Light-induced anomalous Hall effect in graphene.

Many non-equilibrium phenomena have been discovered or predicted in optically-driven quantum solids1. Examples include light-induced superconductivity2,3 and Floquet-engineered topological phases4-8. These are short lived effects that should lead to measurable changes in electrical transport, which can be characterized using an ultrafast device architecture based on photoconductive switches9. Here, we report the observation of a light-induced anomalous Hall effect in monolayer graphene driven by a femtosecond pulse of circularly polarized light. The dependence of the effect on a gate potential used to tune the Fermi level reveals multiple features that reflect a Floquet-engineered topological band structure4,5, similar to the band structure originally proposed by Haldane10. This includes an approximately 60 meV wide conductance plateau centered at the Dirac point, where a gap of equal magnitude is predicted to open. We find that when the Fermi level lies within this plateau, the estimated anomalous Hall conductance saturates around 1.8±0.4 e2/h.

David B. Nash Advocates Better Outcomes And Lower Costs Through Population Health.

As interest grows in the potential impact of population health strategies, a recognized leader in the field-the founding dean of the Jefferson College of Population Health-explains key concepts and the role for this approach in safety, efficacy, and costs.

Seeking Solutions to the Opioid Crisis.

At an event focusing on population-health approaches to the opioid epidemic, discussants agreed that better coordination of care, community involvement in finding solutions, and more consistent use of improved pain-control options are required.

Effects of transients in LIGO suspensions on searches for gravitational waves.

This paper presents an analysis of the transient behavior of the Advanced LIGO (Laser Interferometer Gravitational-wave Observatory) suspensions used to seismically isolate the optics. We have characterized the transients in the longitudinal motion of the quadruple suspensions during Advanced LIGO's first observing run. Propagation of transients between stages is consistent with modeled transfer functions, such that transient motion originating at the top of the suspension chain is significantly reduced in amplitude at the test mass. We find that there are transients seen by the longitudinal motion monitors of quadruple suspensions, but they are not significantly correlated with transient motion above the noise floor in the gravitational wave strain data, and therefore do not present a dominant source of background noise in the searches for transient gravitational wave signals. Using the suspension transfer functions, we compared the transients in a week of gravitational wave strain data with transients from a quadruple suspension. Of the strain transients between 10 and 60 Hz, 84% are loud enough that they would have appeared above the sensor noise in the top stage quadruple suspension monitors if they had originated at that stage at the same frequencies. We find no significant temporal correlation with the suspension transients in that stage, so we can rule out suspension motion originating at the top stage as the cause of those transients. However, only 3.2% of the gravitational wave strain transients are loud enough that they would have been seen by the second stage suspension sensors, and none of them are above the sensor noise levels of the penultimate stage. Therefore, we cannot eliminate the possibility of transient noise in the detectors originating in the intermediate stages of the suspension below the sensing noise.

A P&T Snapshot of the Nation's Progress Against Cancer.

Although the death rate from cancer has fallen in recent years, progress against these diseases is uneven. This issue focuses on research efforts to find treatments.

Control over topological insulator photocurrents with light polarization.

Three-dimensional topological insulators represent a new quantum phase of matter with spin-polarized surface states that are protected from backscattering. The static electronic properties of these surface states have been comprehensively imaged by both photoemission and tunnelling spectroscopies. Theorists have proposed that topological surface states can also exhibit novel electronic responses to light, such as topological quantum phase transitions and spin-polarized electrical currents. However, the effects of optically driving a topological insulator out of equilibrium have remained largely unexplored experimentally, and no photocurrents have been measured. Here, we show that illuminating the topological insulator Bi(2)Se(3) with circularly polarized light generates a photocurrent that originates from topological helical Dirac fermions, and that reversing the helicity of the light reverses the direction of the photocurrent. We also observe a photocurrent that is controlled by the linear polarization of light and argue that it may also have a topological surface state origin. This approach may allow the probing of dynamic properties of topological insulators and lead to novel opto-spintronic devices.

Selective probing of photoinduced charge and spin dynamics in the bulk and surface of a topological insulator.

Topological insulators possess completely different spin-orbit coupled bulk and surface electronic spectra that are each predicted to exhibit exotic responses to light. Here we report time-resolved fundamental and second harmonic optical pump-probe measurements on the topological insulator Bi(2)Se(3) to independently measure its photoinduced charge and spin dynamics with bulk and surface selectivity. Our results show that a transient net spin density can be optically induced in both the bulk and surface, which may drive spin transport in topological insulators. By utilizing a novel rotational anisotropy analysis we are able to separately resolve the spin depolarization, intraband cooling, and interband recombination processes following photoexcitation, which reveal that spin and charge degrees of freedom relax on very different time scales owing to strong spin-orbit coupling.

Nonlinear optical probe of tunable surface electrons on a topological insulator.

We use ultrafast laser pulses to experimentally demonstrate that the second-order optical response of bulk single crystals of the topological insulator Bi(2)Se(3) is sensitive to its surface electrons. By performing surface doping dependence measurements as a function of photon polarization and sample orientation we show that second harmonic generation can simultaneously probe both the surface crystalline structure and the surface charge of Bi(2)Se(3). Furthermore, we find that second harmonic generation using circularly polarized photons reveals the time-reversal symmetry properties of the system and is surprisingly robust against surface charging, which makes it a promising tool for spectroscopic studies of topological surfaces and buried interfaces.

End-compensated magnetostatic cavity for polarized 3He neutron spin filters.

We have expanded upon the "Magic Box" concept, a coil driven magnetic parallel plate capacitor constructed out of mu-metal, by introducing compensation sections at the ends of the box that are tuned to limit end-effects similar to those of short solenoids. This ability has reduced the length of the magic box design without sacrificing any loss in field homogeneity, making the device far more applicable to the often space limited neutron beam line. The appeal of the design beyond affording longer polarized 3He lifetimes is that it provides a vertical guide field, which facilitates neutron spin transport for typical polarized beam experiments. We have constructed two end-compensated magic boxes of dimensions 28.4 x 40 x 15 cm3 (length x width x height) with measured, normalized volume-averaged transverse field gradients ranging from 3.3 x 10(-4) to 6.3 x 10(-4) cm(-1) for cell sizes ranging from 8.1 x 6.0 to 12.0 x 7.9 cm2 (diameter x length), respectively.

Wrinkling of a bilayer membrane.

The buckling of elastic bodies is a common phenomenon in the mechanics of solids. Wrinkling of membranes can often be interpreted as buckling under constraints that prohibit large-amplitude deformation. We present a combination of analytic calculations, experiments, and simulations to understand wrinkling patterns generated in a bilayer membrane. The model membrane is composed of a flexible spherical shell that is under tension and that is circumscribed by a stiff, essentially incompressible strip with bending modulus B . When the tension is reduced sufficiently to a value sigma , the strip forms wrinkles with a uniform wavelength found theoretically and experimentally to be lambda=2pi(B/sigma)(1/3). Defects in this pattern appear for rapid changes in tension. Comparison between experiment and simulation further shows that, with larger reduction of tension, a second generation of wrinkles with longer wavelength appears only when B is sufficiently small.

Metastatic hepatocellular carcinoma presenting as epidural hematoma: case report.

OBJECTIVE AND IMPORTANCE: A case of acutely symptomatic epidural hematoma caused by metastatic hepatocellular carcinoma (HCC) to the cranium is reported. This is a rare case of metastatic HCC without known primary presenting as an epidural hematoma. CLINICAL PRESENTATION: The patient presented with an acute onset of headache, aphasia, and right hemiparesis 2 weeks after he experienced minor trauma to the cranium. An emergency computed tomographic scan of the head revealed the presence of a left parietal epidural hematoma. INTERVENTION: An emergency evacuation of the epidural hematoma was performed, and metastatic HCC was diagnosed. CONCLUSION: The patient's neurological deficits were reversed with surgical intervention, and he is now undergoing palliative chemotherapy. This was the first clinical manifestation of HCC in this patient. This case reaffirms the neurosurgeon's role in the complex, multidisciplinary care of patients with craniospinal metastasis.

Improved immunogenicity of a core-coated tetanus toxoid delivery system.

A new microparticulate delivery system composed of a stabilizing gelatin/poloxamer microcore surrounded by a PLGA coat was designed to improve the stability of tetanus toxoid (TT) encapsulated in PLGA microspheres. Microcores were prepared by a spray-congealing technique and encapsulated within PLGA using an oil-in-oil (o/o) solvent evaporation technique. SEM analysis of the cross-sections of the microcapsules revealed the adequate encapsulation of the cores, showing an intimate contact between the core and the coating. This structure was responsible for an osmotic phenomenon observed in vitro, which led to the release of the encapsulated TT in a short period of time. Nevertheless, it was observed that the release was affected by the presence of the poloxamer in the core: microspheres without poloxamer in the core exhibit a faster release (2 h) than those that incorporate the surfactant (24 h). The in vivo evaluation of this system showed that the encapsulated toxoid induced a low but continuous levels of neutralizing antibodies (Nt), whereas those obtained for the control (aluminum phosphate-adsorbed toxoid) decreased after reaching the maximum level at 14 weeks. Moreover, the administration of a mixture of encapsulated and adsorbed TT led to significant higher and more prolonged Nt levels than those measured for the adsorbed toxoid.

Formulation strategies for the stabilization of tetanus toxoid in poly(lactide-co-glycolide) microspheres.

The development of a single-dose tetanus vaccine based on Poly(Lactic acid) (PLA) or Poly(Lactide-co-Glycolide) (PLGA) microspheres has been complicated due to the instability of tetanus toxoid (TT) inside these systems. Herein we report an attempt to re-design PLGA microspheres by co-encapsulating TT in the dry solid state together with potential protein stabilizers, such as trehalose, bovine serum albumin, alginate, heparin, dextran or poloxamer 188 and by using an appropriate microencapsulation technique. These newly developed PLGA microspheres were able to release in vitro antigenically active TT for at least 5 weeks, the amount released being highly dependent on the stabilizing excipient used. More specifically, results showed that dextran and heparin provided a particularly stabilizing environment for TT inside the microspheres during the polymer degradation process. The efficacy of this strategy was demonstrated by the high, long lasting titers of neutralizing antibodies achieved after in vivo administration of dextran-containing microspheres with a small amount of alum-adsorbed TT, as compared to the commercial adsorbable tetanus vaccine. These findings suggest that future developments in the area of vaccinology depend on ability to combine a detailed knowledge of the microencapsulation technology with a rational choice of stabilizing excipient or combination of excipients.

Characteristics and outcomes of a home and community-based neurorehabilitation programme.

The potential clinical and financial advantages of providing neurorehabilitation directly in patients' homes and communities have recently been discussed. However, the specific characteristics and outcomes of a coordinated, interdisciplinary, home-based programme does not currently exist in the rehabilitation literature. The present paper presents patient demographics, type and intensity of services provided, satisfaction measures, and clinical outcomes for 77 brain injured individuals in an attempt to begin to define and evaluate this new level of care. Additionally, the challenges of conducting home-based rehabilitation, and needs for further research are discussed.

Treatment of severe pertussis: a study of the safety and pharmacology of intravenous pertussis immunoglobulin.

BACKGROUND: Pertussis in infants is often severe, resulting in complications and prolonged hospitalization. Treatment is limited to supportive care. Antibiotics do not significantly alter the course of the disease. Therapies directed at pertussis toxin, a major virulence factor of Bordetella pertussis, might be beneficial. This study examines the safety and pharmacology of intravenous pertussis immunoglobulin (P-IGIV), which has high levels of pertussis toxin antibodies. METHODS: P-IGIV was prepared as a 4% IgG solution from the pooled plasma from donors immunized with inactivated pertussis toxoid. The IgG pertussis toxin antibody concentration of 733 microg/ml is >7-fold higher than contained in conventional intravenous immunoglobulin products. Children with presumptive pertussis were allocated to one of three treatment doses of P-IGIV. RESULTS: Twenty-six of 30 enrolled children had confirmed pertussis. There were no adverse events associated with P-IGIV except one patient who had transient hypotension that responded to an infusion rate decrease. P-IGIV doses of 1500, 750 and 250 mg/kg achieved > or =4-fold, 3-fold and >2-fold rises in peak geometric mean titers of pertussis toxin IgG antibodies, respectively. P-IGIV exhibited a half-life of 38.4 days and a volume of distribution of 87.8 ml/kg. All three treatment groups showed declines in lymphocytosis (P < 0.05) and paroxysmal coughing by the third day after P-IGIV infusion compared with preinfusion values. CONCLUSION: P-IGIV is safe and achieves high pertussis toxin antibody titers in infants. This study provides data for a prospective, controlled trial of P-IGIV.

A novel system based on a poloxamer/PLGA blend as a tetanus toxoid delivery vehicle.

PURPOSE: Previous work on the encapsulation of proteins and antigens in poly(lactic-co-glycolic acid) (PLGA) microspheres has led to the conclusion that microencapsulated antigens are frequently inactivated due to their interaction with the polymer. To improve the compatibility of the antigen with the polymer, we have devised a novel microencapsulated system consisting of a blend of PLGA 50:50 and poloxamer 188 (Pluronic F68) and applied it to the delivery of tetanus antigen. METHODS: Tetanus toxoid was encapsulated in microspheres containing different amounts of poloxamer using an anhydrous procedure based on an oil-in-oil solvent extraction process. The compatibility of the polymers was studied by Fourier transform infrared (FT-IR) spectroscopy. Microspheres were assayed in vitro and in vivo for their ability to deliver active antigen for extended periods of time. RESULTS: Analysis by FT-IR spectroscopy evidenced the miscibility of both polymers by a hydrogen bonding mechanism. In vitro release studies revealed that microspheres containing poloxamer released antigenically active TT, in a pulsatile manner, for up to 50 days. In addition, it was observed that the intensity and duration of the pulses were dependent on both poloxamer content and TT loading in the microspheres. The in vivo evaluation of this new system showed that the neutralizing antibodies elicited by the TT encapsulated in poloxamer-PLGA microspheres were considerably higher and more prolonged than those obtained after administration of the aluminum phosphate-adsorbed toxoid. CONCLUSIONS: These results indicate the importance of devising new microencapsulation approaches specially adapted for preserving the activity of protein antigens incorporated within PLGA microspheres.

Synthesis of potent and selective inhibitors of human plasma kallikrein.

The synthesis and in vitro enzyme inhibition profile of a series of novel trifluoromethylketone (TFMK) inhibitors of human plasma kallikrein (PK) are described. We have developed an efficient method for the construction of peptide TFMKs that provides the final product devoid of compromised stereochemical integrity. Many of these compounds are potent inhibitors of PK and exhibit reduced inhibition of tissue kallikrein (TK) and plasmin (HP).

Peptide aldehyde inhibitors of the kallikreins: an investigation of subsite interactions with tripeptides containing structural variations at the amino terminus.

A series of tripeptide aldehyde derivatives containing variations at the P3 subsite and the amino terminus has been prepared and evaluated for trypsin-like serine protease inhibition. These compounds exhibit strong in vitro inhibition of human plasma kallikrein (HPK), porcine pancreatic kallikrein (PPK) and human plasmin (HP). As suspected from an examination of a related crystal structure, the presence of a hydrophobic residue (adamantyl) at the amino terminus dramatically improves the binding to PPK. The adamantyl group, however, represents a peak in binding; larger residues cause the binding to be reduced, and thus are less well accommodated in this subsite. Although both HP and HPK also can accept large molecular volume at the amino terminus, they do not exhibit the same preference for large residues at this subsite that is demonstrated by PPK. Selectivity differences also are observed with P3 subsite substitution; with PPK preferring a bulky, but compact side-chain (t-butyl) and HP and HPK preferring a more extended (e.g. benzyl) group.

A simple and rapid method for measuring unconjugated capsular polysaccharide (PRP) of Haemophilus influenzae type b in PRP-tetanus toxoid conjugate vaccine.

The authors developed a simple and rapid method for quantitation of free capsular polysaccharide of Haemophilus influenzae type b (polyribosyl ribitol phosphate, PRP) in PRP-tetanus toxoid conjugate vaccine based on acid precipitation of tetanus toxoid (TT). Acid hydrolysis of PRP during the assay was not detected. The conditions used in the assay did not precipitate unconjugated PRP or adipic acid dihydrazide derivatized PRP. The method was highly reliable, reproducible and sensitive. The accuracy of the assay was confirmed by spiking known amounts of unconjugated PRP to PRP-TT conjugate preparations. A PRP-TT preparation, incubated at 37 degrees C for 6 months showing most of the PRP as unconjugated (87% determined by this method), was not immunogenic in mice for the PRP component even after two injections. In contrast, the same preparation held at 4 degrees C for 20 months, showing 17% unconjugated PRP, induced IgG antibodies to PRP which were boosted after second injection. Therefore, this method is very useful to evaluate the stability of PRP-TT conjugate vaccine. The assay may be useful for characterizing other polysaccharide-protein conjugate vaccines.

Removal of viruses from human intravenous immune globulin by 35 nm nanofiltration.

Viral safety is an important prerequisite for clinical immunoglobulin preparations. A common manufacturing practice is to utilize several virus removal/inactivation process steps to ensure the safety of human intravenous immunoglobulin (IVIg). In this regard, we examined the use of Planova 35 nm filters to reduce potential loads of both non-enveloped and enveloped viruses prior to end-stage solvent detergent treatment. The nanofiltration process was validated for removal of a variety of enveloped and non-enveloped viruses ranging in size from 70 nm to 18 nm including: Sindbis virus, Simian Virus 40 (SV40), Bovine Viral Diarrhoea virus (BVDV), Feline Calicivirus, Encephalomyocarditis virus (EMC), Hepatitis A virus (HAV), Bovine Parvovirus (BPV) and Porcine Parvovirus (PPV). The filtration procedure was carried out by first spiking a 7% solution of IVIg with < 10(8) virus. The spiked IVIg solution was then filtered through a 75 nm Planova filter followed by two Planova 35 nm filters in series (75/35/35). The 75 nm prefilter is incorporated into this process to increase the capacity of the 35 nm viral removal filters. As a result of the inclusion of the 75 nm pre-filtration step it was possible to assess the removal of virus by the 35 nm filters independent of possible aggregation of the initial viral spiking material. Samples were collected at each step and immediately titred by viral plaque assay. A process control sample of the spiked load solution was held at the same conditions for the duration of the filtration process and then titred to determine the extent to which antibody neutralization may have contributed to overall viral reduction. Control assays of spiked IVIg were performed to establish the degree of toxicity of the IVIg solution to the indicator cell lines and the extent to which the IVIg interfered with plaque formation in the assay system. This combined data was used to establish assay sensitivity for the calculation of log removal by the filtration process. It was noted that toxicity/interference effects could have a significant effect upon apparent log reductions, and these effects could vary greatly, even within viruses of the same family. The results of these studies indicate that 35 nm filtration is very effective for removing substantial quantities of both non-enveloped and enveloped viruses from IVIg. Complete clearance (to the limits of detection of the assay) was obtained for all viruses larger than 35 nm. Interestingly, viruses reported to have mean diameters of less than 35 nm (EMC and HAV) were at least partially removed by the filtration (4.3 and > 4.7 logs removal, respectively). Even small viruses such as PPV were to some extent removed from the IVIg solution by the filters (2.6 logs removal). Reduction of BPV would not be assessed due to extensive neutralization and interference with plaque formation by the IVIg. Sindbis and SV40 also were subject to neutralization and assay interference due to the IVIg, though to a lesser extent. We conclude from these studies that the 35 nm mean pore size is functionally efficient in removal of smaller size viruses from spiked IVIg concentrates.