Impact of Seismic Risk on Lifetime Property Values

This report presents a methodology for establishing the uncertain net asset value, NAV, of a real-estate investment opportunity considering both market risk and seismic risk for the property. It also presents a decision-making procedure to assist in making real-estate investment choices under conditions of uncertainty and risk-aversion. It is shown that that market risk, as measured by the coefficient of variation of NAV, is at least 0.2 and may exceed 1.0. In a situation of such high uncertainty, where potential gains and losses are large relative to a decision-maker's risk tolerance, it is appropriate to adopt a decision-analysis approach to real-estate investment decision-making. A simple equation for doing so is presented. The decision-analysis approach uses the certainty equivalent, CE, as opposed to NAV as the basis for investment decision-making. That is, when faced with multiple investment alternatives, one should choose the alternative that maximizes CE. It is shown that CE is less than the expected value of NAV by an amount proportional to the variance of NAV and the inverse of the decision-maker's risk tolerance, [rho]. The procedure for establishing NAV and CE is illustrated in parallel demonstrations by CUREE and Kajima research teams. The CUREE demonstration is performed using a real 1960s-era hotel building in Van Nuys, California. The building, a 7-story non-ductile reinforced-concrete moment-frame building, is analyzed using the assembly-based vulnerability (ABV) method, developed in Phase III of the CUREE-Kajima Joint Research Program. The building is analyzed three ways: in its condition prior to the 1994 Northridge Earthquake, with a hypothetical shearwall upgrade, and with earthquake insurance. This is the first application of ABV to a real building, and the first time ABV has incorporated stochastic structural analyses that consider uncertainties in the mass, damping, and force-deformation behavior of the structure, along with uncertainties in ground motion, component damageability, and repair costs. New fragility functions are developed for the reinforced concrete flexural members using published laboratory test data, and new unit repair costs for these components are developed by a professional construction cost estimator. Four investment alternatives are considered: do not buy; buy; buy and retrofit; and buy and insure. It is found that the best alternative for most reasonable values of discount rate, risk tolerance, and market risk is to buy and leave the building as-is. However, risk tolerance and market risk (variability of income) both materially affect the decision. That is, for certain ranges of each parameter, the best investment alternative changes. This indicates that expected-value decision-making is inappropriate for some decision-makers and investment opportunities. It is also found that the majority of the economic seismic risk results from shaking of S[subscript a] < 0.3g, i.e., shaking with return periods on the order of 50 to 100 yr that cause primarily architectural damage, rather than from the strong, rare events of which common probable maximum loss (PML) measurements are indicative. The Kajima demonstration is performed using three Tokyo buildings. A nine-story, steel-reinforced-concrete building built in 1961 is analyzed as two designs: as-is, and with a steel-braced-frame structural upgrade. The third building is 29-story, 1999 steel-frame structure. The three buildings are intended to meet collapse-prevention, life-safety, and operational performance levels, respectively, in shaking with 10%exceedance probability in 50 years. The buildings are assessed using levels 2 and 3 of Kajima's three-level analysis methodology. These are semi-assembly based approaches, which subdivide a building into categories of components, estimate the loss of these component categories for given ground motions, and combine the losses for the entire building. The two methods are used to estimate annualized losses and to create curves that relate loss to exceedance probability. The results are incorporated in the input to a sophisticated program developed by the Kajima Corporation, called Kajima D, which forecasts cash flows for office, retail, and residential projects for purposes of property screening, due diligence, negotiation, financial structuring, and strategic planning. The result is an estimate of NAV for each building. A parametric study of CE for each building is presented, along with a simplified model for calculating CE as a function of mean NAV and coefficient of variation of NAV. The equation agrees with that developed in parallel by the CUREE team. Both the CUREE and Kajima teams collaborated with a number of real-estate investors to understand their seismic risk-management practices, and to formulate and to assess the viability of the proposed decision-making methodologies. Investors were interviewed to elicit their risk-tolerance, r, using scripts developed and presented here in English and Japanese. Results of 10 such interviews are presented, which show that a strong relationship exists between a decision-maker's annual revenue, R, and his or her risk tolerance, [rho is approximately equal to] 0.0075R[superscript 1.34]. The interviews show that earthquake risk is a marginal consideration in current investment practice. Probable maximum loss (PML) is the only earthquake risk parameter these investors consider, and they typically do not use seismic risk at all in their financial analysis of an investment opportunity. For competitive reasons, a public investor interviewed here would not wish to account for seismic risk in his financial analysis unless rating agencies required him to do so or such consideration otherwise became standard practice. However, in cases where seismic risk is high enough to significantly reduce return, a private investor expressed the desire to account for seismic risk via expected annualized loss (EAL) if it were inexpensive to do so, i.e., if the cost of calculating the EAL were not substantially greater than that of PML alone. The study results point to a number of interesting opportunities for future research, namely: improve the market-risk stochastic model, including comparison of actual long-term income with initial income projections; improve the risk-attitude interview; account for uncertainties in repair method and in the relationship between repair cost and loss; relate the damage state of structural elements with points on the force-deformation relationship; examine simpler dynamic analysis as a means to estimate vulnerability; examine the relationship between simplified engineering demand parameters and performance; enhance category-based vulnerability functions by compiling a library of building-specific ones; and work with lenders and real-estate industry analysts to determine the conditions under which seismic risk should be reflected in investors' financial analyses

Male infertility due to germ cell apoptosis in mice lacking the thiamin carrier, Tht1. A new insight into the critical role of thiamin in spermatogenesis.

A mouse model of thiamin-responsive megaloblastic anemia (diabetes mellitus, deafness, megaloblastic anemia) lacking functional Slc19a2 has been generated and unexpectedly found to have a male-specific sterility phenotype. We describe here the characterization of the testis-specific effects of absence of the high-affinity thiamin transporter, Tht1. Null males were found to have hypoplastic testes secondary to germ cell depletion. Morphologic and expression analysis revealed that under conditions of standard thiamin intake, tissues affected in the syndrome (pancreatic beta-cell, hematopoietic cells, auditory nerve) maintained normal function but pachytene stage spermatocytes underwent apoptosis. Under conditions of thiamin challenge, the apoptotic cell loss extended to earlier stages of germ cells but spared Sertoli cells and Leydig cells. Injection of high-dose thiamin was effective in reversing the spermatogenic failure, suggesting that the absence of the thiamin carrier could be overcome by diffusion-mediated transport at supranormal thiamin concentrations. These observations demonstrated that male germ cells, particularly those with high thiamin transporter expression beyond the blood-testis barrier, were more susceptible to apoptosis triggered by intracellular thiamin deficiency than any other tissue type. The findings described here highlight an unexpected and critical role for thiamin transport and metabolism in spermatogenesis

A Three-dimensional Printed Low-cost Anterior Shoulder Dislocation Model for Ultrasound-guided Injection Training.

Anterior shoulder dislocations are the most common, large joint dislocations that present to the emergency department (ED). Numerous studies support the use of intraarticular local anesthetic injections for the safe, effective, and time-saving reduction of these dislocations. Simulation training is an alternative and effective method for training compared to bedside learning. There are no commercially available ultrasound-compatible shoulder dislocation models. We utilized a three-dimensional (3D) printer to print a model that allows the visualization of the ultrasound anatomy (sonoanatomy) of an anterior shoulder dislocation. We utilized an open-source file of a shoulder, available from embodi3D® (Bellevue, WA, US). After approximating the relative orientation of the humerus to the glenoid fossa in an anterior dislocation, the humerus and scapula model was printed with an Ultimaker-2 Extended+ 3D® (Ultimaker, Cambridge, MA, US) printer using polylactic acid filaments. A 3D model of the external shoulder anatomy of a live human model was then created using Structure Sensor®(Occipital, San Francisco, CA, US), a 3D scanner. We aligned the printed dislocation model of the humerus and scapula within the resultant external shoulder mold. A pourable ballistics gel solution was used to create the final shoulder phantom. The use of simulation in medicine is widespread and growing, given the restrictions on work hours and a renewed focus on patient safety. The adage of see one, do one, teach one is being replaced by deliberate practice. Simulation allows such training to occur in a safe teaching environment. The ballistic gel and polylactic acid structure effectively reproduced the sonoanatomy of an anterior shoulder dislocation. The 3D printed model was effective for practicing an in-plane ultrasound-guided intraarticular joint injection. 3D printing is effective in producing a low-cost, ultrasound-capable model simulating an anterior shoulder dislocation. Future research will determine whether provider confidence and the use of intraarticular anesthesia for the management of shoulder dislocations will improve after utilizing this model

Logarithmic perturbation theory for quasinormal modes

Logarithmic perturbation theory (LPT) is developed and applied to quasinormal modes (QNMs) in open systems. QNMs often do not form a complete set, so LPT is especially convenient because summation over a complete set of unperturbed states is not required. Attention is paid to potentials with exponential tails, and the example of a Poschl-Teller potential is briefly discussed. A numerical method is developed that handles the exponentially large wavefunctions which appear in dealing with QNMs.Comment: 24 pages, 4 Postscript figures, uses ioplppt.sty and epsfig.st

An immunotherapy survivor population: health-related quality of life and toxicity in patients with metastatic melanoma treated with immune checkpoint inhibitors

© The Author(s) 2019. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.Purpose The immune checkpoint inhibitors (ICIs) have resulted in subgroups of patients with metastatic melanoma achievinghigh-quality durable responses. Metastatic melanoma survivors are a new population in the era of cancer survivorship. The aimofthis study was to evaluate metastatic melanoma survivors in terms of health-related quality of life (HRQoL), immune-relatedadverse events (irAEs) and exposure to immunosuppressive agents in a large single centre in the UK.Methods We defined the survivor population as patients with a diagnosis of metastatic melanoma who achieved a durableresponse to an ICI and had been followed-up for a minimum of 12 months from initiation of ICI without disease progression.HRQoL was assessed using SF-36. Electronic health records were accessed to collect data on demographics, treatments, irAEsand survival. HRQoL data was compared with two norm-based datasets.Results Eighty-four metastatic melanoma survivors were eligible and 87% (N = 73) completed the SF-36. ICI-related toxicity ofany grade occurred in 92%of patients and 43%had experienced a grade 3 or 4 toxicity. Almost half (49%) of the patients requiredsteroids for the treatment of ICI-related toxicity, whilst 14% required treatment with an immunosuppressive agent beyondsteroids.Melanoma survivors had statistically significant lower HRQoL scores with regard to physical, social and physical rolefunctioning and general health compared with the normative population. There was a trend towards inferior scores in patientswith previous exposure to ipilimumab compared with those never exposed to ipilimumab.Conclusions Our results show that metastatic melanoma survivors have potentially experienced significant ICI-related toxicityand experience significant impairments in specific HRQoL domains. Future service planning is required to meet this population’sunique survivorship needs.Peer reviewe

Exact Ampitude Ratio and Finite-Size Corrections for the M x N Square Lattice Ising Model The :

Let f, U and C represent, respectively, the free energy, the internal energy and the specific heat of the critical Ising model on the square M x N lattice with periodic boundary conditions. We find that N f and U are well-defined odd function of 1/N. We also find that ratios of subdominant (N^(-2 i - 1)) finite-size corrections amplitudes for the internal energy and the specific heat are constant. The free energy and the internal energy at the critical point are calculated asymtotically up to N^(-5) order, and the specific heat up to N^(-3) order.Comment: 18 pages, 4 figures, to be published in Phys. Rev. E 65, 1 February 200

Effect of Gravity and Confinement on Phase Equilibria: A Density Matrix Renormalization Approach

The phase diagram of the 2D Ising model confined between two infinite walls and subject to opposing surface fields and to a bulk "gravitational" field is calculated by means of density matrix renormalization methods. In absence of gravity two phase coexistence is restricted to temperatures below the wetting temperature. We find that gravity restores the two phase coexistence up to the bulk critical temperature, in agreement with previous mean-field predictions. We calculate the exponents governing the finite size scaling in the temperature and in the gravitational field directions. The former is the exponent which describes the shift of the critical temperature in capillary condensation. The latter agrees, for large surface fields, with a scaling assumption of Van Leeuwen and Sengers. Magnetization profiles in the two phase and in the single phase region are calculated. The profiles in the single phase region, where an interface is present, agree well with magnetization profiles calculated from a simple solid-on-solid interface hamiltonian.Comment: 4 pages, RevTeX and 4 PostScript figures included. Final version as published. To appear in Phys. Rev. Let

Exact renormalization-group analysis of first order phase transitions in clock models

We analyze the exact behavior of the renormalization group flow in one-dimensional clock-models which undergo first order phase transitions by the presence of complex interactions. The flow, defined by decimation, is shown to be single-valued and continuous throughout its domain of definition, which contains the transition points. This fact is in disagreement with a recently proposed scenario for first order phase transitions claiming the existence of discontinuities of the renormalization group. The results are in partial agreement with the standard scenario. However in the vicinity of some fixed points of the critical surface the renormalized measure does not correspond to a renormalized Hamiltonian for some choices of renormalization blocks. These pathologies although similar to Griffiths-Pearce pathologies have a different physical origin: the complex character of the interactions. We elucidate the dynamical reason for such a pathological behavior: entire regions of coupling constants blow up under the renormalization group transformation. The flows provide non-perturbative patterns for the renormalization group behavior of electric conductivities in the quantum Hall effect.Comment: 13 pages + 3 ps figures not included, TeX, DFTUZ 91.3

Radiosurgery for brainstem metastases with and without whole brain radiotherapy: clinical series and literature review

Objective The objective of this study was to investigate outcomes for patients with brainstem metastases treated with stereotactic radiosurgery (SRS). Methods Patients with brainstem metastases treated with SRS between April 2006 and June 2012 were identified from a prospective database. Patient and treatment-related factors were recorded. Kaplan-Meier analysis was used to calculate survival and freedom from local and distant brain progression. Univariate and multivariate Cox regression was used to identify factors important for overall survival. Results In total, 44 patients received SRS for 48 brainstem metastases of whom 33 (75 %) also received whole brain radiotherapy (WBRT): 23 patients (52 %) WBRT prior to SRS, 6 (13.6 %) WBRT concurrently with SRS and 4 (9.0 %) WBRT after SRS. Eight patients received a second course ofWBRTat further progression. Median target volume was 1.33 cc (range 0.04–12.17) and median prescribed marginal dose was 15 Gy (range 10–22). There were four cases of local failure, and 6-month and 1-year freedom from local failure was 84.6 and 76.9 %, respectively. Median overall survival (OS) was 5.4 months. There were four cases of radionecrosis, 2 (4.8 %) of which were symptomatic. The absence of external beam brain radiotherapy (predominantly WBRT) showed a trend towards improved OS on univariate analysis. Neither local nor distant brain failure significantly impacted OS. Conclusion This retrospective series of patients treated with SRS for brainstem metastases, largely in combination with at least one course of WBRT, demonstrates that this approach is safe and results in good local control. In this cohort, no variables significantly impacted OS, including intracranial control

De novo variants disturbing the transactivation capacity of POU3F3 cause a characteristic neurodevelopmental disorder

POU3F3, also referred to as Brain-1, is a well-known transcription factor involved in the development of the central nervous system, but it has not previously been associated with a neurodevelopmental disorder. Here, we report the identification of 19 individuals with heterozygous POU3F3 disruptions, most of which are de novo variants. All individuals had developmental delays and/or intellectual disability and impairments in speech and language skills. Thirteen individuals had characteristic low-set, prominent, and/or cupped ears. Brain abnormalities were observed in seven of eleven MRI reports. POU3F3 is an intronless gene, insensitive to nonsense-mediated decay, and 13 individuals carried protein-truncating variants. All truncating variants that we tested in cellular models led to aberrant subcellular localization of the encoded protein. Luciferase assays demonstrated negative effects of these alleles on transcriptional activation of a reporter with a FOXP2-derived binding motif. In addition to the loss-of-function variants, five individuals had missense variants that clustered at specific positions within the functional domains, and one small in-frame deletion was identified. Two missense variants showed reduced transactivation capacity in our assays, whereas one variant displayed gain-of-function effects, suggesting a distinct pathophysiological mechanism. In bioluminescence resonance energy transfer (BRET) interaction assays, all the truncated POU3F3 versions that we tested had significantly impaired dimerization capacities, whereas all missense variants showed unaffected dimerization with wild-type POU3F3. Taken together, our identification and functional cell-based analyses of pathogenic variants in POU3F3, coupled with a clinical characterization, implicate disruptions of this gene in a characteristic neurodevelopmental disorder