Depth-varying rupture properties of subduction zone megathrust faults

Subduction zone plate boundary megathrust faults accommodate relative plate motions with spatially varying sliding behavior. The 2004 Sumatra-Andaman (M_w 9.2), 2010 Chile (Mw 8.8), and 2011 Tohoku (M_w 9.0) great earthquakes had similar depth variations in seismic wave radiation across their wide rupture zones – coherent teleseismic short-period radiation preferentially emanated from the deeper portion of the megathrusts whereas the largest fault displacements occurred at shallower depths but produced relatively little coherent short-period radiation. We represent these and other depth-varying seismic characteristics with four distinct failure domains extending along the megathrust from the trench to the downdip edge of the seismogenic zone. We designate the portion of the megathrust less than 15 km below the ocean surface as domain A, the region of tsunami earthquakes. From 15 to ∼35 km deep, large earthquake displacements occur over large-scale regions with only modest coherent short-period radiation, in what we designate as domain B. Rupture of smaller isolated megathrust patches dominate in domain C, which extends from ∼35 to 55 km deep. These isolated patches produce bursts of coherent short-period energy both in great ruptures and in smaller, sometimes repeating, moderate-size events. For the 2011 Tohoku earthquake, the sites of coherent teleseismic short-period radiation are close to areas where local strong ground motions originated. Domain D, found at depths of 30–45 km in subduction zones where relatively young oceanic lithosphere is being underthrust with shallow plate dip, is represented by the occurrence of low-frequency earthquakes, seismic tremor, and slow slip events in a transition zone to stable sliding or ductile flow below the seismogenic zone

Pediatric Patients with Intravascular Devices: Polymicrobial Bloodstream Infections and Risk Factors

A retrospective study was conducted, including 61 patients with long-term intravascular devices (IVDs) admitted to the Childrens Hospital Los Angeles with diverse underlying diseases, different types of catheters, and culture-proven catheter-related bloodstream infections (BSIs). Within these patients, 125 catheter-related BSIs occurred, and the incidence of monomicrobial and polymicrobial BSIs was evaluated. Risk factors for polymicrobial BSIs were determined. Forty-two BSIs contained more than one pathogen. These polymicrobial BSIs were observed more often in younger patients (<4.1 years versus ≥4.1 years) and less in patients using venous implanted ports. No other associations were found between the occurrences of polymicrobial BSIs and underlying diseases, other types of catheters, host defense status, parenteral nutrition, recurrences, or catheter removal. Patients with long-term IVDs at a younger age have a higher risk of developing a polymicrobial BSI. Future prospective studies should address the issue of polymicrobial infection in IVDs in more detail

Reflection and Remembrance: Oral histories and critical thinking

The research assignment for this class was to interview someone who lived through World War II. The interviewee could be someone who served in the military service, someone on the home front or even a child-anyone who was touched by the experience of World War II

Ethanol-lock technique for persistent bacteremia of long-term intravascular devices in pediatric patients

OBJECTIVES: To use the ethanol-lock technique (in conjunction with systemic antibiotics) to salvage central lines from removal and to prevent persistence of catheter-related infections among pediatric patients with long-term intravascular devices. DESIGN: Medical records of patients treated with ethanol locks were retrospectively reviewed from June 1, 2004, through June 22, 2005. SETTING: Childrens Hospital Los Angeles, Los Angeles, Calif, a tertiary care pediatric hospital.Patients Forty children with diverse underlying disorders were treated for 51 catheter-related infections using the Childrens Hospital Los Angeles ethanol-lock technique. INTERVENTIONS: Eligible infected central lines were instilled with a dose volume of 0.8 to 1.4 mL of 70% ethanol into the catheter lumen during 12 to 24 hours and then withdrawn. The volume of ethanol used was based on the type of intravascular device. MAIN OUTCOME MEASURES: Clearance of infection and incidence of recurrence. RESULTS: Of the 51 ethanol-lock treatments in 40 children, no catheters were removed because of persistent infection. Eighty-eight percent (45/51) of the treated episodes cleared without recurrence (defined as a relapse within 30 days with the same pathogen). Twelve (75%) of 16 polymicrobial isolates and 33 (94%) of 35 monomicrobial isolates were successfully treated. There were no adverse reactions or adverse effects reported. CONCLUSION: This retrospective study supports the use of the ethanol-lock technique in conjunction with systemic antibiotics as an effective and safe method to retain the use of a previously infected central venous catheter, decrease the need for line removal, and eradicate persistent pathogens in catheter-related infection

Repurposing Cytarabine for Treating Primary Effusion Lymphoma by Targeting Kaposi’s Sarcoma-Associated Herpesvirus Latent and Lytic Replications

Oncogenic Kaposi’s sarcoma-associated herpesvirus (KSHV) is etiologically linked to primary effusion lymphoma (PEL), an aggressive and nontreatable malignancy commonly found in AIDS patients. In this study, we performed a high-throughput screening of 3,731 characterized compounds and identified cytarabine, approved by the FDA for treating numerous types of cancer, as a potent inhibitor of KSHV-induced PEL. We showed the high efficacy of cytarabine in the growth inhibition of various PEL cells by inducing cell cycle arrest and apoptosis. Cytarabine inhibited host DNA and RNA syntheses and therefore induced cellular cytotoxicity. Furthermore, cytarabine inhibited viral DNA and RNA syntheses and induced the rapid degradation of KSHV major latent protein LANA (latency-associated nuclear antigen), leading to the suppression of KSHV latent replication. Importantly, cytarabine effectively inhibited active KSHV replication and virion production in PEL cells. Finally, cytarabine treatments not only effectively inhibited the initiation and progression of PEL tumors but also induced regression of grown PEL tumors in a xenograft mouse model. Altogether, our study has identified cytarabine as a novel therapeutic agent for treating PEL as well as eliminating KSHV persistent infection.Primary effusion lymphoma is an aggressive malignancy caused by Kaposi’s sarcoma-associated herpesvirus. The outcome of primary effusion lymphoma is dismal without specific treatment. Through a high-throughput screening of characterized compounds, we identified an FDA-approved compound, cytarabine, as a potent inhibitor of primary effusion lymphoma. We showed that cytarabine induced regression of PEL tumors in a xenograft mouse model. Cytarabine inhibited host and viral DNA and RNA syntheses, resulting in the induction of cytotoxicity. Of interest, cytarabine induced the degradation of KSHV major latent protein LANA, hence suppressing KSHV latent replication, which is required for PEL cell survival. Furthermore, cytarabine inhibited KSHV lytic replication program, preventing virion production. Our findings identified cytarabine as a novel therapeutic agent for treating PEL as well as for eliminating KSHV persistent infection. Since cytarabine is already approved by the FDA, it might be an ideal candidate for repurposing for PEL therapy and for further evaluation in advanced clinical trials