Phase I/II study of nivolumab plus lenvatinib for advanced biliary tract cancer (JCOG1808/NCCH1817, SNIPE).

BACKGROUND: Although cisplatin plus gemcitabine and other combinations have improved the survival of advanced biliary tract cancer (BTC), high unmet medical needs remain. This study aimed to assess the efficacy and safety of nivolumab plus lenvatinib in the second-line treatment for advanced BTC. PATIENTS AND METHODS: Nivolumab (240 mg) was administered biweekly. Phase I determined the recommended phase II dose of lenvatinib (20 mg or 14 mg). In phase II, the primary endpoint was the objective response rate (ORR). Secondary endpoints were disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety. The planned sample size was 32 patients with a power of 80%, a one-sided alpha error of 5%, threshold ORR of 10%, and expected ORR of 30%. RESULTS: In phase I, the recommended dose of lenvatinib was determined to be 20 mg in six patients, with one dose-limiting toxicity (myocarditis). In phase II, we enrolled 26 patients. ORR, DCR, and median OS and PFS were 9.4% [90% confidence interval (CI) 2.6% to 22.5%], 53.1% (95% CI 34.7% to 70.9%), and 6.4 months (95% CI 4.9-9.7 months) and 2.5 months (95% CI 1.5-4.1 months), respectively. No response was observed in patients with the usage of antibiotics. The grade 3 or 4 adverse events were hypertension (59.4%) and biliary tract infection (37.5%). Rash (28.1%) and hypothyroidism (21.9%) were observed as immune-mediated adverse events of any grade. CONCLUSIONS: Nivolumab plus lenvatinib had a manageable safety in advanced BTC, but its efficacy in the second-line treatment was limited.

Search for Antideuterons of Cosmic Origin Using the BESS-Polar II Magnetic-Rigidity Spectrometer.

We searched for antideuterons (d[over ¯]'s) in the 4.7×10^{9} cosmic-ray events observed during the BESS-Polar II flight at solar minimum in 2007-2008 but found no candidates. The resulting 95% C.L. upper limit on the d[over ¯] flux is 6.7×10^{-5} (m^{2} s sr GeV/n)^{-1} in an energy range from 0.163 to 1.100 GeV/n. The result has improved by more than a factor of 14 from the upper limit of BESS97, which had a potential comparable to that of BESS-Polar II in the search for cosmic-origin d[over ¯]'s and was conducted during the former solar minimum. The upper limit of d[over ¯] flux from BESS-Polar II is the first result achieving the sensitivity to constrain the latest theoretical predictions.

Whole-genome sequencing analysis of molecular epidemiology and silent transmissions causing meticillin-resistant Staphylococcus aureus bloodstream infections in a university hospital.

BACKGROUND: The emergence of novel genomic-type clones, such as community-associated meticillin-resistant Staphylococcus aureus (MRSA) and livestock-associated MRSA, and their invasion into hospitals have become major concerns worldwide; however, little information is available regarding the prevalence of MRSA in Japan. Whole-genome sequencing (WGS) has been conducted to analyse various pathogens worldwide. Therefore, it is important to establish a genome database of clinical MRSA isolates available in Japan. AIM: A molecular epidemiological analysis of MRSA strains isolated from bloodstream-infected patients in a Japanese university hospital was conducted using WGS and single-nucleotide polymorphism (SNP) analysis. Additionally, through a review of patients' clinical characteristics, the effectiveness of SNP analysis as a tool for detecting silent nosocomial transmission that may be missed by other methods was evaluated in diverse settings and various time points of detection. METHODS: Polymerase-chain-reaction-based staphylococcal cassette chromosome mec (SCCmec) typing was performed using 135 isolates obtained between 2014 and 2018, and WGS was performed using 88 isolates obtained between 2015 and 2017. FINDINGS: SCCmec type II strains, prevalent in 2014, became rare in 2018, whereas the prevalence of SCCmec type IV strains increased from 18.75% to 83.87% of the population, and became the dominant clones. Clonal complex (CC) 5 CC8 and CC1 were detected between 2015 and 2017, with CC1 being dominant. In 88 cases, SNP analyses revealed nosocomial transmissions among 20 patients which involved highly homologous strains. CONCLUSIONS: Routine monitoring of MRSA by whole-genome analysis is effective not only for gaining knowledge regarding molecular epidemiology, but also for detecting silent nosocomial transmission.

Continuous partially hydrolyzed guar gum intake reduces cold-like symptoms: a randomized, placebo-controlled, double-blinded trial in healthy adults.

OBJECTIVE: Partially hydrolyzed guar gum (PHGG), a water-soluble dietary fiber produced by the controlled partial enzymatic hydrolysis of guar gum beans, has various physiological roles. PHGG is expected to influence the immune function and prevent infections. The objective of this study was to examine the effect of continuous ingestion of PHGG for 12 weeks on the development of cold-like symptoms. PATIENTS AND METHODS: A placebo-controlled, double blind, randomized, parallel-group comparative study was conducted. 96 healthy Japanese adults received 5.2 g PHGG or placebo daily for 12 weeks. Cold-like symptoms were assessed based on patient diary, and the levels of short-chain fatty acids (SCFAs) in stool and blood immune markers at baseline and at weeks 6 and 12. RESULTS: The cumulative number of "no symptoms" days for all symptoms was significantly larger in the PHGG than in the placebo group. The result of the analysis by severity of cold-like symptoms also showed significant differences, with the PHGG group having a lower severity of cold-like symptoms. Propionic acid at weeks 6 and 12 and n-butyric acid and total SCFAs at week 12 were significantly higher in the PHGG than in the placebo group. The Interferon-γ level was significantly lower at week 6 in the PHGG than in the placebo group. CONCLUSIONS: PHGG intake may affect immune function and suppress cold-like symptoms through the production of SCFAs in healthy adults.

Assessment of Heating on Titanium Alloy Cerebral Aneurysm Clips during 7T MRI.

BACKGROUND AND PURPOSE: Patients with cerebral aneurysms often undergo MR imaging after microsurgical clipping. Ultra-high-field MR imaging at 7T may provide high diagnostic capability in such clinical situations. However, titanium alloy clips have safety issues such as adverse interactions with static magnetic fields and radiofrequency-induced heating during 7T MR imaging. The purpose of this study was to quantitatively assess temperature increases on various types of titanium alloy aneurysm clips during 7T MR imaging. MATERIALS AND METHODS: Five types of titanium alloy aneurysm clips were tested, including combinations of short, long, straight, angled, and fenestrated types. Each clip was set in a phantom filled with gelled saline mixed with polyacrylic acid and underwent 7T MR imaging with 3D T1WI with a spoiled gradient recalled acquisition in the steady-state technique. Temperature was chronologically measured at the tips of the clip blade and head, angled part of the clip, and 5 mm from the tip of the clip head using MR imaging-compatible fiber-optic thermometers. RESULTS: Temperature increases at all locations for right-angled and short straight clips were <1°C. Temperature increases at the angled part for the 45° angled clip and the tip of the clip head for the straight fenestrated clip were >1°C. Temperature increases at all locations for the long straight clip were >2°C. CONCLUSIONS: Temperature increases on the right-angled and short straight clips remained below the regulatory limit during 7T MR imaging, but temperature increases on the 45° angled, straight fenestrated, and long straight clips exceeded this limit.

Characteristic endoscopic findings of gastrointestinal malignant lymphomas other than mucosa-associated lymphoid tissue lymphoma.

Background and study aims: The gastrointestinal (GI) tract is the most common site of extra-nodal involvement for non-Hodgkin's lymphoma (NHL). The features of GI NHLs remain unclear. The aim of this study was to clarify endoscopic characteristics of GI NHLs. Patients and methods: We retrospectively analyzed the morphological characteristics of 63 GI malignant lymphomas other than mucosa-associated lymphoid tissue lymphoma. Lesions were diagnosed between 2005 and 2020. Macroscopic findings were classified into five subtypes: superficial (S); protruding without ulcer (P); protruding with ulcer (PU); fungating (F); and multiple nodules (MN). Results: Thirty-one lesions in the stomach were classified as S type in 3 cases (9.6%), P type in 6 (19%), PU type in 13 (42%), and F type in 9 (29%). In the stomach, the ulcerated phenotype was more frequent for diffuse large B-cell lymphoma (DLBCL) (89.5%) than for other histological types (41.7%; P = 0.01). In the intestine, 23 tumors were classified as S type in 4 cases (17%), P type in 1 (4%), PU type in 6 (26%), F type in 1 (4%), and MN in 11 (48%). Eleven of the 14 cases (78.6%) of intestinal follicular lymphoma lesions showed MN type. In the colon, eight tumors were classified as S type in 2 cases (25%), P type in 2 (25%), PU type in 1 (13%), and F type in 3 (38%). Conclusion: We have clarified the endoscopic features of GI NHL using macroscopic classifications. The ulcerated phenotype was the most frequent endoscopic finding for DLBCL.

Is nestin a diagnostic marker for combined hepatocellular-cholangiocarcinoma?

BACKGROUND AND AIMS: The type IV intermediate filament, nestin, may be a candidate diagnostic marker for combined hepatocellular-cholangiocarcinoma (cHCC-CCA). Therefore, the significance of nestin as a diagnostic marker for cHCC-CCA categorized by the World Health Organization (WHO) 2019 classification and its relationship with clinicopathological features were examined in the present study. METHODS AND RESULTS: Nestin expression was immunohistochemically assessed in the liver sections from 75 patients with cHCC-CCA, 22 with small duct-type intrahepatic cholangiocarcinoma (iCCA), 20 with large duct-type iCCA and 35 with hepatocellular carcinoma (HCC). Nestin expression and its relationship with clinicopathological features and genetic alterations were investigated in cHCC-CCA. Nestin expression was detected in significantly more patients with cHCC-CCA (66.7%) than in those with large duct-type iCCA (5%) (P < 0.01), HCC (2.9%) (P < 0.01) and small duct-type iCCA (40.9%) (P < 0.05). Nestin expression was partly associated with neural cell adhesion molecule (NCAM) and vimentin expression. Nestin expression was also observed in significantly more patients with small duct-type iCCA than in those with large duct-type iCCA and HCC (P < 0.01). Nestin-positive cHCC-CCA was characterized by a smaller tumour size, the more frequent presence of cholangiolocellular carcinoma (CLC) components, a higher rate of p53 overexpression and a higher rate of multiple genetic alterations (P < 0.05). Furthermore, p53 overexpression was associated with a higher histological grade and multiple genetic alterations (P < 0.05) in nestin-positive cHCC-CCA. CONCLUSION: Nestin may be a useful diagnostic marker for a specific subgroup of cHCC-CCA and small duct-type iCCA associated with CLC components, p53 mutations and multiple genetic alterations, which are related to stemness and multipotent differentiation.

Bayesian inference of ion velocity distribution function from laser-induced fluorescence spectra.

The velocity distribution function is a statistical description that connects particle kinetics and macroscopic parameters in many-body systems. Laser-induced fluorescence (LIF) spectroscopy is utilized to measure the local velocity distribution function in spatially inhomogeneous plasmas. However, the analytic form of such a function for the system of interest is not always clear under the intricate factors in non-equilibrium states. Here, we propose a novel approach to select the valid form of the velocity distribution function based on Bayesian statistics. We formulate the Bayesian inference of ion velocity distribution function and apply it to LIF spectra locally observed at several positions in a linear magnetized plasma. We demonstrate evaluating the spatial inhomogeneity by verifying each analytic form of the local velocity distribution function. Our approach is widely applicable to experimentally establish the velocity distribution function in plasmas and fluids, including gases and liquids.

Diagnostic Accuracy of Screening Arterial Spin-Labeling MRI Using Hadamard Encoding for the Detection of Reduced CBF in Adult Patients with Ischemic Moyamoya Disease.

BACKGROUND AND PURPOSE: Adult patients with ischemic Moyamoya disease are advised to undergo selective revascularization surgery based on cerebral hemodynamics. The purpose of this study was to determine the diagnostic accuracy of arterial spin-labeling MR imaging using Hadamard-encoded multiple postlabeling delays for the detection of reduced CBF in such patients. MATERIALS AND METHODS: Thirty-seven patients underwent brain perfusion SPECT and pseudocontinuous arterial spin-labeling MR imaging using standard postlabeling delay (1525 ms) and Hadamard-encoded multiple postlabeling delays. For Hadamard-encoded multiple postlabeling delays, based on data obtained from the 7 sub-boluses with combinations of different labeling durations and postlabeling delays, CBF corrected by the arterial transit time was calculated on a voxel-by-voxel basis. Using a 3D stereotaxic template, we automatically placed ROIs in the ipsilateral cerebellar hemisphere and 5 MCA territories in the symptomatic cerebral hemisphere; then, the ratio of the MCA to cerebellar ROI was calculated. RESULTS: The area under the receiver operating characteristic curve for detecting reduced SPECT-CBF ratios (<0.686) was significantly greater for the Hadamard-encoded multiple postlabeling delays-CBF ratios (0.885) than for the standard postlabeling delay-CBF ratios (0.786) (P = .001). The sensitivity and negative predictive value for the Hadamard-encoded multiple postlabeling delays-CBF ratios were 100% (95% confidence interval, 100%-100%) and significantly higher than the sensitivity (95% CI, 44%-80%) and negative predictive value (95% CI, 88%-97%) for the standard postlabeling delay-CBF ratio, respectively. CONCLUSIONS: ASL MR imaging using Hadamard-encoded multiple postlabeling delays may be applicable as a screening tool because it can detect reduced CBF on brain perfusion SPECT with 100% sensitivity and a 100% negative predictive value in adult patients with ischemic Moyamoya disease.

Study of the K_{L}→π

The rare decay K_{L}→π^{0}νν[over ¯] was studied with the dataset taken at the J-PARC KOTO experiment in 2016, 2017, and 2018. With a single event sensitivity of (7.20±0.05_{stat}±0.66_{syst})×10^{-10}, three candidate events were observed in the signal region. After unveiling them, contaminations from K^{±} and scattered K_{L} decays were studied, and the total number of background events was estimated to be 1.22±0.26. We conclude that the number of observed events is statistically consistent with the background expectation. For this dataset, we set an upper limit of 4.9×10^{-9} on the branching fraction of K_{L}→π^{0}νν[over ¯] at the 90% confidence level.

Quality of life of Japanese elderly oral cancer patients during the perioperative period.

Japan's aging society has an increasing incidence of oral cancer. This study investigated perioperative changes in quality of life (QoL) among 172 oral cancer patients (elderly ≥75 years vs non-elderly <75 years), pre-treatment, at treatment completion, and at 1, 3, and 6 months post-treatment, using the following Functional Assessment of Cancer Therapy - Head and Neck (FACT-H&N) subscales: physical well-being (PWB), social/family well-being (SWB), emotional well-being (EWB), functional well-being (FWB), additional head- and neck-specific concerns (H&N). SWB (P=0.026), H&N (P=0.024), and total FACT-H&N (P=0.009) scores were significantly lower in the elderly group than in the non-elderly group at 6 months post-treatment, especially for mastication items (H&N1, P=0.047; H&N11, P=0.004), but not for swallowing items (H&N5 and H&N7, both P> 0.05). PWB (P= 0.004), EWB (P< 0.001), and FWB (P= 0.022) scores in the non-elderly group were significantly higher at 6 months post-treatment than before treatment. In the elderly group, no subscale showed a better score at 6 months post-treatment. Post-treatment QoL in elderly oral cancer patients did not improve, unlike in non-elderly patients.

Detection of large-scale X-ray bubbles in the Milky Way halo.

The halo of the Milky Way provides a laboratory to study the properties of the shocked hot gas that is predicted by models of galaxy formation. There is observational evidence of energy injection into the halo from past activity in the nucleus of the Milky Way1-4; however, the origin of this energy (star formation or supermassive-black-hole activity) is uncertain, and the causal connection between nuclear structures and large-scale features has not been established unequivocally. Here we report soft-X-ray-emitting bubbles that extend approximately 14 kiloparsecs above and below the Galactic centre and include a structure in the southern sky analogous to the North Polar Spur. The sharp boundaries of these bubbles trace collisionless and non-radiative shocks, and corroborate the idea that the bubbles are not a remnant of a local supernova5 but part of a vast Galaxy-scale structure closely related to features seen in γ-rays6. Large energy injections from the Galactic centre7 are the most likely cause of both the γ-ray and X-ray bubbles. The latter have an estimated energy of around 1056 erg, which is sufficient to perturb the structure, energy content and chemical enrichment of the circumgalactic medium of the Milky Way.

New MRI Findings in Fukuyama Congenital Muscular Dystrophy: Brain Stem and Venous System Anomalies.

BACKGROUND AND PURPOSE: Leptomeningeal glioneuronal heterotopia of the brain stem and cerebral migration abnormality were pathologically reported in Fukuyama congenital muscular dystrophy, but the radiologic assessments of the brain stem and cerebral venous system (which may be involved in the development of the anomaly) were insufficient. Here, we evaluated the brain stem and cerebral veins on MR imaging in patients with Fukuyama congenital muscular dystrophy. MATERIALS AND METHODS: We retrospectively reviewed the MR imaging findings of 27 patients with Fukuyama congenital muscular dystrophy. We visually assessed the hypoplasia, superficial structures, and signal intensity of the brain stem on T2WI, FLAIR, and double inversion recovery images and the cerebral, superficial, and deep veins with and without hemorrhage on T2WI and SWI. RESULTS: Brain stem fluffy structures were seen in 96.3% of the cases on T2WI. Superficial high signal intensity on T2WI and FLAIR images was seen in 96.3% and 92.6%, respectively. Abnormally located superficial vessels beneath the cortex were seen in 11.1% on T2WI. Hypoplasia of the superficial cerebral veins was noted in all patients who underwent SWI. Dilated and tortuous subependymal veins were seen in 40.0% on SWI. Hemorrhages were seen in 11.1% on T2WI and in 60.0% on SWI. CONCLUSIONS: Superficial brain stem structural and signal abnormalities would be useful MR imaging findings to diagnose Fukuyama congenital muscular dystrophy as well as venous system abnormalities. Clinicians must keep in mind that this disease has a high risk of hemorrhage.

Acetazolamide-Loaded Dynamic 7T MR Quantitative Susceptibility Mapping in Major Cerebral Artery Steno-Occlusive Disease: Comparison with PET.

BACKGROUND AND PURPOSE: Dynamic changes in cerebrovascular reactivity after acetazolamide administration vary markedly among patients with major cerebral arterial steno-occlusive disease. MR quantitative susceptibility mapping can dynamically quantify the cerebral magnetic susceptibility. The purpose of this study was to determine whether dynamic changes in susceptibility after administration of acetazolamide on 7T quantitative susceptibility mapping are associated with pre-existing states of CBV and the cerebral metabolic rate of oxygen in the cerebral hemispheres with major cerebral arterial steno-occlusive disease. MATERIALS AND METHODS: Sixty-five patients underwent 7T MR imaging at baseline and at 5, 10, 15, and 20 minutes after acetazolamide administration. Differences between the susceptibility of venous structures and surrounding brain tissue were calculated in the quantitative susceptibility mapping images. Susceptibility differences at 5, 10, 15, and 20 minutes after acetazolamide administration relative to baseline were calculated in 97 cerebral hemispheres with major cerebral arterial steno-occlusive disease. CBV and the cerebral metabolic rate of oxygen were also calculated using 15O-gas PET in the resting state. RESULTS: Dynamic changes of susceptibility after acetazolamide administration were classified into 3 patterns: abnormally increasing 5 or 10 minutes after acetazolamide administration; abnormally decreasing within 20 minutes after acetazolamide administration; and remaining unchanged after acetazolamide administration. CBV was significantly greater in the first pattern than in the latter 2. The cerebral metabolic rate of oxygen differed significantly in descending order from the first to middle to last pattern. CONCLUSIONS: Dynamic changes of susceptibility after acetazolamide administration on 7T MR quantitative susceptibility mapping are associated with pre-existing states of CBV and the cerebral metabolic rate of oxygen in major cerebral arterial steno-occlusive disease.

Isotope effects in self-organization of internal transport barrier and concomitant edge confinement degradation in steady-state LHD plasmas.

The isotope effect, which has been a long-standing mystery in the turbulent magnetically confined plasmas, is the phenomena that the plasma generated with heavier hydrogen isotope show a mitigated transport. This is on the contrary to what is predicted with the simple scaling theory, in which the heavier ions easily diffuse because of its larger gyro-radius. Thanks to the newly developed analysis method and a comprehensive parameter scan experiment in the steady-state plasmas in the Large Helical Device (LHD), the isotope effect was clearly observed in the self-organized internal transport barrier (ITB) structure for the first time. Comparing the ITB intensity in deuterium (D) and hydrogen (H) plasmas, two distinct hydrogen isotope effects are found: stronger ITB is formed in D plasmas and a significant edge confinement degradation accompanied by the ITB formation emerges in H plasmas. This observation sheds light on a new aspect of the turbulent plasmas regarding how the basic properties of the fluid material affect the turbulent structure formation in the open-system.

APPLICATION OF THE FOREST SHIELDING FACTOR TO THE MAXIMUM-LIKELIHOOD EXPECTATION MAXIMIZATION METHOD FOR AIRBORNE RADIATION MONITORING.

The maximum-likelihood expectation maximization (ML-EM) method is expected to improve the accuracy of airborne radiation monitoring using an unmanned aerial vehicle. The accuracy of the ML-EM method depends on various parameters, including detector efficiency, attenuation factor, and shielding factor. In this study, we evaluate the shielding factor of trees based on several field radiation measurements. From the actual measurement, the shielding factors were well correlated with the heights of the trees. The evaluated shielding factors were applied to the ML-EM method in conjunction with the measured data obtained from above the Fukushima forest. Compared with the conventional methods used for calculating the dose rate, the proposed method is found to be more reliable.

Radiologic and Pathologic Features of the Transmantle Sign in Focal Cortical Dysplasia: The T1 Signal Is Useful for Differentiating Subtypes.

BACKGROUND AND PURPOSE: The transmantle sign is a characteristic MR imaging finding often seen in focal cortical dysplasia type IIb. The transmantle sign is typically hyperintense on T2WI and FLAIR and hypointense on T1WI. However, in some cases, it shows T1 high signal. We evaluated the imaging and pathologic findings to identify the causes of the T1 high signal in the transmantle sign. MATERIALS AND METHODS: We retrospectively reviewed the preoperative imaging data of 141 consecutive patients with histologically proved focal cortical dysplasia. We selected 25 patients with focal cortical dysplasia with the transmantle sign and divided them into groups based on the pathologic focal cortical dysplasia subtype and T1 signal of the transmantle sign. We evaluated the clinical, radiologic, and pathologic findings, including the number of balloon cells and dysmorphic neurons and the severity of gliosis or calcifications and compared them among the groups. RESULTS: Nine of the 25 patients had a T1-high-signal transmantle sign; the other 16 patients did not. All 9 patients with a T1-high-signal transmantle sign were diagnosed as type IIb (group A). Of the 16 patients with no T1-high-signal transmantle sign, 13 were diagnosed as having type IIb (group B), and the other 3 patients, as type IIa (group C). The number of balloon cells was significantly higher in group A than in the other groups, but there were no differences regarding dysmorphic neurons, the severity of gliosis, or calcifications. CONCLUSIONS: Approximately 6% (9/141) of this patient series had a T1-high-signal transmantle sign, and all were type IIb. The signal may reflect a rich density of balloon cells. This finding could support the differentiation of subtypes, especially type IIb.

Search for K_{L}→π

A search for the rare decay K_{L}→π^{0}νν[over ¯] was performed. With the data collected in 2015, corresponding to 2.2×10^{19} protons on target, a single event sensitivity of (1.30±0.01_{stat}±0.14_{syst})×10^{-9} was achieved and no candidate events were observed. We set an upper limit of 3.0×10^{-9} for the branching fraction of K_{L}→π^{0}νν[over ¯] at the 90% confidence level (C.L.), which improved the previous limit by almost an order of magnitude. An upper limit for K_{L}→π^{0}X^{0} was also set as 2.4×10^{-9} at the 90% C.L., where X^{0} is an invisible boson with a mass of 135 MeV/c^{2}.

Influence of loading rate and limb position on patellar tendon mechanical properties in vivo.

BACKGROUND: The aims of this study were to clarify the changes of patellar tendon length during isometric knee joint extension and the double leg squat position using ultrasonography. METHODS: The left legs of 17 healthy adults were investigated. Isometric knee extension motion was performed at three positions of knee flexion 30° (knee 30°), knee flexion 60° (knee 60°), knee flexion 90° (knee 90°), and at each limb position, 0% (0% peak torque (PT)), 40% (40% PT), 50% (50% PT), and 60% (60% PT) of the maximum knee joint extension torque were executed at random. Both double leg squat motions were randomly performed in three positions: hip flexion 30°, knee flexion 30°, ankle dorsiflexion 10° (squat 30°); hip joint flexion 60°, knee joint flexion 60°, ankle dorsiflexion 20° (squat 60°); and hip joint flexion 90°, knee joint flexion 90°, ankle dorsiflexion 30° (squat 90°). Ultrasonography was used to measure patellar tendon length. FINDINGS: There were no significant changes in patellar tendon length and strain between knee flexion angles of 30°, 60°, and 90° in isometric knee joint extension and the double leg squat limb position. INTERPRETATION: The loading rate and limb position do not appear to affect the length and strain of the patellar tendon.

Morphological and molecular data for species of Lecithaster Lühe, 1901 and Hysterolecithoides Yamaguti, 1934 (Digenea: Lecithasteridae) from fish of East Asia and phylogenetic relationships within the Hemiuroidea Looss, 1899.

Four representatives of the genus Lecithaster and one representative of the genus Hysterolecithoides were found during investigation of the trematode fauna of fish species in Vietnamese, Japanese and eastern coastal waters of the Russian Far East. Based on morphometric data, adult trematodes from Vietnamese Strongylura strongylura and Russian Acanthogobius flavimanus were identified as Lecithaster confusus, trematodes from Vietnamese Hemirhamphus marginatus as L. sayori and from osmerid fishes as L. salmonis. Further, a single specimen of Lecithaster sp. and representatives of Hysterolecithoides epinepheli were found in Vietnamese Siganus fuscescens. Morphological and molecular data, including 18S ribosomal DNA (rDNA) V4 fragment, 28S rDNA D1-D3 fragment, internal transcribed spacers (ITS) and a mitochondrial COI gene fragment were analysed for Lecithaster spp. The results revealed that L. sayori and L. salmonis are not synonyms of L. stellatus and L. gibbosus, respectively, but that Hysterolecithoides frontilatus and H. guangdongensis are junior synonyms of H. epinepheli. The 28S-rDNA-based phylogenetic tree of Hemiuroidea showed a distinct position for the genus Lecithaster with internal differentiation into three subclades, including L. confusus, L. sayori and Lecithaster sp. within the first subclade, L. mugilis and L. sudzuhensis within the second subclade and L. salmonis and L. gibbosus within the third subclade. Bayesian phylogenetic reconstructions of Hemiuroidea showed four clades for members of Hemiuridae and Lecithasteridae. The first clade consisted of Hemiuridae representatives and the second clade represented the genus Lecithaster. The third clade included genera Aponurus and Lecithophyllum (Lecithasteridae) and the fourth clade combined members of lecithasterid Quadrifoliovariinae and Hysterolecithinae and hemiurid Opisthadeninae and Bunocotylidae with high statistical support.