolised goal-directed fluid management using a non-invasive cardiac output monitor to the standard assessment of hypotensive ward patients. METHODS: We introduced the use of a goal-directed fluid management protocol into our critical care outreach teams' standard clinical assessment. Forty-nine sequential patients before and thirty-nine after its introduction were included in the assessment. RESULTS: Patients in the post-intervention cohort received less fluid in the 6 h following outreach assessment (750mls vs 1200mls). There were no differences in clinical background or rates of renal replacement therapy, but rates of invasive and non-invasive ventilation were reduced (0% vs 31%). Although the groups were similar, the post-intervention patients had lower recorded blood pressures. CONCLUSION: IV fluid therapy in the patient with hypotension complicating sepsis can be challenging. Excessive IV fluid administration is commonplace and associated with harm, and the use of advanced non-invasive haemodynamic monitoring by trained nurses can provide objective evaluation of individualised response to treatment. Avoiding excessive IV fluid and earlier institution of appropriate vasopressor therapy may improve patient outcomes. IMPLICATIONS FOR CLINICAL PRACTICE: Adoption of dynamic measures of cardiac output outside of critical care by trained critical care nurses is feasible and may translate into improved patient outcomes. In hospitals with a nurse-led critical care outreach service, consideration should be given to such an approach.

Cystic fibrosis-related diabetes onset can be predicted using biomarkers measured at birth.

PURPOSE: Cystic fibrosis (CF), caused by pathogenic variants in the CF transmembrane conductance regulator (CFTR), affects multiple organs including the exocrine pancreas, which is a causal contributor to cystic fibrosis-related diabetes (CFRD). Untreated CFRD causes increased CF-related mortality whereas early detection can improve outcomes. METHODS: Using genetic and easily accessible clinical measures available at birth, we constructed a CFRD prediction model using the Canadian CF Gene Modifier Study (CGS; n = 1,958) and validated it in the French CF Gene Modifier Study (FGMS; n = 1,003). We investigated genetic variants shown to associate with CF disease severity across multiple organs in genome-wide association studies. RESULTS: The strongest predictors included sex, CFTR severity score, and several genetic variants including one annotated to PRSS1, which encodes cationic trypsinogen. The final model defined in the CGS shows excellent agreement when validated on the FGMS, and the risk classifier shows slightly better performance at predicting CFRD risk later in life in both studies. CONCLUSION: We demonstrated clinical utility by comparing CFRD prevalence rates between the top 10% of individuals with the highest risk and the bottom 10% with the lowest risk. A web-based application was developed to provide practitioners with patient-specific CFRD risk to guide CFRD monitoring and treatment.

The silicon cycle impacted by past ice sheets.

Globally averaged riverine silicon (Si) concentrations and isotope composition (δ30Si) may be affected by the expansion and retreat of large ice sheets during glacial-interglacial cycles. Here we provide evidence of this based on the δ30Si composition of meltwater runoff from a Greenland Ice Sheet catchment. Glacier runoff has the lightest δ30Si measured in running waters (-0.25 ± 0.12‰), significantly lower than nonglacial rivers (1.25 ± 0.68‰), such that the overall decline in glacial runoff since the Last Glacial Maximum (LGM) may explain 0.06-0.17‰ of the observed ocean δ30Si rise (0.5-1.0‰). A marine sediment core proximal to Iceland provides further evidence for transient, low-δ30Si meltwater pulses during glacial termination. Diatom Si uptake during the LGM was likely similar to present day due to an expanded Si inventory, which raises the possibility of a feedback between ice sheet expansion, enhanced Si export to the ocean and reduced CO2 concentration in the atmosphere, because of the importance of diatoms in the biological carbon pump.

Quantitative comparison of taxa and taxon concepts in the diatom genus Fragilariopsis: a case study on using slide scanning, multiexpert image annotation, and image analysis in taxonomy1.

Semiautomated methods for microscopic image acquisition, image analysis, and taxonomic identification have repeatedly received attention in diatom analysis. Less well studied is the question whether and how such methods might prove useful for clarifying the delimitation of species that are difficult to separate for human taxonomists. To try to answer this question, three very similar Fragilariopsis species endemic to the Southern Ocean were targeted in this study: F. obliquecostata, F. ritscheri, and F. sublinearis. A set of 501 extended focus depth specimen images were obtained using a standardized, semiautomated microscopic procedure. Twelve diatomists independently identified these specimen images in order to reconcile taxonomic opinions and agree upon a taxonomic gold standard. Using image analyses, we then extracted morphometric features representing taxonomic characters of the target taxa. The discriminating ability of individual morphometric features was tested visually and statistically, and multivariate classification experiments were performed to test the agreement of the quantitatively defined taxa assignments with expert consensus opinion. Beyond an updated differential diagnosis of the studied taxa, our study also shows that automated imaging and image analysis procedures for diatoms are coming close to reaching a broad applicability for routine use.

Temporal controls on silicic acid utilisation along the West Antarctic Peninsula.

The impact of climatic change along the Antarctica Peninsula has been widely debated in light of atmospheric/oceanic warming and increases in glacial melt over the past half century. Particular concern exists over the impact of these changes on marine ecosystems, not only on primary producers but also on higher trophic levels. Here we present a record detailing of the historical controls on the biogeochemical cycling of silicic acid [Si(OH)4] on the west Antarctica Peninsula margin, a region in which the modern phytoplankton environment is constrained by seasonal sea ice. We demonstrate that Si(OH)4 cycling through the Holocene alternates between being primarily regulated by sea ice or glacial discharge from the surrounding grounded ice sheet. With further climate-driven change and melting forecast for the twenty-first century, our findings document the potential for biogeochemical cycling and multi-trophic interactions along the peninsula to be increasingly regulated by glacial discharge, altering food-web interactions.

Late Cretaceous seasonal ocean variability from the Arctic.

The modern Arctic Ocean is regarded as a barometer of global change and amplifier of global warming and therefore records of past Arctic change are critical for palaeoclimate reconstruction. Little is known of the state of the Arctic Ocean in the greenhouse period of the Late Cretaceous epoch (65-99 million years ago), yet records from such times may yield important clues to Arctic Ocean behaviour in near-future warmer climates. Here we present a seasonally resolved Cretaceous sedimentary record from the Alpha ridge of the Arctic Ocean. This palaeo-sediment trap provides new insight into the workings of the Cretaceous marine biological carbon pump. Seasonal primary production was dominated by diatom algae but was not related to upwelling as was previously hypothesized. Rather, production occurred within a stratified water column, involving specially adapted species in blooms resembling those of the modern North Pacific subtropical gyre, or those indicated for the Mediterranean sapropels. With increased CO(2) levels and warming currently driving increased stratification in the global ocean, this style of production that is adapted to stratification may become more widespread. Our evidence for seasonal diatom production and flux testify to an ice-free summer, but thin accumulations of terrigenous sediment within the diatom ooze are consistent with the presence of intermittent sea ice in the winter, supporting a wide body of evidence for low temperatures in the Late Cretaceous Arctic Ocean, rather than recent suggestions of a 15 degrees C mean annual temperature at this time.

Interhemispheric Atlantic seesaw response during the last deglaciation.

The asynchronous relationship between millennial-scale temperature changes over Greenland and Antarctica during the last glacial period has led to the notion of a bipolar seesaw which acts to redistribute heat depending on the state of meridional overturning circulation within the Atlantic Ocean. Here we present new records from the South Atlantic that show rapid changes during the last deglaciation that were instantaneous (within dating uncertainty) and of opposite sign to those observed in the North Atlantic. Our results demonstrate a direct link between the abrupt changes associated with variations in the Atlantic meridional overturning circulation and the more gradual adjustments characteristic of the Southern Ocean. These results emphasize the importance of the Southern Ocean for the development and transmission of millennial-scale climate variability and highlight its role in deglacial climate change and the associated rise in atmospheric carbon dioxide.

Dissociation of inflammatory markers and natural killer cell activity in major depressive disorder.

Major depressive disorder is associated with increases in infectious disease risk as well as the incidence of inflammatory disorders. Declines of natural killer (NK) cell activity are reliably found in depression, whereas other studies report evidence of inflammation in depressed patients. The potential association between NK activity and circulating markers of immune activation has not been previously examined in the context of major depression. In this study, we measured levels of NK activity, circulating levels of interleukin-6 (IL-6), soluble interleukin-2 receptor, and acute phase proteins in 25 male patients with current major depressive disorder and 25 age, gender, and body weight comparable controls. As compared to controls, patients with major depressive disorder showed lower NK activity (p = .05) and higher circulating levels of IL-6 (p < .05). Levels of NK activity were not correlated with IL-6 or with other markers of immune activation. The independent effect of depression on inflammatory markers and natural killer immune responses has implications for understanding individual differences in the adverse health effects of major depressive disorder.

Shingles Immunity and Health Functioning in the Elderly: Tai Chi Chih as a Behavioral Treatment.

Both the incidence and severity of herpes zoster (HZ) or shingles increase markedly with increasing age in association with a decline in varicella zoster virus (VZV)-specific immunity. Considerable evidence shows that behavioral stressors, prevalent in older adults, correlate with impairments of cellular immunity. Moreover, the presence of depressive symptoms in older adults is associated with declines in VZV-responder cell frequency (VZV-RCF), an immunological marker of shingles risk. In this review, we discuss recent findings that administration of a relaxation response-based intervention, tai chi chih (TCC), results in improvements in health functioning and immunity to VZV in older adults as compared with a control group. TCC is a slow moving meditation consisting of 20 separate standardized movements which can be readily used in elderly and medically compromised individuals. TCC offers standardized training and practice schedules, lending an important advantage over prior relaxation response-based therapies. Focus on older adults at increased risk for HZ and assay of VZV-specific immunity have implications for understanding the impact of behavioral factors and a behavioral intervention on a clinically relevant end-point and on the response of the immune system to infectious pathogens.

Effects of a behavioral intervention, Tai Chi Chih, on varicella-zoster virus specific immunity and health functioning in older adults.

OBJECTIVE: Both the incidence and severity of herpes zoster (shingles) increase markedly with increasing age in association with a decline in varicella-zoster virus (VZV) specific cell-mediated immunity (CMI). This study examined whether a behavioral intervention, Tai Chi Chih (TCC), affects VZV specific immunity and health functioning in older adults who, on average, show impairments of health status and are at risk for shingles. METHODS: Thirty-six men and women (age > or =60 years) were assigned randomly to a 15-week program of TCC instruction (three 45 minute classes per week; N = 18) or a wait list control condition (N = 18). VZV-specific CMI was measured at baseline and at 1-week postintervention. Health functioning (Medical Outcome scale: SF-36) was assessed at baseline, and at 5, 10, and 15 weeks during the intervention, and at 1-week postintervention. RESULTS: In the intent-to-treat sample, VZV-specific CMI increased 50% from baseline to 1-week postintervention in the TCC group (p < 0.05) but was unchanged in the wait list control group. In those who completed the study, 1-week postintervention SF-36 scale scores for role-physical (p < 0.05) and physical functioning (p < 0.05) were higher in the TCC group (N = 14) as compared with controls (N = 17). Older adults who had impairments of physical status at baseline showed the greatest increases of SF-36 role-physical (p < 0.01) and physical functioning (p < 0.001) during the TCC intervention. CONCLUSIONS: Administration of TCC for 15 weeks led to an increase in VZV-specific CMI. Gains in health functioning were found in participants who received TCC and were most marked in those older adults who had the greatest impairments of health status.