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BACKGROUND von Willebrand disease (VWD) is characterized by a bleeding tendency due to abnormalities in von Willebrand factor (VWF). Severe traumatic brain injury (TBI) can induce secondary coagulopathy and hemostatic disorders. We herein present a rare case of multiple trauma, including severe TBI, in a patient with VWD who was successfully treated with repeated factor VIII/VWF transfusion in addition to standard critical care. CASE REPORT A 22-year-old man with type 2A VWD sustained head and lower limb injuries in a traffic accident and was comatose. Computed tomography indicated multiple trauma, including severe TBI (left-sided traumatic epidural hematoma, left-sided traumatic subdural hematoma, traumatic subarachnoid hemorrhage, skull fracture, and skull base fracture). The patient underwent emergency craniotomy for hematoma removal, external decompression, and intracranial pressure monitoring along with massive transfusion and repeated perioperative transfusion of factor VIII/VWF concentrates according to the level of bleeding. He recovered consciousness and eventually survived without neurological deficits. CONCLUSIONS Multiple trauma including TBI in patients with VWD is a critical condition. The active transfusion of factor VIII/VWF is essential for controlling hemorrhage early and in the perioperative period.

BACKGROUND Secondary thrombotic microangiopathies (TMAs) are induced by several underlying conditions and most are resolved by treating the underlying disease. Eculizumab, a human monoclonal antibody, blocks the final stages of the complement system. Several studies have shown that complement C5 monoclonal antibodies are effective in treating secondary TMA. Systemic sclerosis (SSc) is one of the most common causes of secondary TMA, and early diagnosis is important because TMA secondary to SSc has a poor prognosis. We report a case of TMA secondary to SSc that did not respond to eculizumab, despite the presence of severe complement activation. CASE REPORT A 61-year-old previously healthy man was admitted for acute renal failure and thrombocytopenia. TMA was suspected because hemolytic anemia, thrombocytopenia, and organ damage were detected. Based on the physical findings, we suspected SSc as the underlying cause. All tests for specific antibodies, including Scl-70, were negative, and C5b-9 levels were markedly elevated (11 041 ng/mL). We initiated plasma exchange on day 3, followed by eculizumab therapy, but with limited improvement. SSc with secondary TMA was identified upon further testing. After completion of the plasma exchange, the platelet count was maintained above 30 000/μL. Creatinine levels gradually decreased, and the patient was weaned off dialysis. Steroid treatment for SSc was continued, and the patient was eventually discharged. CONCLUSIONS A case of SSc-TMA was ineffectively treated with eculizumab, despite abnormal activation of the complement system. Continuous monitoring and investigation are required, and discontinuation of eculizumab should be determined according to the final diagnosis.

Background Although atypical hemolytic uremic syndrome (aHUS) is a life-threatening clinical entity that was characterized by thrombotic microangiopathy (TMA) with the activation of the complement system and the efficient treatment of eculizumab, the clinical features of aHUS have been unclear because of the rare incidence. Case presentation We retrospectively analyzed 4 aHUS cases at a single institution during 2015–2019. Here, we presented 4 aHUS cases with renal transplantation (one case), influenza/acute interstitial pneumonia/disseminated intravascular coagulation (two cases), and severe fever with thrombocytopenia syndrome (one case), respectively. Initial clinical symptoms were microangiopathic hemolytic anemia (four cases), renal dysfunction (four cases), thrombocytopenia (four cases), and pulmonary hemorrhage (three cases) consisted with TMA features. Subsequent further examinations ruled out thrombotic thrombocytopenic purpura, Shiga toxin-producing E.coli-induced hemolytic uremic syndrome, and secondary TMA. Taken these findings together, we made the clinical diagnosis of aHUS. Furthermore, all cases also presented the high levels of plasma soluble C5b-9 (871.1 ng/ml, 1144.3 ng/ml, 929.2 ng/ml, and 337.5 ng/ml), suggesting persistent activation of complementary system. Regarding the treatment, plasma exchange (PE) (four cases) and eculizumab (two cases) therapy were administered for aHUS cases. Consequently, case 2 and case 4 were still alive with 768 days and 235 days, respectively. The other two cases were dead at 34 days and 13 days, respectively. Finally, although the previous reported genetic pathogenetic mutations were not detected in our cases, multiple genetic variants of complement factors were detected as CFH (H402Y, E936D), and THBD (A473V) in case 1, CFH (V62I, H402Y, V837I) in case 2, and CFH (H402Y, E 936D) and THBD (A473V) in case 3, CFH (V62I, H402Y, E936D) and THBD (473V) in case 4, respectively. Conclusions Because of still high mortality in our study, an urgent diagnosis of aHUS and subsequent immediate treatment including PE and eculizumab should be essential in clinical practice. Furthermore, the multiple genetic variants and the triggers may be related to one of the pathogenesis of aHUS. Thus, we assume that such a case-oriented study would be highly useful to the physicians who directly care for aHUS cases in clinical practice.

In human sepsis, little is known about the relationships between complement activation and the clinical characteristics of sepsis, including disseminated intravascular coagulation (DIC), interventions, and prognosis.Adult patients with sepsis admitted from November 2016 to December 2018 were included. We used the plasma levels of soluble C5b-9 (SC5b-9) as a marker of complement activation. We compared the clinical characteristics and complement components between patients with and without DIC. We also compared the clinical characteristics and each DIC parameter across quartile groups for the SC5b-9 value.Forty-nine sepsis patients were eligible. Thirty-four patients developed DIC, and eight patients died. The median (interquartile range) SC5b-9 value was 342 (261-501) ng/mL. Compared with patients without DIC, patients with DIC showed lower C3 levels (mean, 95.7 vs. 70.4 mg/dL, P 0.01) and higher SC5b-9 levels (median, 287 vs. 400 ng/mL, P = 0.01). Patients were stratified by SC5b-9 quartile (ng/mL: low:260, moderate: 260-342, high: 343-501, highest:501). The mean Sequential Organ Failure Assessment score varied across these groups (P = 0.02). In the high and highest groups, many more patients received vasopressors and developed DIC. In the highest group, the coagulation parameters were severe, and thrombocytopenia was prolonged. In-hospital mortality tended to be high (33%) in the highest group.The degree of complement activation is related to DIC, severity, intensive interventions, and mortality. Further studies are needed to confirm the usefulness of SC5b-9 for stratifying sepsis patients.

We successfully developed a novel time-resolved synchrotron-radiation X-ray diffraction (t-SXRD) measurement system with high temporal resolution (minimum time: 50 ms) at the BL02B2 facility at SPr...

Anti-vascular endothelial growth factor (VEGF) therapy is the first-choice treatment for neovascular age-related macular degeneration (nvAMD); however, patients often are burdened physically, financially, and mentally. We investigated the relationship between mental status and feasibility of an intravitreal ranibizumab treat-and-extend (TAE) regimen for nvAMD.In this prospective, multicenter study, 75 patients with nvAMD received ranibizumab intravitreally in a TAE regimen. After two monthly injections, the injection intervals were extended step-by-step to 6, 8, 12, and 16 weeks in eyes with dry maculas on optical coherence tomography (OCT) and, if exudation persisted or relapsed, shortened by one step. The best corrected visual acuity (BCVA) measurement and OCT were performed at baseline and on the same days of the scheduled injections. At baseline, all patients completed a survey, the Hospital Anxiety and Depression Scale (HADS), regarding mental burden. At week 52, patients on the TAE regimen for 1 year completed the HADS and a questionnaire designated to assess treatment-associated mental status.Fifty-one patients (68%) completed the 1-year TAE regimen; 24 eyes (32%) discontinued the TAE regimen because of the rescue treatment, difficulty in completing clinical visits, or financial burden. In 51 eyes on the TAE regimen for 1 year, the mean BCVAs improved from 64.3 letters at baseline to 71.6 letters at week 52. The mean anxiety and depression scores on HADS decreased significantly (p 0.01) after the 1-year treatment. Women tended to have higher anxiety scores, possibly associated with fear of injection and recurrence, while some men had higher depression scores potentially associated with financial burden, difficulty in completing clinical visits, and subsequent interruption of the TAE regimen especially in eyes with low treatment efficacy.A TAE regimen of intravitreal ranibizumab injections preserves vision in eyes with nvAMD and reduces mental burden associated with disease relapse.This clinical study was registered retrospectively on December 22, 2014 with the ClinicalTrials.gov identifier NCT02321839.

Intestinal sodium-dependent phosphate transport protein 2b (SLC34A2, NaPi2b) inhibitors are expected to be potential new candidates for anti-hyperphosphatemia drugs. However, a risk of on-target side effects based on the inhibition of NaPi2b in the lung and testis has been reported. To identify gut-selective (minimally systemic) NaPi2b inhibitors, we prepared and evaluated 1H-pyrazole-4-carbonyl-4,5,6,7-tetrahydrobenzo[b]thiophene derivatives with highly polar functional groups to reduce systemic exposure. As a result, compounds 36a and 36b showed a good activity in vitro and a low bioavailability in Sprague-Dawley (SD) rats. However, these compounds did not suppress phosphate absorption in SD rats. This lack of in vivo efficacy could be due to the high hydrophobicity of these compounds. The results of further investigations of other classes of compounds with appropriate physical properties will be reported in due course.

Objective: Nitroglycerin is a first-line treatment for hypertensive acute heart failure syndrome (AHFS). However, nicardipine is frequently used to treat hypertensive emergencies, including AHFS. In this study, we compared the effectiveness of nicardipine and nitroglycerin in patients with hypertensive AHFS. Patients and Methods: This single-center, retrospective, observational study was conducted at the intensive care unit of a Japanese hospital. Patients diagnosed with AHFS and systolic blood pressure 140 mmHg on arrival between April 2013 and March 2021 were included. The outcomes were the time to optimal blood pressure control, duration of continuous infusion of antihypertensive agents, duration of positive pressure ventilation, need for additional antihypertensive agents, length of hospital stay, and body weight changes. Outcomes were compared between the nicardipine and nitroglycerin groups. We also compared these outcomes between the groups after excluding patients who received renal replacement therapy. Results: Fifty-eight patients were enrolled (26 and 32 patients were treated with nitroglycerin and nicardipine, respectively). The nicardipine group had a shorter time to optimal blood pressure control (2.0 [interquartile range, 2.0–8.5] h vs. 1.0 [0.5–2.0] h), shorter duration of continuous anti-hypertensive agent infusion (3.0 [2.0–5.0] days vs. 2.0 [1.0–2.0] days), less frequent need for additional anti-hypertensive agents (1 patients [3.1%] vs. 11 patients [42.3%]), and shorter length of hospital stay (17.5 [10.0–33.0] days vs. 9.0 [5.0–15.0] days) than the nitroglycerin group. The duration of positive pressure ventilation and body weight changes were similar between the groups. The outcomes were similar after excluding patients who received renal replacement therapy. Conclusion: Nicardipine may be more effective than nitroglycerin for treating hypertensive AHFS.

Patient: Female, 57-year-old Final Diagnosis: Acquired thrombocytopenic purpura • influenza A virus infection Symptoms: Hypoxemia Medication:— Clinical Procedure: Plasma exchange Specialty: Critical Care Medicine • Hematology Objective: Rare disease Background: Thrombotic microangiopathy, characterized by microangiopathic hemolytic anemia, thrombocytopenia, and organ damage by microvascular thrombosis, has a high mortality rate; therefore, early diagnosis and treatment are important. Thrombotic thrombocytopenic purpura is caused by a deficiency of a disintegrin-like and metalloproteinase with thrombospondin type 1 motifs 13 (ADAMTS13), and results in thrombotic microangiopathy. Influenza virus causes thrombotic thrombocytopenic purpura by inducing immunoglobulin G autoantibodies against ADAMTS13. We report a rare case of thrombotic thrombocytopenic purpura caused by influenza A without anti-ADAMTS13 antibody that was treated by plasma exchange. Case Report: A 57-year-old woman was admitted to our hospital because of hypoxemia. We diagnosed pneumonia and disseminated intravascular coagulation. Despite treatment, she developed thrombocytopenia, and we diagnosed thrombotic microangiopathy and started plasma exchange. With a PLASMIC score of 6 points and neuropsychiatric symptoms, we strongly suspected thrombotic thrombocytopenic purpura and started rituximab. However, ADAMTS13 activity by FRETS-VWF73 assay was 65%, and anti-ADAMTS13 antibody was negative. After 4 plasma exchanges and 2 rounds of rituximab, platelet numbers and lactate dehydrogenase and creati-nine concentrations normalized on the 16th day of hospitalization. Subsequently, influenza A (H1N1) was identified in a nasopharyngeal swab collected on admission. Plasma enzyme-linked immunosorbent assay testing for chromogenic ADAMTS13 activity showed a significant decrease (

Layered double hydroxides (LDHs) are promising compounds in a wide range of fields. However, exchange of CO32– anions with other anions is necessary, because the CO32– anions are strongly affixed i...

A series of sequence-regulated vinyl copolymers with high-order and long vinyl monomer sequences were constructed via a combination of iterative single vinyl monomer additions, which were mediated by radical and cationic intermediates, and subsequent metal-catalyzed step-growth radical polymerization. The construction of vinyl monomer sequences was attained by iterative single monomer radical and cationic additions between a dichloride, having a similar substituent to that of vinyl monomers, and vinyl monomers such as styrenes, acrylates, and acrylonitrile. The resulting products were converted into sequence-regulated ab-type monomers that have embedded vinyl monomer sequences between an unconjugated C═C bond and reactive C–Cl bond via selective allylation of one of the two C–Cl bonds at their terminals. The synthesized sequence-regulated ab-type monomers were polymerized via metal-catalyzed step-growth radical polymerization, which resulted in vinyl chloride units via repetitive intermolecular addition reactions between the C═C and C–Cl terminals. Alternatively, aa- and bb-type sequence-regulated monomers, which have two unconjugated C═C and two reactive C–Cl bonds, respectively, were prepared by similar iterative single monomer additions and were subsequently polymerized via metal-catalyzed step-growth radical polymerization. The repeating vinyl monomer sequence codes in the resulting polymers, such as ABCC, ABCD, ABBAC, ABDBAC, and ABDBACAEEAC, varied from 4 to 11 monomer units in which the embedded vinyl monomer units were styrenes, acrylates, acrylamides, acrylonitrile, vinyl chloride, vinylidene chloride, and ethylene.

Intestinal sodium-dependent phosphate transport protein 2b (SLC34A2, NaPi2b) inhibitors are expected to be potential new candidates for anti-hyperphosphatemia drugs. However, a risk of on-target side effects based on the inhibition of NaPi2b in the lung and testis has been reported.In this article, we report on our identification of novel indole derivatives as gut-selective NaPi2b inhibitors with good activity, low systemic exposure and moderate hydrophobicity.In particular, gut-selective compound 27, with even lower bioavailability and lower systemic exposure as compared to previously reported pyridine derivatives, demonstrated excellent phosphate absorption-inhibitory effect in SD rats. Compound 27 has an ideal profile and appears to offer promise as a candidate drug for the treatment of hyperphosphatemia, with minimal risk of side effects due to systemic exposure.

We previously reported thiophene derivatives as gut-selective (minimally systemic) and potent sodium-dependent phosphate transport protein 2b (SLC34A2, NaPi2b) inhibitors. However, these derivatives did not suppress phosphate absorption form the intestinal tract in Sprague-Dawley (SD) rats. The lack of efficacy in vivo could be due to the high hydrophobicity of these compounds. In this report, we identified novel pyridine derivatives as gut-selective NaPi2b inhibitors with good activity in vitro and relatively low hydrophobicity. Especially, gut-selective compound 20b suppressed phosphate absorption in SD rats. These results suggest that physical properties, such as the hydrophobicity of the compounds, might affect the in vivo efficacy.

A 67-year-old female with a history of autoimmune hepatitis was admitted for fever, acute hepatic dysfunction, and acute kidney injury. She was diagnosed with multiple duodenal ulcers. Despite the administration of proton pump inhibitor and red blood cells, her black stool and anemia progressed, and she was therefore transferred to our hospital. Despite hemostatic treatments, she continued to bleed. On the 21st day of admission, an endoscopic examination showed the oozing of blood from the duodenal mucosa. A low factor XIII (FXIII) activity level was detected, and she was administered FXIII concentrate. The bleeding stopped and she was thereafter discharged.

Background Endovascular treatment is used for traumatic arterial injuries in the torso. However, the effectiveness of endovascular covered stent‐graft treatment for peripheral artery injury is unclear. We present a case of superficial femoral artery (SFA) injury successfully treated with a covered stent‐graft. Case Report A 68‐year‐old man presented with traumatic lower limb injury and shock. Computed tomography angiography revealed left subtrochanteric fracture and hematoma with extravasation. Digital subtraction angiography revealed extravasation from a left SFA branch, and a pseudoaneurysm at the SFA trunk. We coil embolized the SFA branch, and treated the pseudoaneurysm with a covered stent‐graft. Computed tomography carried out 22 days later showed complete pseudoaneurysm exclusion and sufficient stent patency. Conclusion We successfully used a covered stent‐graft to treat SFA injury due to blunt trauma. A covered stent‐graft could be effective for peripheral artery injury., A 68‐year‐old man presented with lower limb injury and shock after a fall, and digital subtraction angiography revealed extravasation from a proximal branch of the left superficial femoral artery and a pseudoaneurysm at the superficial femoral artery trunk. We used a coil to embolize the superficial femoral arterial branch, and a covered stent graft to treat the pseudoaneurysm. A covered stent graft could be effective for peripheral artery injury; however, the long‐term complications are unclear.

We study gamma-ray line signatures from electroweakly interacting non-abelian spin-1 dark matter (DM). In this model, $Z_2$-odd spin-1 particles including a DM candidate have the SU(2)$_L$ triplet-like features, and the Sommerfeld enhancement is relevant in the annihilation processes. We derive the annihilation cross sections contributing to the photon emission and compare with the SU(2)$_L$ triplet fermions, such as Wino DM in the supersymmetric Standard Model. The Sommerfeld enhancement factor is approximately the same in both systems, while our spin-1 DM predicts the larger annihilation cross sections into $\gamma \gamma/ Z \gamma$ modes than those of the Wino by $\frac{38}{9}$. This is because a spin-1 DM pair forms not only $J=0$ but also $J=2$ partial wave states where $J$ denotes the total spin angular momentum. Our spin-1 DM also has a new annihilation mode into $Z_2$-even extra heavy vector and photon, $Z' \gamma$. For this mode, the photon energy depends on the masses of DM and the heavy vector, and thus we have a chance to probe the mass spectrum. The latest gamma-ray line search in the Galactic Center region gives a strong constraint on our spin-$1$ DM. We can probe the DM mass for $\lesssim 25.3~$TeV by the Cherenkov Telescope Array experiment even if we assume a conservative DM density profile., Comment: 31 pages, 6 figures, 2 tables, the version published in JHEP

Background: Nitroglycerin is considered a first-line agent for hypertensive acute heart failure syndromes (AHFS). In this study, we compared the effectiveness of nicardipine and nitroglycerin in patients with hypertensive AHFS. Methods: We conducted a single-center, retrospective, observational study at the intensive care unit of a Japanese hospital. Patients diagnosed with AHFS and systolic blood pressure exceeding 140 mmHg on arrival between April 2013 and August 2019 were included. The outcomes were the time to optimal blood pressure control, duration of the continuous infusion of anti-hypertensive agents, duration of positive pressure ventilation, need for additional anti-hypertensive agents, length of hospital stay, and body weight changes. Outcomes were compared between the nicardipine and nitroglycerin groups. We also compared these outcomes between the groups after excluding patients who received renal replacement therapy. Results: Forty-five patients were enrolled (25 and 20 were treated with nitroglycerin and nicardipine, respectively). The nicardipine group had a shorter time to optimal blood pressure control (1.0 [interquartile range, 1.0–3.0] h vs. 0.5 [0.5–1.0] h), shorter duration of the continuous infusion of anti-hypertensive agents (65.5 [32.5–127.5] h vs. 31.0 [18.5–61.0] h), less frequent need for additional anti-hypertensive agents (0 patients vs. 10 patients [40.0%]), and shorter length of hospital stay (19.0 [10.0–33.0] days vs. 8.0 [5.0–12.3] days) than the nitroglycerin group. The duration of positive pressure ventilation and body weight changes were similar between the groups. These outcomes were similar after excluding patients who received renal replacement therapy. Conclusions: Nicardipine may be more effective than nitroglycerin for treating hypertensive AHFS.

We study the effect of the early kinetic decoupling in a model of fermionic dark matter (DM) that interacts with the standard model particles only by exchanging the Higgs boson. There are two DM-Higgs couplings, namely CP-conserving and CP-violating couplings. If the mass of the DM is slightly below half of the Higgs boson mass, then the couplings are suppressed to obtain the measured value of the DM energy density by the freeze-out mechanism. In addition, the scattering processes of DM off particles in the thermal bath are suppressed by the small momentum transfer if the CP-violating DM-Higgs coupling is larger than the CP-conserving one. Due to the suppression, the temperature of the DM can differ from the temperature of the thermal bath. By solving coupled equations for the number density and temperature of the DM, we calculate the DM-Higgs couplings that reproduce the right amount of the DM relic abundance. We find that the couplings have to be larger than the one obtained without taking into account the difference in the temperatures. A consequence of the enhancement of the DM-Higgs couplings is the enhancement of the Higgs invisible decay branching ratio. The enhancement is testable at current and future collider experiments., Comment: 18 pages, 3 figures; typo corrected, updated the constraint from the Higgs invisible decay

We propose an electroweakly interacting spin-1 dark matter (DM) model. The electroweak gauge symmetry, SU(2)$_L\times$U(1)$_Y$, is extended into SU(2)$_0\times$SU(2)$_1 \times $SU(2)$_2 \times$U(1)$_Y$. A discrete symmetry exchanging SU(2)$_0$ and SU(2)$_2$ is imposed. This discrete symmetry stabilizes the DM candidate. The spin-1 DM particle ($V^0)$ and its SU(2)$_L$ partners ($V^\pm$) interact with the Standard Model (SM) electroweak gauge bosons without any suppression factors. Consequently, pairs of DM particles efficiently annihilate into the SM particles in the early universe, and the measured value of the DM energy density is easily realized by the thermal freeze-out mechanism. The model also predicts a heavy vector triplet ($W'^\pm$ and $Z'$) in the visible sector. They contribute to the DM annihilation processes. The mass ratio of $Z'$ and $V^0$ determines values of various couplings, and constraints on $W'$ and $Z'$ restrict regions of the parameter space that are viable for DM physics. We investigate the constraints from perturbative unitarity of scalar and gauge couplings, the Higgs signal strength, $W'$ search at the LHC, and DM direct detection experiments. It is found that the relic abundance of $V^0$ explains the right amount of the DM energy density for 3 TeV $\lesssim m_{V^0} \lesssim$ 19 TeV., 29 pages, 7 figures, 2 tables, the version published in JHEP

Twenty‐nine cases (55.7%) showed traumatic intracranial hemorrhagic injury progression during interventional radiology. Age (P = 0.029), Glasgow Coma Scale at admission (P = 0.001), Revised Trauma Score (P = 0.036), Trauma and Injury Severity Score probability of survival (P = 0.043), platelet count (P = 0.005), D‐dimer level (P = 0.046), fibrinogen level (P = 0.016), and hemoglobin level (P = 0.003) differed significantly between the enlarged and non‐enlarged groups., Aim To identify factors affecting the progression of traumatic intracranial hemorrhagic injury (t‐ICH) during interventional radiology (IVR) for the hemostasis of extracranial hemorrhagic injury. Methods This was a retrospective comparative study. Fifty‐two patients with t‐ICH who underwent hemostasis using IVR for extracranial trauma at our institute were included. Clinical and computed tomography scan data were collected to investigate factors associated with t‐ICH progression. Results Fifty‐two subjects (36 men/16 women) with a mean age of 70.9 ± 19.2 years were analyzed. The mean Injury Severity Score was 34.9 ± 11.2. In 29 patients (55.7%), t‐ICH progressed during IVR. Hematoma progression frequently occurred in patients with acute subdural hematoma (56.2%) and traumatic intracerebral hematoma/hemorrhagic brain contusion (66.6%). Factors associated with t‐ICH progression included age (P = 0.029), consciousness level at admission (P = 0.001), Revised Trauma Scale (P = 0.036), probability of survival (P = 0.043), platelet count (P = 0.005), fibrinogen level (P = 0.016), hemoglobin level (P = 0.003), D‐dimer level (P = 0.046), and red blood cell transfusion volume (P = 0.023). Conclusion Aggressive correction of anemia, thrombocytopenia, and low fibrinogen levels in severe consciousness disturbance patients with acute subdural hematoma and traumatic intracerebral hematoma/hemorrhagic brain contusion could improve the prognosis after IVR for hemostasis of extracranial hemorrhagic injuries.

The aim of this study was to investigate a failure criterion to predict flexural strengths of composite resins (CR) by three-dimensional finite element analysis (3D-FEA). Models of flexural strength for test specimens of CR and rods comprising a three-point loading were designed. Calculation of Young's moduli and Poisson's ratios of CR were conducted using a modified McGee-McCullough model. Using the experimental CR, flexural strengths were measured by three-point bending tests with crosshead speed 1.0 mm/min and compared with the values determined by in silico analysis. The flexural strengths of experimental CR calculated using the maximum principal strain significantly correlated with those obtained in silico amongst the four types of failure criteria applied. The in silico analytical model established in this study was found to be effective to predict the flexural strengths of CR incorporating various silica filler contents by maximum principal strain.

We report the improvement of an apparatus for Bragg coherent x-ray diffraction imaging (Bragg-CDI) at BL22XU in SPring-8 to expand the applicable particle size and the application of the Bragg-CDI technique for Pd and ferroelectric barium titanate (BaTiO3) fine crystals with particle sizes of 40–500 nm. Preparing a vacuum environment around the sample enabled us to obtain the high-contrast diffraction pattern of a 40-nm particle. The reconstructed three-dimensional image showed the outer shape, size, and internal phase (strain) for a single particle. A single 500-nm BaTiO3 particle showed a straight and sharp antiphase-boundary shape, whereas smaller BaTiO3 particles showed different phase boundary shapes. The present Bragg-CDI apparatus, thus, allows the observation of the outer shape, size, and inner phase distribution for a single particle with a size of 40–500 nm.

Objective: Involvement of all regional medical facilities in a trauma system is challenging in rural regions. We hypothesized that the physician-staffed helicopter emergency medical service potentially encouraged local facilities to participate in trauma systems by providing the transport of patients with trauma to those facilities in a rural setting. Materials and Methods: We performed two retrospective observational studies. First, yearly changes in the numbers of patients with trauma and destination facilities were surveyed using records from the Miyazaki physician-staffed helicopter emergency medical service from April 2012 to March 2014. Second, we obtained data from medical records regarding the mechanism of injury, severity of injury, resuscitative interventions performed within 24 h after admission, secondary transports owing to undertriage by attending physicians, and deaths resulting from potentially preventable causes. Data from patients transported to the designated trauma center and those transported to non-designated trauma centers in Miyazaki were compared. Results: In total, 524 patients were included. The number of patients transported to non-designated trauma centers and the number of non-designated trauma centers receiving patients increased after the second year. We surveyed 469 patient medical records (90%). There were 194 patients with major injuries (41%) and 104 patients with multiple injuries (22%), and 185 patients (39%) received resuscitative interventions. The designated trauma centers received many more patients with trauma (366 vs. 103), including many more patients with major injuries (47% vs. 21%, p < 0.01) and multiple injuries (25% vs. 13%, p < 0.01), than the non-designated trauma centers. The number of patients with major injuries and patients who received resuscitative interventions increased for non-designated trauma centers after the second year. There were 9 secondary transports and 26 deaths. None of these secondary transports resulted from undertriage by staff physicians and none of these deaths resulted from potentially preventable causes. Conclusion: The rural physician-staffed helicopter emergency medical service potentially encouraged non-designated trauma centers to participate in trauma systems while maintaining patient safety.

Kuwazuimo (Alocasia odora) and shimakuwazuimo (Alocasia cucullata) are evergreen perennial plants that originated in East Asia. Although inedible, they are occasionally eaten by mistake because they resemble satoimo (Colocasia esculenta), and this has caused food poisoning in Japan. It is not easy to determine the cause of a food poisoning outbreak from the shape or chemical composition when the available sample is small. Therefore, we developed a new primer pair for PCR to identify kuwazuimo and shimakuwazuimo in small samples, based on the internal transcribed spacer (ITS) region of ribosomal DNA. Using PCR with the developed primer pair, we detected all samples of kuwazuimo obtained from the market, while excluding 17 other kinds of crops. The samples were identified as shimakuwazuimo by DNA sequencing of the PCR products. The present PCR method showed high specificity and was confirmed to be applicable to the identification of kuwazuimo and shimakuwazuimo from various crops.

Structural phase transitions of calcium strontium sulfoaluminate series, (Ca1-xSrx)8[AlO2]12(SO4)2 ((CS)AS-x) with x = 0.80-1.00, are systematically investigated by powder X-ray diffraction, dielectric measurements, and pyroelectric measurements, to clarify a phase diagram of (CS)AS-x (x = 0.80-1.00). A pure strontium sulfoaluminate, (CS)AS-1.00, is found to undergo three phase transitions, which take place successively on cooling from a prototypical cubic phase with the symmetry of Im3m. Though the room-temperature phase of (CS)AS-1.00 was previously reported to be of polar Pcc2, the pyroelectric measurements clarified a nonpolar character of the crystal symmetry. The dielectric measurements suggest a possibility of an antiferroelectric ground state of (CS)AS-x in the Sr-rich compositions. As x decreases, the ground state changes to a short-range-ordered state, implying a unique phase transition from the antiferroelectric state to the antiferroelectric-relaxor state. The present study provides an intriguing playground for designing new ferro/antiferroelectric materials.

ObjectivesPhysician-staffed prehospital units are widely used in many countries. The criteria for predicting fatal injury are well recognised for trauma victims, but there are no criteria for predicting critical condition for non-trauma patients. This study aimed to identify the factors associated with non-trauma cases receiving prehospital interventions by physicians.DesignRetrospective observational study.SettingPhysician-staffed prehospital unit (car) at a single-base hospital in a suburban city in Japan.ParticipantsParticipants were 1058 non-trauma patients who received prehospital medical examinations from April 2014 to December 2017.Outcome measuresThe outcome was the occurrence of physician-only interventions (POIs) exceeding paramedics’ competencies. Univariate analysis and multiple logistic regression analysis were performed. Patient’s age and gender, presumed disease category, type of location of the emergency, time of alarm, activation time, activator’s occupation, time to arrival, transportation time and the destination facility were included as covariates.ResultsPOIs were provided to 380 (36%) patients. Patient’s age, presumed disease category, type of location of the emergency, activator’s occupation, time to arrival, transportation time and the destination facility were identified as potential independent factors. Multiple logistic regression analysis found that patient’s age, presumed disease category, type of location of the emergency, transportation time and destination facility were the significant independent factors. Transportation times of more than 15 min (adjusted ORs (AORs)=4.17, 95% CI 2.59 to 6.72, pConclusionsThis study identified the factors associated with non-trauma cases receiving prehospital POIs. Patient’s age, presumed disease category, type of location of the emergency and transportation time are independent factors associated with requiring POIs.

Physics of the Dark Universe 27, 100351 (2019). doi:10.1016/j.dark.2019.100351, Dark matter (DM) simplified models are by now commonly used by the ATLAS and CMS Collaborations to interpret searches for missing transverse energy ( ETmiss ). The coherent use of these models sharpened the LHC DM search program, especially in the presentation of its results and their comparison to DM direct-detection (DD) and indirect-detection (ID) experiments. However, the community has been aware of the limitations of the DM simplified models, in particular the lack of theoretical consistency of some of them and their restricted phenomenology leading to the relevance of only a small subset of ETmiss signatures. This document from the LHC Dark Matter Working Group identifies an example of a next-generation DM model, called 2HDM+a , that provides the simplest theoretically consistent extension of the DM pseudoscalar simplified model. A comprehensive study of the phenomenology of the 2HDM+a model is presented, including a discussion of the rich and intricate pattern of mono- X signatures and the relevance of other DM as well as non-DM experiments. Based on our discussions, a set of recommended scans are proposed to explore the parameter space of the 2HDM+a model through LHC searches. The exclusion limits obtained from the proposed scans can be consistently compared to the constraints on the 2HDM+a model that derive from DD, ID and the DM relic density., Published by Elsevier, Amsterdam [u.a.]

In this study, we accurately visualized the valence electron density distributions of ferroelectrics PbTiO3 and BaTiO3 by analyzing synchrotron-radiation powder x-ray diffraction (SXRD) data using the Rietveld method and the maximum entropy method. Clear SXRD evidence indicates that the Pb ion in PbTiO3 is polarized in the ferroelectric phase, whereas the Ba ion in BaTiO3 is not polarized and fully ionized as a Ba2+ ion. The large electronic polarization of the Pb ion is attributed to the anisotropic spatial distribution of the lone-pair electrons of the Pb2+ ion, particularly the anisotropic p-like orbital of the lone-pair electrons caused by the formation of Pb–O covalent bonds. In PbTiO3, the contribution of the electronic polarization of the Pb ion to the spontaneous polarization is significant. We experimentally evaluate the contributions of the ionic polarization and the electronic polarization, respectively, from the valence electron density distribution map and demonstrate that the spontaneous polarization can be calculated from the SXRD data as the sum of them. One of the Ti–O covalent bonds is broken at the phase transition in PbTiO3, whereas no change in the atomic coordination is observed in BaTiO3. When focusing on the covalent bonding network, we propose using a layered material for PbTiO3 in the ferroelectric phase. These results agree well with those of first-principles calculations. We expect further comprehensive valence electron density studies can be performed by combining SXRD experiments and first-principles calculations to better understand the emergence of ferroelectricity.

Reproduction is essential for life, but its regulatory mechanism is diverse. The analysis of this diversity should lead us to understand the evolutionary process of the regulation of reproduction. In mammals, the hypothalamic-pituitary-gonadal axis plays an essential role in such regulation, and each component, hypothalamic GnRH, and pituitary gonadotropins, LH, and FSH, is indispensable. However, the common principle of the hypothalamic-pituitary-gonadal axis regulation among vertebrates remains unclear. Here, we used a teleost medaka, which is phylogenetically distant from mammals, and analyzed phenotypes of gene knockouts (KOs) for GnRH, LH, and FSH. We showed that LH release, which we previously showed to be directly triggered by GnRH, is essential for ovulation in females, because KO medaka of GnRH and LH were anovulatory in spite of the full follicular growth and normal gonadosomatic index, and spawning could be induced by a medaka LH receptor agonist. On the other hand, we showed that FSH is necessary for the folliculogenesis, because the follicular growth of FSH KO medaka was halted at the previtellogenic stage, but FSH release does not necessarily require GnRH. By comparing these results with the previous studies in mammals that both GnRH and LH are necessary for folliculogenesis, we propose a hypothesis as follows. During evolution, LH was originally specialized for ovulation, and regulation of folliculogenesis by GnRH-LH (pulsatile release) was newly acquired in mammals, which enabled fine tuning of reproduction through hypothalamus.

OBJECTIVE: Rescuing severe trauma patients who are injured far from a trauma center is challenging for rural emergency systems. We report a severe trauma case that occurred at a remote location, in which the patient's life was saved by a dispatched doctor car and a physician from a local medical facility. PATIENT: A 31-year-old man experienced a left femur injury due to a fallen tree. The fire station requested a doctor car from our center, approximately 56 km away. Meanwhile, a paramedic team reported that the patient was in a state of shock. The doctor car docked over 1 h after the accident. Pressure hemostasis, rapid intravenous infusion, and tracheal intubation were performed en route. After arrival at our hospital, an emergency blood transfusion was administered; the injured blood vessel was sutured and the wound closed. On day 22, the patient was transferred to another hospital for rehabilitation. DISCUSSION: Rapid response-type doctor car is often considered ineffective for distant severe trauma cases. However, this case demonstrates the benefits of a doctor car working with local medical facilities. CONCLUSION: The rapid response-type doctor car is effective even in remote severe trauma cases. Language: en

Crystallography and dielectric properties in Dion-Jacobson layered perovskites, CsNdNb$_2$O$_7$ and RbNdNb$_2$O$_7$, have been examined in dense polycrystalline samples, and polarization hysteresis loops that substantiate ferroelectricity have been observed at room temperature. The theoretical mechanism for the spontaneous polarization, "hybrid improper ferroelectric mechanism,'' induced by a combination of two types of non-polar octahedral rotations, is confirmed in these two phases. Our samples show remanent polarizations of 2-3 $\mu$C/cm$^2$, which are much larger than those obtained in polycrystalline samples with the hybrid improper ferroelectricity reported so far. A dielectric constant in CsNdNb$_2$O$_7$ exhibits an anomaly at 625 K, corresponding to the ferroelectric transition, as previously revealed by x-ray and neutron diffractometry. No dielectric anomaly is observed for RbNdNb$_2$O$_7$ throughout the temperature range studied here ($\leq$ 773 K), which is consistent with the previous diffractometry showing the persistence of polar $I2cm$ symmetry up to 790 K., Comment: 7 pages, 3 figures, accepted for publication by JJAP

Structural characteristics of a bismuth titanate (Bi4Ti3O12, BiT) ceramic powder material and the polycrystalline film formed by the aerosol deposition (AD) method are investigated by synchrotron-radiation X-ray diffraction. The BiT powders without clear plate-like shapes are prepared as stating powders for the film deposition. The electron charge density analysis demonstrates that the particular BiT powders synthesized in this study have the same layered crystal structure as well-known BiT powder materials. The c-oriented polycrystalline film is deposited at room temperature onto a glass substrate without any heat treatment by the AD method. The high orientation of the BiT as-deposited AD film is attributed to the layered crystal structure essentially originated from the anisotropic nature of chemical bonds in the BiT crystal rather than the shapes of particles of the starting powders.

We investigated the correlations between the crystal structures and electrical properties of the double-perovskite GdBaFe2O5 over a broad range of temperatures. We examined the successive phase transitions and determined the crystal structures of four crystallographic phases of GdBaFe2O5 using electron diffraction and synchrotron radiation X-ray powder diffraction (SRXRD). The valence states of the Fe sites in the respective phases were deduced from the SRXRD data. We observed two types of charge-ordered states caused by charge and orbital orderings at Fe ions. The electrical resistivity displayed a metal-insulator transition, which is compatible with charge-ordered states. The structural phase transitions in GdBaFe2O5 were observed to be related to the charge-, magnetic-, and orbital-ordered states.

We investigate decay modes of spin-1 heavy vector bosons (V’) from the viewpoint of perturbative unitarity in a model independent manner. Perturbative unitarity requires some relations among couplings, which are called unitarity sum rules. We derive the relation between V’ couplings to the SM fermions (f) and V’ couplings to the SM gauge bosons (V). Using the coupling relations, we calculate partial decay widths for V’ decays into VV and ff. We show that Br(W’ → WZ) 0.02.

The aim of this study was to investigate a failure criterion to predict flexural strengths of composite resins (CR) by three-dimensional finite element analysis (3D-FEA). Models of flexural strength for test specimens of CR and rods comprising a three-point loading were designed. Calculation of Young's moduli and Poisson's ratios of CR were conducted using a modified McGee-McCullough model. Using the experimental CR, flexural strengths were measured by three-point bending tests with crosshead speed 1.0 mm/min and compared with the values determined by in silico analysis. The flexural strengths of experimental CR calculated using the maximum principal strain significantly correlated with those obtained in silico amongst the four types of failure criteria applied. The in silico analytical model established in this study was found to be effective to predict the flexural strengths of CR incorporating various silica filler contents by maximum principal strain.

The objective of this study was to assess the effect of silica nano-filler particle diameters in a computer-aided design/manufacturing (CAD/CAM) composite resin (CR) block on physical properties at the multi-scale in silico. CAD/CAM CR blocks were modeled, consisting of silica nano-filler particles (20, 40, 60, 80, and 100 nm) and matrix (Bis-GMA/TEGDMA), with filler volume contents of 55.161%. Calculation of Young's moduli and Poisson's ratios for the block at macro-scale were analyzed by homogenization. Macro-scale CAD/CAM CR blocks (3 × 3 × 3 mm) were modeled and compressive strengths were defined when the fracture loads exceeded 6075 N. MPS values of the nano-scale models were compared by localization analysis. As the filler size decreased, Young's moduli and compressive strength increased, while Poisson's ratios and MPS decreased. All parameters were significantly correlated with the diameters of the filler particles (Pearson's correlation test, r = -0.949, 0.943, -0.951, 0.976, p 0.05). The in silico multi-scale model established in this study demonstrates that the Young's moduli, Poisson's ratios, and compressive strengths of CAD/CAM CR blocks can be enhanced by loading silica nanofiller particles of smaller diameter. CAD/CAM CR blocks by using smaller silica nano-filler particles have a potential to increase fracture resistance.

Kuwazuimo (Alocasia odora) and shimakuwazuimo (Alocasia cucullata) are evergreen perennial plants that originated in East Asia. Although inedible, they are occasionally eaten by mistake because they resemble satoimo (Colocasia esculenta), and this has caused food poisoning in Japan. It is not easy to determine the cause of a food poisoning outbreak from the shape or chemical composition when the available sample is small. Therefore, we developed a new primer pair for PCR to identify kuwazuimo and shimakuwazuimo in small samples, based on the internal transcribed spacer (ITS) region of ribosomal DNA. Using PCR with the developed primer pair, we detected all samples of kuwazuimo obtained from the market, while excluding 17 other kinds of crops. The samples were identified as shimakuwazuimo by DNA sequencing of the PCR products. The present PCR method showed high specificity and was confirmed to be applicable to the identification of kuwazuimo and shimakuwazuimo from various crops.

We report the development of an apparatus for Bragg coherent X-ray diffraction imaging (Bragg-CDI) at BL22XU of SPring-8, and show some typical results of the three dimensional imaging of BaTiO3 fine particles obtained using the apparatus. We studied two types of sample—particles with cubic-like shapes, and particles rich in curved surfaces. The shapes and sizes of the particles were successfully reconstructed, and are approximately consistent with results from scanning electron microscope (SEM) measurements. Further, details of the internal structure and reverse surface of the particles was obtained, information which is not available from SEM measurements. Our technique can currently be used to study particles as small as around 100 nm in size. Bragg-CDI is a powerful technique for investigating nanosized crystalline particles, and will open the door to studying particles located within devices such as multi-layered ceramic capacitors, inaccessible by electron beam techniques.

Platinum (Pt) dissolution has been elucidated by measuring a mass loss of Pt black-deposited Au quartz resonators in 0.1 mol dm-3 HClO4 containing NaNO2. A continuous weight loss of ca. 50 ng cm-2 cycle-1 was detected at [NaNO2] = 0.01 mol dm-3 under the potential cycling between 0.6 and 1.4 V vs. RHE. The magnitude of Pt dissolution depends on the concentration of NaNO2 and the range of potential cycling. The average mass loss decreases to 5~10 ng cm-2 cycle-1 at [NaNO2] = 1 mmol dm-3. The Pt dissolution occurs when the higher potential limit is more than 1.0 V vs. RHE and the lower potential limit is less than 0.9 V vs. RHE, suggesting that the reduction of Pt oxide in the presence of NaNO2 in the bulk solution contributes to the dissolution.

Electron charge density studies of stoichiometric LiNbO3 and LiTaO3 ferroelectrics have been carried out by analyzing the synchrotron radiation X-ray powder diffraction data using a combination of the Rietveld and maximum entropy methods. The clear relationships between the Nb(Ta)–O bond length, the electron charge density on the Nb(Ta)–O bond, and the phase transition temperature T C are revealed for isomorphic structures. Nb(Ta)–O bonding plays an important role in the elevation of T C. The T C in LiNbO3 being higher than that in LiTaO3 is attributed to the larger lattice distortion of the Nb–O oxygen octahedron in LiNbO3. The validity of estimating T C for LiNbO3 family crystals from the degree of lattice distortion in the ferroelectric structure is discussed.