Correlative metabologenomics of 110 fungi reveals metabolite-gene cluster pairs.

Natural products research increasingly applies -omics technologies to guide molecular discovery. While the combined analysis of genomic and metabolomic datasets has proved valuable for identifying natural products and their biosynthetic gene clusters (BGCs) in bacteria, this integrated approach lacks application to fungi. Because fungi are hyper-diverse and underexplored for new chemistry and bioactivities, we created a linked genomics-metabolomics dataset for 110 Ascomycetes, and optimized both gene cluster family (GCF) networking parameters and correlation-based scoring for pairing fungal natural products with their BGCs. Using a network of 3,007 GCFs (organized from 7,020 BGCs), we examined 25 known natural products originating from 16 known BGCs and observed statistically significant associations between 21 of these compounds and their validated BGCs. Furthermore, the scalable platform identified the BGC for the pestalamides, demystifying its biogenesis, and revealed more than 200 high-scoring natural product-GCF linkages to direct future discovery.

Effects of Endotracheal Epinephrine on Pharmacokinetics and Survival in a Swine Pediatric Cardiac Arrest Model.

OBJECTIVES: The aim of this study was to compare the endotracheal tube (ET) and intravenous (IV) administration of epinephrine relative to concentration maximum, time to maximum concentration, mean concentration over time (MC), area under the curve, odds, and time to return of spontaneous circulation (ROSC) in a normovolemic pediatric cardiac arrest model. METHODS: Male swine weighing 24-37 kg were assigned to 4 groups: ET (n = 8), IV (n = 7), cardiopulmonary resuscitation (CPR) + defibrillation (CPR + Defib) (n = 5), and CPR only (n = 3). Swine were placed arrest for 2 minutes, and then CPR was initiated for 2 minutes. Epinephrine (0.1 mg/kg) for the ET group or 0.01 mg/kg for the IV was administered every 4 minutes or until ROSC. Defibrillation started at 3 minutes and continued every 2 minutes for 30 minutes or until ROSC for all groups except the CPR-only group. Blood samples were collected over a period of 5 minutes. RESULTS: The MC of plasma epinephrine for the IV group was significantly higher at the 30- and 60-second time points (P = 0.001). The ET group had a significantly higher MC of epinephrine at the 180- and 240-second time points (P < 0.05). The concentration maximum of plasma epinephrine was significantly lower for the ET group (195 ± 32 ng/mL) than for the IV group (428 ± 38 ng/mL) (P = 0.01). The time to maximum concentration was significantly longer for the ET group (145 ± 26 seconds) than for the IV group (42 ± 16 seconds) (P = 0.01). No significant difference existed in area under the curve between the 2 groups (P = 0.62). The odds of ROSC were 7.7 times greater for the ET versus IV group. Time to ROSC was not significantly different among the IV, ET, and CPR + Defib groups (P = 0.31). CONCLUSIONS: Based on the results of this study, the ET route of administration should be considered a first-line intervention.

A Survey of Didemnin Depsipeptide Production in Tistrella.

As one of the first families of marine natural products to undergo clinical trials, the didemnin depsipeptides have played a significant role in inspiring the discovery of marine drugs. Originally developed as anticancer therapeutics, the recent re-evaluation of these compounds including synthetically derived dehydrodidemnin B or Aplidine, has led to their advancement towards antiviral applications. While conventionally associated with production in colonial tunicates of the family Didemnidae, recent studies have identified their biosynthetic gene clusters from the marine-derived bacteria Tistrella mobilis. While these studies confirm the production of didemnin X/Y, the low titer and general lack of understanding of their biosynthesis in Tistrella currently prevents the development of effective microbial or synthetic biological approaches for their production. To this end, we conducted a survey of known species of Tistrella and report on their ability to produce the didemnin depsipeptides. These data were used to develop conditions to produce didemnin B at titers over 15 mg/L.

Endotracheal Administered Epinephrine Is Effective in Return of Spontaneous Circulation Within a Pediatric Swine Hypovolemic Cardiac Arrest Model.

OBJECTIVE: Early administration of epinephrine increases the incidence of return of spontaneous circulation (ROSC) and improves outcomes among pediatric cardiac arrest victims. Rapid endotracheal (ET) intubation can facilitate early administration of epinephrine to pediatric victims. To date, no studies have evaluated the use of ET epinephrine in a pediatric hypovolemic cardiac arrest model to determine the incidence of ROSC. METHODS: This prospective, experimental study evaluated the pharmacokinetics and/or incidence of ROSC following ET administered epinephrine and compared it to these experimental groups: intravenous (IV) administered epinephrine, cardiopulmonary resuscitation only (CPR), and CPR + defibrillation (CPR + Defib). RESULTS: Endotracheal administered epinephrine, at the Pediatric Advanced Life Support (PALS) recommended dose, was not significantly different than IV administered epinephrine in maximum plasma concentrations, time to maximum plasma concentration, area under the curve, or ROSC, or mean plasma concentrations at various time points (P > 0.05). The odds of ROSC in the ET group were 2.4 times greater than the IV group. The onset to ROSC in the ET group was significantly shorter than the IV group (P < 0.0001). CONCLUSIONS: These data support that ET epinephrine administration remains an alternative to IV administered epinephrine and faster at restoring ROSC among pediatric hypovolemic cardiac arrest victims in the acute setting when an endotracheal tube is present. Although further research is required to determine long-term outcomes of high-dose ET epinephrine administration, these data reinforce the therapeutic potential of ET administration of epinephrine to restore ROSC before IV access.

Tibial Intraosseous Administration of Epinephrine Is Effective in Restoring Return of Spontaneous Circulation in a Pediatric Normovolemic But Not Hypovolemic Cardiac Arrest Model.

OBJECTIVE: We compared the efficacy of tibial intraosseous (TIO) administration of epinephrine in a pediatric normovolemic versus hypovolemic cardiac arrest model to determine the incidence of return of spontaneous circulation (ROSC) and plasma epinephrine concentrations over time. METHODS: This experimental study evaluated the pharmacokinetics of epinephrine and/or incidence of ROSC after TIO administration in either a normovolemic or hypovolemic pediatric swine model. RESULTS: All subjects in the TIO normovolemia cardiac arrest group experienced ROSC after TIO administration of epinephrine. In contrast, subjects experiencing hypovolemia and cardiac arrest were significantly less likely to experience ROSC when epinephrine was administered TIO versus intravenous (TIO hypovolemia: 14% [1/7] vs IV hypovolemia: 71% [5/7]; P = 0.031). The TIO hypovolemia group exhibited significantly lower plasma epinephrine concentrations versus IV hypovolemia at 60, 90, 120, and 150 seconds (P < 0.05). Although the maximum concentration of plasma epinephrine was similar, the TIO hypovolemia group exhibited significantly slower time to maximum concentration times versus TIO normovolemia subjects (P = 0.004). CONCLUSIONS: Tibial intraosseous administration of epinephrine reliably facilitated ROSC among normovolemic cardiac arrest pediatric patients, which is consistent with published reports. However, TIO administration of epinephrine was ineffective in restoring ROSC among subjects experiencing hypovolemia and cardiac arrest. Tibial intraosseous-administered epinephrine during hypovolemia and cardiac arrest may have resulted in a potential sequestration of epinephrine in the tibia. Central or peripheral intravascular access attempts should not be abandoned after successful TIO placement in the resuscitation of patients experiencing concurrent hypovolemia and cardiac arrest.

Durability and disinfection of single-use endotracheal tubes following exposure to commonly available medical disinfecting compounds.

BACKGROUND: Reusing single-use medical supplies offers a capability enhancement during massive casualty incidents when resupply of medical supplies is unavailable in times of national health care crises. This pilot study determined the feasibility of disinfection of endotracheal tubes with commonly used chemical disinfecting agents. METHODS: Endotracheal tubes (ETTs) were subjected to either CaviCide, Neutral Disinfectant Cleaner, Cidex, or saline according to the manufacturer's recommended disinfection contact times. Alterations to the polyvinyl chloride (PVC) integrity by disinfecting agents were determined by volume/pressure measurements within the ETT cuff. To test the disinfection rate, ETTs were inoculated with Staphylococcus Aureus and subjected to experimental disinfection protocol. FINDINGS: There were no significant alterations to ETT tracheal cuff function and mixed results in disinfection among ETTs. ETTs bacterial culture data presented possible contamination among the groups. DISCUSSION: These data support the feasibility of single-use ETT reuse as a last resort while making every attempt and effort to follow established protocols to minimize harm to the patient.

Effects of tibial intraosseous and IV administration of vasopressin on kinetics and survivability in cardiac arrest.

PURPOSE: Purposes of this study were to compare tibial intraosseous (TIO) and intravenous (IV) administration of vasopressin relative to return of spontaneous circulation (ROSC) and time to ROSC in an adult swine cardiac arrest model. In addition, the purposes were to compare the concentration maximum (Cmax), time to maximum concentration (Tmax), and odds of ROSC. METHODS: This was a between-subjects, prospective experimental study. Yorkshire swine (N = 21) were randomly assigned to 1 of 3 groups: TIO, IV, or control groups. The swine were anesthetized and instrumented, and then cardiac arrest was induced and sustained for 2 minutes. Cardiopulmonary resuscitation was initiated and continued for 2 minutes. Vasopressin was then administered via the TIO or IV route. Blood samples were collected for 4 minutes to determine the Cmax and Tmax of vasopressin. Concentration maximum and Tmax were calculated by use of liquid chromatography with mass spectrometry. RESULTS: There was no difference in ROSC between the TIO and IV groups (P = .63). The Cmax of vasopressin was significantly higher in the IV group compared to the TIO group (P = .017). However, there was no significant difference in ROSC, time to ROSC, or Tmax between groups (P > .05). All subjects had ROSC in both the IV and TIO groups, and none had ROSC in the control group. There was 225 times greater chance of survival for both the IV and TIO groups compared to the control group. CONCLUSION: The data support that the TIO is an effective route for vasopressin in a cardiac arrest model.

Investigation of the anxiolytic effects of xanthohumol, a component of humulus lupulus (Hops), in the male Sprague-Dawley rat.

The purpose of this study was to investigate the anxiolytic effects of xanthohumol, a component of Humulus lupulus (hops), and its potential interaction with the benzodiazepine binding site on the y-aminobutyric acid (GABAA) receptor in the male Sprague-Dawley rat. This was a prospective, randomized, between-subjects experimental study. Fifty-five rats were assigned to 1 Sof 5 groups with 11 rats per group: control (vehicle), xanthohumol, midazolam, midazolam with xanthohumol, and flumazenil with xanthohumol. In this study the elevated plus maze measured the behavioral components of anxiety and motor movements. A 2-tailed multivariate analysis of variance and least significant difference post hoc test was used to determine if a significant difference existed. Our data suggest that xanthohumol does not produce anxiolysis by modulation of the GABAA receptor; however, there may be a possible interaction between xanthohumol and midazolam, or xanthohumol may influence the modulation of another neurotransmitter site in the central nervous system. Alone, xanthohumol does not show significant modulation of the benzodiazepine receptor. Additional research should investigate if xanthohumol acts as a benzodiazepine GABAA partial agonist or antagonist or if it modulates another neurotransmitter system in the central nervous system.

Electrodeposition and analysis of thick bismuth films.

Due to its unique physical and chemical properties, bismuth is an attractive candidate for a wide range of applications such as battery anodes, radiation shielding, and semiconductors, to name a few. This work presents the electrodeposition of mechanically stable and homogenous bismuth films at micron-scale thicknesses. A simple one-step electrodeposition process using either a pulse/reverse or direct current source yielded thick, homogenous, and mechanically stable bismuth films. Morphology, electrochemical behavior, adhesion, and mechanical stability of bismuth coatings plated with varying parameters were characterized via optical profilometry, cyclic voltammetry, electron microscopy, and tribology. Scratch testing on thick electroplated coatings (> 100 µm) revealed similar wear resistance properties between the pulse/reverse plated and direct current electroplated films. This study presents a versatile bismuth electroplating process with the possibility to replace lead in radiation shields with an inexpensive, non-toxic metal, or to make industrially relevant electrocatalytic devices.

The effects of a human patient simulator vs. a CD-ROM on performance.

OBJECTIVES: Military health care personnel need to have skills relative to caring for patients on the battlefield. No studies have compared the two teaching strategies of using the human patient simulator (HPS) and a CD-ROM in caring for combat injuries. The objective of this study was to determine if there were statistically significant differences in HPS and CD-ROM educational strategies relative to caring for patients who have trauma. METHODS: A pretest/post-test prospective experimental design was used. Anesthesia students were randomly assigned to one of three groups: HPS, CD-ROM, or a control group. A valid and reliable instrument, Combat Performance, was used to evaluate the participant's ability to give care to trauma patients. RESULTS: A repeated analysis of variance and a least significant difference post hoc test were used to analyze the data. The HPS group performed better than the CD-ROM and control groups relative to performance (p = 0.001). There was no difference between the CD-ROM and control group (p = 0.171). DISCUSSION: We speculate that the HPS group performed better than the CD-ROM group because of the realism. CONCLUSION: In this study, the HPS method of instruction was a more effective method of teaching than the CD-ROM approach.

The effects of QuikClot Combat Gauze and movement on hemorrhage control in a porcine model.

The purpose of this study was twofold: (1) to examine the effectiveness of QuikClot Combat Gauze (QCG) compared to a control group and (2) investigate the effect of movement on hemorrhage control when QCG is employed. This was a prospective, experimental design employing an established porcine model of uncontrolled hemorrhage. The minimum number of animals (n = 11 per group) was used to obtain a statistically valid result. There were no statistically significant differences between the groups (p > 0.05) indicating that the groups were equivalent on the following parameters: activating clotting time, the subject weights, core body temperatures, amount of 1 minute hemorrhage, arterial blood pressures, and the amount and percentage of total blood volume. There were significant differences in the amount of hemorrhage (p = 0.018) and the number of movements (p = 0.000) between the QCG and control. QCG is statistically and clinically superior at controlling hemorrhage compared to the standard pressure dressing control group. Furthermore, it produces a more robust clot that can withstand significant movement. In conclusion, QCG is an effective hemostatic agent for use in civilian and military trauma management.

Comparison of tibial intraosseous, sternal intraosseous, and intravenous routes of administration on pharmacokinetics of epinephrine during cardiac arrest: a pilot study.

The purpose of this study was to determine and compare the maximum concentration (C(max)) and time to maximum concentration (T(max)) of epinephrine administered via tibial intraosseous (IO), sternal IO, and intravenous (i.v.) routes in a porcine model of cardiac arrest during cardiopulmonary resuscitation. Five pigs each were randomly assigned to 3 groups: tibial IO, sternal IO, and i.v. Cardiac arrest was induced with i.v. potassium chloride. After 2 minutes, cardiopulmonary resuscitation was initiated. Epinephrine was administered to each animal, and serial blood samples were collected over the next 3 minutes. Enzyme-linked immunosorbent assay was used to determine the epinephrine concentration. Multivariate analysis of variance helped determine if there were statistically significant differences between groups. There were significant differences in Cmax between the sternal IO and i.v. (P = .009) and tibial IO and i.v. (P = .03) groups but no significant difference between tibial and sternal IO groups (P = .75). Significant differences existed in Tmax between the tibial IO and i.v. (P = .04) and between tibial IO and sternal IO (P = .02) groups but no difference between the sternal IO and i.v. groups (P = .56). Intravenous administration of 1 mg of epinephrine resulted in a serum concentration 5.87 and 2.86 times greater than for the tibial and sternal routes, respectively.

Humerus Intraosseous and Intravenous Administration of Epinephrine in Normovolemic and Hypovolemic Cardiac Arrest Porcine Models.

OBJECTIVE: The aim of this study was to compare area under the curve (AUC), frequency, and odds of return of spontaneous circulation (ROSC) when epinephrine was administered in hypovolemic and normovolemic cardiac arrest models. METHODS: Twenty-eight adult swine were randomly assigned to 4 groups: HIO Normovolemia Group (HIONG); HIO Hypovolemia Group (HIOHG); IV Normovolemia (IVNG); and IV Hypovolemia Group (IVHG). Swine were anesthetized. The HIOH and IVH subjects were exsanguinated 35% of their blood volume. Each was placed into arrest. After 2 minutes, cardiopulmonary resuscitation was initiated. After another 2 minutes, 1 mg of epinephrine was given by IV or HIO routes; blood samples were collected over 5 minutes and analyzed by high-performance liquid chromatography. Subjects were defibrillated every 2 minutes. RESULTS: The AUC in the HIOHG was significantly less than both the HIONG (p = 0.047) and IVHG (p = 0.021). There were no other significant differences in the groups relative to AUC (p > 0.05). HIONG had a significantly higher occurrence of ROSC compared to HIOHG (p = 0.018) and IVH (p =0.018) but no other significant differences (p > 0.05). The odds of ROSC were 19.2 times greater for HIONG compared to the HIOHG. CONCLUSION: The study strongly supports the effectiveness of HIO administration of epinephrine and should be considered as a first-line intervention for patients in cardiac arrest related to normovolemic causes. However, our findings do not support using HIO access for epinephrine administration for patients in cardiac arrest related to hypovolemic reasons.

The effects of BleedArrest, Celox, and TraumaDex on hemorrhage control in a porcine model.

BACKGROUND: Hemorrhage is the second leading cause of death in civilian trauma and the leading cause of preventable death in military trauma. The purpose of this study was to examine the effectiveness of three hemostatic agents: BleedArrest, TraumaDex, and Celox. MATERIALS AND METHODS: This was a prospective, experimental study using male Yorkshire swine. The pigs (n = 5 per group) were randomly assigned to one of the following: BleedArrest, TraumaDex, Celox, or control. To simulate a trauma injury, the investigators generated a complex groin injury with transection of the femoral artery and vein in all pigs. After 1 min of uncontrolled hemorrhage, one of the hemostatic agents was poured into the wound, followed by standard wound packing. The control group underwent the same procedures with the exception of the hemostatic agents. In all groups, 5 min of direct manual pressure was applied to the wound followed by a standard pressure dressing. After 30 min, dressings were removed, and the amount of bleeding was determined. RESULTS: There were significant differences between the BleedArrest (mean = 21.2, SD ± 36.6 mL) TraumaDex (mean = 68, SD ± 103.5 mL) and Celox (mean = 18.l6, SD ± 41.6 mL) groups compared with Control group (mean = 230, SD ± 154 mL) (P < 0.05). However, there were no statistically significant difference between BleedArrest, TraumaDex, and Celox groups (P = 0.478). CONCLUSIONS: BleedArrest, Celox, and TraumaDex were statistically and clinically superior at controlling hemorrhage compared with the standard pressure dressing in the control group.

Effects of the HEET garment in the prevention of hypothermia in a porcine model.

BACKGROUND: Hypothermia is a common battlefield trauma occurrence. This study compared the effectiveness of the hypothermia, environmental, exposure, and trauma (HEET) garment (Trident Industries, Beaufort, SC) with and without thermal inserts with a control group of two wool blankets in the prevention of hypothermia in a treated hypovolemic porcine model. MATERIALS AND METHODS: Five female swine (Sus scrofa-Yorkshire cross) were assigned to each of three groups: HEET with thermal inserts (n=5); HEET without thermal inserts (n=5); or control (n=5). After the animals were anesthetized and stabilized for 30 min, the swine were hemorrhaged to a mean arterial pressure (MAP) of 30 mm Hg, simulating a battlefield injury. Hetastarch 6% (500 mL) was rapidly administered, simulating initial field resuscitation. One hour later, the animals' shed blood was reinfused, simulating transfusion at a field medical facility. The investigators moved the animal into a cooler set at 10°C ± 0.5°C. A pulmonary artery catheter was used to monitor core body temperature over a 6-h period. RESULTS: A repeated measures ANOVA and Tukey's post hoc test were used to analyze the data. There was a significant difference between the groups. At the end of 6h, the mean core temperature for the HEET with inserts group was 32.69°C ± 1.5; the HEET without inserts, 31.02°C ± 1.8; and control, 34.78°C ± 1.2 (P<0.05). While all groups became hypothermic, the wool blanket group was most effective in maintaining body temperature closer to normothermia. CONCLUSION: The HEET garments with and without heaters are ineffective in preventing hypothermia.

Effects of arterial blood pressure on rebleeding using Celox and TraumaDEX in a porcine model of lethal femoral injury.

This study was designed to identify the systolic blood pressure (SBP) and mean arterial pressure (MAP) at which rebleeding occurs when a clot is formed by a hemostatic agent, Celox or TraumaDEX, compared with a standard dressing. Fifteen pigs (5 each) were assigned randomly to 1 of 3 groups: Celox, TraumaDEX, or standard pressure dressing as a control. In all animals, the femoral artery and vein were transected to simulate traumatic injury. Subjects were allowed to hemorrhage 1 minute before treatment. Direct pressure was held 5 minutes followed by application of elastic dressings for 30 minutes. Dressings were removed after 30 minutes, and the wound was observed for rebleeding. Animals demonstrating hemostasis received phenylephrine infusion to increase SBP in 10-mm Hg increments until SBP reached 210 mm Hg or hemorrhage recurred. There were statistically significant differences between Celox (mean SBP, 166.4 mm Hg; mean MAP, 1376 mm Hg) and the control (mean SBP, 88.25 mm Hg; mean MAP, 59.7 mm Hg), and between TraumaDEX (mean SBP, 152.2 mm Hg; mean MAP, 113.2 mm Hg) and the control (P < .05). However, no statistically significant difference existed between Celox and TraumaDEX. Celox and TraumaDEX effectively prevent rebleeding compared with standard dressing.

Effects of Celox and TraumaDEX on hemorrhage control in a porcine model.

The purpose of this study was to compare the effectiveness of 2 hemostatic agents, chitosan-based Celox and the biopolymeric, microporous particles TraumaDEX, with a control group in a porcine model of hemorrhage. The animals were randomly assigned to 1 of 3 groups: Celox (n = 5), TraumaDEX (n = 5), or a standard pressure dressing alone (n = 5). To simulate a battlefield injury, the investigators generated a compound groin injury with transection of the femoral artery and vein in 15 pigs. After 1 minute of uncontrolled hemorrhage, Celox or TraumaDEX was poured into the wound, followed by standard wound packing. The control group underwent the same procedures with the exception of the hemostatic agents. In all groups, 5 minutes of direct manual pressure was applied to the wound, followed by a standard pressure dressing (3M Coban). After 30 minutes, dressings were removed, and the amount of bleeding was measured. There were statistically significant differences in bleeding between Celox and control (P = .01) and between TraumaDEX and control (P = .038), but no statistically significant difference in bleeding between Celox and TraumaDEX (P = .478). Celox and TraumaDEX may be effective hemostatic agents for use in civilian and military trauma.

Effects of humeral intraosseous epinephrine in a pediatric hypovolemic cardiac arrest porcine model.

BACKGROUND: Aims of the study were to determine the effects of humerus intraosseous (HIO) versus intravenous (IV) administration of epinephrine in a hypovolemic, pediatric pig model. We compared concentration maximum (Cmax), time to maximum concentration (Tmax), mean concentration (MC) over time and return of spontaneous circulation (ROSC). METHODS: Pediatric pig were randomly assigned to each group (HIO (n=7); IV (n=7); cardiopulmonary resuscitation (CPR)+defibrillation (defib) (n=7) and CPR-only group (n=5)). The pig were anesthetized; 35% of the blood volume was exsanguinated. pigs were in arrest for 2 min, and then CPR was performed for 2 min. Epinephrine 0.01 mg/kg was administered 4 min postarrest by either route. Samples were collected over 5 min. After sample collection, epinephrine was administered every 4 min or until ROSC. The Cmax and MC were analyzed using high-performance liquid chromatography. Defibrillation began at 3 min postarrest and administered every 2 min or until ROSC or endpoint at 20 min after initiation of CPR. RESULTS: Analysis indicated that the Cmax was significantly higher in the IV versus HIO group (p=0.001). Tmax was shorter in the IV group but was not significantly different (p=0.789). The MC was significantly greater in the IV versus HIO groups at 90 and 120 s (p<0.05). The IV versus HIO had a significantly higher MC (p=0.001). χ2 indicated the IV group (5 out of 7) had significantly higher rate of ROSC than the HIO group (1 out of 7) (p=0.031). One subject in the CPR+defib and no subjects in the CPR-only groups achieved ROSC. DISCUSSION: Based on the results of our study, the IV route is more effective than the HIO route.

The effects of QuikClot Combat Gauze and Celox Rapid on hemorrhage control.

OBJECTIVE: Compare QuikClot Combat Gauze (QCG) and Celox Rapid (CR) for initial hemostasis and over a 1-hour period. DESIGN: Experimental study. SETTING: Approved animal laboratory. SUBJECTS: Twenty-one Yorkshire swine. INTERVENTIONS: Subjects were randomly assigned to either the QCG (n = 11) or CR (n = 10) group. An arteriotomy was made in the right femoral artery with a 6-mm vascular punch. Bleeding was allowed for 45 seconds. QCG or CR was applied followed by firm pressure for 3 minutes according to Committee on Tactical Combat Casualty Care guidelines. A 10-pound weight simulating a pressure dressing was applied, and the wound was observed for 1 hour. Dressing failure was bleeding > 2 percent of blood volume. MAIN OUTCOME MEASURES: Achievement and maintenance of hemostasis and amount of hemorrhage during observation. Odds of successful hemostasis. RESULTS: QCG was significantly better than CR in initial hemostasis (p = 0.049) and maintaining hemostasis over 1 hour (p = 0.020). One hundred percent of QCG subjects and 70 percent of CR subjects achieved initial hemostasis. During the 1-hour observation, one additional CR subject failed to maintain hemostasis. CR had significantly more hemorrhage than QCG during the 1-hour observation (p = 0.027). QCG had no bleeding compared to CR that had a mean of 162 ± 48 mL (standard error of mean) over 2 minutes. QCG had 15.9 times greater odds of success compared to CR over a period of 1 hour. Over the 1-hour observation time, 100 percent of QCG achieved hemostasis compared to 60 percent of CR.

Inferring the capacity of the vector Poisson channel with a Bernoulli model.

The capacity defines the ultimate fidelity limits of information transmission by any system. We derive the capacity of parallel Poisson process channels to judge the relative effectiveness of neural population structures. Because the Poisson process is equivalent to a Bernoulli process having small event probabilities, we infer the capacity of multi-channel Poisson models from their Bernoulli surrogates. For neural populations wherein each neuron has individual innervation, inter-neuron dependencies increase capacity, the opposite behavior of populations that share a single input. We use Shannon's rate-distortion theory to show that for Gaussian stimuli, the mean-squared error of the decoded stimulus decreases exponentially in both the population size and the maximal discharge rate. Detailed analysis shows that population coding is essential for accurate stimulus reconstruction. By modeling multi-neuron recordings as a sum of a neural population, we show that the resulting capacity is much less than the population's, reducing it to a level that can be less than provided with two separated neural responses. This result suggests that attempting neural control without spike sorting greatly reduces the achievable fidelity. In contrast, single-electrode neural stimulation does not incur any capacity deficit in comparison to stimulating individual neurons.