Precision gamma-ray constraints for sub-GeV dark matter models

The indirect detection of dark matter particles with mass below the GeV scale has recently received significant attention. Future space-borne gamma-ray telescopes, including All-Sky-ASTROGAM, AMEGO, and GECCO, will probe the MeV gamma-ray sky with unprecedented precision, offering an exciting test of particle dark matter in the MeV-GeV mass range. While it is typically assumed that dark matter annihilates into only one Standard Model final state, this is not the case for realistic dark matter models. In this work we analyze existing indirect detection constraints and the discovery reach of future detectors for the well-motivated Higgs and vector-portal models using our publicly-available code Hazma. In particular, we show how to leverage chiral perturbation theory to compute the dark matter self-annihilation cross sections into final states containing mesons, the strongly-interacting Standard Model dynamical degrees of freedom below the GeV scale. We find that future telescopes could probe dark matter self-annihilation cross sections orders of magnitude smaller than those presently constrained by cosmic microwave background, gamma-ray and terrestrial observations.Comment: 20 pages, 4 figure

Blunt traumatic aortic injury: Initial experience with endovascular repair

ObjectivesEndovascular treatment of traumatic aortic injury (TAI) is an alternative to open repair (OR) in patients with blunt trauma. We report our initial experience after integration of endovascular repair using thoracic devices.MethodsA retrospective review of a prospectively collected institutional trauma registry was performed. Between September 2005 and November 2008, 71 patients with TAI presented to our institution. Based on imaging, TAIs were classified into grade 1-4 in severity. These included: grade 1, intimal tear; grade 2, intramural hematoma; grade 3, aortic pseudoaneurysm; and grade 4, free rupture. Initial management included resuscitation, blood pressure control, and treatment of associated injuries. After stabilization, all patients were considered for thoracic endovascular aortic repair (TEVAR) using a thoracic device. If contraindicated, candidates underwent OR. Outcome measures were mortality, stroke, paraplegia, intensive care unit (ICU), and hospital stay.ResultsThe mean age was 39.8 years, with 50 males. The mean injury severity score (ISS) was 42.6. Nineteen (27%) patients with a mean ISS of 60 died shortly after arrival prior to any vascular intervention. Ten (14%) patients with grade 1 injuries were managed medically. The remaining 42 (59%) patients with grade 2 and 3 injuries underwent repair. Median interval between admission and repair was 4.3 days (range, 0-109 days). Fifteen (21%) patients with a mean ISS of 34.4 underwent OR with no mortality, stroke, or paraplegia. Twenty-seven (38%) patients with a mean ISS of 36.7 underwent TEVAR with no mortality or paraplegia. One TEVAR patient suffered a perioperative stroke. Twenty-two patients had a TAG (W.L. Gore & Associates, Flagstaff, Ariz) device. Four patients had a Talent Thoracic (Medtronic Vascular, Santa Rosa, Calif), and 1 patient had an Excluder (W.L. Gore) device. The left subclavian artery was covered in 13 (48%) patients. Patients who underwent TEVAR were older than those who had OR (47.8 vs 31.1 years, P < .006). The aortic diameter proximal to the injury was larger in the TEVAR group (24.4 vs 19.6 mm, P < .0001). There was no difference in the mean ICU or hospital length of stay between the two groups. Mortality correlated with the ISS score (P < .0001). Median follow-up time was 19.4 months (range, 0-27). Only 56% of the TEVAR patients were fully compliant with their surveillance imaging protocol.ConclusionIn this initial experience, the results of TEVAR did not differ from OR. Long-term follow-up is required to determine the effectiveness of this treatment strategy. Adherence to follow-up imaging protocols is challenging in this patient population. Next generation devices will make TEVAR applicable to a wider range of patients

The redox-active drug metronidazole and thiol-depleting garlic compounds act synergistically in the protist parasite Spironucleus vortens

Spironucleus vortens is a protozoan parasite associated with significant mortalities in the freshwater angelfish, Pterophyllum scalare. Control of this parasite is especially problematic due to restrictions on the use of the drug of choice, metronidazole (MTZ), on fish farms. Use of garlic (Allium sativum) is undergoing a renaissance following experimental validations of its antimicrobial efficiency. Ajoene ((E,Z)-4,5,9-trithiadodeca-1,6,11-triene 9-oxide), is a stable transformation product of allicin, the primary biologically active component of garlic. In the current study, an ajoene oil crude extract had a minimum inhibitory concentration (MIC) of 40 μg/ml against S. vortens. GC-MS and NMR spectroscopy revealed this ajoene extract contained a mixture of the (E) and (Z)-ajoene isomers along with diallyl disulphide (DADS) and diallyl trisulphide (DATS). The only component of the ajoene crude oil found to substantially inhibit S. vortens growth by optical density monitoring (Bioscreen C Reader) was (Z)-ajoene (MIC 16 μg/ml). Ajoene oil acted in synergy with MTZ in vitro, reducing the individual MIC of this drug (4 μg/ml) by 16-fold, and that of ajoene oil by 200-fold with a fractional inhibitory concentration (FIC) index of 0.263. This synergistic interaction was confirmed in vivo. S. vortens-infected P. scalare angelfish dosed orally with 0.5% (v/w) MTZ combined with 0.05% (v/w) ajoene displayed a significant reduction in faecal trophozoite count, whilst those fed on 0.5% MTZ flakes (half the recommended oral dose) alone did not. This study demonstrates for the first time the synergistic interaction between the synthetic drug MTZ and natural ajoene oil both in vitro and in vivo. Future work should evaluate the potential synergy of ajoene and MTZ against MTZ-resistant bacteria and protists

Computational Fluid Dynamic Simulations for Determination of Ventricular Workload in Aortic Arch Obstructions

Objective The cardiac workload associated with various types of aortic obstruction was determined using computational fluid dynamic simulations. Methods Computed tomography image data were collected from 4 patients with 4 distinct types of aortic arch obstructions and 4 controls. The categorization of arch hypoplasia corresponded to the “A, B, C” nomenclature of arch interruption; a type “D” was added to represent diffuse arch hypoplasia. Measurements of the vessel diameter were compared against the normal measurements to determine the degree of narrowing. Three-dimensional models were created for each patient, and additional models were created for type A and B hypoplasia to represent 25%, 50%, and 75% diameter narrowing. The boundary conditions for the computational simulations were chosen to achieve realistic flow and pressures in the control cases. The simulations were then repeated after changing the boundary conditions to represent a range of cardiac and vascular adaptations. The resulting cardiac workload was compared with the control cases. Results Of the 4 patients investigated, 1 had aortic coarctation and 3 had aortic hypoplasia. The cardiac workload of the patients with 25% narrowing type A and B hypoplasia was not appreciably different from that of the control. When comparing the different arch obstructions, 75% type A, 50% type B, and 50% type D hypoplasia required a greater workload increase than 75% coarctation. Conclusions The present study has determined the hemodynamic significance of aortic arch obstruction using computational simulations to calculate the cardiac workload. These results suggest that all types of hypoplasia pose more of a workload challenge than coarctation with an equivalent degree of narrowing

Update on blunt thoracic aortic injury: Fifteen-year single-institution experience

ObjectivesDespite improvements in the management of blunt thoracic aortic injury, mortality remains high. We report our experience with blunt thoracic aortic injury at a level 1 trauma center over the past 15 years.MethodsBetween January 1, 1997, and January 1, 2012, data on 338 patients who presented with suspected blunt thoracic aortic injury were entered into the University of Texas Medical School at Houston Trauma Center Registry. A total of 175 patients (52%) underwent thoracic aortic repair; 29 (17%) had open repair with aortic crossclamping, 77 (44%) had open repair with distal aortic perfusion, and 69 (39%) had thoracic endovascular aortic repair. Outcomes were determined, including early mortality, morbidity, length of stay, and late survival. Multiple logistic regression analysis was used to compute adjusted estimates for the effects of the operative technique.ResultsThe early mortality for all patients with blunt thoracic aortic injury was 41% (139/338). Early mortality was 17% (27/175) for operative aortic interventions, 4% (3/69) for thoracic endovascular aortic repairs, 31% (11/29) for open repairs with aortic crossclamping, and 14% (11/77) for open repairs with distal aortic perfusion. Survival for thoracic endovascular aortic repair at 1 year and 5 years was 92% and 87%, respectively. Survival for open repair at 1, 5, 10, and 15 years was 76%, 75%, 72%, and 68%, respectively.ConclusionsBlunt thoracic aortic injury remains associated with significant early mortality. Delayed selective management, when applied with open repair with distal aortic perfusion and the use of thoracic endovascular aortic repair, has been associated with improved early outcomes. The long-term durability of thoracic endovascular aortic repair is unknown, necessitating close radiographic follow-up

Postoperative renal function preservation with nonischemic femoral arterial cannulation for thoracoabdominal aortic repair.

BACKGROUND: Renal failure after thoracoabdominal aortic repair is a significant clinical problem. Distal aortic perfusion for organ and spinal cord protection requires cannulation of the left femoral artery. In 2006, we reported the finding that direct cannulation led to leg ischemia in some patients and was associated with increased renal failure. After this finding, we modified our perfusion technique to eliminate leg ischemia from cannulation. In this article, we present the effects of this change on postoperative renal function. METHODS: Between February 1991 and July 2008, we repaired 1464 thoracoabdominal aortic aneurysms. Distal aortic perfusion was used in 1088, and these were studied. Median patient age was 68 years, and 378 (35%) were women. In September 2006, we began to adopt a sidearm femoral cannulation technique that provides distal aortic perfusion while maintaining downstream flow to the leg. This was used in 167 patients (15%). We measured the joint effects of preoperative glomerular filtration rate (GFR) and cannulation technique on the highest postoperative creatinine level, postoperative renal failure, and death. Analysis was by multiple linear or logistic regression with interaction. RESULTS: The preoperative GFR was the strongest predictor of postoperative renal dysfunction and death. No significant main effects of sidearm cannulation were noted. For peak creatinine level and postoperative renal failure, however, strong interactions between preoperative GFR and sidearm cannulation were present, resulting in reductions of postoperative renal complications of 15% to 20% when GFR was \u3c60 mL\u3e/min/1.73 m(2). For normal GFR, the effect was negated or even reversed at very high levels of GFR. Mortality, although not significantly affected by sidearm cannulation, showed a similar trend to the renal outcomes. CONCLUSION: Use of sidearm cannulation is associated with a clinically important and highly statistically significant reduction in postoperative renal complications in patients with a low GFR. Reduced renal effect of skeletal muscle ischemia is the proposed mechanism. Effects among patients with good preoperative renal function are less clear. A randomized trial is needed