Three Essays on Health Care

This dissertation has been motivated by the question of how countries should optimally structure health care. Especially, there are two important economic and policy questions asked that extend beyond the area of health economics. The first is how the expansion of health insurance coverage affects the utilization and health of its beneficiaries (extensive margin); the second is how generous should health insurance be (intensive margin) to balance the provision of care and financial protection against risk while containing medical expenditures. The three chapters in this dissertation aim to make empirical contributions to these ongoing research questions. First chapter, "The Effect of Patient Cost-Sharing on Utilization, Health and Risk Protection: Evidence from Japan" addresses the second question. It investigates how cost-sharing, requiring patients to pay a share of the cost of care, affects the demand for care, health itself, and risk protection among the elderly, the largest consumers of health service. Previous studies of cost-sharing have had difficulty separating the effect of cost-sharing on patients from the influence of medical providers and insurers. This paper overcomes that limitation by examining a sharp reduction in cost-sharing at age 70 in Japan in a regression discontinuity design. I find that price elasticities of demand for both inpatient admissions and outpatient visits among the elderly are comparable to prior estimates for the non-elderly. I also find that the welfare gain from risk protection is relatively small compared to the deadweight loss of program financing, suggesting that the social cost of lower cost-sharing may outweigh social benefit. Taken together, this study shows that an increase in cost-sharing may be achieved without decreasing total welfare. Third chapter, "Effects of Universal Health Insurance on Health Care Utilization, Supply-Side Responses and Mortality Rates: Evidence from Japan" (with Ayako Kondo) address the first question. Even though most developed countries have implemented some form of universal public health insurance, most studies on the impact of the health insurance coverage have been limited to specific subpopulations, such as infants and children, the elderly or the poor. We investigate the effects of a massive expansion in health insurance coverage on utilization and health by examining the introduction of universal health insurance in Japan in 1961. We find that health care utilization increases more than would be expected from previous estimates of the elasticities of individual-level changes in health insurance status such as RAND Health Insurance Experiment in the US. The two chapters addressed above focus on consumers' incentives. Second chapter, "Supply-Induced Demand in Newborn Treatment: Evidence from Japan" (with Kiyohide Fushimi) examines the incentives faced by medical providers. Since medical providers exert a strong influence over the quantity and types of medical care demanded, measuring the size of supply-induced demand (SID) has been a long-standing controversy in health economics. However, past studies may underestimate the size of SID since it is empirically difficult to isolate SID from other confounding hospital behaviors, such as changes in the selection of patients. We overcome these empirical challenges by focusing on a specific population: at-risk newborns, and we measure the degree of SID by exploiting changes in reimbursement caused by the introduction of the partial prospective payment system (PPS) in Japan, which makes some procedures relatively more profitable than other procedures. We find that hospitals respond to PPS adoption by increasing utilization and increasing their manipulation of infant's reported birth weight, which determines infants reimbursement and maximum length of stay. We also find that this induced demand substantially increases hospital reimbursements without improving infant health, implying that the additional money spent has no commensurate health gains

Suppression of nonsense-mediated mRNA decay permits unbiased gene trapping in mouse embryonic stem cells

An international collaborative project has been proposed to inactivate all mouse genes in embryonic stem (ES) cells using a combination of random and targeted insertional mutagenesis techniques. Random gene trapping will be the first choice in the initial phase, and gene-targeting experiments will then be carried out to individually knockout the remaining ‘difficult-to-trap’ genes. One of the most favored techniques of random insertional mutagenesis is promoter trapping, which only disrupts actively transcribed genes. Polyadenylation (poly-A) trapping, on the other hand, can capture a broader spectrum of genes including those not expressed in the target cells, but we noticed that it inevitably selects for the vector integration into the last introns of the trapped genes. Here, we present evidence that this remarkable skewing is caused by the degradation of a selectable-marker mRNA used for poly-A trapping via an mRNA-surveillance mechanism, nonsense-mediated mRNA decay (NMD). We also report the development of a novel poly-A-trap strategy, UPATrap, which suppresses NMD of the selectable-marker mRNA and permits the trapping of transcriptionally silent genes without a bias in the vector-integration site. We believe the UPATrap technology enables a simple and straightforward approach to the unbiased inactivation of all mouse genes in ES cells

Ferromagnetic feature from Mn near room temperature in the fine particles of GdMn2Ge2 and TbMn2Ge2

The magnetization behaviors of GdMn2Ge2 and TbMn2Ge2 in the bulk and in the fine particles obtained by high-energy ball-milling are compared. Pronounced modificayions in the spontaneous, remnent and high-field magnetization in the fine particle form, attributable to Mn are observed. The results indicate that the antiferromagnetism of Mn sub-lattice known for the bulk form in the range 100-300 K gets weakened in favor of ferromagnetism in the fine particles. On the basis of this observation, we infer that there are other factors like size (and possibly defects) also play a role to decide the exact nature of magnetic ordering of Mn in this ternary family of compounds, contrasting the traditionally held view that the basal plane Mn-Mn distance is the crucial controlling parameter.Comment: Communicated for publication on 2nd January 201

Regeneration in Cirrhosis of the Liver Following Partial Hepatectomy

Distribution of regenerative hepatocytes was observed by autoradiographic study in at liver after partial hepatectomy in order to investigate the relationship between hepatic blood flow around the pseudolobule and regeneration in cirrhosis of the liver. In cirrhotic liver, pseudolobules were mostly supplied by hepatic arterial flow as most of portal blood flow were bypassed around the pseudolobule resulting in marked decrease of sinusoidal blood flow. Regenerative rate of liver remnant was not increased in cirrhotic hepatectomized group during the experimental period, while it was increased to 105.0±21.2% at 48 hours in normal hepatectomized group after operation (P<0. 01). Unelevated regenerative rate in cirrhotic liver may have been induced by marked decrease of sinusoidal portal blood flow caused by intrahepatic portavenous shunt. As judged by H3-thymidine incorporation, DNA synthesis was increased to a maximum of 8335.1±1668.8 dpm/mg/min. at 36 hours in normal liver, and of 6538.9±2898.5 dpm/mg/min. at 48 hours in cirrhotic liver after partial hepatectomy (P<0.01). Average labeled hepatocyte number was also significantly increased to a peak of 48.0±9.1 at 36 hours in lobules of normal liver (P<0.001) and of 12.9±4.8 at 48 hours in pseudolobules of cirrhotic liver after partial hepatectomy (P< 0.01). Dissociation of unelevated regenerative rate of liver remnant from increase of DNA synthesis in cirrhotic hepatectomized group may indicate that cell volume stimulating factor is entirely different from cell number stimulating factor, and each factor plays a role individually. Direction of spreading of regeneration in normal liver was from peripheral zone to central zone, while spreading of regeneration in cirrhotic liver did not have specific direction in the pseudolobule. Direction of spreading of regeneration in normal hepatectomized group may substantiate the relation between direction of intralobular blood flow and liver regeneration. Nonspecific distribution in cirrhotic liver which has no direction of regeneration, indicates that regeneration does not always need the portal blood flow and can be supported by hepatic arterial flow which is expected to contain the portal blood factor after systemic circulation

Occurrence of thiamin pyrophosphate-dependent 2-oxoglutarate decarboxylase in mitochondria of Euglena gracilis

Abstract2-Oxoglutarate decarboxylase which catalyzes the conversion of 2-oxoglutarate into succinate semialdehyde occurs in mitochondria of Euglena gracilis which lacks a 2-oxoglutarate dehydrogenase complex. The enzyme reaction required thiamin pyrophosphate, MgCl2, 2-mercaptoethanol and NADP+ for the maximum activity, and was not affected by pyruvate and oxalacetate. In the reaction, the enzyme consumed 2-oxoglutarate, evolved CO2 and formed succinate semialdehyde in stoichiometric relationship. The maximum enzyme activity was found at pH 7.0 and 40° C, and Km values for 2-oxoglutarate and thiamin pyrophosphate were 0.33 and 0.056 mM, respectively. These results indicate that the thiamin pyrophosphate-dependent Euglena decarboxylase belongs to a new type of decarboxylase to be designated as 2-oxoglutarate decarboxylase. The probable role of the new decarboxylase in Euglena mitochondria is discussed with regard to the tricarboxylic acid cycle

Direct evidence for the magnetic ordering of Nd ions in NdMn2_2Si2_2 and NdMn2_2Ge2_2 by high resolution inelastic neutron scattering

We have investigated the low energy nuclear spin excitations in NdMn$_2$Si$_2$ and NdMn$_2$Ge$_2$ by high resolution inelastic neutron scattering. Previous neutron diffraction investigations gave ambiguous results about Nd magnetic ordering at low temperatures. The present element-specific technique gave direct evidence for the magnetic ordering of Nd ions. We found considerable difference in the process of the Nd magnetic ordering at low temperature in NdMn$_2$Si$_2$ and NdMn$_2$Ge$_2$. Our results are consistent with those of magnetization and recent neutron diffraction measurements

Rapid Cue-Specific Remodeling of the Nascent Axonal Proteome.

Axonal protein synthesis and degradation are rapidly regulated by extrinsic signals during neural wiring, but the full landscape of proteomic changes remains unknown due to limitations in axon sampling and sensitivity. By combining pulsed stable isotope labeling of amino acids in cell culture with single-pot solid-phase-enhanced sample preparation, we characterized the nascent proteome of isolated retinal axons on an unparalleled rapid timescale (5 min). Our analysis detects 350 basally translated axonal proteins on average, including several linked to neurological disease. Axons stimulated by different cues (Netrin-1, BDNF, Sema3A) show distinct signatures with more than 100 different nascent protein species up- or downregulated within the first 5 min followed by further dynamic remodeling. Switching repulsion to attraction triggers opposite regulation of a subset of common nascent proteins. Our findings thus reveal the rapid remodeling of the axonal proteomic landscape by extrinsic cues and uncover a logic underlying attraction versus repulsion