Highly sensitive and ultrafast read mapping for RNA-seq analysis.

As sequencing technologies progress, the amount of data produced grows exponentially, shifting the bottleneck of discovery towards the data analysis phase. In particular, currently available mapping solutions for RNA-seq leave room for improvement in terms of sensitivity and performance, hindering an efficient analysis of transcriptomes by massive sequencing. Here, we present an innovative approach that combines re-engineering, optimization and parallelization. This solution results in a significant increase of mapping sensitivity over a wide range of read lengths and substantial shorter runtimes when compared with current RNA-seq mapping methods available.

Genome-wide association study of bipolar disorder in European American and African American individuals.

To identify bipolar disorder (BD) genetic susceptibility factors, we conducted two genome-wide association (GWA) studies: one involving a sample of individuals of European ancestry (EA; n=1001 cases; n=1033 controls), and one involving a sample of individuals of African ancestry (AA; n=345 cases; n=670 controls). For the EA sample, single-nucleotide polymorphisms (SNPs) with the strongest statistical evidence for association included rs5907577 in an intergenic region at Xq27.1 (P=1.6 x 10(-6)) and rs10193871 in NAP5 at 2q21.2 (P=9.8 x 10(-6)). For the AA sample, SNPs with the strongest statistical evidence for association included rs2111504 in DPY19L3 at 19q13.11 (P=1.5 x 10(-6)) and rs2769605 in NTRK2 at 9q21.33 (P=4.5 x 10(-5)). We also investigated whether we could provide support for three regions previously associated with BD, and we showed that the ANK3 region replicates in our sample, along with some support for C15Orf53; other evidence implicates BD candidate genes such as SLITRK2. We also tested the hypothesis that BD susceptibility variants exhibit genetic background-dependent effects. SNPs with the strongest statistical evidence for genetic background effects included rs11208285 in ROR1 at 1p31.3 (P=1.4 x 10(-6)), rs4657247 in RGS5 at 1q23.3 (P=4.1 x 10(-6)), and rs7078071 in BTBD16 at 10q26.13 (P=4.5 x 10(-6)). This study is the first to conduct GWA of BD in individuals of AA and suggests that genetic variations that contribute to BD may vary as a function of ancestry.

Hemodynamic support in fluid-refractory pediatric septic shock.

OBJECTIVE: Assess outcome in children treated with inotrope, vasopressor, and/or vasodilator therapy for reversal of fluid-refractory and persistent septic shock. DESIGN: Survey; case series. SETTING: Three pediatric hospitals. PATIENTS: Fifty consecutive patients with fluid-refractory septic shock with a pulmonary artery catheter within 6 hours of resuscitation. INTERVENTIONS: Patients were categorized according to hemodynamic state and use of inotrope, vasopressor, and/or vasodilator therapy to maintain cardiac index (CI) >3.3 L/min/m2 and systemic vascular resistance >800 dyne-sec/cm/m to reverse shock. OUTCOME MEASURES: Hemodynamic state, response to class of cardiovascular therapy, and mortality. RESULTS: After fluid resuscitation, 58% of the children had a low CI and responded to inotropic therapy with or without a vasodilator (group I), 20% had a high CI and low systemic vascular resistance and responded to vasopressor therapy alone (group II), and 22% had both vascular and cardiac dysfunction and responded to combined vasopressor and inotropic therapy (group III). Shock persisted in 36% of the children. Of the children in group I, 50% needed the addition of a vasodilator, and in group II, 50% of children needed the addition of an inotrope for evolving myocardial dysfunction. Four children showed a complete change in hemodynamic state and responded to a switch from inotrope to vasopressor therapy or vice versa. The overall 28-day survival rate was 80% (group I, 72%; group II, 90%; group III, 91%). CONCLUSIONS: Unlike adults, children with fluid-refractory shock are frequently hypodynamic and respond to inotrope and vasodilator therapy. Because hemodynamic states are heterogeneous and change with time, an incorrect cardiovascular therapeutic regimen should be suspected in any child with persistent shock. Outcome can be improved compared with historical literature.

Overview of a general orthopedic practice.

Records from a 36-year general orthopedic practice were analyzed for patient demographics and clinical findings. Results showed that low back pain was the most frequent chief complaint and that the majority of the cases were treated nonsurgically in the office. A history of trauma was present in 58.8% of cases, and job-related injuries were present in 10.6% of cases. The most frequent diagnoses are reported for all cases and for some subgroups.

Electromyographic activity of selected shoulder muscles in commonly used therapeutic exercises.

BACKGROUND AND PURPOSE: The purpose of this study was to evaluate and compare the muscle activity of the supraspinatus, infraspinatus, teres minor, and lower trapezius muscles during commonly prescribed therapeutic exercises in subjects with and without shoulder pathology. SUBJECTS: Twenty healthy subjects (9 male, 11 female) and 20 subjects with recurrent unilateral shoulder pain and weakness (14 male, 6 female), aged 18 to 40 years (mean = 28, SD = 5.8), participated in this study. METHODS: Subjects performed each of the following exercises using a hand-held weight: prone lateral (external) rotation, sidelying lateral rotation, and arm elevation in the scapular plane. Indwelling fine-wire electrodes recorded electromyographic (EMG) activity during each exercise. The EMG activity in five phases of concentric contraction of each exercise was averaged and divided into three equal time intervals. Mean EMG values normalized to maximal activity for the entire phase of concentric contraction and for each of the three intervals were used in subsequent analyses. RESULTS: Two-way repeated-measures analyses of variance (ANOVAs) revealed between-group differences only in the prone lateral rotation exercise. Compared with subjects without shoulder pathology, subjects with shoulder pain showed significantly greater EMG activity in the infraspinatus muscle and less activity in the supraspinatus muscle during this exercise. CONCLUSION AND DISCUSSION: These results suggest that the pattern of muscle activation during specific shoulder movements in patients with shoulder pain may be related to pathology. Future studies are needed to determine whether an imbalance in neuromuscular control is a factor contributing directly to shoulder dysfunction or whether such an imbalance is secondary to some pathology.

Amrinone during porcine intraperitoneal sepsis.

Seven Yucatan minipigs with chronic, severe intraperitoneal sepsis were given amrinone i.v. (loading dose of 0.75 mg/kg, followed by continuous infusion of 10, 20, 40, and 80 micrograms/kg/min) during the hyperdynamic phase of sepsis. Hemodynamic variables and oxygen utilization, delivery, and extraction were recorded throughout the study. Pulmonary capillary wedge pressure was kept constant to ensure a fixed ventricular filling pressure. Intravenous amrinone modestly augmented cardiac index without altering heart rate. Mean systemic and pulmonary arterial pressures decreased. Systemic and pulmonary vascular resistance fell significantly (P less than 0.05). Amrinone did not significantly alter oxygen utilization or oxygen extraction, although oxygen delivery increased (P less than .05). During the hyperdynamic phase of sepsis in this animal model, amrinone elicits vasodilatation with a modest improvement in stroke volume index. Consequently, cardiac output and oxygen delivery increased modestly. Because of its vasodilating properties and small salutary effects, amrinone is not an optimal first-line medication for hemodynamic stabilization during hyperdynamic sepsis.

Awake porcine model of intraperitoneal sepsis and altered oxygen utilization.

We have characterized an awake swine model of septic shock. Hemodynamic, serum chemistry, and oxygen metabolism parameters were compared between eight septic and five sham animals. Eight male Yucatan miniature swine, weighing 20-28 kg, were anesthetized and catheters were placed in the pulmonary artery, external jugular, and the carotid artery. On day 2, 1.1-4.0 x 10(10) cfu Escherichia coli/kg were administered via an intraperitoneal catheter. Hemodynamic parameters were monitored hourly for 6 hours in awake animals. The animals were then placed back into the animal holding facility for clinical observation until the 24 hour post infusion measurements were taken. Septic animals were initially hypodynamic, with a decrease in cardiac index (CI) from a baseline value of 152.8 +/- 24.8 to 87.9 +/- 17.8 ml/kg/min (P less than .05) and an increased systemic vascular resistance index (SVRI) from a control value of 48.1 +/- 9.5 to 65.0 +/- 16.7 dynes*sec*cm-5/kg. At 24 hours post infusion, the animals were hyperdynamic with the CI increased to 211.0 +/- 27.2 ml/kg/min (P less than .05) and a decreased SVRI to 30.64 +/- 3.9 dynes*sec*cm-5/kg (P less than .05). Oxygen utilization (VO2) increased during sepsis from 6.6 +/- 0.8 to 8.1 +/- 0.8 ml/kg/min at 6 hours (P less than .05) and remained elevated at 24 hours at 7.7 +/- 0.4 (P less than .05). Increased oxygen consumption was attained with an increase in oxygen extraction (O2 ext) from 0.34 +/- 0.03 to 0.56 +/- 0.07 (P less than .05) during the first 6 hours of sepsis. At 24 hours, increased oxygen utilization was maintained by high oxygen delivery state. Significant alterations in serum chemistries in conjunction with post mortem evidence of multiple organ system failure were observed. Mortality on or before 4 days post infusion was 50% and positive blood cultures were obtained in 38% of the animals studied. This awake swine model serves as an excellent model to study metabolic pathophysiology and the treatment of septic shock.