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Organic dye aggregates have been shown to exhibit exciton delocalization in natural and synthetic systems. Such dye aggregates show promise in the emerging area of quantum information science (QIS). We believe that the difference in static dipole (Δ d ) is an essential dye parameter in the development of molecular QIS systems. However, a foundational understanding of the structural factors influencing Δ d remains elusive. Bacteriochlorins play a vital role in photosynthesis due to their exceptional photophysical properties. Therefore, bacteriochlorins are particularly suitable dyes for the construction of aggregate systems for QIS. Synthetic bacteriochlorins further offer stability and tunability via chemical modifications. Here, the influence of substituents on the Δ d of monomeric (nonaggregated) dyes was investigated via density functional theory (DFT) and time-dependent (TD)DFT in a set of 5-methoxybacteriochlorins progressively substituted with ethynyl, phenyl, and phenylethynyl substituents at the 3,13 and 3,13,15 positions of the macrocycle. Symmetrically substituted 5-methoxybacteriochlorins were shown to have the largest Δ d . The increase in Δ d in the series of dyes was largely due to changes in the orientation of the static dipole upon excitation rather than large changes in magnitude. In addition, the transition dipole ( μ ) and the angle between Δ d and μ ( ζ ) were calculated. Three 5-methoxybacteriochlorins with large predicted Δ d and μ values were synthesized and characterized spectroscopically. The trend in Δ d values empirically determined using the solvatochromic Stokes shift method was comparable to the DFT calculations.

We report developmental details of a high-sensitivity Stark absorption spectrometer featuring a laser-driven light source. The light source exhibits intensity fluctuations of ∼0.3% over timescales ranging from 1 min to 12 h, minimal drift (≤0.1%/h), and very little 1/f noise at frequencies greater than 200 Hz, which are comparable to or better than an arc-driven light source. Additional features of the spectrometer include balanced detection with multiplex sampling, which yielded lower noise in A, and constant wavelength or wavenumber (energy) spectral bandpass modes. We achieve noise amplitudes of ∼7 × 10-4 and ∼6 × 10-6 in measurements of single A and ΔA spectra (with 92 data points) taking ∼7 and ∼19 min, respectively., (© 2023 Author(s). All article content, except where otherwise noted, is licensed under a Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).)

Time-resolved fluorescence spectroscopy in combination with differential scanning calorimetry (DSC) was used to study the chemical interactions that occur when l-phenylalanine is introduced to solutions containing phosphatidylcholine vesicles. Studies reported in this work address open questions about l-Phe's affinity for lipid vesicle bilayers, the effects of l-Phe partitioning on bilayer properties, l-Phe's solvation within a lipid bilayer, and the amount of l-Phe within that local solvation environment. DSC data show that l-Phe reduces the amount of heat necessary to melt saturated phosphatidylcholine bilayers from their gel to liquid-crystalline state but does not change the transition temperature ( T gel-lc ). Time-resolved emission shows only a single l-Phe lifetime at low temperatures corresponding to l-Phe remaining solvated in aqueous solution. At temperatures close to T gel-lc , a second, shorter lifetime appears that is assigned to l-Phe already embedded within the membrane that becomes hydrated as water starts to permeate the lipid bilayer. This new lifetime is attributed to a conformationally restricted rotamer in the bilayer's polar headgroup region and accounts for up to 30% of the emission amplitude. Results reported for dipalmitoylphosphatidylcholine (DPPC, 16:0) lipid vesicles prove to be general, with similar effects observed for dimyristoylphosphatidylcholine (DMPC, 14:0) and distearoylphosphatidylcholine (DSPC, 18:0) vesicles. Taken together, these results create a complete and compelling picture of how l-Phe associates with model biological membranes. Furthermore, this approach to examining amino acid partitioning into membranes and the resulting solvation forces points to new strategies for studying the structure and chemistry of membrane-soluble peptides and selected membrane proteins.

Aggregates of conjugated organic molecules (i.e., dyes) may exhibit relatively large one- and two-exciton interaction energies, which has motivated theoretical studies on their potential use in quantum information science (QIS). In practice, one way of realizing large one- and two-exciton interaction energies is by maximizing the transition dipole moment (μ) and difference static dipole moment (Δ d ) of the constituent dyes. In this work, we characterized the electronic structure and excited-state dynamics of monomers and aggregates of four asymmetric polymethine dyes templated via DNA. Using steady-state and time-resolved absorption and fluorescence spectroscopy along with quantum-chemical calculations, we found the asymmetric polymethine dye monomers exhibited a large μ, an appreciable Δ d , and a long excited-state lifetime (τ p ). We formed dimers of all four dyes and observed that one dye, Dy 754, displayed the strongest propensity for aggregation and exciton delocalization. Motivated by these results, we undertook a more comprehensive survey of Dy 754 dimer and tetramer aggregates using steady-state absorption and circular dichroism spectroscopy. Modeling these spectra revealed an appreciable excitonic hopping parameter ( J ). Lastly, we used femtosecond transient absorption spectroscopy to characterize τ p of the dimer and tetramer, which we observed to be exceedingly short. This work revealed that asymmetric polymethine dyes exhibited μ, Δ d , monomer τ p , and J values promising for QIS; however, further work is needed to overcome excited-state quenching and achieve long aggregate τ p .

Molecular (dye) aggregates are a materials platform of interest in light harvesting, organic optoelectronics, and nanoscale computing, including quantum information science (QIS). Strong excitonic interactions between dyes are key to their use in QIS; critically, properties of the individual dyes govern the extent of these interactions. In this work, the electronic structure and excited-state dynamics of a series of indolenine-based squaraine dyes incorporating dimethylamino (electron donating) and/or nitro (electron withdrawing) substituents, so-called asymmetric dyes, were characterized. The dyes were covalently tethered to DNA Holliday junctions to suppress aggregation and permit characterization of their monomer photophysics. A combination of density functional theory and steady-state absorption spectroscopy shows that the difference static dipole moment (Δ d ) successively increases with the addition of these substituents while simultaneously maintaining a large transition dipole moment (μ). Steady-state fluorescence and time-resolved absorption and fluorescence spectroscopies uncover a significant nonradiative decay pathway in the asymmetrically substituted dyes that drastically reduces their excited-state lifetime (τ). This work indicates that Δ d can indeed be increased by functionalizing dyes with electron donating and withdrawing substituents and that, in certain classes of dyes such as these asymmetric squaraines, strategies may be needed to ensure long τ, e.g., by rigidifying the π-conjugated network.

Molecular aggregates are of interest to a broad range of fields including light harvesting, organic optoelectronics, and nanoscale computing. In molecular aggregates, nonradiative decay pathways may emerge that were not present in the constituent molecules. Such nonradiative decay pathways may include singlet fission, excimer relaxation, and symmetry-breaking charge transfer. Singlet fission, sometimes referred to as excitation multiplication, is of great interest to the fields of energy conversion and quantum information. For example, endothermic singlet fission, which avoids energy loss, has been observed in covalently bound, linear perylene trimers and tetramers. In this work, the electronic structure and excited-state dynamics of dimers of a perylene derivative templated using DNA were investigated. Specifically, DNA Holliday junctions were used to template the aggregation of two perylene molecules covalently linked to a modified uracil nucleobase through an ethynyl group. The perylenes were templated in the form of monomer, transverse dimer, and adjacent dimer configurations. The electronic structure of the perylene monomers and dimers were characterized via steady-state absorption and fluorescence spectroscopy. Initial insights into their excited-state dynamics were gleaned from relative fluorescence intensity measurements, which indicated that a new nonradiative decay pathway emerges in the dimers. Femtosecond visible transient absorption spectroscopy was subsequently used to elucidate the excited-state dynamics. A new excited-state absorption feature grows in on the tens of picosecond timescale in the dimers, which is attributed to the formation of perylene anions and cations resulting from symmetry-breaking charge transfer. Given the close proximity required for symmetry-breaking charge transfer, the results shed promising light on the prospect of singlet fission in DNA-templated molecular aggregates.

Time-resolved fluorescence and differential scanning calorimetry (DSC) were used to examine how two amino acids, L-phenylalanine (L-PA) and N-acetyl-DL-tryptophan (NAT), affect the temperature-dependent membrane affinity of two structurally similar coumarin solutes for 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) vesicles. The 7-aminocoumarin solutes, coumarin 151 (C151) and coumarin 152 (C152), differ in their substitution at amine position-C151 is a primary amine, and C152 is a tertiary amine-and both solutes show different tendencies to associate with lipid bilayers consistent with differences in their respective log-P-values. Adding L-PA to the DPPC vesicle solution did not change C151's propensity to remain freely solvated in aqueous solution, but C152 showed a greater tendency to partition into the hydrophobic bilayer interior at temperatures below DPPC's gel-liquid crystalline transition temperature (T gel-lc ). This finding is consistent with L-PA's ability to enhance membrane permeability by disrupting chain-chain interactions. Adding NAT to DPPC-vesicle-containing solutions changed C151 and C152 affinity for the DPPC membranes in unexpected ways. DSC data show that NAT interacts strongly with the lipid bilayer, lowering T gel-lc by up to 2°C at concentrations of 10 mM. These effects disappear when either C151 or C152 is added to solution at concentrations below 10 μM, and T gel-lc returns to a value consistent with unperturbed DPPC bilayers. Together with DSC results, fluorescence data imply that NAT promotes coumarin adsorption to the vesicle bilayer surface. NAT's effects diminish above T gel-lc and imply that unlike L-PA, NAT does not penetrate into the bilayer but instead remains adsorbed to the bilayer's exterior. Taken in their entirety, these discoveries suggest that amino acids-and by inference, polypeptides and proteins-change solute affinity for lipid bilayers with specific effects that depend on individualized amino-acid-lipid-bilayer interactions., (Copyright © 2021 Biophysical Society. Published by Elsevier Inc. All rights reserved.)

Time-resolved fluorescence measurements were used to quantify partitioning of three different 7-aminocoumarin derivatives into DPPC vesicle bilayers as a function of temperature. The coumarin derivatives were structurally equivalent except for the degree of substitution at the 7-amine position. Calculated log  P (octanol: water partitioning) coefficients, a common indicator that correlates with bioconcentration, predict that the primary amine (coumarin 151 or C151) would experience a ∼40-fold partition enrichment in polar organic environments (log  P C151 = 1.6) while the tertiary amine's (coumarin 152 or C152) concentration should be >500 times enhanced (log  P C152 = 2.7). Both values predict that partitioning into lipid membranes is energetically favorable. Time-resolved emission spectra from C151 in solutions containing DPPC vesicles showed that within detection limits, the solute remained in the aqueous buffer regardless of temperature and vesicle bilayer phase. C152 displayed a sharp uptake into DPPC bilayers as the temperature approached DPPC's gel-liquid crystalline transition temperature, consistent with previously reported results ([ J. Phys. Chem. B 2017, 121, 4061-4070]). The secondary amine, synthesized specifically for these studies and dubbed C151.5 with a measured log  P value of 1.9, partitioned into the bilayer's polar head group with no pronounced temperature dependence. These experiments illustrate the limitations of using a gross descriptor of preferential solvation to describe solute partitioning into complex, heterogeneous systems having nanometer-scale dimensions. From a broader perspective, results presented in this work illustrate the need for more chemically informed tools for predicting a solute tendency for where and how much it will bioconcentrate within a biological membrane.

Full breastfeeding (FBF) is promoted as effective for losing pregnancy weight during the postpartum period. This study evaluated whether longer FBF is associated with lower maternal postpartum weight retention (PPWR) as compared to a shorter FBF duration. The MILK (Mothers and Infants Linked for Healthy Growth) study is an ongoing prospective cohort of 370 mother-infant dyads, all of whom fully breastfed their infants for at least 1 month. Breastfeeding status was subsequently self-reported by mothers at 3 and 6 months postpartum. Maternal PPWR was calculated as maternal weight measured at 1, 3, and 6 months postpartum minus maternal prepregnancy weight. Using linear mixed effects models, by 6 months postpartum, adjusted means ± standard errors for weight retention among mothers who fully breastfed for 1-3 (3.40 ± 1.16 kg), 3-6 (1.41 ± 0.69 kg), and ≥6 months (0.97 ± 0.32 kg) were estimated. Compared to mothers who reported FBF for 1-3 months, those who reported FBF for 3-6 months and ≥6 months both had lower PPWR over the period from 1 to 6 months postpartum ( p = 0.04 and p < 0.01, respectively). However, PPWR from 3 to 6 months was not significantly different among those who reported FBF for 3-6 versus ≥6 months ( p > 0.05). Interventions to promote FBF past 3 months may increase the likelihood of postpartum return to prepregnancy weight.

Maternal pregnancy nutrition influences fetal growth. Evidence is limited, however, on the relationship of maternal diet during pregnancy and lactation on infant postnatal growth and adiposity. Our purpose was to examine associations between maternal diet quality during pregnancy and lactation with offspring growth and body composition from birth to six months. Maternal diet quality was serially assessed in pregnancy and at one and three months postpartum, using the Healthy Eating Index⁻2015 in a cohort of 354 fully breastfeeding mother⁻infant dyads. Infant length-for-age (LAZ), weight-for-age (WAZ), and weight-for-length (WLZ) Z-scores were assessed at birth, one, three, and six months. Infant body fat percent (BF%), fat mass (FM), and fat-free mass (FFM) were measured at six months using dual-energy X-ray absorptiometry. Higher maternal diet quality from pregnancy through three months postpartum was associated with lower infant WLZ from birth to six months ( p = 0.02) and BF% at six months ( p ≤ 0.05). Higher maternal diet quality at one and three months postpartum was also associated with lower infant FM at six months ( p < 0.01). In summary, maternal diet quality during pregnancy and lactation was inversely associated with infant relative weight and adiposity in early postnatal life. Additional research is needed to explore whether associations persist across the life course.

Zebrafish is a model organism that affords experimental advantages toward investigating the normal function of genes associated with congenital birth defects. Here we summarize zebrafish studies of genes implicated in orofacial cleft (OFC). The most common use of zebrafish in this context has been to explore the normal function an OFC-associated gene product in craniofacial morphogenesis by inhibiting expression of its zebrafish ortholog. The most frequently deployed method has been to inject embryos with antisense morpholino oligonucleotides targeting the desired transcript. However, improvements in targeted mutagenesis strategies have led to widespread adoption of CRISPR/Cas9 technology. A second application of zebrafish has been for functional assays of gene variants found in OFC patients; such in vivo assays are valuable because the success of in silico methods for testing allele severity has been mixed. Finally, zebrafish have been used to test the tissue specificity of enhancers that harbor single nucleotide polymorphisms associated with risk for OFC. We review examples of each of these approaches in the context of genes that are implicated in syndromic and non-syndromic OFC. Developmental Dynamics 246:897-914, 2017. © 2017 Wiley Periodicals, Inc., (© 2017 Wiley Periodicals, Inc.)

Background: This systematic review of economic evaluations of universal preventative or targeted treatment parenting interventions that aim to enhance parent-infant interaction is primarily intended to inform decision makers who have to make difficult spending decisions, especially at a time of reduced spending allocations. A synthesis of available costs and savings about parenting interventions that set out to enhance parent-infant interaction is presented. This topic is important specifically in view of the UK Governments' emphasis on the equalities agenda and the early years. The benefits of positive early life experiences, which include good parent-infant interaction, are far reaching and may be positively correlated with improved educational, health and well-being outcomes and reduced criminality., Methods: A literature search was undertaken using on-line indexing databases between 2004 and 2014 that included the search terms 'parent', 'infant', 'interaction', 'cost benefit analysis' and their synonyms., Results: Despite existing economic studies generally focusing upon targeted short-run outcomes, significant savings were observed in the included studies. Parenting interventions could save the health service around £2.5k per family over 25 years and could save the criminal justice system over £145k per person over the life course. In light of the escalating costs of remedial services, these potential savings may provide the UK and other governments with a robust incentive to invest in early years parenting interventions., Conclusions: Parenting interventions can be economically efficient and return savings on investment. Moreover, and one might argue as a moral imperative of democratic societies, population health can be improved and health inequalities reduced. An important debate is needed about early years policy, to include acknowledgement of the differences between UK and international healthcare systems and the potential savings from the synergistic and spin-off effects of early years interventions to inform decision-making to fund and implement appropriate action., (© 2017 John Wiley & Sons Ltd.)

Several methods are currently employed to evaluate expression of steroid hormone receptors in tissues and cells, including real-time reverse-transcriptase polymerase chain reaction (real-time RT-PCR) and western blot assays. These methods require homogenization of cells, thereby preventing evaluation of individual cells or specific cell types in a given tissue sample. In addition, methods such as real-time RT-PCR assess mRNA levels, which may be subject to posttranslational modifications that prevent subsequent production of functional proteins. Flow cytometry is a fluorescence-based technique commonly used to evaluate expression of cell surface and intracellular proteins. This method is especially useful as it allows for single-cell analysis and can be utilized to determine the amount of receptor expressed by individual cells. Flow cytometry is commonly used to analyze immune cell activity and determine functionality based on changes in expression of cell surface molecules, as well as intracellular proteins (such as cytokines). Here, we describe a method to identify protein expression of steroid hormone receptors by rat leukocytes from different organs (spleen, liver and thymus) using flow cytometry. We examined expression of glucocorticoid receptor (GR), androgen receptor (AR) and progesterone receptor (PR) by cells at these sites and were able to demonstrate expression of receptors, as well as the intensity of expression of each receptor. This method is useful for rapid, high throughput measurement of steroid hormone receptors at the protein level in single, intact cells and would be valuable to determine which cells are more likely to respond to steroid hormone treatment.

Glucocorticoids have been reported to affect immunity at varying concentrations. While glucocorticoids have shown profound effects on innate immunity, their effects on rat dendritic cells have not been fully examined. In this study, we evaluated the effects of the synthetic glucocorticoid dexamethasone on cultured rat dendritic cells (DCs) from spleen and derived from bone marrow cells to determine whether responsiveness to dexamethasone varies between DCs from different organ sites. Cells were analyzed for expression of glucocorticoid receptor (GR), the primary receptor through which dexamethasone exerts its effects and was found to be primarily located in the cytoplasm of immature DCs. Bone marrow-derived DCs showed more sensitivity to dexamethasone treatment compared to splenic DCs. Dexamethasone treatment of LPS-matured DCs had profound dose-dependent effects on cytokine production. Dexamethasone treatment also led to a dose-dependent downregulation of expression of costimulatory molecules by mature DCs. Dexamethasone modified immature DC uptake of antigen (FITC-Dextran), with slightly higher numbers of splenic DCs taking up antigen compared to bone marrow-derived DCs. These data suggest that dexamethasone is able to similarly affect both bone marrow-derived and splenic DC function at the immature and mature DC states and could contribute to exacerbation of infection by hindering DC-mediated immune responses.

A variety of extraimmune system factors, including hormones, play a critical role in regulating immunity. Progesterone has been shown to affect immunity in rodents and humans, mainly at concentrations commensurate with pregnancy. These effects are primarily mediated via the progesterone receptor (PR), which acts as a transcription factor, although non-genomic effects of PR activation have been reported. In this study, we evaluated the effects of progesterone on rat dendritic cells (DCs) at ranges encompassing physiologic and pharmacologic concentrations to determine whether progesterone plays a role in modulating DC-mediated immune responses. DCs were derived by culturing rat bone marrow cells in granulocyte macrophage colony-stimulating factor and IL-4. Cells were analyzed for expression of PR using FACS analysis, real-time reverse transcriptase-PCR and fluorescent microscopy. Progesterone treatment of LPS-activated, mature bone marrow-derived dendritic cells (BMDCs) suppressed production of the pro-inflammatory response-promoting cytokines tumor necrosis factor-alpha and IL-1beta in a dose-dependent manner but did not affect production of the pro-inflammatory response-inhibiting cytokine IL-10. Treatment of cells with progesterone also resulted in down-regulation of co-stimulatory molecule CD80 and MHC class II molecule RT1B expression. In addition, progesterone inhibited DC-stimulated proliferation of T cells. Suppression of pro-inflammatory response-promoting cytokine production by progesterone was prevented using the PR antagonist RU486. There was no dose-dependent effect of progesterone treatment on immature DC capacity to take up antigenic peptide. These data indicate that progesterone directly inhibits mature rat BMDC capacity to drive pro-inflammatory responses. This mechanism could contribute to or account for some of the differential expression of autoimmune/inflammatory disease in females.

Large marine fishes typically have little population genetic structure. The exceptions are associated with sedentary behaviour, disjunct distributions, or reproductive philopatry. Scalloped hammerhead sharks (Sphyrna lewini) incorporate the contrasting traits of oceanic habitat (usually associated with high dispersal) and possible fidelity to nursery grounds (for reproductive females). To evaluate the expectations of these contrasting behaviours, we examined the global genetic structure of S. lewini based on collections (n = 271 individuals) from 20 nursery areas. A 548-bp fragment of mitochondrial DNA control region revealed 22 polymorphic sites, 24 haplotypes, and three lineages distinguished by 2.56-3.77% sequence divergence. Coalescence analyses based on a provisional molecular clock indicate an origin in the Indo-West Pacific with late Pleistocene radiations into the central Pacific (Hawaii) and eastern Pacific (Central America), as well as recent interchange between oceans via southern Africa. Population subdivisions are strong (overall Phi(ST) = 0.749, P < 0.0001 and among oceans Phi(ST) = 0.598, P < 0.0098). Genetic discontinuity within oceans (Phi(ST) = 0.519, P < 0.0001) is primarily associated with oceanic barriers (migration across oceans M approximately 0), with much less structure along continental margins (M > 10). We conclude that nursery populations linked by continuous coastline have high connectivity, but that oceanic dispersal by females is rare. Although we cannot rule out philopatry to natal nurseries, oceanic barriers appear to have a much stronger influence on the genetic architecture of this species and may indicate a mechanism for recent evolutionary radiations in the genus Sphyrna.

While it has been commonly assumed that a deficit in semantic memory underlies many of the clinical and cognitive features of early Alzheimer's disease (AD), there has been little agreement on what constitutes a proper theoretical description of this impaired system. Currently, most theories of this disorder fall into two categories: those that posit degraded semantic representations, and those that posit impaired retrieval operations with relatively intact semantic representations. It is argued that each position has both empirical and logical disadvantages that have prevented the development of a consensus on how to describe the pathology of semantic memory in AD. In this paper we present the details and supportive evidence for an alternative account of the semantic memory deficit of AD: the Gain/Decay hypothesis. The core claim of the Gain/Decay hypothesis is that a reduction in the time constant of spreading activation in AD produces dynamic changes in the availability of semantic representations that depend on the time frame in which this information must be accessed. The implications of this hypothesis for a range of experimental and clinical phenomena are discussed, as are possible biological correlates of the hypothesized alterations in the modulation of activation.

Objective: To review recent acute pain management care issues in a pediatric emergency department (ED) in order to identify opportunities for a performance improvement program., Design: Descriptive, retrospective chart review., Setting: Urban pediatric hospital ED., Participants: Between January 1 and December 31, 1994 consecutive patients identified by ED chart review with the following three acute painful conditions were included; sickle cell vasoocclusive crisis (VOC) not complicated by fever or neurologic symptoms, isolated lower extremity long bone fractures < 12 hours old that did not require a reduction, and second degree burns < 12 hours old. Data collection concluded when between 50 and 55 episodes of each painful condition were identified., Main Outcome Measures: ED analgesic administration, initial analgesic dose, initial time elapsed to analgesic administration, notation of pain relief, and home analgesic instruction. Recommended analgesic starting doses were chosen from the 1992 Agency for Health Care Policy and Research Clinical Practice Guidelines., Interventions: None., Results: ED analgesic use for VOC was 100%, for fracture was 31%, and for burn was 26%. A recommended starting analgesic dose was given to 78% with VOC, 69% with fracture, and 79% with burn. Mean time to initial analgesic for VOC was 52 minutes, for fracture was 86 minutes, and for burn was 29 minutes. In those given analgesics, notation of pain relief for fracture was 19% and for burn was 29%, this improved for VOC where it was 88%. Home analgesic instruction for VOC was 100%, for fracture was 74%, and for burn was 27%., Conclusion: These data from 1994 document suboptimal analgesic use and home analgesic instruction for children in our ED with burns and fractures. Other opportunities in our ED for acute pain management improvement include optimizing initial analgesic doses, shortening the time elapsed to initial analgesic administration, and documenting the response to pain management.

Objective: To determine the value of tumor necrosis factor alpha (TNF) and interleukin 1 beta (IL1) levels in predicting Streptococcus pneumoniae bacteremia in nontoxic-appearing, febrile children who do not have a bacterial source for their fever on physical examination., Methods: A prospective, nested case-control study was conducted in a children's hospital ED. All febrile children < 3 years old who were believed to be immunocompetent and not in shock, had no obvious bacterial source for their fever on physical examination, and had a blood culture obtained were eligible. Plasma obtained at the time of the blood culture was available for analysis by enzyme-linked immunosorbent assays for TNF and IL1. Children who had positive blood cultures for Streptococcus pneumoniae were the cases. The controls were selected from children who had negative blood cultures., Results: During a 1-year period, 12 cases and 65 controls were identified. There was no significant difference in age, height or duration of fever, or illness acuity between the groups. The following were used as threshold values for positive test: white blood cell (WBC) count > 15.0 x 10(9) cells/L, TNF > 21.5 ng/mL, and IL1 > 9.0 ng/mL. Using an estimated prior probability of bacteremia of 4%, the positive predictive value (PPV) and the negative predictive value (NPV) for bacteremia were 11.7% and 98.6% using the WBC count, 11.1% and 98.6% using the IL1 level, and 9.0% and 98.9% using the TNF level. The combination of WBC count with either TNF or IL1 gave an NPV of 100%, with PPVs of 8.5% for TNF and 9.9% for IL1., Conclusions: Like the WBC count, TNF and IL1 are good negative but poor positive predictors of Streptococcus pneumoniae bacteremia in nontoxic-appearing, febrile children. At present, the addition of plasma TNF or IL1 levels would add little to emergency physicians' ability to predict Streptococcus pneumoniae bacteremia. However, as the quantification of these cytokines becomes more rapid, available, and standardized, and more knowledge of TNF and IL1 levels during various illnesses is gained, their utility in the clinical setting for ruling out bacteremia should be further assessed.

Data collected from a survey instrument mailed to all 188 NATA-approved allied clinical setting directors were analyzed to assess the current levels of professional preparation as related to the NATA competencies, job roles, and responsibilities of certified athletic trainers in the allied clinical setting. The topics examined included specific roles and responsibilities of certified athletic trainers currently employed in an allied clinical setting. A response rate of 70.5% was obtained. Skills and services provided by the clinical ATC rated as very important were: evaluation, prevention, and rehabilitation/reconditioning of athletic injuries. Competency regarding recognition and evaluation received the highest relative importance score, which is consistent with the findings of the 1982 NATA Role Delineation Study and the 1991 NATA Validation Study. Educational preparation through NATA-approved curriculums had the highest importance in professional preparation for a career in athletic training. The data indicated that educational emphasis for athletic training students interested in employment in the nontraditional setting has diverged from the guidelines established in the 1982 Role Delineation Study. The results of this study suggest that students preparing for a career in a nontraditional (clinical) setting should focus on developing skills in athletic injury evaluation, rehabilitation and reconditioning, and prevention. While these results support findings of the 1982 Role Delineation Study, additional research is needed to address the levels of professional preparation as related to the NATA competencies, job roles, and responsibilities of the clinical athletic trainer.