White coat hypertension in acute retinal vein occlusion.

PURPOSE: To investigate the association between white-coat hypertension (WCH) and acute retinal vein occlusion (RVO). METHODS: In this retrospective case-control study, patients aged 40 years or older diagnosed with acute-phase RVO were included. Patients with other pathologies served as non-RVO controls. Blood pressure (BP) was measured in the office during their initial visit, and information about home BP and hypertension (HTN) medication was obtained through interviews. After 1:2 age and sex-matching between the RVO and non-RVO groups, the proportions of HTN cases were compared. A similar comparison was made in subgroups with or without HTN medication. RESULTS: Fifty-one patients with RVO and 102 with non-RVO were included in the analysis. For the entire cohort, the RVO group exhibited a significantly greater proportion of WCH and sustained HTN compared to the non-RVO group. In the subgroup without HTN treatment, the proportion of WCH or sustained HTN was still significantly higher in the RVO group. However, in the subgroup receiving HTN treatment, the proportion of WCH or sustained HTN was higher in the RVO group than in the non-RVO group, though not statistically significant. CONCLUSION: This case-control study suggests that WCH may be associated with RVO, particularly in patients without HTN treatment. Given that interventions for WCH have not been standardized, a more detailed and prospective study is warranted to elucidate the risk of WCH for RVO and other retinal vascular diseases.

Successful catheter ablation in an octogenarian with persistent atrial fibrillation complicated by cor triatriatum sinister: a case report.

Background: Cor triatriatum sinister (CTS) is a rare congenital heart defect sometimes complicated with atrial fibrillation (AF). Catheter ablation (CA) relieves the AF-associated symptoms, but CA for AF with CTS has been reported rarely. Because CTS can be associated with other congenital heart disease, detailed preoperative assessment is important. Case summary: An 80-year-old man was referred to our institution for shortness of breath that had persisted for 2 months when he was first diagnosed with AF. Transthoracic echocardiography revealed an enlarged left atrium (LA) divided into two chambers by a membrane. Transoesophageal echocardiography showed the membrane extending from the fossa ovalis (FO) to the Coumadin ridge, with the accessory (dorsal) chamber (AC) in closer proximity to the FO. Computed tomography showed that all pulmonary veins (PVs) flowed into the AC, with no PV anomalies. No other heart anomaly was identified, with no thrombus in the LA. With these findings, PV isolation (PVI) with CA was considered safe. Transseptal puncture was performed with intracardiac echocardiography for precise catheterization of the AC. Pulmonary vein isolation was performed successfully. The patient was discharged 4 days after the procedure, without any complications. His symptoms improved post-procedure, and sinus rhythm was maintained without antiarrhythmic drug therapy during the 18-month follow-up. Discussion: Cor triatriatum sinister is a rare anomaly that accounts for 0.1% of all congenital heart diseases. Cor triatriatum sinister sometimes complicated with symptomatic AF. Detailed preoperative anatomical assessment with multiple imaging modalities helped us achieve safe and effective CA for a patient with AF and CTS, even in an octogenarian.

Preclinical toxicological assessment of amido-bridged nucleic acid-modified antisense oligonucleotides targeting synaptotagmin XIII for intra-abdominal treatment of peritoneal metastasis of gastric cancer.

BACKGROUND: Peritoneal metastasis of gastric cancer is closely associated with dismal prognosis. In previous preclinical proof-of-concept studies, an amido-bridged nucleic acid (AmNA)-modified antisense oligonucleotide (ASO), designated ASO-4733 that targets the gene encoding synaptotagmin XIII (SYT13), inhibited cellular functions required for the formation of peritoneal metastasis of gastric cancer cells. ASO-4733 achieved therapeutic effects when intra-abdominally administered to mouse xenograft models. Here, we conducted an analysis of Syt13-deficient mice to determine the pharmacokinetics and toxicity of intra-abdominal administration of ASO-4733. METHODS: The effects of Syt13-deficiency in mice were determined. Good Laboratory Practice toxicity tests and the toxicokinetics of intra-abdominal administration of ASO-4733 were conducted in cynomolgus monkeys and rats. The pharmacokinetics of ASO-4733 administered intravenously or intra-abdominally to rats were investigated. RESULTS: Syt13-deficient mice exhibited normal reproduction, organ functions, and motor functions. Weekly intra-abdominal administration of ASO-4733 (125 mg/kg), corresponding to a 50-fold increase of the estimated clinical dose for 4 weeks, was well tolerated by cynomolgus monkeys. In rats, off-target toxicity (not attributable to hybridization) was observed after weekly intra-abdominal administration of ASO-4733. Blood concentrations of ASO-4733 were lower and rose more slowly after intra-abdominal administration compared with intravenous administration. CONCLUSIONS: The preclinical profile of intra-abdominal administration of ASO-4733 demonstrated its suitability for entry into clinical trials of patients with peritoneal metastasis of gastric cancer.

Regulating distal nephron functions and salt sensitivity.

This review highlights the molecular basis of salt sensitivity in hypertension, with a focus on the regulation of sodium transport in the distal nephron. Sodium reabsorption in this region is often linked to the actions of aldosterone, although in recent years numerous findings have been reported on the aldosterone-independent pathway of acquiring salt sensitivity by potassium deficiency or potassium loading. The key to this discussion is the interplay, through extracellular potassium concentration, between the first part of the tubules expressing the Na+-Cl- cotransporter (NCC) and the second part expressing the epithelial Na+ channel (ENaC). The molecular pathways such as with-no-lysine 1 (WNK)-STE20/SPS1-related proline-alanine-rich kinase (SPAK)/oxidative stress-responsive kinase 1 (OSR1) signaling, Kelch-like family member 3 (KLHL3)-cullin 3 (CUL3) complex, protein phosphatases, and mechanistic target of rapamycin complex 2 (mTORC2)-Nedd4L pathway are described as the mechanism by which salt sensitivity on blood pressure is acquired in response to changes in physiological conditions including potassium depletion or loading. This review highlights the potential for targeting these molecular pathways to develop novel therapeutic strategies for the treatment of salt-sensitive hypertension, the mechanism of which remains to be elucidated.

Three-year outcome of photodynamic therapy combined with VEGF inhibitor for pachychoroid neovasculopathy.

BACKGROUND: Long-term results of photodynamic therapy (PDT) combined with vascular endothelial growth factor (VEGF) inhibitors for pachychoroid neovasculopathy (PNV) are not yet clear. METHODS: This study is a retrospective, observational case series. We retrospectively examined untreated PNV cases (22 cases, 22 eyes, mean age of 71.0 years) who underwent PDT therapy in combination with VEGF inhibitors followed by additional treatments with pro re nata protocol. Visual acuity, number of treatments, and time to recurrence were examined. In addition, foveal choroidal thickness and choroidal vascularity index (CVI) were evaluated in 13 of 22 patients who were followed up with SpectralisOCTR from baseline. RESULTS: Fifteen (68%) cases had polyps at baseline. LogMAR visual acuity averaged 0.24 ± 0.20 (range, - 0.079 to 0.82) at baseline and significantly improved after 1, 2, and 3 years (p = 0. 004, 0.0003, 0.002, respectively). Fourteen patients (64%) recurred, with an average time to recurrence of 1.8 ± 0.9 years. Foveal choroidal thickness decreased significantly after 1 year (average from 326 µm to 263 µm) and remained unchanged up to 3 years (255 µm). CVI also decreased after 1 year (average from 0.62 to 0.61) and remained unchanged until 3 years later (0.60). CONCLUSIONS: We examined the 3-year course of PDT in combination with the VEGF inhibitor for untreated PNV. Visual acuity was improved, foveal choroidal thickness and CVI were decreased after 3 years.

Intravitreal anti-vascular endothelial growth factor and combined photodynamic therapy for pachychoroid neovasculopathy: long-term treatment outcomes.

PURPOSE: To examine the long-term visual outcomes after initial treatment with combined photodynamic therapy (PDT) or aflibercept treat-and-extend (TAE) monotherapy in patients with pachychoroid neovasculopathy (PNV). METHODS: Patients diagnosed with PNV, initially treated with PDT combined with anti-vascular endothelial growth factor (VEGF) or intravitreal aflibercept (IVA) monotherapy in the TAE protocol and followed up for at least 6 months, were included in the study. Medical records were retrospectively reviewed. Survival analysis was performed, in which deterioration in logMAR visual acuity by 0.1 or 0.3 is defined as "death." The annual number of treatments was also analyzed. Sub-analysis was performed on 33 patients diagnosed with PNV without polypoidal lesions. RESULTS: This study included 46 patients (23 in the initial combined PDT group and 23 in the IVA TAE group). Mean age, sex, mean baseline logMAR visual acuity, or duration of observation (3.6 ± 3.2 years vs. 3.1 ± 1.9 years) in both groups were comparable. As for visual outcome, no significant differences were found in survival analysis based on worsening of 0.1 or 0.3 logMAR (3-year survival; 26% vs. 26%, 91% vs. 90%, respectively). Meanwhile, the additional number of anti-VEGF injections per year was significantly lower in the initial combined PDT group than in the IVA TAE group (1.0 ± 1.3 vs. 4.1 ± 1.5, p < 0.0001). No significant differences were found in the number of additional PDTs per year (0.07 ± 0.20 vs. 0.02 ± 0.09, p = 0.27). Similar results were found in a sub-analysis of 33 patients without polyps. CONCLUSION: In the treatment of PNV, regardless of the presence of polyps, the long-term visual outcomes were similar between the initial combined PDT and IVA TAE monotherapy. However, the annual number of anti-VEGF injections was lower in the initial combined PDT group than in the aflibercept TAE group, whereas that of PDT was comparable.

Biomechanical properties measured with dynamic Scheimpflug analyzer in central serous chorioretinopathy.

PURPOSE: Recent evidence suggests that venous congestion at the vortex vein significantly contributes to the development of central serous chorioretinopathy (CSCR), and sclera is observed to be thicker in affected eyes. This study aims to investigate whether eyes with CSCR exhibit stiff corneas, measured using Corneal Visualization Scheimflug Technology (Corvis ST), which may serve as an indicator of scleral stiffness. METHODS: This retrospective case-control study comprises 52 eyes from 33 patients diagnosed with CSCR and 52 eyes from 32 normal controls without CSCR. We compared biomechanical parameters measured with Corvis ST and anterior scleral thickness measured using anterior segment swept-source optical coherence tomography between the two groups. RESULTS: Age, sex, axial length, intraocular pressure, and central corneal thickness showed no significant differences between the two groups (p > 0.05, linear mixed model). Three biomechanical parameters-peak distance, maximum deflection amplitude, and integrated inverse radius-indicated less deformability in CSCR eyes compared to control eyes. The stress-strain index (SSI), a measure of stiffness, and anterior scleral thickness (AST) at temporal and nasal points were significantly higher in the CSCR eyes. SSI and AST were not correlated, yet both were significantly and independently associated with CSCR in a multivariate logistic regression model. CONCLUSIONS: Eyes affected by CSCR have stiffer corneas, irrespective of thicker scleral thickness. This suggests that stiffer sclera may play a role in the pathogenesis of CSCR.

Long-term visual outcomes in pachychoroid spectrum diseases and its associating factors of eyes with chronic central serous chorioretinopathy.

To analyze the long-term visual outcomes of pachychoroid spectrum diseases (PSD). Retrospective study. We reviewed the medical charts of consecutive patients with PSD, including focal choroidal excavation (FCE), pachychoroid pigment epitheliopathy (PPE), central serous chorioretinopathy (CSC), and pachychoroid neovasculopathy (PNV). The patients initially visited the Tokyo University Hospital from January 2008 to March 2021. Survival analyses were performed, in which loss of vision was defined as visual acuity (VA) of 0.2 logarithm of minimal angle of resolution (logMAR) or worse, 0.5 logMAR or worse, or VA worsening by 0.3 logMAR or greater. Moreover, we further investigated factors associated with visual prognosis, particularly in the CSC group. A total of 741 eyes of 638 patients were included in this analysis. The CSC or PNV group showed significantly worse visual prognosis than the FCE&PPE group for VA to 0.2 logMAR or worse (P = 0.0117 or 0.0001, respectively) and for VA worsening by 0.3 logMAR or greater (P = 0.0283 or 0.0037, respectively). In the CSC group, unlike age, sex, or treatment history, the accumulative duration of subfoveal fluid existence ≥ 12 months (continuous or intermittent) was significantly associated with visual prognosis (P < 0.0001). Among PSD, CSC and PNV were associated with a higher risk of vision loss in the long term than FCE and PPE. The duration of subretinal fluid existence was identified as a significant factor affecting long-term visual outcomes in CSC.

Immunogammopathy Maculopathy Secondary to Waldenström's Macroglobulinemia Complicated With Diabetic Retinopathy: A Case Report and Literature Review.

In Waldenström's Macroglobulinemia (WM), increased immunoglobulin M causes various signs and symptoms. It sometimes presents with macular edema. A 65-year-old WM patient with a five-year history of diabetes mellitus was evaluated for ocular complications. Fundus examination and optical coherence tomography showed retinal changes consistent with non-proliferative diabetic retinopathy and foveal detachment with intraretinal cysts in the right eye, suggesting diabetic macular edema. However, on fluorescein angiography, there was no leakage over the area of foveal detachment, which led to the diagnosis of immunogammopathy maculopathy secondary to WM for macular edema and foveal detachment. The patient's ocular manifestation remained unchanged through a follow-up period of 11 months without therapeutic interventions. Immunogammopathy maculopathy, a rare ocular manifestation of monoclonal gammopathy, demands differentiation from other causes of macular edema in WM patients. The present case highlights the importance of fluorescein angiography, or silent macula, in diabetic patients to distinguish immunogammopathy maculopathy from diabetic macular edema.

NGAL is a Novel Target in Hypertension by Modulating the NCC-Mediated Renal Na Balance.

BACKGROUND: The expression of NGAL/lcn2 (neutrophil gelatinase-associated lipocalin) is directly modulated by mineralocorticoid receptor activation but its role in blood pressure control is unclear. METHODS: a potential relationship between NGAL plasma levels, systolic blood pressure and urinary Na excretion was assessed in the STANISLAS cohort. The specific role of NGAL/lcn2 in salt-sensitive hypertension was studied using lcn2-knockout mice (lcn2 KO) fed with low-Na diet (0Na). RESULTS: we show that NGAL plasma levels positively correlate with systolic blood pressure, whereas they negatively correlate with urinary Na excretion in subjects of the STANISLAS cohort. Prolonged feeding of lcn2 KO mice with a 0Na diet induced lower systolic blood pressure than that of the control group (wildtype), suggesting a role for NGAL/lcn2 in Na-balance homeostasis. Short-term or prolonged 0Na increased Na-Cl cotransporter (NCC) phosphorylation in the cortex of wildtype mice, which was prevented in lcn2 KO mice. Recombinant mouse lcn2 injections in lcn2 KO mice induced NCC phosphorylation in the kidney cortex, associated with decreased urinary Na excretion. Ex vivo experiments using kidney slices from lcn2 KO mice showed increased NCC phosphorylation by recombinant murine lcn2. In addition, recombinant murine lcn2 induced activation of CamK2ß (calcium/calmodulin-dependent protein kinase II ß subunit) phosphorylation in lcn2 KO mice and in kidney slices, providing an underlying mechanism involved in lcn2-induced NCC phosphorylation. Indeed, the inhibition of CamK2ß prevented NCC phosphorylation induced by recombinant lcn2 in kidney slices. CONCLUSIONS: we highlight a novel role of NGAL/lcn2 as a modulator of the activity of the renal sodium transporter NCC affecting salt-sensitive blood pressure.

Is the past farther than the future? A registered replication and test of the time-expansion hypothesis based on the filling rate of duration.

Caruso et al. (2013) reported the Temporal Doppler Effect (TDE), in which people feel that the past is farther than the future. In this study, we made two high-power (N = 2244 in total), direct replication studies of Caruso et al. and additionally examined whether illusory temporal expansion, depending on the degree of fulfillment in durations, is related to the TDE. We predicted that the past would be felt farther than the future because the filling rate of duration of the past should be higher than that of the future. The results showed that psychological distance was significantly closer in the past than in the future and was inconsistently correlated with the filling rate of duration or the number and length of events and errands. Further, in some cases, the correlations were significant in the opposite direction of the predictions. Overall, our results did not replicate the previous findings but were reversed, and the filling rate of duration failed to explain the psychological distance. Based on these findings, we highlight the aspects that need to be clarified in future TDE studies. Preregistered Stage 1 protocol: https://osf.io/d9ec3/ (date of in-principle acceptance: 19/04/2022).

Autonomous, bidding, credible, decentralized, ethical, and funded (ABCDEF) publishing.

Scientists write research articles, process ethics reviews, evaluate proposals and research, and seek funding. Several strategies have been proposed to optimize these operations and to decentralize access to research resources and opportunities. For instance, we previously proposed the trinity review method, combining registered reports with financing and research ethics assessments. However, previously proposed systems have a number of shortcomings, including how to implement them, e.g., who manages them, how incentives for reviewers are paid, etc. Various solutions have been proposed to address these issues, employing methods based on blockchain technologies, called "decentralized science (DeSci)". Decentralized approaches that exploit these developments offer potentially profound improvements to the troubled scientific ecosystem. Here, we propose a system that integrates ethics reviews, peer reviews, and funding in a decentralized manner, based on Web3 technology. This new method, named ABCDEF publishing, would enhance the speed, fairness, and transparency of scientific research and publishing.

Productivity and firm exit during the COVID-19 crisis: cross-country evidence.

This paper examines whether the economic crisis induced by the COVID-19 pandemic exhibits a Schumpeterian "cleansing" of less productive firms. Using firm-level data collected for 34 economies up to 18 months into the crisis, the study finds that less productive firms have a higher probability of permanently closing during the crisis, suggesting that the process of cleansing out unproductive activities is occurring. The paper also uncovers strong and negative relationships of firm exit with digital presence and with innovation. These relationships are driven by small firms. The study further finds that a burdensome business environment increases the probability of firm exit, also driven by small firms, and that a negative relationship exists between firm exit and age. Finally, evidence shows that the cleansing process is disrupted in countries which have introduced policies imposing a moratorium on insolvency procedures.

LOCATIONAL AGREEMENT OF NEAR-INFRARED AUTOFLUORESCENCE WITH CHOROIDAL VASCULAR HYPERPERMEABILITY IN CENTRAL SEROUS CHORIORETINOPATHY.

PURPOSE: To characterize the findings of eyes with choroidal vascular hyperpermeability (CVH), a hallmark of central serous chorioretinopathy, using multimodal imaging and investigate the locational agreement between these findings and CVH. METHODS: Among patients with central serous chorioretinopathy in either eye, eyes with CVH identified using indocyanine green angiography without exudative changes were included. All eyes were examined using funduscopy, fluorescein angiography, spectral-domain optical coherence tomography, and short-wavelength or near-infrared autofluorescence (SWAF or NIRAF). The locational agreement between CVH and imaging findings was evaluated for each modality. The relative index on how they overlapped was calculated as the overlapping index. Binarized images, particularly for NIRAF, were also evaluated. RESULTS: This study included 69 CVH sites in 33 eyes of 28 patients. Pachydrusen was detected in 36% of CVH sites. Fluorescein angiography revealed hyperfluorescent areas in 39% of CVH sites. Optical coherence tomography findings identified 65% of CVH sites, but the overlapping index was 5%. Short-wavelength or near-infrared autofluorescence imaging identified 89% of CVH sites, but they exhibited variable autofluorescence. NIRAF imaging revealed hypoautofluorescence findings in all CVH sites. When binarized, near-infrared autofluorescent dark dots were observed in all CVH sites. Overlapping indices before and after binarization were 78% and 98%, respectively. The near-infrared autofluorescent dark dots area corresponded well with that of CVH (intraclass correlation coefficient, 0.987 [95% confidence interval, 0.952-0.995]). CONCLUSION: Hypoautofluorescent findings revealed on NIRAF imaging, especially after binarization processing, corresponded well with CVH sites. These multimodal imaging results may help investigate the anatomical or locational characteristics of CVH in patients with central serous chorioretinopathy.

Association between retinal sensitivity and the presence of quiescent choroidal neovascularization in pachychoroid diseases.

This study was conducted to examine retinal sensitivity (RS) in eyes with pachychoroid diseases and to analyze its association with the presence or absence of quiescent choroidal neovascularization (CNV), that can be protective against retinal dysfunction or atrophy in other macular diseases such as age-related macular degeneration. A total of 12 eyes of 12 patients aged ≥45 years having the characteristic findings of central serous chorioretinopathy but not presenting any exudative changes were included in this study. Choroidal vascular hyper permeability (CVH) was identified by indocyanine green angiography, and the presence or absence of CNV was evaluated by optical coherence tomography angiography. RS at 68 points was examined by microperimetry. The average RS corresponding to within and outside CVH was compared. The association between the difference in RS and the presence or absence of CNV was also analyzed. CNV was detected in six eyes (50%). In eyes without CNV, the RS within CVH was similar compared with that outside CVH. However, in eyes with CNV, the RS within CVH was significantly decreased compared with that outside CVH. Multiple regression analysis revealed the presence of CNV as an independent factor associated with RS. In eyes with pachychoroid diseases, RS decreased within the CVH area under the coexistence of nonexudative CNV.

Trinity review: integrating Registered Reports with research ethics and funding reviews.

One major source of exhaustion for researchers is the redundant paperwork of three different documents-research papers, ethics review applications, and research grant applications-for the same research plan. This is a wasteful and redundant process for researchers, and it has a more direct impact on the career development of early-career researchers. Here, we propose a trinity review system based on Registered Reports that integrates scientific, ethics, and research funding reviews. In our proposed trinity review system, scientific and ethics reviews are undertaken concurrently for a research protocol before running the study. After the protocol is approved in principle through these review processes, a funding review will take place, and the researchers will begin their research. Following the experiments or surveys, the scientific review will be conducted on a completed version of the paper again, including the results and discussions (i.e., the full paper), and the full paper will be published once it has passed the second review. This paper provides the brief process of the trinity review system and discusses the need for and benefits of the proposed system. Although the trinity review system only applies to a few appropriate disciplines, it helps improve reproducibility and integrity.

Retinal pigment epithelium melanin distribution estimated by polarisation entropy and its association with retinal sensitivity in patients with high myopia.

PURPOSE: To investigate retinal sensitivity of highly myopic eyes without choroidal neovascularisation (CNV) or patchy chorioretinal atrophy (PCA) and investigated its association with anatomical characteristics including melanin distribution at the retinal pigment epithelium (RPE), which was evaluated with polarisation-sensitive optical coherence tomography (PS-OCT). DESIGN: Retrospective consecutive observational cohort study. METHODS: We included highly myopic eyes (refractive error ≤-8.0 dioptres or axial length of ≥26.5 mm) from patients at the University of Tokyo Hospital. Retinal sensitivity was measured by microperimetry at 25 sectors within 6 degrees from the fovea. Depolarisation value, which reflected melanin pigmentation, was measured by a clinical prototype of PS-OCT and was parameterised as polarimetric entropy. Retinal sensitivity or entropy at the RPE in high myopia was compared with emmetropic control subjects. The association of retinal sensitivity with age, axial length, entropy, or choroidal thickness was assessed in per-eye and per-sector analysis. RESULTS: Twenty-three highly myopic eyes (age, 66.6±12.3 years) were included. The average retinal sensitivity was 25.3±3.0 dB, which was significantly decreased compared with the control (p<0.0001). The average entropy at the RPE in the highly myopic eyes was significantly lower than in the control (p<0.0001). Univariate analysis followed by multivariate analysis showed that besides age, axial length or choroidal thickness, RPE entropy was independently associated with retinal sensitivity (ß=4.4; 95% CI 0.5 to 8.3; p=0.03). CONCLUSIONS: Decreased depolarisation at the RPE measured with PS-OCT, which reflected altered melanin pigmentation, was independently associated with reduced retinal sensitivity in patients with early stages of myopic maculopathy without CNV or PCA.

Aortic valve insufficiency after Impella device insertion that required aortic valve replacement after Heart Mate III left ventricular assist device implantation: a case report.

The Impella (Abiomed, Danvers, MA, USA) is a minimally invasive axial-flow catheter used in severe heart failure. We describe a case in which aortic insufficiency occurred after Impella insertion, required extra surgical intervention twice. A 33-year-old man with familial dilated cardiomyopathy was admitted to our hospital due to acute decompensation of heart failure. Despite intensive medical treatment, his hemodynamic status did not improve. Firstly, Impella was emergently implanted, and HeartMate III (Abbott, Plymouth, MN, USA) implantation was performed 2 weeks after. In the HeartMate III implantation, new aortic insufficiency had revealed and central aortic valve closure was performed concomitantly. However, on postoperative Day1, the coaptation stitch had untied, causing severe aortic insufficiency which led to another emergent operation of aortic valve replacement. We suggest that indications for Impella implantation need to be carefully discussed beforehand, especially with patients who may undergo implantation of left ventricular assist device.

Reliability of the Phonon Density of States Determined by Real-Coded Genetic Algorithm from Heat Capacities of Benzoic Acid Crystals.

Constant-pressure heat capacities (CPs) of crystalline benzoic acid (BAh) and its deuterated analogue (C6H5COOD, BAd) were measured by adiabatic calorimetry, and the phonon density (g(ω)) of states was determined from their CP data using a real-coded genetic algorithm (RCGA) with just generation gap + real-coded ensemble cross-over. The distribution of g(ω) was in reasonable agreement with the spectroscopic one observed for molecular vibration modes, indicating sufficient reliability of g(ω) determined by the RCGA. Based on the fact that CPs reveals an inverse-isotope effect in the temperature range 30-130 K, the determined g(ω)s were used to investigate the molecular mechanism of the effect: g(ω) of BAd revealed blue shifts in the ranges of ω = 80-100 and 150-230 K, as referred to that of BAh. It was suggested from the combined considerations on g(ω) and spectroscopic results that an anticooperative correlation exists between O-H···O hydrogen bonds and interdimer interactions in BA.