External Workloads Vary by Position and Game Result in US-based Professional Soccer Players.

Professional soccer is a physically demanding sport that requires players to be highly trained. Advances using GPS allow the tracking of external workloads for individual players in practice and competition, however, there is a lack of evidence on how these measures impact match results. Therefore, we analyzed external workloads by player position and determined if they vary depending on the result of competitive matches. External workloads were analyzed in professional soccer players (n = 25) across 28 competitive games. One-way ANOVA determined if workloads varied by position (striker - ST, wide midfielder - WM, central midfielder - CM, wide defender - WD, central defender - CD) or across games won (n = 8), lost (n = 13) or tied (n = 7). Repeated-measures ANOVA assessed differences in workloads specific to each position in each of the result categories. Statistical significance was set at p < 0.05. Across all games, more high-speed and very-high speed running was done by ST and WD compared to CD (p < 0.001) and CM (p < 0.001 - 0.02). Whole-team data showed no differences in any external workload variable with respect to match result (p > 0.05), however, in games won ST did more very high-speed running than in losing games (p = 0.03) and defending players did more high and very high-speed running in games tied vs. those won or lost (p < 0.05). Whole-team external workloads do not vary depending on the match result; however, high speed running may be a differentiating factor at the positional level. Coaches should consider position-specific analysis when examining player workloads.

An oropharyngeal device for airway management of conscious and semiconscious patients: A randomized clinical trial.

OBJECTIVE: No oropharyngeal devices exist for use in conscious and semiconscious trauma patients during emergency evacuation, transport, or resuscitation. We aimed to test the hypotheses that the ManMaxAirway (MMA) is better tolerated than the standard Guedel-style device in awake volunteers and that it produces a jaw thrust and improves air flow. METHODS: This was a randomized cross-over study of healthy volunteers with either the MMA or standard device. The primary outcome of tolerability was defined as maintaining the device in place for 60 seconds. Secondary outcomes included respiratory system function and jaw thrust. Resistance to airflow through the device lumen was measured in situ and when placed in subjects in the pulmonary laboratory alone. Jaw thrust was quantified as displacement between the mandibular condyle and condylar fossa apex relative to baseline visualized with magnetic resonance imaging (MRI). RESULTS: We enrolled 19 subjects. Of these, a convenience sample of 5 individuals was selected for MRI; the remaining individuals (n = 14) were randomized for the cross-over study. All 14 subjects were able to maintain the MMA for 60 seconds compared with 2/14 (14%) with the standard device (odds ratio, 145; 95% confidence interval, 6.3-3314). Subjects reported that the experimental device was more comfortable and its placement did not trigger the gag reflex. Airway resistance produced by the MMA in an oscillatory flow model was nearly an order of magnitude lower than that of the standard device (experimental vs standard, 8 Hz-0.092 vs 0.786 cmH20·s/L; 15 Hz-0.193 vs 1.321 cmH20·s/L). Rapid induction of the gag reflex precluded further measurements with the standard device. Forced oscillation pulmonary testing in conscious volunteers with and without the MMA demonstrated that the device decreased respiratory system resistance to airflow and reduced respiratory elastance (31% ± 8% and 44% ± 13.4%, respectively; P < 0.05). MRIs of the subjects (n = 5) with the MMA in place showed a significant jaw thrust compared with baseline (7 ± 1 mm). CONCLUSIONS: The MMA proved well tolerated in conscious subjects, resulting in an opening of the anatomic airway and a decreased resistance to airflow.

Diagnostic Performance of Carbon Monoxide Testing by Pulse Oximetry in the Emergency Department.

BACKGROUND: Carbon monoxide (CO) exposure causes roughly 40,000 emergency department (ED) visits annually and is commonly misdiagnosed. Whereas the standard method of carboxyhemoglobin (HbCO) measurement utilizes blood gas analysis, a noninvasive, FDA-cleared alternative exists. We evaluated the performance of pulse oximetry (SpCO) for identification of CO exposure in ED patients. METHODS: We compared pulse oximetry to blood HbCO levels in a prospective observational study of adult and pediatric subjects recruited from the ED. Nurses screened a convenience sample of patients and referred those with SpCO ≥ 10% to research staff. Researchers also approached individuals who presented with signs and symptoms of CO toxicity. We determined diagnostic performance with a Bland-Altman analysis and calculated sensitivity and specificity for detection of elevated HbCO at thresholds of ≥ 10% and ≥ 15%. To optimize the potential sensitivity of SpCO for detection of CO toxicity, research technicians performed 3 SpCO readings within 5 min of the blood draw for laboratory measurement. A positive SpCO test was defined as any SpCO ≥ 10%. RESULTS: 42,000 patients were screened, 212 were evaluated, and 126 subjects were enrolled. Median HbCO level was 6% (range 1.6-21.9%). Limits of agreement were -10.3% and 8.1%. Of 23 individuals with elevated HbCO ≥ 10%, 13 were not suspected based on clinical assessment. Critically elevated HbCO was present in 6 individuals. Based on our a priori threshold of 10% for a positive test, pulse oximetry identified 14 of 23 subjects with HbCO ≥ 10%, with a sensitivity of 61% (95% CI 39-80%) and a specificity of 86% (95% CI 78-92%), and 5 of 6 subjects with HbCO ≥ 15%, with a sensitivity of 83% (95% CI 36-100%) and a specificity of 81% (95% CI 73-87%). CONCLUSIONS: Pulse oximetry underestimated HbCO and produced false negative results (ie, SpCO < 10% for all three measurements) in 17% of ED subjects with elevated HbCO ≥ 15%. Triage screening with pulse oximetry detected cases of elevated HbCO that were not suspected by the clinical provider.

Cord blood expansion. Pyrimidoindole derivatives are agonists of human hematopoietic stem cell self-renewal.

The small number of hematopoietic stem and progenitor cells in cord blood units limits their widespread use in human transplant protocols. We identified a family of chemically related small molecules that stimulates the expansion ex vivo of human cord blood cells capable of reconstituting human hematopoiesis for at least 6 months in immunocompromised mice. The potent activity of these newly identified compounds, UM171 being the prototype, is independent of suppression of the aryl hydrocarbon receptor, which targets cells with more-limited regenerative potential. The properties of UM171 make it a potential candidate for hematopoietic stem cell transplantation and gene therapy.

Lnk adaptor suppresses radiation resistance and radiation-induced B-cell malignancies by inhibiting IL-11 signaling.

The Lnk (Sh2b3) adaptor protein dampens the response of hematopoietic stem cells and progenitors (HSPCs) to a variety of cytokines by inhibiting JAK2 signaling. As a consequence, Lnk(-/-) mice develop hematopoietic hyperplasia, which progresses to a phenotype resembling the nonacute phase of myeloproliferative neoplasm. In addition, Lnk mutations have been identified in human myeloproliferative neoplasms and acute leukemia. We find that Lnk suppresses the development of radiation-induced acute B-cell malignancies in mice. Lnk-deficient HSPCs recover more effectively from irradiation than their wild-type counterparts, and this resistance of Lnk(-/-) HSPCs to radiation underlies the subsequent emergence of leukemia. A search for the mechanism responsible for radiation resistance identified the cytokine IL-11 as being critical for the ability of Lnk(-/-) HSPCs to recover from irradiation and subsequently become leukemic. In IL-11 signaling, wild-type Lnk suppresses tyrosine phosphorylation of the Src homology region 2 domain-containing phosphatase-2/protein tyrosine phosphatase nonreceptor type 11 and its association with the growth factor receptor-bound protein 2, as well as activation of the Erk MAP kinase pathway. Indeed, Src homology region 2 domain-containing phosphatase-2 has a binding motif for the Lnk Src Homology 2 domain that is phosphorylated in response to IL-11 stimulation. IL-11 therefore drives a pathway that enhances HSPC radioresistance and radiation-induced B-cell malignancies, but is normally attenuated by the inhibitory adaptor Lnk.

GATA-3 regulates the self-renewal of long-term hematopoietic stem cells.

The transcription factor GATA-3 is expressed and required for differentiation and function throughout the T lymphocyte lineage. Despite evidence it may also be expressed in multipotent hematopoietic stem cells (HSCs), any role for GATA-3 in these cells has remained unclear. Here we found GATA-3 was in the cytoplasm in quiescent long-term stem cells from steady-state bone marrow but relocated to the nucleus when HSCs cycled. Relocation depended on signaling via the mitogen-activated protein kinase p38 and was associated with a diminished capacity for long-term reconstitution after transfer into irradiated mice. Deletion of Gata3 enhanced the repopulating capacity and augmented the self-renewal of long-term HSCs in cell-autonomous fashion without affecting the cell cycle. Our observations position GATA-3 as a regulator of the balance between self-renewal and differentiation in HSCs that acts downstream of the p38 signaling pathway.

Neurokinin-1 receptor signalling impacts bone marrow repopulation efficiency.

Tachykinins are a large group of neuropeptides with both central and peripheral activity. Despite the increasing number of studies reporting a growth supportive effect of tachykinin peptides in various in vitro stem cell systems, it remains unclear whether these findings are applicable in vivo. To determine how neurokinin-1 receptor (NK-1R) deficient hematopoietic stem cells would behave in a normal in vivo environment, we tested their reconstitution efficiency using competitive bone marrow repopulation assays. We show here that bone marrow taken from NK-1R deficient mice (Tacr1(-/-)) showed lineage specific B and T cell engraftment deficits compared to wild-type competitor bone marrow cells, providing evidence for an involvement of NK-1R signalling in adult hematopoiesis. Tachykinin knockout mice lacking the peptides SP and/or HK-1 (Tac1 (-/-), Tac4 (-/-) and Tac1 (-/-)/Tac4 (-/-) mice) repopulated a lethally irradiated wild-type host with similar efficiency as competing wild-type bone marrow. The difference between peptide and receptor deficient mice indicates a paracrine and/or endocrine mechanism of action rather than autocrine signalling, as tachykinin peptides are supplied by the host environment.

Intermediate-term hematopoietic stem cells with extended but time-limited reconstitution potential.

Sustained blood cell production depends on divisions by hematopoietic stem cells (HSCs) that yield both differentiating progeny as well as new HSCs via self-renewal. Differentiating progeny remain capable of self-renewal, but only HSCs sustain self-renewal through successive divisions securely enough to maintain clones that persist life-long. Until recently, the first identified next stage consisted of "short-term" reconstituting cells able to sustain clones of differentiating cells for only 4-6 weeks. Here we expand evidence for a numerically dominant "intermediate-term" multipotent HSC stage in mice whose clones persist for 6-8 months before becoming extinct and that are separable from both short-term as well as permanently reconstituting "long-term" HSCs. The findings suggest that the first step in stem cell differentiation consists not in loss of initial capacity for serial self-renewal divisions, but rather in loss of mechanisms that stabilize self-renewing behavior throughout successive future stem cell divisions.

Identification of gene 3' ends by automated EST cluster analysis.

The properties and biology of mRNA transcripts can be affected profoundly by the choice of alternative polyadenylation sites, making definition of the 3' ends of transcripts essential for understanding their regulation. Here we show that 22-52% of sequences in commonly used human and murine "full-length" transcript databases may not currently end at bona fide polyadenylation sites. To identify probable transcript termini over the entire murine and human genomes, we analyzed the EST databases for positional clustering of EST ends. The analysis yielded 58,282 murine- and 86,410 human-candidate polyadenylation sites, of which 75% mapped to 23,091 known murine transcripts and 22,891 known human transcripts. The murine dataset correctly predicted 97% of the 3' ends in a manually curated and experimentally supported benchmark transcript set. Of currently known genes, 15% had no associated prediction and 25% had only a single predicted termination site. The remaining genes had an average of 3-4 alternative polyadenylation sites predicted for each murine or human transcript, respectively. The results are made available in the form of tables and an interactive web site that can be mined for rapid assessment of the validity of 3' ends in existing collections, enumeration of potential alternative 3' polyadenylation sites of known transcripts, direct retrieval of terminal sequences for design of probes, and detection of polyadenylation sites not currently mapped to known genes.

Distance impacts mortality in trauma patients with an intubation attempt.

OBJECTIVE: Out-of-hospital endotracheal intubation (OOH-ETI) has been associated with adverse outcomes; whether transport distance changes this relationship is unclear. We sought to determine whether patients injured farther from the hospital benefit more from OOH-ETI than those injured closer. METHODS: We performed a retrospective cohort analysis of trauma patients > 14 years old transported to two Level 1 trauma centers and surviving to admission from 2000 to 2003. We used probabilistically linked geographic data to calculate transport distance. To adjust for the nonrandom selection of patients for OOH-ETI, we used a propensity score based on clinical variables: prehospital physiology, demographics, transport mode, mechanism, comorbidities, Abbreviated Injury Scale head injury score >or= 3, Injury Severity Score, blood transfusion, and major surgery. Propensity-adjusted multivariable logistic regression with mode of transport was used to test the interaction between distance and OOH-ETI. RESULTS: 8,786 patients were included, 534 with OOH-ETI. Patients with OOH-ETI had higher adjusted mortality (odds ratio [OR] 2.06, 95% confidence interval [CI] 1.33-3.18), and there was a significant interaction between distance and OOH-ETI (p = 0.02). Patients with shortest distances had the highest mortality (OR 3.98, 95% CI 2.08-7.60). Probability of mortality was higher with OOH-ETI across all distances and increased for patients closest to the hospital. Helicopter transport was associated with improved survival. CONCLUSIONS: Prehospital intubation is associated with increased mortality among trauma patients at all distances from the hospital. Patients with the shortest transport distances had the greatest mortality associated with OOH-ETI, whereas helicopter transport was associated with improved survival. The event location and ensuing distance to the hospital are another factor to consider when instituting and modifying OOH airway protocols.