A magnetic map leads juvenile European eels to the Gulf Stream

Migration allows animals to track the environmental conditions that maximize growth, survival, and reproduction [ 1–3 ]. Improved understanding of the mechanisms underlying migrations allows for improved management of species and ecosystems [ 1–4 ]. For centuries, the catadromous European eel (Anguilla anguilla) has provided one of Europe’s most important fisheries and has sparked considerable scientific inquiry, most recently owing to the dramatic collapse of juvenile recruitment [ 5 ]. Larval eels are transported by ocean currents associated with the Gulf Stream System from Sargasso Sea breeding grounds to coastal and freshwater habitats from North Africa to Scandinavia [ 6, 7 ]. After a decade or more, maturing adults migrate back to the Sargasso Sea, spawn, and die [ 8 ]. However, the migratory mechanisms that bring juvenile eels to Europe and return adults to the Sargasso Sea remain equivocal [ 9, 10 ]. Here, we used a “magnetic displacement” experiment [ 11, 12 ] to show that the orientation of juvenile eels varies in response to subtle differences in magnetic field intensity and inclination angle along their marine migration route. Simulations using an ocean circulation model revealed that even weakly swimming in the experimentally observed directions at the locations corresponding to the magnetic displacements would increase entrainment of juvenile eels into the Gulf Stream System. These findings provide new insight into the migration ecology and recruitment dynamics of eels and suggest that an adaptive magnetic map, tuned to large-scale features of ocean circulation, facilitates the vast oceanic migrations of the Anguilla genu

Acute Cryptococcal Immune Reconstitution Inflammatory Syndrome in a Patient on Natalizumab

Presented is the first case of acute immune reconstitution inflammatory syndrome (IRIS)-associated cryptococcal meningoencephalitis in a patient on natalizumab for multiple sclerosis. The patient developed acute cerebral edema after initiation of amphotericin B. We propose several mechanisms that explain the acuity of IRIS in this specific patient population and suggest possible therapies

New N=2 Superconformal Field Theories in Four Dimensions

New examples of N=2 supersymmetric conformal field theories are found as fixed points of SU(2) N=2 supersymmetric QCD. Relations among the scaling dimensions of their relevant chiral operators, global symmetries, and Higgs branches are understood in terms of the general structure of relevant deformations of non-trivial N=2 conformal field theories. The spectrum of scaling dimensions found are all those compatible with relevant deformations of a y^2 = x^3 singular curve.Comment: 17 pages, harvma

Prognostic Value and Agreement of Achieving Lactate Clearance or Central Venous Oxygen Saturation Goals During Early Sepsis Resuscitation

Objectives:  Lactate clearance (LC) and central venous oxygen saturation (ScvO2) have been proposed as goals of early sepsis resuscitation. The authors sought to determine the agreement and prognostic value of achieving ScvO2 or LC goals in septic shock patients undergoing emergency department (ED)-based early resuscitation. Methods:  This was a preplanned analysis of a multicenter ED randomized controlled trial of early sepsis resuscitation targeting three variables: central venous pressure, mean arterial pressure, and either ScvO2 or LC. Inclusion criteria included suspected infection, two or more systemic inflammation criteria, and either systolic blood pressure of 4 mmol/L. Both ScvO2 and LC were measured simultaneously. The ScvO2 goal was defined as ≥70%. Lactate was measured at enrollment and every 2 hours until the goal was reached or up to 6 hours. LC goal was defined as a decrease of ≥10% from initial measurement. The primary outcome was in-hospital mortality. Results:  A total of 203 subjects were included, with an overall mortality of 19.7%. Achievement of the ScvO2 goal only was associated with a mortality rate of 41% (9/22), while achievement of the LC goal only was associated with a mortality rate of 8% (2/25; proportion difference = 33%; 95% confidence interval [CI] = 9% to 55%). No agreement was found between goal achievement (κ = –0.02), and exact test for matched pairs demonstrated no significant difference between discordant pairs (p = 0.78). Conclusions:  No agreement was found between LC and ScvO2 goal achievement in early sepsis resuscitation. Achievement of a ScvO2≥ 70% without LC ≥ 10% was more strongly associated with mortality than achievement of LC ≥ 10% with failure to achieve ScvO2≥ 70%

Lactate Clearance vs Central Venous Oxygen Saturation as Goals of Early Sepsis Therapy: A Randomized Clinical Trial

Context Goal-directed resuscitation for severe sepsis and septic shock has been reported to reduce mortality when applied in the emergency department. Objective To test the hypothesis of noninferiority between lactate clearance and central venous oxygen saturation (ScvO2) as goals of early sepsis resuscitation. Design, Setting, and Patients Multicenter randomized, noninferiority trial involving patients with severe sepsis and evidence of hypoperfusion or septic shock who were admitted to the emergency department from January 2007 to January 2009 at 1 of 3 participating US urban hospitals. Interventions We randomly assigned patients to 1 of 2 resuscitation protocols. The ScvO2 group was resuscitated to normalize central venous pressure, mean arterial pressure, and ScvO2 of at least 70%; and the lactate clearance group was resuscitated to normalize central venous pressure, mean arterial pressure, and lactate clearance of at least 10%. The study protocol was continued until all goals were achieved or for up to 6 hours. Clinicians who subsequently assumed the care of the patients were blinded to the treatment assignment. Main Outcome Measure The primary outcome was absolute in-hospital mortality rate; the noninferiority threshold was set at Δ equal to −10%. Results Of the 300 patients enrolled, 150 were assigned to each group and patients were well matched by demographic, comorbidities, and physiological features. There were no differences in treatments administered during the initial 72 hours of hospitalization. Thirty-four patients (23%) in the ScvO2 group died while in the hospital (95% confidence interval [CI], 17%-30%) compared with 25 (17%; 95% CI, 11%-24%) in the lactate clearance group. This observed difference between mortality rates did not reach the predefined −10% threshold (intent-to-treat analysis: 95% CI for the 6% difference, −3% to 15%). There were no differences in treatment-related adverse events between the groups. Conclusion Among patients with septic shock who were treated to normalize central venous and mean arterial pressure, additional management to normalize lactate clearance compared with management to normalize ScvO2 did not result in significantly different in-hospital mortality

The novel mu-opioid antagonist, GSK1521498, reduces ethanol consumption in C57BL/6J mice.

RATIONALE Using the drinking-in-the-dark (DID) model, we compared the effects of a novel mu-opioid receptor antagonist, GSK1521498, with naltrexone, a licensed treatment of alcohol dependence, on ethanol consumption in mice. OBJECTIVE We test the ability of GSK1521498 to reduce alcohol consumption and compare its intrinsic efficacy to that of naltrexone by comparing the two drugs at doses matched for equivalent receptor occupancy. METHODS Thirty-six C57BL/6J mice were tested in a DID procedure. In 2-day cycles, animals experienced one baseline, injection-free session, and one test session when they received two injections, one of test drug and one placebo. All animals received GSK1521498 (0, 0.1, 1 and 3 mg/kg, i.p., 30 min pre-treatment) and naltrexone (0, 0.1, 1 and 3 mg/kg, s.c. 10 min pre-treatment) in a cross-over design. Receptor occupancies following the same doses were determined ex vivo in separate groups by autoradiography, using [3H]DAMGO. Binding in the region of interest was measured integrally by computer-assisted microdensitometry and corrected for non-specific binding. RESULTS Both GSK1521498 and naltrexone dose-dependently decreased ethanol consumption. When drug doses were matched for 70-75 % receptor occupancy, GSK1521498 3 mg/kg, i.p., caused a 2.5-fold greater reduction in alcohol consumption than naltrexone 0.1 mg/kg, s.c. Both GSK1521498 and naltrexone significantly reduced sucrose consumption at a dose of 1 mg/kg but not 0.1 mg/kg. In a test of conditioned taste aversion, GSK1521498 (3 mg/kg) reduced sucrose consumption 24 h following exposure to a conditioning injection. CONCLUSIONS Both opioid receptor antagonists reduced alcohol consumption but GK1521498 has higher intrinsic efficacy than naltrexone

Outcomes of Patients Undergoing Early Sepsis Resuscitation for Cryptic Shock Compared with Overt Shock

Introduction We sought to compare the outcomes of patients with cryptic versus overt shock treated with an emergency department (ED) based early sepsis resuscitation protocol. Methods Pre-planned secondary analysis of a large, multicenter ED-based randomized controlled trial of early sepsis resuscitation. All subjects were treated with a quantitative resuscitation protocol in the ED targeting 3 physiological variables: central venous pressure, mean arterial pressure and either central venous oxygen saturation or lactate clearance. The study protocol was continued until all endpoints were achieved or a maximum of 6 h. Outcomes data of patients who were enrolled with a lactate ≥4 mmol/L and normotension (cryptic shock) were compared to those enrolled with sustained hypotension after fluid challenge (overt shock). The primary outcome was in-hospital mortality. Results A total of 300 subjects were enrolled, 53 in the cryptic shock group and 247 in the overt shock group. The demographics and baseline characteristics were similar between the groups. The primary endpoint of in-hospital mortality was observed in 11/53 (20%, 95% CI 11–34) in the cryptic shock group and 48/247 (19%, 95% CI 15–25) in the overt shock group, difference of 1% (95% CI −10 to 14; log rank test p = 0.81). Conclusion Severe sepsis with cryptic shock carries a mortality rate not significantly different from that of overt septic shock. These data suggest the need for early aggressive screening for and treatment of patients with an elevated serum lactate in the absence of hypotension

Benefits of robotic cystectomy with intracorporeal diversion for patients with low cardiorespiratory fitness: a prospective cohort study

Background: Patients undergoing radical cystectomy have associated comorbidities resulting in reduced cardiorespiratory fitness. Preoperative cardiopulmonary exercise testing (CPET) measures including anaerobic threshold (AT) can predict major adverse events (MAE) and hospital length of stay (LOS) for patients undergoing open and robotic cystectomy with extracorporeal diversion. Our objective was to determine the relationship between CPET measures and outcome in patients undergoing robotic radical cystectomy and intracorporeal diversion (intracorporeal robotic assisted radical cystectomy [iRARC]). Methods: A single institution prospective cohort study in patients undergoing iRARC for muscle invasive and high-grade bladder cancer. Inclusion: patients undergoing standardised CPET before iRARC. Exclusions: patients not consenting to data collection. Data on CPET measures (AT, ventilatory equivalent for carbon dioxide [VE/VCO2] at AT, peak oxygen uptake [VO2]), and patient demographics prospectively collected. Outcome measurements included hospital LOS; 30-day MAE and 90-day mortality data, which were prospectively recorded. Descriptive and regression analyses were used to assess whether CPET measures were associated with or predicted outcomes. Results: From June 2011 to March 2015, 128 patients underwent radical cystectomy (open cystectomy, n = 17; iRARC, n = 111). A total of 82 patients who underwent iRARC and CPET and consented to participation were included. Median (interquartile range): age = 65 (58–73); body mass index = 27 (23–30); AT = 10.0 (9–11), Peak VO2 = 15.0 (13–18.5), VE/VCO2 (AT) = 33.0 (30–38). 30-day MAE = 14/111 (12.6%): death = 2, multiorgan failure = 2, abscess = 2, gastrointestinal = 2, renal = 6; 90-day mortality = 3/111 (2.7%). AT, peak VO2, and VE/VCO2 (at AT) were not significant predictors of 30-day MAE or LOS. The results are limited by the absence of control group undergoing open surgery. Conclusions: Poor cardiorespiratory fitness does not predict increased hospital LOS or MAEs in patients undergoing iRARC. Overall, MAE and LOS comparable with other series

Evidence of the Harmonic Faraday Instability in Ultrasonic Atomization Experiments with a Deep, Inviscid Fluid

A popular method for generating micron-sized aerosols is to submerge ultrasonic (ω~MHz) piezoelectric oscillators in a water bath. The submerged oscillator atomizes the fluid, creating droplets with radii proportional to the wavelength of the standing wave at the fluid surface. Classical theory for the Faraday instability predicts a parametric instability driving a capillary wave at the subharmonic (ω/2) frequency. For many applications it is desirable to reduce the size of the droplets; however, using higher frequency oscillators becomes impractical beyond a few MHz. Observations are presented that demonstrate that smaller droplets may also be created by increasing the driving amplitude of the oscillator, and that this effect becomes more pronounced for large driving frequencies. It is shown that these observations are consistent with a transition from droplets associated with subharmonic (ω/2) capillary waves to harmonic (ω) capillary waves induced by larger driving frequencies and amplitudes, as predicted by a stability analysis of the capillary waves