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Shih Wei Chiang Department of Colorectal Surgery, Chiayi Branch, Taichung Veterans General Hospital, Chiayi City, Taiwan, Republic of ChinaCorrespondence: Shih Wei Chiang, Department of Colorectal Surgery, Chiayi branch, Taichung Veterans General Hospital, No. 600, Sec. 2, Shixian Road, West Dist, Chiayi City, 600, Taiwan, Republic of China, Tel +886-4-23592525, Email opzimbardo@gmail.comBackground: Colorectal cancer (CRC) is a common malignancy, especially among older adults. Inflammation has been implicated in cancer progression, making inflammatory indices potential prognostic markers. This study aimed to evaluate the prognostic significance of the Glasgow prognostic score (GPS), neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), lymphocyte/C-reactive protein ratio (LCR), and C-reactive protein/albumin ratio (CAR) in older adults with CRC.Methods: This population-based, retrospective observational study included patients aged ≥ 65 years with colorectal adenocarcinoma who were admitted to Taichung Veterans General Hospital (Chiayi branch) between 2017 and 2022. Demographic and clinicopathological characteristics, and results of inflammatory indices were collected from medical records for all patients. Receiver operating characteristic (ROC) curve analyses were performed to determine the optimal cutoffs of the inflammatory indices in predicting overall mortality. Associations between the inflammatory indices, overall survival (OS) and progression-free survival (PFS) were determined using univariate and multivariable Cox proportional hazard regression analyses, with model performance evaluated using the C-index.Results: Data of 106 patients were analyzed. After adjusting for confounders, GPS ≥ 1 (vs 0) significantly predicted poor OS (adjusted hazard ratio [aHR]: 3.80, 95% confidence interval [CI]: 1.30– 11.10, p= 0.015, C-index= 0.825) and PFS (aHR: 3.19, 95% CI: 1.34– 7.57, p= 0.008, C-index= 0.785). CAR ≥ 1.0 (vs < 1) significantly predicted poor OS (aHR: 2.36, 95% CI: 1.01– 5.48), p=0.046, C-index= 0.825) and PFS (aHR: 2.33, 95% CI: 1.14– 4.76, p= 0.020, C-index= 0.786).Conclusion: Among hospitalized older adults with CRC in Taiwan, high GPS and CAR, but not NLR, PLR or LCR, are potentially useful prognostic indicators for poor OS and PFS.Keywords: Colorectal cancer, CRC, prognosis, mortality, inflammation index, Taiwan

Shu-Wan Chiang, Shiou-Fang Lu, Shu-Chen Wu, Tai-Chu Peng Department of Nursing, Tzu Chi University, Hualien, TaiwanCorrespondence: Tai-Chu Peng, Department of Nursing, Tzu Chi University, Hualien, Taiwan, Email ptc2008@gms.tcu.edu.twPurpose: The purpose of this study was to explore the experiences of nursing managers in implementing palliative care in long-term care facilities and to provide recommendations for managers who plan to introduce palliative care into their facilities.Methods: This study used semi-structured interviews and grounded theory methodology, with purposive sampling. A total of 11 long-term care facilities in eastern Taiwan that had implemented palliative care were selected, and 11 facility nursing managers participated in in-depth, face-to-face interviews.Results: The introduction of palliative care in long-term care facilities can be divided into four stages: (1) the opportunity for change, (2) playing a supportive role, (3) a new collaboration model, and (4) facility transformation. The core category shared by the participants may be summed up as “the palliative care captain in the facility”. It reflects the spirit of the successful implementation of palliative care by managers in long-term care facilities.Conclusion: The study reveals that during the initial phases of implementing palliative care, the palliative care teams assume a crucial leadership role, while the facilities play a supportive role. At this stage, managers should focus on personnel training and addressing internal issues within the facilities to facilitate successful collaboration with the palliative care teams. In the later stages, the facilities transition from a supportive role to one of independence, marking a critical juncture for the facilities’ potential stable development. During this period, managers are tasked not only with establishing the facilities’ own palliative care team but also with facilitating the transformation of staff from learners to instructors. Finally, even after successful implementation, managers must contemplate how to innovate and set more ambitious goals.Keywords: nursing managers, long-term care, palliative care, hospice, grounded theory

Wen-Shan Liu,1– 3 Ju-Chun Chien,1 Yu-Hsien Huang,1 Po-Chun Chen,4,5 Wei-Lun Huang,1 Shao-Wei Chiang,1 Ching-Chih Lee,6 Bor-Hwang Kang,3,6 Yu-Chang Hu1 1Department of Radiation Oncology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan; 2Department of Nursing, Meiho University, Pingtung, Taiwan; 3School of Medicine, National Defense Medical Center, Taipei, Taiwan; 4Department of Radiation Oncology, Pingtung Christian Hospital, Pingtung, Taiwan; 5Graduate Institute of Bioresources, National Pingtung University of Science and Technology, Pingtung, Taiwan; 6Department of Otorhinolaryngology - Head and Neck Surgery, Kaohsiung Veterans General Hospital, Kaohsiung, TaiwanCorrespondence: Wen-Shan Liu, Department of Radiation Oncology, Kaohsiung Veterans General Hospital, No. 386, Dazhong 1st Road, Zuoying Dist., Kaohsiung City, 813414, Taiwan, Tel +886934075313, Email wsliu@vghks.gov.twPurpose: The study aimed to evaluate 1) the correlation of doses of swallowing-related organs at risk (OAR) with severe swallowing-related late adverse effects (AE) in nasopharyngeal carcinoma (NPC) patients and 2) the effect of high mean doses of OARs on overall survival (OS).Patients and Methods: This retrospective cohort study enrolled non-metastatic Stage I–IV NPC patients from January 2012 to June 2017. OAR mean doses and severe (≥G3) swallowing-related late AE (xerostomia, dysphagia, and lung infection) were evaluated by t-test and validated using receiver operating characteristic curves. The risk factors of OS were calculated by Cox regression methods.Results: This study enrolled 185 (43 female, 142 male) NPC patients, mean age 52.4 years, primarily with Stage III (93, 50.3%) or Stage IV (67, 36.2%) disease. The mean doses of pharyngeal constrictor muscle (PCM), superior-middle PCM (SMPCM), and superior PCM (SPCM) were significantly higher in those with severe (≥G3) lung infection than in those without (65.7 vs 62.2 Gy, p = 0.036; 68.1 vs 64.2 Gy, p = 0.015; and 70.0 vs 65.9 Gy, p = 0.012, respectively). Patients with severe (≥G3) dysphagia had significant higher mean doses of base of tongue (56.2 vs 50.2 Gy, p = 0.008), laryngeal box (50.6 vs 46.4 Gy, p = 0.036), PCM (65.4 vs 62.1 Gy, p = 0.008), SMPCM (67.1 vs 64.2 Gy, p = 0.014), and SPCM (69.3 vs 65.8 Gy, p = 0.004). Mean SMPCM dose > 64.9 Gy (adjusted hazard ratio [aHR] = 3.2, 95% confidence interval [CI] 1.2– 8.8, p = 0.021), age > 62 years (aHR = 2.7, 95% CI 1.1– 6.9, p = 0.032), N3 status (aHR = 4.0, 95% CI 1.8– 9.0, p = 001), and severe late AE of lung infection (aHR = 4.6, 95% CI 1.5– 14.0, p = 0.007) significantly affected OS.Conclusion: Severe lung infection and dysphagia were associated with significantly higher mean doses of PCM, SMPCM, and SPCM. Among these OARs, only a high SMPCM mean dose was a risk factor for OS in NPC patients.Keywords: nasopharyngeal carcinoma, late adverse effect, pneumonia, dysphagia, pharyngeal constrictor muscle, intensity-modulated radiotherapy

Objectives: Given increasing research suggesting the utility of positron emission tomography/magnetic resonance imaging (PET/MRI) in identifying the pain generator of low back pain, our study aims to assess its effectiveness in evaluating the source of pain in patients with failed back surgery syndrome (FBSS) by comparing the performance of fluorine-18-labeled fluorodeoxyglucose ( 18 F-FDG) PET/MRI with conventional MRI., Methods: We retrospectively analyzed data from patients with FBSS who underwent 18 F-FDG PET and MRI of the lumbar vertebrae and lower extremities for undetermined sources of pain. We assessed 1) The diagnostic reliability and efficacy of MRI and 18 F-FDG PET/MRI according to correct differential diagnosis, affected level, and affected side of the pain source compared to the findings of selective root or peripheral nerve block or revision lumbar spine surgery; and 2) The association between standardized uptake value (SUV) and standardized uptake value ratio (SUVR) threshold and accuracy of the suspected pathology on 18 F-FDG PET/MRI., Results: Among 30 included patients, the diagnostic accuracy of pain source recognition was higher for 18 F-FDG PET/MRI than for MRI alone (1.0 vs. 0.4 in spinal disease and 0.8 vs. 0 in lower extremity disease, both p < 0.05). SUVR values of 1.4-1.5 showed the highest accuracy (0.93), higher than the accuracy obtained using the SUV threshold (0.87)., Conclusion: 18 F-FDG PET/MRI added value to MRI alone in detecting of hypermetabolic activity associated with pain from spinal and non-spinal sources., (© 2024. The Author(s) under exclusive licence to Japan Radiological Society.)

Time-restricted eating (TRE) has gained popularity in recent years as a weight loss option. Although many studies have explored the effectiveness of fasting, few have investigated the successful implementation of this method. Therefore, the purpose of this study is to examine the successful and failed experiences of overweight adults who have implemented TRE for weight loss, in order to identify strategies for maintaining a favorable weight over time. The study utilized semi-structured interviews and followed Constructivist Grounded Theory to collect and analyze data. Data saturation was achieved through purposive and theoretical sampling of 30 overweight adults. The research confirms four stages in the process of weight loss using a TRE strategy, namely, preparation, adaptation, challenge, and maintenance. The findings revealed that the successful implementation of TRE and its maintenance over time require viewing TRE as a lifestyle rather than a tool for short-term weight loss, the development of specific action plans to overcome obstacles, and a positive attitude and self-belief as important sources of support. Based on the study's results, a guide has been provided for those who wish to use TRE as a dietary control method., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

This paper outlines the use of charge detection mass spectrometry to simultaneously measure the charge and mass of micron-sized particles. In a flow-through instrument, the detection of charge was achieved through charge induction onto cylindrical electrodes that connect to a differential amplifier. Mass was determined by particle acceleration under the influence of an electric field. Particles ranging from 30 to 400 fg (3 to 7 µm diameter) were tested. The detector design can measure particle mass within 10% accuracy for particles up to 620 fg with total charge ranging from 500e - to 56 ke - . This charge and mass range are expected to be relevant for dust on Mars.

Whey protein (WP) can increase insulin secretion, produce an incretin effect, delay gastric emptying, and regulate appetite, resulting in improved glycemic control. We hypothesized that WP supplementation is associated with postprandial glycemia regulation in persons with type 2 diabetes mellitus (T2DM) and conducted a quantitative meta-analysis of randomized controlled trials (RCTs) to test this hypothesis. We searched PubMed, Embase, Cochrane Library, Scopus databases, and the ClinicalTrials.gov registry for relevant RCTs published before March 2022. We assessed the pooled effects using a random-effects model on glucose and insulin levels at 60 and 120 minutes, total glucagon-like peptide-1 (tGLP-1) at 30 and 60 minutes, and the incremental area under the curve (iAUC) of glucose, insulin, tGLP-1, and glucose-dependent insulinotropic polypeptide. Five RCTs involving 134 persons were included. Postprandial glycemia was significantly lower at 60 minutes (weighted mean difference: -2.67 mmol/L; 95% confidence interval, -3.62 to -1.72 mmol/L) and 120 minutes (-1.59 mmol/L; -2.91 to -0.28 mmol/L) in WP group than in placebo group. The iAUC of insulin was significantly higher in WP group (24.66 nmol/L × min, 1.65-47.66 nmol/L × min) than in placebo group. Although other results favored the WP group, differences between the groups were not statistically significant. The present study showed that premeal WP supplementation is beneficial for postprandial glycemia in persons with mild or well-controlled T2DM without substantial adverse effects. However, the level of certainty of current evidence is not high enough. Further larger and well-designed clinical trials are warranted for evaluating optimal dose and long-term effects of WP supplementation., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Introduction and Importance: The most common symptoms of primary gastrointestinal (GI) lymphoma are non-specific, such as nausea, vomiting, diarrhea, weight loss, and abdominal pain. The rare acute symptoms include bowel obstruction, intussusception, and perforation. Primary small bowel lymphoma accounts for the smallest proportion of all GI malignancies. We report a case of intestinal lymphoma presenting with bloody stools and anemia., Case Presentation: The patient initially underwent both duodenoscopy and colonoscopy with negative findings. Isotopic red blood cell (RBC) scan was then performed due to persistent bleeding along with computed tomography angiography (CTA) because of suspected bleeding in the left abdomen. Successful embolization over the arcade of the sigmoid and left colic arteries was performed. However, the bleeding did not stop, and ischemic colitis was diagnosed by repeat colonoscopy. A coloenteric fistula was finally discovered during emergent laparotomy., Clinical Discussion: GI lymphomas are a rare disease entity among the all GI malignancies. Despite acute abdominal symptoms including obstruction, perforation, bleeding and intussusception, enteral fistula is also one of the complications. It was seen to be a long-term complication after treatment or disease process in most of cases, however it could occur as the initial manifestation. GI bleeding is a life-threatening condition and commonly needs prompt decision making. There were no standard managements for these patients, it depends on clinical judgements from physician individually., Conclusion: This is a rare condition that has not been previously described in Taiwan. Early diagnosis and timely management will decrease morbidity and mortality in the GI lymphoma population., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Ischemia before the development of dysbaric osteonecrosis (DON) in femoral heads has never been investigated. We assessed whether quantitative magnetic resonance spectroscopy (MRS) and diffusion weighted imaging (DWI) could detect dysbaric changes in divers with hip pain., Methods: This IRB-approved exploratory study recruited 17 divers [9 with hip pain (Group 1); 8 asymptomatic (Group 2)] with normal findings on radiographs and conventional magnetic resonance imaging scans were age-, gender- and body-mass-index matched to 17 non-divers as controls (Group 1C, 2C). Apparent diffusion coefficients (ADCs) and MRS spectra were obtained from regions/voxels of interest on the femoral heads of all subjects. LCModel was used to determine water content, lipid composition, and the unsaturation index in bone marrow. Mann-Whitney non-parametric test was used to compare results of quantitative MRS and ADCs of ipsilateral femoral heads between divers and controls., Results: MRS of the ipsilateral femoral heads revealed higher water (peak: 4.7 ppm) content, lower total lipid fraction (TLF), and higher unsaturation index (UI) of lipids in Group 1 than in Group 2 (water: P=0.040; UI: P=0.022) and Group 1C (water: P=0.027; TLF: P=0.039; UI: P=0.009). In contrast, femoral head ADCs were comparable between divers and controls. Five out of nine symptomatic divers were contacted for follow-up MRS and DWI studies, and the mean difference in water content in the femoral heads of patients with osteonecrosis was also higher than that in patients with symptom relief (osteonecrosis: 0.077±0.130 vs. symptom relief: 0.003±0.010)., Conclusions: Dysbaric change in the femoral heads of divers with hip pain can be detected using quantitative MRS, which reveals increases in water content and UI of lipids, and a decrease in TLF., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/qims-21-148). The authors have no conflicts of interest to declare., (2022 Quantitative Imaging in Medicine and Surgery. All rights reserved.)

The purpose of present study was to longitudinally investigate the alterations in infrapatellar fat pad (IPFP) vascularity in 5/6 nephrectomized rats by using dynamic contrast enhanced (DCE) MRI and IPFP degeneration by using MRI T2* relaxation time. Twelve male Sprague-Dawley rats were assigned to a control group and a 5/6 nephrectomy CKD group. The right knees of all rats were longitudinally scanned by 4.7 T MRI, and serial changes in the IPFP were assessed at 0, 8, 16, 30, and 44 weeks by DCE-MRI (parameters A, k el and k ep ) and MRI T2* mapping. After MRI measurements, knee specimens were obtained and evaluated histologically. The CKD group had IPFPs with lower blood volume A and lower permeability k ep values from 16 weeks (p < 0.05), lower venous washout k el value from 30 weeks (p < 0.001), and significantly higher T2* values reflecting adipocyte degeneration beginning at 16 weeks (p < 0.05). The histopathological results confirmed the MRI findings. Hypoperfusion and adipocytes degeneration related to CKD were demonstrated in a rodent 5/6 nephrectomy model. DCE parameters and MRI T2* can serve as imaging biomarkers of fat pad degeneration during CKD progression.

Objective: The vascularization of subchondral bone plays a significant role in the progression of knee osteoarthritis (OA). Treatment with platelet-rich plasma (PRP) has positive effects on cartilage lesions. However, PRP's efficacy for subchondral bone marrow lesions and the relationship of these lesions to cartilage are still undiscovered. Therefore, our aims were first to longitudinally investigate the change in subchondral flow by dynamic contrast enhanced MRI and degeneration of cartilage by MRI T2 ∗ in an anterior cruciate transection rodent (ACLT) model, and second to examine changes in parameters after intra-articular PRP injection., Design: A 32-week investigation in 18 rats allocated to sham-control, ACLT with normal saline injection (ACLT + NS), and ACLT with PRP injection groups ended with histological evaluation. Another rat was used as a donor of allogenic PRP., Results: Compared to the sham-control group, the ACLT + NS group had higher subchondral blood volume A (0.051, 95% confidence interval: 0.009, 0.092) and lower venous washout k el (-0.030: -0.055, -0.005) from week 4; lower permeability k ep from week 18 (-0.954: -1.339, -0.569); higher cartilage T2 ∗ values (1.803: 1.504, 2.102) reflecting collagen loss beginning at week 10. For the PRP treatment group, subchondral bone marrow A and cartilage T2 ∗ decreased from week 10. Histological results confirmed and were correlated with the MRI findings., Conclusion: Subchondral hyper-perfusion plays a vital role in the pathogenesis of OA and was associated with cartilage degeneration. The efficacy of PRP can be observed from reduced perfusion and MRI T2 ∗ values., (Copyright © 2021 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Future electronic packaging technology requires semiconductor chips having a larger size and higher power for advanced applications, e.g., new energy conversion systems, electric vehicles, and data center servers, yet traditional thermal interface materials (TIMs) with a high thermal conductivity are generally stiff materials with weak joints, which cause the accumulated thermal stress to concentrate at the chip corners, leading to cracking and popcorn problems. To address such a critical challenge, herein for the first time we report a low-cost and high-performance porous copper (Cu)-indium (In) laminar structure as TIM, which can provide a superior thermal conductivity (50 W m -1 K -1 ) comparable to indium, yet the Young's modulus (1.0 GPa) is an order of magnitude lower than indium, which is a state-of-the-art value. Additionally, the In-based intermetallic compound (IMC) joints enable more robust mechanical interconnection above the melting point of pure indium, providing better high-temperature performance. The discontinuous IMCs spread the global interfacial thermal stress into numerous isolated local areas, ensuring a reliable joint to resist thermal-mechanical fatigue. In the silicon-TIM-copper package testing vehicles with a large die size (1 × 1 square inch), this structure shows excellent thermal management ability and superior reliability, compared with classical indium and classic commercial silver pastes.

Mass production of defect-free and large-lateral-size 2D materials via cost-effective methods is very important. Recently, shear exfoliation has shown great promise for large-scale production due to its simple operation, environmental-benignity and wide adaptability. However, a long-standing challenge is that with the production of more nanosheets, a ceiling yield and shattered products are encountered, which significantly limits their wider application. The method and efficiency of energy transfer in fluid is undoubtedly the key point in determining exfoliation efficiency, yet its in-depth mechanism has not yet been described. Thus, a thorough investigation of turbulence energy transfer is critically necessary. Herein, we identify two main factors that critically determine the exfoliation yield and provide a statistical analysis of the relationship between these factors and the exfoliation yield. In the initial shearing process, the coexistence of the 2D nanosheets and raw particles is the dominant factor; as time passes, the dimensional change of raw materials gradually has a greater influence on the energy transfer. These factors together lead to attenuated efficiency and a power function relationship between yield and exfoliation time. This investigation gives a statistical explanation of shear exfoliation technology for 2D material preparation and provides valuable insights for mechanical exfoliating high-quality 2D materials., (© 2021 IOP Publishing Ltd.)

Purpose: The purpose of this study was to explore the experiences of caregivers in long-term care facilities as they implement palliative care. Although palliative care has been available in Taiwan for more than 30 years, it is often provided in hospitals, few models in the long-term care facilities., Methods: Semi-structured interviews using grounded theory methodology and purposive sampling. Two small long-term care facilities that had performed well in palliative care were selected from eastern Taiwan. A total of 12 caregivers participated in in-depth semi-structured face-to-face interviews., Results: Four major stages in the implementation of palliative care were identified: (1) feeling insecure, (2) clarifying challenges, (3) adapting to and overcoming the challenges, and (4) comprehending the meaning of palliative care. The core category of these caregivers as "the guardians at the end of life" reflects the spirit of palliative care., Conclusion: This study demonstrates that successful palliative care implementation would benefit from three conditions. First, the institution requires a manager who is enthusiastic about nursing care and who sincerely promotes a palliative care model. Second, the institution should own caregivers who possess personality traits reflective of enthusiasm for excellence, unusual ambition, and a true sense of mission. Third, early in the implementation phase of the hospice program, the institution must have the consistent support of a high-quality hospice team., Competing Interests: Conflict of interest The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2021. Published by Elsevier B.V.)

Suppressing the dendrite formation and managing the volume change of lithium (Li) metal anode have been global challenges in the lithium batteries community. Herein, a duplex copper (Cu) foil with an ant-nest-like network and a dense substrate is reported for an ultrastable Li metal anode. The duplex Cu is fabricated by sulfurization of thick Cu foil with a subsequent skeleton self-welding procedure. Uniform Li deposition is achieved by the 3D interconnected architecture and lithiophilic surface of self-welded Cu skeleton. The sufficient space in the porous layer enables a large areal capacity for Li and significantly improves the electrode-electrolyte interface. Simulations reveal that the structure allows proper electric field penetration into the connected tunnels. The assembled Li anodes exhibit high coulombic efficiency (97.3% over 300 cycles) and long lifespan (>880 h) at a current density of 1 mA cm -2 with a capacity of 1 mAh cm -2 . Stable and deep cycling can be maintained up to 50 times at a high capacity of 10 mAh cm -2 ., (© 2020 Wiley-VCH GmbH.)

High areal capacity and stable Coulombic efficiency (CE) in lithium metal anodes (LMAs) play pivotal roles in developing high-energy-density rechargeable batteries. However, few reported LMAs delivering high and stable CE (>50 cycles) under ultrahigh areal capacity (>10 mA h cm -2 ). We demonstrated that the simultaneous homogenization of electric field and Li ion flux by using self-supported and surface-oxidized 3D hollow porous copper fibers (3D-HPCFs) can greatly increase both the areal capacity and reversibility of Li deposition. Li can be easily confined inside the hollow porous fibers and within the interspaces among fibers without uncontrollable Li dendrites. The 3D-HPCF-based anode can be deeply cycled at high capacity of 15 mA h cm -2 with average CE of 98.87% for 53 cycles, enabling a practical cell to realize high capacity retentions at a surplus Li of 10%. This work provides a novel Li deposition-regulation technology in LMAs targeting for next generation high-energy-density batteries.

We present a novel and thorough simulation technique to understand image charge generated from charged particles on a printed-circuit-board detector. We also describe a custom differential amplifier to exploit the near-differential input to improve the signal-to-noise-ratio of the measured image charge. The simulation technique analyzes how different parameters such as the position, velocity, and charge magnitude of a particle affect the image charge and the amplifier output. It also enables the designer to directly import signals into circuit simulation software to analyze the full signal conversion process from the image charge to the amplifier output. A novel measurement setup using a Venturi vacuum system injects single charged particles (with diameters in the 100 s of microns range) through a PCB detector containing patterned electrodes to verify our simulation technique and amplifier performance. The measured differential amplifier presented here exhibits a gain of 7.96 µV/e - and a single-pass noise floor of 1030 e - , which is about 13× lower than that of the referenced commercial amplifier. The amplifier also has the capability to reach a single-pass noise floor lower than 140 e - , which has been shown in Cadence simulation.

In this study, biomass of rice straw (RS) and wood (WD) and their torrefied biomass (RS T and WD T ) were used as solid biofuel (SBF) for co-firing individually with coal in a commercial continuous chain-grate steam boiler system, which was conducted at fixed input rate of heating value of mixture of SBF and coal and at fixed airflow rate. The effects of key system parameters on the gaseous and particulate pollutions and ash were examined. These include SBF type and blending ratio (R BL ) of biomass (i.e., SBF) in the mixture of coal and biomass based on heating values for co-firing.The results indicated that wood, which possesses high heating value while less amount of ash, is more suitable for co-firing with coal than rice straw. Torrefaction can increase the heating value of biomass and homogenize its property, being beneficial to co-firing. Also, torrefaction can decompose the hydroxyl group of biomass, which makes biomass tending to possess hydrophobicity. This, in turn, helps the storage and transportation of biomass. Generally, adding the RS (with R BL = 5-10%), WD (2-15%), RS T (2-10%) and WD T (2-20%), respectively, with coal decreases the emissions of NO x and SO 2 , but increases that of CO (except RS T ). The emission of HCl is little. The addition of biomass also increases the emission of fine particulate matters (PM) especially PM 2.5 in the flue gases, raising PM 2.5 /PM 100 from 34.87 to 78.35 wt.% (Case 50%WD T ). These emissions for the Cases tested satisfy with Taiwanese emission standards of stationary sources which set limitations of NOx, SO 2 , CO and HCl < 350, 300, 2000 and 80 ppmv, while PM < 50 mg/m 3 , respectively. The results support the use of RS, WD, RS T and WD T for co-firing with coal. Implications : This study examined the suitability of using solid bio-fuels to co-fire with coal in an industrial chain-grate steam boiler system with a capacity of 100 kW, in order to achieve carbon-free emissions. Both biomass and torrefied biomass of solid bio-fuel were tested. The findings would be useful for proper design and rational operation of solid bio-fuel/coal co-firing combustion matching the appeal of sustainable material management and circular economy of biomass, and of adaptation of global warming induced by greenhouse gases. It also provides information for policy-makers to promote the co-firing application of biomass and related bio-waste materials.

Objectives: To compare diffusion tensor (DT)-derived indices from the thalamic nuclei and cerebrospinal fluid (CSF) hydrodynamic parameters for the prediction of gait responsiveness to the CSF tap test in early iNPH patients., Methods: In this study, 22 patients with iNPH and 16 normal controls were enrolled with the approval of an institutional review board. DT imaging and phase-contrast magnetic resonance imaging were performed in patients and controls to determine DT-related indices of the sensorimotor-related thalamic nuclei and CSF hydrodynamics. Gait performance was assessed in patients using gait scale before and after the tap test. The Mann-Whitney U test and receiver operating characteristic (ROC) curve analysis were applied to compare group differences between patients and controls and assess the predictive performance of gait responsiveness to the tap test in the patients., Results: Fractional anisotropy (FA) and axial diffusivity showed significant increases in the ventrolateral (VL) and ventroposterolateral (VPL) nuclei of the iNPH group compared with those of the control group (p < 0.05). The predictions of gait responsiveness of ventral thalamic FA alone (area under the ROC curve [AUC] < 0.8) significantly outperformed those of CSF hydrodynamics alone (AUC < 0.6). The AUC curve was elevated to 0.812 when the CSF peak systolic velocity and FA value were combined for the VPL nucleus, yielding the highest sensitivity (0.769) and specificity (0.778) to predict gait responses., Conclusions: Combined measurements of sensorimotor-related thalamic FA and CSF hydrodynamics can provide potential biomarkers for gait response to the CSF tap test in patients with iNPH., Key Points: • Ventrolateral and ventroposterolateral thalamic FA may predict gait responsiveness to tap test. • Thalamic neuroplasticity can be assessed through DTI in idiopathic normal-pressure hydrocephalus. • Changes in the CST associated with gait control could trigger thalamic neuroplasticity. • Activities of sensorimotor-related circuits could alter in patients with gait disturbance. • Management of patients with iNPH could be more appropriate.

Background and Objective: To investigate the feasibility of histogram analysis of the T2*-based permeability parameter volume transfer constant (K trans ) for glioma grading and to explore the diagnostic performance of the histogram analysis of K trans and blood plasma volume (v p )., Methods: We recruited 31 and 11 patients with high- and low-grade gliomas, respectively. The histogram parameters of K trans and v p , derived from the first-pass pharmacokinetic modeling based on the T2* dynamic susceptibility-weighted contrast-enhanced perfusion-weighted magnetic resonance imaging (T2* DSC-PW-MRI) from the entire tumor volume, were evaluated for differentiating glioma grades., Results: Histogram parameters of K trans and v p showed significant differences between high- and low-grade gliomas and exhibited significant correlations with tumor grades. The mean K trans derived from the T2* DSC-PW-MRI had the highest sensitivity and specificity for differentiating high-grade gliomas from low-grade gliomas compared with other histogram parameters of K trans and v p ., Conclusions: Histogram analysis of T2*-based pharmacokinetic imaging is useful for cerebral glioma grading. The histogram parameters of the entire tumor K trans measurement can provide increased accuracy with additional information regarding microvascular permeability changes for identifying high-grade brain tumors., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Uncontrolled growth of lithium dendrites during cycling has remained a challenging issue for lithium metal batteries. Thus far, various approaches have been proposed to delay or suppress dendrite growth, yet little attention has been paid to the solutions that can make batteries keep working when lithium dendrites are already extensively present. Here we develop an industry-adoptable technology to laterally direct the growth of lithium dendrites, where all dendrites are retained inside the compartmented copper current collector in a given limited cycling capacity. This featured electrode layout renders superior cycling stability (e.g., smoothly running for over 150 cycles at 0.5 mA cm -2 ). Numerical simulations indicate that reduced dendritic stress and damage to the separator are achieved when the battery is abusively running over the ceiling capacity to generate protrusions. This study may contribute to a deeper comprehension of metal dendrites and provide a significant step towards ultimate safe batteries.

The pathogenesis of chronic kidney disease (CKD) is multifactorial. In the progression of CKD arthropathy, arteriosclerosis may alter the knee subchondral bone marrow by altering blood flow through the bone vasculature. Herein, multi-parametric MRI assessment, including dynamic contrast enhanced magnetic resonance imaging (DCE-MRI), magnetic resonance spectroscopy (MRS), MRI T2*, contrast enhanced MR angiography (CE-MRA), and micro-CT were applied in a rodent nephrectomy model to: 1) investigate the blood perfusion of subchondral bone marrow and its relationship to fat water content and trabeculation pattern in CKD and 2) demonstrate the feasibility of using multi-parametric MRI parameters as imaging biomarkers to evaluate the disease's progression. Two groups of rats in our study underwent either 1) no intervention or 2) 5/6 nephrectomy. We found that in the CKD group, perfusion amplitude A and elimination constant k el values were significantly decreased, and vascular permeability k ep was significantly increased. MRS showed that fat fraction (FF) was significantly lower, water fraction (WF) was significantly higher in the CKD group. Micro-CT showed a significant loss of trabecular bone. Knee subchondral bone marrow perfusion deficiency in experimental CKD may be associated with decreased fat content, increased water content, and sparse trabeculation.

Objective: Chronic kidney disease (CKD) is characterized by metabolic disturbances in calcium and phosphorus homeostasis as kidney function declines. Alterations in blood perfusion in bone resulting from arteriosclerosis of bone vessels may relate to the progression of CKD. Herein, change in dynamic contrast enhanced (DCE) MRI parameters (A: amplitude, k el : elimination constant, and k ep : permeability rate constant) and MRI T2 ∗ relaxation time of the knee cartilage were measured in a rodent nephrectomy model in order to (1) examine the relationship of peripheral blood perfusion to CKD and (2) demonstrate the feasibility of using DCE-MRI parameters and MRI T2 ∗ as imaging biomarkers to monitor disease progression., Design: Two groups of male Sprague-Dawley rats received either (1) no intervention or (2) 5/6 nephrectomy., Results: We found that the CKD group (compared with the control group) had lower A and k el values and similar k ep value in the lateral and medial articular cartilages beginning at 12 weeks (P < 0.05); statistically significantly higher T2 ∗ values in the lateral and medial articular cartilages beginning at 18 weeks (P < 0.05); statistically significantly decreased inner luminal diameter of the popliteal artery, and altered structure of the lateral and medial articular cartilages (P < 0.05)., Conclusion: Perfusion deficiency and CKD may be related. DCE parameters and MRI T2 ∗ could serve as imaging biomarkers of cartilage degeneration in CKD progression., (Copyright © 2016 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Evaluation of acute white matter injuries caused by carbon monoxide (CO) poisoning can be limited by conventional magnetic resonance (MR) imaging. We aim to evaluate the feasibility of diffusion kurtosis imaging (DKI) for early detection of white matter alterations in patients with acute CO intoxication.A total of 30 subjects including 15 acute CO patients and 15 age- and sex-matched healthy volunteers were enrolled in this study. MR examinations were performed on a 3T MR scanner within 8 days after CO intoxication. DKI data were acquired to derive axial, radial, and mean kurtosis, as well as fractional anisotropy (FA), axial, radial, and mean diffusivity for tract-specific comparisons between the 2 groups.Significant decreases of mean kurtosis were shown in the genu of corpus callosum, cingulum, and motor-related tracts (corticospinal and corticobulbar tracts) in patients with acute CO intoxication as compared with controls. On the contrary, significant differences of FA values were merely shown in the regions of corticospinal tracts.DKI demonstrated comparably stronger potential than diffusion tensor imaging in terms of early detection of white matter changes in patients with acute CO intoxication. This may have implications in therapeutic strategy for managing acute CO intoxication patients.

A single-nucleotide polymorphism (SNP) rs4236601 at the CAV1/CAV2 locus is associated with primary open-angle glaucoma (POAG). Rs4236601 is common in Caucasians but rare in East Asians. Here we conducted a haplotype-tagging SNP analysis followed by replication in a total of 848 POAG cases and 1574 controls drawn from 3 cities in China and 1 city in Japan. Two SNPs, rs4236601 (odds ratio [OR] = 6.25; P = 0.0086) and a tagging-SNP rs3801994 (OR = 1.32; P = 0.042), were associated with POAG in the Hong Kong Chinese cohort after age and gender adjustments. Rs4236601 was associated with POAG also in Shantou (OR = 6.09; P = 0.0037) and Beijing (OR = 3.92; P = 0.030) cohorts after age and gender adjustment, with a pooled-OR of 5.26 (P = 9.0 × 10(-6)) in Chinese; but it is non-polymorphic in the Osaka cohort. SNP rs3801994 showed a similar trend of effect in the Shantou and Beijing cohorts, with a pooled-OR of 1.23 (P = 0.022) and 1.20 (P = 0.063) in Chinese, prior to and after age and gender adjustment, respectively; but it showed a reverse effect in the Osaka cohort (OR = 0.58; P = 0.033) after the adjustments. We have thus confirmed the association of rs4236601 with POAG in different Chinese cohorts. Also, we found a common SNP rs3801994 of diverse associations with POAG between Chinese and Japanese.

In this study, we aimed to investigate the reactive changes in diffusion tensor imaging (DTI)-derived diffusion metrics of the anterior thalamic nucleus (AN), a relaying center for the Papez circuit, in early idiopathic normal pressure hydrocephalus (iNPH) patients with memory impairment, as well as its correlation with the patients' neuropsychological performances. In total, 28 probable iNPH patients with symptom onset within 1 year and 17 control subjects were prospectively recruited between 2010 and 2013 for this institutional review board-approved study. Imaging studies including DTI and a neuropsychological assessment battery were performed in all subjects. Diffusion metrics were measured from the region of the AN using tract-deterministic seeding method by reconstructing the mammillo-thalamo-cingulate connections within the Papez circuit. Differences in diffusion metrics and memory assessment scores between the patient and control group were examined via the Mann-Whitney U test. Spearman correlation analyses were performed to examine associations between diffusion metrics of AN and neuropsychological tests within the patient group. We discovered that early iNPH patients exhibited marked elevations in fractional anisotropy, pure diffusion anisotropy, and axial diffusivity (all P < 0.01), as well as lower neuropsychological test scores including verbal and nonverbal memory (all P < 0.05) compared with normal control. Spearman rank correlation analyses did not disclose significant correlations between AN diffusion metrics and neuropsychological test scores in the patient group, whereas ranked scatter plots clearly demonstrated a dichotic sample distribution between patient and control samples. In summary, our study highlighted the potential compensatory role of the AN by increasing thalamocortical connectivity within the Papez circuit because memory function declines in early iNPH when early shunt treatment may potentially reverse the memory deficits.

Calcification of the middle cerebral artery (MCA) is uncommon in the healthy elderly. Whether calcification of the MCA is associated with cerebral ischemic stroke remains undetermined. We intended to investigate the association using Agatston calcium scoring of the MCA. This study retrospectively included 354 subjects with ischemic stroke in the MCA territory and 1518 control subjects who underwent computed tomography (CT) of the brain. We recorded major known risk factors for ischemic stroke, including age, gender, hypertension, diabetes mellitus, smoking, hyperlipidemia, and obesity, along with the MCA calcium burden, measured with the Agatston calcium scoring method. Univariate and modified logistic regression analyses were performed to examine the association between the MCA calcification and ischemic stroke. The univariate analyses showed significant associations of ischemic stroke with age, hypertension, diabetes mellitus, smoking, total MCA Agatston score, and the presence of calcification on both or either side of the MCA. Subjects with the presence of MCA calcification on both or either side of the MCA were 8.46 times (95% confidence interval, 4.93-14.53; P < 0.001) more likely to have a cerebral infarct than subjects without MCA calcification after adjustment for the major known risk factors, including age, hypertension, diabetes mellitus, and smoking. However, a higher degree of MCA calcification reflected by the Agatston score was not associated with higher risk of MCA ischemic stroke after adjustment for the confounding factors and presence of MCA calcification. These results suggest that MCA calcification is associated with ischemic stroke in the MCA territory. Further prospective studies are required to verify the clinical implications of the MCA calcification., Competing Interests: The authors have no conflicts of interest to disclose.

Fractal metallic dendrites have been drawing more attentions recently, yet they have rarely been explored in electronic printing or packaging applications because of the great challenges in large-scale synthesis and limited understanding in such applications. Here we demonstrate a controllable synthesis of fractal Ag micro-dendrites at the hundred-gram scale. When used as the fillers for isotropically electrically conductive composites (ECCs), the unique three-dimensional fractal geometrical configuration and low-temperature sintering characteristic render the Ag micro dendrites with an ultra-low electrical percolation threshold of 0.97 vol% (8 wt%). The ultra-low percolation threshold and self-limited fusing ability may address some critical challenges in current interconnect technology for microelectronics. For example, only half of the laser-scribe energy is needed to pattern fine circuit lines printed using the present ECCs, showing great potential for wiring ultrathin circuits for high performance flexible electronics.

The Hoffa fat pad (infrapatellar fat pad) is a source of post-traumatic anterior knee pain, and Hoffa disease is a syndrome leading to chronic inflammation of the fat pad. Herein, change in T2* relaxation time of the fat pad was measured in a rodent anterior cruciate ligament transection (ACLX) model in order to (i) examine the causal relationship of anterior cruciate ligament (ACL) deficiency and Hoffa disease and (ii) demonstrate the feasibility of using T2* as an imaging biomarker to monitor disease progression. Three groups of male Sprague Dawley rats (n = 6 each group), received either (i) no intervention; (ii) sham surgery at the right knee; or (iii) right ACLX. T2* relaxation time was measured and histology was examined in the Hoffa fat pad after surgery. At 13 and 18 weeks after surgery, T2* values were significantly higher in the right fat pad than the left (p < 0.001) and significantly higher in the ACLX group than the control and sham groups (p < 0.001). Histology showed fibrosis and degeneration of adipocytes in the right knees of the ACLX group. We conclude that ACL deficiency and Hoffa disease are causally related and that MRI T2* value can serve as an imaging biomarker of Hoffa disease progression., (© 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.)

The effect of intracranial internal carotid artery (ICA) calcification on cognitive impairment is uncertain. Our objective was to investigate whether intracranial ICA calcification is a significant cognitive predictor for cognitive impairment. Global cognition and degrees of intracranial ICA calcification of 579 subjects were assessed with Mini-Mental State Examination (MMSE) and Agatston calcium scoring method, respectively. Other risk factors for cognitive impairment, including age, education level, hypertension, diabetes mellitus, smoking, hyperlipidemia, and body mass index, were documented and analyzed for their associations with cognitive function. In univariate analyses, older age, lower education level, hypertension, diabetes mellitus, and higher intracranial ICA Agatston scores were significantly associated with cognitive impairment. In ordinal logistic regression, only age and total intracranial ICA Agatston score were significant risk factors for cognitive impairment. After adjustment for the other documented risk factors, subjects were 7% (95% CI: 5-10; P < 0.001) and 6% (95% CI: 0-13; P = 0.04) more likely to have lower cognitive category with every year increment of age and every 100-point increment of the total intracranial ICA Agatston score respectively. These results suggest an important role of the intracranial ICA calcification on cognitive impairment.

Electrically small antennas (ESAs) are becoming one of the key components in the compact wireless devices for telecommunications, defence, and aerospace systems, especially for the spherical one whose geometric layout is more closely approaching Chu's limit, thus yielding significant bandwidth improvements relative to the linear and planar counterparts. Yet broad applications of the volumetric ESAs are still hindered since the low cost fabrication has remained a tremendous challenge. Here we report a state-of-the-art technology to transfer electrically conductive composites (ECCs) from a planar mould to a volumetric thermoplastic substrate by using pad-printing technology without pattern distortion, benefit from the excellent properties of the ECCs as well as the printing-calibration method that we developed. The antenna samples prepared in this way meet the stringent requirement of an ESA (ka is as low as 0.32 and the antenna efficiency is as high as 57%), suggesting that volumetric electronic components i.e. the antennas can be produced in such a simple, green, and cost-effective way. This work can be of interest for the development of studies on green and high performance wireless communication devices.

Dimethyl phthalate (DMP) was treated via wet oxygen oxidation process (WOP). The decomposition efficiency η DMP of DMP and mineralization efficiency η TOC of total organic carbons were measured to evaluate the effects of operation parameters on the performance of WOP. The results revealed that reaction temperature T is the most affecting factor, with a higher T offering higher η DMP and η TOC as expected. The η DMP increases as rotating speed increases from 300 to 500 rpm with stirring enhancement of gas liquid mass transfer. However, it exhibits reduction effect at 700 rpm due to purging of dissolved oxygen by overstirring. Regarding the effects of pressure P T, a higher P T provides more oxygen for the forward reaction with DMP, while overhigh P T increases the absorption of gaseous products such as CO2 and decomposes short-chain hydrocarbon fragments back into the solution thus hindering the forward reaction. For the tested P T of 2.41 to 3.45 MPa, the results indicated that 2.41 MPa is appropriate. A longer reaction time of course gives better performance. At 500 rpm, 483 K, 2.41 MPa, and 180 min, the η DMP and η TOC are 93 and 36%, respectively.

Neovascular age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV) are leading causes of irreversible blindness in developed countries. In this study, we investigated the associations of haplotype-tagging single nucleotide polymorphisms (SNPs) in the complement component 3 (C3) gene with both neovascular AMD and PCV, and potential epistatic effects on C3. Eight tagging SNPs in C3 were genotyped in 708 unrelated study subjects: 200 neovascular AMD patients, 233 PCV patients and 275 controls. Among the eight C3 SNPs, rs17030 was associated with PCV after adjusted for gender and SNP-gender interaction (P = 0.008, OR = 2.94; 95% CI: 1.32-6.52). Moreover, an interaction between rs17030 and gender was identified in PCV (P = 0.02). After stratification by gender, the rs17030 G allele was found to confer an increased risk for PCV in male (P = 0.010, OR = 1.56) but not in female. The haplotype AG defined by the major alleles of rs17030 and rs344555 was also associated with PCV in male (P = 0.010, OR = 0.64). In contrast to PCV, none of the eight SNPs was significantly associated with neovascular AMD. This study shows an association of C3 rs17030 with PCV in male, indicating that C3 may have an epistatic effect with gender in the pathogenesis of PCV.

Direct printing nanoparticle-based conductive inks onto paper substrates has encountered difficulties e.g. the nanoparticles are prone to penetrate into the pores of the paper and become partially segmented, and the necessary low-temperature-sintering process is harmful to the dimension-stability of paper. Here we prototyped the paper-based circuit substrate in combination with printed thermoplastic electrically conductive adhesives (ECA), which takes the advantage of the capillarity of paper and thus both the conductivity and mechanical robustness of the printed circuits were drastically improved without sintering process. For instance, the electrical resistivity of the ECA specimen on a pulp paper (6 × 10(-5)Ω · cm, with 50 wt% loading of Ag) was only 14% of that on PET film than that on PET film. This improvement has been found directly related to the sizing degree of paper, in agreement with the effective medium approximation simulation results in this work. The thermoplastic nature also enables excellent mechanical strength of the printed ECA to resist repeated folding. Considering the generality of the process and the wide acceptance of ECA technique in the modern electronic packages, this method may find vast applications in e.g. circuit boards, capacitive touch pads, and radio frequency identification antennas, which have been prototyped in the manuscript.

Purpose: To investigate the associations of genetic variants in the high-density lipoprotein (HDL) metabolism pathway with neovascular age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV)., Design: Cross-sectional, case-control association study., Participants: A Chinese case-control group of 200 neovascular AMD patients, 233 PCV patients, and 275 control subjects., Methods: Eight single nucleotide polymorphisms (SNPs) from 6 genes of the HDL metabolism pathway and 2 known AMD-associated SNPs, rs800292 (from complement factor H [CFH]) and rs11200638 (from HtrA serine peptidase 1 [HTRA1]), were genotyped in all study subjects using the TaqMan genotyping technology (Applied Biosystems, Foster City, CA)., Main Outcome Measures: Allele and genotypic frequencies of selected SNPs., Results: The SNP rs3764261 in the cholesteryl ester transfer protein (CETP) gene was associated significantly with neovascular AMD (P = 1.82×10(-4); odds ratio [OR], 1.89) and PCV (P = 4.04×10(-4); OR, 1.80). The associations remained significant after adjusting for the CFH SNP rs800292 and the HTRA1 SNP rs11200638. A significant interaction between the CETP SNP rs3764261 and the CFH SNP rs800292 existed in both neovascular AMD and PCV, the rs800292 G allele conferring a significantly increased risk of the diseases only in individuals carrying the risk allele T of rs3764261. A borderline association was detected between the ATP-binding cassette, subfamily G, member 1 (ABCG1) gene SNP rs57137919 and PCV (P = 0.03)., Conclusions: Our results showed that CETP is a susceptibility gene for neovascular AMD and PCV and that ABCG1 a putative gene for PCV. CETP exerts a modifying effect on CFH in the genetic risk. Our data suggest a link of the HDL metabolism pathway with neovascular AMD and PCV., (Copyright © 2014 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Aims: To investigate the association of the complement factor H (CFH) and complement component 1 inhibitor (SERPING1) genes with anterior uveitis (AU)., Methods: A total of 406 subjects (98 patients with AU and 308 controls) were recruited for this study. Two CFH polymorphisms (rs3753394 and rs1065489) and two SERPING1 polymorphisms (rs1005511 and rs3824988) were genotyped using TaqMan genotyping assays. Analyses were stratified for gender and human leukocyte antigen (HLA)-B27 status. Correlations of the genotypes with multiple clinical features were also evaluated., Results: No significant association was found between any of the four polymorphisms and AU after multiple testing corrections. However, stratified analyses showed that there were significant increases in the frequencies of T allele and TT homozygosity for CFH-rs1065489 in female patients compared with that of controls (pcorr=0.004 and pcorr=0.012 respectively). In addition, CFH-rs1065489 was also associated with AU in patients who were HLA-B27 positive. No significant association with AU was found for the other three single nucleotide polymorphisms (SNPs), even stratified by gender or HLA-B27 status. Genotype-phenotype analyses found that CFH-rs1065489 TT genotype was associated with higher uveitis recurrence frequency. No correlation was found between CFH-rs1065489 and other clinical features., Conclusions: This study revealed an association of CFH-rs1065489 with AU as well as uveitis recurrence frequency. The influence on AU could be gender specific and dependent on HLA-B27 status. Our results also suggested that SERPING1 does not play a significant role in the development of AU.

Purpose: Mutations in the SNRNP200 gene have been reported to cause autosomal dominant retinitis pigmentosa (adRP). In this study, we evaluate the mutation profile of SNRNP200 in a cohort of southern Chinese RP patients., Methods: Twenty adRP patients from 11 families and 165 index patients with non-syndromic RP with mixed inheritance patterns were screened for mutations in the mutation hotspots of SNRNP200. These included exons 12-16, 22-32, and 38-45, which covered the two helicase ATP-binding domains in DEAD-box and two sec-63 domains. The targeted regions were amplified by polymerase chain reaction and analyzed by direct DNA sequencing, followed by in silico analyses., Results: Totally 26 variants were identified, 18 of which were novel. Three non-synonymous variants (p.C502R, p.R1779H and p.I698V) were found exclusively in patients. Two of them, p.C502R and p.R1779H, were each identified in one simplex RP patient, whereas p.I698V occurred in one patient with unknown inheritance pattern. All three residues are highly conserved in SNRNP200 orthologs. Nevertheless, only p.C502R and p.R1779H were predicted to affect protein function by in silico analyses, suggesting these two variants are likely to be disease-causing mutations. Notably, all mutations previously identified in other study populations were not detected in this study., Conclusions: Our results reveal a distinct mutation profile of the SNRNP200 gene in a southern Chinese cohort of RP patients. The identification of two novel candidate mutations in two respective patients affirmed that SNRNP200 contributes to a proportion of overall RP.

Background and Purpose: Brain enhancement on contrast-enhanced T1-weighted imaging (CET1-WI) after ischemic stroke is generally accepted as an indicator of the blood-brain barrier disruption. However, this phenomenon usually starts to become visible at the subacute phase. The purpose of this study was to evaluate the time-course profiles of K(trans), cerebral blood volume (vp), and CET1-WI with early detection of blood-brain barrier changes on K(trans) maps and their role for prediction of subsequent hemorrhagic transformation in acute middle cerebral arterial infarct., Methods: Twenty-six patients with acute middle cerebral arterial stroke and early spontaneous reperfusion, whose MR images were obtained at predetermined stroke stages, were included. T2*-based MR perfusion-weighted images were acquired using the first-pass pharmacokinetic model to derive K(trans) and vp. Parenchymal enhancement observed on maps of K(trans), vp, and CET1-WI at each stage was compared. Association among these measurements and hemorrhagic transformation was analyzed., Results: K(trans) map showed significantly higher parenchymal enhancement in ischemic parenchyma as compared with that of vp map and CET1-WI at early stroke stages (P<0.05). The increased K(trans) at acute stage was not associated with parenchymal enhancement in CET1-WI at the same stage. Parenchymal enhancement in CET1-WI started to occur at the late subacute stage and tended to be luxury reperfusion-dependent. Patients with hemorrhagic transformation showed higher mean K(trans) values as compared with patients without hemorrhagic transformation (P=0.02)., Conclusions: Postischemic brain enhancement on routine CET1-WI seems to be closely related to the luxury reperfusion at the late subacute stage and is not dependent on microvascular permeability changes at the acute stage.

Purpose: To investigate the associations of the C2-CFB-RDBP-SKIV2L region with neovascular age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV)., Design: Cross-sectional, case-control association study., Participants: A Chinese case-control group of 200 neovascular AMD patients, 233 PCV patients, and 275 control subjects., Methods: An association analysis was performed of the C2-CFB-RDBP-SKIV2L locus with both neovascular AMD and PCV in a Chinese population using 19 haplotype-tagging single nucleotide polymorphisms (SNPs) and 6 previously reported SNPs across the C2-CFB-RDBP-SKIV2L region. All SNPs were genotyped using the TaqMan genotyping technology (TaqMan; Applied Biosystems [ABI], Foster City, CA)., Main Outcome Measures: Allele and haplotype frequencies of the SNPs in the C2-CFB-RDBP-SKIV2L region., Results: The SKIV2L SNPs rs429608 and rs453821 were significantly associated with neovascular AMD (P = 7.39 × 10(-5); odds ratio [OR], 0.22; 95% confidence interval [CI], 0.10-0.50; and P = 0.001; OR, 0.38; 95% CI, 0.21-0.70, respectively), whereas borderline associations were detected for C2 rs547154 (P = 0.002) and RDBP rs760070 (P = 0.003). Conditional haplotype analysis revealed that SKIV2L rs429608 could account fully for the global haplotype association identified in this region. The association of SKIV2L rs429608 with neovascular AMD remained significant after adjusting for CFH rs800292 and HTRA1 rs11200638. No individual SNP or haplotype was associated significantly with PCV., Conclusions: In this concurrent investigation of the associations of the entire C2-CFB-RDBP-SKIV2L region with neovascular AMD and PCV, the results suggested that SKIV2L is a likely causal gene for neovascular AMD, conferring a significant protective effect independent of CFH and HTRA1. These data do not support a significant role of this region in PCV, suggesting different molecular mechanisms between neovascular AMD and PCV., (Copyright © 2013 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: The magnetic resonance (MR) T2 value of cartilage is a reliable indicator of tissue properties and therefore may be used as an objective diagnostic tool in early meniscal degeneration. The purpose of this study was to investigate age, gender, location, and zonal differences in MR T2 value of the posterior horns of knee menisci in asymptomatic subjects., Methods: Sixty asymptomatic volunteers (30 men and 30 women) were enrolled and divided into three different age groups: 20-34, 35-49 and 50-70 years. The inclusion criteria were BMI<30 kg/cm(2), normalized Western Ontario and McMaster Universities (WOMAC) pain score of zero, and no evidence of meniscal and ligamentous abnormalities on routine knee MR imaging. The T2 values were measured on images acquired with a T2-weighted fat-suppressed turbo spin-echo sequence at 3T., Results: The mean T2 values in both medial and lateral menisci for the 20-34, 35-49, and 50-70 age groups were 9.94 msec±0.94, 10.73 msec±1.55, and 12.36 msec±2.27, respectively, for women and 9.17 msec±0.74, 9.64 msec±0.67, and 10.95 msec±1.33, respectively, for men. The T2 values were significantly higher in the 50-70 age group than the 20-34 age group (P<0.001) and in women than in men (P = 0.001, 0.004, and 0.049 for each respective age group). T2 values were significantly higher in medial menisci than in lateral menisci only in women age 50-70 (3.33 msec, P = 0.006) and in the white zone and red/white zone of the 50-70 and 35-49 age groups than that of the 20-34 age group (2.47, 1.02; 2.77, 1.16 msec, respectively, all P<0.01)., Conclusion: The MR T2 values of the posterior meniscal horns increase with increasing age in women and are higher in women than in men. The age-related rise of T2 values appears to be more severe in medial menisci than in lateral menisci. Differences exist in the white zone and red/white zone.

Recent advances in the treatment of cerebral gliomas have increased the demands on noninvasive neuroimaging for the diagnosis, therapeutic planning, tumor monitoring, and patient outcome prediction. In the meantime, improved magnetic resonance (MR) imaging techniques have shown much potentials in evaluating the key pathological features of the gliomas, including cellularity, invasiveness, mitotic activity, angiogenesis, and necrosis, hence, further shedding light on glioma grading before treatment. In this paper, an update of advanced MR imaging techniques is reviewed, and their potential roles as biomarkers of tumor grading are discussed.

Purpose: To quantitatively investigate signal alterations of the substantia nigra in patients with delayed parkinsonism following CO intoxication, as seen on gray matter (GM)-suppressed inversion-recovery (IR) magnetic resonance (MR) images., Materials and Methods: This prospective study was approved by the local institutional review board, and written informed consent was obtained from all subjects. Thirteen patients with delayed onset of CO-induced parkinsonism (nine men and four women; mean age, 40.3 years), 13 age-matched CO-intoxicated patients without parkinsonism, and 13 age-matched healthy volunteers were examined with GM-suppressed IR MR imaging. The signal intensity of the substantia nigra was normalized to the adjacent normal-appearing white matter in the temporal lobe, followed by semiautomatic segmentation into medial, middle, and lateral parts by using a skeleton-based algorithm. Multivariate and univariate analyses and Spearman rank correlation test were performed to examine the relationships between variables. Clinical severity was assessed with the modified Hoehn and Yahr rating scale., Results: The normalized signal ratios in the middle and lateral segments of the substantia nigra were significantly higher in those with CO-induced parkinsonism, compared with those with CO intoxication without parkinsonism or normal volunteers (P=.02). For the medial segments, the ratios showed no significant differences among the groups. The normalized signal ratios of substantia nigra were correlated with the severity of parkinsonism, particularly in the lateral segments (ρ=0.927, P<.001)., Conclusion: CO toxicity to the substantia nigra plays a role in pathophysiologic mechanisms of CO-induced parkinsonism. GM-suppressed IR MR imaging is a useful tool in depicting substantia nigra injury following CO intoxication., (© RSNA, 2012.)

Purpose: Association of rs800292 (I62V) in the complement factor H (CFH) gene with anterior uveitis (AU) was identified in our previous study. We proceeded to investigate whether polymorphisms of two tightly linked genes in the complement pathway, complement component 2 (C2) and complement factor B (CFB), are associated with AU., Methods: Five single-nucleotide polymorphisms (SNPs), rs1048709, rs537160, rs4151657, rs2072633 in CFB, and rs3020644 in C2, were examined using genotyping assays in 98 Chinese AU patients and 291 unrelated controls. Adjustments and stratifications were given for sex, clinical manifestations, and HLA-B27 status., Results: There were significant increases in the frequency of A allele and AA homozygosity for CFB-rs1048709 in AU patients compared with that of controls (P value after Bonferroni correction [P(corr)] = 2.67 × 10⁻⁴, P(corr) = 0.001, respectively). No association was found between AU and the other four SNPs after adjustment for multiple testing. Logistic regression analysis showed none of the 5 SNPs had significant interaction with sex. Stratified analyses showed that only rs1048709 was significantly associated with AU in HLA-B27-positive patients but not in HLA-B27-negative patients. No association was found in the 5 tested SNPs with clinical manifestations. A haplotype block across CFB (AATA) was significantly predisposed to AU with increased risk of 1.97 (P(corr) = 0.0005). Additive effect of CFB-rs1048709 and CFH-rs800292 was identified with an odds ratio of 7.48., Conclusions: Our results revealed an association between AU and CFB-rs1048709. The influence on AU might differ depending on HLA-B27 status. The joint effect in CFB and CFH strengthens the concept that the complement system plays an important role in the pathogenesis of AU.

Purpose: differentiate the associations of exudative age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV) with the ARMS2/HTRA1 locus., Methods: The entire ARMS2 sequence was sequenced and HTRA1 rs11200638 genotyped in 568 unrelated Chinese individuals: 156 exudative AMD patients, 164 PCV patients, and 248 controls. A meta-analysis was performed to examine the effects of rs10490924 and rs11200638 at the ARMS2/HTRA1 locus in PCV., Results: In total, 31 polymorphisms in ARMS2 were identified. Significant associations with both exudative AMD and PCV were observed in 11 of them and HTRA1 rs11200638, with different genotypic distributions between exudative AMD and PCV (P < 0.001). After adjusting for rs11200638, ARMS2 rs10490924 remained significantly associated with exudative AMD (P = 0.011), but not with PCV (P = 0.077). Meta-analysis showed consistent allelic associations of rs10490924 and rs11200638 with PCV in different study populations., Conclusions: There is a strong and consistent association of the ARMS2/HTRA1 locus with both exudative AMD and PCV, suggesting the two disorders share, at least partially, similar molecular mechanisms. Different effect sizes indicate the existence of additional genetic and environmental factors affecting them to different extents.

Objective: To investigate the associations of complement factor H (CFH), KIAA1109, and interleukin-27 (IL-27) gene polymorphisms in patients with non-infectious intermediate and posterior uveitis., Methods: The study cohort consisted of a total of 95 Chinese non-infectious uveitis patients, including 38 patients with intermediate uveitis (IU), 38 patients with Vogt-Koyanagi-Harada disease (VKH), and 19 patients with Behçet's disease and 308 healthy controls. The genotypes of CFH-rs800292, KIAA1109-rs4505848, and IL27-rs4788084 were determined using TaqMan single nucleotide polymorphism genotyping assays., Results: The frequency of carriers of G allele for CFH-rs800292 was significantly higher in patients with non-infectious intermediate and posterior uveitis than in controls (GG/AG versus AA; p=0.02). No significant association was found between uveitis and both KIAA1109-rs4505848 and IL27-rs4788084. In stratified analysis by gender, the frequency of carriers with G allele for KIAA1109-rs4505848 was significantly higher in male uveitis patients than in male controls (GG/AG versus AA; p=0.034). There was no significant difference in allelic and genotypic frequencies for CFH-rs800292 and IL27-rs4788084 in either male or female groups. In addition, higher frequency of KIAA1109-rs4505848 G allele was found in Behçet's disease patients compared with controls and IU patients (p=0.01 and p=0.003, respectively)., Conclusions: Our results demonstrated that CFH-rs800292 and KIAA1109-rs4505848 are associated with non-infectious intermediate and posterior uveitis. Moreover, gender susceptibility for uveitis might be involved in the KIAA1109 gene and the KIAA1109-rs4505848 polymorphism might be associated with the development of Behçet's disease.

Purpose: To investigate the associations between gene variants in cholesterol 24S-hydroxylase (CYP46A1), LIM homeobox transcription factor 1-beta (LMX1B), plexin domain containing 2 (PLXDC2), toll-like receptor 4 (TLR4), transmembrane and tetratricopeptide repeat containing 2 (TMTC2), zona pellucida glycoprotein 4 (ZP4), chromosome 2p16.3, and primary open-angle glaucoma (POAG)., Methods: We studied 462 POAG patients and 577 controls from three cohorts (Hong Kong, Shantou, and Beijing, China). Twelve single-nucleotide polymorphisms (SNPs) were genotyped in the Hong Kong cohort using TaqMan genotyping assay. Significant associations were validated in the Shantou and Beijing cohorts., Results: Association of POAG with TLR4 rs7037117, in a recessive model, was identified in the Hong Kong and Shantou cohorts (both southern Chinese, p(rec)=0.0019) but not the Beijing cohort (northern Chinese). rs1533428 at chromosome 2p16.3 showed a consistent trend of age-specific association in all three cohorts. Genotypes TT + CT conferred a 2.16 fold of significantly increased risk to late-onset POAG (p(dom)=0.00025), but no significant risk to POAG of younger ages of onset in the combined cohort. A joint effect was found between rs7037117 and rs1533428, with carriers of both higher-risk genotypes having a 4.53 fold of increased disease risk (p=0.00028)., Conclusions: Our study reveals discrepant association patterns of 12 candidate SNPs in 7 genes/loci with POAG in Chinese, provides positive replications for POAG markers rs1533428 at 2p16.3 and TLR4 rs7037117, and suggests that rs1533428 is a putative risk variant for late-onset POAG. The identification of an age-specific association between rs1533428 and late-onset POAG highlights a new genotype-phenotype association in POAG. Further studies are warranted to confirm the age-specific association.

Purpose: The neurotrophin-4 (NTF4) gene has been recently implicated in primary open-angle glaucoma (POAG). In this study, we investigated the implication of NTF4 in POAG among three Chinese cohorts., Methods: The coding regions and exon-intron boundaries of NTF4 was sequenced in 950 unrelated Chinese subjects, including a Hong Kong cohort of 390 patients and 230 controls, a Shantou cohort of 130 patients, and a Beijing cohort of 200 patients. Constructs carrying the detected variants were generated using site-directed mutagenesis and transfected into HeLa cells, followed by solubility and migration analyses., Results: Three variants were identified. p.Pro151Pro was detected in three POAG patients and one control subject. Two novel missense variants, p.Gly157Ala and p.Ala182Val, were identified each in one POAG patient from the Hong Kong cohort, but not in controls. Functional assays showed that the p.Gly157Ala mutant protein was less soluble in Triton X-100, and that migration of HeLa cells transfected with either mutant construct was less than cells transfected with the wildtype., Conclusions: The NTF4 variants p.Gly157Ala and p.Ala182Val have been shown to be functional mutations, occurring in 2 of a total of 720 Chinese POAG patients. NTF4 is functionally related to POAG pathogenesis but its mutation frequency is low. Therefore, NTF4 does not have a major contribution in the molecular genetics of POAG.

This study investigated the feasibility of analyzing a full range of ambient volatile organic compounds (VOCs) from C(3) to C(12) using gas chromatograph mass spectrometry (GC/MS) coupled with thermal desorption. Two columns were used: a PLOT column separated compounds lighter than C(6) and a DB-1 column separated C(6)-C(12) compounds. An innovative heart-cut technique based on the Deans switch was configured to combine the two column outflows at the ends of the columns before entering the MS. To prevent the resolved peaks from re-converging after combining, two techniques were attempted (hold-up vs. back-flush) to achieve the intended "delayed" elution of heavier components. Thus, the resulting chromatogram covering the full range of VOCs is a combination of two separate elutions, with the heavier section following the lighter section. With the hold-up method, band-broadening inevitably occurred for the delayed C(6)-C(7) DB-1 compounds while the light compounds eluted from the PLOT column. This broadening problem resulted in peak tailing that was largely alleviated by adding a re-focusing stage while the DB-1 compounds were back-flushed, and this modified technique is referred to as the back-flush method. With this modification, the separation of the C(6)-C(7) compounds improved dramatically, as revealed by the decrease in peak asymmetry (As) and increase in resolution. Linearity and precision for these peaks also improved, yielding R(2) and RSD values better than 0.9990 and 2.8%, respectively., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Purpose: To investigate the effects of 3,4-methylenedioxymethamphetamine (MDMA, commonly known as "ecstasy") on the alterations of brain metabolites and anatomic tissue integrity related to the function of the basal ganglia-thalamocortical circuit by using proton magnetic resonance (MR) spectroscopy and diffusion-tensor MR imaging., Materials and Methods: This study was approved by a local institutional review board, and written informed consent was obtained from all subjects. Thirty-one long-term (>1 year) MDMA users and 33 healthy subjects were enrolled. Proton MR spectroscopy from the middle frontal cortex and bilateral basal ganglia and whole-brain diffusion-tensor MR imaging were performed with a 3.0-T system. Absolute concentrations of metabolites were computed, and diffusion-tensor data were registered to the International Consortium for Brain Mapping template to facilitate voxel-based group comparison., Results: The mean myo-inositol level in the basal ganglia of MDMA users (left: 4.55 mmol/L ± 2.01 [standard deviation], right: 4.48 mmol/L ± 1.33) was significantly higher than that in control subjects (left: 3.25 mmol/L ± 1.30, right: 3.31 mmol/L ± 1.19) (P < .001). Cumulative lifetime MDMA dose showed a positive correlation with the levels of choline-containing compounds (Cho) in the right basal ganglia (r = 0.47, P = .02). MDMA users also showed a significant increase in fractional anisotropy (FA) in the bilateral thalami and significant changes in water diffusion in several regions related to the basal ganglia-thalamocortical circuit as compared with control subjects (P < .05; cluster size, >50 voxels)., Conclusion: Increased myo-inositol and Cho concentrations in the basal ganglia of MDMA users are suggestive of glial response to degenerating serotonergic functions. The abnormal metabolic changes in the basal ganglia may consequently affect the inhibitory effect of the basal ganglia to the thalamus, as suggested by the increased FA in the thalamus and abnormal changes in water diffusion in the corresponding basal ganglia-thalamocortical circuit., (© RSNA, 2011.)

Objective: To investigate the association of three single nucleotide polymorphisms (SNPs) in the complement factor H (CFH), KIAA1109, and interleukin-27 (IL-27) genes in patients with anterior uveitis (AU)., Methods: A case-control study was performed in 98 Chinese AU patients and 308 healthy controls. Three SNPs including CFH-rs800292, KIAA1109-rs4505848, and IL27-rs4788084 were detected using TaqMan SNP Genotyping Assays. Analyses were also stratified according to gender, clinical features and human leukocyte antigen (HLA)-B27 status of the patients., Results: No significant association was found between all three SNPs and AU. However, when stratified by gender, there were significant increases in the frequency of the CFH-rs800292 184G allele and GG homozygosity in female patients compared with control subjects (p=0.003 and p=0.009, respectively). Similar association was not detected in males. No significant association was found between AU and KIAA1109-rs4505848 or IL27-rs4788084 even stratified by gender. There was no significant difference in genotypes of AU patients stratified by various clinical features. Subgroup analyses showed that all three SNPs (rs800292, rs4505848, and rs4788084) were not associated with AU in HLA-B27-positive patients, neither in HLA-B27-negative patients., Conclusions: Our results showed an association between AU and CFH polymorphism in Chinese female patients but not in males, indicating gender-specific genetic differences in CFH. Gender should be considered in genetic studies of anterior uveitis even extending to other immunologic diseases.