Haptic feedback intervention decreases the spatial margin when older adults walk through a narrow space.

BACKGROUND: The ability to avoid obstacles efficiently and safely is important for older adults to prevent injuries from tripping and falling. It is important to find an optimal spatial margin between the body and an obstacle considering both safety and efficiency. One side of finding the optimal margin is to decrease the margin in terms of motor efficiency. In this study, we tested whether fingertip-contact intervention to obtain haptic feedback information to perceive the relationship between body and the environment could immediately improve spatial perception and collision avoidance behavior (an instantaneous effect). METHODS: Twenty-seven older adults (12 males and 15 females) participated in the experiment. In the intervention of the fingertip-contact group, they lightly touched the edge of a door with both fingertips while walking. The test task before and after the intervention involved grasping a horizontal bar and passing through a narrow opening. As dependent variables, we measured the spatial margin and the collision rate. RESULTS: The fingertip-contact group showed a significant decrease in the spatial margin after the intervention. On the other hand, there was no significant improvement in the collision rate after the intervention but rather a decrease only in the control group. CONCLUSION: The results obtained in this study indicate that touching obstacles with the fingertips had an instantaneous effect, leading to efficient movement learning, although a possible side effect of an increased collision rated was also found. The proposed intervention might promote an efficiency-based strategy due to learning the spatial relationship between the body and the environment, and it may suppress the excessive avoidance of older adults.

High-power laser experiment on developing supercritical shock propagating in homogeneously magnetized plasma of ambient gas origin.

A developing supercritical collisionless shock propagating in a homogeneously magnetized plasma of ambient gas origin having higher uniformity than the previous experiments is formed by using high-power laser experiment. The ambient plasma is not contaminated by the plasma produced in the early time after the laser shot. While the observed developing shock does not have stationary downstream structure, it possesses some characteristics of a magnetized supercritical shock, which are supported by a one-dimensional full particle-in-cell simulation taking the effect of finite time of laser-target interaction into account.

High-power laser experiment forming a supercritical collisionless shock in a magnetized uniform plasma at rest.

We present an experimental method to generate quasiperpendicular supercritical magnetized collisionless shocks. In our experiment, ambient nitrogen (N) plasma is at rest and well magnetized, and it has uniform mass density. The plasma is pushed by laser-driven ablation aluminum (Al) plasma. Streaked optical pyrometry and spatially resolved laser collective Thomson scattering clarify structures of plasma density and temperatures, which are compared with one-dimensional particle-in-cell simulations. It is indicated that just after the laser irradiation, the Al plasma is magnetized by a self-generated Biermann battery field, and the plasma slaps the incident N plasma. The compressed external field in the N plasma reflects N ions, leading to counterstreaming magnetized N flows. Namely, we identify the edge of the reflected N ions. Such interacting plasmas form a magnetized collisionless shock.

A 16-parts-per-trillion measurement of the antiproton-to-proton charge-mass ratio.

The standard model of particle physics is both incredibly successful and glaringly incomplete. Among the questions left open is the striking imbalance of matter and antimatter in the observable universe1, which inspires experiments to compare the fundamental properties of matter/antimatter conjugates with high precision2-5. Our experiments deal with direct investigations of the fundamental properties of protons and antiprotons, performing spectroscopy in advanced cryogenic Penning trap systems6. For instance, we previously compared the proton/antiproton magnetic moments with 1.5 parts per billion fractional precision7,8, which improved upon previous best measurements9 by a factor of greater than 3,000. Here we report on a new comparison of the proton/antiproton charge-to-mass ratios with a fractional uncertainty of 16 parts per trillion. Our result is based on the combination of four independent long-term studies, recorded in a total time span of 1.5 years. We use different measurement methods and experimental set-ups incorporating different systematic effects. The final result, [Formula: see text], is consistent with the fundamental charge-parity-time reversal invariance, and improves the precision of our previous best measurement6 by a factor of 4.3. The measurement tests the standard model at an energy scale of 1.96 × 10-27 gigaelectronvolts (confidence level 0.68), and improves ten coefficients of the standard model extension10. Our cyclotron clock study also constrains hypothetical interactions mediating violations of the clock weak equivalence principle (WEPcc) for antimatter to less than 1.8 × 10-7, and enables the first differential test of the WEPcc using antiprotons11. From this interpretation we constrain the differential WEPcc-violating coefficient to less than 0.030.

Associations of PD-L1, PD-L2, and HLA class I expression with responses to immunotherapy in patients with advanced sarcoma: post hoc analysis of a phase 1/2 trial

Background Although immunotherapy is thought to be a promising cancer treatment, most patients do not respond to immunotherapy. In this post hoc analysis of a phase 1/2 study, associations of programmed death ligand 1 (PD-L1), PD-L2, and HLA class I expressions with responses to dendritic cells (DCs)-based immunotherapy were investigated in patients with advanced sarcoma. Methods This study enrolled 35 patients with metastatic and/or recurrent sarcomas who underwent DC-based immunotherapy. The associations of PD-L1, PD-L2, and HLA class I expressions in tumor specimens, which were resected before immunotherapy, with immune responses (increases of IFN-γ and IL-12) and oncological outcomes were evaluated. Results Patients who were PD-L2 (+) showed lower increases of IFN-γ and IL-12 after DC-based immunotherapy than patients who were PD-L2 (−). The disease control (partial response or stable disease) rates of patients who were PD-L1 (+) and PD-L1 (−) were 0% and 22%, respectively. Disease control rates of patients who were PD-L2 (+) and PD-L2 (−) were 13% and 22%, respectively. Patients who were PD-L1 (+) tumors had significantly poorer overall survival compared with patients who were PD-L1 (−). No associations of HLA class I expression with the immune response or oncological outcomes were observed. Conclusions This study suggests that PD-L1 and PD-L2 are promising biomarkers of DC-based immunotherapy, and that addition of immune checkpoint inhibitors to DC-based immunotherapy may improve the outcomes of DC-based immunotherapy (AU)

Test of Lepton-Flavor Universality in B→K

We present a measurement of R_{K^{*}}, the branching fraction ratio B(B→K^{*}µ^{+}µ^{-})/B(B→K^{*}e^{+}e^{-}), for both charged and neutral B mesons. The ratio for the charged case R_{K^{*+}} is the first measurement ever performed. In addition, we report absolute branching fractions for the individual modes in bins of the squared dilepton invariant mass q^{2}. The analysis is based on a data sample of 711 fb^{-1}, containing 772×10^{6} BB[over ¯] events, recorded at the ϒ(4S) resonance with the Belle detector at the KEKB asymmetric-energy e^{+}e^{-} collider. The obtained results are consistent with standard model expectations.

Associations of PD-L1, PD-L2, and HLA class I expression with responses to immunotherapy in patients with advanced sarcoma: post hoc analysis of a phase 1/2 trial.

BACKGROUND: Although immunotherapy is thought to be a promising cancer treatment, most patients do not respond to immunotherapy. In this post hoc analysis of a phase 1/2 study, associations of programmed death ligand 1 (PD-L1), PD-L2, and HLA class I expressions with responses to dendritic cells (DCs)-based immunotherapy were investigated in patients with advanced sarcoma. METHODS: This study enrolled 35 patients with metastatic and/or recurrent sarcomas who underwent DC-based immunotherapy. The associations of PD-L1, PD-L2, and HLA class I expressions in tumor specimens, which were resected before immunotherapy, with immune responses (increases of IFN-γ and IL-12) and oncological outcomes were evaluated. RESULTS: Patients who were PD-L2 (+) showed lower increases of IFN-γ and IL-12 after DC-based immunotherapy than patients who were PD-L2 (-). The disease control (partial response or stable disease) rates of patients who were PD-L1 (+) and PD-L1 (-) were 0% and 22%, respectively. Disease control rates of patients who were PD-L2 (+) and PD-L2 (-) were 13% and 22%, respectively. Patients who were PD-L1 (+) tumors had significantly poorer overall survival compared with patients who were PD-L1 (-). No associations of HLA class I expression with the immune response or oncological outcomes were observed. CONCLUSIONS: This study suggests that PD-L1 and PD-L2 are promising biomarkers of DC-based immunotherapy, and that addition of immune checkpoint inhibitors to DC-based immunotherapy may improve the outcomes of DC-based immunotherapy.

Relationship between environmental radiation and radioactivity and childhood thyroid cancer found in Fukushima health management survey.

Environmental radioactive contamination caused by the Fukushima Dai-ichi Nuclear Power Plant accident has aroused great concern regarding a possible increase in the incidence of childhood thyroid cancer. The ultrasound examinations were conducted immediately after the accident as part of the Fukushima Health Management Survey (FHMS), which is divided into the preliminary baseline survey (PBLS) and the full-scale survey (FSS). Some of their outcomes are reported regularly and made available to the public. We have detailed measurements of the air-dose rates and radioactive elements in soil in many places all over the Fukushima prefecture. To study the dose-response relationship, we begin with the assumption that the external and internal doses are correlated with the air-dose rate and the amount of 131I in soil, respectively. We then investigate the relationship between these estimated doses and the PBLS and FSS thyroid cancer cases. Our analysis shows that the dose-response curve with the FSS data clearly differs from that with the PBLS data. Finally, we consider the potential mitigating effects of evacuation from highly contaminated areas in both external and internal exposure scenarios.

Surface Proton Conduction of Sm-Doped CeO2-δ Thin Film Preferentially Grown on Al2O3 (0001).

Sm-doped CeO2-δ (Ce0.9Sm0.1O2-δ; SDC) thin films were prepared on Al2O3 (0001) substrates by radio frequency magnetron sputtering. The prepared thin films were preferentially grown along the [111] direction, with the spacing of the (111) plane (d111) expanded by 2.6% to compensate for a lattice mismatch against the substrate. The wet-annealed SDC thin film, with the reduced d111 value, exhibited surface protonic conduction in the low-temperature region below 100 °C. The O1s photoemission spectrum exhibits H2O and OH- peaks on the SDC surface. These results indicate the presence of physisorbed water layers and the generation of protons on the SDC (111) surface with oxygen vacancies. The protons generated on the SDC surface were conducted through a physisorbed water layer by the Grotthuss mechanism.

Modulation of methotrexate-induced intestinal mucosal injury by dietary factors.

Methotrexate (MTX)-induced intestinal mucosal injury in animals has been studied to understand how MTX can cause gastrointestinal disorders, but the pathogenesis of gastrointestinal disorders is still uncertain. We have attempted to reveal how dietary factors influence intestinal toxicity due to MTX. Mice were fed normal chow (NC) or a high-fat high-sucrose diet (HFHSD) before oral administration of MTX. While MTX significantly decreased the survival rates of mice fed HFHSD, the intestinal epithelial injury was detected. MTX excretion in the feces of mice fed HFHSD was reduced. Change of diets between NC and HFHSD influences the survival. The survival rates of the mice fed a high-sucrose diet or control diet were higher than those fed HFHSD. Higher survival rates were observed in mice fed a high-fat high-sucrose diet modified (HFHSD-M) in which casein was replaced by soybean-derived proteins. The survival rates of mice treated with vancomycin were lower than those administered neomycin. Microbiome and metabolome analyses on feces suggest a similarity of the intestinal environments of mice fed NC and HFHSD-M. HFHSD may modify MTX-induced toxicity in intestinal epithelia on account of an altered MTX distribution as a result of change in the intestinal environment.

Direct limits on the interaction of antiprotons with axion-like dark matter.

Astrophysical observations indicate that there is roughly five times more dark matter in the Universe than ordinary baryonic matter1, and an even larger amount of the Universe's energy content is attributed to dark energy2. However, the microscopic properties of these dark components remain unknown. Moreover, even ordinary matter-which accounts for five per cent of the energy density of the Universe-has yet to be understood, given that the standard model of particle physics lacks any consistent explanation for the predominance of matter over antimatter3. Here we present a direct search for interactions of antimatter with dark matter and place direct constraints on the interaction of ultralight axion-like particles (dark-matter candidates) with antiprotons. If antiprotons have a stronger coupling to these particles than protons do, such a matter-antimatter asymmetric coupling could provide a link between dark matter and the baryon asymmetry in the Universe. We analyse spin-flip resonance data in the frequency domain acquired with a single antiproton in a Penning trap4 to search for spin-precession effects from ultralight axions, which have a characteristic frequency governed by the mass of the underlying particle. Our analysis constrains the axion-antiproton interaction parameter to values greater than 0.1 to 0.6 gigaelectronvolts in the mass range from 2 × 10-23 to 4 × 10-17 electronvolts, improving the sensitivity by up to five orders of magnitude compared with astrophysical antiproton bounds. In addition, we derive limits on six combinations of previously unconstrained Lorentz- and CPT-violating terms of the non-minimal standard model extension5.

Size for gestational age at birth according to offspring sex and gestational weight gain in underweight women.

Although maternal pre-pregnancy body mass index (BMI) and gestational weight gain (GWG) are related to fetal growth, there is a paucity of data regarding how offspring sex affects the relationship between maternal BMI in underweight mothers (pre-pregnancy BMI <18.5 kg/m2) and size for gestational age at birth. The aim of this study was to investigate the effect of offspring sex on the relationships among maternal pre-pregnancy BMI, GWG and size for gestational age at birth in Japanese underweight mothers. Records of women with full-term pregnancies who underwent perinatal care at Kawasaki Municipal Hospital (Kawasaki, Japan) between January 2013 and December 2017 were retrospectively reviewed. The study cohort included underweight (n=566) and normal-weight women (18.5 kg/m2⩽pre-pregnancy BMI<25 kg/m2; n=2671). The incidence of small for gestational age (SGA) births in the underweight group was significantly higher than that in the normal-weight group (P<0.01). Additionally, SGA incidence in the underweight group was significantly higher than that in the normal-weight group (P<0.01) in female, but not male (P=0.30) neonates. In the women with female neonates, pre-pregnancy underweight was associated with a significantly increased probability of SGA (odds ratio [OR]: 1.80; P<0.01), but inadequate GWG was not (OR: 1.38; P=0.11). In contrast, in women with male neonates, inadequate GWG was associated with a significantly increased probability of SGA (OR: 1.53; P=0.03), but not with pre-pregnancy underweight (OR: 1.30; P=0.10). In conclusion, the present results suggest that pre-pregnancy underweight is associated with SGA in female offspring but not in male offspring.

Measurement of Ultralow Heating Rates of a Single Antiproton in a Cryogenic Penning Trap.

We report on the first detailed study of motional heating in a cryogenic Penning trap using a single antiproton. Employing the continuous Stern-Gerlach effect we observe cyclotron quantum transition rates of 6(1) quanta/h and an electric-field noise spectral density below 7.5(3.4)×10^{-20} V^{2} m^{-2} Hz^{-1}, which corresponds to a scaled noise spectral density below 8.8(4.0)×10^{-12} V^{2} m^{-2}, results which are more than 2 orders of magnitude smaller than those reported by other ion-trap experiments.

Long-term patient survival after the surgical treatment of bone and soft-tissue metastases from renal cell carcinoma.

Aims: The aims of this study were to evaluate the long-term outcome of surgery for bone or soft-tissue metastases from renal cell carcinoma (RCC) and to determine factors that affect prognosis. Patients and Methods: Between 1993 and 2014, 58 patients underwent surgery for bone or soft-tissue metastases from RCC at our hospital. There were 46 men and 12 women with a mean age of 60 years (25 to 84). The mean follow-up period was 52 months (1 to 257). The surgical sites included the spine (33 patients), appendicular skeleton (ten patients), pelvis (eight patients), thorax (four patients), and soft tissue (three patients). The surgical procedures were en bloc metastasectomy in 46 patients (including 33 patients of total en bloc spondylectomy (TES)) and intralesional curettage in 12 patients. These patients were retrospectively evaluated for factors associated with prognosis. Results: The one-, three-, five-, ten-, and 15-year overall survival (OS) rates were 89%, 75%, 62%, 48%, and 25%, respectively. The median survival time (MST) was 127 months for en bloc metastasectomy and 54 months for intralesional curettage and bone grafting. The median survival time was 127 months for the spine, 140 months for lesions of the appendicular skeleton, and 54 months for the pelvis. Multivariate analysis showed that non-clear cell type RCC and metastases to more than two sites were independent risk factors for a poor prognosis. Conclusion: Patients with bone or soft-tissue metastases from a RCC have a reasonable prognosis, making surgical resection a viable option even in patients in whom the metastases are advanced. Cite this article: Bone Joint J 2018;100-B:1241-8.

A parts-per-billion measurement of the antiproton magnetic moment.

Precise comparisons of the fundamental properties of matter-antimatter conjugates provide sensitive tests of charge-parity-time (CPT) invariance, which is an important symmetry that rests on basic assumptions of the standard model of particle physics. Experiments on mesons, leptons and baryons have compared different properties of matter-antimatter conjugates with fractional uncertainties at the parts-per-billion level or better. One specific quantity, however, has so far only been known to a fractional uncertainty at the parts-per-million level: the magnetic moment of the antiproton, . The extraordinary difficulty in measuring with high precision is caused by its intrinsic smallness; for example, it is 660 times smaller than the magnetic moment of the positron. Here we report a high-precision measurement of in units of the nuclear magneton µN with a fractional precision of 1.5 parts per billion (68% confidence level). We use a two-particle spectroscopy method in an advanced cryogenic multi-Penning trap system. Our result = -2.7928473441(42)µN (where the number in parentheses represents the 68% confidence interval on the last digits of the value) improves the precision of the previous best measurement by a factor of approximately 350. The measured value is consistent with the proton magnetic moment, µp = 2.792847350(9)µN, and is in agreement with CPT invariance. Consequently, this measurement constrains the magnitude of certain CPT-violating effects to below 1.8 × 10-24 gigaelectronvolts, and a possible splitting of the proton-antiproton magnetic moments by CPT-odd dimension-five interactions to below 6 × 10-12 Bohr magnetons.

Systematic review of bladder cancer outcomes in patients with spina bifida.

BACKGROUND: In patients with congenital bladder anomalies, bladder augmentation is used as a last resort to reduce intravesical pressure, but concerns about malignant transformation in augmented patients were first raised in the 1980s. The best evidence to date indicates that augmentation does not appear to increase the risk of bladder cancer in spina bifida patients. To date, oncologic outcomes from patients with spina bifida with and without augmentation have only been available in small case reports. OBJECTIVE: To systematically evaluate factors in myelomeningocele patients with bladder cancer, including bladder augmentation, that contribute to overall survival (OS). STUDY DESIGN: A systematic review using PubMed was conducted by cross referencing terms 'myelomeningocele,' 'cystoplasty,' 'bladder cancer' and respective synonyms according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Inclusion criteria were studies with patients with an underlying diagnosis of myelomeningocele and bladder cancer with data on age, stage, and mortality status. Studies were excluded for spinal cord injury, history of tuberculosis or schistosomiasis, or prior ureterosigmoidostomy. RESULTS: Fifty-two patients were identified from 28 studies with a median age at bladder cancer diagnosis of 41 years (range 13-73); 37 (71%) presented with stage III or IV bladder cancer. Overall survival at 1 year and 2 years was 48.5% and 31.5%, respectively. Overall survival was different between those with and without augmentation (P = 0.009) by log-rank analysis. No between-group differences in OS were seen based on age, management with indwelling catheter, diversion with ileal conduit or being on a surveillance program. Only stage remained a significant predictor of OS on multivariate analysis (HR 2.011, 95% CI 1.063-3.804, P = 0.032). Secondary analysis was performed after removing patients with gastric augmentation (n = 8), and no difference in OS was seen between patients with (n = 8) and without augmentation (n = 36, P = 0.112). Of augmented patients, latency to development of bladder cancer was variable (Summary Figure). DISCUSSION: Bladder cancer is a deadly diagnosis in patients with congenital bladder anomalies like spina bifida, and while overall prevalence of the two conditions occurring together is low, bladder cancer will go on to affect 2-4% of spina bifida patients. The present study examined overall survival, and further characterized outcomes in these patients. Presence of a bladder augment did not appear to worsen overall survival. CONCLUSIONS: Patients with myelomeningocele who developed bladder cancer had aggressive disease. Augmentation did not worsen OS, based on cases reported in the literature. Risk of bladder cancer should be discussed with all myelomeningocele patients.

Flagellar filament structural protein induces Sjögren's syndrome-like sialadenitis in mice.

OBJECTIVE: Sjögren's syndrome (SS) is a systemic autoimmune disease that primarily affects lacrimal and salivary glands. We previously reported that FliC derived from Escherichia coli could induce autoimmune pancreatitis-like lesions. From these results, we speculated that FliC could also induce SS-like exocrinopathy. In this study, we investigated the effects of chronic exposure to FliC on lacrimal and salivary glands and the possibility that it might lead to an autoimmune response. METHODS: C57BL/6 mice were repeatedly injected with FliC and histological changes, serum levels of cytokine/chemokines and autoantibodies were evaluated at different time points after the final injection. The presence of sialadenitis was diagnosed by histological methods. RESULTS: In FliC-treated groups, 57% of subjects developed inflammatory cell infiltrates around ducts in mandibular salivary glands, but not lacrimal glands. In addition, serum levels of total IgG, IgG1, and IgG2a were significantly higher in FliC-treated groups. Intriguingly, serum anti-SSA/Ro levels were also significantly higher in FliC-treated groups. Cytokine analysis revealed that serum levels of IL-1ß, IL-12p70, IL-13, IFN-γ, IL-15, and IL-23 seemed to be higher in FliC-treated mice. CONCLUSIONS: Our data suggest that FliC-treated mice develop an SS-like phenotype. Our model may elucidate the relationship between commensal bacteria and SS.

Sixfold improved single particle measurement of the magnetic moment of the antiproton.

Our current understanding of the Universe comes, among others, from particle physics and cosmology. In particle physics an almost perfect symmetry between matter and antimatter exists. On cosmological scales, however, a striking matter/antimatter imbalance is observed. This contradiction inspires comparisons of the fundamental properties of particles and antiparticles with high precision. Here we report on a measurement of the g-factor of the antiproton with a fractional precision of 0.8 parts per million at 95% confidence level. Our value /2=2.7928465(23) outperforms the previous best measurement by a factor of 6. The result is consistent with our proton g-factor measurement gp/2=2.792847350(9), and therefore agrees with the fundamental charge, parity, time (CPT) invariance of the Standard Model of particle physics. Additionally, our result improves coefficients of the standard model extension which discusses the sensitivity of experiments with respect to CPT violation by up to a factor of 20.

Highly sensitive superconducting circuits at ∼700 kHz with tunable quality factors for image-current detection of single trapped antiprotons.

We developed highly sensitive image-current detection systems based on superconducting toroidal coils and ultra-low noise amplifiers for non-destructive measurements of the axial frequencies (550-800 kHz) of single antiprotons stored in a cryogenic multi-Penning-trap system. The unloaded superconducting tuned circuits show quality factors of up to 500 000, which corresponds to a factor of 10 improvement compared to our previously used solenoidal designs. Connected to ultra-low noise amplifiers and the trap system, signal-to-noise-ratios of 30 dB at quality factors of >20 000 are achieved. In addition, we have developed a superconducting switch which allows continuous tuning of the detector's quality factor and to sensitively tune the particle-detector interaction. This allowed us to improve frequency resolution at constant averaging time, which is crucial for single antiproton spin-transition spectroscopy experiments, as well as improved measurements of the proton-to-antiproton charge-to-mass ratio.

Thyroglobulin fluctuations in patients with iodine-refractory differentiated thyroid carcinoma on lenvatinib treatment - initial experience.

Tyrosine kinase inhibitors (TKI) have shown clinical effectiveness in iodine-refractory differentiated thyroid cancer (DTC). The corresponding role of serum thyroglobulin (Tg) in iodine-refractory DTC has not been investigated yet. 9 patients (3 female, 61 ± 8y) with progressive iodine-refractory DTC starting on lenvatinib were considered. Tumor restaging was performed every 2-3 months including contrast-enhanced computed tomography (CT, RECIST 1.1). Serum Tg was measured and compared to imaging findings. After treatment initiation, serum Tg levels dropped in all patients with a median reduction of 86.2%. During long-term follow-up (median, 25.2 months), fluctuations in Tg could be observed in 8/9 subjects. According to RECIST, 6/9 subjects achieved a partial response or stable disease with the remaining 3/9 experiencing progressive disease (2/3 with Tg levels rising above baseline). All of the patients with disease progression presented with a preceding continuous rise in serum Tg, whereas tumor marker oscillations in the subjects with controlled disease were only intermittent. Initiation of lenvatinib in iodine-refractory DTC patients is associated with a significant reduction in serum Tg levels as a marker of treatment response. In the course of treatment, transient Tg oscillations are a frequent phenomenon that may not necessarily reflect morphologic tumor progression.