Evaluation of a hapten conjugate vaccine against the "zombie drug" xylazine.

Xylazine has emerged as a primary adulterant in fentanyl, exacerbating the complexity of the opioid crisis. Yet, there is no approved drug that can reverse xylazine's pathophysiology. As a prelude to monoclonal antibodies being assessed as a viable therapeutic, a vaccine inquiry was conducted evaluating the immune response in reversing xylazine induced behavior effects.

Discovery of PLD4 modulators by high-throughput screening and kinetic analysis.

Phospholipase D3 (PLD3) and D4 (PLD4) are endolysosomal exonucleases of ssDNA and ssRNA that regulate innate immunity. Polymorphisms of these enzymes are correlated with numerous human diseases, including Alzheimer's, rheumatoid arthritis, and systemic sclerosis. Pharmacological modulation of these immunoregulatory proteins may yield novel immunotherapies and adjuvants. A previous study reported a high-throughput screen (N = 17,952) that discovered a PLD3-selective activator and inhibitor, as well as a nonselective inhibitor, but failed to identify selective modulators of PLD4. However, modulators selective for PLD4 are therapeutically pertinent, since recent reports have shown that regulating this protein has direct implications in cancer and autoimmune diseases. Furthermore, the high expression of PLD4 in dendritic and myeloid cells, in comparison to the broader expression of PLD3, presents the opportunity for a cell-targeted immunotherapy. Here, we describe screening of an expended diversity library (N = 45,760) with an improved platform and report the discovery of one inhibitor and three activators selective for PLD4. Furthermore, kinetic modeling and structural analysis suggest mechanistic differences in the modulation of these hits. These findings further establish the utility of this screening platform and provide a set of chemical scaffolds to guide future small-molecule development for this novel immunoregulator target.

Novel patient-specific helical maxillary distractor: an in vitro feasibility study.

At present, stock linear distractors are used for internal maxillary distraction osteogenesis. However, the authors' research group has demonstrated, through an in silico analysis, that linear distraction leads to bone deformities and malocclusion, whereas helical distraction can yield ideal outcomes. A system for designing and manufacturing custom helical distractors has recently been developed, and the feasibility of these appliances now needs to be assessed. This study was, therefore, conducted to gain an initial insight into their feasibility. The study had two goals. First, it aimed to demonstrate, in an in vitro model, that the novel system of custom helical distraction can produce appropriate clinical outcomes. The second aim was to compare the performance of custom helical distractors with that of stock devices and hybrid devices (i.e., linear appliances that feature patient-specific footplates). Interpreting the results as trends, this study showed that the system of custom helical distraction resulted in in vitro outcomes that were superior to those obtained with stock and hybrid devices.

Mucosal barrier status in Atlantic salmon fed rapeseed oil and Schizochytrium oil partly or fully replacing fish oil through winter depression.

The study was designed to investigate the effects of replacing fish oil by algal oil and rapeseed oil on histomorphology indices of the intestine, skin and gill, mucosal barrier status and immune-related genes of mucin and antimicrobial peptide (AMP) genes in Atlantic salmon (Salmo salar). For these purposes, Atlantic salmon smolts were fed three different diets. The first was a control diet containing fish oil but no Schizochytrium oil. In the second diet, almost 50 % of the fish oil was replaced with algal oil, and in the third diet, fish oil was replaced entirely with algal oil. The algal oil contained mostly docosahexaenoic acid (DHA) and some eicosapentaenoic acid (EPA). The study lasted for 49 days in freshwater (FW), after which some fish from each diet group were transferred to seawater (SW) for a 48-h challenge test at 33 ppt to test their ability to tolerate high salinity. Samples of skin, gills, and mid intestine [both distal (DI) and anterior (AI) portions of the mid intestine] were collected after the feeding trial in FW and after the SW-challenge test to assess the effects of the diets on the structure and immune functions of the mucosal surfaces. The results showed that the 50 % VMO (Veramaris® algal oil) dietary group had improved intestinal, skin, and gill structures. Principal component analysis (PCA) of the histomorphological parameters demonstrated a significant effect of the algal oil on the intestine, skin, and gills. In particular, the mucosal barrier function of the intestine, skin, and gills was enhanced in the VMO 50 % dietary group after the SW challenge, as evidenced by increased mucous cell density. Immunolabelling of heat shock protein 70 (HSP70) in the intestine (both DI and AI) revealed downregulation of the protein expression in the 50 % VMO group and a corresponding upregulation in the 100 % VMO group compared to 0 % VMO. The reactivity of HSP70 in the epithelial cells was higher after the SW challenge compared to the FW phase. Immune-related genes related to mucosal defense, such as mucin genes [muc2, muc5ac1 (DI), muc5ac1 (AI), muc5ac2, muc5b (skin), and muc5ac1 (gills)], and antimicrobial peptide genes [def3 (DI), def3 (AI), and cath1 (skin)] were significantly upregulated in the 50 % VMO group. PCA of gene expression demonstrated the positive influences on gene regulation in the 50 % VMO dietary group. In conclusion, this study demonstrated the positive effect of substituting 50 % of fish oil with algal oil in the diets of Atlantic salmon. The findings of histomorphometry, mucosal mapping, immunohistochemistry, and immune-related genes connected to mucosal responses all support this conclusion.

Leveraging the biotechnological promise of the hagfish variable lymphocyte receptors: tools for aquatic microbial diseases.

The jawless vertebrates (agnathans or cyclostomes) are ancestral animals comprising lampreys and hagfishes, which are the only extant representatives. They possess an alternative adaptive immune system (AIS) that uses leucine-rich repeats (LRR)-based variable lymphocyte receptors (VLRs) instead of the immunoglobulin (Ig)-based antigen receptors of jawed vertebrates (gnathostomes). The five VLR types (VLRA-VLRE) are expressed on agnathan lymphocytes and functionally resemble lymphocyte antigen receptors. In particular, VLRB is functionally similar to the B cell receptor expressed and secreted by B-like lymphocytes as VLRB antibodies that bind antigens with high affinity and specificity. The potential repertoire scale of VLR-based antigen receptors is believed to be at least comparable to that of Ig-based systems. VLR proteins inherently possess characteristics that render them excellent candidates for biotechnological development, including tractability to recombinant approaches. In recent years, scientists have explored the biotechnological development and utility of VLRB proteins as alternatives to conventional mammalian antibodies. The VLRB antibody platform represents a non-traditional approach to generating a highly diverse repertoire of unique antibodies. In this review, we first describe some aspects of the biology of the AIS of the jawless vertebrates, which recognize antigens by means of unique receptors. We then summarize reports on the development of VLRB-based antibodies and their applications, particularly those from the inshore hagfish (Eptatretus burgeri) and their potential uses to address microbial diseases in aquaculture. Hagfish VLRB mAbs are being developed and improved, while obstacles to the advancement of the VLRB platform are being addressed to utilize VLRBs effectively as tools in immunology. Hence, mAbs for novel antigen targets are expected to emerge to provide new opportunities to tackle various scientific questions. We anticipate a greater interest in the agnathan AIS in general and particularly in the hagfish AIS for greater elucidation of the evolution of adaptive immunity and its applications to tackle microbial pathogens in farmed aquatic animals and beyond.

Recommendations for Uniform Variant Calling of SARS-CoV-2 Genome Sequence across Bioinformatic Workflows.

Genomic sequencing of clinical samples to identify emerging variants of SARS-CoV-2 has been a key public health tool for curbing the spread of the virus. As a result, an unprecedented number of SARS-CoV-2 genomes were sequenced during the COVID-19 pandemic, which allowed for rapid identification of genetic variants, enabling the timely design and testing of therapies and deployment of new vaccine formulations to combat the new variants. However, despite the technological advances of deep sequencing, the analysis of the raw sequence data generated globally is neither standardized nor consistent, leading to vastly disparate sequences that may impact identification of variants. Here, we show that for both Illumina and Oxford Nanopore sequencing platforms, downstream bioinformatic protocols used by industry, government, and academic groups resulted in different virus sequences from same sample. These bioinformatic workflows produced consensus genomes with differences in single nucleotide polymorphisms, inclusion and exclusion of insertions, and/or deletions, despite using the same raw sequence as input datasets. Here, we compared and characterized such discrepancies and propose a specific suite of parameters and protocols that should be adopted across the field. Consistent results from bioinformatic workflows are fundamental to SARS-CoV-2 and future pathogen surveillance efforts, including pandemic preparation, to allow for a data-driven and timely public health response.

Effect of Moringa oleifera Leaf Extract on the Growth Performance, Hematology, Innate Immunity, and Disease Resistance of Nile Tilapia (Oreochromis niloticus) against Streptococcus agalactiae Biotype 2.

The present study aimed to investigate the effects of Moringa oleifera leaf (MLE) extract-supplemented diets on the growth, feed utilization, hematology, innate immune response, and disease resistance of Nile tilapia against Streptococcus agalactiae Biotype 2. Four hundred and fifty Nile tilapia (32.61 ± 0.2 g/fish) were randomly allocated into fifteen tanks (30 fish/tank). Different concentrations of MLE at 0%, 0.5%, 1%, 1.5%, and 2% were fed to the Nile tilapia for 30 days, and the growth, feed utilization, hematology, and innate immune response of the Nile tilapia were determined. After the feeding trial, the Nile tilapia were challenged with a S. agalactiae Biotype 2 infection, and the relative percentage of survival (RPS) was determined. Results revealed the presence of quercetin, kaempferol, and p-coumaric acid in the MLE extract, exhibiting stronger antimicrobial activity against S. agalactiae Biotype 2. The diets supplemented with the MLE-0.5 group showed a significantly higher growth, feed utilization, hematology, and innate immune response in the Nile tilapia compared to the control and other MLE groups. Additionally, the MLE-0.5 group exhibited a significantly higher RPS of the Nile tilapia against S. agalactiae Biotype 2. Therefore, MLE-0.5 can be employed as an alternative feed supplement in sustainable Nile tilapia farming to protect against S. agalactiae Biotype 2.

Mass, Spectroscopy, and Two-Neutron Decay of

The structure and decay of the most neutron-rich beryllium isotope, ^{16}Be, has been investigated following proton knockout from a high-energy ^{17}B beam. Two relatively narrow resonances were observed for the first time, with energies of 0.84(3) and 2.15(5) MeV above the two-neutron decay threshold and widths of 0.32(8) and 0.95(15) MeV, respectively. These were assigned to be the ground (J^{π}=0^{+}) and first excited (2^{+}) state, with E_{x}=1.31(6) MeV. The mass excess of ^{16}Be was thus deduced to be 56.93(13) MeV, some 0.5 MeV more bound than the only previous measurement. Both states were observed to decay by direct two-neutron emission. Calculations incorporating the evolution of the wave function during the decay as a genuine three-body process reproduced the principal characteristics of the neutron-neutron energy spectra for both levels, indicating that the ground state exhibits a strong spatially compact dineutron component, while the 2^{+} level presents a far more diffuse neutron-neutron distribution.

Priorities, needs and willingness of use of nerve stimulation devices for bladder and bowel function in people with spinal cord injury (SCI): an Australian survey.

STUDY DESIGN: Anonymous online survey OBJECTIVES: To investigate the priorities, needs and willingness to adopt nerve stimulation devices for managing neurogenic bladder and bowel function in people with spinal cord injury (SCI) living in Australia. SETTING: Online survey of people living with SCI in Australia. METHODS: This anonymous online survey used Qualtrics and was advertised via standard communication channels, such as advocacy groups representing the SCI community in Australia, social media, attending SCI sporting events and by word-of-mouth. RESULTS: Responses from 62 individuals (32% female, 68% male) were included. Bladder emptying through urethra without catheter was the highest priority for bladder function. Reducing time required for bowel routines and constipation were the top priorities regarding bowel function. The highest concern for internal/implanted devices was the 4% chance of device surgical removal, while wearing wires under the clothes was the main concern for external devices. 53% of respondents were willing to trial an implanted nerve stimulation device, while 70% would trial an external device to improve and gain independence in bladder and bowel function. CONCLUSION: The findings of this study highlighted the potential role in which nerve stimulation can have in addressing bladder and bowel dysfunction in people with SCI, and have also identified that there was a need for Australian physiotherapists to evaluate their role in bladder and bowel dysfunction. Results from this study can help guide further research in nerve stimulation devices for bladder and bowel dysfunction in people with SCI. SPONSORSHIP: n/a.

Comparative Efficacy of Subcutaneous and Intravenous Infliximab and Vedolizumab for Maintenance Treatment of TNF-naive Adult Patients with Inflammatory Bowel Disease: A Systematic Literature Review and Network Meta-analysis.

BACKGROUND: Infliximab and vedolizumab are widely used to treat Crohn's disease (CD) and ulcerative colitis (UC). AIMS: This systematic review and network meta-analysis evaluated comparative efficacy of various regimens for intravenous or subcutaneous infliximab and vedolizumab during maintenance treatment in CD and UC. METHODS: Parallel-group randomized controlled trials (RCTs) were identified by a systematic literature review (CRD42022383401) and included if they evaluated therapeutics of interest for maintenance treatment of adults with moderate-to-severe luminal CD or UC and assessed clinical remission between Weeks 30 and 60. Clinical remission rates in CD or UC and mucosal healing rates in UC were analyzed in a Bayesian network meta-analysis model. Endoscopic outcomes in CD were synthesized by proportional meta-analysis. RESULTS: Overall, 13 RCTs were included in the analyses. All vedolizumab studies randomized induction responders to maintenance treatment; infliximab studies used a treat-through design. Subcutaneous infliximab 120 mg every 2 weeks had the highest odds ratio (OR) [95% credible interval] versus placebo for clinical remission during the maintenance phase (CD: 5.90 [1.90-18.2]; UC: 5.45 [1.94-15.3]), with surface under the cumulative ranking curve (SUCRA) values of 0.91 and 0.82, respectively. For mucosal healing in UC, subcutaneous infliximab 120 mg every 2 weeks showed the highest OR (4.90 [1.63-14.1]), with SUCRA value of 0.73, followed by intravenous vedolizumab 300 mg every 4 weeks (SUCRA value, 0.70). Endoscopic outcomes in CD were better with subcutaneous infliximab 120 mg every 2 weeks than intravenous infliximab 5 mg/kg every 8 weeks. CONCLUSIONS: Subcutaneous infliximab showed a favorable efficacy profile for achieving clinical remission and endoscopic outcomes during maintenance treatment in CD or UC.

The lived experiences of play and the perspectives of disabled children and their parents surrounding brain-computer interfaces.

Brain-computer interfaces (BCI) offer promise to the play of children with significant physical impairments, as BCI technology can enable disabled children to control computer devices, toys, and robots using only their brain signals. However, there is little research on the unique needs of disabled children when it comes to BCI-enabled play. Thus, this paper explored the lived experiences of play for children with significant physical impairments and examined how BCI could potentially be implemented into disabled children's play experiences by applying a social model of childhood disability. Descriptive qualitative methodology was employed by conducting four semi-structured interviews with two children with significant physical impairments and their parents. We found that disabled children's play can be interpreted as passive or active depending on one's definition and perceptions surrounding play. Moreover, disabled children continue to face physical, economic, and technological barriers in their play, as well as play restrictions from physical impairments. We urge that future research should strive to directly hear from disabled children themselves, as their perspectives may differ from their parents' views. Also, future BCI development should strive to incorporate video games, recreational and entertainment applications/platforms, toys and switch-adapted toys, and power wheelchairs to better support the play of children with significant physical impairments.Implications for RehabilitationAssistive technology research should strive to examine the social, infrastructural, and environmental barriers that continue to disable and restrict participation for disabled children and their families through applying a social model of childhood disability and other holistic frameworks that look beyond individual factorsFuture research that examines the needs and lives of disabled children should strive to directly seek the opinions and perspectives of disabled children themselvesBrain-computer interface development should strive to incorporate video games, recreational and entertainment applications/platforms, toys and switch-adapted toys, and power wheelchairs to better support the play of children with significant physical impairments.

Knowns and unknowns of TiLV-associated neuronal disease.

Tilapia Lake Virus (TiLV) is associated with pathological changes in the brain of infected fish, but the mechanisms driving the virus's neuropathogenesis remain poorly characterized. TiLV establishes a persistent infection in the brain of infected fish even when the virus is no longer detectable in the peripheral organs, rendering therapeutic interventions and disease management challenging. Moreover, the persistence of the virus in the brain may pose a risk for viral reinfection and spread and contribute to ongoing tissue damage and neuroinflammatory processes. In this review, we explore TiLV-associated neurological disease. We discuss the possible mechanism(s) used by TiLV to enter the central nervous system (CNS) and examine TiLV-induced neuroinflammation and brain immune responses. Lastly, we discuss future research questions and knowledge gaps to be addressed to significantly advance this field.

Rapid and sensitive detection of genome contamination at scale with FCS-GX.

Assembled genome sequences are being generated at an exponential rate. Here we present FCS-GX, part of NCBI's Foreign Contamination Screen (FCS) tool suite, optimized to identify and remove contaminant sequences in new genomes. FCS-GX screens most genomes in 0.1-10 min. Testing FCS-GX on artificially fragmented genomes demonstrates high sensitivity and specificity for diverse contaminant species. We used FCS-GX to screen 1.6 million GenBank assemblies and identified 36.8 Gbp of contamination, comprising 0.16% of total bases, with half from 161 assemblies. We updated assemblies in NCBI RefSeq to reduce detected contamination to 0.01% of bases. FCS-GX is available at https://github.com/ncbi/fcs/ or https://doi.org/10.5281/zenodo.10651084 .

Definitions of recovery and reintegration across the first year: A qualitative study of perspectives of persons with spinal cord injury and caregivers.

STUDY DESIGN: Longitudinal, qualitative cohort study. OBJECTIVES: To understand how people with newly acquired spinal cord injury (PWS) and their support person (SP) define recovery and successful community reintegration (CR) across the first 12 months post-injury (mpi) and their satisfaction with the rate of recovery and reintegration experienced. SETTING: Academic and Veterans hospitals in Midwest USA. METHODS: In-depth, semi-structured interviews were conducted in two cohorts of PWS and SP during the initial inpatient rehabilitation stay, at 6 mpi, and at 12 mpi. Recordings were transcribed; four authors independently undertook line-by-line coding. The team discussed codes to reach consensus and synthesize into broader themes within the International Classification of Function, Disability, and Health and Transformative frameworks. RESULTS: Data are reported on 23 PWS and 21 SP. PWS and SP are similar in defining recovery as gaining motor function and achieving independence. However, SP more frequently define recovery in terms of maintaining positivity and emotional recovery. At 12 mpi both groups shift to define recovery according to progress. Social roles, being active, and employment are persistent themes of how PWS and SP define successful CR. However, SP also frequently define successful CR as reestablishing identity and emotional adjustment. Veterans with SCI less frequently defined successful CR as employment. CONCLUSIONS: This study is the first to reveal how PWS and SP define recovery and reintegration during the first 12 mpi. Given decreasing lengths of stay, this information can be used to tailor rehabilitation strategies during the critical first year of injury to optimize recovery.

Translational insights and overall survival in the U31402-A-U102 study of patritumab deruxtecan (HER3-DXd) in EGFR-mutated NSCLC.

BACKGROUND: Human epidermal growth factor receptor 3 (HER3) is broadly expressed in non-small-cell lung cancer (NSCLC) and is the target of patritumab deruxtecan (HER3-DXd), an antibody-drug conjugate consisting of a HER3 antibody attached to a topoisomerase I inhibitor payload via a tetrapeptide-based cleavable linker. U31402-A-U102 is an ongoing phase I study of HER3-DXd in patients with advanced NSCLC. Patients with epidermal growth factor receptor (EGFR)-mutated NSCLC that progressed after EGFR tyrosine kinase inhibitor (TKI) and platinum-based chemotherapy (PBC) who received HER3-DXd 5.6 mg/kg intravenously once every 3 weeks had a confirmed objective response rate (cORR) of 39%. We present median overall survival (OS) with extended follow-up in a larger population of patients with EGFR-mutated NSCLC and an exploratory analysis in those with acquired genomic alterations potentially associated with resistance to HER3-DXd. PATIENTS AND METHODS: Safety was assessed in patients with EGFR-mutated NSCLC previously treated with EGFR TKI who received HER3-DXd 5.6 mg/kg; efficacy was assessed in those who also had prior PBC. RESULTS: In the safety population (N = 102), median treatment duration was 5.5 (range 0.7-27.5) months. Grade ≥3 adverse events occurred in 76.5% of patients; the overall safety profile was consistent with previous reports. In 78/102 patients who had prior third-generation EGFR TKI and PBC, cORR by blinded independent central review (as per RECIST v1.1) was 41.0% [95% confidence interval (CI) 30.0% to 52.7%], median progression-free survival was 6.4 (95% CI 4.4-10.8) months, and median OS was 16.2 (95% CI 11.2-21.9) months. Patients had diverse mechanisms of EGFR TKI resistance at baseline. At tumor progression, acquired mutations in ERBB3 and TOP1 that might confer resistance to HER3-DXd were identified. CONCLUSIONS: In patients with EGFR-mutated NSCLC after EGFR TKI and PBC, HER3-DXd treatment was associated with a clinically meaningful OS. The tumor biomarker characterization comprised the first description of potential mechanisms of resistance to HER3-DXd therapy.

Healing patient, harming planet? A drive towards sustainable surgery: review of waste production and recyclability of surgical instrument packaging.

INTRODUCTION: Healthcare contributes more than 1% of all domestic waste in the United Kingdom (UK), with operating theatre waste alone accounting for approximately 50% of all hospital waste. In November 2022, the UK Surgical Royal Colleges issued an Intercollegiate Climate Emergency Declaration and called for urgent action. We review waste production and the recyclability of surgical instrument packaging used in a common ear, nose and throat procedure (thyroidectomy) and suggest strategies to make this surgery more sustainable,. These strategies can be generalised to other surgeries. METHODS: We prospectively audited packaging waste from 20 thyroidectomies performed at the Royal Marsden Hospital in the UK between July and December 2022. All packaging was weighed, categorised and analysed after the operation. RESULTS: On average, each thyroidectomy produced packaging waste comprising 183g (34%) of plain paper/cardboard, 167g (31%) of soft plastic film, 142g (26%) of laminated paper, 37g (7%) of hard plastic and 11g (2%) of metal foil. Of all the packaging collected, only one item had a recycling label. When extrapolated to the 7,851 thyroidectomies performed in the National Health Service during the fiscal year 2021/2022, the estimated total weight of packaging waste would be 4.2 tonnes, of which only 31.4kg would be indicated as recyclable. When converted to an estimated carbon footprint, total carbon emissions would be 1,048kg CO2e, equivalent to three round trips from London to Edinburgh in a petrol car. CONCLUSION: This audit demonstrates the different categories and vast amount of packaging waste from a common operation. Manufacturers should place clear recyclability labels on packaging, and switch to recyclable materials and a digital information booklet where possible. Local waste audit and analysis can be simple first steps towards making surgery more sustainable.

Sport-related concussion alters cerebral hemodynamic activity during controlled respiration.

Sport-related concussion (SRC) is known to disrupt neurohemodynamic activity, cardiac function, and blood pressure (BP) autoregulation. This study aims to observe changes in cerebrovascular and cardiovascular responses during controlled respiration after sustaining an SRC. University varsity athletes (n = 81) completed a preseason physiological assessment and were followed up within 5 days of sustaining an SRC. During preseason and follow-up assessments, participants' continuous beat-to-beat BP was collected by finger photoplethysmography, and right prefrontal cortex oxygenation was collected using near-infrared spectroscopy (NIRS). Participants completed 5 min of seated rest and 5 min of a 6-breaths per minute controlled breathing protocol (5 s inhale and 5 s exhale; 0.10 Hz). Wavelet transformation was applied to the NIRS and BP signals, separating them into respiratory (0.10-0.6 Hz) and cardiac (0.6-2 Hz) frequency intervals. Of the 81 participants, 74 had a usable BP signal, 43 had usable NIRS signals, and 28 had both usable BP and NIRS signals. Wavelet amplitudes were calculated and coherence between NIRS and BP on the 28 participants were assessed. There was a significant (P < 0.05) decrease in oxygenated hemoglobin amplitude from 0.062 to 0.054 Hz and hemoglobin difference amplitude from 0.059 to 0.051 Hz, both at the respiratory (0.10-0.6 Hz) frequency interval, from preseason to acute SRC, respectively. Therefore, during controlled respiration, there was a reduction in intensity at the respiratory band, suggesting a protective, reduced respiratory contribution to cerebral hemodynamic activity following acute SRC.NEW & NOTEWORTHY This study investigated cerebral hemodynamic activity following sport-related concussion. Prefrontal cortex oxygenation was assessed by near-infrared spectroscopy (NIRS) during a controlled breathing protocol. Wavelet transformation of the NIRS signals showed significant decreases in HbO2 and HbD amplitude at the respiratory frequency interval (0.10-0.6 HZ) from preseason baseline to acute concussion. These results suggest a decreased respiratory contribution to cerebral hemodynamic activity following acute concussion.

Increased leaf area index and efficiency drive enhanced production under elevated atmospheric [CO2 ] in a pine-dominated stand showing no progressive nitrogen limitation.

Enhancement of net primary production (NPP) in forests as atmospheric [CO2 ] increases is likely limited by the availability of other growth resources. The Duke Free Air CO2 Enrichment (FACE) experiment was located on a moderate-fertility site in the southeastern US, in a loblolly pine (Pinus taeda L.) plantation with broadleaved species growing mostly in mid-canopy and understory. Duke FACE ran from 1994 to 2010 and combined elevated [CO2 ] (eCO2 ) with nitrogen (N) additions. We assessed the spatial and temporal variation of NPP response using a dataset that includes previously unpublished data from 6 years of the replicated CO2 × N experiment and extends to 2 years beyond the termination of enrichment. Averaged over time (1997-2010), NPP of pine and broadleaved species were 38% and 52% higher under eCO2 compared to ambient conditions. Furthermore, there was no evidence of a decline in enhancement over time in any plot regardless of its native site quality. The relation between spatial variation in the response and native site quality was suggested but inconclusive. Nitrogen amendments under eCO2 , in turn, resulted in an additional 11% increase in pine NPP. For pine, the eCO2 -induced increase in NPP was similar above- and belowground and was driven by both increased leaf area index (L) and production efficiency (PE = NPP/L). For broadleaved species, coarse-root biomass production was more than 200% higher under eCO2 and accounted for the entire production response, driven by increased PE. Notably, the fraction of annual NPP retained in total living biomass was higher under eCO2 , reflecting a slight shift in allocation fraction to woody mass and a lower mortality rate. Our findings also imply that tree growth may not have been only N-limited, but perhaps constrained by the availability of other nutrients. The observed sustained NPP enhancement, even without N-additions, demonstrates no progressive N limitation.