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Inherited retinal diseases (IRDs) comprise a phenotypically and genetically heterogeneous group of ocular disorders that cause visual loss via progressive retinal degeneration. Here, we report the genetic characterization of 1210 IRD pedigrees enrolled through the Japan Eye Genetic Consortium and analyzed by whole exome sequencing. The most common phenotype was retinitis pigmentosa (RP, 43%), followed by macular dystrophy/cone- or cone-rod dystrophy (MD/CORD, 13%). In total, 67 causal genes were identified in 37% (448/1210) of the pedigrees. The first and second most frequently mutated genes were EYS and RP1, associated primarily with autosomal recessive (ar) RP, and RP and arMD/CORD, respectively. Examinations of variant frequency in total and by phenotype showed high accountability of a frequent EYS missense variant (c.2528GA). In addition to the two known EYS founder mutations (c.4957dupA and c.8805CG) of arRP, we observed a frequent RP1 variant (c.5797CT) in patients with arMD/CORD.

The contents and distribution of radionuclides in activated metallic wastes are major concerns while designing a leaching model in a safety case. This study investigated 60Co as a typical activation product in the lower tie plate (i.e., stainless steel endpiece of BWR fuel assembly) irradiated for 35.0 GWd/tHM burnup, using the imaging plate (IP) method. The activation calculations coupled with the Monte Carlo burnup and neutron transport calculation code (MCNP-BURN2) were also performed based on the burnup and operation conditions. The Co impurity content in the irradiated tie plate was obtained and used as an input to MCNP-BURN2. The IP method results showed that the intensity of photostimulated luminescence decreased with increasing distance from the top (near fuels) to bottom. This trend was consistent with that exhibited by MCNP-BURN2.Therefore, the simulations allowed us to model the three-dimensional radionuclide distribution within the tie plate. Graphical abstract Distribution of 60Co in the irradiated lower tie plate. Left shows the vertical distribution comparing the measurements and the MCNP-BURN2 results. Right represents the 3D model of 60Co distribution in the lower tie plate.

Metastasis to the pancreas is rare, especially for malignant melanoma. In these scarce cases, tumors normally present in the parenchyma of the pancreas. A 70-year-old woman was referred to our hospital for an asymptomatic pancreatic tumor detected by contrast-enhanced computed tomography (CE-CT). She had undergone a pneumonectomy for primary malignant melanoma (MM) of the lung approximately 3 years prior and was receiving nivolumab for recurrent intrapulmonary metastasis. CE-CT revealed a hypo-vascular lesion occluding the main pancreatic duct (MPD) which was consequently dilated. On magnetic resonance imaging, the MPD lesion had high signal intensity on T1-weighted and diffusion-weighted images. Contrast-enhanced endoscopic ultrasonography revealed that the low echoic tumor had heterogenous enhancement in the early phase. Endoscopic retrograde pancreatography (ERP) was performed for evaluation of tumor area and histological diagnosis. A contrast agent defected lesion was observed in the dilated MPD from the pancreas body to tail suggesting the tumor totally occluded the MPD. Biopsy was performed and the specimens obtained from the defect lesion were black in color. Histopathological examination of the black specimens revealed substantial growth of tumor cells with eosinophilic cytoplasm and unequal nuclei size. The tumor cells had a brownish pigmentation of melanin. From these findings, the tumor was diagnosed as pancreatic metastasis of MM. The patient underwent chemotherapy with ipilimumab and nivolumab. The final diagnosis was pancreatic metastasis of MM occurring as a tumor occluding the MPD. ERP was useful for histological diagnosis and could be useful for future cases.

Background Human cytomegalovirus (HCMV) colitis can be involved in active ulcerative colitis (UC) in patients refractory to steroid and immunosuppressive drugs. Histological examination with colonic biopsy specimens and antigenemia assays are the standard tests for diagnosing HCMV enterocolitis, and we have previously reported the usefulness of mucosal polymerase chain reaction (PCR) methods. However, the associations among histopathological tests, antigenemia assays, and mucosal PCR are unknown. Methods We retrospectively analyzed 82 UC patients who underwent mucosal biopsy from inflamed colonic tissues for histological evaluation and mucosal PCR to detect HCMV. We analyzed the relationships between the HCMV-DNA copy number in colonic mucosa and other HCMV tests. Results In total, 131 HCMV mucosal PCR tests from 82 UC patients were positive. The HCMV-DNA copy number was significantly higher in patients with positive immunohistochemistry (IHC) (p p p p = 0.013) and the bleeding score (p = 0.014). For each individual patient, a positive correlation between the change in total UCEIS score and HCMV-DNA copy number was observed (p = 0.040). Conclusion The antigenemia assay and histopathological test with IHC were significantly associated with the HCMV-DNA copy number in colonic tissues. Moreover, endoscopic examination with the UCEIS can help diagnose the HCMV colitis in UC patients.

Objectives The association of preoperative RV function with hemodynamics during OPCAB or emergency conversion is not clear. The aim of this study was to investigate the association of vasoactive-inotropic score with tricuspid annular plane systolic excursion and tricuspid regurgitation in off-pump coronary artery bypass grafting, and to calculate the optimal cut-off value of tricuspid annular plane systolic excursion to predict emergency conversion to cardiopulmonary bypass. Methods Patients over 20 years of age who had undergone off-pump coronary artery bypass grafting between April 2015 and March 2020 were enrolled in this study. We retrospectively assessed the association of intraoperative maximum “vasoactive-inotropic score”, a weighted sum of various inotropes and vasoconstrictors, with tricuspid annular plane systolic excursion and tricuspid regurgitation. A receiver operating characteristic curve of conversion on tricuspid annular plane systolic excursion was also constructed. Results 135 patients were included in final analysis. Conversion was performed in 10 cases. Multiple regression analysis showed that tricuspid annular plane systolic excursion, mild or more tricuspid regurgitation and experienced surgeon were significantly related to vasoactive-inotropic score. The receiver operating characteristic curve to predict conversion by tricuspid annular plane systolic excursion showed an optimal cut-off value of 15.0 mm and area under the curve of 0.808. Conclusions Tricuspid annular plane systolic excursion and tricuspid regurgitation were associated with vasoactive-inotropic score in off-pump coronary artery bypass grafting. The optimal cut-off value of tricuspid annular plane systolic excursion to predict emergency conversion was 15 mm.

At initial diagnosis, central nervous system (CNS) involvement in acute promyelocytic leukemia (APL) is rare. Here, we report a case of newly diagnosed APL with CNS involvement that was successfully treated with all-trans retinoic acid (ATRA)-combined chemotherapy. A 64-year-old woman was referred to our hospital to evaluate a bleeding tendency, and she was diagnosed with APL. Induction chemotherapy with ATRA via a nasogastric tube was initiated under mechanical ventilation because of respiratory failure and disturbance of consciousness. Although her respiratory condition improved a few days after initiating treatment, the disturbance of consciousness remained. Brain magnetic resonance imaging showed mixed signals of tumor infiltration and acute cerebral infarction with a focus on the right cerebellum. The patient was diagnosed with CNS involvement of APL and acute cerebral infarction. Three months after the initiation of induction therapy, her consciousness improved along with the reduction in CNS involvement, and complete molecular remission was achieved. Thus, patients with APL can have CNS involvement at initial diagnosis. Administering ATRA via nasogastric tube can be a good therapeutic option in patients with difficulty swallowing due to disturbance of consciousness.

Intestinal amoebiasis is caused by Entamoeba histolytica (E. histolytica) and is characterised by cecal lesions, multiple lesions, aphthae, and multiple exudative erosions. Intestinal Behçet’s disease (BD) is a chronic inflammatory disorder that is characterised by multiple ulcers. Although the aetiologies of these two bowel diseases are unrelated, they are difficult to distinguish because they present similarly with inflammation and ulcers, especially if evidence of specific pathogens is not detected. Herein, we report a case of intestinal amoebiasis in a patient with BD. The patient underwent colonoscopy four times before intestinal amoebiasis was diagnosed. As intestinal BD was initially suspected, she received high-dose glucocorticoid therapy, which exacerbated her condition. Following exacerbation, she underwent colonoscopy, and E. histolytica was revealed. Deliberate care should be taken to distinguish between intestinal amoebiasis and intestinal BD, as the appropriate treatments for these diseases are entirely different.

BACKGROUND Direct-acting oral anticoagulant use for stroke prevention in atrial fibrillation is limited by bleeding concerns. Asundexian, a novel, oral small molecule activated coagulation factor XIa (FXIa) inhibitor, might reduce thrombosis with minimal effect on haemostasis. We aimed to determine the optimal dose of asundexian and to compare the incidence of bleeding with that of apixaban in patients with atrial fibrillation. METHODS In this randomised, double-blind, phase 2 dose-finding study, we compared asundexian 20 mg or 50 mg once daily with apixaban 5 mg twice daily in patients aged 45 years or older with atrial fibrillation, a CHA2DS2-VASc score of at least 2 if male or at least 3 if female, and increased bleeding risk. The study was conducted at 93 sites in 14 countries, including 12 European countries, Canada, and Japan. Participants were randomly assigned (1:1:1) to a treatment group using an interactive web response system, with randomisation stratified by whether patients were receiving a direct-acting oral anticoagulant before the study start. Masking was achieved using a double-dummy design, with participants receiving both the assigned treatment and a placebo that resembled the non-assigned treatment. The primary endpoint was the composite of major or clinically relevant non-major bleeding according to International Society on Thrombosis and Haemostasis criteria, assessed in all patients who took at least one dose of study medication. This trial is registered with ClinicalTrials.gov, NCT04218266, and EudraCT, 2019-002365-35. FINDINGS Between Jan 30, 2020, and June 21, 2021, 862 patients were enrolled. 755 patients were randomly assigned to treatment. Two patients (assigned to asundexian 20 mg) never took any study medication, resulting in 753 patients being included in the analysis (249 received asundexian 20 mg, 254 received asundexian 50 g, and 250 received apixaban). The mean age of participants was 73·7 years (SD 8·3), 309 (41%) were women, 216 (29%) had chronic kidney disease, and mean CHA2DS2-VASc score was 3·9 (1·3). Asundexian 20 mg resulted in 81% inhibition of FXIa activity at trough concentrations and 90% inhibition at peak concentrations; asundexian 50 mg resulted in 92% inhibition at trough concentrations and 94% inhibition at peak concentrations. Ratios of incidence proportions for the primary endpoint were 0·50 (90% CI 0·14-1·68) for asundexian 20 mg (three events), 0·16 (0·01-0·99) for asundexian 50 mg (one event), and 0·33 (0·09-0·97) for pooled asundexian (four events) versus apixaban (six events). The rate of any adverse event occurring was similar in the three treatment groups: 118 (47%) with asundexian 20 mg, 120 (47%) with asundexian 50 mg, and 122 (49%) with apixaban. INTERPRETATION The FXIa inhibitor asundexian at doses of 20 mg and 50 mg once daily resulted in lower rates of bleeding compared with standard dosing of apixaban, with near-complete in-vivo FXIa inhibition, in patients with atrial fibrillation. FUNDING Bayer.

We introduce a family of multilinear operators on a quasi-shuffle algebra H , which we call Hoffman-Ihara operators. It generalizes the linear operators constructed by Hoffman and further studied by Hoffman and Ihara. We prove the formula on the composition of these operators, and show that this formula provides a unified and transparent understanding of some results on shuffle and quasi-shuffle products. An interpretation as an action of the operad of formal power series is also given.

The purpose of this article is to describe explicitly the polylogarithm class in absolute Hodge cohomology of a product of multiplicative groups, in terms of the Bloch-Wigner-Ramakrishnan polylogarithm functions. We will use the logarithmic Dolbeault complex defined by Burgos to calculate the corresponding absolute Hodge cohomology groups., 28 pages

The purpose of this article is to investigate the properties of the category of mixed plectic Hodge structures defined by Nekov\'a\v{r} and Scholl. We give an equivalent description of mixed plectic Hodge structures in terms of the weight and partial Hodge filtrations. We also construct an explicit complex calculating the extension groups in this category., Comment: 43 pages, Corrected calculation in Example 5.28

Chronic inflammation is accompanied by recurring cycles of tissue destruction and repair and is associated with an increased risk of cancer1–3. However, how such cycles affect the clonal composition of tissues, particularly in terms of cancer development, remains unknown. Here we show that in patients with ulcerative colitis, the inflamed intestine undergoes widespread remodelling by pervasive clones, many of which are positively selected by acquiring mutations that commonly involve the NFKBIZ, TRAF3IP2, ZC3H12A, PIGR and HNRNPF genes and are implicated in the downregulation of IL-17 and other pro-inflammatory signals. Mutational profiles vary substantially between colitis-associated cancer and non-dysplastic tissues in ulcerative colitis, which indicates that there are distinct mechanisms of positive selection in both tissues. In particular, mutations in NFKBIZ are highly prevalent in the epithelium of patients with ulcerative colitis but rarely found in both sporadic and colitis-associated cancer, indicating that NFKBIZ-mutant cells are selected against during colorectal carcinogenesis. In further support of this negative selection, we found that tumour formation was significantly attenuated in Nfkbiz-mutant mice and cell competition was compromised by disruption of NFKBIZ in human colorectal cancer cells. Our results highlight common and discrete mechanisms of clonal selection in inflammatory tissues, which reveal unexpected cancer vulnerabilities that could potentially be exploited for therapeutics in colorectal cancer. In patients with ulcerative colitis, chronic inflammation can lead to remodelling of the colorectal epithelium through positive selection of clones with mutations in genes related to IL-17 signalling, which, however, might be negatively selected during colitis-associated carcinogenesis.

Background Myxedema coma, which occurs due to hypothyroidism, is a rare and life-threatening condition. Some patients have hemodynamic dysfunction, which consequently leads to cardiac arrest. The rarity of this condition makes it difficult to determine the cause of cardiac arrest. It is important to diagnose myxedema coma based on clinical findings, including physical examination and laboratory parameters. We present a case of undiagnosed and untreated hypothyroidism that initially caused myxedema coma and then led to cardiac arrest. Case presentation A 56-year-old woman who had no medical history was transferred to our hospital for the management of return of spontaneous circulation due to sudden cardiac arrest. Findings of laboratory tests revealed that she had hypothyroidism. On physical examination, she was found to have a puffy face, thin eyebrows, and severe systemic non-pitting edema. Therefore, the patient was clinically diagnosed with myxedema coma, which was the cause of cardiac arrest. She was treated with thyroid hormone and hydrocortisone, resulting in improvement in her general condition, except for the neurological dysfunction. Conclusions This case suggests that myxedema coma is caused by undiagnosed and untreated hypothyroidism, leading to sudden cardiac arrest. Our findings are useful in the differential diagnosis of hypothyroidism based on characteristic physical examination findings. Clinicians should be aware of the differential diagnosis of myxedema coma based on findings from physical examination and laboratory testing of thyroid function, and the treatment should be started immediately.

Immune-related adverse events (irAEs) are commonly observed in patients treated with immune checkpoint inhibitors (ICI), and prompt diagnosis and treatment of irAEs is of utmost importance. Gastrointestinal (GI) events are among the most frequent irAEs and the hallmark symptom is diarrhea. Intestinal hypomotility as irAEs is exceedingly rare, and needs wider recognition given that the presentation is insidious.Here, we report a case of 79-year-old woman with metastatic melanoma under nivolumab and ipilimumab combination therapy. She developed ileus symptom, and was diagnosed with acute colonic pseudo-obstruction. The symptom relieved soon after administering high-dose prednisolone five days after the onset. ICI therapy was discontinued.Intestinal hypomotility as GI irAEs is exceedingly rare and there have been five reported cases to our knowledge. In reviewing past cases, we speculate that the prompt initiation of corticosteroids resulted in a favorable outcome. Our case illustrates that early recognition of these rare irAEs is essential in order to ensure prompt treatment.

A 56-year-old man with COVID-19 pneumonia, requiring mechanical ventilation and extracorporeal membrane oxygenation, was transferred to our hospital. He was successfully treated with dexamethasone and remdesivir, followed by favipiravir, and he was extubated on day 30. Eighteen days after admission, he developed severe watery diarrhoea (passing more than 7000 mL/day). Subsequently, he went into shock due to hypovolaemia and hypoalbuminaemia (2.3 g/dL), and norepinephrine and albumin administration were commenced. Contrast-enhanced CT showed thickening of the small and large intestinal walls without findings suggesting intestinal ischaemia, such as decreased bowel wall enhancement and mesenteric thrombosis (figure 1A). Sigmoidoscopy on day 32 (figure 1B) showed prominent detachment of the colonic mucosa, and peroral enteroscopy …

Background: Healthcare workers must be protected during extubation of patients with coronavirus disease 2019 (COVID-19) owing to the presence of aerosolized droplets. Herein, we report a technique for extubating a patient with COVID-19 while minimizing aerosol dispersion. Case Report: We retrospectively identified a total of 79 patients admitted to our hospital from February 2020 to January 2021. Six of these patients were intubated for mechanical ventilation, 2 of whom had to be extubated. We prepared a clear vinyl sheet in the shape of a tent to place over the patient, and 2 staff members, both well experienced in airway management, stood outside the tent on either side of the patient. Before extubation, we confirmed that the patient’s consciousness level was good and the patient had no distress by adjusting the dose of sedative drugs. After extubation, a surgical mask was placed on the patient’s face. Conclusion: Our experience indicates that this method of extubation in a patient with COVID-19 could be safely implemented to protect healthcare workers.

Monoclonal antibodies have accelerated the availability of treatment options for many diseases in which the molecular mechanism has been elucidated in detail. Therefore, an assay that can universally analyze antibodies for clinical pharmacokinetics and cross-sectional studies would be indispensable. We have developed a universal antibody bioanalysis with a Fab-selective tryptic reaction, named nano-surface and molecular-orientation limited (nSMOL) proteolysis, that collects the specific antibody signature peptides in biological samples. Using the nSMOL method, we have fully validated the bioanalysis of many antibodies, Fc-fusion proteins, and their biosimilars. Inflammatory immune diseases often require long-term clinical management because of the remission and relapse observed. Accurate antibody monitoring in systemic circulation could contribute to the improvement of clinical outcomes. Because several biopharmaceuticals can be selected as practical treatment options, the assay development that quantitates many antibodies simultaneously would be applicable in many theraprutic monitoring. In this study, we have validated the LC-MS bioanalysis method for seven-mixed antibodies (Infliximab, Adalimumab, Ustekinumab, Golimumab, Eculizumab, Etanercept, and Abatacept) using the nSMOL normal reaction condition and two-mixed antibodies (Tocilizumab and Mepolizumab) using the acidified reduction acceleration condition, as reported in our previous papers. Moreover, this multiplexed assay has been verified using clinical patient samples. The nSMOL approach enables the quantitation of several immunosuppressive antibodies simultaneously in human serum, and nSMOL can potentially be applicable to the drug-drug interaction assays or therapeutic antibody monitoring of several inflammatory immune diseases to optimize administration.

Kawashima's relation is conjecturally one of the largest classes of relations among multiple zeta values. Gaku Kawashima introduced and studied a certain Newton series, which we call the Kawashima function, and deduced his relation by establishing several properties of this function. We present a new approach to the Kawashima function without using Newton series. We first establish a generalization of the theory of regularizations of divergent multiple zeta values to Hurwitz type multiple zeta values, and then relate it to the Kawashima function. Via this connection, we can prove a key property of the Kawashima function to obtain Kawashima's relation., 14 pages

The Jurassic Plover Formation is one of two reservoirs in the Ichthys Field, North West Shelf of Australia. It consists of fluvial to shallow-marine sandstones, shales and igneous rocks. The objective of this study is to build multiple scenario-based models to optimise development planning in preparation for the upcoming production phase. We have integrated data and interpretations of thin sections, cores, well logs and seismic data to create multiple geological concepts for the field and to identify key geological uncertainties. As the reservoir is geologically complex and many uncertainties were initially identified, it is essential to single out those uncertainties which have a significant impact on the development planning. We have established the key uncertainties and optimal model design for practical use through multi-disciplinary discussions and by running sensitivity models to check the production performance. A rock type (RT) scheme has been devised based on detailed petrographic observations and justified in terms of sedimentology and diagenesis. Using the scheme, a wide range of permeability variations in the sandstones has been captured and modelled. Environments of deposition (EOD) are firstly interpreted at core and well-log scales, then upscaled to the model zone scale. The EOD interpretations are laterally extended using lithology (sandstone, shale and igneous rock) probability maps derived from quantitative seismic interpretation (QSI). Multiple EOD scenarios are generated to capture the possible range of reservoir distributions. Each EOD is characterised by a unique net-sand porosity and RT proportion based on the well data. These values are used to define multiple possible porosity trends and RT proportions, guided by the EOD maps. The distribution and quality of the reservoir sandstones have been identified as key uncertainties. Another key uncertainty is reservoir compartmentalisation, thought to be mainly caused by sheet-like igneous intrusions. Subtle seismic lineaments are regarded as possible indications of such igneous intrusions, and multiple compartmentalisation scenarios have been prepared based on our understanding of igneous activity across the field. Reservoir structure and water saturation are also recognised as key uncertainties. Integrating the key uncertainties, we have established a practical modelling workflow and built multiple scenario-based models to cover a sufficient range of geological uncertainty. The workflow is also adaptive for future history matching, enabling us to flexibly edit the model properties under geological constraints. A decision tree for development planning, which defines a series of decisions for the well sequence depending on the well results, will be prepared based on the multiple scenario-based models delivered in this study. This will enable us to prepare for any potential decision-making in advance. The development planning will be continuously optimised throughout the production phase by simply selecting the scenario-based models most in line with the well results.

We establish Ohno-type identities for multiple harmonic ($q$-)sums which generalize Hoffman's identity and Bradley's identity. Our result leads to a new proof of the Ohno-type relation for $\mathcal{A}$-finite multiple zeta values recently proved by Hirose, Imatomi, Murahara and Saito. As a further application, we give certain sum formulas for $\mathcal{A}_2$- or $\mathcal{A}_3$-finite multiple zeta values., Comment: 14 pages, Some minor corrections

Background and Aims: Ulcerative colitis is the most frequent type of inflammatory bowel disease and is characterized by colonic epithelial cell damage. Although involvement of autoimmunity has been suggested in ulcerative colitis, specific autoantigens/antibodies have yet to be elucidated. Methods: Using 23 recombinant integrin proteins, we performed enzyme-linked immunosorbent assays on sera from patients with ulcerative colitis and controls. Integrin expression and IgG binding in the colon tissues of patients with ulcerative colitis and controls were examined using immunofluorescence and coimmunoprecipitation, respectively. The blocking activity of autoantibodies was examined using solid-phase binding and cell adhesion assays. Results: Screening revealed that patients with ulcerative colitis had IgG antibodies against integrin αvβ6. In the training and validation groups, 103 of 112 (92.0%) patients with ulcerative colitis and only 8 of 155 (5.2%) controls had anti–integrin αvβ6 antibodies (P < .001), resulting in a sensitivity of 92.0% and a specificity of 94.8% for diagnosing ulcerative colitis. Anti–integrin αvβ6 antibody titers coincided with ulcerative colitis disease activity, and IgG1 was the major subclass. Patient IgG bound to the integrin αvβ6 expressed on colonic epithelial cells. Moreover, IgG of patients with ulcerative colitis blocked integrin αvβ6–fibronectin binding through an RGD (Arg-Gly-Asp) tripeptide motif and inhibited cell adhesion. Conclusions: A significant majority of patients with ulcerative colitis had autoantibodies against integrin αvβ6, which may serve as a potential diagnostic biomarker with high sensitivity and specificity., 指定難病「潰瘍性大腸炎」の自己抗体発見 --新たな診断や治療開発へ--. 京都大学プレスリリース. 2021-03-09.

We study a refinement of the symmetric multiple zeta value, called the $t$-adic symmetric multiple zeta value, by considering its finite truncation. More precisely, two kinds of regularizations (harmonic and shuffle) give two kinds of the $t$-adic symmetric multiple zeta values, thus we introduce two kinds of truncations correspondingly. Then we show that our truncations tend to the corresponding $t$-adic symmetric multiple zeta values, and satisfy the harmonic and shuffle relations, respectively. This gives a new proof of the double shuffle relations for $t$-adic symmetric multiple zeta values, first proved by Jarossay. In order to prove the shuffle relation, we develop the theory of truncated $t$-adic symmetric multiple zeta values associated with $2$-colored rooted trees. Finally, we discuss a refinement of Kaneko-Zagier's conjecture and the $t$-adic symmetric multiple zeta values of Mordell-Tornheim type., Comment: 34 pages

Carbon nanofiber (CNF)-reinforced aluminum-matrix composites were fabricated via ball milling and spark plasma sintering (SPS), SPS followed by hot extrusion and powder extrusion. Two mixing conditions of CNF and aluminum powder were adopted: milling at 90 rpm and milling at 200 rpm. After milling at 90 rpm, the mixed powder was sintered using SPS at 560 °C. The composite was then extruded at 500 °C at an extrusion ratio of 9. Composites were also fabricated via powder extrusion of powder milled at 200 rpm and 550 °C with an extrusion ratio of 9 (R9) or 16 (R16). The thermal conductivity and tensile properties of the resultant composites were evaluated. Anisotropic thermal conductivity was observed even in the sintered products. The anisotropy could be controlled via hot extrusion. The thermal conductivity of composites fabricated via powder extrusion was higher than those fabricated using other methods. However, in the case of specimens with a CNF volume fraction of 4.0%, the thermal conductivity of the composite fabricated via SPS and hot extrusion was the highest. The highest thermal conductivity of 4.0% CNF-reinforced composite is attributable to networking and percolation of CNFs. The effect of the fabrication route on the tensile strength and ductility was also investigated. Tensile strengths of the R9 composites were the highest. By contrast, the R16 composites prepared under long heating duration exhibited high ductility at CNF volume fractions of 2.0% and 5.0%. The microstructures of composites and fracture surfaces were observed in detail, and fracture process was elucidated. The results revealed that controlling the heating and plastic deformation during extrusion will yield strong and ductile composites.

Purpose The authors previously revealed the association of the follicular fluid (FF) volume with oolemma stretchability following the gonadotropin‐releasing hormone (GnRH) antagonist protocol during intracytoplasmic sperm injection (ICSI). However, the impact of the GnRH agonist protocol on oolemma stretchability remains unclear. Methods Data that were obtained from 74 ICSI cycles were reviewed retrospectively. Controlled ovarian stimulation was performed in accordance with the short GnRH agonist protocol. Each follicle was individually aspirated and assigned to one of six groups, according to the FF volume. The oolemma stretchability during ICSI was evaluated by using a mechanical stimulus for oolemma penetration; that is, oolemma penetration with or without aspiration (high vs low stretchability, respectively). Results The incidence of low oolemma stretchability was significantly higher in the

Aluminum matrix composites reinforced by carbon nanotubes (CNTs) were fabricated by ball-milling (with aluminum powder; average diameter 30 µm), followed by hot extrusion of the powders encapsulated in aluminum containers (at 550° with an extrusion ratio of 9). The CNTs were intended to improve the mechanical properties and thermal conductivity of the aluminum composites formed by powder metallurgy. The CNTs were of two types—vapor-grown carbon fibers (VGCFs) with a diameter of 150 nm and multiwalled CNTs (MWCNTs) with a diameter of 65 nm. The composites were evaluated by their Vickers microhardness, tensile strength, and thermal conductivity. The microhardness exceeded 100 HV and increased with increasing volume fraction of reinforcement. The MWCNT-reinforced composites were harder than the VGCF-reinforced composites and exhibited higher ultimate tensile strength (over 450 MPa). The maximum fracture strain (37.2%, observed at a volume fraction of 0.5%) is the highest reported in the literature. Conversely, the VGCF-reinforced composites exhibited higher thermal conductivity than the MWCNT-reinforced composites. The thermal conductivity of the 0.5% VGCF-reinforced composites (203.7 W/m K) also exceeds any previously reported value. In summary, composites with unprecedentedly high ultimate tensile strength, fracture strain, and thermal conductivity were fabricated by a simple process that minimized damage to the CNTs during mixing, protected them from oxidation and excessive reaction with the aluminum matrix and effectively densified composites by hot extrusion.