Trends in pediatric-adjusted shock index predict morbidity in children with moderate blunt injuries

Purpose Trending the pediatric-adjusted shock index (SIPA) after admission has been described for children suffering severe blunt injuries (i.e., injury severity score (ISS) ≥ 15). We propose that following SIPA in children with moderate blunt injuries, as defined by ISS 10–14, has similar utility. Methods The trauma registry at a single institution was queried over a 7 year period. Patients were included if they were between 4 and 16 years old at the time of admission, sustained a blunt injury with an ISS 10–14, and were admitted less than 12 h after their injury (n = 501). Each patient’s SIPA was then calculated at 0, 12, 24, 36, and 48 h (h) after admission and then categorized as elevated or normal at each time frame based on previously reported values. Trends in outcome variables as a function of time from admission for patients with an abnormal SIPA to normalize as well as patients with a normal admission SIPA to abnormal were analyzed. Results In patients with a normal SIPA at arrival, elevation within the first 24 h of admission correlated with increased length of stay (LOS). Increased transfusion requirement, incidence of infectious complications, and need for in-patient rehabilitation were also seen in analyzed sub-groups. An elevated SIPA at arrival with increased length of time to normalize SIPA correlated with increased length of stay LOS in the entire cohort and in those without head injury, but not in patients with a head injury. No deaths occurred within the study cohort. Conclusions Patients with an ISS 10–14 and a normal SIPA at time of arrival who then have an elevated SIPA in the first 24 h of admission are at increased risk for morbidity including longer LOS and infectious complications. Similarly, time to normalize an elevated admission SIPA appears to directly correlate with LOS in patients without head injuries. No correlations with markers for morbidity could be identified in patients with a head injury and an elevated SIPA at arrival. This may be due to small sample size, as there were no relations to severity of head injury as measured by head abbreviated injury scale (head AIS) and the outcome variables reported. This is an area of ongoing analysis. This study extends the previously reported utility of following SIPA after admission into milder blunt injuries

Trends in pediatric adjusted shock index predict morbidity and mortality in children with severe blunt injuries

Purpose The utility of measuring the pediatric adjusted shock index (SIPA) at admission for predicting severity of blunt injury in pediatric patients has been previously reported. However, the utility of following SIPA after admission is not well described. Methods The trauma registry from a level-one pediatric trauma center was queried from January 1, 2010 to December 31, 2015. Patients were included if they were between 4 and 16 years old at the time of admission, sustained a blunt injury with an Injury Severity Score ≥ 15, and were admitted less than 12 h after their injury (n = 286). Each patient's SIPA was then calculated at 0, 12, 24, 36, and 48 h after admission and then categorized as elevated or normal at each time frame based upon previously reported values. Trends in outcome variables as a function of time from admission for patients with an abnormal SIPA to normalize as well as patients with a normal admission SIPA to abnormal were analyzed. Results In patients with a normal SIPA at arrival, 18.4% of patients who developed an elevated SIPA at 12 h after admission died, whereas 2.4% of patients who maintained a normal SIPA throughout the first 48 h of admission died (p < 0.01). Among patients with an elevated SIPA at arrival, increased length of time to normalize SIPA correlated with increased length of stay (LOS) and intensive care unit (ICU) LOS. Similarly, elevation of SIPA after arrival in patients with a normal initial SIPA correlated to increased LOS and ICU LOS. Conclusions Patients with a normal SIPA at time of arrival who then have an elevated SIPA in the first 24 h of admission are at increased risk for morbidity and mortality compared to those whose SIPA remains normal throughout the first 48 h of admission. Similarly, time to normalize an elevated admission SIPA appears to directly correlate with LOS, ICU LOS, and other markers of morbidity across a mixed blunt trauma population. Whether trending SIPA early in the hospital course serves only as a marker for injury severity or if it has utility as a resuscitation metric has not yet been determined

Granular spirals on erodible sand bed submitted to a circular fluid motion

An experimental study of a granular surface submitted to a circular fluid motion is presented. The appearance of an instability along the sand-water interface is observed beyond a critical radius $r_c$. This creates ripples with a spiral shape on the granular surface. A phase diagram of such patterns is constructed and discussed as a function of the rotation speed $\omega$ of the flow and as a function of the height of water $h$ above the surface. The study of $r_c$ as a function of $h$, $\omega$ and $r$ parameters is reported. Thereafter, $r_c$ is shown to depend on the rotation speed according to a power law. The ripple wavelength is found to decrease when the rotation speed increases and is proportional to the radial distance $r$. The azimuthal angle \az of the spiral arms is studied. It is found that \az scales with $h\omega r$. This lead to the conclusion that \az depends on the fluid momentum. Comparison with experiments performed with fluids allows us to state that the spiral patterns are not the signature of an instability of the boundary layer.Comment: 7 pages, 10 figures, 1 table, using RevTeX4, submitted for publication (2002

Non-Visual Effects of Light on Melatonin, Alertness and Cognitive Performance: Can Blue-Enriched Light Keep Us Alert?

Light exposure can cascade numerous effects on the human circadian process via the non-imaging forming system, whose spectral relevance is highest in the short-wavelength range. Here we investigated if commercially available compact fluorescent lamps with different colour temperatures can impact on alertness and cognitive performance

Characterization of Sleep Stages by Correlations of Heartbeat Increments

We study correlation properties of the magnitude and the sign of the increments in the time intervals between successive heartbeats during light sleep, deep sleep, and REM sleep using the detrended fluctuation analysis method. We find short-range anticorrelations in the sign time series, which are strong during deep sleep, weaker during light sleep and even weaker during REM sleep. In contrast, we find long-range positive correlations in the magnitude time series, which are strong during REM sleep and weaker during light sleep. We observe uncorrelated behavior for the magnitude during deep sleep. Since the magnitude series relates to the nonlinear properties of the original time series, while the signs series relates to the linear properties, our findings suggest that the nonlinear properties of the heartbeat dynamics are more pronounced during REM sleep. Thus, the sign and the magnitude series provide information which is useful in distinguishing between the sleep stages.Comment: 7 pages, 4 figures, revte

366 Combined exploratory immunophenotyping and transcriptomic tumor analysis in patients treated with OSE2101 vaccine in HLA-A2+ advanced non-small cell lung cancer (NSCLC) from the ATALANTE-1 trial

BackgroundOSE2101 (Tedopi®) is an anticancer vaccine with HLA-A2+ restricted modified epitopes targeting five tumor-associated antigens (TAAs) frequently expressed in lung cancer (CEA, HER2, MAGE2, MAGE3, P53). Step-1 results of the phase III, randomized, open-label ATALANTE-1 study comparing Tedopi® vs standard treatment (SoC) showed a favorable benefit/risk of Tedopi® over SoC (HR 0.71 for overall survival OS) in HLA-A2+ NSCLC patients in 2nd or 3rd line treatment after progression on immune checkpoint blockers (ICB).1 We analyze available tumor biopsies at initial diagnosis from some patients treated with Tedopi® to determine the expression of the 5 TAAs and to identify other tumor factors associated with long-term survival.MethodsTumor biopsies were available for 8 HLA-A2+ (blood test) stage IV NSCLC patients included in the trial. Primary (<12 weeks) and secondary (≥ 12 weeks) resistance to ICB were observed in 3 (38%) and 5 (62%) of patients. Best response to Tedopi® and OS were: 1 partial response (PR) (OS of 33 months), 3 stable disease (SD) (OS of 22, 26 and 41 mo.) and 4 disease progression (PD) (OS of 3, 4, 30 and 31 mo.). HLA-class I, PD-L1, CD8 T-cells, HER2, CEA and P53 tumor expression were evaluated by immunohistochemistry (IHC). NanoString gene expression profiling was performed using the Pan Cancer Immune gene set.ResultsHLA-class I was expressed in all tumor samples. IHC analysis revealed that P53, CEA and HER2 were expressed in 6/7, 5/7 and 0/7 patients, respectively. P53, CEA, HER2, MAGE2, and MAGE3 were detected at RNA level in 5/5 tested patients (table 1). IMMUNOSCORE® IC CD8/PDL1 analysis showed High/High, High/Low and Low/Low scores for 1/7, 1/7 and 5/7 patients, respectively. The High/High IMMUNOSCORE® with a pronounced CD8+ T-cell tumor infiltration was observed in the patient with PR. High percentage of tumor cells expressing P53 (69%–97%) and overexpression of genes associated with activated macrophages (TREM2, MARCO, SLC11A1, CHIT1, SERPINB2) were observed in the PR and SD patients. High IFN-gamma and Expanded Immune Gene Signature scores were observed in long-term survivor patients with secondary resistance to ICB, even after progressive disease.Abstract 366 Table 1Summary of clinical and translational dataCEACarcinoembryonic antigen; HER2: Human Epidermal Growth Factor Receptor-2; ICB: Immune checkpoint blocker; IHC: Immunohistochemistry; ND: Not determined; OS: Overall Survival; Patient ID: Patient identification; PDL1: Programmed death-ligand 1; PFS: Progression-free survival; ssGSEA: Single-sample Gene Set Enrichment Analysis. Blue bars = Length of overall survival; Green bars = Gene Signature upregulation; Red bars = Gene Signature downregulationConclusionsThis study shows that all HLA-A2+ patients (blood test), expressed HLA class I in the tumors at initial diagnosis. Transcriptomic data in the patients that benefited from Tedopi® showed activated macrophage pathway, high IFN-gamma and Expanded Immune Gene Signatures scores. These data will be validated on larger number of patients treated with Tedopi® after the step 2 analysis.AcknowledgementsWe thank Julie Le Boulicaut, François Montestruc and Constant Josse (eXYSTAT, Malakoff, France) for the statistical analysis, and HalioDx for the IHC and NanoString analysis.Trial RegistrationEudraCT number2015-003183-36; NCT number: NCT02654587ReferenceGiaccone, et al. Activity of OSE-2101 in HLA-A2+ non-small cell lung cancer (NSCLC) patients after failure to immune checkpoint inhibitors (ICI): step 1 results of phase III ATALANTE-1 randomised trial. ESMO meeting 2020, abstract #1260MO.Ethics ApprovalThe study protocol and its related documents (including the patient information and informed consent form) received approval from the Institutional Review Board (IRB), and the Competent Authority prior to study initiation.ConsentEach patient gave his/her written informed consent prior to study enrolment

Thriving at work: Toward its measurement, construct validation, and theoretical refinement

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90225/1/job756.pd

Climatic and geographic predictors of life history variation in Eastern Massasauga (Sistrurus catenatus): A range-wide synthesis

Elucidating how life history traits vary geographically is important to understanding variation in population dynamics. Because many aspects of ectotherm life history are climate-dependent, geographic variation in climate is expected to have a large impact on population dynamics through effects on annual survival, body size, growth rate, age at first reproduction, size-fecundity relationship, and reproductive frequency. The Eastern Massasauga (Sistrurus catenatus) is a small, imperiled North American rattlesnake with a distribution centered on the Great Lakes region, where lake effects strongly influence local conditions. To address Eastern Massasauga life history data gaps, we compiled data from 47 study sites representing 38 counties across the range. We used multimodel inference and general linear models with geographic coordinates and annual climate normals as explanatory variables to clarify patterns of variation in life history traits. We found strong evidence for geographic variation in six of nine life history variables. Adult female snout-vent length and neonate mass increased with increasing mean annual precipitation. Litter size decreased with increasing mean temperature, and the size-fecundity relationship and growth prior to first hibernation both increased with increasing latitude. The proportion of gravid females also increased with increasing latitude, but this relationship may be the result of geographically varying detection bias. Our results provide insights into ectotherm life history variation and fill critical data gaps, which will inform Eastern Massasauga conservation efforts by improving biological realism for models of population viability and climate change