Current Noise of Hydrodynamic Electrons.

A resistor at finite temperature produces white noise fluctuations of the current called Johnson-Nyquist noise. Measuring the amplitude of this noise provides a powerful primary thermometry technique to access the electron temperature. In practical situations, however, one needs to generalize the Johnson-Nyquist theorem to handle spatially inhomogeneous temperature profiles. Recent work provided such a generalization for Ohmic devices obeying the Wiedemann-Franz law, but there is a need to provide a similar generalization for hydrodynamic electron systems, since hydrodynamic electrons provide unusual sensitivity for Johnson noise thermometry but they do not admit a local conductivity nor obey the Wiedemann-Franz law. Here we address this need by considering low-frequency Johnson noise in the hydrodynamic setting for a rectangular geometry. Unlike in the Ohmic setting, we find that the Johnson noise is geometry dependent due to nonlocal viscous gradients. Nonetheless, ignoring the geometric correction only leads to an error of at most 40% as compared to naively using the Ohmic result.

Cascade of Multielectron Bubble Phases in Monolayer Graphene at High Landau Level Filling.

The phase diagram of an interacting two-dimensional electron system in a high magnetic field is enriched by the varying form of the effective Coulomb interaction, which depends strongly on the Landau level index. While the fractional quantum Hall states that dominate in the lower-energy Landau levels have been explored experimentally in a variety of two-dimensional systems, much less work has been done to explore electron solids owing to their subtle transport signatures and extreme sensitivity to disorder. Here, we use chemical potential measurements to map the phase diagram of electron solid states in N=2, N=3, and N=4 Landau levels in monolayer graphene. Direct comparison between our data and theoretical calculations reveals a cascade of density-tuned phase transitions between electron bubble phases up to two, three, or four electrons per bubble in the N=2, 3, and 4 Landau levels, respectively. Finite-temperature measurements are consistent with melting of the solids for T≈1 K.

A gap-protected zero-Hall effect state in the quantum limit of the non-symmorphic metal KHgSb.

A recurring theme in topological matter is the protection of unusual electronic states by symmetry, for example, protection of the surface states in Z2 topological insulators by time-reversal symmetry1-3. Recently, interest has turned to unusual surface states in the large class of non-symmorphic materials4-12. In particular, KHgSb is predicted to exhibit double quantum spin Hall states10. Here we report measurements of the Hall conductivity in KHgSb in a strong magnetic field B. In the quantum limit, the Hall conductivity is observed to fall exponentially to zero, but the diagonal conductivity is finite. A large gap protects this unusual zero-Hall state. We theoretically propose that, in this quantum limit, the chemical potential drops into the bulk gap, intersecting equal numbers of right- and left-moving quantum spin Hall surface modes to produce the zero-Hall state. The zero-Hall state illustrates how topological protection in a non-symmorphic material with glide symmetry may lead to highly unusual transport phenomena.

Band-Gap-Dependent Electronic Compressibility of Carbon Nanotubes in the Wigner Crystal Regime.

Electronic compressibility, the second derivative of ground-state energy with respect to total electron number, is a measurable quantity that reveals the interaction strength of a system and can be used to characterize the orderly crystalline lattice of electrons known as the Wigner crystal. Here, we measure the electronic compressibility of individual suspended ultraclean carbon nanotubes in the low-density Wigner crystal regime. Using low-temperature quantum transport measurements, we determine the compressibility as a function of carrier number in nanotubes with varying band gaps. We observe two qualitatively different trends in compressibility versus carrier number, both of which can be explained using a theoretical model of a Wigner crystal that accounts for both the band gap and the confining potential experienced by charge carriers. We extract the interaction strength as a function of carrier number for individual nanotubes and show that the compressibility can be used to distinguish between strongly and weakly interacting regimes.

Effect of Magnetization on the Tunneling Anomaly in Compressible Quantum Hall States.

Tunneling of electrons into a two-dimensional electron system is known to exhibit an anomaly at low bias, in which the tunneling conductance vanishes due to a many-body interaction effect. Recent experiments have measured this anomaly between two copies of the half-filled Landau level as a function of in-plane magnetic field, and they suggest that increasing spin polarization drives a deeper suppression of tunneling. Here, we present a theory of the tunneling anomaly between two copies of the partially spin-polarized Halperin-Lee-Read state, and we show that the conventional description of the tunneling anomaly, based on the Coulomb self-energy of the injected charge packet, is inconsistent with the experimental observation. We propose that the experiment is operating in a different regime, not previously considered, in which the charge-spreading action is determined by the compressibility of the composite fermions.

Benzodiazepine Initiation and Dose Escalation.

BACKGROUND: Benzodiazepines (BZDs) place patients at a significant risk of falling. The current literature does not address if this risk is increased during initiation or dose escalations of BZDs. OBJECTIVE: To determine if initiation or dose escalations of BZD regimens are associated with an increased risk of falls in hospitalized patients compared with patients maintained on their home dose or who had their dose decreased from baseline. METHODS: This retrospective case-control study evaluated hospitalized patients aged 45 years or older who received a BZD. Patients who did not fall were collected in a 3:1 ratio to patients who fell. Comparisons were made between BZD regimens prior to admission and those 48 hours prior to the index date. The date of fall served as the index date for patients who fell, and the median time-to-fall served as the index date for all other patients. RESULTS: A total of 132 patients were included in the study (33 falls and 99 without a fall). No significant differences were noted in demographics, baseline mobility, or past medical history. Patients who fell had a significantly longer median length of stay (15 vs 10 days; P = 0.025). Additionally, patients who fell were more likely to have had their BZD regimen initiated or dose escalated compared with patients who did not fall (63.6% vs 41.4%; P = 0.043). CONCLUSIONS: The risk of falling while on a BZD is increased on initiation and dose escalations. Hospitals should ensure judicious use of BZDs in inpatients to reduce the risk of falls.

Impact of Evidence-Based Guidelines on Outcomes of Hospitalized Patients With Clostridium difficile Infection.

OBJECTIVES: Clostridium difficile infection (CDI) is the most common healthcare-associated infection in the United States. Clinical practice guidelines for the treatment of CDI were updated in 2010 by the Society for Healthcare Epidemiology of America and the Infectious Diseases Society of America. An institutional guideline for the classification and management of CDI in accordance with the 2010 Society for Healthcare Epidemiology of America/Infectious Diseases Society of America guideline was developed and provided to attending physicians and medical residents in multiple formats. METHODS: We sought to determine the impact of an evidence-based guideline for the treatment of CDI at a community teaching hospital. A retrospective chart review was conducted to identify length of stay (LOS), readmission rates, direct cost, mortality, and physician adherence to guidelines in patients with International Classification of Diseases, Ninth Edition codes and laboratory confirmation of CDI between February 1, 2013 and January 31, 2014. Endpoints included LOS after diagnosis of CDI, 30-day readmission rates, direct cost after diagnosis of CDI, and mortality. RESULTS: A total of 351 patient encounters were included in the study. Although not statistically significant, it was found that guideline-based therapy (n = 131) was associated with a lower median LOS (6 days vs 8 days; P = 0.06). Thirty-day hospital readmission (25.2% vs 29.5%; P = 0.39) and median cost after diagnosis of CDI ($7238.48 vs $8794.81; P = 0.10) also were lower but not statistically significant. Patients with mild-to-moderate infection were found to have a significantly lower median LOS (5 days vs 7 days; P = 0.03) and median cost after diagnosis ($5257.85 vs $7680.56; P = 0.03) when treated with guideline-based therapy. Overall physician adherence to guidelines was low, at 38%. CONCLUSIONS: Treatment with guideline-based therapy for CDI was associated with a trend toward a significantly lower LOS and cost. Barriers to physician adherence to guidelines still exist, despite education and guideline availability. Electronic health record-based order sets or clinical decision tools may improve recognition of and adherence to guidelines.

Universal power law governing pedestrian interactions.

Human crowds often bear a striking resemblance to interacting particle systems, and this has prompted many researchers to describe pedestrian dynamics in terms of interaction forces and potential energies. The correct quantitative form of this interaction, however, has remained an open question. Here, we introduce a novel statistical-mechanical approach to directly measure the interaction energy between pedestrians. This analysis, when applied to a large collection of human motion data, reveals a simple power-law interaction that is based not on the physical separation between pedestrians but on their projected time to a potential future collision, and is therefore fundamentally anticipatory in nature. Remarkably, this simple law is able to describe human interactions across a wide variety of situations, speeds, and densities. We further show, through simulations, that the interaction law we identify is sufficient to reproduce many known crowd phenomena.

Building Interprofessional Competencies Through a Collaborative Prescribing Activity With Osteopathic, Pharmacy, and Physician Assistant Students.

Introduction: Medication errors can lead to significant adverse events. Nearly 50% of medication errors occur during the prescription-writing stage of the medication use process, and effective interprofessional collaboration and communication are key to reducing error in this process. Methods: We developed a three-part, 60-minute, interprofessional education activity providing medical, physician assistant, and pharmacy students the opportunity to practice collegial interprofessional communication surrounding prescribing practices. Learners met virtually initially as a large group and divided into small groups facilitated by a health professional. Part 1 involved reviewing two prescriptions prepared by learners; part 2 was a discussion about the education, roles, and responsibilities of each profession; and part 3 focused on identifying prescription errors in examples provided by faculty. Students completed a post-pre survey measuring their perception of learning the Interprofessional Collaborative Competency Attainment Survey (ICCAS) areas. Results: Of 317 participants (151 doctor of osteopathy, 68 master of physician assistant studies, and 98 doctor of pharmacy students), 286 completed the post-pre survey, for a 90% response rate. Students reported statistically significant (p < .001) increases in all 20 questions spanning the six ICCAS areas. Discussion: The virtual format allowed multiple institutions to participate from various locations. It broadened the learners' experience by fostering interaction among those with varied perspectives and allowed collaboration between locations and programs that otherwise could not have participated. The activity introduced students to virtual collaboration and key telehealth skills, enhancing their confidence and familiarity with virtual interactions in a professional setting.

Casimersen (AMONDYS 45™): An Antisense Oligonucleotide for Duchenne Muscular Dystrophy.

Casimersen (AMONDYS 45TM) is an antisense oligonucleotide of the phosphorodiamidate morpholino oligomer subclass developed by Sarepta therapeutics. It was approved by the Food and Drug Administration (FDA) in February 2021 to treat Duchenne muscular dystrophy (DMD) in patients whose DMD gene mutation is amenable to exon 45 skipping. Administered intravenously, casimersen binds to the pre-mRNA of the DMD gene to skip a mutated region of an exon, thereby producing an internally truncated yet functional dystrophin protein in DMD patients. This is essential in maintaining the structure of a myocyte membrane. While casimersen is currently continuing in phase III of clinical trials in various countries, it was granted approval by the FDA under the accelerated approval program due to its observed increase in dystrophin production. This article discusses the pathophysiology of DMD, summarizes available treatments thus far, and provides a full drug review of casimersen (AMONDYS 45TM).

Why is the bulk resistivity of topological insulators so small?

As-grown topological insulators (TIs) are typically heavily doped n-type crystals. Compensation by acceptors is used to move the Fermi level to the middle of the band gap, but even then TIs have a frustratingly small bulk resistivity. We show that this small resistivity is the result of band bending by poorly screened fluctuations in the random Coulomb potential. Using numerical simulations of a completely compensated TI, we find that the bulk resistivity has an activation energy of just 0.15 times the band gap, in good agreement with experimental data. At lower temperatures activated transport crosses over to variable range hopping with a relatively large localization length.

Coulomb gap triptych in a periodic array of metal nanocrystals.

The Coulomb gap in the single-particle density of states (DOS) is a universal consequence of electron-electron interaction in disordered systems with localized electron states. Here we show that in arrays of monodisperse metallic nanocrystals, there is not one but three identical adjacent Coulomb gaps, which together form a structure that we call a "Coulomb gap triptych." We calculate the DOS and the conductivity in two- and three-dimensional arrays using a computer simulation. Unlike in the conventional Coulomb glass models, in nanocrystal arrays the DOS has a fixed width in the limit of large disorder. The Coulomb gap triptych can be studied via tunneling experiments.

Electronic thermal transport measurement in low-dimensional materials with graphene non-local noise thermometry.

In low-dimensional systems, the combination of reduced dimensionality, strong interactions and topology has led to a growing number of many-body quantum phenomena. Thermal transport, which is sensitive to all energy-carrying degrees of freedom, provides a discriminating probe of emergent excitations in quantum materials and devices. However, thermal transport measurements in low dimensions are dominated by the phonon contribution of the lattice, requiring an experimental approach to isolate the electronic thermal conductance. Here we measured non-local voltage fluctuations in a multi-terminal device to reveal the electronic heat transported across a mesoscopic bridge made of low-dimensional materials. Using two-dimensional graphene as a noise thermometer, we measured the quantitative electronic thermal conductance of graphene and carbon nanotubes up to 70 K, achieving a precision of ~1% of the thermal conductance quantum at 5 K. Employing linear and nonlinear thermal transport, we observed signatures of energy transport mediated by long-range interactions in one-dimensional electron systems, in agreement with a theoretical model.

Osilodrostat for the treatment of Cushing's disease.

INTRODUCTION: The treatment of Cushing's disease (CD) has been advanced well with the introduction of treatment options like transsphenoidal surgery, radiosurgery, bilateral adrenalectomy, and various classes of medication; however, many patients still fail to achieve disease remission. Osilodrostat, an orally bioavailable adrenal steroidogenesis inhibitor, was approved in the USA and EU in 2020 for the treatment of CD. AREAS COVERED: This review provides an overview of Cushing's disease and the newly FDA approved 11ß-hydroxylase inhibitor, osilodrostat, for CD with a focus on pharmacodynamics, pharmacokinetics, safety and efficacy data, and phase 2 and 3 clinical trials. EXPERT OPINION: Osilodrostat has proven clinical efficacy and tolerability in phase 2 and 3 trials with CD patients who had an inadequate or reoccurring response to transsphenoidal surgery (TSS) and conventional first-line treatment. The phase 3 trial (LINC3) had 86% of the treatment group respond with normal urinary free cortisol (UFC) level compared to 29% in the placebo group (p < 0.001). Deemed as well-tolerated in all current pivotal trials, oral osilodrostat provides a noninvasive option for patients who cannot undergo surgery or patients who have reoccurring hypercortisolemia.

Superspreading of SARS-CoV-2 in the USA.

A number of epidemics, including the SARS-CoV-1 epidemic of 2002-2004, have been known to exhibit superspreading, in which a small fraction of infected individuals is responsible for the majority of new infections. The existence of superspreading implies a fat-tailed distribution of infectiousness (new secondary infections caused per day) among different individuals. Here, we present a simple method to estimate the variation in infectiousness by examining the variation in early-time growth rates of new cases among different subpopulations. We use this method to estimate the mean and variance in the infectiousness, ß, for SARS-CoV-2 transmission during the early stages of the pandemic within the United States. We find that σß/µß ≳ 3.2, where µß is the mean infectiousness and σß its standard deviation, which implies pervasive superspreading. This result allows us to estimate that in the early stages of the pandemic in the USA, over 81% of new cases were a result of the top 10% of most infectious individuals.

The Metabolic Bone Disease X-linked Hypophosphatemia: Case Presentation, Pathophysiology and Pharmacology.

The authors present a stereotypical case presentation of X-linked hypophosphatemia (XLH) and provide a review of the pathophysiology and related pharmacology of this condition, primarily focusing on the FDA-approved medication burosumab. XLH is a renal phosphate wasting disorder caused by loss of function mutations in the PHEX gene (phosphate-regulating gene with homologies to endopeptidases on the X chromosome). Typical biochemical findings include elevated serum levels of bioactive/intact fibroblast growth factor 23 (FGF23) which lead to (i) low serum phosphate levels, (ii) increased fractional excretion of phosphate, and (iii) inappropriately low or normal 1,25-dihydroxyvitamin D (1,25-vitD). XLH is the most common form of heritable rickets and short stature in patients with XLH is due to chronic hypophosphatemia. Additionally, patients with XLH experience joint pain and osteoarthritis from skeletal deformities, fractures, enthesopathy, spinal stenosis, and hearing loss. Historically, treatment for XLH was limited to oral phosphate supplementation, active vitamin D supplementation, and surgical intervention for cases of severe bowed legs. In 2018, the United States Food and Drug Administration (FDA) approved burosumab for the treatment of XLH and this medication has demonstrated substantial benefit compared with conventional therapy. Burosumab binds circulating intact FGF23 and blocks its biological effects in target tissues, resulting in increased serum inorganic phosphate (Pi) concentrations and increased conversion of inactive vitamin D to active 1,25-vitD.

Capacitance of the double layer formed at the metal/ionic-conductor interface: how large can it be?

The capacitance of the double layer formed at a metal/ionic-conductor interface can be remarkably large, so that the apparent width of the double layer is as small as 0.3 A. Mean-field theories fail to explain such large capacitance. We propose an alternate theory of the ionic double layer which allows for the binding of discrete ions to their image charges in the metal. We show that at small voltages the capacitance of the double layer is limited only by the weak dipole-dipole repulsion between bound ions, and is therefore very large. At large voltages the depletion of bound ions from one of the capacitor electrodes triggers a collapse of the capacitance to the mean-field value.

Observation of a thermoelectric Hall plateau in the extreme quantum limit.

The thermoelectric Hall effect is the generation of a transverse heat current upon applying an electric field in the presence of a magnetic field. Here, we demonstrate that the thermoelectric Hall conductivity αxy in the three-dimensional Dirac semimetal ZrTe5 acquires a robust plateau in the extreme quantum limit of magnetic field. The plateau value is independent of the field strength, disorder strength, carrier concentration, or carrier sign. We explain this plateau theoretically and show that it is a unique signature of three-dimensional Dirac or Weyl electrons in the extreme quantum limit. We further find that other thermoelectric coefficients, such as the thermopower and Nernst coefficient, are greatly enhanced over their zero-field values even at relatively low fields.

Quantized thermoelectric Hall effect induces giant power factor in a topological semimetal.

Thermoelectrics are promising by directly generating electricity from waste heat. However, (sub-)room-temperature thermoelectrics have been a long-standing challenge due to vanishing electronic entropy at low temperatures. Topological materials offer a new avenue for energy harvesting applications. Recent theories predicted that topological semimetals at the quantum limit can lead to a large, non-saturating thermopower and a quantized thermoelectric Hall conductivity approaching a universal value. Here, we experimentally demonstrate the non-saturating thermopower and quantized thermoelectric Hall effect in the topological Weyl semimetal (WSM) tantalum phosphide (TaP). An ultrahigh longitudinal thermopower [Formula: see text] and giant power factor [Formula: see text] are observed at ~40 K, which is largely attributed to the quantized thermoelectric Hall effect. Our work highlights the unique quantized thermoelectric Hall effect realized in a WSM toward low-temperature energy harvesting applications.