Background: Tracheal aspirate bacterial cultures are routinely collected in mechanically ventilated children for the evaluation of ventilator-associated infections (VAIs). However, frequent bacterial colonization of endotracheal and tracheostomy tubes contribute to the marginal performance characteristics of the test for diagnosing VAI. Published literature characterizing drivers of culture collection and the predictive value of positive cultures are limited. Methods: This single-center, retrospective cohort study included children admitted to the pediatric intensive care unit who were receiving mechanical ventilation for at least 48 hours and had 1 or more semiquantitative tracheal aspirate cultures collected between September 1, 2019, and August 31, 2020. Indications for culture collection were determined through medical record review and included fever, hypothermia, tracheal secretion changes, radiographic pneumonia, increased oxygen requirement, and/or increased positive end-expiratory pressure (PEEP). A positive culture was defined as moderate or heavy growth of a noncommensal bacterial organism. A purulent Gram stain was defined as detection of moderate or many white blood cells. Diagnosis of VAI was based on treating-clinician documentation and was ascertained through medical record review. Logistic regression accounting for clustering by patient was performed to estimate the association between indications for culture collection and (1) culture positivity, (2) purulent Gram stain, and (3) diagnosis of VAI. Results: In total, 625 tracheal aspirate cultures were performed in 261 unique patients. Common indications for culture collection included isolated fever or hypothermia (n = 124, 20%), fever with an increase in oxygen requirement or PEEP (n = 71, 11%), isolated increase in oxygen requirement or PEEP (n = 67, 11%), or isolated secretion change (n = 54, 9%) (Figure 1). Overall, 230 cultures (37%) were positive and 218 (35%) Gram stains were purulent. There were no associations between culture indications and a positive culture. Presence of isolated fever was negatively associated with a purulent Gram stain (odds ratio [OR], 0.49; 95% CI, 0.30–0.81; P = .005); otherwise, there were no associations between indication and purulent Gram stain. Finally, in a multivariable model, odds of VAI diagnosis increased with both the number of indications for culture collection and purulent Gram stain, but not with positive culture (Figure 2). Conclusions: Number and type of clinical signs were not associated with tracheal aspirate culture positivity or purulence on Gram stain, but they were associated with a clinical diagnosis of VAI. These findings suggest that positive tracheal aspirate cultures may not aid clinicians in the diagnosis of VAI, and they highlight the opportunity for improved diagnostic stewardship.

Funding: No

Disclosures: None

Figure 1.

Figure 2.

During glacial times, the North Atlantic region was affected by serious climate changes corresponding to Dansgaard-Oeschger cycles that were linked to dramatic shifts in sea temperature and moisture transfer to the continents. However, considerable efforts are still needed to understand the effects of these shifts on terrestrial environments. In this context, the Iberian Peninsula is particularly interesting because of its close proximity to the North Atlantic, although the Iberian interior lacks paleoenvironmental information so far because suitable archives are rare. Here we provide an accurate impression of the last glacial environmental developments in central Iberia based on comprehensive investigations using the upper Tagus loess record. A multi-proxy approach revealed that phases of loess formation during Marine Isotope Stage (MIS) 2 (and upper MIS 3) were linked to utmost aridity, coldness, and highest wind strengths in line with the most intense Greenland stadials also including Heinrich Events 3–1. Lack of loess deposition during the global last glacial maximum (LGM) suggests milder conditions, which agrees with less-cold sea surface temperatures (SST) off the Iberian margin. Our results demonstrate that geomorphological system behavior in central Iberia is highly sensitive to North Atlantic SST fluctuations, thus enabling us to reconstruct a detailed hydrological model in relation to marine–atmospheric circulation patterns.

In connection with the work of Anscombe, Macpherson, Steinhorn and the present author in [1] we investigate the notion of a multidimensional exact class (R-mec), a special kind of multidimensional asymptotic class (R-mac) with measuring functions that yield the exact sizes of definable sets, not just approximations. We use results about smooth approximation [24] and Lie coordinatization [13] to prove the following result (Theorem 4.6.4), as conjectured by Macpherson: For any countable language $\mathcal {L}$ and any positive integer d the class $\mathcal {C}(\mathcal {L},d)$ of all finite $\mathcal {L}$-structures with at most d 4-types is a polynomial exact class in $\mathcal {L}$, where a polynomial exact class is a multidimensional exact class with polynomial measuring functions.

Pulmonary hypertension is a complex and progressive condition that is either idiopathic or heritable, or associated with one or multiple health conditions, with or without congenital or acquired cardiovascular disease. Recent developments have tremendously increased the armamentarium of diagnostic and therapeutic approaches in children and young adults with pulmonary hypertension that is still associated with a high morbidity and mortality. These modalities include non-invasive imaging, pharmacotherapy, interventional and surgical procedures, and supportive measures. The optimal, tailored diagnostic and therapeutic strategies for pulmonary hypertension in the young are rapidly evolving but still face enormous challenges: Healthcare providers need to take the patient’s age, development, disease state, and family concerns into account when initiating advanced diagnostics and treatment. Therefore, there is a need for guidance on core and advanced medical training in paediatric pulmonary hypertension. The Association for European Paediatric and Congenital Cardiology working group “pulmonary hypertension, heart failure and transplantation” has produced this document as an expert consensus statement; however, all recommendations must be considered and applied in the context of the local and national infrastructure and legal regulations.

Compound-specific radiocarbon (14C) dating often requires working with small samples of < 100 µg carbon (µgC). This makes the radiocarbon dates of biomarker compounds very sensitive to biases caused by extraneous carbon of unknown composition, a procedural blank, which is introduced to the samples during the steps necessary to prepare a sample for radiocarbon analysis by accelerator mass spectrometry (i.e., isolating single compounds from a heterogeneous mixture, combustion, gas purification and graphitization). Reporting accurate radiocarbon dates thus requires a correction for the procedural blank. We present our approach to assess the fraction modern carbon (F14C) and the mass of the procedural blanks introduced during the preparation procedures of lipid biomarkers (i.e. n-alkanoic acids) and lignin phenols. We isolated differently sized aliquots (6–151 µgC) of n-alkanoic acids and lignin phenols obtained from standard materials with known F14C values. Each compound class was extracted from two standard materials (one fossil, one modern) and purified using the same procedures as for natural samples of unknown F14C. There is an inverse linear relationship between the measured F14C values of the processed aliquots and their mass, which suggests constant contamination during processing of individual samples. We use Bayesian methods to fit linear regression lines between F14C and 1/mass for the fossil and modern standards. The intersection points of these lines are used to infer F14Cblank and mblank and their associated uncertainties. We estimate 4.88 ± 0.69 μgC of procedural blank with F14C of 0.714 ± 0.077 for n-alkanoic acids, and 0.90 ± 0.23 μgC of procedural blank with F14C of 0.813 ± 0.155 for lignin phenols. These F14Cblank and mblank can be used to correct AMS results of lipid and lignin samples by isotopic mass balance. This method may serve as a standardized procedure for blank assessment in small-scale radiocarbon analysis.

Timely access to care services is crucial to support people with dementia and their family carers to live well. Carers of people with dementia (N = 390), recruited from eight countries, completed semi-structured interviews about their experiences of either accessing or not using formal care services over a 12-month period in the Access to Timely Formal Care (Actifcare) study. Participant responses were summarised using content analysis, categorised into clusters and frequencies were calculated. Less than half of the participants (42.3%) reported service use. Of those using services, 72.8 per cent reported timely access and of those not using services 67.2 per cent were satisfied with this situation. However, substantial minorities either reported access at the wrong time (27.2%), or feeling dissatisfied or mixed feelings about not accessing services (32.8%). Reasons for not using services included use not necessary yet, the carer provided support or refusal. Reasons given for using services included changes in the condition of the person with dementia, the service's ability to meet individual needs, not coping or the opportunity to access services arose. Facilitators and barriers to service use included whether participants experienced supportive professionals, the speed of the process, whether the general practitioner was helpful, participant's own proactive attitude and the quality of information received. To achieve timely support, simplified pathways to use of formal care services are needed.

The appearances of palaeosurfaces intercalated into palaeo-dune fields on Fuerteventura are multifaceted. Although reddened layers in these dune sediments might suggest that strong soil-formation processes have taken place, the combination of aridity and parent material, namely biogenic carbonate sand of shelf origin, reveals that strong soil formation seems unlikely. These sediments rather represent de- and recalcification processes only. Solely in the case of admixed material of volcanic origin and dust deposits further soil-forming processes seem to be possible. Hematite-rich Saharan dust contributes to reddish colouration of the palaeosurfaces. In addition, CaCO3-coated iron particles appear to be ingredients of dust being leached after deposition and transformed to hematite. Overall, we propose much weaker soil-forming processes during the Pleistocene than previously postulated. Our findings support the relevance of local environments. Carbonate sands of shelf origin hinder strong soil formation and the reddish layers separating dune generations are palaeosurfaces, which mainly consist of Saharan dust. After deposition of allochthonous material, these layers are overprinted by weak soil-forming processes. The formation of palaeosurfaces primarily depends on morphodynamically stable periods during limited sand supply. Our data suggest a cyclicity of processes in the following order: (1) sand accumulation, (2) dust accumulation and weak soil formation, and (3) water-induced erosion. For the Canary Islands, we support the assumption of glacial maxima being periods of increased levels of moisture. In combination with rising sea level, we propose that favorable conditions of surface stability occur immediately after glacial maxima during periods of starting transgression, whereas regression periods immediately after sea-level high stands seem to yield the highest sand supply for the study area.

OBJECTIVES/SPECIFIC AIMS: Parkinson’s disease (PD) is a condition that affects over a million Americans, and despite current medical therapies, the progression of the disease results in impaired generation of internally timed or guided (IG) movements. To address this loss of motor function, previous rehabilitation therapies have focused on remediating the affected striatal-thalamic-cortical circuits (STC), primarily thought to be responsible in generating timed motor patterns. However, given the disease leads to the cell death of dopaminergic cells that are essential for proper STC function, we propose a motor therapy aimed at utilizing a compensatory parallel cerebellar-thalamic-cortical (CTC) pathway, recruited to perform externally guided (EG) movements, in which gait initiation is driven from sensory input. Our previous study has shown efficacy in our novel argentine tango therapy and improves behavioral measures above the relevant MCID threshold, but it has not been established that the CTC are in the causal pathway that are responsible for these changes. Using neural measures from task fMRI, we have begun to characterize networks that have changed and quantify any associations with behavioral metrics. METHODS/STUDY POPULATION: Patients were randomly assigned to an IG (n=18), EG (n=18), or education contact control (n=14). Participants were assessed preintervention and postintervention for behavioral motor and cognitive measures and neurophysiologically with task based fMRI. In the task, participants performed a foot tapping task under both IG (tap their foot in previously learned rhythm) or EG (tap immediately after receiving a tactile cue on their hand) conditions. The fMRI data were preprocessed using AFNI and registered to MNI standard space. The brainnetome atlas was applied and the average time series of each region of interest (ROI) was used to increase the signal to noise ratio. The activation of these ROI with respect to the stimulus was modeled using GLM, and we estimated the area under the curve during the task blocks. A 1-way ANOVA analysis on these betas were performed between the pre and the post intervention time points and the ROIs that were above a significance of 0.95 were identified and corrected for multiple comparisons. The change in beta in all ROIs for each individual were calculated and then correlated with the changes in the behavioral data, to see which changes in ROI areas matched the best with the behavioral changes. RESULTS/ANTICIPATED RESULTS: The EG group showed significant changes only in the EG task in 2 areas—inferior frontal gyrus and inferior temporal sulcus. Correlating to the cognitive behavioral measures show reduced error from the Inferior frontal gyrus (corr>0.5) best reflect changes in observed. There were no changes to either the STC or the CTC pathways. The IG group showed no changes behaviorally and showed no changes neurally as well. The control group showed no changes behaviorally, but neuronally certain DMN nodes, such as the precuneus and inferior temporal regions showed a significant change for both tasks. DISCUSSION/SIGNIFICANCE OF IMPACT: Addressing the damaged STC pathway directly through IG therapy may not be effective. The EG therapy may not be able to enhance the STC pathway. However, the therapy appears to utilize new areas in the frontal regions and correlates with positively with changes in spatial memory and balance tasks. Contrary to our hypothesis the CTC circuit was not upregulated for performance of the IG or EG task, but therapy may have enhanced recruitment of other cognitively engaged areas. The educational control group interestingly showed changes in the DMN network, which has been shown to be linked to attention during tasks blocks.