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Harlequin ichthyosis (HI), which is the most severe genodermatosis, is caused by loss-of-function mutations in ABCA12, a member of the ATP-binding cassette transporter family. To investigate the pathomechanism of HI and the function of the ABCA12 protein, we generated ABCA12-deficient mice (Abca12 −/− ) by targeting Abca12 . Abca12 −/− mice closely reproduce the human HI phenotype, showing marked hyperkeratosis with eclabium and skin fissure. Lamellar granule abnormalities and defective ceramide distribution were remarkable in the epidermis. Skin permeability assay of Abca12 −/− fetuses revealed severe skin barrier dysfunction after the initiation of keratinization. Surprisingly, the Abca12 −/− mice also demonstrated lung alveolar collapse immediately after birth. Lamellar bodies in alveolar type II cells of the Abca12 −/− mice lacked normal lamellar structures. The level of surfactant protein B, an essential component of alveolar surfactant, was reduced in the Abca12 −/− mice. Fetal therapeutic trials with systemic administration of retinoid or dexamethasone, which are effective for HI and respiratory distress, respectively, to the pregnant mother mice neither improved the skin phenotype nor extended the survival period. Our HI model mice reproduce the human HI skin phenotype soon after the initiation of fetal skin keratinization and provide evidence that ABCA12 plays pivotal roles in lung and skin barrier functions.
Harlequin ichthyosis (HI) (OMIM 242500) is the most severe ichthyosis, and its clinical features at birth include severe ectropion, eclabium, flattening of the ears and large thick plate-like scales over the entire body. Infants affected with HI frequently die within the first days of life. In 2005, we and other independent research groups identified mutations in the ATP-binding cassette transporter A12 (ABCA12) gene as the cause of HI ( 1 , 2 ). We previously demonstrated that a severe ABCA12 deficiency causes defective lipid transport within lamellar granules (LGs) in the granular layer keratinocytes, resulting in malformation of intercellular lipid layers in the stratum corneum and severe thickening of the stratum corneum of the HI phenotype. We also reported that LG lipid secretion could be recovered in cultured keratinocytes by corrective gene transfer of functional ABCA12 (1).
Formation of the intercellular lipid layer is essential for proper epidermal barrier function. Defective formation of the lipid layers is thought to result in the loss of such function and abnormal hyperkeratosis ( 3 ). Defective formation of the intercellular lipid layers in the stratum corneum due to abnormal keratinocyte lipid metabolism, transport and/or secretion is the major pathogenic mechanism in congenital ichthyoses ( 3 ).
ABCA12 belongs to a large superfamily of ATP-binding cassette (ABC) transporters that aid in the transport of various biomolecules across the cell membrane ( 4–6 ). The ABCA subfamily consists of 12 full transporters and one pseudogene (ABCA11), which are essential for lipid transport and secretion ( 7 ). Several genetic diseases are caused by mutations in ABCA subfamily genes. ABCA3, a molecule that is close to ABCA12 in the phylogenic tree of ABCA subfamily proteins ( 8 ), aids lipid secretion from alveolar type II cells via lamellar bodies ( 9 ). The ABCA3 deficiency underlies a fatal surfactant deficiency and associated lung collapse in newborns ( 10 ). Recently, several groups have reported on ABCA3-deficient mice ( 11–14 ). These mice showed neonatal lethality due to respiratory failure and that ABCA3 is necessary for lamellar body biogenesis and proper surfactant protein processing.
In the present study, to clarify the function of ABCA12 and investigate the pathomechanisms of the most severe ichthyosis, HI, we generated ABCA12-deficient mice by homologous recombination.
Generation of mice with targeted disruption of Abca12
To inactivate Abca12, we constructed a targeting vector to delete exon 30 of the Abca12 gene by homologous recombination, replacing that exon with a neomycin-resistance cassette (Fig. 1 A). We intercrossed the heterozygous mice, which were phenotypically indistinguishable from their wild-type (WT) littermates, to generate Abca12 −/− mice. PCR analysis confirmed correct targeting of Abca12 (Fig. 1 B). Reverse transcription–PCR (RT–PCR) and western blot analysis using rabbit anti-mouse Abca12 antibody showed that expression of Abca12 mRNA and protein was abolished in the Abca12 −/− mice (Fig. 1 C and D). The anti-mouse Abca12 antibody used in the present study recognizes a 14-amino acid sequence in the C-terminal region of mouse Abca12. This antibody is unable to detect the truncated Abca12 proteins lacking the C-terminal region. Thus, we could not detect a protein with different size in the western blotting.
The Abca12 −/− mice were born with smaller bodies than the WT mice (WT neonate 1.34 ± 0.17 g, Abca12 −/− neonate 0.91 ± 0.27 g; mean ± 2SD, n = 5) and erythematous skin covered the entire body of the Abca12 −/− mice, making their skin less flexible than that of the WT mice (Fig. 2 A). The entire skin surface was covered with thick scales and some of the Abca12 −/− mice developed skin fissures and eversions of the lips (eclabium) (Fig. 2 B, D and F), which are characteristic of HI in humans (Fig. 2 C, E and G). The Abca12 −/− mice died within a few hours, with none surviving the postnatal period ( n = 20). We examined the development of fetal skin phenotype of the Abca12 −/− . There was no significant difference between Abca12 −/− and WT fetuses until E15.5, before the skin keratinization started. At E18.5, Abca12 −/− fetuses developed taut and shiny skin without normal skin folds and showed contractures of the limbs (Fig. 2 A). At E18.5, the size of Abca12 −/− fetuses seemed to be smaller than WT littermates (E18.5 WT fetus 1.07 ± 0.14 g, E18.5 Abca12 −/− fetus 0.96 ± 0.14 g; mean ± 2SD, n = 5).
Morphological observation of the skin showed that the Abca12 −/− mice exhibited features similar to those of human HI patients. Light microscopy showed strikingly thick, compact stratum corneum without the normal basket-weave appearance (Fig. 3 A). Electron microscopy demonstrated numerous defective LGs and lipid droplets in the upper epidermis (Fig. 3 B). By immnostaining with goat anti-ABCA12 antibody, Abca12 was detected mainly in the granular layer of the WT mice skin; the skin of the Abca12 −/− mice lacked ABCA12 (Fig. 3 C). Immunofluorescent staining showed that ceramide, a major lipid component of LGs ( 15 , 16 ) and an essential component of the epidermal permeability barrier ( 17 ), was sparsely distributed in the Abca12 −/− mice stratum corneum, in marked contrast to the restricted, intense distribution in the stratum corneum of the WT skin (Fig. 3 D). Glucosylceramide immunocytochemistry showed congested patterns in differentiated keratinocytes of the Abca12 −/− mice, in contrast to the peripheral patterns that were shown in the differentiated keratinocytes of the WT mice, when both cell types were cultured under high (1.2 m m ) Ca 2+ conditions (Fig. 3 E).
Skin barrier function of the Abca12 −/− mice
We first examined the development and patterning of the skin barrier in Abca12 −/− mice using an in situ skin permeability assay. In WT E15.5 fetuses, the entire skin stained with Toluidine blue. In fetuses after E18.5 and in neonates, the skin did not stain. In contrast, the skin of the Abca12 −/− fetuses from E15.5 to E18.5, and even neonates, stained completely blue (Fig. 4 A).
The development of the skin barrier in the late gestational period was also assessed by measuring trans-epidermal water loss (TEWL) (Fig. 4 B). No significant difference in TEWL was found between the WT and Abca12 −/− E15.5 fetuses. However, the Abca12 −/− E18.5 fetuses showed much higher levels of TEWL than the WT E18.5 fetuses.
To confirm the 'inward out' defect in the skin in the Abca12 −/− mice, we evaluated the rate of fluid loss through evaporation in the Abca12 −/− and WT mice by monitoring body weight as a function of time. The Abca12 −/− E15.5 fetuses, E18.5 fetuses and neonates lost 14.5, 14 and 13.5% of their body weight in 3 h, respectively (Fig. 4 C). This weight loss was attributed to trans-epidermal fluid evaporation due to compromised skin barrier function in fetuses and neonates, in the absence of either feeding or urinating during the evaluation period.
To evaluate the correlation between developing skin barrier function and epidermal structural changes, we performed light microscopy on the E15.5 and E18.5 fetuses and electron microscopy on the E18.5 fetuses. There was no significant difference between unkeratinized Abca12 −/− and WT mice skin at E15.5; however, at E18.5, Abca12 −/− fetuses started to show hyperkeratosis by light microscopy and cytoplasmic lipid droplets in the upper epidermis including the stratum corneum by electron microscopy (Fig. 4 D and E). Thus, keratinization was disturbed and the development of the skin barrier was clearly defective even during fetal development in Abca12 −/− mice.
Alveolar surfactant deficiency in the Abca12 −/− lungs
We confirmed Abca12 mRNA expression in WT lung tissue through RT–PCR (Fig. 5 A). Histological examination of the Abca12 −/− mice lungs revealed alveolar collapse and pulmonary congestion. The Abca12 −/− mice lungs had thicker interalveolar septa and smaller alveolar spaces than the WT mice (Fig. 5 B and C). Ultrastructural analysis of alveolar type II cells in Abca12 −/− mice showed that lamellar body like organelles in Abca12 −/− mice lungs lacked the typically clear lamellar structure compared with that of WT mice (Fig. 5 D and E).
We performed double staining with goat anti-ABCA12 antibody and rabbit anti-surfactant protein-B (SP-B) antibody (Fig. 6 A). In the neonatal lung cryosections, Abca12 was expressed in the lung epithelial cell cytosol of the WT mice but not in the lungs of the Abca12 −/− mice. By immunostaining and western blotting, SP-B expression was found to be lower in the Abca12 −/− mice than in the WT mice (Fig. 6 B). No significant differences in mRNA levels of SP-B, ABCA3 and GAPDH were found between the WT and Abca12 −/− lungs (Fig. 6 C). These data suggested that Abca12 protein is involved in lipid metabolism of certain pulmonary components including surfactant and plays a significant role in surfactant biogenesis.
Fetal therapy with oral or intrauterine administration of retinoid or subcutaneous administration of corticosteroid to pregnant mice
Protocol 1: Systemic administration of etretinate
Oral administration of any dose of etretinate (1, 10 or 100 mg/kg daily, 5 consecutive days) or intrauterine administration (intra-amniotic fluid administration) of etretinate (one 1 µg shot) to the pregnant mice did not change the skin phenotype at birth in any way. All the Abca12 −/− newborns who had received the fetal therapy died within a few hours after birth. Congenital abnormalities (limb defects and anencephaly) were observed in several of the Abca12 +/+ or Abca12 +/− littermates who had received fetal therapy of oral etretinate (100 mg/kg daily, 5 consecutive days) via the pregnant mother mice.
Protocol 2: systemic administration of corticosteroid
Subcutaneous administration of any dose of dexamethasone (0.1 mg or 1 mg, one shot, 5 consecutive days from E15 to delivery) to the pregnant mice did not achieve neither improvement in clinical appearance of the skin nor extension of the survival period of the Abca12 −/− neonates.
Previously, we identified mutations in ABCA12 gene as the cause of HI and demonstrated that severe ABCA12 deficiency causes defective lipid transport of LGs in the upper epidermal keratinocytes, resulting in the abnormal thickening of the stratum corneum and HI phenotype ( 1 ). Subsequently, our group showed that ABCA12 is highly expressed in the fetal skin, and we developed an HI skin model in immunodeficient mice ( 18 ). More recently, we demonstrated that ABCA12 protein localizes from Golgi apparatuses to LGs with glucosylceramide ( 19 ). Furthermore, we conducted DNA-based prenatal diagnosis and exclusion from identification of the gene whose abnormality causes HI, ABCA12 ( 20 , 21 ). Based on this research, to clarify the function of ABCA12 and investigate the pathomechanisms of the most severe ichthyosis, HI, we generated ABCA12-deficient mice by homologous recombination.
Here we have succeeded in generating Abca12 −/− mice as a human disease model of HI. The model mice showed severe skin barrier defect and skin histopathology similar to that of HI patients. Interestingly, the lungs of the present model mice showed signs of alveolar collapse. Western blotting and immunostaining of the Abca12 −/− mice lung showed the SP-B expression to be decreased. These findings suggest that ABCA12 is involved in not only lipid transport in the epidermis, but also in surfactant biogenesis and/or transport in the lung.
The Abca12 −/− mice were born with smaller bodies and with erythematous, less flexible skin covering the entire body. The entire skin surface was covered with thick scales, and some of the Abca12 −/− mice developed skin fissures and eversions of the lips. From histopathological observation, we detected thickening of the stratum corneum and many lipid droplets in the upper epidermis, which are characteristic of HI in humans. Immunostaining with anti-ceramide antibody showed that ceramide was sparsely distributed in the Abca12 −/− mice stratum corneum. Immunocytochemistry with an anti-glucosylceramide antibody demonstrated differentiated Abca12 −/− mouse keratinocytes with congested perinuclear lipids, similar to that reported for HI keratinocytes ( 1 ). From analysis of the skin and keratinocytes, we conclude that our new model mice accurately reproduce the condition of human HI. In situ dye skin permeability assay, dehydration and TEWL measurement clearly demonstrated that the present model mice, Abca12 −/− mice, had severe skin barrier dysfunction not only at birth, but also in the fetal period after keratinization started.
Interestingly, the Abca12 −/− mice in the present study showed that ABCA12 plays a crucial role in the lungs. High-dose systemic retinoid treatment is applied to the neonates recently and effective in many HI cases. However, the mortality rate of HI is high even now and more than half of the affected neonates die within a few weeks of life. Until now, the cause of HI death has not been elucidated completely, and it has been thought that respiratory distress, bacterial infection, feeding problems and dehydration are associated with HI death ( 2 , 22–24 ).
ABCA3, a molecule closely related to ABCA12 ( 8 ), aids lipid secretion from alveolar type II cells via lamellar bodies ( 9 ). ABCA3 deficiency underlies a fatal surfactant deficiency in newborns ( 10 ), and ABCA3-deficient mice show neonatal lethality from respiratory failure ( 11–14 ). Apart from the skin, it has been reported that ABCA12 is expressed in the lungs, testis and placenta ( 25 ); however, the precise function of ABCA12 in the lungs had not been investigated in detail. In the present study, we investigated the effect of Abca12 disruption in our Abca12 −/− mice lungs. Histological examination of lungs from the Abca12 −/− mice revealed alveolar collapse and pulmonary congestion. Double staining with anti-ABCA12 antibody and anti-SP-B antibody revealed that Abca12 is co-expressed with SP-B in the cytoplasm of type II alveolar epithelial cells in WT mice. Immunostaining and western blotting revealed SP-B expression to be lower in the Abca12 −/− mice than in the WT mice. Ultrastructural analysis of alveolar type II cells in the Abca12 −/− mice showed that lamellar-body-like organelles lacked a normal lamellar structure in Abca12 −/− mice compared with that of WT mice.
It is well known that expression of surfactant proteins in the peripheral lung normally increases just prior to birth ( 26 ). In particular, hydrophobic SP-B plays crucial roles in surfactant function and homeostasis; the proteins enhance the spreading, absorption and stability of required surfactant lipid ( 27 ). We were unable to clarify the precise details of ABCA12's role in lipid transport in the lung tissue, but the present data suggest that the ABCA12 protein is involved in the metabolism or transport of lipid components in pulmonary surfactant and that this protein plays a role in surfactant biogenesis and/or secretion. Our results support the hypothesis that respiratory distress may contribute to the observed high mortality rate in HI neonates to a significant extent.
The development of treatments for this condition is crucial to improve patient survival, and the high-dose systemic retinoid therapy that has been applied to HI newborns in neonatal intensive care unit has produced several long time survivors ( 28–31 ). Based on these clinical reports, we conducted systemic etretinate administration to the pregnant mice to clarify the efficacy of retinoid therapy as an HI treatment. We gave high-dose retinoid to the pregnant mother mice orally and directly into the uterus (amniotic fluid) by intrauterine (intra-amniotic fluid) injection. Unfortunately, neither improvement of the skin manifes t ations nor extension of the survival period was obtained by systemic retinoid administration. We do not know why the systemic retinoid had no effect, but from the results of our retinoid fetal therapy, we conjecture that retinoid therapy is effective against hyperkeratosis only after birth and not against the development of skin lesions during the fetal period.
Systemic steroids have been used to treat respiratory distress syndrome. Steroids have been shown, in vitro and in vivo , to enhance fetal lung maturation including differentiation of alveolar type II cells and production of both lipid and protein components of surfactant. Prenatal steroid treatment decreases the incidence of respiratory distress syndrome in premature infants by promoting the maturation of fetal lungs, including the surfactant system ( 32 ). That is why we conducted the systemic steroid therapy on the pregnant mice by subcutaneous injection. However, we obtained positive effects on neither the skin symptoms nor the lung manifestations. Probably, a combination of alveolar surfactant compensation therapy and intra-amniotic gene therapy might be the next logical treatment approach.
In conclusion, our findings suggest that ABCA12 is involved not only in lipid transport and assembly of a proper skin barrier, but also in lung surfactant biogenesis. Both these tissues heavily depend on ABCA12 function and are essential for survival of organisms in a dry environment. Our novel findings together demonstrate that ABCA12 is a crucially important protein for life in dry environment.
All the studies involving animals were reviewed and approved by the Animal Use and Care Committee of the Hokkaido University Graduate School of Medicine. All animals used for this study were maintained under pathogen-free conditions.
Generation of Abca12 −/− mice
We cloned mouse genomic DNA Abca12 fragments from the mouse 129Sv/Ev genomic library (Bacpac Resources Center, Children's Hospital Oakland Research Institute, Oakland, CA, USA). We subcloned a 10.6 kb fragment to make the targeting vector. We inserted the PGK/Neo cassette between 47 bp upstream of the exon 30 and 203 bp downstream of exon 30. We transfected the targeting vector by electroporation into 129Sv/Ev embryonic stem cells, then microinjected the correctly targeted embryonic stem cell line into blastocysts obtained from C57BL/6J mice (Jackson Laboratories) to generate chimeric mice, which we then mated with C57BL/6J females. We crossed the heterozygotes with C57BL/6J over at least five generations, and then intercrossed them to generate the Abca12 −/− mice.
PCR screening of the Abca12 −/− mice
Genotypes of fetuses and neonates were determined by PCR analysis of tail tissue DNA using the following primers: P1 (5′-CACCTCACTGAAGACGTATC-3′), P2 (5′-TCGAGTTATGACTGTGCCAT-3′), P3 (5′-TGAGACTTTCGTGCTGAATGGAG-3′) and P4 (5′-TGCGAGGCCAGAGGCCAGTTGTGTAGC-3′). Primer sets P1–P2 and P3–P4 correspond to WT allele 310 bp and knockout allele 2.2 kb, respectively. As controls for these experiments, we used Abca12 +/− or Abca12 +/+ of the Abca12 −/− mice.
Extraction of total RNA and RT–PCR
We isolated total RNA from skin and lung tissue of the WT and Abca12 −/− mice pups using the QuickGene RNA Tissue Kit SII (Fujifilm Corp). We reverse-transcribed RNA using Superscript II following the manufacturer's instructions (Invitrogen Corp.). Specific Abca12 primers for cDNA to PCR amplification were as follows: forward 5′-CATCGGTGGCTCCAGGGTAG-3′ and reverse 5′-CTTGGTGAGTGTGAGGTGGTAAC-3′. These primers were used for amplification of a 256 bp fragment around exons 30–31 boundary of normal cDNA. For semi-nested RT–PCR of lung mRNA, forward primer was changed to 5′-TGATTTTGGATGAACCATCCAC -3′. Specific primers of Abca3 cDNA for PCR amplification were as follows: forward 5′-AAGGTTCTAGTGACAGTCCTG-3′ and reverse 5′-GAGGAGTGGTTGTCATAGCG-3′. Specific primers of SP-B cDNA to PCR amplification were as follows: forward 5′-CTGAGCAACAGCTCCCCATT-3′ and reverse 5′-TGGCATAGCCTGTTCACTGG-3′. As a control, we amplified GAPDH cDNA as a housekeeping gene.
Western blotting
For western blotting, we used lung tissue protein homogenates and primary cultured keratinocyte proteins prepared from a lysis buffer of 50 m m Tris–HCl, pH7.5, 150 m m NaCl, 1% Nonidet P-40, 0.5% deoxycholate, 0.1% SDS and Roche protease cocktail 1 tablet. The lysates were separated by 5–10% gradient gel SDS–PAGE and transferred to polivinylidene difluoride membranes. Membrane blocking and incubation with antibodies were carried out in Tris-buffered saline with 2% skim milk. Signals were revealed with chemiluminescence reagents.
Rabbit polyclonal affinity purified anti-mouse Abca12 antibody was raised in rabbits using a 14-amino acid sequence synthetic peptide (residues 2581–2594) derived from the mouse Abca12 sequence (XM001002308) as the immunogen. The other primary antibodies were mouse monoclonal anti-ceramide antibody (Alexis Biochemicals), rabbit anti-glucosylceramide antibody (Glycobiotech), rabbit anti-mouse surfactant protein-B antibody (SP-B, AB3780; Chemicon), mouse monoclonal anti-beta actin antibody (Sigma) and goat anti-ABCA12 antibody (N-20; Santa Cruz Biotechnology). We used rabbit anti-mouse Abca12 antibody for western blotting and goat anti-ABCA12 antibody for immunostaining. As the secondary antibodies, Alexa Fluor 488-conjugated donkey anti-rabbit IgG (Molecular Probes), TRITC-conjugated goat anti-rabbit IgG (Southern Biotech), FITC conjugated donkey anti-goat IgG (Jackson Immuno Research), horseradish peroxidase-conjugated goat anti-rabbit IgG or horseradish peroxidase-conjugated anti-mouse F(ab′) (Biosource) were used.
Establishment of Abca12 −/− mice keratinocyte culture
Skin samples from WT and Abca12 −/− mice were processed for primary keratinocyte culture, and cells were grown according to standard procedures in CnT-57 medium (Cellntec Advanced Cell Systems). For differentiation, cultures were grown for several passages in CnT-57 medium and then switched to CnT-02 medium (Cellntec Advanced Cell Systems), and 24 h later, the calcium concentration was changed to 1.2 m m . Forty-eight hours later, we performed immunocytochemistry or protein extraction.
Light microscopy and immunofluorescence analysis
We killed the newborn pups, fixed them for 24 h in 10% neutral buffered formalin, dehydrated them for 24 h in 70% ethanol and embedded them in paraffin. We cut 4 µm sagittal sections and stained them with hematoxylin–eosin and Elastica–Masson. Immunofluorescent labeling was performed on frozen tissue sections and keratinocyte cultures as previously described ( 33 ). Fluorescent labeling was performed with secondary antibodies, followed by 10 µg/ml of propidium iodide (Sigma) to counter-stain the nuclei. The stained samples were observed under a confocal laser-scanning microscope.
Electron microscopy
Skin and lung samples were fixed in 5% glutaraldehyde solution, post-fixed in 1% OsO 4 , dehydrated and embedded in Epon 812. The samples were sectioned for electron microscopy. The thin sections were stained with uranyl acetate and lead citrate and examined by transmission electron microscopy.
Skin permeability assay
In situ skin permeability assay using Toluidine blue was performed as described by Hardman et al . ( 34 ). Briefly, we subjected fatal and neonatal mice to methanol dehydration and subsequent rehydration as described. We then washed them in phosphate-buffered saline (PBS) for 1 min, stained them for 5 min at room temperature in 0.1% Toluidine blue. They were briefly washed in PBS for 15 min in PBS at room temperature and immediately photographed.
TEWL was measured on live mouse pups by evaporimeter (AS-VT100RS: Asahibiomed Corp.). The AS-VT100RS utilizes the ventilated-chamber method of measuring TEWL. Its hygrometer measures the humidity of incoming air and of outgoing air that has passed over the test area of skin, and TEWL is calculated from the difference. TEWL measurements were done on the back of the embryos and neonates.
Therapeutic trials for the fetuses
Protocol 1: systemic administration of etretinate
We dissolved several doses of etretinate (a sample drug from Chugai Pharmaceuticals, Tokyo, Japan) in water, and single oral doses (1, 10, 100 mg/kg) of etretinate were administrated to the pregnant mice every day from E15 to delivery. We also tried 1 µg etretinate injection to the intra-amniotic fluid of every yolk sac at E15.
Protocol 2: systemic administration of corticosteroid
We dissolved the several doses of dexamethasone (Sigma) in the water, and single doses (0.1 mg or 1 mg) of dexamethasone were administrated by subcutaneous injection to the pregnant mice every day from E15 to delivery.
This work was supported in part by a grant-in-aid from the Ministry of Education, Science, Sports and Culture of Japan (Kiban B 18390310 and Kiban B 20390304 to M.A.).
We wish to thank James R. McMillan for proofreading this manuscript.
Conflict of Interest statement . None declared.


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Tag: health insurance
Blog Posts (62)
January 17, 2017
The Future of Health Insurance May Look A Lot Like Our Past
by Craig Klugman, Ph.D.
This week marks the transition of power from President Obama to President-elect Trump. One issue that has been high on Trump's list of policy changes is a repeal and replace of the Affordable Care Act (a.k.a.…
December 13, 2016
Imminent Threats To Healthcare and Medical Professionalism: We Must Remain Vigilant
In a previous blog I expressed concerns about the possible direction of politics in our country and the risks it poses to the larger procedural, democratic framework, which I take to be essential to the work of contemporary bioethics. Now that the election is over and a new administration is taking shape, I have many grave concerns about the fundamentally new policy directions our nation will be taking. None concern me more than how the planned changes in our healthcare system in the United States and, if they happen, how our most vulnerable patients will be affected. This is because a top agenda for them on day one will be to repeal the Affordable Care Act (ACA), which has provided healthcare coverage for about 21 million more people since its inception in 2009.
The ACA was an imperfect healthcare plan from the start. But after decades of false starts to reform a system that does not have a close second in terms of excessive costs and inefficiencies among industrialized nations, especially in relation to outcomes, in 2009 it was the best option our country had at that time. In spite of some problems in its implementation, due largely to lack of cooperation and critics setting up obstacles, the ACA has become entrenched into our healthcare system. If it is repealed, there will be widespread suffering and chaos. Just recently the nations' hospital industry "…warned President-elect Donald Trump and congressional leaders on Tuesday that repealing the Affordable Care Act could cost hospitals $165 billion by the middle of the next decade and trigger "an unprecedented public health crisis."
The eagerness of the new administration to gut the ACA was affirmed by the appointment of Tom Price, Representative from Georgia who has been a ferocious and over the top critic of this law from its inception. A prominent orthopedic surgeon prior to running for Congress, Dr. Price seems to advocate for a system that is extricated from government as much as possible and placed in the hands of the private insurance companies. His plan, which provides for individual fixed tax credits and health savings accounts and allows insurance companies to cross state lines, may be helpful for many Americans who are relatively well off and have healthcare to start with. But for most of the sickest patient in lower income brackets, these market-based ideas will do nothing to help them and in fact make them worse off. But real world, harmful consequences are the concerns of an ideologue: All that matters is having in place a policy that accords with an ideal vision of how the world should work.
There is no practical way that a purely market based approached to providing access to healthcare to Americans will accomplish the goals of healthcare that the majority of Americans have, which is to provide some type of basic, quality healthcare to all citizens, at an affordable cost. Price's approach will leave millions of American citizens, many already with serious health problems without access to health except via the emergency rooms. The predictable consequences will be astronomically increasing costs because healthcare will retreat to its pre-ACA days of inefficiency by focusing more on rescuing patients from acute conditions than preventing them from occurring in the first place; and physicians caring for patients with insurance will be doing more and more procedures for which they will be handsomely paid, without improving quality for patients. Which makes it all the sadder to see the American Medical Association (AMA), as it has done at prior critical historical junctures as it did in standing against the passage of Medicare and Medicaid in 1965, endorsing Price's nomination.
Though Price's nomination may be bad for patients, it likely represents good news for physicians in terms of their incomes from reimbursement rates. Which is the reason why the AMA supports him and why, in my judgment, it is an abdication of professional, ethical good judgment and responsibility. Their support violates the basic tenant of professionalism as stated in the American College of Physicians (ACP) Ethics Manual that require its members "…to teach and expand, by a code of ethics and a duty of service that put patient care above self-interest, and by the privilege of self-regulation granted by society. Physicians must individually and collectively fulfill the duties of the profession."
I am heartened by practicing physicians and physicians-in-training who speak out and refuse to be a part of the AMA and its support of Price's appointment to be Secretary of HHS. Most notably a petition has gained over 5,000 physicians' signatures that make it clear "The AMA Does Not Speak For Us". As they state in the petition:
"We are practicing physicians who deliver healthcare in hospitals and clinics, in cities and rural towns; we are specialists and generalists, and we care for the poor and the rich, the young and the elderly. We see firsthand the difficulties that Americans face daily in accessing affordable, quality healthcare. We believe that in issuing this statement of support for Dr. Price, the AMA has reneged on a fundamental pledge that we as physicians have taken?—?to protect and advance care for our patients."
Medical professionalism always exists in relationship to the prevailing economic and political order in society. Because economic and political winds can shift, so can medical professionalism that at times can put it at risk of losing its moral compass. We do not know yet just how strong the head winds will be. But medical professionals and all citizens who care about the future of just and quality healthcare should be especially vigilant in the coming days and remain prepared to show resistance when necessary.
The Alden March Bioethics Institute offers a Master of Science in Bioethics, a Doctorate of Professional Studies in Bioethics, and Graduate Certificates in Clinical Ethics and Clinical Ethics Consultation. For more information on AMBI's online graduate programs, please visit our website.
September 22, 2016
Did You Know That Obamacare Causes Diabetes? Here's Why It Happens And Why It's A Good Thing
Obamacare is a big, messy law with so many moving parts, it is often hard to tell how well it's working. People debate whether it is killing jobs or creating them; they argue about whether it is lowering medical expenses … Continue reading →
The post Did You Know That Obamacare Causes Diabetes? Here's Why It Happens And Why It's A Good Thing appeared first on PeterUbel.com.
September 9, 2016
Americans Love Their Healthcare But Hate Their Healthcare System — Here's Why
There's lots to love about American healthcare. We have some of the best clinicians in the world, as evidenced by the huge number of people who come to the U.S. from other countries when they are sick. Yet the American … Continue reading →
The post Americans Love Their Healthcare But Hate Their Healthcare System — Here's Why appeared first on PeterUbel.com.
August 15, 2016
If You Don't Have Employer Insurance, You Probably Have a High Deductible
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Forum - View topicHelp us get the first onmyoji novel translated!
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Onmyoji (yin yang diviners) have been a very popular topic in Japanese media for a while, especially in manga and anime. Popular series such as TOKYO BABYLON, X, NURA: RISE OF THE YOKAI CLAN, SHONEN ONMYOUJI, etc are also notable for featuring onmyoji in primary roles. But many anime and manga fans don't know is that the first novel which started this "boom" of interest in onmyoji was an acclaimed bestseller from the 1980's entitled TEITO MONOGATARI. TEITO MONOGATARI is a historical fantasy epic set in prewar Japan and revolves around Yasunori Kato, a master onmyoji who is also a demon that wants to cripple the Japanese Empire. Eventually he runs afoul of the Tsuchimikado Family, the official descendants of Abe no Seimei (greatest onmyoji in history, for those who don't know), leading to a magical conflict spanning 90 years of Tokyo's history. It is also a meticulously researched historical fiction featuring many figures from Japanese history in primary and supporting roles, including:
*writers Kōda Rohan, Mori Ōgai (doctor and author of Gan/The Wild Geese), Kyōka Izumi, and even the legendary Yukio Mishima
*author and physicist Torahiko Terada
*biologist Makoto Nishimura, creator of Japan's first working robot, Gakutensoku
*Shibusawa Eiichi, "father of Japanese capitalism," who practically invented Japan's modern banking system
*Masatoshi Ōkōchi, third director of the RIKEN (Institue of Physical and Chemical Research), who expanded scientific advances for commercial ends
*Noritsugu Hayakawa, founder of the Tokyo Underground Railway and subsequent father of the modern day Japanese subway system
*author and philosopher Ikki Kita, who writings led to the 1936 attempted takeover of the Japanese government
*Kanji Ishiwara, noted general and proponent of the pan-asianist movement
*Gen'yoshi Kadokawa, founder of the Kadokawa Shoten publishing company and even his son (!!) Haruki Kadokawa
*Karl Haushofer, who writings indirectly influenced Adolf Hitler's expansionist strategies. He was also featured in FULLMETAL ALCHEMIST.
This novel has sold over 3.5 million copies in Japan alone, won the 1987 Nihon SF Taisho Prize for Best Japanese Fantasy/Sci-Fi Story, and is considered a groundbreaking work in Japanese occult literature. For example, it is believed CLAMP took inspiration from it to create both TOKYO BABYLON and X. The Subaru/Seishiro conflict in the aforementioned series is very reminiscent of the war between the good and evil onmyoji at the beginning of TEITO MONOGATARI. Also, the title "TOKYO BABYLON" is just a reversal of "BABYLON TOKYO", which was the English title of the manga adaptation of TEITO MONOGATARI.
The SHIN MEGAMI TENSEI: DEVIL SUMMONER series has many homages to this work in its plot and setting, including the design of the protagonist Raidou Kuzunoha (who resembles Kato).
It's also believed that Baku Yumemakura was inspired by the success of this novel to create his monumentally popular and influential ONMYOJI series (made into two live action films of the same name), which were released a few years after TEITO.
You may have run into the plot of TEITO MONOGATARI before in the form of the anime DOOMED MEGALOPOLIS. However that anime is a highly stylized (not to mention nastier), compressed and incomplete version of the story and cannot be used as an accurate representation of the novel. The whole story in its unedited, unstylized form, has yet to be told to an English audience.
We have already contacted the author, but he is convinced there is no interest in his work in the English speaking world as it is too "Japanese-centric". We would like to prove to him otherwise. If you would like to see TEITO MONOGATARI translated, please visit this Facebook page and show your support, specifically clicking the "Like" button:
I really hope you will consider this. Had it not been for this novel, it's unlikely that the aforementioned franchises would even exist!
We also hope to use this a springboard to get more popular onmyoji literature translated such as Baku Yumemakura's ONMYOJI novels and Natsuhiko Kyogoku's KYOGOKUDO novels as we'll have finally have an audience.
Last edited by cormacmacart on Fri Sep 21, 2012 11:16 pm; edited 2 times in total
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Teito Monogatari is indeed a very important cultural property of Japan, especially in the history of the Japanese Onmyodo ("The Way of Yin and Yang") tradition. It seems that Teito Monogatari was written as a history of 20th century Japan, but through the lens of magic, the occult, and Onmyodo itself. It thus served as a great reintroduction of these elements to the literary realm.
As was said previously, there are NUMEROUS novels, manga, films, and anime that followed Teito Monogatari's lead and took off. Some of the ones that I can remember just off the top of my head are the following:
-- Onmyoji (manga/novels/films) by Yumemakura Baku
-- Tokyo Babylon (manga/anime) by Clamp
-- X (manga/anime) by Clamp
-- The Kyogokudo series (novels/anime) by Kyogoku Natsuhiko
-- Shonen Onmyoji (manga/anime/light novels) by Yuki Mitsuru
-- Onmyo Taisenki (manga/anime) by Tomizawa Yoshihiko
-- Steel Angel Kurumi (manga/anime) by Kaishaku
-- Magical Shopping District Abenobashi (manga/anime) by Gainax
-- Nurarihyon no Mago (manga/anime) by Shiibashi Hiroshi
-- Shaman King (manga/anime) by Takei Hiroyuki
-- Harukanaru Toki no Naka de (manga/anime/games) by Ruby Party
-- Negima (manga/anime) by Akamatsu Ken
-- Ask Dr. Rin! (manga/anime) by Arai Kiyoko
-- Rental Magica (light novels/anime) by Sanda Makoto
......and probably MANY more.
The point being that Teito Monogatari is indirectly responsible for inspiring all of the above series, whether directly or indirectly. Thus, it is a very important cultural phenomenon and should be translated into English eventually.
If you are interested in Teito Monogatari, please show your support by joining the facebook group mentioned above (http://www.facebook.com/
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I had read Teito Monogatari in the original, and recently I happened to re-read essays on the supernatural by Kōda Rohan.
It is interesting that Aramata Hiroshi chose him as a principal character of Teito Monogatari.
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Thank you for commenting! It is always good to find someone else who has read it and can speak English as well.
Regarding Rohan, I agree! It's an interesting situation. I also assumed that Aramata gave him this role of a primary character partly due to his involvement with the supernatural during his literary career. But it might have been partly his historical character that fascinated Aramata too. Iirc Rohan was very learned in several different areas of study and was also physically active (a practiced swordsman). Although I'm sure there are many other authors Aramata could have used, Rohan just seemed like a natural fit as a primary hero in a story about the supernatural.
Anyone who's wondering what we're talking about...as mentioned above, Kōda Rohan is a classic writer from the Meiji Era. He is probably the most active hero at the beginning of Teito Monogatari. Some of his works that have been translated into English:
A collection of two of his novellas (including "Five Storied Pagoda", arguably his most famous work) and a short story.
One of his supernatural short stories is translated in this collection.
His English biography.
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It's a pleasure.
Anothe factor which can be taken into account about Mr Aramata's having chosen Rohan as a principal character is that Rohan also wrote a book and articles on (Edo/)Tokyo, which is the 'capital' of Teito Monogatari.
Yes, Rohan was very erudite on various literary and scholarly things, and his essays on those things are always fascinating.
I have heard that Rohan practiced kendō with his disciples at his house in Terajima.
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I forgot about that, but you're right! This is even directly referenced in the cinematic adaptations of ''Teito Monogatari''. In the live action version, Noritsugu Hayakawa is talking to him at the festival and mentioning some of the books he's written on Tokyo. And in the anime (Doomed Megalopolis), the ending narration is supposedly a direct quote pulled from his writings on Tokyo.
Thank you for the quote. I wish I could translate it for the other readers here, but unfortunately I must admit my Japanese is still not terribly advanced. I read Rohan's English biography a year ago though, so maybe some of his writings on Tokyo are translated in there. I can check through and transcribe any I find.
Kind of like Aramata-san himself. Maybe Aramata identified or idolized him more than the other authors.
Ah, that might be it. I also remember though that his daughter, Aya Koda, also had memories of him training by himself with a short sword. I will have to find the quote by her.
It is great to find someone who is knowledgeable about the subject matter. Question: Since you've read Teito Monogatari, I must ask: Does Kyōka Izumi have a larger role in the novel than in the movie versions? His cameo in the live action film version was one of my favorite scenes in the movie, but I understand the movie versions are very compressed. For example, I know there are a lot more scenes in the book with Ogai Mori that don't make it into the film and anime. Do you remember if there are any more scenes with Kyōka Izumi? I assume there must be.
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I dug up Teito Monogatari and riffled through the pages.
It seems that Izumi Kyōka appeared in the scenes where:
・ He said to Tatsumiya Keiko that she had the Power of the Kannon at Kagura-zaka.
・ Later, near to Iidabashi, he helped Tatsumiya Keiko, who was injured due to her having fought against supernatural monsters.
Mr Aramata said essays by Rohan were a must-read for readers of Teito Monogatari. So, if an English edition of Teito Monogatari is published, probably also those works by Rohan will be needed to be translated into English.
It will be tough work for the translator, though.
Speaking of Kōda Aya, Nagareru by Kōda Aya was made into a film, which was directed by Naruse Mikio.
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I am well aware of the importance of Teito monogatari and Hiroshi Aramata, and have been interested in them since I discovered that he was one of the members of Sekai Youkai Kyoukai (The World Yokai Organization), along with Shigeru Mizuki and Natsuhiko Kyougoku, both of whom I respect very much.
Surely I would like to see it in English, although I plan to read it in the original language someday, when my knowledge of kanji is up to the task.
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Tatsumiya Keiko also bought books by Kyōka, including Uta Andon, at a bookshop in Kōjimachi.
And according to a letter by Tatsumiya Keiko to Kyōka, he asked after injured Keiko at her house and gave her an incense burner.
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That is great to hear. I've really been perplexed with how little known Teito Monogatari is in the West. If any work can lay claim to being the father (or "grandfather") of an entire genre, then that work should automatically be noted in relation to that genre. But Teito Monogatari has not gotten this credit in the English speaking world until relatively recently. Onmyoji are quite well known in anime/manga/video game works hugely popular in the West, so why hasn't anybody taken the time to research their history in modern Japanese fiction?
I'm guessing it's because Japanese literature is simply not something that has a concentrated fanabase in the West. So important facts like these will automatically slip by the noses of English enthusiasts. Even those who do did research would face translation barriers (I can testify to that).
Although the onmyoji "genre" has grown exponentially since Teito, I still think the work has many unique merits, such as being a meticuloulsy researched retelling of modern Japanese history (as opposed yet another retelling of ancient or mythical history). Of course Aramata himself, who has been a major contributor to these "supernatural folklore revival groups" in Japan (such as The World Yokai Organization you mention) basically owes his entire career and status to the success of the work. For these reasons and its classic status, I really think it should be translated eventually so English speakers can appreciate it in its entirety.
Oh that would be wonderful! It would be a great boon for English speakers wanting to learn more about Japanese supernatural culture. Only problem is it might not be practical at off-hand since the publishers would also have to work with whoever owns Rohan's works to get it published, Still ideally, I would love Teito Monogatari to attract enough attention to be the beginning of a resurgence of English interest in the historical characters featured in its story (but I know that'll be VERY unlikely).
Indeed! Chieko Mulhern in her introduction to Pagoda, Skull and Samurai (the story collection I linked to earlier) notes that although she tried to imitate Rohan's complex prose to the best of her ability, her final translation is ultimately much, much simpler than Rohan's original works. Rohan's style is beautiful to read though if you can understand it. As always, a translation simply cannot capture the lyrical essence of such a learned person.
Before I run in danger of getting shut down due to speaking about non-anime/manga topics, let me post a picture of Koda Rohan from the from the animated Teito Monogatari contrasted with his historical image:
Thank you very much! It's interesting how Aramata portrays him as this saint-like figure who offers assistance to the heroine when she is in peril or lost. Still given Izumi Kyōka's great status in the world of Japanese gothic/supernatural literature though, I do wonder why he doesn't have a bigger role like Rohan. Still it's great to see he has a bigger role in the book than his one encounter with Keiko in the film would suggest.
And here's Izumi Kyōka from the aforementioned anime:
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On second thought, I think Kamui Fujiwara's depiction of Rohan from the manga Teito Monogatari looks much closer to his historical counterpart:
Ah excellent! Yes, Aya became a very successful writer herself. I wasn't aware though that there had been films made of her works too. That is very interesting!
Speaking of which, this is the translated quote from Aya Koda describing her father's swordsmanship practice that I kept referring to earlier:
"With the moon on his back, he was swinging a sword, his white undergarment exposed down to the sash. Flying downward, the white blade glistened and elongated as if to slice the earth. Swung up, it looked short, contracting like a snake. Behind the wall, watching the moonlight and the shadow and the blade and my father, I stood transfixed."--Aya Koda
Though short, I thought it was an evocative description. It alone exudes the image of the disciplined swordsman that Aramata builds upon in his novel.
BTW, have you ever read Musubi no Yama Hiroku (産霊山秘録) by Ryo Hanmura? It is widely considered a masterpiece of Japanese fantasy literature. Looking at the description, I can't help but wonder if it was a direct influence for works like Teito Monogatari...
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The Chinese edition?
I have read Fujiwara Kamui's Teito Monogatari manga in the original, and an interesting thing about the Dragon Comics edition of Teito Monogatari is that the appendix was printed in formal kanji and it gives the text a historical feel.
That is from the 'Katana (Sword)' chapter of Kōda Aya's Misokkasu.
I have read Musubi no Yama Hiroku, which received an Izumi Kyōka Prize for Literature.
I don't know whether it directly affected Teito Monogatari, but its 'history + fantasy/science fiction' story-making might have influenced Teito Monogatari.
Hanmura Ryō also wrote Ishi no Ketsumyaku, and it, too, is pretty good. Fukushima Masami, the 1st editor-in-chief of SF Magazine, included it in '100 Best Science Fiction', when he made the list in 1976.
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I was actually referring to just the illustration. Unfortunately, I wasn't able to find the original Japanese edition here in America. I'm guessing if I raid a few more Japanese bookstores, it may turn up though.
I was able to find the original Japanese version of the Yohsuke Takahashi manga (which covers books 5+6 of Teito Monogatari). Have you read this one also?
That's a good idea. I like that. I will have to find the Japanese version one of these days.
From what I understand, the manga adaptations are more faithful to the original novel than either the films or the anime.
Thank you! It's good to have the original quote and a professional English translation side by side.
Misokkasu is one of Koda Aya's memoirs as I understand it.
I think it's primarily focused on the relationship between her and her father.
It's just that Teito Monogatari began being written only 10 years after Musubi no Yama Hiroku and the concepts are very similar. One major difference is that Musubi no Yama Hiroku starts in the Warring States period...but it ends in the mid 20th century (iirc). Teito Monogatari starts in early 20th century, but it ends at the end of the century. But if you were to combine the prequels (Teito Gendan and Shin Teito Monogatari) with the main novel, it would start near the end of the Edo era, meaning that it rebuilds almost 200 years of history (like Musubi rebuilds 400 years).
From what I understand...what Musubi no Yama Hiroku and Teito Monogatari both brought to modern Japanese fantasy/science fiction literature was meticulously researched settings based on modern Japanese history. Japan had has many historical fantasy novels prior (such as the works of Futaro Yamada, like Makai Tensho), but they were usually set in ancient, pre-industrialized Japan. Very few of these fantasy stories were set in eras like the Meiji Restoration or early Showa Period. Musubi no Yama Hiroku and Teito Monogatari broke the mold. They were both post-war fantasy epics with detailed recreations of modern early 20th century history as the setting (although I should mention that Musubi doesn't to mid-20th century until later on in the novel) and their popularity helped revive interest in these eras in popular culture. That is part of the reason they are significant in the history of Japanese fantasy literature.
Does that sound right or appropriate?
There's one other thing I'm confused about too...Musubi no Yama Hiroku is considered one of the greatest Japanese science fiction/fantasy novels of all time, but Teito Monogatari has had more visual adaptations and seems to be more known in pop culture. Why is this?
Ah, that's the one about the "immortals"!
Indeed, that sounds like another classic novel that should be translated too. I'll recommend it to our publisher.
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I have read the Takahashi Yōsuke version, too. Since Takahashi writes and illustrates horror/fantasy/mystery manga, a character from a fantasy-mystery manga by him set in the early 20th century made a guest appearance in the Teito Monogatari manga
Sakaguchi Ango and Yamada Fūtarō wrote works set in the Meiji period. Shiba Ryōtarō has been very popular in Japan. In 1965 Hirose Tadashi wrote an SF novel set in the 1930s.
If you write an outline of a genealogical table of that genre, it might be better to take other factors into account.
What I can think of right now is:
1. Accessibility. I wouldn't say Musubi no Yama Hiroku is high-cultural, but Teito Monogatari is far more accessible, probably accessible even to lower-middlebrow younger readers.
So, Teito Monogatari sold well.
2. 'How popular fantasy/science fiction was in Japan in 19XX.' As Tsutsui Yasutaka, too, occasionally said, very roughly speaking, fantasy and science fiction were special genres mainly for buffs and not necessarily very popular among other people in the olden days. At least not popular enough to be eagerly jumped at by many mainstream executives of publishing industry and entertainment industries.
So, Fukushima Masami had to write a primer in science fiction to educate mainstream readers even in the 70s.
In a funny scene in A Spaceship Lit by the Lemon-like Moon by Noda Masahiro, the Customs were infuriated at imported Weird Tales.
And, well, a person who is a buff of genre X thinking 'This is a great work' is one thing. Whether executives of entertainment/publishing industries and mainstream people think so is another.
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This character!
Ah! This is why I'm so glad to be talking to someone who is familiar with this material! Yes, indeed it would be a good idea to write an outline.
Shiba Ryōtarō though...didn't he write mainly historical fiction? Did he write a historical fantasy novel as well?
Anyways...that makes sense. Maybe there had not been many fantasy "epics" set in those periods before?
Another factor I didn't take into account was that by the time Teito Monogatari came along (1985), there was a new generation of readers who were growing up during Japan's economic boom. Maybe to them, a fantasy work about the Meiji Era seemed more "nostalgic" or "mythical" since they were more distanced from that time period.
That doesn't apply so much to Musubi no Yama Hiroku though (which was published in 1973). However the reason for that might also apply to what you say below.
That makes sense. I went back and consulted some notes from a translator who works in the publishing industry. I had actually asked him about Musubi no Yama Hiroku before, and he told me the novel is VERY HEAVY with historical references, much more so than Teito. He said if the reader does not have an incredibly solid, working understanding of those 400 years of Japanese history the book touches upon prior to reading the book, then he/she will be lost or lose interest very quickly. He also told me for that reason, it will probably never be translated.
This is ironic because so many Westerners who watch the film versions of Teito Monogatari complain the story is "too complicated"; they complain there's too many historical and mythological references that they don't understand. But, as you said, in Japan, Teito Monogatari is considered accessible fiction! It's easier than a work like Musubi no Yama Hiroku.
BTW, another thing I wanted to ask you...as someone who has read the novel, which visual adaptation of Teito Monogatari would you recommend to someone unfamiliar with the novel?
I always thought they all had major problems:
1) The 1988 Akio Jissoji movie is fun and has the right tone, but the plot is too compressed and nearly incomprehensible.
2) The anime (Doomed Megalopolis) has a plot that's easier to follow, but the tone is overwhelmingly dark, grim and serious.
3) The Kamui Fujiwara manga is the most accurate, but it cuts out way too many plot points and characters (Gakutensoku, Shigemaru Kuroda, the underground railroad, etc.)
Basically all of them are very compressed, incomplete and somewhat inaccessible without the novel. Personally I would just encourage people to read the book first. But if you had to choose...which one do you think is the best?
And that makes sense too. From an elitist or well bred enthusiast's point of view, most of the stuff that appeals to mainstream audiences will seem "dumbed down" compared to the material they digest.
I read that in the mid-90's, there was a big debate in Japan among literature buffs about how the quality of science fiction literature was declining in recent years. Apparently, many people were outraged that the film Gamera 2 won the Nihon SF Taisho Award, and started complaining that the only reason such a thing could happen was that contemporary fantasy/sci-fi literature was becoming "trash" (the debate was actually called the "trash debate" iirc). Maybe this was a result of fantasy/sci-fi literature becoming more mainstream?
PS: I asked my friend in the publishing business about Ishi no Ketsumyaku. He told me though that although the novel is significant, it's way too long and for that reason, he's not going to translate it.
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The Supreme Court will hold oral arguments this week on the big Obamacare case of the term, King v. Burwell. At stake: the potential collapse of the individual-insurance market in states using the federal system (Healthcare.gov) instead of setting up their own exchanges.
Megan McArdle of Bloomberg View explains some of what a King victory would mean. Policy holders receiving subsidies would suddenly find their insurance unaffordable; even those with high incomes might find their costs doubling or more, or possibly have their policies canceled. On the business side, it would likely be a disaster for insurers, hospitals, doctors and others.
Yes, an incredibly easy fix is available. Congress could pass -- and Democrats would demand -- a simple one-page bill making the entire problem go away.
Of course, Republicans wouldn't want to do that because the whole point of the lawsuit was to undermine the Affordable Care Act. But as Byron York at the Washington Examiner said, without some plan they'll be the proverbial dog who caught the car. That's why three Republican senators claim to have worked out a plan for putting things right in case the King plaintiffs win.
Unfortunately, as Ezra Klein points out, the "plan" is mostly platitudes, and at any rate most Republicans will oppose any efforts to fix, rather than repeal, Obamacare (see also Vox's Sarah Kliff on how the DHS mess suggests the problems Republicans will have).
So if the King plaintiffs win and people lose their health care, is chaos the certain result?
Perhaps not.
Republicans will have three realistic options. They can do nothing. That's probably what they will do, but it isn't risk free. A lot of Republican voters and Republican-aligned interest groups will be taking a big hit and asking their politicians for help, even if they believe it is all the Democrats' fault.
The Republicans' most sensible option would be to use the situation to negotiate for modifications in the law. Yet this is the least likely outcome, for reasons Kliff and Klein explain. If Republicans had wanted to cut a deal, they would have done so long ago, and they won't change their minds just because they might be able to get a slightly better deal.
The third option? Though the plan offered by Senators Orrin Hatch, Lamar Alexander and John Barrasso is mostly platitudes, what matters is their pledge to "provide financial assistance to help Americans keep the coverage they picked for a transitional period."
Now, they don't speak for other Republicans, especially not (as Klein points out) those in the House. Still, it isn't difficult to imagine a lot of Republicans, especially senators in swing states, wanting to install a temporary fix until (supposedly) the final details are worked out on that Republican replacement plan that's always, but not quite, ready to roll out. And they might sell it to Obamacare-hating colleagues by pointing out that a repeal has no chance of beating a veto now, so they might as well wait until 2017.
The model might be the Arkansas "private option" Medicaid extension. The Republican governor and legislature wouldn't admit to supporting Medicaid expansion there, but they allowed it to continue for two more years while they (supposedly) work out a new system.
Given how a "temporary" two-year delay would be so simple it might not be easy for House Republicans to walk away from this third option. But if some of them do opt for a fix, expect a fight among Republicans far more bitter than the current one over Homeland Security funding and immigration.
The specifics: Republicans claim that the Affordable Care Act only allows subsidies if a state has set up its own exchange, and that this help should not be available for people in states using the federal exchange. If this is what the Supreme Court finds, Congress could simply add the words "or the federal government" at the appropriate place in the statute, as Charles Gaba suggests. Note that the Obama administration and most experts in statutory interpretation say the original law allows for subsidies on the federal exchange. For the background on the lawsuit, see Sarah Kliff here and Jeffrey Toobin here.
Warning: Some of those arguments on both sides may be spin intended to influence the court. Republicans have an incentive to argue that a ruling for King would be no big deal, while Democrats want the justices to believe such a decision would be disruptive, especially given a Congress too dysfunctional to act.
This column does not necessarily reflect the opinion of Bloomberg View's editorial board or Bloomberg LP, its owners and investors.
To contact the author on this story:
Jonathan Bernstein at email@example.com
To contact the editor on this story:
Katy Roberts at email@example.com


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Limited edition and unlimited creativity
The grand hall of the Casanatense Library, a treasure chest of rare manuscripts, will be the setting of the second edition of Limited/Unlimited, "Small Objects of Desire", a curatorial project promoted by Silvia Venturini Fendi, the President of Altaroma. Alongside the installation's path, each item, each shoe, each object is seen as a "whole", the protagonist of stylistic individualities.
40 designers - from Claudio Montias to Fabio Quaranta, to Moi Multiple to Max Kibardin - took part with a design representing their style and fashion concept, sharing a common thread: craftsmanship and the value of creations 'Made in Italy'.
In July 2011, moreover, yoox.com will become part in the project as a partner. Within the initiative, Limited/Unlimited hosts an exhibition curated by Sofia Gnoli, dedicated to Italian haute couture: Out of the Time - Guardaroba di Signora, (Out of the Time - A lady's wardrobe) dedicated to Italian high fashion from the '60s to the '80s.
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Vittoria Mentasti - Dead Sea
Vittoria Mentasti's Dead Sea takes us to a place where the sky and the sea are one
Kristin Prim and The Provocateur's letters
A chat with Kristin Prim, the founder of The Provocateur, the site that publishes letters written expressely by leading women addressing the whole female world. Vogue.it presents you an exclusive preview of the letter written by Dresden Dolls' Amanda Palmer
Fashion shows are changing: Burberry and all that's new on the runways
Menswear and womenswear collections will walk together and will be on sale right after the show. These are the news from Burberry but the evolution is generalized: runway shows are changing


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Several matter pinch shares of The Gap, Inc. (NYSE:GPS) [Trend Analysis], as shares surging 1.98% to $30.43 with a share volume of 4.98 Million. Apparel retailer Gap Inc. (GPS) released that it has designated Teri List-Stoll as executive vice president and chief financial officer, effective January 17, 2017. She will report to Gap chief executive officer Art Peck and will serve on the firm's senior leadership team. List-Stoll will succeed Sabrina Simmons, whose departure was before reported on November 2, 2016 and will have oversight of the firm's global finance function, as well as loss prevention and corporate administration divisions.
Once List-Stoll joins Gap in mid-January, Simmons will shift into an advisory role through the end of the firm's fiscal year. Most recently, List-Stoll held the position of executive vice president and chief financial officer for Dick's Sporting Goods, Inc (DKS). Before, she served in senior finance roles, comprising chief financial officer for Kraft Foods Group, Inc. The stock is going forward its 52-week low with 82.85% and moving down from its 52-week high price with -0.23%. To have technical analysis views, liquidity ratio of a firm was calculated 1.50 as evaluated with its debt to equity ratio of 0.68. The float short ratio was 16.46%, as compared to sentiment indicator; Short Ratio was 6.14.
Shares of Valhi, Inc. (NYSE:VHI) [Trend Analysis] runs in leading trade, it moving up 4.63% to traded at $2.71. The firm has price volatility of 9.05% for a week and 7.31% for a month. Its beta stands at 2.05 times. EnergySolutions and Valhi, Inc. (NYSE:VHI) reported that plans to vigorously defend EnergySolutions' pending acquisition of Waste Control Specialists LLC (WCS) in response to a U.S. Department of Justice (DOJ) court case looking for to block the transaction.
This combination is in the best interest of the nuclear industry as it delivers on part of the "Nuclear Promise" strategic plan. Through merging the two companies, the new entity will realize important cost synergies through a decrease in management, selling, and administration expenses. Those savings, in turn, can be passed on to utilities and consumers of nuclear electricity. In addition, this merger will save costs on nuclear decommissioning.
The DOJ contends that the combined firm would be "the only option for consumers in about 40 states." In fact, there are numerous disposal sites for LLRW waste operated by the contenders of the two companies. In addition, consumers have the option to store on-site, as many have done, rather than ship to one of the many companies offering LLRW disposal. Narrow down four to firm performance, its weekly performance was 19.91% and monthly performance was 27.83%. The stock price of VHI is moving up from its 20 days moving average with 27.20% and isolated positively from 50 days moving average with 21.51%.


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Central, busy location
285 Nguyen Hue, Qui Nhon T: (056) 816 085, (0977) 907 085
One reason to consider the Huy Bao is that it's on a section of Nguyen Hue that is full of local food stalls and easy access to internet places.
Last updated on 23rd July, 2007.
The Travelfish newsletter is sent out every Monday and is jammed full of free advice for travel in Southeast Asia. You can see past issues here.


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Student Achievement
The following links are resources that examine the retention and graduation of UW-Superior students. The Office of Institutional Effectiveness also conducts more granular studies for administration, faculty, and staff in order to understand and better serve student needs.
- UW-Superior Retention and Graduation Rates
- Student Achievement Measure
- UW-System Office of Policy Analysis and Research Report
- College Portrait Student Success and Progress Rate
- UW-Superior Equity Gaps - Pell
- UW-Superior Retention and Graduation Rates - by Gender
- UW-Superior Retention and Graduation Rates - by URM
Equity Scorecard
Equity Scorecard is an evidence-based assessment of inequities that exist in educational outcomes, particularly for students of color. The premise is that "an academic institution is a community whose characteristics can systematically generate gaps in educational outcomes among student groups." Four Perspectives were reviewed:
- Access: enrollment, majors, financial aid
- Retention: persistence, course taking patterns, graduation
- Excellence: achievement, academic opportunities
- Institutional Receptivity: openness to diversity, campus climate
- Equity Scorecard Final Report
- Executive Summary
Accountability Report
This report is produced annually for the UW Board of Regents. It features various measures of effectiveness and accountability.


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created by Viacom New Media and published by Viacom New Media
A game based on the 90s cartoon on the same name, the player (taking the role of Rocko) must protect Spunky on his promenade to the red fire hydrant at the end of the level.
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Tarot Readings
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Last updated on 26th Jul 2014
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Tarot Readings
The list of psychic reading methods might be never ending and many professionals may have their very own unique methods of providing psychic readings.
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Cinnamon Powder - 250g
True Cinnamon powder from Sri Lanka, that is sweet and warming in flavour. Ideal for adding delicate flavour to pastries, puddings, hot drinks and sauces.
Buy 1 Kg Cinnamon Sticks at just £ 26.95
Ceylon Cinnamon offers 1 Kg cinnamon sticks at just £ 26.95. These cinnamon sticks are the inner bark of a tropical evergreen tree in Sri Lanka. It has a sweet, woody flavour and aroma.
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- Airplanes
- Multirotors
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Contains everything needed to power one of our Mighty Mini (single engined) Planes. This kit completes everything you need to build our single engined Mighty Minis. The only other components you will need to fly is a battery/charger and transmitter/reciever. The included motor and ESC comes presoldered with 2mm Bullets and Xt-30 Connector. We set out from the beginning to make this great hobby more approachable and these all in one electronics packs are another step in that direction.
NOTE: Our 12 Amp Esc's now contain Xt-30 connectors! The industry is moving toward a shift in connectors for a higher safety and satisfaction rating for customers. We are excited to see this shift impact RC enthusiasts in a positive way!
Pack Includes:
I have not flown on them yet but they are in great shape. Love Lipo bag. Unknown on 11th Feb 2017
The product was packaged in sealed bag with all components visible. All components were excellent quality. Exactly as described. Unknown on 7th Jan 2017
I have purchased (20) sparrow sets for Civil AIR Patrol training of cadets. We could use electronics for these kits. It would be nice to have a: 1 motor, 2 servo, ESC, receiver, 2 prop kit with STEM discount options. You can email me if you can make something like this happen.
Thanks, Kirk Rasmussen on 7th Nov 2016
I am working on my first foam airplane, and I like how everything I need is supplied in the power pack kit. I will definitely be buying more power packs in the future. Michael on 21st Oct 2016
Pleased as always with everything Ray Welch on 2nd Sep 2016
Wanted to put power to my little sparrow. Everything I needed, other than receiver and battery. Now, just need to go out and trim the little bugger. Would definitely go this route again gary zion on 30th Aug 2016
Great way to buy the electronics G Partington on 22nd Jul 2016
In this day and age, it's seldom that my expectations are exceeded. However, I must say the this power pack kit exceeded my expectations. Everything I needed (or didn't even know I needed) was there, even down to the screwdriver tools. Being new to the hobby, Flight Test has been an invaluable resource for information and knowledge contributing to the build. I'm so encouraged by the "build your own" spirit and nature of the business. And, oh yeah..... have fun doing it. Excellent job Flite Test! Unknown on 15th Jul 2016
I was impressed with what all came in this Power Pack. The motor seems so small but really delivers with the 800mAh 2S battery. The tools are great and the rest of the components are great quality too. If you are considering buying a mini SBK then save the guesswork and hassle of shopping around and buy this Power Pack to go with it. You will be glad you did. Rick H. on 27th Jun 2016
I ordered this kit for the" Mini Trainer" The only issue I have,is I forgot to get the LiPo battery to go with it ! I need to watch more Youtube Flitetest Videos Mike I on 20th Jun 2016


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$250 free shippingShop Now
Kicker 400W Subwoofer Amplifier w/ Headphones
Crutchfield offers the Kicker 400-watt Mono Subwoofer Amplifier, model no. 40KX400.1, bundled with a pair of Kicker Phenom Talk In-Ear Headphones, model no. EB92MB, for $249.99 with free shipping. (Add the amplifier to your cart and the headphones will be automatically included.) That's the lowest price we could find for these items sold separately elsewhere by $30. The subwoofer features variable low-pass filter, Kick EQ, parametric bass boost, front-mounted controls, variable subsonic filter, wired remote level control, and 4-gauge power and ground leads. The headphones feature a frequency response of 10Hz to 50,000kHz, 8mm dynamic drivers, and two ohms impedance.


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I was introduced to buying pizza by weight when I lived in Italy as a student, so I thought it would be fun to try the same thing here in New York City.
Although I don't consider myself a stickler for upscale surroundings when heading out for some pizza, while waiting for the pie to be served, it was hard not to notice what an unattractive hodgepodge the decor at Pie is.
Trying to keep an open mind, though, I waited for my garden vegetable pizza (called Fresh Cubed) to arrive. This variety was one of the more attractive toppings of the long counter's worth of (glutenous) pizzas for regular eaters to choose from.
The pizza arrived looking bright and cheerful. The crust was crispy. But the pizza, although we were the only customers ordering, wasn't hot. The cubes of mozzarella were not melted. The tomatoes were cold. When I asked the server, she said, "Oh, that's the fresh mozzarella. The other mozzarella is melted." And she was correct.
There was a layer of mozzarella and (good-tasting) sauce UNDER the cold greens, tomato and fresh mozzarella. This idea that several cold toppings would be served on a hot pizza, thereby rendering it cool or lukewarm at best, was something it was impossible to determine from examining the toppings lineup behind the glass. Although she offered to heat it to melting, I declined, wondering what would happen to the chopped salad tomatoes and delicate leaves of basil.


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It's easy to see why residents of the poorest of the neighborhoods that the Route 6-10 connector snakes through in Providence have felt forgotten by city and state leaders. More than one-quarter of the residents of the six predominantly … more
It was no secret that Providence officials and the R.I. Department of Transportation had differing views of how the deteriorating Route 6-10 connector should be replaced. So when Gov. Gina M. Raimondo appeared to cut short the public discussion in … more
It was clear from PBN's most recent Health Care Reform Summit, held on Oct. 20, that there are still more questions than answers concerning the national debate over rising health care costs. Several panelists cited continued resistance from … more
Providence City Council's rejection of a proposed $40 million infrastructure bond issuance has laid bare the shortcomings of the current system for electing its members. Citing concerns about the city's fiscal condition, the group against … more
When people talk about the big picture, it is usually a metaphor. But in the case of offshore wind energy, it's a lot more than that. As this week's cover story and photo, "Will being first pay off for Ocean State?" make clear, offshore … more
When Dunkin' Brands Group Inc. CEO Nigel Travis took the time on Oct. 5 to speak at Johnson & Wales University, he was modeling behavior that the entire business community could learn from. His appointment as a distinguished professor at … more
For those thinking that the finalized reforms to the state-worker pension system took care of all its issues, think again. The outstanding problem is the fund's assumed rate of return. At the moment it is 7.5 percent. And with the reforms, … more
Rhode Islanders face seven ballot questions this year, and few of them are simple to endorse or reject. Question 1 Does the state need to replace the diminishing asset that is Newport Grand? Absolutely. And the proposal by Twin … more
General Treasurer Seth Magaziner has said he is going to reduce the use of hedge funds in the state's $7.6 billion pension fund. Given the poor returns and high fee structures of hedge funds, a change makes sense. But there is a much larger … more
The Working Cities Challenge is a Federal Reserve Bank of Boston program designed to create an economic resurgence in communities after "years of population and economic decline." To that end, the Boston Fed is having seven of the state's urban-core … more


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Uniquely Modern Stainless Steel Floor Clock Table by Benzara
- Stainless Steel Floor Clock Table Dimensions (inches): L 21 x W 21 x H 25
- Frame in a silver color dial is black
- Beautifully shaped
Imagine a table that has a clock for its surface! Well, that ingenuity you will find in this Stainless steel flood clock table. A very wholesome and appealing creation, this clock table has a uniquely shaped frame that is in a silver color. Also it is a very visible dial and numbers. Perfect for having a cup of coffee over with your friend; this table will inspire forth creative feeling. Also this clock's ingenious theme will go very well with modern decors and modern art. This Floor clock table can also be turned into a great gifting item; you could gift it to near and dear ones. Also the clock being made from quality materials means that it will last in tiptop condition for years to come. It is sure to draw forth many complements and kudos is sure to be heaped on its designer. Indeed, this is the Floor clock table for the modern home.


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Dog Walkers in Wilsie, CA
Book a dog walker to give your dog a 30-minute walk around your neighborhood.
Kayla's Pet Sitting/Walking!
El Centro, CA, 92243
House Sitting, Drop-In Visits, Dog Walking
About: Hello fellow animal lovers! My name is Kayla. I am a student at Imperial Valley College, and looking to get my degree in Animal Sciences. I am also... (more)
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Rover also offers dog walking in:
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We've been there: rushing home during every lunch break to take the dog for a quick walk around the block. Good news: You can easily find and book Wilsie dog walking services on Rover. Whether you need a one-time dog walker or someone to take your dog for a stroll every day, we've got you covered. Exercise for your dog and peace of mind for you are just a few clicks away. Every walk is covered by premium pet insurance, at no extra cost to you. You can even ask your dog walker to send you a photo update. Whether you already have a favorite pet sitter on Rover or you're new to the site, we'd love to connect you with a dog walker in Wilsie the next time you're unavailable. We're confident you and your dog will love it.
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