Ariel - Volume 5 Number 6

Editors J.D. Kanofsky Mark Dembert Entertainment Robert Breckenridge Joe Conti Gary Kaskey Photographer Scot Kastner Overseas Editor Mike Sinason Circulation Jay Amsterdam Humorist Jim McCann Staff Ken Jaffe Bob Sklaroff Janet Welsh Dave Jacoby Phil Nimoityn Frank Chervane

Why do banks promise to pay par on demand?

We survey the theories of why banks promise to pay par on demand and examine evidence about the conditions under which banks have promised to pay the par value of deposits and banknotes on demand when holding only fractional reserves. The theoretical literature can be broadly divided into four strands: liquidity provision, asymmetric information, legal restrictions, and a medium of exchange. We assume that it is not zero cost to make a promise to redeem a liability at par value on demand. If so, then the conditions in the theories that result in par redemption are possible explanations of why banks promise to pay par on demand. If the explanation based on customers’ demand for liquidity is correct, payment of deposits at par will be promised when banks hold assets that are illiquid in the short run. If the asymmetric-information explanation based on the difficulty of valuing assets is correct, the marketability of banks’ assets determines whether banks promise to pay par. If the legal restrictions explanation of par redemption is correct, banks will not promise to pay par if they are not required to do so. If the transaction explanation is correct, banks will promise to pay par value only if the deposits are used in transactions. After the survey of the theoretical literature, we examine the history of banking in several countries in different eras: fourth-century Athens, medieval Italy, Japan, and free banking and money market mutual funds in the United States. We find that all of the theories can explain some of the observed banking arrangements, and none explain all of them

Intratumoral pan-ErbB targeted CAR-T for head and neck squamous cell carcinoma: interim analysis of the T4 immunotherapy study

Background: Locally advanced/recurrent head and neck squamous cell carcinoma (HNSCC) is associated with significant morbidity and mortality. To target upregulated ErbB dimer expression in this cancer, we developed an autologous CD28-based chimeric antigen receptor T-cell (CAR-T) approach named T4 immunotherapy. Patient-derived T-cells are engineered by retroviral transduction to coexpress a panErbB-specific CAR called T1E28ζ and an IL-4-responsive chimeric cytokine receptor, 4αβ, which allows IL-4-mediated enrichment of transduced cells during manufacture. These cells elicit preclinical antitumor activity against HNSCC and other carcinomas. In this trial, we used intratumoral delivery to mitigate significant clinical risk of on-target off-tumor toxicity owing to low-level ErbB expression in healthy tissues. // Methods: We undertook a phase 1 dose-escalation 3+3 trial of intratumoral T4 immunotherapy in HNSCC (NCT01818323). CAR T-cell batches were manufactured from 40 to 130 mL of whole blood using a 2-week semiclosed process. A single CAR T-cell treatment, formulated as a fresh product in 1–4 mL of medium, was injected into one or more target lesions. Dose of CAR T-cells was escalated in 5 cohorts from 1×107−1×109 T4+ T-cells, administered without prior lymphodepletion. // Results: Despite baseline lymphopenia in most enrolled subjects, the target cell dose was successfully manufactured in all cases, yielding up to 7.5 billion T-cells (67.5±11.8% transduced), without any batch failures. Treatment-related adverse events were all grade 2 or less, with no dose-limiting toxicities (Common Terminology Criteria for Adverse Events V.4.0). Frequent treatment-related adverse events were tumor swelling, pain, pyrexias, chills, and fatigue. There was no evidence of leakage of T4+ T-cells into the circulation following intratumoral delivery, and injection of radiolabeled cells demonstrated intratumoral persistence. Despite rapid progression at trial entry, stabilization of disease (Response Evaluation Criteria in Solid Tumors V.1.1) was observed in 9 of 15 subjects (60%) at 6 weeks post-CAR T-cell administration. Subsequent treatment with pembrolizumab and T-VEC oncolytic virus achieved a rapid complete clinical response in one subject, which was durable for over 3 years. Median overall survival was greater than for historical controls. Disease stabilization was associated with the administration of an immunophenotypically fitter, less exhausted, T4 CAR T-cell product. // Conclusions: These data demonstrate the safe intratumoral administration of T4 immunotherapy in advanced HNSCC

Development of a Kemp\u27s Ridley Sea Turtle Stock Assessment Model

We developed a Kemp’s ridley (Lepidochelys kempii) stock assessment model to evaluate the relative contributions of conservation efforts and other factors toward this critically endangered species’ recovery. The Kemp’s ridley demographic model developed by the Turtle Expert Working Group (TEWG) in 1998 and 2000 and updated for the binational recovery plan in 2011 was modified for use as our base model. The TEWG model uses indices of the annual reproductive population (number of nests) and hatchling recruitment to predict future annual numbers of nests on the basis of a series of assumptions regarding age and maturity, remigration interval, sex ratios, nests per female, juvenile mortality, and a putative ‘‘turtle excluder device effect’’ multiplier starting in 1990. This multiplier was necessary to fit the number of nests observed in 1990 and later. We added the effects of shrimping effort directly, modified by habitat weightings, as a proxy for all sources of anthropogenic mortality. Additional data included in our model were incremental growth of Kemp’s ridleys marked and recaptured in the Gulf of Mexico, and the length frequency of stranded Kemp’s ridleys. We also added a 2010 mortality factor that was necessary to fit the number of nests for 2010 and later (2011 and 2012). Last, we used an empirical basis for estimating natural mortality, on the basis of a Lorenzen mortality curve and growth estimates. Although our model generated reasonable estimates of annual total turtle deaths attributable to shrimp trawling, as well as additional deaths due to undetermined anthropogenic causes in 2010, we were unable to provide a clear explanation for the observed increase in the number of stranded Kemp’s ridleys in recent years, and subsequent disruption of the species’ exponential growth since the 2009 nesting season. Our consensus is that expanded data collection at the nesting beaches is needed and of high priority, and that 2015 be targeted for the next stock assessment to evaluate the 2010 event using more recent nesting and in-water data

The rise and fall of the king : the correlation between FO Aquarii's low states and the White Dwarf's Spindown

The intermediate polar FO Aquarii experienced its first-reported low-accretion states in 2016, 2017, and 2018. We establish that these low states occurred shortly after the system's white dwarf (WD) began spinning down, after having spent a quarter-century spinning up. FO Aquarii is the only intermediate polar whose period derivative has undergone a sign change, and it has now done so twice. By combining our spin-pulse timings with previous data, we determine that the WD's spin period has varied quasi-sinusoidally since the system's discovery, and an extrapolation predicts that the white dwarf was spinning down during newly discovered low states in photographic plates from 1964, 1965, and 1974. Thus, FO Aquarii's low states appear to occur exclusively during epochs of spindown. Additionally, our time-series photometry of the 2016-18 low states reveals that the mode of accretion is extremely sensitive to the accretion rate; when the system is fainter than V~14.0, the accretion onto the WD is largely stream-fed, but when it is brighter, it is almost exclusively disk-fed. The system's grazing eclipse remained detectable throughout all observations, confirming the uninterrupted presence of a disk-like structure, regardless of the accretion state. Our observations are consistent with theoretical predictions that during the low states, the accretion disk dissipates into a ring of diamagnetic blobs. Finally, a new XMM-Newton observation from 2017 indicates that the system's anomalously soft X-ray spectrum and diminished X-ray luminosity in the wake of the 2016 low state appear to be long-lasting changes compared to pre-2016 observations.peer-reviewe

Electromagnetic Treatment to Old Alzheimer's Mice Reverses β-Amyloid Deposition, Modifies Cerebral Blood Flow, and Provides Selected Cognitive Benefit

Few studies have investigated physiologic and cognitive effects of “long-term" electromagnetic field (EMF) exposure in humans or animals. Our recent studies have provided initial insight into the long-term impact of adulthood EMF exposure (GSM, pulsed/modulated, 918 MHz, 0.25–1.05 W/kg) by showing 6+ months of daily EMF treatment protects against or reverses cognitive impairment in Alzheimer's transgenic (Tg) mice, while even having cognitive benefit to normal mice. Mechanistically, EMF-induced cognitive benefits involve suppression of brain β-amyloid (Aβ) aggregation/deposition in Tg mice and brain mitochondrial enhancement in both Tg and normal mice. The present study extends this work by showing that daily EMF treatment given to very old (21–27 month) Tg mice over a 2-month period reverses their very advanced brain Aβ aggregation/deposition. These very old Tg mice and their normal littermates together showed an increase in general memory function in the Y-maze task, although not in more complex tasks. Measurement of both body and brain temperature at intervals during the 2-month EMF treatment, as well as in a separate group of Tg mice during a 12-day treatment period, revealed no appreciable increases in brain temperature (and no/slight increases in body temperature) during EMF “ON" periods. Thus, the neuropathologic/cognitive benefits of EMF treatment occur without brain hyperthermia. Finally, regional cerebral blood flow in cerebral cortex was determined to be reduced in both Tg and normal mice after 2 months of EMF treatment, most probably through cerebrovascular constriction induced by freed/disaggregated Aβ (Tg mice) and slight body hyperthermia during “ON" periods. These results demonstrate that long-term EMF treatment can provide general cognitive benefit to very old Alzheimer's Tg mice and normal mice, as well as reversal of advanced Aβ neuropathology in Tg mice without brain heating. Results further underscore the potential for EMF treatment against AD

A cluster randomized trial of standard quality improvement versus patient-centered interventions to enhance depression care for African Americans in the primary care setting: study protocol NCT00243425

<p>Abstract</p> <p>Background</p> <p>Several studies document disparities in access to care and quality of care for depression for African Americans. Research suggests that patient attitudes and clinician communication behaviors may contribute to these disparities. Evidence links patient-centered care to improvements in mental health outcomes; therefore, quality improvement interventions that enhance this dimension of care are promising strategies to improve treatment and outcomes of depression among African Americans. This paper describes the design of the BRIDGE (Blacks Receiving Interventions for Depression and Gaining Empowerment) Study. The goal of the study is to compare the effectiveness of two interventions for African-American patients with depression--a standard quality improvement program and a patient-centered quality improvement program. The main hypothesis is that patients in the patient-centered group will have a greater reduction in their depression symptoms, higher rates of depression remission, and greater improvements in mental health functioning at six, twelve, and eighteen months than patients in the standard group. The study also examines patient ratings of care and receipt of guideline-concordant treatment for depression.</p> <p>Methods/Design</p> <p>A total of 36 primary care clinicians and 132 of their African-American patients with major depressive disorder were recruited into a cluster randomized trial. The study uses intent-to-treat analyses to compare the effectiveness of standard quality improvement interventions (academic detailing about depression guidelines for clinicians and disease-oriented care management for their patients) and patient-centered quality improvement interventions (communication skills training to enhance participatory decision-making for clinicians and care management focused on explanatory models, socio-cultural barriers, and treatment preferences for their patients) for improving outcomes over 12 months of follow-up.</p> <p>Discussion</p> <p>The BRIDGE Study includes clinicians and African-American patients in under-resourced community-based practices who have not been well-represented in clinical trials to improve depression care. The patient-centered and culturally targeted approach to depression care is a relatively new one that has not been tested in most previous studies. The study will provide evidence about whether patient-centered accommodations improve quality of care and outcomes to a greater extent than standard quality improvement strategies for African Americans with depression.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov NCT00243425</p