Free Will and the Divergence Problem

This paper presents what the authors call the ‘divergence problem’ regarding choosing between different future possibilities. As is discussed in the first half, the central issue of the problem is the difficulty of temporally locating the ‘active cause’ on the modal divergent diagram. In the second half of this paper, we discuss the ‘second-person freedom’ which is, strictly, neither compatibilist negative freedom nor incompatibilist positive freedom. The divergence problem leads us to two hypothetical views (i.e. the view of single-line determination and that of one-off chance), and these views bring humans closer to the afree side – i.e. outside of the contrast between being free and being unfree. The afree side is greatly different from the ordinary human side. This paper tries to secure the second-person freedom as a substitute for the ordinary human freedom while preventing the divergence problem from arising

bFGFの皮下注射は授乳期における新生児マウスの下顎頭の発育を促進する

To elucidate the effect of local bFGF administration, we administered a total of 0.3μg rhbFGF was to the left mandibular condyle by three injections of 0.1μl bFGF solution for 3 days after birth. The contralateral condyles with three injections of 0.1μl physiologic saline served as controls. Serial sections including the widest condyle were evaluated with H-E staining and immunostaining for PCNA. The maximum width of condyle, proliferative zone thickness, proliferative zone thickness ratio and proliferating index were analyzed using image analysis software after digital image capture of H-E stained sections. All condyles were composed of fibrous, proliferative, maturation and hypertrophic cell zones without significant abnormal findings. Experimental condyles demonstrated a markedly thickened proliferative zone compared with that of the controls at 1 day after the injection. At 4 and 7 days, chondrocytes and hypertrophic chondrocytes of the experiments increased in thickness. However, at 14 days after the injection, both the controls and experiments showed similar features with an upward shift of ossification front and active formation of bone trabeculae. Morphometrically, all values of experiments were significantly higher than those of the controls. Especially at 4 days after the final injection, proliferative zone thickness and proliferative index values of the experiment reached a peak and were nearly 1.6-fold higher than those of the control, which were statistically significant compared to other experimental groups. Despite the short half-life of rhbFGF, its effect seems to be prolonged by synergic actions of growth factors such as bFGF or TGF beta1. In conclusion, we showed that local administration of bFGF was feasible for accelerating mesenchymal cell proliferation of mandibular condyles of newborn mice in the lactation period after birth.2013博士（歯学）松本歯科大

Effects of ezetimibe add-on therapy for high-risk patients with dyslipidemia

<p>Abstract</p> <p>Background</p> <p>Ezetimibe (Zetia^®) is a potent inhibitor of cholesterol absorption that has been approved for the treatment of hypercholesterolemia. Statin, an inhibitor of cholesterol synthesis, is the first-choice drug to reduce low-density lipoprotein-cholesterol (LDL-C) for patients with hypercholesterolemia, due to its strong effect to lower the circulating LDL-C levels. Because a high dose of statins cause concern about rhabdomyolysis, it is sometimes difficult to achieve the guideline-recommended levels of LDL-C in high-risk patients with hypercholesterolemia treated with statin monotherapy. Ezetimibe has been reported to reduce LDL-C safely with both monotherapy and combination therapy with statins.</p> <p>Results</p> <p>To investigate the effect of ezetimibe as "add-on" therapy to statin on hypercholesterolemia, we examined biomarkers and vascular endothelial function in 14 patients with hypercholesterolemia before and after the 22-week ezetimibe add-on therapy. Ezetimibe add-on therapy reduced LDL-C by 24% compared with baseline (p < 0.005), with 13 patients (93%) reaching their LDL cholesterol goals. Of the Ezetimibe add-on therapy significantly improved not only LDL-C, high-density lipoprotein-cholesterol (HDL-C), and apolipoprotein (apo)B levels, but also reduced levels of triglyceride (TG), the ratio of LDL/HDL-C, the ratio of apoB/apoA-I, and a biomarker for oxidative stress (d-ROMs). Furthermore, ezetimibe add-on therapy improved vascular endothelial function in high-risk patients with hypercholesterolemia.</p> <p>Conclusion</p> <p>In conclusion, ezetimibe as add-on therapy to statin might be a therapeutic good option for high-risk patients with atherosclerosis.</p

Diagnostic accuracy of frozen section biopsy for early gastric cancer extent during endoscopic submucosal dissection: a prospective study

Background Accurate diagnosis of the lateral extent of early gastric cancer during endoscopic submucosal dissection (ESD) is crucial to achieve negative resection margins. Similar to intraoperative consultation with a frozen section in surgery, rapid frozen section diagnosis with endoscopic forceps biopsy may be useful in assessing tumor margins during ESD. This study aimed to evaluate the diagnostic accuracy of frozen section biopsy. Methods We prospectively enrolled 32 patients undergoing ESD for early gastric cancer. Biopsy samples for the frozen sections were randomly collected from fresh resected ESD specimens before formalin fixation. Two different pathologists independently diagnosed 130 frozen sections as “neoplasia,” “negative for neoplasia,” or “indefinite for neoplasia,” and the frozen section diagnosis was compared with the final pathological results of the ESD specimens. Results Among the 130 frozen sections, 35 were from cancerous areas, and 95 were from non-cancerous areas. The diagnostic accuracies of the frozen section biopsies by the two pathologists were 98.5 and 94.6%, respectively. Cohen’s kappa coefficient of diagnoses by the two pathologists was 0.851 (95% confidence interval: 0.837–0.864). Incorrect diagnoses resulted from freezing artifacts, a small volume of tissue, inflammation, the presence of well-differentiated adenocarcinoma with mild nuclear atypia, and/or tissue damage during ESD. Conclusions Pathological diagnosis of frozen section biopsy is reliable and can be applied as a rapid frozen section diagnosis for evaluating the lateral margins of early gastric cancer during ESD

An α-synuclein decoy peptide prevents cytotoxic α-synuclein aggregation caused by fatty acid binding protein 3

α-synuclein (αSyn) is a protein known to form intracellular aggregates during the manifestation of Parkinson’s disease. Previously, it was shown that αSyn aggregation was strongly suppressed in the midbrain region of mice that did not possess the gene encoding the lipid transport protein fatty acid binding protein 3 (FABP3). An interaction between these two proteins was detected in vitro, suggesting that FABP3 may play a role in the aggregation and deposition of αSyn in neurons. In order to characterize the molecular mechanisms that underlie the interactions between FABP3 and αSyn that modulate the cellular accumulation of the latter, in this report, we used in vitro fluorescence assays combined with fluorescence microscopy, transmission electron microscopy, and quartz crystal microbalance assays to characterize in detail the process and consequences of FABP3-αSyn interaction. We demonstrated that binding of FABP3 to αSyn results in changes in the aggregation mechanism of the latter; specifically, a suppression of fibrillar forms of αSyn, and also the production of aggregates with an enhanced cytotoxicity toward mice neuro2A cells. Since this interaction involved the C-terminal sequence region of αSyn, we tested a peptide derived from this region of αSyn (αSynP130-140) as a decoy to prevent the FABP3-αSyn interaction. We observed that the peptide competitively inhibited binding of αSyn to FABP3 in vitro and in cultured cells. We propose that administration of αSynP130-140 might be used to prevent the accumulation of toxic FABP3-αSyn oligomers in cells, thereby preventing the progression of Parkinson’s disease

Validity and reliability of a smartphone application for self-measurement of active shoulder range of motion in a standing position among healthy adults

[Background] Shoulder range of motion (ROM) is one of the most important indicators of shoulder disease severity, function, and physical assessment. A universal goniometer (UG) was used as a gold standard for ROM measurement. Recently, smartphone applications for ROM measurement have attracted attention as alternatives to UG. This study aimed to investigate the validity and reliability of active ROM measurements using a smartphone application goniometer that can be used by patients in a standing position. [Methods] The dominant shoulders of 19 healthy participants were included in the study. The 2 observers who were physical therapists used the UG, whereas the participants used a smartphone application goniometer to measure the shoulder ROM. A recorder, who is a physical therapist independent of the observer and participant, read and recorded the shoulder ROM measurements. The order of the measurement movements and devices used was randomized. [Results] Agreement between the smartphone application goniometer and UG (percentage of participants for whom the difference between the UG and application measurements was within ±20% of the mean of the goniometer and application measurements) ranged between 42% and 100%. The intraclass correlation coefficient values (3, 1) for the agreement between the smartphone application goniometer and UG was between 0.72 and 0.97, showing significant and approximately perfect correlations. [Conclusion] High agreement with the UG showed excellent validity, indicating that the smartphone application goniometer used by the participants in the standing position is an excellent method and instrument. The results suggest a simpler, more reliable, practical, and inexpensive method for measuring ROM required for telerehabilitation

Utility of Combined Use of Transabdominal Ultrasonography and Fecal Immunochemical Test Examinations in Ulcerative Colitis

This study examined the utility of the combined use of transabdominal ultrasonography (TUS) and fecal immunochemical testing (FIT) to detect mucosal inflammation, vis-a-vis the Mayo endoscopic subscore (MES), in ulcerative colitis (UC). Sixty-three UC patients who underwent TUS and FIT were retrospectively enrolled. For TUS, the colon was divided into five segments, and the bowel wall thickness was measured and evaluated. The accuracy of FIT (> 100 ng/ml) in detecting mucosal inflammation (MES>0) was 0.93, whereas that of TUS (BWT>2 mm) in each segment was 0.84-0.97. The combined use of TUS and FIT may be helpful in noninvasive treatment strategies

EMPRESS. XIV. Strong High Ionization Lines of Young Galaxies at z=0−8z=0-8: Ionizing Spectra Consistent with the Intermediate Mass Black Holes with MBH∼103−106 M⊙M_{\rm BH}\sim 10^3-10^6\ M_\odot

We present ionizing spectra estimated at 13.6--100 eV for ten dwarf galaxies with strong high ionization lines of He {\sc {ii}}$\lambda$4686 and [Ne {\sc{v}}]$\lambda$3426 ([Ne {\sc{iv}}]$\lambda$2424) at $z=0$ ($z=8$) that are identified in our Keck/LRIS spectroscopy and the literature (the JWST ERO program). With the flux ratios of these high ionization lines and $>10$ low-ionization lines of hydrogen, helium, oxygen, neon, and sulfur, we determine ionizing spectra consisting of stellar and non-thermal power-law radiation by photoionization modeling with free parameters of nebular properties including metallicity and ionization parameter, cancelling out abundance ratio differences. We find that all of the observed flux ratios are well reproduced by the photoinization models with the power law index $\alpha_{\rm EUV}$ of $\alpha_{\rm EUV}\sim (-1)-0$ and the luminosity $L_{\rm EUV}$ of $L_{\rm EUV}\sim 10^{40}-10^{42}$ erg s$^{-1}$ at $\sim 55-100$ eV for six galaxies, while four galaxies include large systematics in $\alpha_{\rm EUV}$ caused by stellar radiation contamination. We then compare $\alpha_{\rm EUV}$ and $L_{\rm EUV}$ of these six galaxies with those predicted by the black hole (BH) accretion disk models, and find that $\alpha_{\rm EUV}$ and $L_{\rm EUV}$ are similar to those of the intermediate mass black holes (IMBHs) in BH accretion disk models {albeit with possibilities of the other scenarios.} Confirming these results with a known IMBH having a mass $M_{\rm BH}$ of $M_{\rm BH}=10^{5.75} \ M_\odot$, we find that four local galaxies and one $z=7.665$ galaxy have ionizing spectra consistent with those of IMBHs with $M_{\rm BH} \sim 10^3-10^5 \ M_\odot$.Comment: Accepted for publication in ApJ and 25 pages, 12 figure