Constraints on the origin of the ultra-high energy cosmic-rays using cosmic diffuse neutrino flux limits: An analytical approach

Astrophysical neutrinos are expected to be produced in the interactions of ultra-high energy cosmic-rays with surrounding photons. The fluxes of the astrophysical neutrinos are highly dependent on the characteristics of the cosmic-ray sources, such as their cosmological distributions. We study possible constraints on the properties of cosmic-ray sources in a model-independent way using experimentally obtained diffuse neutrino flux above 100 PeV. The semi-analytic formula is derived to estimate the cosmogenic neutrino fluxes as functions of source evolution parameter and source extension in redshift. The obtained formula converts the upper-limits on the neutrino fluxes into the constraints on the cosmic-ray sources. It is found that the recently obtained upper-limit on the cosmogenic neutrinos by IceCube constrains the scenarios with strongly evolving ultra-high energy cosmic-ray sources, and the future limits from an 1 km^3 scale detector are able to further constrain the ultra-high energy cosmic-rays sources with evolutions comparable to the cosmic star formation rate.Comment: 9 pages, 3 figures and 1 table. Accepted by Phys. Rev.

Identifying High Energy Neutrino Transients by Neutrino Multiplet-Triggered Followups

Transient sources such as supernovae (SNe) and tidal disruption events are candidates of high energy neutrino sources. However, SNe commonly occur in the universe and a chance coincidence of their detection with a neutrino signal cannot be avoided, which may lead to a challenge of claiming their association with neutrino emission. In order to overcome this difficulty, we propose a search for $\sim10-100$ TeV neutrino multiple events within a timescale of $\sim 30$ days coming from the same direction, called neutrino multiplets. We show that demanding multiplet detection by a $\sim 1$ km$^3$ neutrino telescope limits distances of detectable neutrino sources, which enables us to identify source counterparts by multiwavelength observations owing to the substantially reduced rate of the chance coincidence detection of transients. We apply our results by constructing a feasible strategy for optical followup observations and demonstrate that wide-field optical telescopes with a $\gtrsim4$ m dish should be capable of identifying a transient associated with a neutrino multiplet. We also present the resultant sensitivity of multiplet neutrino detection as a function of the released energy of neutrinos and burst rate density. A model of neutrino transient sources with an emission energy greater than ${\rm a~few}\times 10^{51}$erg and a burst rate rarer than ${\rm a~few}\times 10^{-8}\ {\rm Mpc}^{-3}\ {\rm yr}^{-1}$ is constrained by the null detection of multiplets by a $\sim 1$km$^3$ scale neutrino telescope. This already disfavors the canonical high-luminosity gamma ray bursts and jetted tidal disruption events as major sources in the TeV-energy neutrino sky.Comment: The version accepted for publication in Ap

Ixodes persulcatus Ticks as Vectors for the Babesia microti U.S. Lineage in Japan

The U.S. lineage, one of the major clades in the Babesia microti group, is known as a causal agent of human babesiosis mostly in the northeastern and upper midwestern United States. This lineage, however, also is distributed throughout the temperate zone of Eurasia with several reported human cases, although convincing evidence of the identity of the specific vector(s) in this area is lacking. Here, the goal was to demonstrate the presence of infectious parasites directly in salivary glands of Ixodes persulcatus, from which U.S. lineage genetic sequences have been detected in Asia, and to molecularly characterize the isolates. Five PCR-positive specimens were individually inoculated into hamsters, resulting in infections in four; consequently, four strains were newly established. Molecular characterization, including 18S rRNA, β-tubulin, and CCT7 gene sequences, as well as Western blot analysis and indirect fluorescent antibody assay, revealed that all four strains were identical to each other and to the U.S. lineage strains isolated from rodents captured in Japan. The 18S rRNA gene sequence from the isolates was identical to those from I. persulcatus in Russia and China, but the genetic and antigenic profiles of the Japanese parasites differ from those in the United States and Europe. Together with previous epidemiological and transmission studies, we conclude that I. persulcatus is likely the principal vector for the B. microti U.S. lineage in Japan and presumably in northeastern Eurasia. IMPORTANCE The major cause of human babesiosis, the tick-borne blood parasite Babesia microti, U.S. lineage, is widely distributed in the temperate Northern Hemisphere. However, the specific tick vector(s) remains unidentified in Eurasia, where there are people with antibodies to the B. microti U.S. lineage and cases of human babesiosis. In this study, the first isolation of B. microti U.S. lineage from Ixodes persulcatus ticks, a principal vector for many tick-borne diseases, is described in Japan. Limited antigenic cross-reaction was found between the Japan and United States isolates. Thus, current serological tests based on U.S. isolates may underestimate B. microti occurrence outside the United States. This study and previous studies indicate that I. persulcatus is part of the B. microti U.S. lineage life cycle in Japan and, presumably, northeastern Eurasia. This report will be important for public health, especially since infection may occur through transfusion, and also to researchers in the field of parasitology

Utility of Endoscopic Ultrasound-Guided Fine Needle Aspiration in the Diagnosis of Local Recurrence of Pancreaticobiliary Cancer after Surgical Resection

Background/Aims: Endoscopic ultrasound (EUS)-guided fine needle aspiration (FNA; EUS-FNA) allows for diagnostic tissue specimens from various regions to be analyzed. However, diagnosing recurrent pancreaticobiliary cancer after surgery is sometimes difficult. We evaluated the efficacy of EUS-FNA in the diagnosis of local recurrence of pancreaticobiliary cancer and analyzed the factors associated with falsenegative results. Methods: Fifty-one consecutive patients who underwent EUS-FNA due to suspected recurrence of pancreaticobiliary cancer after surgery in an academic center were retrospectively analyzed. The criteria for EUS-FNA were a resected margin or remnant pancreas mass, round swollen lymph node (≥10 mm in diameter), and soft-tissue enhancement around a major artery. Patients with suspected liver metastasis or malignant ascites were excluded. Results: Thirty-nine of the 51 patients had pancreatic cancer; the remaining 12 had biliary cancer. The target sites for EUS-FNA were the soft tissue around a major artery (n=22, 43%), the resected margin or remnant pancreas (n=12, 24%), and the lymph nodes (n=17, 33%). The median size of the suspected recurrent lesions was 15 mm (range, 8 to 40 mm). The overall sensitivity, specificity and accuracy of EUS-FNA for the diagnosis of recurrence was 84% (32/38), 100% (13/13), and 88% (45/51), respectively. FNA of the soft tissue around major arteries (odds ratio, 8.23; 95% confidence interval, 1.2 to 166.7; p=0.033) was significantly associated with a falsenegative diagnosis in the multivariate analysis. Conclusions: EUS-FNA is useful for diagnosing recurrent cancer, even after pancreaticobiliary surgery. The diagnoses of recurrence at soft-tissue sites should be interpreted with caution

健常者における主観的身体垂直の再テスト法による信頼性と加齢による差異

The subjective postural vertical (SPV) reflects gravity perception when the eyes are closed. Changes in the SPV on both the frontal and sagittal planes occur in response to neurological disorders and aging; however, these changes on the diagonal plane are unclear. Here we examined test–retest reliability (n=16) of and age-related changes (n=38) in the SPVon the diagonal plane. Subjects sat on an electrical vertical board (EVB), which was used to measure the SPVon the diagonal plane. An experimenter controlled and moved the EVB seat at a constant speed on the diagonal plane and measured the seat’s tilt using a digital inclinometer when subjects verbally reported that they had reached a true vertical position. Measurement was performed for eight trials, and the mean (tilt direction) and standard deviation (variability) were calculated. To determine test–retest reliability, the same experimenter repeatedly measured the SPV 1 week later. To assess age-related changes, tilt direction and variability were compared between the young (n=20) and elderly (n=18) groups. Test–retest reliability on the right and left diagonal planes was 0.61 or more. Moreover, tilt direction on the right diagonal plane – but not on the left diagonal plane – indicated a significant diagonally backward deviation in the elderly group compared with that in the young group.Variability was significantly higher in the elderly group on both planes. SPV measurement on the diagonal plane was indicated, and age-related changes were identified. Thus, future studies should assess the potential clinical applications of SPV in neurological disorders.首都大学東京学位論文甲第966号副論

Need for Flexible Adjustment of the Treatment Schedule for Aprepitant Administration against Erlotinib-Induced Refractory Pruritus and Skin Rush

Common dermatological side-effects associated with erlotinib, epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), include pruritus and skin rash, which are mediated by substance P, leading to the occasional discontinuation of cancer treatment. Aprepitant is an antagonist of neurokinin-1 receptor, through which substance P activates the pruritogens. Thus, aprepitant is expected to offer a promising option for the treatment of erlotinib-induced pruritus. However, the appropriate treatment schedule for aprepitant administration is under consideration. Here, we discuss the need for flexible adjustment of the treatment schedule for aprepitant administration against erlotinib-induced refractory pruritus and skin rush. A 71-year-old female smoker presented with stage IV EGFR-mutated lung adenocarcinoma. She was started on erlotinib at 150 mg/day. However, by 28 days, severe pruritus and acneiform skin rush resistant to standard therapies occurred, resulting in the interruption of erlotinib therapy. After recovery, she was restarted on erlotinib at 100 mg/day. However, severe pruritus and skin rush developed again within 2 weeks. Then, we started the first 3-day dose of aprepitant (125 mg on day 1, 80 mg on day 3, and 80 mg on day 5) based on the results of the previous prospective study, which showed the success rate of 100% with at least the second dose of aprepitant. However, the pruritus and skin rush exacerbated again within 4 weeks. Therefore, we started the second 3-day dose of aprepitant, but in vain. At this point, as the patient-centered medicine, bi-weekly schedule of the 3-day dose of aprepitant was considered and, then, adopted. As the results, the pruritus and skin rush remained well-controlled throughout the subsequent treatment with erlotinib