Establishing peat-forming plant communities: A comparison of wetland reclamation methods in Alberta's oil sands region.

The Sandhill Wetland (SW) and Nikanotee Fen (NF) are two wetland research projects designed to test the viability of peatland reclamation in the Alberta oil sands post-mining landscape. To identify effective approaches for establishing peat-forming vegetation in reclaimed wetlands, we evaluated how plant introduction approaches and water level gradients influence species distribution, plant community development, and the establishment of bryophyte and peatland species richness and cover. Plant introduction approaches included seeding with a Carex aquatilis-dominated seed mix, planting C. aquatilis and Juncus balticus seedlings, and spreading a harvested moss layer transfer. Establishment was assessed 6 years after the introduction at SW and 5 years after the introduction at NF. In total, 51 species were introduced to the reclaimed wetlands, and 122 species were observed after 5 and 6 years. The most abundant species in both reclaimed wetlands was C. aquatilis, which produced dense canopies and occupied the largest water level range of observed plants. Introducing C. aquatilis also helped to exclude marsh plants such as Typha latifolia that has little to no peat accumulation potential. Juncus balticus persisted where the water table was lower and encouraged the formation of a diverse peatland community and facilitated bryophyte establishment. Various bryophytes colonized suitable areas, but the moss layer transfer increased the cover of desirable peat-forming mosses. Communities with the highest bryophyte and peatland species richness and cover (averaging 9 and 14 species, and 50%-160% cover respectively) occurred where the summer water level was between -10 and -40 cm. Outside this water level range, a marsh community of Typha latifolia dominated in standing water and a wet meadow upland community of Calamagrostis canadensis and woody species established where the water table was deeper. Overall, the two wetland reclamation projects demonstrated that establishing peat-forming vascular plants and bryophytes is possible, and community formation is dependent upon water level and plant introduction approaches. Future projects should aim to create microtopography with water tables within 40 cm of the surface and introduce vascular plants such as J. balticus that facilitate bryophyte establishment and support the development of a diverse peatland plant community.

The effect of recombinant erythropoietin on long-term outcome after moderate-to-severe traumatic brain injury.

PURPOSE: Recombinant erythropoietin (EPO) administered for traumatic brain injury (TBI) may increase short-term survival, but the long-term effect is unknown. METHODS: We conducted a pre-planned long-term follow-up of patients in the multicentre erythropoietin in TBI trial (2010-2015). We invited survivors to follow-up and evaluated survival and functional outcome with the Glasgow Outcome Scale-Extended (GOSE) (categories 5-8 = good outcome), and secondly, with good outcome determined relative to baseline function (sliding scale). We used survival analysis to assess time to death and absolute risk differences (ARD) to assess favorable outcomes. We categorized TBI severity with the International Mission for Prognosis and Analysis of Clinical Trials in TBI model. Heterogeneity of treatment effects were assessed with interaction p-values based on the following a priori defined subgroups, the severity of TBI, and the presence of an intracranial mass lesion and multi-trauma in addition to TBI. RESULTS: Of 603 patients in the original trial, 487 patients had survival data; 356 were included in the follow-up at a median of 6 years from injury. There was no difference between treatment groups for patient survival [EPO vs placebo hazard ratio (HR) (95% confidence interval (CI) 0.73 (0.47-1.14) p = 0.17]. Good outcome rates were 110/175 (63%) in the EPO group vs 100/181 (55%) in the placebo group (ARD 8%, 95% CI [Formula: see text] 3 to 18%, p = 0.14). When good outcome was determined relative to baseline risk, the EPO groups had better GOSE (sliding scale ARD 12%, 95% CI 2-22%, p = 0.02). When considering long-term patient survival, there was no evidence for heterogeneity of treatment effect (HTE) according to severity of TBI (p = 0.85), presence of an intracranial mass lesion (p = 0.48), or whether the patient had multi-trauma in addition to TBI (p = 0.08). Similarly, no evidence of treatment heterogeneity was seen for the effect of EPO on functional outcome. CONCLUSION: EPO neither decreased overall long-term mortality nor improved functional outcome in moderate or severe TBI patients treated in the intensive care unit (ICU). The limited sample size makes it difficult to make final conclusions about the use of EPO in TBI.

The High-Elevation Peatlands of the Northern Andes, Colombia.

Andean peatlands are important carbon reservoirs for countries in the northern Andes and have a unique diversity. Peatland plant diversity is generally related to hydrology and water chemistry, and the response of the vegetation in tropical high-elevation peatlands to changes in elevation, climate, and disturbance is poorly understood. Here, we address the questions of what the main vegetation types of peat-forming vegetation in the northern Andes are, and how the different vegetation types are related to water chemistry and pH. We measured plant diversity in 121 peatlands. We identified a total of 264 species, including 124 bryophytes and 140 vascular plants. We differentiated five main vegetation types: cushion plants, Sphagnum, true mosses, sedges, and grasses. Cushion-dominated peatlands are restricted to elevations above 4000 m. Variation in peatland vegetation is mostly driven be elevation and water chemistry. Encroachment of sedges and Sphagnum sancto-josephense in disturbed sites was associated with a reduction in soil carbon. We conclude that peatland variation is driven first by elevation and climate followed by water chemistry and human disturbances. Sites with higher human disturbances had lower carbon content. Peat-forming vegetation in the northern Andes was unique to each site bringing challenges on how to better conserve them and the ecosystem services they offer.

The roles and impacts of worldviews in the context of meditation-related challenges.

Previous research has shown that worldviews can serve as a coping response to periods of difficulty or struggle, and worldviews can also change on account of difficulty. This paper investigates the impacts worldviews have on the nature and trajectory of meditation-related challenges, as well as how worldviews change or are impacted by such challenges. The context of meditation-related challenges provided by data from the Varieties of Contemplative Experience research project offers a unique insight into the dynamics between worldviews and meditation. Buddhist meditation practitioners and meditation experts interviewed for the study report how, for some, worldviews can serve as a risk factor impacting the onset and trajectory of meditation-related challenges, while, for others, worldviews (e.g., being given a worldview, applying a worldview, or changing a worldview) were reported as a remedy for mitigating challenging experiences and/or their associated distress. Buddhist meditation practitioners and teachers in the contemporary West are also situated in a cultural context in which religious and scientific worldviews and explanatory frameworks are dually available. Furthermore, the context of "Buddhist modernism" has also promoted a unique configuration in which the theory and practice of Buddhism is presented as being closely compatible with science. We identify and discuss the various impacts that religious and scientific worldviews have on meditation practitioners and meditation teachers who navigate periods of challenge associated with the practice.

Distributions of baseline categorical variables were different from the expected distributions in randomized trials with integrity concerns.

BACKGROUND AND OBJECTIVES: Comparing observed and expected distributions of baseline continuous variables in randomized controlled trials (RCTs) can be used to assess publication integrity. We explored whether baseline categorical variables could also be used. METHODS: The observed and expected (binomial) distribution of all baseline categorical variables were compared in four sets of RCTs: two controls, and two with publication integrity concerns. We also compared baseline calculated and reported P-values. RESULTS: The observed and expected distributions of baseline categorical variables were similar in the control datasets, both for frequency counts (and percentages) and for between-group differences in frequency counts. However, in both sets of RCTs with publication integrity concerns, about twice as many variables as expected had between-group differences in frequency counts of one or 2, and far fewer variables than expected had between-group differences of >4 (P < 0.001 for both datasets). Furthermore, about one in six reported P-values for baseline categorial variables differed by > 0.1 from the calculated P-value in trials with publication integrity concerns. CONCLUSION: Comparing the observed and expected distributions and reported and calculated P-values of baseline categorical variables may help in the assessment of publication integrity of a body of RCTs.

CoreView: fresh tissue biopsy assessment at the bedside using a millifluidic imaging chip.

Minimally invasive core needle biopsies for medical diagnoses have become increasingly common for many diseases. Although tissue cores can yield more diagnostic information than fine needle biopsies and cytologic evaluations, there is no rapid assessment at the point-of-care for intact tissue cores that is low-cost and non-destructive to the biopsy. We have developed a proof-of-concept 3D printed millifluidic histopathology lab-on-a-chip device to automatically handle, process, and image fresh core needle biopsies. This device, named CoreView, includes modules for biopsy removal from the acquisition tool, transport, staining and rinsing, imaging, segmentation, and multiplexed storage. Reliable removal from side-cutting needles and bidirectional fluid transport of core needle biopsies of five tissue types has been demonstrated with 0.5 mm positioning accuracy. Automation is aided by a MATLAB-based biopsy tracking algorithm that can detect the location of tissue and air bubbles in the channels of the millifluidic chip. With current and emerging optical imaging technologies, CoreView can be used for a rapid adequacy test at the point-of-care for tissue identification as well as glomeruli counting in renal core needle biopsies.

Defining and measuring meditation-related adverse effects in mindfulness-based programs.

BACKGROUND: Research on the adverse effects of mindfulness-based programs (MBPs) has been sparse and hindered by methodological imprecision. METHODS: The 44-item Meditation Experiences Interview (MedEx-I) was used by an independent assessor to measure meditation-related side effects (MRSE) following three variants of an 8-week program of mindfulness-based cognitive therapy (n = 96). Each item was queried for occurrence, causal link to mindfulness meditation practice, duration, valence, and impact on functioning. RESULTS: Eighty-three percent of the MBP sample reported at least one MRSE. Meditation-related adverse effects (MRAEs) with negative valences or negative impacts on functioning occurred in 58% and 37% of the sample, respectively. Lasting bad effects occurred in 6-14% of the sample and were associated with signs of dysregulated arousal (hyperarousal and dissociation). CONCLUSION: Meditation practice in MBPs is associated with transient distress and negative impacts at similar rates to other psychological treatments.

Participant withdrawals were unusually distributed in randomized trials with integrity concerns: a statistical investigation.

OBJECTIVES: Comparing observed and expected distributions of categorical outcome variables in randomized controlled trials (RCTs) has been previously used to assess publication integrity. We applied this technique to withdrawals from RCTs. STUDY DESIGN AND SETTING: We compared the observed distribution of withdrawals with the expected binomial distribution in six sets of RCTs: four control sets and two sets with concerns about their publication integrity. RESULTS: In the control data sets (n = 13, 115, 71, and 36 trials, respectively), the observed distributions of withdrawals were consistent with the expected distributions, both for the numbers of withdrawals per trial arm and for the differences in withdrawals between trial arms in two-arm RCTs. In contrast, in both sets of RCTs with concerns regarding publication integrity (n = 151 and 35 trials, respectively), there were striking differences between the observed and expected distributions of trial withdrawals. Two-arm RCTs from the two sets with publication integrity concerns were 2.6 (95% confidence interval 2.0-3.3) times more likely to have a difference of 0 or 1 withdrawals between trial arms than control RCTs (P < 0.001). Simulating a 50% higher rate of withdrawals in active treatment arms in the largest set of control RCTs still produced an observed distribution of withdrawals per trial arm consistent with the expected distribution. CONCLUSION: Comparing the observed and expected distribution of trial withdrawals may be a useful technique when considering publication integrity of a body of RCTs.

Progress or Pathology? Differential Diagnosis and Intervention Criteria for Meditation-Related Challenges: Perspectives From Buddhist Meditation Teachers and Practitioners.

Studies in the psychology and phenomenology of religious experience have long acknowledged similarities with various forms of psychopathology. Consequently, it has been important for religious practitioners and mental health professionals to establish criteria by which religious, spiritual, or mystical experiences can be differentiated from psychopathological experiences. Many previous attempts at differential diagnosis have been based on limited textual accounts of mystical experience or on outdated theoretical studies of mysticism. In contrast, this study presents qualitative data from contemporary Buddhist meditation practitioners and teachers to identify salient features that can be used to guide differential diagnosis. The use of certain existing criteria is complicated by Buddhist worldviews that some difficult or distressing experiences may be expected as a part of progress on the contemplative path. This paper argues that it is important to expand the framework for assessment in both scholarly and clinical contexts to include not only criteria for determining normative fit with religious experience or with psychopathology, but also for determining need for intervention, whether religious or clinical. Qualitative data from Buddhist communities shows that there is a wider range of experiences that are evaluated as potentially warranting intervention than has previously been discussed. Decision making around these experiences often takes into account contextual factors when determining appraisals or need for intervention. This is in line with person-centered approaches in mental health care that emphasize the importance of considering the interpersonal and cultural dynamics that inevitably constitute the context in which experiences are evaluated and rendered meaningful.

Short- and long-term responses of riparian cottonwoods (Populus spp.) to flow diversion: Analysis of tree-ring radial growth and stable carbon isotopes.

Long duration tree-ring records with annual precision allow for the reconstruction of past growing conditions. Investigations limited to the most common tree-ring proxy of ring width can be difficult to interpret, however, because radial growth is affected by multiple environmental processes. Furthermore, studies of living trees may miss important effects of drought on tree survival and forest changes. Stable carbon isotopes can help distinguish drought from other environmental factors that influence tree-ring width and forest stand condition. We quantified tree-ring radial expansion and stable carbon isotope ratios (δ13C) in riparian cottonwoods (Populus angustifolia and P. angustifolia x P.trichocarpa) along Snake Creek in Nevada, USA. We investigated how hydrological drought affected tree growth and death at annual to half-century scales in a partially dewatered reach (DW) compared to reference reaches immediately upstream and downstream. A gradual decline in tree-ring basal area increment (BAI) began at DW concurrent to streamflow diversion in 1961. BAI at DW diverged from one reference reach immediately but not from the other until nearly 50 years later. In contrast, tree-ring δ13C had a rapid and sustained increase following diversion at DW only, providing the stronger and clearer drought signal. BAI and δ13C were not significantly correlated prior to diversion; after diversion they both reflected drought and were correlated for DW trees only. Cluster analyses distinguished all trees in DW from those in reference reaches based on δ13C, but BAI patterns left trees intermixed across reaches. Branch and tree mortality were also highest and canopy vigor was lowest in DW. Results indicate that water scarcity strongly limited cottonwood photosynthesis following flow diversion, thus reducing carbon assimilation, basal growth and survival. The dieback was not sudden, but occurred over decades as carbon deficits mounted and depleted streamflow left trees increasingly vulnerable to local meteorological drought.

EPO treatment does not alter acute serum profiles of GFAP and S100B after TBI: A brief report on the Australian EPO-TBI clinical trial.

PURPOSE: To determine the diagnostic and prognostic value of glial fibrillary acidic protein (GFAP) and S100B after traumatic brain injury (TBI) in an Erythropoietin (EPO) clinical trial and examine whether EPO therapy reduces biomarker concentrations. MATERIALS AND METHODS: Forty-four patients with moderate-to-severe TBI were enrolled to a sub-study of the EPO-TBI trial. Patients were randomized to either Epoetin alfa 40,000 IU or 1 ml sodium chloride 0.9 as subcutaneous injection within 24 h of TBI. RESULTS: GFAP and S100B were measured in serum by ELISA from D0 (within 24 h of injury, prior to EPO/vehicle administration) to D5. Biomarker concentrations were compared between injury severities, diffuse vs. focal TBI, 6-month outcome scores (GOS-E) and EPO or placebo treatments. At D0 GFAP was significantly higher than S100B (951 pg/mL vs. 476 pg/mL, p = 0.018). ROC analysis of S100B at 1D post-injury distinguished favorable vs. unfavorable outcomes (area under the curve = 0.73; p = 0.01). EPO did not reduce concentration of either biomarker. CONCLUSIONS: Elevated serum concentrations of GFAP and S100B after TBI reflect a robust, acute glial response to injury. Consistent with lack of improved outcome in TBI patients treated with EPO and prior findings on neuronal and axonal markers, glial biomarker concentrations and acute profiles were not affected by EPO.

A new approach for hydrologic performance standards in wetland mitigation.

Wetland restoration performed as a requirement of compensatory mitigation does not always replace lost acreage or functions. Most new projects are required to identify performance standards to evaluate restoration outcomes. Current performance standards are primarily related to vegetation with little to no evaluation of wetland hydrologic regimes. Because of the agreement in the scientific literature about the role of hydrology in creating and maintaining wetland structure and function, hydrologic performance standards may be an ecologically meaningful way to evaluate restoration outcomes. This research tests the use of water level data from project specific reference sites to evaluate restored water levels for three distinct wetland types across the United States. We analyzed existing datasets from past and ongoing wetland mitigation projects to identify the number of years it took water levels in restored wetlands to match reference sites, and to test whether similar water levels between restored and reference sites leads to increased vegetation success. Wetland types differed in the number of years it took for water levels to match reference sites. Vernal pools in California took nine years to match reference sites, fens and wet meadows in Colorado took four years, and forested wetlands in the southeastern US were hydrologically similar to reference sites the first year following restoration. Plant species cover in all three restored wetland types was related to the water level similarity to reference sites. Native cover was higher when water levels were more similar to reference sites, and was lower in areas where water levels were different. Exotic species cover showed the opposite relationship in fens and wet meadows, where hydrologic similarity led to low cover of exotic species. Along with the general agreement of the importance of hydrology for wetland form and function, this research shows that hydrologic performance standards may also lead to increased vegetation success in some wetland types.

Erythropoietin in traumatic brain injury associated acute kidney injury: A randomized controlled trial.

BACKGROUND: Acute kidney injury (AKI) in traumatic brain injury (TBI) is poorly understood and it is unknown if it can be attenuated using erythropoietin (EPO). METHODS: Pre-planned analysis of patients included in the EPO-TBI (ClinicalTrials.gov NCT00987454) trial who were randomized to weekly EPO (40 000 units) or placebo (0.9% sodium chloride) subcutaneously up to three doses or until intensive care unit (ICU) discharge. Creatinine levels and urinary output (up to 7 days) were categorized according to the Kidney Disease Improving Global Outcome (KDIGO) classification. Severity of TBI was categorized with the International Mission for Prognosis and Analysis of Clinical Trials in TBI. RESULTS: Of 3348 screened patients, 606 were randomized and 603 were analyzed. Of these, 82 (14%) patients developed AKI according to KDIGO (60 [10%] with KDIGO 1, 11 [2%] patients with KDIGO 2, and 11 [2%] patients with KDIGO 3). Male gender (hazard ratio [HR] 4.0 95% confidence interval [CI] 1.4-11.2, P = 0.008) and severity of TBI (HR 1.3 95% CI 1.1-1.4, P < 0.001 for each 10% increase in risk of poor 6 month outcome) predicted time to AKI. KDIGO stage 1 (HR 8.8 95% CI 4.5-17, P < 0.001), KDIGO stage 2 (HR 13.2 95% CI 3.9-45.2, P < 0.001) and KDIGO stage 3 (HR 11.7 95% CI 3.5-39.7, P < 0.005) predicted time to mortality. EPO did not influence time to AKI (HR 1.08 95% CI 0.7-1.67, P = 0.73) or creatinine levels during ICU stay (P = 0.09). CONCLUSIONS: Acute kidney injury is more common in male patients and those with severe compared to moderate TBI and appears associated with worse outcome. EPO does not prevent AKI after TBI.

Irrigation canals are newly created streams of semi-arid agricultural regions.

The natural hydrologic processes that create and maintain the diversity of aquatic and riparian habitats along the World's streams and rivers have been profoundly altered by humans. Diversion of surface water to support production agriculture in arid and semi-arid regions has degraded ecosystems but also created potential habitat along and in canals specifically designed to transport water. The prevalence of canals and the immense amount of water used for agriculture have created these new artificial stream systems. This study demonstrates the potential for irrigation canals to support riparian and aquatic communities similar to natural streams in urban/residential and agricultural landscapes. We examined the hydrological and ecological characteristics of streams and irrigation canals in urban and agricultural landscapes in northeastern Colorado, typical of regions dominated by irrigation-supported agriculture. Flow patterns in canals depended on their size and had a range of patterns with potential ecological consequences such as rapidly rising and falling water stage, intermittent dry periods, and delayed peak and base flows compared to natural streams. Despite these hydrologic differences, the taxonomic and functional composition of riparian plant and aquatic macroinvertebrate communities indicated that ecological similarities exist between streams and canals, but are dependent, in part, on their landscape setting with stronger similarities in agricultural areas. We also tested the influence of characterizing taxa by functional groups using physiology, ecology and life history traits to explore attributes of habitats including woody canopy structure and water quality. We used a Habitat Quality Index (HQI) that combined physical and biological measures into a single index. Streams scored higher on average within agriculture and urban/residential settings compared to canals; however, one third of urban canals scored above the average of agricultural streams. This multidisciplinary study shows that irrigation canals can be valuable riparian and aquatic habitat, especially in regions with severely degraded streams.

Changes in bone mineral density in women before critical illness: a matched control nested cohort study.

The contribution of premorbid bone health to accelerated bone loss following critical illness is unknown. This study compared bone density in women before critical illness to women who did not become critically ill. Overall bone density was similar, although femoral neck bone mass increased immediately prior to critical illness. PURPOSE: The relative contribution of acute and chronic factors to accelerated loss of bone mineral density (BMD) following critical illness is unknown. This study compared the BMD trajectory of women before critical illness to the BMD trajectory of women who did not become critically ill. METHODS: This prospective, nested, age- and medication-matched, case-control study compared trajectory of BMD in women in the Geelong Osteoporosis study (GOS) requiring admission to an Australian Intensive Care Unit (ICU) between June 1998 and March 2016, to women not admitted to ICU. The main outcome was age and medication use adjusted change in BMD. RESULTS: A total of 52 women, with a mean age of 77 ± 9 years were admitted to ICU, predominantly post-surgery (75%), during the study period. A greater age-adjusted annual rate of decline was observed for pre-ICU women compared to no-ICU women for AP spine BMD (-0.010 ± 0.002 g/cm2 vs -0.005 ± 0.002 g/cm2, p = 0.01) over the 15-year study period. In participants with multiple BMDs 2 years before critical illness, a significantly greater increase in femoral neck BMD compared to age- and medication-matched controls was observed (difference in BMD, ICU vs no-ICU = 0.037 ± 0.013 g/cm2, p = 0.006). CONCLUSION: In a cohort of women with predominantly surgical ICU admission, bone health prior to critical illness was comparable to age- and medication-matched controls, with a relative increase in femoral neck bone mass immediately prior to critical illness. These findings suggest critical illness-related bone loss cannot be entirely explained as a continuation of pre-morbid bone trajectory.

Effect of age of red cells for transfusion on patient outcomes: a systematic review and meta-analysis.

Longer storage duration of red blood cell (RBC) units prior to transfusion has been associated with worse outcomes in observational studies. We performed a systematic review, including recently published randomized trials, to determine if storage age of RBCs is associated with mortality, morbidity or adverse events in patients. Searches were performed up to 21st July 2017 in Medline (OvidSP), 20 July in EMBASE (OvidSP) and June 2017 in Cochrane Library. Eligible studies were randomized controlled trials comparing transfusion of fresher or freshest available with older or standard issue RBCs. Human volunteer and autologous RBC transfusion studies were excluded. Data were extracted from published reports independently by 2 authors and strength of evidence assessed according to GRADE criteria. The primary outcome was latest-reported mortality. Sixteen trials randomizing 31,359 patients were identified. Transfusion with fresher compared with older RBC was not associated with risk of death (relative risk [RR] 1.04, 95% CI 0.98-1.09; P=.20, I2=0%, high quality evidence), but was associated with higher risk of transfusion reactions (RR 1.35, 95% CI 1.04-1.76; P=.02; I2=0%; high quality evidence) and infection (RR 1.08, 95% CI 1.00-1.17; P=.05; I2=0%, moderate evidence). Trial sequential analysis showed required information size has now been reached to exclude a 10% relative risk increase or decrease in mortality. Transfusion of fresher RBCs is not associated with decreased risk of death but is associated with higher rates of transfusion reactions and possibly infection. The current evidence does not support a change from current usual transfusion practice.

Erythropoietin Does Not Alter Serum Profiles of Neuronal and Axonal Biomarkers After Traumatic Brain Injury: Findings From the Australian EPO-TBI Clinical Trial.

OBJECTIVE: To determine profiles of serum ubiquitin carboxy-terminal hydrolase L1 and phosphorylated neurofilament heavy-chain, examine whether erythropoietin administration reduce their concentrations, and whether biomarkers discriminate between erythropoietin and placebo treatment groups. DESIGN: Single-center, prospective observational study. SETTING: A sub-study of the erythropoietin-traumatic brain injury clinical trial, conducted at the Alfred Hospital, Melbourne, Australia. PATIENTS: Forty-four patients with moderate-to-severe traumatic brain injury. INTERVENTIONS: Epoetin alfa 40,000 IU or 1 mL sodium chloride 0.9 as subcutaneous injection within 24 hours of traumatic brain injury. MEASUREMENTS AND MAIN RESULTS: Ubiquitin carboxy-terminal hydrolase L1, phosphorylated neurofilament heavy-chain, and erythropoietin concentrations were measured in serum by enzyme-linked immunosorbent assay from D0 (within 24 hr of injury, prior to erythropoietin/vehicle administration) to D5. Biomarker concentrations were compared between injury severities, diffuse versus focal traumatic brain injury and erythropoietin or placebo treatment groups. Ubiquitin carboxy-terminal hydrolase L1 peaked at 146.0 ng/mL on D0, significantly decreased to 84.30 ng/mL on D1, and declined thereafter. Phosphorylated neurofilament heavy-chain levels were lowest at D0 and peaked on D5 at 157.9 ng/mL. D0 ubiquitin carboxy-terminal hydrolase L1 concentrations were higher in diffuse traumatic brain injury. Peak phosphorylated neurofilament heavy-chain levels on D3 and D4 correlated with Glasgow Outcome Score-Extended, predicting poor outcome. Erythropoietin did not reduce concentrations of ubiquitin carboxy-terminal hydrolase L1 or phosphorylated neurofilament heavy-chain. CONCLUSIONS: Serum ubiquitin carboxy-terminal hydrolase L1 and phosphorylated neurofilament heavy-chain increase after traumatic brain injury reflecting early neuronal and progressive axonal injury. Consistent with lack of improved outcome in traumatic brain injury patients treated with erythropoietin, biomarker concentrations and profiles were not affected by erythropoietin. Pharmacokinetics of erythropoietin suggest that the dose given was possibly too low to exert neuroprotection.