High-resolution three-dimensional imaging of topological textures in nanoscale single-diamond networks.

Topological defects-extended lattice deformations that are robust against local defects and annealing-have been exploited to engineer novel properties in both hard and soft materials. Yet, their formation kinetics and nanoscale three-dimensional structure are poorly understood, impeding their benefits for nanofabrication. We describe the fabrication of a pair of topological defects in the volume of a single-diamond network (space group Fd 3 ¯ m) templated into gold from a triblock terpolymer crystal. Using X-ray nanotomography, we resolve the three-dimensional structure of nearly 70,000 individual single-diamond unit cells with a spatial resolution of 11.2 nm, allowing analysis of the long-range order of the network. The defects observed morphologically resemble the comet and trefoil patterns of equal and opposite half-integer topological charges observed in liquid crystals. Yet our analysis of strain in the network suggests typical hard matter behaviour. Our analysis approach does not require a priori knowledge of the expected positions of the nodes in three-dimensional nanostructured systems, allowing the identification of distorted morphologies and defects in large samples.

Prognostic significance of absolute lymphocyte count in patients with metastatic renal cell carcinoma receiving first-line combination immunotherapies: results from the International Metastatic Renal Cell Carcinoma Database Consortium.

BACKGROUND: Lymphocytes are closely linked to mechanisms of action of immuno-oncology (IO) agents. We aimed to assess the prognostic significance of absolute lymphocyte count (ALC) in patients with metastatic renal cell carcinoma (mRCC). PATIENTS AND METHODS: Using the International mRCC Database Consortium (IMDC), patients receiving first-line IO-based combination therapy were analysed. Baseline patient characteristics, objective response rates (ORRs), time to next treatment (TTNT), and overall survival (OS) were compared. RESULTS: Of 966 patients included, 195 (20%) had lymphopenia at baseline, and they had a lower ORR (37% versus 45%; P < 0.001), shorter TTNT (10.1 months versus 24.3 months; P < 0.001), and shorter OS (30.4 months versus 48.2 months; P < 0.001). Among 125 patients with lymphopenia at baseline, 52 (42%) experienced ALC recovery at 3 months, and they had longer OS (not reached versus 30.4 months; P = 0.012). On multivariable analysis for OS, lymphopenia was an independent adverse prognostic factor (hazard ratio 1.68; P < 0.001). Incorporation of lymphopenia into the IMDC criteria improved OS prediction accuracy (C-index from 0.688 to 0.707). CONCLUSIONS: Lymphopenia was observed in one-fifth of treatment-naive patients with mRCC and may serve as an indicator of unfavourable oncologic outcomes in the contemporary IO era.

Downward Terrestrial Gamma-Ray Flash Observed in a Winter Thunderstorm.

During a winter thunderstorm on 24 November 2017, a strong burst of gamma rays with energies up to ∼10 MeV was detected coincident with a lightning discharge, by scintillation detectors installed at the Kashiwazaki-Kariwa Nuclear Power Station at sea level in Japan. The burst had a subsecond duration, which is suggestive of photoneutron production. The leading part of the burst was resolved into four intense gamma-ray bunches, each coincident with a low-frequency radio pulse. These bunches were separated by 0.7-1.5 ms, with a duration of ≪1 ms each. Thus, the present burst may be considered as a "downward" terrestrial gamma-ray flash (TGF), which is analogous to upgoing TGFs observed from space. Although the scintillation detectors were heavily saturated by these bunches, the total dose associated with them was successfully measured by ionization chambers, employed by nine monitoring posts surrounding the power plant. From this information and Monte Carlo simulations, the present downward TGF is suggested to have taken place at an altitude of 2500±500 m, involving 8_{-4}^{+8}×10^{18} avalanche electrons with energies above 1 MeV. This number is comparable to those in upgoing TGFs.

Real-world outcomes of nivolumab and cabozantinib in metastatic renal cell carcinoma: results from the International Metastatic Renal Cell Carcinoma Database Consortium.

Objectives: In the present study, we explored the real-world efficacy of the immuno-oncology checkpoint inhibitor nivolumab and the tyrosine kinase inhibitor cabozantinib in the second-line setting. Methods: Using the International Metastatic Renal Cell Carcinoma Database Consortium (imdc) dataset, a retrospective analysis of patients with metastatic renal cell carcinoma (mrcc) treated with nivolumab or cabozantinib in the second line after prior therapy targeted to the vascular endothelial growth factor receptor (vegfr) was performed. Baseline characteristics and imdc risk factors were collected. Overall survival (os) and time to treatment failure (ttf) were calculated using Kaplan-Meier curves. Overall response rates (orrs) were determined for each therapy. Multivariable Cox regression analysis was performed to determine survival differences between cabozantinib and nivolumab treatment. Results: The analysis included 225 patients treated with nivolumab and 53 treated with cabozantinib. No significant difference in median os was observed: 22.10 months [95% confidence interval (ci): 17.18 months to not reached] with nivolumab and 23.70 months (95% ci: 15.52 months to not reached) with cabozantinib (p = 0.61). The ttf was also similar at 6.90 months (95% ci: 4.60 months to 9.20 months) with nivolumab and 7.39 months (95% ci: 5.52 months to 12.85 months) with cabozantinib (p = 0.20). The adjusted hazard ratio (hr) for nivolumab compared with cabozantinib was 1.30 (95% ci: 0.73 to 2.3), p = 0.38. When adjusted by imdc criteria and age, the hr was 1.32 (95% ci: 0.74 to 2.38), p = 0.35. Conclusions: Real-world imdc data indicate comparable os and ttf for nivolumab and cabozantinib. Both agents are reasonable therapeutic options for patients progressing after initial first-line vegfr-targeted therapy.

Synchrotron-based XRD from rat bone of different age groups.

Synchrotron-based XRD spectra from rat bone of different age groups (w, 56 w and 78w), lumber vertebra at early stages of bone formation, Calcium hydroxyapatite (HAp) [Ca10(PO4)6(OH)2] bone fill with varying composition (60% and 70%) and bone cream (35-48%), has been acquired with 15keV synchrotron X-rays. Experiments were performed at Desy, Hamburg, Germany, utilizing the Resonant and Diffraction beamline (P9), with 15keV X-rays (λ=0.82666 A0). Diffraction data were quantitatively analyzed using the Rietveld refinement approach, which allowed us to characterize the structure of these samples in their early stages. Hydroxyapatite, received considerable attention in medical and materials sciences, since these materials are the hard tissues, such as bone and teeth. Higher bioactivity of these samples gained reasonable interest for biological application and for bone tissue repair in oral surgery and orthopedics. The results obtained from these samples, such as phase data, crystalline size of the phases, as well as the degree of crystallinity, confirm the apatite family crystallizing in a hexagonal system, space group P63/m with the lattice parameters of a=9.4328Å and c=6.8842Å (JCPDS card #09-0432). Synchrotron-based XRD patterns are relatively sharp and well resolved and can be attributed to the hexagonal crystal form of hydroxyapatite. All the samples were examined with scanning electron microscope at an accelerating voltage of 15kV. The presence of large globules of different sizes is observed, in small age groups of the rat bone (8w) and lumber vertebra (LV), as distinguished from, large age groups (56 and 78w) in all samples with different magnification, reflects an amorphous phase without significant traces of crystalline phases. Scanning electron microscopy (SEM) was used to characterize the morphology and crystalline properties of Hap, for all the samples, from 2 to 100µm resolution.

Diagnosis and treatment of bone metastasis: comprehensive guideline of the Japanese Society of Medical Oncology, Japanese Orthopedic Association, Japanese Urological Association, and Japanese Society for Radiation Oncology.

Diagnosis and treatment of bone metastasis requires various types of measures, specialists and caregivers. To provide better diagnosis and treatment, a multidisciplinary team approach is required. The members of this multidisciplinary team include doctors of primary cancers, radiologists, pathologists, orthopaedists, radiotherapists, clinical oncologists, palliative caregivers, rehabilitation doctors, dentists, nurses, pharmacists, physical therapists, occupational therapists, medical social workers, etc. Medical evidence was extracted from published articles describing meta-analyses or randomised controlled trials concerning patients with bone metastases mainly from 2003 to 2013, and a guideline was developed according to the Medical Information Network Distribution Service Handbook for Clinical Practice Guideline Development 2014. Multidisciplinary team meetings are helpful in diagnosis and treatment. Clinical benefits such as physical or psychological palliation obtained using the multidisciplinary team approaches are apparent. We established a guideline describing each specialty field, to improve understanding of the different fields among the specialists, who can further provide appropriate treatment, and to improve patients' outcomes.

Small femoral offset is a risk factor for lateral femoral cutaneous nerve injury during total hip arthroplasty using a direct anterior approach.

INTRODUCTION: Lateral femoral cutaneous nerve (LFCN) injury is a risk specific to the direct anterior approach (DAA) for total hip arthroplasty (THA). However, prevention strategies have not been established. This study aimed to identify the predisposing factors determining LFCN injury during THA via a DAA. HYPOTHESIS: Patients with LFCN injury after THA via DAA would demonstrate predisposing factors. MATERIAL AND METHODS: LFCN injury was identified using a patient questionnaire. Potential factors predisposing to LFCN injury were identified in four categories in patient records: patient factors (age, sex, BMI, diagnosis and range of hip motion), surgical factors (surgical time and surgeon's experience of the DAA), preoperative radiographic factors (neck-shaft angle, femoral offset, acetabular offset, total offset and length of muscle on computed tomography axial image) and radiographic changes (differences between each offset pre- and post-surgery). Multivariate analysis was performed to identify risk factors for LFCN injury during this surgery. RESULTS: After application of inclusion and exclusion criteria, 102 hips (28 with LFCN injury; 74 without) in 102 patients (17 males, 85 females; mean age 66.0 years [range, 26-88 years]) were included. Univariate analysis of patients with and without LFCN injury revealed that small preoperative femoral offset and short preoperative long axis of the tensor fascia lata were statistically significant risk factors for LFCN injury (P=0.004, and P=0.01, respectively). Multivariate analysis showed that small preoperative femoral offset was the only independent risk factor for LFCN injury (odds ratio, 0.895; 95% Confidence Interval, 0.817-0.981; P=0.0018). DISCUSSION: Smaller femoral offset was a significant risk factor for LFCN injury following THA via a DAA. Our recommendations are that careful attention should be paid to the skin-fascia incision and subcutaneous exposure, and that excessive retraction of the sartorius muscle and tensor fascia lata should be avoided, to reduce the risk of LFCN injury in patients with a small femoral offset. LEVEL OF EVIDENCE: IV, retrospective historical cohort study.

Midterm outcome of total hip arthroplasty for rapidly destructive coxarthrosis.

PURPOSE: To compare the midterm outcome in 12 women who underwent total hip arthroplasty (THA) for rapidly destructive coxarthrosis (RDC) and in 12 controls who underwent THA for osteoarthritis. METHODS: Records of 12 women aged 50 to 80 (mean, 72.3) years who underwent THA for RDC after a mean of 9 (range, 4-11) months since symptom onset were reviewed. They were compared with 12 age-and sex-matched controls who underwent THA for primary or secondary osteoarthritis. Acetabular bone deficiency of the 12 RDC patients was classified as type I (n=7), type II (n=4), or type III (n=1). Type I was treated with cementless THA, and types II and III were treated with THA with a cemented acetabular component. The femoral component was cementless. Pre- and post-operative Harris Hip Score was assessed. Radiographs of the hip were evaluated for implant migration, osteolysis, and periprosthetic radiolucency in the acetabulum and proximal femur. RESULTS: The 12 women who underwent THA for RDC and the 12 controls who underwent THA for osteoarthritis were comparable in terms of pre-, intra-, and post-operative parameters. After a mean follow-up of 9.3 years, the mean Harris Hip Score improved from 38.3 to 81.1 in RDC patients and from 43.6 to 84.2 in controls (p=0.13). One RDC patient had dislocation but did not require revision surgery. One RDC patient developed a radiolucent line <2 mm in zones 1 and 7 of the femoral component, but no migration occurred. No patient had progression of bony destruction, loosening, osteolysis, migration, or radiolucency of the acetabular component. CONCLUSION: Despite the rapid destruction of the acetabulum and femoral head in RDC patients, cemented or cementless THA achieved a good midterm outcome comparable to that for patients with primary or secondary osteoarthritis.

On-ground detection of an electron-positron annihilation line from thunderclouds.

Thunderclouds can produce bremsstrahlung gamma-ray emission, and sometimes even positrons. At 00:27:00 (UT) on 13 January 2012, an intense burst of gamma rays from a thundercloud was detected by the GROWTH experiment, located in Japan, facing the Sea of Japan. The event started with a sharp gamma-ray flash with a duration of <300 ms coincident with an intracloud discharge, followed by a decaying longer gamma-ray emission lasting for ∼60 s. The spectrum of this prolonged emission reached ∼10 MeV, and contained a distinct line emission at 508±3(stat.)±5(sys.) keV, to be identified with an electron-positron annihilation line. The line was narrow within the instrumental energy resolution (∼80keV), and contained 520±50 photons which amounted to ∼10% of the total signal photons of 5340±190 detected over 0.1-10 MeV. As a result, the line equivalent width reached 280±40 keV, which implies a nontrivial result. The result suggests that a downward positron beam produced both the continuum and the line photons.

First-, second-, third-line therapy for mRCC: benchmarks for trial design from the IMDC.

BACKGROUND: Limited data exist on outcomes for metastatic renal cell carcinoma (mRCC) patients treated with multiple lines of therapy. Benchmarks for survival are required for patient counselling and clinical trial design. METHODS: Outcomes of mRCC patients from the International mRCC Database Consortium database treated with 1, 2, or 3+ lines of targeted therapy (TT) were compared by proportional hazards regression. Overall survival (OS) and progression-free survival (PFS) were calculated using different population inclusion criteria. RESULTS: In total, 2705 patients were treated with TT of which 57% received only first-line TT, 27% received two lines of TT, and 16% received 3+ lines of TT. Overall survival of patients who received 1, 2, or 3+ lines of TT were 14.9, 21.0, and 39.2 months, respectively, from first-line TT (P<0.0001). On multivariable analysis, 2 lines and 3+ lines of therapy were each associated with better OS (HR=0.738 and 0.626, P<0.0001). Survival outcomes for the subgroups were as follows: for all patients, OS 20.9 months and PFS 7.2 months; for those similar to eligible patients in the first-line ADAPT trial, OS 14.7 months and PFS 5.6 months; for those similar to patients in first-line TIVO-1 trial, OS 24.8 months and PFS 8.2 months; for those similar to patients in second-line INTORSECT trial, OS 13.0 months and PFS 3.9 months; and for those similar to patients in the third-line GOLD trial, OS 18.0 months and PFS 4.4 months. CONCLUSIONS: Patients who are able to receive more lines of TT live longer. Survival benchmarks provide context and perspective when interpreting and designing clinical trials.

Outcomes of patients with metastatic renal cell carcinoma that do not meet eligibility criteria for clinical trials.

BACKGROUND: Targeted therapies in metastatic renal cell carcinoma (mRCC) have been approved based on registration clinical trials that have strict eligibility criteria. The clinical outcomes of patients treated with targeted agents but are ineligible for trials are unknown. PATIENTS AND METHODS: mRCC patients treated with vascular endothelial growth factor-targeted therapy were retrospectively deemed ineligible for clinical trials (according to commonly used inclusion/exclusion criteria) if they had a Karnofsky performance status (KPS) <70%, nonclear-cell histology, brain metastases, hemoglobin ≤9 g/dl, creatinine >2× the upper limit of normal, corrected calcium ≥12 mg/dl, platelet count of <100 × 10(3)/uL, or neutrophil count <1500/mm(3). RESULTS: Overall, 768 of 2210 (35%) patients in the International Metastatic RCC Database Consortium (IMDC) were deemed ineligible for clinical trials by the above criteria. Between ineligible versus eligible patients, the response rate, median progression-free survival (PFS) and median overall survival of first-line targeted therapy were 22% versus 29% (P = 0.0005), 5.2 versus 8.6 months, and 12.5 versus 28.4 months (both P < 0.0001), respectively. Second-line PFS (if applicable) was 2.8 months in the trial ineligible versus 4.3 months in the trial eligible patients (P = 0.0039). When adjusted by the IMDC prognostic categories, the HR for death between trial ineligible and trial eligible patients was 1.55 (95% confidence interval 1.378-1.751, P < 0.0001). CONCLUSIONS: The number of patients that are ineligible for clinical trials is substantial and their outcomes are inferior. Specific trials addressing the unmet needs of protocol ineligible patients are warranted.

Orientation based segmentation for phase-contrast microscopic image of confluent cell.

In this research, we propose a novel segmentation method for image of cultured cell at a confluent state, obtained by phase-contrast microscope, based on the orientation. First, we assign to each pixel in the image the direction of an eigenvector corresponding to a smaller eigenvalue of the 2 by 2 Hessian matrix with respect to brightness. Next, we define the orientation at a certain pixel as the histograms of the direction at pixels in the surrounding regions. Then, we evaluate deviation of histograms in the individual regions by entropy, and regard the series of entropy as a multi-dimensional vector, the dimension of which corresponds with the number of regions. We suppose that the vector is assigned to the pixel of interest. Finally, we segment the image based on the multi-dimensional vector using K-means method. We investigate the efficacy of the proposed method using an actual human confluent fibroblast image acquired by phase-contrast microscopy.

Hardening and termination of long-duration γ rays detected prior to lightning.

We report the first observation of 3-30 MeV prolonged gamma-ray emission that was abruptly terminated by lightning. The gamma-ray detection was made during winter thunderstorms on December 30, 2010, by the Gamma-Ray Observation of Winter Thunderclouds experiment carried out in a coastal area along the Sea of Japan. The gamma-ray flux lasted for less than 3 min, continuously hardening closer to the lightning occurrence. The hardening at energies of 3-10 MeV energies was most prominent. The gamma-ray flux abruptly ceased less than 800 ms before the lightning flash that occurred over 5 km away from the experimental site. In addition, we observed a clear difference in the duration of the 3-10 MeV gamma rays and those >10 MeV, suggesting that the area of >10 MeV gamma-ray emission is considerably smaller than that of the lower-energy gamma rays. This work may give a manifestation that a local region emitting prolonged gamma rays connects with a distant region to initiate lightning.

Immunophenotypical characterization of macrophages in rat bleomycin-induced scleroderma.

Scleroderma is a skin disorder characterized by persistent fibrosis. Macrophage properties influencing cutaneous fibrogenesis remain to be fully elucidated. In this rat (F344 rats) model of scleroderma, at 1, 2, 3, and 4 weeks after initiation of daily subcutaneous injections of bleomycin (BLM; 100 µl of 1 mg/ml daily), skin samples were collected for histological and immunohistochemical evaluations. Immunohistochemically, the numbers of cells reacting to ED1 (anti-CD68; phagocytic activity) and ED2 (anti-CD163; inflammatory factor production) began to increase at week 1, peaked at week 2, and decreased thereafter. In contrast, the increased number of cells reacting to OX6 (anti-MHC class II molecules) was seen from week 2 and remained elevated until week 4. α-Smooth muscle actin-positive myofibroblasts were increased for 4 weeks. Double labeling revealed that galectin-3, a regulator of fibrogenic factor TGF-ß1, was expressed in CD68+, CD163+, and MHC class II+ macrophages and myofibroblasts. mRNA expression of TGF-ß1, as well as MCP-1 and CSF-1 (both macrophage function modulators), were significantly elevated at weeks 1 to 4. This study shows that the increased number of macrophages with heterogeneous immunophenotypes, which might be induced by MCP-1 and CSF-1, could participate in the sclerotic lesion formation, presumably through increased fibrogenic factors such as galectin-3 and TGF-ß1; the data may provide useful information to understand the pathogenesis of the human scleroderma condition.

Immunophenotypical analyses of myofibroblasts in rat excisional wound healing: possible transdifferentiation of blood vessel pericytes and perifollicular dermal sheath cells into myofibroblasts.

Cutaneous fibrosis after wound is evoked by myofibroblasts capable of producing collagen; the derivation and features remain to be investigated. Immunophenotypical characteristics of myofibroblasts were analysed in excisional rat wound healing, of which samples were obtained on post-wounding (PW) days 1 to 26. Myofibroblasts were characterized for expressions of intermediate cytoskeletons such as vimentin, desmin, and α-smooth muscle actin (α-SMA). To pursue the progenitor, immunolabeling analyses were performed using stromal-/bone marrow-stem cell markers (Thy-1 and A3). Myofibroblasts reacting to vimentin and α-SMA were first seen on PW day 5, then peaked on PW day 9 in granulation tissues, and gradually decreased in remodeling tissues; these immunopositive cells reacted simultaneously to Thy-1. Desmin-reacting cells were limited to newly-formed blood vessels in wound bed. The single/double immunolabelings revealed that pericytes (identified by positive reaction to PDGFR-ß and negative reaction to endothelial markers) in newly-developing blood vessels reacted to vimentin, α-SMA, Thy-1 and A3, and occasionally to desmin, and that perifollicular dermal sheath cells in the wound periphery showed increased expressions for vimentin, Thy-1 and A3. There is considerable immunophenotypical similarity between myofibroblasts (expressing vimentin, α-SMA and Thy-1), pericytes (reacting to vimentin, α-SMA, Thy-1 and A3) in newly-developing blood vessels, and perifollicular dermal sheath cells (reacting to vimentin, Thy-1 and A3). Collectively, myofibroblasts in rat cutaneous fibrosis are characterized by vimentin, α-SMA and Thy-1 expressions, and the cells might be generated from the pericytes or perifollicular dermal sheath cells in the lineage of stroma-/bone marrow-stem cells.

White matter alteration in idiopathic normal pressure hydrocephalus: tract-based spatial statistics study.

BACKGROUND AND PURPOSE: White matter alteration in iNPH has not been well-investigated. TBSS is a voxelwise statistical analysis developed for DTI data. We aimed to elucidate the cerebral white matter alteration in patients with iNPH by using DTI and to test the accuracy of TBSS analysis. MATERIALS AND METHODS: DTI data were obtained from 20 patients with iNPH and 20 age- and sex-matched controls. The FA values were evaluated by using TBSS, region-of-interest and tract-specific analysis of the CST. The accuracy of TBSS analysis was tested by using "back-projection" of TBSS results and by comparing the TBSS analysis results with those of region-of-interest and tract-specific analysis. RESULTS: Back-projection of the TBSS results showed accurate registration of the whole brain, with the exception of parts of the thalamus, fornix, and white matter around the posterior body of the lateral ventricle. The TBSS analysis results were consistent with those of the region-of-interest analysis and tract-specific analysis. In patients with iNPH compared with control subjects, the FA values were significantly decreased in parts of the corpus callosum, periventricular white matter, and juxtacortical white matter in the frontal and parietal lobes. In contrast, FA values were significantly increased in the internal capsule, extending to the white matter in the centrum semiovale. CONCLUSIONS: Our results suggest that patients with iNPH have various patterns of white matter damage and that TBSS analysis is a promising tool for performing accurate voxelwise statistical analysis of the iNPH brain, with the exception of misregistered areas.

Different patterns of fornix damage in idiopathic normal pressure hydrocephalus and Alzheimer disease.

BACKGROUND AND PURPOSE: The fornix contains efferent fibers of the hippocampus and is in close contact with the corpus callosum. Part of the fornix is directly attached to the corpus callosum, and another part is suspended from the corpus callosum via the septum pellucidum. DTI can be used to evaluate the morphology and microstructural integrity of the fornix. We examined the pattern of fornix damage in patients with iNPH or AD. MATERIALS AND METHODS: We enrolled 22 patients with iNPH, 20 with AD, and 20 healthy controls. DTI data were obtained. The morphology (volume, length, and mean cross-sectional area) and FA values of the fornix were evaluated by using tract-specific analysis and compared among groups. RESULTS: The volume, cross-sectional area, and FA value of the fornix were significantly smaller in patients with iNPH than in controls, whereas the length was significantly greater. In patients with AD, the volume, mean cross-sectional area, and FA value of the fornix were significantly smaller than those in controls, whereas the length was not altered. The fornix was significantly longer in patients with iNPH than in patients with AD, whereas the volume and cross-sectional areas were significantly smaller. CONCLUSIONS: Our results suggest that the different pathogeneses of these diseases lead to fornix damage through different mechanisms: through mechanical stretching due to lateral ventricular enlargement and corpus callosum deformation in patients with iNPH, and through degeneration secondary to hippocampal atrophy in patients with AD.

Altered microstructure in corticospinal tract in idiopathic normal pressure hydrocephalus: comparison with Alzheimer disease and Parkinson disease with dementia.

BACKGROUND AND PURPOSE: Previous neuropathologic studies in chronic hydrocephalus have suggested the presence of white matter damage, presumably from mechanical pressure due to ventricular enlargement and metabolic derangement. This study aimed to investigate the diffusional properties of the CST in patients with iNPH by using DTI and to determine whether this method could be used as a new diagnostic tool to differentiate patients with iNPH from those with AD and PDD and control subjects. MATERIALS AND METHODS: We enrolled 18 patients with iNPH, 11 patients with AD, 11 patients with PDD, and 19 healthy control subjects. Diffusion tensor metrics of the segmented CST, including FA values, axial eigenvalues, and radial eigenvalues, were evaluated by using tract-specific analysis. The anisotropy color-coding tractography of the CST was visually evaluated. The DTI findings were compared among groups. RESULTS: Tract-specific analysis of the CST showed that FA values and axial eigenvalues were significantly increased (P < .001), whereas radial eigenvalues were not significantly altered, in patients with iNPH compared with other subjects. The CST tractographic images in patients with iNPH was visually different from those in other subjects (P < .001). In discriminating patients with iNPH from other subjects, the CST FA values had a sensitivity of 94% and specificity of 80% at a cutoff value of 0.59. CONCLUSIONS: Our results suggest that patients with iNPH have altered microstructures in the CST. Quantitative and visual CST evaluation by using DTI may be useful for differentiating patients with iNPH from patients with AD or PDD or healthy subjects.

Investigation of the distribution of elements in snail shell with the use of synchrotron-based, micro-beam X-ray fluorescence spectrometry.

In this study, synchrotron-based micro-beam was utilized for elemental mapping of a small animal shell. A thin X-ray spot of the order of approximately 10microm was focused on the sample. With this spatial resolution and high flux throughput, the X-ray fluorescent intensities for Ca, Mn, Fe, Ni, Zn, Cr and Cu were measured using a liquid-nitrogen-cooled 13-element energy-dispersive HpGe detector. The sample is scanned in a 'step-and-repeat' mode for fast elemental mapping and generated elemental maps at 8, 10 and 12keV. All images are of 10microm resolution and the measurement time was 1s per point. The accumulation of trace elements was investigated from the soft-tissue in small areas. Analysis of the small areas will be better suited to establish the physiology of metals in specific structures like small animal shell and the distribution of other trace elements.