Untangling the environmental and tectonic drivers of the Noto earthquake swarm in Japan.

The underlying mechanism of the ongoing seismic swarm in the Noto Peninsula, Japan, which generates earthquakes at 10 times the average regional rate, remains elusive. We capture the evolution of the subsurface stress state by monitoring changes in seismic wave velocities over an 11-year period. A sustained long-term increase in seismic velocity that is seasonally modulated drops before the earthquake swarm. We use a three-dimensional hydromechanical model to quantify environmentally driven variations in excess pore pressure, revealing its crucial role in governing the seasonal modulation with a stress sensitivity of 6 × 10-9 per pascal. The decrease in seismic velocity aligns with vertical surface uplift, suggesting potential fluid migration from a high-pore pressure zone at depth. Stress changes induced by abnormally intense snow falls contribute to initiating the swarm through subsequent perturbations to crustal pore pressure.

Gastrointestinal complications after cardiac surgery.

Gastrointestinal complications after cardiac surgery are relatively rare entities but carry a high mortality. We identified over 70 articles written since 2010 using the PubMed database. We included 40 in our review. The most common complications include paralytic ileus, gastrointestinal bleeding, and bowel ischemia. Patients who undergo cardiac procedures are at risk for poor perfusion of the gastrointestinal tract and, thus, at risk for resulting complications. Risk factors for these complications include peri-operative use of vasopressors, prolonged operative time, and the time of cardiopulmonary bypass. Presentation of gastrointestinal complications tends to differ as patients after open heart surgery can remain intubated, and exams can be limited. Early recognition and aggressive therapy are paramount. We aim to provide a review that will help the reader get familiar with the most common gastrointestinal complications that can negatively affect outcomes after cardiac surgery.

The Prognostic Role of Platelet-to-Lymphocyte Ratio in Acute Coronary Syndromes: A Systematic Review and Meta-Analysis.

This study aimed to investigate the potential prognostic role of the platelet-to-lymphocyte (PLR) ratio in patients presenting with suspected acute coronary syndromes (ACS). A systematic search of PubMed Central, Scopus, EMBASE, and the Cochrane Library from conception through 20 August 2023 was conducted. We used odds ratios (OR) as the effect measure with 95% confidence intervals (CIs) for dichotomous data and mean differences (MD) with a 95% CI for continuous data. If I2 was less than 50% or the p value of the Q tests was less than 0.05, a random synthesis analysis was conducted. Otherwise, a fixed pooled meta-analysis was performed. Nineteen studies fulfilled the eligibility criteria and were included in the meta-analysis. PLR was higher in MACE-positive (164.0 ± 68.6) than MACE-negative patients (115.3 ± 36.9; MD = 40.14; 95% CI: 22.76 to 57.52; p < 0.001). Pooled analysis showed that PLR was higher in AMI patients who died (183.3 ± 30.3), compared to survivors (126.2 ± 16.8; MD = 39.07; 95% CI: 13.30 to 64.84; p = 0.003). It was also higher in the ACS vs. control group (168.2 ± 81.1 vs. 131.9 ± 37.7; MD = 39.01; 95% CI: 2.81 to 75.21; p = 0.03), STEMI vs. NSTEMI cohort (165.5 ± 92.7 vs. 159.5 ± 87.8; MD = 5.98; 95% CI: -15.09 to 27.04; p = 0.58), and MI vs. UAP populations (162.4 ± 90.0 vs. 128.2 ± 64.9; MD = 18.28; 95% CI: -8.16 to 44.71; p = 0.18). Overall, our findings confirmed the potential prognostic role of the plate-let-to-lymphocyte (PLR) ratio in patients presenting with suspected acute coronary syndromes (ACS). Its use as a risk stratification tool should be examined prospectively to define its capability for evaluation in cardiovascular patients.

Uncovering the effects of COVID-19 on in-hospital cardiac arrest - a living systematic review and meta-analysis.

INTRODUCTION AND OBJECTIVE: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused a global pandemic and had a negative impact on the entire health care system. To understand the effect of COVID-19 on outcomes of in-hospital cardiac arrest (IHCA), a systematic review and meta-analysis of studies was designed to compare the pre- and intra-pandemic periods of adult patients who suffered cardiac arrest, and additionally by performing a sub-analysis related to COVID-19 positive vs. negative patients in the same group of patients. MATERIAL AND METHODS: To evaluate the impact of COVID-19 on IHCA outcomes a systematic review and meta-analysis was performed. Pubmed (MEDLINE), Scopus, Embase, Web of Science, and Cochrane database were searched for articles published from 1 January 2020 - 8 April 2023. RESULTS: Return of spontaneous circulation events among IHCA patients in pre-COVID-19 and COVID-19 pandemic periods varied and amounted to 64.0% vs. 60.0%, respectively (OR=1.23; 95%CI: 1.19 to 1.26; p<0.001). Re-arrest occurrence was 4.5% vs. 4.9%, respectively (OR=1.24; 95%CI: 1.00 to 1.53; p=0.05). Survival to hospital discharge (SHD) was 25.1% compared to 20.9% for COVID-19 period (OR = 1.17; 95%CI: 0.96 to 1.41; p=0.12). During the COVID-19 period, SHD in COVID-19 positive patients was 14.0% compared to 25.9% for patients without COVID-19 (OR=0.72; 95%CI: 0.28 to 1.86; p=0.50). 30-day survival rate among COVID-19 positive vs. negative patients was 62.6% vs. 58.3%, respectively (OR =0.99; 95%CI: 0.23 to 4.24; p=0.99). CONCLUSIONS: Patients with SARS-CoV-2 infection had reduced rates of ROSC and SDH, as well as poorer neurologic outcomes and increased in hospital re-arrests during the COVID-19 period. However, the 30-day survival rate was similar in SARS-CoV-2 positive and negative patients.

What makes low-frequency earthquakes low frequency.

Low-frequency earthquakes, atypical seismic events distinct from regular earthquakes, occur downdip of the seismogenic megathrust where an aseismic rheology dominates the subduction plate boundary. Well situated to provide clues on the slip regime of this unique faulting environment, their distinctive waveforms reflect either an unusual rupture process or unusually strong attenuation in their source zone. We take advantage of the unique geometry of seismicity in the Nankai Trough to isolate the spectral signature of low-frequency earthquakes after correcting for empirically derived attenuation. We observe that low-frequency earthquake spectra are consistent with the classical earthquake model, yet their rupture duration and stress drop are orders of magnitude different from ordinary earthquakes. We conclude their low-frequency nature primarily results from an atypical seismic rupture process rather than near-source attenuation.

Systematic review with meta-analysis of mid-regional pro-adrenomedullin (MR-proadm) as a prognostic marker in Covid-19-hospitalized patients.

BACKGROUND: Mid-regional pro-adrenomedullin (MR-proADM) is useful for risk stratification in patients with sepsis and respiratory infections. The study's purpose was to assess the available data and determine the association between MR-proADM levels and mortality in COVID-19 participants. METHODS: A comprehensive literature search of medical electronic databases was performed including PubMed, Web of Science, Scopus, Cochrane, and grey literature for relevant data published from 1 January 2020, to 20 November 2022. Mean differences (MD) with 95% confidence intervals (CI) were calculated. RESULTS: Fourteen studies reported MR-proADM levels in survivors vs. non-survivors of COVID-19 patients. Pooled analysis showed that MR-proADM level in the survivor group was 0.841 ± 0.295 nmol/L for patients who survive COVID-19, compared to 1.692 ± 0.761 nmol/L for non-survivors (MD = -0.78; 95%CI: -0.92 to -0.64; p < 0.001). CONCLUSIONS: The main finding of this study is that mortality of COVID-19 is linked to MR-proADM levels, according to this meta-analysis. The use of MR-proADM might be extremely beneficial in triaging, assessing probable therapy escalation, predicting potential complications during therapy or significant clinical deterioration of patients, and avoiding admission which may not be necessary. Nevertheless, in order to confirm the obtained data, it is necessary to conduct large prospective studies that will address the potential diagnostic role of MR-proADM as a marker of COVID-19 severity.KEY MESSAGESSeverity of COVID-19 seems to be linked to MR-proADM levels and can be used as a potential marker for predicting a patient's clinical course.The use of MR-proADM might be beneficial in triaging, assessing probable therapy escalation, predicting potential complications during therapy or significant clinical deterioration of patients, and avoiding admission which may not be necessary.For patients with COVID-19, MR-proADM may be an excellent prognostic indicator because it is a marker of endothelial function that may predict the precise impact on the equilibrium between vascular relaxation and contraction and lowers platelet aggregation inhibitors, coagulation inhibitors, and fibrinolysis activators in favor of clotting factors.

The effect of zinc supplementation on the course of COVID-19 - A systematic review and meta-analysis.

INTRODUCTION AND OBJECTIVE: Zinc is a trace element that plays a role in stimulating innate and acquired immunity. The aim of the study was to determine the antiviral effect of the administration of zinc in COVID-19 patients. MATERIAL AND METHODS: A literature search was performed in P Web of Science, PubMed, Scopus and Cochrane databases from 1 January 2020 - 22 August 2022. In addition, reference lists of the included articles and their related citations in PubMed were also reviewed for additional pertinent studies. RESULTS: A total of 9 eligible studies were identified. In-hospital mortality in zinc supplementation patients, and patients treated without zinc, varied and amounted to 21.6% vs. 23.04% difference (OR=0.71; 95%CI: 0.62-0.81; p<0.001). 28-day to 30-day mortality in patients treated with zinc was 7.7%, compared to 11.9% for patients treated without zinc (OR=0.61; 95%CI: 0.35-1.06; p=0.08). In-hospital adverse events among patients treated with and without COVID-19 did not show any statistically significant differences in relation to acute kidney injury occurrence (12.8% vs. 12.4%, respectively; OR=0.63; 95%CI: 0.19-2.12; p=0.45, as well as need for mechanical ventilation (13.2% vs. 14.1%; OR=0.83; 95%CI: 0.52-1.32; p=0.43). CONCLUSIONS: Zinc supplementation is associated with lower COVID-19 in-hospital mortality. Additionally, it is risk-free in COVID-19 patients since there have been no negative side effects, such as acute renal damage or the requirement for mechanical ventilation compared to patients without COVID-19. Due to scientific evidence and the role it represents in the human body, zinc supplementation should be taken into consideration for COVID-19 patients as an adjunct therapy.

Efficacy and Safety of Video-Laryngoscopy versus Direct Laryngoscopy for Double-Lumen Endotracheal Intubation: A Systematic Review and Meta-Analysis.

The available meta-analyses have inconclusively indicated the advantages of video-laryngoscopy (VL) in different clinical situations; therefore, we conducted a systematic review and meta-analysis to determine efficacy outcomes such as successful first attempt or time to perform endotracheal intubation as well as adverse events of VL vs. direct laryngoscopes (DL) for double-lumen intubation. First intubation attempt success rate was 87.9% for VL and 84.5% for DL (OR = 1.64; 95% CI: 0.95 to 2.86; I2 = 61%; p = 0.08). Overall success rate was 99.8% for VL and 98.8% for DL, respectively (OR = 3.89; 95%CI: 0.95 to 15.93; I2 = 0; p = 0.06). Intubation time for VL was 43.4 ± 30.4 s compared to 54.0 ± 56.3 s for DL (MD = -11.87; 95%CI: -17.06 to -6.68; I2 = 99%; p < 0.001). Glottic view based on Cormack-Lehane grades 1 or 2 equaled 93.1% and 88.1% in the VL and DL groups, respectively (OR = 3.33; 95% CI: 1.18 to 9.41; I2 = 63%; p = 0.02). External laryngeal manipulation was needed in 18.4% cases of VL compared with 42.8% for DL (OR = 0.28; 95% CI: 0.20 to 0.40; I2 = 69%; p < 0.001). For double-lumen intubation, VL offers shorter intubation time, better glottic view based on Cormack-Lehane grade, and a lower need for ELM, but comparable first intubation attempt success rate and overall intubation success rate compared with DL.

The Influence of COVID-19 on Out-Hospital Cardiac Arrest Survival Outcomes: An Updated Systematic Review and Meta-Analysis.

Cardiopulmonary resuscitation in patients with out-of-hospital cardiac arrest (OHCA) is associated with poor prognosis. Because the COVID-19 pandemic may have impacted mortality and morbidity, both on an individual level and the health care system as a whole, our purpose was to determine rates of OHCA survival since the onset of the SARS-CoV2 pandemic. We conducted a systematic review and meta-analysis to evaluate the influence of COVID-19 on OHCA survival outcomes according to the PRISMA guidelines. We searched the literature using PubMed, Scopus, Web of Science and Cochrane Central Register for Controlled Trials databases from inception to September 2021 and identified 1775 potentially relevant studies, of which thirty-one articles totaling 88,188 patients were included in this meta-analysis. Prehospital return of spontaneous circulation (ROSC) in pre-COVID-19 and COVID-19 periods was 12.3% vs. 8.9%, respectively (OR = 1.40; 95%CI: 1.06-1.87; p < 0.001). Survival to hospital discharge in pre- vs. intra-COVID-19 periods was 11.5% vs. 8.2% (OR = 1.57; 95%CI: 1.37-1.79; p < 0.001). A similar dependency was observed in the case of survival to hospital discharge with the Cerebral Performance Category (CPC) 1-2 (6.7% vs. 4.0%; OR = 1.71; 95%CI: 1.35-2.15; p < 0.001), as well as in the 30-day survival rate (9.2% vs. 6.4%; OR = 1.63; 95%CI: 1.13-2.36; p = 0.009). In conclusion, prognosis of OHCA is usually poor and even worse during COVID-19.

Direct vs. Video-Laryngoscopy for Intubation by Paramedics of Simulated COVID-19 Patients under Cardiopulmonary Resuscitation: A Randomized Crossover Trial.

A safe way of securing the airway with an endotracheal tube is one of the priorities of an advanced cardiovascular life support algorithm for suspected or confirmed COVID-19 patients. The aim of this study was to compare intubation success rates (ISR) and intubation time (IT) of different laryngoscopes for simulated COVID-19 patients under cardiopulmonary resuscitation. The study was designed as a prospective, randomized, crossover trial. Fifty four active paramedics performed endotracheal intubation with a Macintosh direct laryngoscope (MAC) and McGrath videolaryngoscope (McGrath) with and without personal protective equipment (PPE). Without PPE, ISRs were 87% and 98% for MAC and McGrath, respectively (p = 0.32). ITs were 22.5 s (IQR: 19-26) and 19.5 s (IQR: 17-21) for MAC and McGrath, respectively (p = 0.005). With PPE, first-pass ISR were 30% and 89% with MAC and McGrath, respectively (p < 0.001). The overall success rates were 83% vs. 100% (p = 0.002). Median ITs were 34.0 s (IQR: 29.5-38.5) and 24.8 s (IQR: 21-29) for MAC and McGrath, respectively (p < 0.001). In conclusion, the McGrath videolaryngoscope appears to possess significant advantages over the Macintosh direct laryngoscope when used by paramedics in suspected or confirmed COVID-19 intubation scenarios.

Flight tone characterisation of the South American malaria vector Anopheles darlingi (Diptera: Culicidae).

BACKGROUND: Flight tones play important roles in mosquito reproduction. Several mosquito species utilise flight tones for mate localisation and attraction. Typically, the female wingbeat frequency (WBF) is lower than males, and stereotypic acoustic behaviors are instrumental for successful copulation. Mosquito WBFs are usually an important species characteristic, with female flight tones used as male attractants in surveillance traps for species identification. Anopheles darlingi is an important Latin American malaria vector, but we know little about its mating behaviors. OBJECTIVES: We characterised An. darlingi WBFs and examined male acoustic responses to immobilised females. METHODS: Tethered and free flying male and female An. darlingi were recorded individually to determine their WBF distributions. Male-female acoustic interactions were analysed using tethered females and free flying males. FINDINGS: Contrary to most mosquito species, An. darlingi females are smaller than males. However, the male's WBF is ~1.5 times higher than the females, a common ratio in species with larger females. When in proximity to a female, males displayed rapid frequency modulations that decreased upon genitalia engagement. Tethered females also modulated their frequency upon male approach, being distinct if the interaction ended in copulation or only contact. MAIN CONCLUSIONS: This is the first report of An. darlingi flight acoustics, showing that its precopulatory acoustics are similar to other mosquitoes despite the uncommon male:female size ratio, suggesting that WBF ratios are common communication strategies rather than a physical constraint imposed by size.

Flight tone characterisation of the South American malaria vector Anopheles darlingi (Diptera: Culicidae)

BACKGROUND Flight tones play important roles in mosquito reproduction. Several mosquito species utilise flight tones for mate localisation and attraction. Typically, the female wingbeat frequency (WBF) is lower than males, and stereotypic acoustic behaviors are instrumental for successful copulation. Mosquito WBFs are usually an important species characteristic, with female flight tones used as male attractants in surveillance traps for species identification. Anopheles darlingi is an important Latin American malaria vector, but we know little about its mating behaviors. OBJECTIVES We characterised An. darlingi WBFs and examined male acoustic responses to immobilised females. METHODS Tethered and free flying male and female An. darlingi were recorded individually to determine their WBF distributions. Male-female acoustic interactions were analysed using tethered females and free flying males. FINDINGS Contrary to most mosquito species, An. darlingi females are smaller than males. However, the male's WBF is ~1.5 times higher than the females, a common ratio in species with larger females. When in proximity to a female, males displayed rapid frequency modulations that decreased upon genitalia engagement. Tethered females also modulated their frequency upon male approach, being distinct if the interaction ended in copulation or only contact. MAIN CONCLUSIONS This is the first report of An. darlingi flight acoustics, showing that its precopulatory acoustics are similar to other mosquitoes despite the uncommon male:female size ratio, suggesting that WBF ratios are common communication strategies rather than a physical constraint imposed by size.

Daily measurement of slow slip from low-frequency earthquakes is consistent with ordinary earthquake scaling.

Slow slip transients on faults can last from seconds to months and stitch together the earthquake cycle. However, no single geophysical instrument is able to observe the full range of slow slip because of bandwidth limitations. Here, we connect seismic and geodetic data from the Mexican subduction zone to explore an instrumental blind spot. We establish a calibration of the daily median amplitude of the seismically recorded low-frequency earthquakes to the daily geodetically recorded moment rate of previously established slow slip events. This calibration allows us to use the precise evolution of low-frequency earthquake activity to quantitatively measure the moment of smaller, subdaily slip events that are unresolvable by geodesy alone. The resulting inferred slow slip moments scale with duration and inter-event time like ordinary earthquakes. These new quantifications help connect slow and fast events in a broad spectrum of transient slip and suggest that slow slip events behave much like ordinary earthquakes.

CD8+ lymphocytes but not B lymphocytes are required for protection against chronic hepatitis E virus infection in chickens.

Hepatitis E is an important global disease, causing outbreaks of acute hepatitis in many developing countries and sporadic cases in industrialized countries. Hepatitis E virus (HEV) infection typically causes self-limiting acute hepatitis but can also progress to chronic disease in immunocompromised individuals. The immune response necessary for the prevention of chronic infection is T cell-dependent; however, the arm of cellular immunity responsible for this protection is not currently known. To investigate the contribution of humoral immunity in control of HEV infection and prevention of chronicity, we experimentally infected 20 wild-type (WT) and 18 immunoglobulin knockout (JH-KO) chickens with a chicken strain of HEV (avian HEV). Four weeks postinfection (wpi) with avian HEV, JH-KO chickens were unable to elicit anti-HEV antibody but had statistically significantly lower liver lesion scores than the WT chickens. At 16 wpi, viral RNA in fecal material and liver, and severe liver lesions were undetectable in both groups. To determine the role of cytotoxic lymphocytes in the prevention of chronicity, we infected 20 WT and 20 cyclosporine and CD8+ antibody-treated chickens with the same strain of avian HEV. The CD8 + lymphocyte-depleted, HEV-infected chickens had higher incidences of prolonged fecal viral shedding and statistically significantly higher liver lesion scores than the untreated, HEV-infected birds at 16 wpi. The results indicate that CD8 + lymphocytes are required for viral clearance and reduction of liver lesions in HEV infection while antibodies are not necessary for viral clearance but may contribute to the development of liver lesions in acute HEV infection.

Revealing the cluster of slow transients behind a large slow slip event.

Capable of reaching similar magnitudes to large megathrust earthquakes [Mw (moment magnitude) > 7], slow slip events play a major role in accommodating tectonic motion on plate boundaries through predominantly aseismic rupture. We demonstrate here that large slow slip events are a cluster of short-duration slow transients. Using a dense catalog of low-frequency earthquakes as a guide, we investigate the Mw 7.5 slow slip event that occurred in 2006 along the subduction interface 40 km beneath Guerrero, Mexico. We show that while the long-period surface displacement, as recorded by Global Positioning System, suggests a 6-month duration, the motion in the direction of tectonic release only sporadically occurs over 55 days, and its surface signature is attenuated by rapid relocking of the plate interface. Our proposed description of slow slip as a cluster of slow transients forces us to re-evaluate our understanding of the physics and scaling of slow earthquakes.

Extracorporeal cellular therapy (ELAD) in severe alcoholic hepatitis: A multinational, prospective, controlled, randomized trial.

Severe alcoholic hepatitis (sAH) is associated with a poor prognosis. There is no proven effective treatment for sAH, which is why early transplantation has been increasingly discussed. Hepatoblastoma-derived C3A cells express anti-inflammatory proteins and growth factors and were tested in an extracorporeal cellular therapy (ELAD) study to establish their effect on survival for subjects with sAH. Adults with sAH, bilirubin ≥8 mg/dL, Maddrey's discriminant function ≥ 32, and Model for End-Stage Liver Disease (MELD) score ≤ 35 were randomized to receive standard of care (SOC) only or 3-5 days of continuous ELAD treatment plus SOC. After a minimum follow-up of 91 days, overall survival (OS) was assessed by using a Kaplan-Meier survival analysis. A total of 203 subjects were enrolled (96 ELAD and 107 SOC) at 40 sites worldwide. Comparison of baseline characteristics showed no significant differences between groups and within subgroups. There was no significant difference in serious adverse events between the 2 groups. In an analysis of the intent-to-treat population, there was no difference in OS (51.0% versus 49.5%). The study failed its primary and secondary end point in a population with sAH and with a MELD ranging from 18 to 35 and no upper age limit. In the prespecified analysis of subjects with MELD < 28 (n = 120), ELAD was associated with a trend toward higher OS at 91 days (68.6% versus 53.6%; P = .08). Regression analysis identified high creatinine and international normalized ratio, but not bilirubin, as the MELD components predicting negative outcomes with ELAD. A new trial investigating a potential benefit of ELAD in younger subjects with sufficient renal function and less severe coagulopathy has been initiated. Liver Transplantation 24 380-393 2018 AASLD.

Investigation of Medium Chain Fatty Acid Feed Supplementation for Reducing Salmonella Typhimurium Colonization in Turkey Poults.

Studies indicate that persistent Salmonella colonization occurs in poultry that are infected early in life, leading to both food safety and public health concerns. Development of improved preharvest Salmonella management strategies is needed to reduce poultry product contamination. The objective of this study was to evaluate the efficacy of a product containing medium chain fatty acids (MCFA) for reducing early Salmonella colonization in turkey poults. Day-of-hatch turkeys were provided a standard starter diet supplemented with MCFA at 0 (negative and positive controls), 1.5, 3, 4.5, or 6 lbs/ton of feed. Positive control and MCFA treated birds were also crop-gavaged with 108 colony forming units (CFU) of bioluminescent Salmonella Typhimurium. Gastrointestinal tissue samples were collected at 3 days postinoculation for bioluminescence imaging (Meckel's diverticulum to the cloaca) and selective enumeration (cecal contents). Quantification of bioluminescence indicated that the 4.5 and 6 lbs/ton MCFA groups had significantly less colonization than the positive control group (p = 0.0412 and p < 0.0001, respectively). Similarly, significantly lower numbers (1-log10 CFU/g reduction) of Salmonella were observed in the ceca of the 6 lbs/ton MCFA group compared to the positive control group (p = 0.0153). These findings indicate that incorporation of MCFA in turkey diets can significantly reduce early Salmonella colonization. In addition, this study highlights the utility of bioluminescence imaging as a screening methodology for assessing the efficacy of treatments that may reduce Salmonella in poultry.

Ultrasound Molecular Imaging of Inflammation in Mouse Abdominal Aorta.

OBJECTIVES: The aim of this study was to demonstrate a new clinically translatable ultrasound molecular imaging approach, modulated acoustic radiation force-based imaging, which is capable of rapid and reliable detection of inflammation as validated in mouse abdominal aorta. MATERIALS AND METHODS: Animal studies were approved by the Institutional Animal Care and Use Committee at the University of Virginia. C57BL/6 mice stimulated with tumor necrosis factor α, or fed with a high-fat diet, were used as inflammation (MInflammation) and diet-induced obesity (DIO) (MDIO) models, respectively. C57BL/6 mice, not exposed to tumor necrosis factor α or DIO, were used as controls (MNormal). P-selectin-targeted (MBP-selectin), vascular cell adhesion molecule (VCAM)-1-targeted (MBVCAM-1), and isotype control (MBControl) microbubbles were synthesized by conjugating anti-P-selectin, anti-VCAM-1, and isotype control antibodies to microbubbles, respectively. The abdominal aortas were imaged for 180 seconds during a constant infusion of microbubbles. A parameter, residual-to-saturation ratio (RSR), was used to assess P-selectin and VCAM-1. Statistical analysis was performed with the Student t test. RESULTS: For the inflammation model, RSR of the MInflammation + MBP-selectin group was significantly higher (40.9%, P < 0.0005) than other groups. For the DIO model, RSR of the MDIO + MBVCAM-1 group was significantly higher (60.0%, P < 0.0005) than other groups. Immunohistochemistry staining of the abdominal aorta confirmed the expression of P-selectin and VCAM-1. CONCLUSIONS: A statistically significant assessment of P-selectin and VCAM-1 in mouse abdominal aorta was achieved. This technique yields progress toward rapid targeted molecular imaging in large blood vessels and thus has the potential for early diagnosis, treatment selection, and risk stratification of atherosclerosis.

The Use of Acoustic Radiation Force Decorrelation-Weighted Pulse Inversion for Enhanced Ultrasound Contrast Imaging.

OBJECTIVES: The use of ultrasound imaging for cancer diagnosis and screening can be enhanced with the use of molecularly targeted microbubbles. Nonlinear imaging strategies such as pulse inversion (PI) and "contrast pulse sequences" (CPS) can be used to differentiate microbubble signal, but often fail to suppress highly echogenic tissue interfaces. This failure results in false-positive detection and potential misdiagnosis. In this study, a novel acoustic radiation force (ARF)-based approach was developed for superior microbubble signal detection. The feasibility of this technique, termed ARF decorrelation-weighted PI (ADW-PI), was demonstrated in vivo using a subcutaneous mouse tumor model. MATERIALS AND METHODS: Tumors were implanted in the hindlimb of C57BL/6 mice by subcutaneous injection of MC38 cells. Lipid-shelled microbubbles were conjugated to anti-VEGFR2 antibody and administered via bolus injection. An image sequence using ARF pulses to generate microbubble motion was combined with PI imaging on a Verasonics Vantage programmable scanner. ADW-PI images were generated by combining PI images with interframe signal decorrelation data. For comparison, CPS images of the same mouse tumor were acquired using a Siemens Sequoia clinical scanner. RESULTS: Microbubble-bound regions in the tumor interior exhibited significantly higher signal decorrelation than static tissue (n = 9, P < 0.001). The application of ARF significantly increased microbubble signal decorrelation (n = 9, P < 0.01). Using these decorrelation measurements, ADW-PI imaging demonstrated significantly improved microbubble contrast-to-tissue ratio when compared with corresponding CPS or PI images (n = 9, P < 0.001). Contrast-to-tissue ratio improved with ADW-PI by approximately 3 dB compared with PI images and 2 dB compared with CPS images. CONCLUSIONS: Acoustic radiation force can be used to generate adherent microbubble signal decorrelation without microbubble bursting. When combined with PI, measurements of the resulting microbubble signal decorrelation can be used to reconstruct images that exhibit superior suppression of highly echogenic tissue interfaces when compared with PI or CPS alone.

The evolving interaction of low-frequency earthquakes during transient slip.

Observed along the roots of seismogenic faults where the locked interface transitions to a stably sliding one, low-frequency earthquakes (LFEs) primarily occur as event bursts during slow slip. Using an event catalog from Guerrero, Mexico, we employ a statistical analysis to consider the sequence of LFEs at a single asperity as a point process, and deduce the level of time clustering from the shape of its autocorrelation function. We show that while the plate interface remains locked, LFEs behave as a simple Poisson process, whereas they become strongly clustered in time during even the smallest slow slip, consistent with interaction between different LFE sources. Our results demonstrate that bursts of LFEs can result from the collective behavior of asperities whose interaction depends on the state of the fault interface.